Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Yacoob Omar Carrim, Luvo Gaxa, Francisca van der Schyff, Nndweleni Meshack Bida, Fareed Omar, Zarina Lockhat
Colorectal carcinoma in children and adolescents is extremely rare, with an annual incidence <0.3 cases per million, most frequently reported in the second decade of life. It accounts for severe morbidity and poor prognosis owing to the low index of suspicion, delayed diagnosis, advanced stage at presentation and the aggressive tumor nature. Patients present with abdominal pain, vomiting, constipation, abdominal distension, rectal tenesmus, iron-deficiency anemia, change in bowel habit and weight loss. Rectal bleeding is an uncommon presentation in children. Bowel obstruction presents frequently in children compared to adults. In 90% of pediatric cases, colorectal carcinoma occurs sporadically. In 10%, predisposing conditions and syndromes are identified. We present a case study of a 12-year-old female with advanced colorectal cancer without a predisposing disease or syndrome, who received radio-chemotherapy ten weeks prior to radical abdominopelvic surgery, followed by radio-chemotherapy postoperatively, with a positive outcome.
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Πέμπτη 7 Δεκεμβρίου 2017
Does radiotherapy prior to surgery improve long term prognosis in pediatric colorectal cancer in lower- and upper-middle income countries with limited resources? Our experience and literature review
Downregulation of Caspase 8 in a group of Iranian breast cancer patients – A pilot study
Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Masoumeh Aghababazadeh, Najmeh Dorraki, Fahimeh Afzal Javan, Asieh Sadat Fattahi, Masoumeh Gharib, Alireza Pasdar
PurposeIt is now well known that evading apoptosis, as a cancer hallmark, can lead to tumour initiation, progression and metastasis. As a result of genome wide association studies, an initiator protease in this pathway, caspase 8 (CASP8), has been found to be an important gene regarding breast cancer susceptibility. The alterations of the expression of this gene have been reported in breast cancer cell lines. Given that in previous studies expression analysis of this gene had only been done in breast cancer cell lines, in this study we aimed to evaluate the expression of this gene in breast cancer tissues versus adjacent normal tissues, using real-time quantitative method.MethodsCaspase 8 mRNA expression was quantified using comparative RT-qPCR in 27 fresh frozen breast tumours and 27 adjacent normal tissues. Moreover, relationship between the expression changes of CASP8 in tumour tissue and various clinical and pathological features were evaluated in an Iranian population.ResultsThe present study showed that expression of CASP8 was significantly reduced in tumour tissues compared to neighbouring normal tissues (p = .004). CASP8 expression was significantly correlated with the status of hormone receptors (ER and PR).ConclusionTo the best of our knowledge, this study is the first report on reduced expression of CASP8 in breast cancer versus adjacent normal tissues. Our data support previous results obtained from cell lines and therefore highlights the seminal role of the induction of CASP8 expression, as a novel therapeutic approach, in order to sensitize tumour cells to apoptotic stimuli.
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Cytological diagnosis of a rare case of cutaneous metastasis from transitional cell carcinoma, renal pelvis
Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Pragya Singh, Sachin Kolte, Gunjesh Kumar Singh
Transitional cell carcinoma (TCC) arising from renal pelvis rarely gives rise to cutaneous metastasis. Due to the insufficient literature, the exact incidence is not known till date. Moreover, the diagnosis is confirmed on histopathological examination with the aid of immunohistochemistry wherever needed. We are presenting a case of a 70-year-old female with metastatic TCC from the renal pelvis to the abdominal skin, which was diagnosed on cytology alone along with the cell block preparation. We also highlight the important cytomorphological and immunohistochemical features noted, which need to be known to avoid any diagnostic delay.
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Reconstruction Special Edition, Issue 2
The following three articles comprise the second edition of a special series highlighting important aspects of Head and Neck Reconstruction. These peer-reviewed papers highlight current standards, unique practices, and quality and value projects within our field of head and neck reconstruction. The articles are grouped into three different categories: 1) Subsite reconstruction 2) Versatile microvascular free flaps and 3) Perioperative considerations.
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Psychometric validation of the Center for Epidemiological Studies Depression Scale in Head and Neck Cancer patients
Depression is a common complication in patients with cancer [1]. Studies have shown that patients with head and neck cancer (HNC) experience higher rates of depression than other groups with an incidence of 15–50% as compared to 15–25% in other cancers [2]. Depression associated with cancer treatment in HNC patients has also been shown to contribute to lower quality of life, high levels of fatigue, low motivation, and higher suicide rates [2]. Early detection of depression and treatment would facilitate better treatment outcomes and quality of life [3].
http://ift.tt/2j6JZfl
Hypermethylated ZNF582 and PAX1 genes in oral scrapings collected from cancer-adjacent normal oral mucosal sites are associated with aggressive progression and poor prognosis of oral cancer
The estimated annual incidence of oral squamous cell carcinoma (OSCC) is approximately 275,000 new cases worldwide. OSCC is the eighth most prevalent cancer in the world [1]. In Taiwan, OSCC ranks fifth among the predominant cancers for both sexes and accounts for the fourth most common cancer for males [2]. Development of recurrent cancer and second primary cancer is one of the major causes of the poor 5-year overall survival of OSCC patients [3]. Therefore, it is crucial to find a biomarker that can predict the progression, recurrence, and prognosis of OSCC at its earliest stage.
http://ift.tt/2kBhgzq
Definitive (chemo)radiotherapy is a curative alternative for standard of care in advanced stage squamous cell carcinoma of the oral cavity
Head and neck squamous cell carcinoma is the 7th most common cancer in men and the 9th most common cancer in women in The Netherlands. Per year, 900 out of 2900 head and neck cancer patients are diagnosed with oral cavity carcinoma (OCC) [1]. Although there has been a shift towards organ preservation treatment in other head and neck cancer subsites [2], the standard of care for advanced oral cavity cancer is surgery with adjuvant (chemo)radiotherapy (CRT). However, especially in patients with locally advanced disease, this surgery may lead to extensive mutilation and results in a disappointing 5-year overall survival of 65% in stage III and 37% in stage IV disease [3].
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Differential roles of kallikrein-related peptidase 6 in malignant transformation and ΔNp63β-mediated epithelial-mesenchymal transition of oral squamous cell carcinoma
Oral squamous cell carcinoma (OSCC) accounts for approximately 3% of all malignancies worldwide [1]. Due to a high rate of local invasion and recurrence, the overall survival rate of OSCC patients has failed to substantially rise over the last decade [2]. Especially, locally advanced OSCC remains refractory and lethal in more than 50% cases [1]. Distant metastases are rarely found on initial presentation; therefore, locoregional disease control and the elucidation of the mechanism underlying OSCC invasion are critical to improving the survival rate of OSCC patients [3].
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Unplanned readmission following transoral robotic surgery
The Hospital Readmissions Reduction Program (HRRP), established by the Affordable Care Act, aims to reduce unplanned hospital readmissions by 20% and requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals that do not meet a certain national benchmark for acceptable readmission rates [1]. Although head and neck oncologic procedures are not yet included in the HRRP, future expansion or iterations may affect otolaryngologists. Moreover, unplanned readmission negatively affects patient quality of life [2].
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Utilization of a pre-bent plate-positioning surgical guide system in precise mandibular reconstruction with a free fibula flap
Extensive repair of mandibular defects is challenging. Reconstructive options have included the use of microvascular free flaps, non-vascularized bone grafts, and alloplastic implants, including titanium reconstruction plates. In 1989, Hidalgo [1] reported the usefulness of free vascularized fibula flaps for mandibular reconstruction. This flap has many advantages, including a long pedicle, wide vessel diameter, sufficient bone components, and the ability to incorporate the skin paddle [2,3]. Since then, the fibula has been commonly chosen as the donor site for mandibular reconstruction.
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Cancer stem cell and its niche in malignant progression of oral potentially malignant disorders
Oral cancer, which is the sixth most common cancer, accounts for 300,000 cases worldwide [1]. A large proportion of oral cancer is preceded by the development of oral leukoplakia [2,3], an oral potentially malignant disorder (OPMD). The histologic progression of OPMD from hyperplasia, different grades of dysplasia to carcinoma-in-situ and invasive carcinoma and the associated genomic changes are well studied [4]. Cancer stem cells (CSCs) have been increasingly implicated in oral carcinogenesis and field cancerization [5], and are known to be regulated by stroma and endothelial cells constituting the CSC-niche [6,7].
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Delayed clinical complete response to intensity-modulated radiotherapy in nasopharyngeal carcinoma
Nasopharyngeal carcinoma (NPC) is a common head and neck cancer in China, especially the southern regions, with 60,600 new cases reported in 2015 [1]. Unlike other head and neck cancers, radiotherapy (RT) is the primary treatment modality for non-disseminated NPC due to its anatomical location and sensitivity to radiation. The optimal time-point for assessing the tumor response to RT is very important in NPC, as it determines whether the patient has residual or persistent disease and whether salvage treatment should be initiated [2–4].
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Oncogenic DNA viruses found in salivary gland tumors
Salivary gland tumors (SGTs) are rare, extremely complex entities posing a major challenge for both pathologists and clinicians [1,2]. Despite intensive research beginning in the early '90, the etiology of SGTs is still unclear [3]. Several human DNA viruses, including human papillomaviruses (HPVs), herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), and polyomaviruses, have been implicated in a wide variety of tumors, and the majority of these can be detected in saliva samples [4–7].
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Construction of mass spectra database and diagnosis algorithm for head and neck squamous cell carcinoma
Although complete tumor resection leads to improved prognosis in patients with head and neck squamous cell carcinoma (HNSCC), functional disabilities such as dysphagia and dysphonia are sometimes unavoidable. The risk of these complications can be minimized by careful dissection [1–4]. Intraoperative rapid diagnosis using frozen sections is the standard means of determining appropriate tumor margins [5,6]. This process requires several steps, including tissue freezing, cryosectioning, hematoxylin and eosin (H&E) staining, and microscopic examination, the whole process usually taking >30 min.
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Reconstruction of oral cavity defect using versatile buccinator myomucosal flaps in the treatment of cT2–3, N0 oral cavity squamous cell carcinoma: Feasibility, morbidity, and functional/oncological outcomes
In the surgical management of oral cavity squamous cell carcinoma (OCSCC), radical resection with adequate margins is paramount in achieving local control. To obtain microscopically clear margins >0.5 cm, additional resection of normal tissue >1.0–1.5 cm from the gross tumor border is recommended [1,2]. Therefore, defect size is always significantly larger than the tumor itself, and reconstruction is commonly required to establish form and function in the resected organ, with the exception of some T1 and T2 OCSCCs.
http://ift.tt/2j3mX90
Prognostic value of masticatory muscle involvement in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy
In 2017, the UICC/AJCC published the 8th edition of their staging manual for NPC, which has gained universal acceptance. This is a revision based on the UICC/AJCC's 7th edition and the 2008 Chinese staging system. There are three important adjustments for primary tumor site (T) classifications: (1) T0 is added for Epstein-Barr virus (EBV)-positive cancers with cervical lymph node involvement and no identifiable primary tumor; (2) New evidence has confirmed the prognostic value of the prevertebral muscle in NPC patients with tumors designated as T2; (3) The previous T4 criteria of "masticator space" and "infratemporal fossa" are now replaced by a specific description of soft tissue involvement and tumors that invade the medial pterygoid muscle (MP) and/or the lateral pterygoid muscle (LP) are now down-staged as T2 [1].
http://ift.tt/2kEjIFK
A network meta-analysis in comparing prophylactic treatments of radiotherapy-induced oral mucositis for patients with head and neck cancers receiving radiotherapy
Head and neck cancers (HNSCC) account for 5% of all cancers, and squamous cell carcinoma or a variant is the main histologic type in more than 90% of these tumors [1]. Single-modality treatment with surgery or radiotherapy is usually recommended for early disease (stage I or II). Due to complicated anatomy and the wide extension of local or regionally advanced disease, the combined treatment strategy of radical radiotherapy with chemotherapy or cetuximab [2] is a preferred option for unresectable disease.
http://ift.tt/2j8dHk1
Humidification mitigates acute mucosal toxicity during radiotherapy when factoring volumetric parameters. Trans Tasman Radiation Oncology Group (TROG) RadioHUM 07.03 substudy
The rationale for domiciliary humidification during head and neck radiotherapy to ameliorate symptoms associated with mucositis using a high flow rate humidifier with nasal prong interface is based on principles of moist wound care, or in other words to reduce the impact of wound desiccation on tissue injury. This may help mitigate the intense pro-inflammatory environment characteristic of mucositis pathobiology [1,2]. Moisturisation aids nutrient delivery and facilitates migration of cells across epithelial surfaces during wound healing.
http://ift.tt/2kAF1Ib
Plasticity of oral mucosal cell sheets for accelerated and scarless skin wound healing
This study examined the potential utility of a newly developed oral mucosal cell sheet in skin excisional wounds. The oral mucosal cell sheet promoted wound healing with early wound closure and less scarring and demonstrated in vivo tissue plasticity through good adaptation in cutaneous wounds.
http://ift.tt/2j7Zgwf
Evaluation of the diagnostic efficacy and spectrum of autofluorescence of benign, dysplastic and malignant lesions of the oral cavity using VELscope
In individuals exposed to risk factors; the prevention and early detection of oral cancer play a significant role in increasing the survival rates [1,2]. In the absence of a definitive approach, screening of oral cancer is still largely based on conventional oral examination (COE) and scalpel biopsy in case of suspicious lesions [3,4]. Since visible changes in the oral mucosa are known to precede the development of virtually all oral squamous cell carcinomas (OSCCs), various adjunctive techniques have been introduced with the aim to assist in the detection of early cancerous mucosal changes that can be occult to visual inspection [5,6].
http://ift.tt/2kzYsAE
Head and neck reconstruction with free flaps based on the thoracodorsal system
Evolution in the range of free flaps available for head and neck cancer has facilitated successful reconstructive surgery in increasingly demanding defects. Patients presenting with extensive primary or recurrent tumours, as well as cases of osteoradionecrosis, form a significant part of the head and neck reconstructive surgeon's practice. These cases often incorporate complex three-dimensional defects that include both osseous and soft tissue components as well as more than one epithelial surface (e.g.
http://ift.tt/2j76Asn
Results of a phase II randomized controlled clinical trial comparing efficacy of Cabazitaxel versus Docetaxel as second line or above therapy in recurrent head and neck cancer
Head and neck squamous cell cancer (SCCHN) is the fifth most common cancer worldwide and is the most common neoplasm in central Asia [1]. Head and neck malignancies are common in regions of the world where tobacco use and alcohol consumption is high [2]. The five-year survival ranges from 20 to 90% depending upon the subsite of origin and the clinical extent of disease [3]. Current therapy consists of surgery, radiotherapy and chemotherapy [3]. More than 60% patients develop recurrence in locally advanced head and neck cancer [4].
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Comments on “Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome”
Source:European Journal of Surgical Oncology
Author(s): Xing Wang, Xubao Liu
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Reply letter to: Comments on "Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome"
Source:European Journal of Surgical Oncology
Author(s): Nir Lubezky
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Tennis leg: A mimic of deep venous thrombosis
Source:Medical Journal Armed Forces India
Author(s): Mukul Bhatia, Vinay Maurya, J. Debnath, Preeti Gupta
http://ift.tt/2j4h8s0
Antibacterial resistance patterns of extended spectrum β-lactamase -producing enteropathogenic Escherichia coli strains isolated from children
Publication date: Available online 7 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Pejman Karami, Hassan Bazmamoun, Iraj Sedighi, Amir Sasan Mozaffari Nejad, Mohammad Mehdi Aslani, Mohammad Yousef Alikhani
Background and study aimThis study aimed to determine the antibacterial resistance patterns of extended spectrum β-lactamase (ESBL)-producing enteropathogenic Escherichia coli (EPEC) isolated from Iranian children and to investigate its genetic patterns.Patients and methods192 non-repeats EPEC isolates were collected from stool samples of the children with and without diarrhoea. The EPEC strains were isolated from 1355 stool specimens obtained from 247 children with diarrhoea (0–10 years old; mean age, 5.5 years) and 1108 children without any gastrointestinal symptoms (0–10 years old; mean age, 6.8 years) during the summer months in three Iranian provinces, Tehran, Ilam and Mazandaran. Strains biochemically identified as E. coli were selected and were identified by the presence of eaeA and bfpA as EPEC virulence genes. Antimicrobial susceptibilities were determined by disc diffusion method. The isolates were confirmed to be ESBL producers by the double disk synergy test (DDST). The β-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaOXA) and insertion sequence ISEcp1 were detected by PCR method.ResultsThe highest antibiotic susceptibility was detected to imipenem (100%), followed by gentamicin (82.3%) and ciprofloxacin (79.2%). The highest resistance was detected to cefpodoxime (97.9%), trimethoprim (60.7%), and tetracycline (58.4%), respectively. Totally, 153 EPEC strains (79.7%) were ESBL-producing by DDST test. The PCR showed that 84 (43.8%) EPEC isolates were positive for ESBLs encoding genes. Among 153 ESBLs-producing EPEC, TEM was present in 9.2% of isolates. Also, CTX-M and SHV genes were detected in 7.2% and 7.8%, respectively. The SHV positive strains were associated with the highest resistance rate to tetracycline (56.5%), although the TEM and OXA were associated with the highest resistance rate to gentamicin (23.1%) and ciprofloxacin (21.4%).ConclusionsThe study revealed that 79.7% of EPEC isolates from Iranian children were ESBL-producing and were comparable with the non ESBL-producing isolates regarding susceptibility to the antibiotics.
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Preface – Part 2: Circadian and endocrine rhythms
Publication date: December 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 31, Issue 6
Author(s): Andries Kalsbeek, Eric Fliers
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Bone Marrow Edema Syndrome Of The Medial Femoral Condyle Treated With Extracorporeal Shock Wave Therapy: A Clinical And MRI Retrospective Comparative Study
Publication date: Available online 7 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Matteo Vitali, Nadim Naim Rodriguez, Alberto Pedretti, Andreas Drossinos, Pierluigi Pironti, Gaia Di Carlo, Gianfranco Fraschini
ObjectiveTo determine the validity of Extracorporeal Shock Wave Therapy (ESWT) in the treatment of Bone Marrow Edema (BME) of the medial condyle of the kneeDesignRetrospectiveStudy SettingIRCCS San Raffaele Hospital, Orthopedics Outpatient ClinicParticipantsFifty-six symptomatic patients affected by bone marrow edema of the medial condyle of the knee. Patients were equally divided in a ESWT (Extracorporeal Shock Wave Therapy) treated group and a control group, which was managed conservatively.InterventionsExtracorporeal Shock Wave Therapy delivery to the medial condyle of the affected knee.Main Outcome MeasuresClinical and Functional assessment done with the use of the Knee Society Score (KSS), both clinical and functional scores. Pain was measured with Visual Analog Scale (VAS). Bone marrow edema area was measured with Magnetic Resonance Imaging before treatment and at 4 months follow-up.ResultsClinical evaluation of patients at final follow-up of 4 months post-treatment showed a significant improvement (p< 0.0001) of symptoms and knee functionality, both for range of motion and strength in both groups VAS values saw a significant improvement (p< 0.0001) in both groups; with 3 patients in the ESWT group being pain-free (VAS=0) at 4 months follow-up. At 4 months MRI assessments on both sagittal and coronal views showed a significant reduction in bone marrow edema in the ESWT as compared to the control group.ConclusionOur findings show that this type of therapy has shown to be a valid non-pharmacological and non-invasive therapy in the treatment of spontaneous BME of the medial condyle, producing an improvement of the affected vascular and metabolic state present in this pathology through its metabolic mechanisms of action.
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Comparison of neuroplastic responses to cathodal transcranial direct current stimulation and continuous theta burst stimulation in subacute stroke
Publication date: Available online 7 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Pierre Nicolo, Cécile Magnin, Elena Pedrazzini, Gijs Plomp, Anaïs Mottaz, Armin Schnider, Adrian G. Guggisberg
ObjectiveTo investigate the effects of cathodal transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural network connectivity and motor recovery in individuals with subacute stroke.DesignDouble-blinded, randomized, placebo-controlled study.SettingStroke subjects recruited through a university hospital rehabilitation program.ParticipantsStroke inpatients (N=41; mean age 65y, range 28-85; mean weeks poststroke 5, range 2-10) with resultant paresis in the upper extremity (mean Fugl-Meyer score 14, range 3-48).InterventionStroke subjects were randomly assigned to neuronavigated cTBS (N=14), cathodal tDCS (N=14), or sham TMS/sham tDCS (N=13) over the contralesional primary motor area (M1). Each subject completed nine stimulation sessions over three weeks, combined with physical therapy.Main outcome measuresBrain function was assessed with resting-state directed and non-directed functional connectivity based on high-density electroencephalography (EEG) before and after stimulation sessions. Primary clinical endpoint was the change in slope of multifaceted motor score composed of the Upper-Extremity Fugl-Meyer Assessment (UE-FMA), Box and Block test (BBT), Nine Hole Peg Test (NHPT), Jamar dynamometer between the baseline period and the treatment time.ResultsNeither stimulation treatment enhanced clinical motor gains. Cathodal tDCS and cTBS induced different neural effects. Only cTBS was able to reduce transcallosal influences from the contralesional to the ipsilesional M1 during rest. Conversely, tDCS enhanced perilesional beta-band oscillation coherence as compared to cTBS and sham groups. Correlation analyses indicated that the modulation of interhemispheric driving and perilesional beta-band connectivity were not independent mediators for functional recovery across all patients. However, exploratory subgroup analyses suggest that the enhancement of perilesional beta-band connectivity through tDCS might have more robust clinical gains if started within the first 4 weeks after stroke.ConclusionsThe inhibition of the contralesional primary motor cortex or the reduction of interhemispheric interactions was not clinically useful in heterogeneous group of subacute stroke subjects. An early modulation of perilesional oscillation coherence seems to be a more promising strategy for brain stimulation interventions.
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Author Index to Volume 119, 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
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Development of a brief assessment of activity limitations in children with food allergy
Source:Annals of Allergy, Asthma & Immunology
Author(s): Catherine C. Peterson, Lauren E. Harrison
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IgG4-related disease presenting as hoarseness and postcricoid ulcer
Source:Annals of Allergy, Asthma & Immunology
Author(s): Syeda Hamadani, Beverly Wang, Sudhir Gupta
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Effect of inhaled allergens and air pollutants on childhood rhinitis development
Source:Annals of Allergy, Asthma & Immunology
Author(s): Hui Zhou, Xia (Iona) Li, Jeong Hee Kim, Muhammad T. Salam, Hyo Bin Kim, Rob S. McConnell, Rima Habre, Tracy Bastain, Shohreh F. Farzan, Jill Johnston, Frank D. Gilliland
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Information for Readers
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
http://ift.tt/2BXN7i7
Table of Contents
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
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rAsp f 3 and rAsp f 4 are associated with bronchiectasis in allergic fungal airways disease
Source:Annals of Allergy, Asthma & Immunology
Author(s): Kerry Woolnough, Michelle Craner, Catherine H. Pashley, Andrew J. Wardlaw
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Instructions for Authors
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
http://ift.tt/2k8BBIO
Toxocara species exposure, symptoms of asthma, and fractional exhaled nitric oxide in the US population
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Funmilola Ogundipe, Edward Christian Anselm Hennis, Alem Mehari, Richard F. Gillum
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Editorial Board
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
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Could calcium channel blockers treat 2 illnesses with 1 pill?
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): John Oppenheimer, H. William Kelly
http://ift.tt/2BVRqdO
Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): John J. Oppenheimer, Paul A. Greenberger
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Increasing our knowledge base of asthma
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): John J. Oppenheimer, Gailen D. Marshall
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Innate lymphoid cells and allergic disease
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Matthew T. Stier, R. Stokes Peebles
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Rare cause of periorbital and eyelids lesions: Discoid lupus erythematosus misdiagnosed as allergy
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Anzelika Chomiciene, Ruta Stankeviciute, Laura Malinauskiene, Jurate Grigaitiene, Audra Blaziene
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Spectrum and prevalence of reactions to marijuana in a Colorado allergy practice
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): William S. Silvers, Tiana Bernard
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Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Bradley E. Chipps, Robert S. Zeiger, Allan T. Luskin, William W. Busse, Benjamin L. Trzaskoma, Evgeniya N. Antonova, Hooman Pazwash, Susan L. Limb, Paul G. Solari, Noelle M. Griffin, Thomas B. Casale
BackgroundPatients included in clinical trials do not necessarily reflect the real-world population.ObjectiveTo understand the characteristics, including disease and comorbidity burden, of patients with asthma receiving omalizumab in a real-world setting.MethodsThe Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) was a US-based, multicenter, single-arm, and prospective study. Patients (≥12 years of age) with allergic asthma initiating omalizumab treatment based on physician-assessed need were included and followed for 12 months. Exacerbations, health care use, adverse events, and Asthma Control Test (ACT) scores were assessed monthly. Biomarkers (blood eosinophils, fractional exhaled nitric oxide, and periostin) were evaluated and patient-reported outcomes (Asthma Quality of Life Questionnaire for 12 Years and Older [AQLQ+12] and Work Productivity and Activity Impairment: Asthma questionnaire [WPAI:Asthma]) were completed at baseline and months 6 and 12. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) was completed at baseline and 12 months.ResultsMost of the 806 enrollees (91.4%) were adults (mean age 47.3 years, SD 17.4), white (70.3%), and female (63.5%). Allergic comorbidity was frequently reported (84.2%), as were hypertension (35.5%) and depression (22.1%). In the 12 months before study entry, 22.1% of patients reported at least 1 asthma-related hospitalization, 60.7% reported at least 2 exacerbations, and 83.3% reported ACT scores no higher than 19 (uncontrolled asthma). Most patients had low biomarker levels based on prespecified cut-points. Baseline mean patient-reported outcome scores were 4.0 (SD 1.4) for AQLQ+12, 2.7 (SD 1.4) for MiniRQLQ, and 47.7 (SD 28.9) for WPAI:Asthma percentage of activity impairment and 33.5 (SD 28.7) for percentage of overall work impairment.ConclusionThe population initiating omalizumab in PROSPERO reported poorly controlled asthma and a substantial disease burden.Trial RegistrationClinicalTrials.gov Identifier: NCT01922037.
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The clinical role of fractional exhaled nitric oxide in asthma control
Publication date: December 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Suguru Sato, Junpei Saito, Atsuro Fukuhara, Manabu Uematsu, Yasuhito Suzuki, Ryuichi Togawa, Yuki Sato, Takefumi Nikaido, Xintao Wang, Yoshinori Tanino, Mitsuru Munakata
BackgroundThe potential role and characteristics of fractional exhaled nitric oxide (FeNO) remain unclear in the treatment of asthma.ObjectiveTo explore the clinical role of FeNO in asthmatic treatment.MethodsWe evaluated whether the mean or change of FeNO levels in the treatment period is associated with other conventional control parameters and predicted some clinical outcomes of asthma. We retrospectively analyzed the mean and percentage change of FeNO levels in the first 5 measurements at our hospital.ResultsThe study found a significantly strong correlation between FeNO level at diagnosis and the largest changes of FeNO values from diagnosis. No significant correlations were observed between FeNO levels and other parameters (Asthma Control Test [ACT] score or forced expiratory volume in one second [FEV1]) in mean and percentage change of values under treatment of asthma; however, significant positive correlations were found between ACT scores and FEV1. The mean FeNO level revealed a significant negative correlation with an annual change in FEV1 in individuals with asthma who were followed up for more than 2 years. Both the mean ACT score and percent predicted FEV1 revealed a significant negative correlation with occasional use of systemic corticosteroids.ConclusionDuring conventional treatment of asthma, the largest changes of FeNO values from diagnosis were strongly correlated with FeNO levels at diagnosis. As for the unlikely conventional parameters, no significant associations were observed between FeNO levels and deterioration of asthma during the treatment periods. An elevated mean FeNO level may be a marker of decreased lung function in individuals with asthma.
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Burden of skin pain in atopic dermatitis
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Paras P. Vakharia, Rishi Chopra, Ryan Sacotte, Kevin R. Patel, Vivek Singam, Neha Patel, Supriya Immaneni, Takeshia White, Robert Kantor, Derek Y. Hsu, Jonathan I. Silverberg
BackgroundAtopic dermatitis (AD) is associated with itch, skin inflammation and barrier disruption, and scratching, all of which may be associated with skin pain.ObjectiveTo characterize the patient burden of skin pain in AD.MethodsWe performed a prospective dermatology practice–based study using questionnaires and evaluation by a dermatologist.ResultsOverall, 305 patients (age range, 13–97 years) were included in the study, with 564 encounters. The cohort included 195 females (63.9%) and 193 whites (63.7%). The mean (SD) age at enrollment was 42.3 (18.1) years, and the mean (SD) age of patient-reported AD onset was 29.6 (31.9) years. At baseline, 144 patients (42.7%) reported skin pain in the past week, with 42 (13.8%) reporting severe or very severe pain. Twenty-four (16.8%) thought the skin pain was part of their itch, 16 (11.2%) from scratching, and 77 (72.0%) from both. Patients with skin pain were more likely to describe their itch using terms that resembled neuropathic pain. Prevalence of skin pain was increased in patients with vs without excoriations (72.6% vs 57.6%; χ2 test P = .02) but not other morphologic characteristics. Skin pain severity was most strongly correlated with the Patient-Oriented Eczema Measure (Spearman ρ = 0.54), followed by ItchyQOL (ρ = 0.52), 5-dimensions of itch scale (ρ = 0.47), Dermatology Life Quality Index (ρ = 0.45), numeric rating scale for itch (ρ = 0.43) and sleep (ρ = 0.36), Patient Health Questionnaire 9 (ρ = 0.36), patient-reported global AD severity (ρ = 0.34), Eczema Area and Severity Index (ρ = 0.23), and objective Scoring AD index (ρ = 0.20) (P < .001 for all). Patients with both severe itch and pain vs those with only one or neither symptom being severe had significant increases in all these measures.ConclusionSkin pain is a common and burdensome symptom in AD. Skin pain severity should be assessed with itch severity in AD patients and may be an important end point for monitoring treatment response.
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Intraoperative anaphylaxis to bacitracin during scleral buckle surgery
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 6
Author(s): Juline Caraballo, Elaine Binkley, Ian Han, Amy Dowden
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Disrupted circuits in mouse models of autism spectrum disorder and intellectual disability
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Carla EM Golden, Joseph D Buxbaum, Silvia De Rubeis
Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity. Treatments that target the balance between excitation and inhibition in these regions are able to reverse pathological phenotypes, elucidating this deficit as a commonality across models and opening new avenues for intervention.
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Dengue hemorrhagic fever complicated with acute liver failure: a case report
Dengue is a common arboviral infection with a clinically diverse spectrum of presentations. Although hepatic dysfunction is commonly identified in patients will dengue illness, acute liver failure is rare. The...
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Clinical examination and X-ray: an old approach to a current problem
Description
Ingesting a foreign body is not an uncommon occurrence. Most pass through the gastrointestinal tract uneventfully, and perforation is rare.1 The preoperative diagnosis, in these cases, is always very difficult and the radiological examinations are not always able to resolve the diagnostic. The mortality and the morbidity remain still high first of all for the delay in the diagnosis and the advanced age of patients.2
A 50-year-old man without relevant medical history was admitted to the emergency department with 4 days evolution of abdominal pain. The patient presented continuous abdominal pain at the left lower quadrant. There was no nausea, vomiting, alterations of bowel habits or fever.
On examination, the patient was in painful distress. Vital signs revealed tachycardia at 110 bpm, blood pressure of 120/64 mm Hg but no fever (36.8°C). Abdominal examination revealed diffuse tenderness and pain more intense at the left lower abdomen,...
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Necrotising pneumonia caused by non-PVL Staphylococcus aureus with 2-year follow-up
Necrotising pneumonia (NP) is a rare but life-threatening complication of pulmonary infection. It is characterised by progressive necrosis of lung parenchyma with cavitating foci evident upon radiological investigation. This article reports the case of a 52-year-old woman, immunocompetent healthcare professional presenting to Accident and Emergency with NP and Staphylococcus aureus septicaemia. The cavitating lesion was not identified on initial chest X-ray leading to a delay in antimicrobial optimisation. However, the patient went on to achieve a full symptomatic recovery in 1 month and complete radiological recovery at 2-year follow-up. Long-term prognosis for adult cases of NP currently remains undocumented. This case serves as the first piece of published evidence documenting full physiological and radiological recovery following appropriate treatment of NP in an immunocompetent adult patient.
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Interhemispheric subdural and subarachnoid haemorrhage in a patient with amphetamine-induced vasculitis
Description
A 27-year-old woman with a history of pulmonary embolism presented with confusion and depressed arousal after a night of alcohol and drug use. On examination, she was found to have lack of motivation and right leg weakness but had no other significant neurological findings. Trauma survey did not detect any signs of injury. CT scan of the head revealed interhemispheric subdural and subarachnoid haemorrhage with the highest volume in left frontoparietal region (figure 1). Urine toxicology showed presence of tetrahydrocannabinol and amphetamines. CT angiography demonstrated a small, incidental left supraclinoid internal carotid artery aneurysm but no other significant findings (figure 1). MRI was remarkable only for the haemorrhage and MR venogram confirmed patent venous sinuses (figure 1). Given the patient's history of drug use and the presence of amphetamines in her urine, conventional cerebral angiography was obtained to evaluate for vasculopathy. Cerebral...
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Fat embolism: a rare cause of perioperative renal transplant dysfunction
Fat embolism is a recognised complication of bony injury and orthopaedic surgery, commonly involving the long bones and pelvis. We report on the case of a 68-year-old renal transplant recipient who developed acute kidney injury following surgical stabilisation of metastatic carcinoma of the acetabulum and replacement of the proximal femur. A CT renal angiogram demonstrated a large fat embolus in the inferior vena cava (IVC) and left iliac veins below the level of IVC filter, with impaired renal perfusion. The risks of open or endovascular lipothrombectomy were felt to outweigh the potential benefits. The patient was managed with systemic anticoagulation and prepared for transplant failure. Subsequently, there was spontaneous improvement in urine output and 4 months postoperatively her transplant function had returned to her baseline level and this has remained stable at 1 year postsurgery.
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Perineal aggressive angiomyxoma in a menopausal woman
Aggressive angiomyxoma (AA) is an uncommon mesenchymal tumour that is principally located in the soft tissues of the pelvis and perineum of young women. The primary features of this benign tumour are a local invasion, a high local recurrence rate and non-specific local clinical signs. We describe the case of a 58-year-old woman, initially treated for a Bartholin's cyst. Histological examination indicated the presence of an AA. The MRI showed a 7 cm soft tissue mass extending from the lateral wall of the vagina, into the left buttock and down into the subcutaneous tissue. We performed a radical excision with wide resection, which is considered the standard gold treatment.
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An uncommon diagnosis for a recurrent erythematous patch in a paediatric patient
A 14-year-old girl presented with a circular erythematous patch over the left buttock for approximately 10 years, with ongoing ulceration and papules developing over the last 4 years. Punch biopsies were taken within and above the patch for diagnosis. Both revealed marked inflammatory infiltrates with atypical, irregular lymphocytes and increased mitosis. Immunostaining revealed CD8 positivity and a pan T helper cell phenotype. T cell receptor gene rearrangement analysis showed T cell clonality in both biopsies. These findings were consistent with mycosisfungoides and associated lymphomatoid papulosis. Both are rare conditions but have been associated in 5%–20% of cases. A definitive association has not yet been established; however, T cell monoclonality shows 50%–60% share a common origin. Management options are extensive with no one treatment showing superiority. Our patient received low-dose radiotherapy with good outcomes, but subsequently required further radiotherapy.
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Development of forced normalisation psychosis with ethosuximide
A 50-year-old man with known multidrug resistant coexistent focal and generalised epilepsy was commenced on ethosuximide, with normalisation of his electroencephalogram and cessation of absence seizures. Within 3 weeks, he developed a rapidly worsening paranoid psychosis with visual and olfactory hallucinations. A month after the cessation of ethosuximide and concurrent treatment with olanzapine, his psychosis resolved and permitted reinitiation of ethosuximide at a lower dose without recurrence of psychotic symptoms.
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Pleural lipoma clinically mimicking the presentation of superior sulcus tumour upon initial evaluation
Here we present a case of a large pleural lipoma which presented with paresthesias of the hand. This is an unusual presentation of an uncommon tumour.
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Pulmonary embolism caused by thrombin-based haemostatic matrix
Description
A 38-year-old woman underwent an outpatient L5/S1 discectomy. The procedure was complicated by intraoperative bleeding, and haemostasis was achieved using a thrombin-based haemostatic matrix (TBHM). She presented to our facility on postoperative day 5 with left-sided chest pain and dyspnoea. CT pulmonary angiography (CTPA) showed a heterogeneous filling defect with mixed attenuation and a 'pseudoair pattern' in the left main pulmonary artery (figure 1). Duplex ultrasound of the upper and lower extremities was negative for venous thrombus. An echocardiogram was normal. Pulmonary angiography showed occlusion of the basal branches of the left pulmonary artery (figure 2). Therapeutic anticoagulation with unfractionated heparin was started, and the patient was discharged home on warfarin. Repeat CT angiography 6 months later revealed no filling defect in the pulmonary arteries.
Figure 1
CT chest with contrast demonstrating the 'pseudoair' filling defect (arrow) in the left main pulmonary...
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Acute pancreatitis following oesophagogastroduodenoscopy.
Acute pancreatitis is a well-recognised complication of endoscopic procedures like endoscopic retrograde cholangiopancreatography but not oesophagogastroduodenoscopy (OGD). I report a case of a 33-year-old woman, admitted with severe epigastric pain and vomiting 2 hours after an elective OGD for evaluation of chronic gastrointestinal symptoms. Pancreatitis was diagnosed on the basis of elevated lipase (40 790 U/L; normal 11–82) and findings on imaging studies. Other common causes of acute pancreatitis such as gallstones, alcohol and medications were ruled out. She had an extended hospital course because of severe disease, characterised by systemic inflammatory response syndrome, pleural effusion and ascites but was successfully managed conservatively with bowel rest, hydration and pain management. Acute pancreatitis should be considered a rare complication of OGD and should be considered in differential diagnosis for abdominal pain post OGD. Pathogenesis is likely from direct trauma to pancreas or gas insufflation.
http://ift.tt/2BW9Mvp
Hypersomatotropism induced secondary polycythaemia leading to spontaneous pituitary apoplexy resulting in cure of acromegaly and remission of polycythaemia: 'The virtuous circle
A young man with subtle clinical features suggestive of hypersomatotropism presented with acute-onset severe headache. Relevant investigations confirmed polycythaemia and growth hormone (GH)-secreting pituitary macroadenoma with apoplexy. Secondary polycythaemia and myeloproliferative disorders were ruled out. At follow-up after 3 months, resolution of polycythaemia and acromegaly was observed, evident on normal haemoglobin levels, a normocellular marrow, and normal insulin-like growth factor-1 (IGF-1) with glucose-suppressed GH levels. Direct mitogenic properties of GH-IGF-1 axis on bone marrow progenitor cells may very rarely lead to erythroid hyperplasia and subsequent polycythaemia, reversible with successful therapy of acromegaly. In this case, polycythaemia secondary to hypersomatotropism likely resulted in pituitary apoplexy with subsequent remission of both acromegaly and resultant polycythaemia.
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Inguinoscrotal herniation of a caecal adenocarcinoma
An 84-year-old man with multiple comorbidities presented from a residential care home with a 1-month history of asthenia and moderate abdominal pain. On examination, he was found to have an irreducible right-sided inguinoscrotal hernia. Subsequent blood tests revealed a significant anaemia (haemoglobin 48 g/L), for which he was transfused. A CT scan of the abdomen and pelvis revealed a large caecal tumour, herniating through the right inguinal canal into the scrotum. The patient underwent an elective open right hemicolectomy with inguinal hernia defect repair, from which he recovered well. He was discharged from the ward 12 days postoperatively and is awaiting outpatient follow-up.
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Double duodenal perforation following foreign body ingestion
Intentional ingestion of a foreign body in adults is a rare clinical presentation. This case is one of a 27-year-old Sudanese man who presented having swallowed a ballpoint pen intentionally. Clinical examination and plain chest radiograph exhibited no signs indicative of perforation with only a raised C reactive protein identified on blood tests. Subsequent gastroscopy revealed that the pen had simultaneously perforated the duodenum at both D1 and D3 requiring removal via a laparotomy. The patient fully recovered and was discharged 2 weeks postoperatively following psychiatric input.
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Novel use of a trabecular metal spacer in the treatment of a long-standing ulnar fracture non-union
The use of trabecular metal (TM) implants in spine and joint surgery is well documented. However, their use has yet to be reported as an alternative to either allograft or autograft in the management of fracture non-unions. We present our experience in using a TM implant for treating a patient with a long-standing ulnar fracture non-union. Excision of devitalised bone resulted in a 17 mm defect which the TM implant was used to infill. The defect was then bridged with a locking plate. At 2-year clinical and radiographic review, bony union and a pain-free return to full function was noted. In this case, the use of a TM implant avoided the morbidity associated with an iliac crest autograft.
http://ift.tt/2BW9vZp
One long umbilical cord, four nuchal cord loops and a true knot
Description
A 43-year-old woman G4 P2101 at 36 weeks of gestation presented to the labour floor with non-reactive fetal heart tracing and decreased fetal movement. She had a second-trimester ultrasound showing intrauterine growth retardation (IUGR). Patient had a history of hypothyroidism, two fetal demises at term and a planned preterm delivery at 34 weeks of gestation via caesarean section. Workup was negative for thrombophilia (lupus anticoagulant, anticardiolipin, anti-b2-glycoprotein, factor V Leiden, protein S, protein C, G20210 mutation, antithrombin III, antinuclear antibodies) and infectious diseases. Placental pathology following her second fetal demise revealed chorioamnionitis and necrotising funisitis with negative amniotic fluid cultures. There was no information regarding umbilical cord (UC) length or entanglements in previous pregnancies.
Given her history and the current non-reactive fetal heart tracing, the patient was taken for emergency caesarean delivery. A female infant was born with four loops of nuchal cord and a true knot (
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Catastrophic catheter-induced coronary artery vasospasm successfully rescued using intravascular ultrasound imaging guidance
A 46-year-old man underwent coronary angiography for stable angina. He developed inferior ST-segment myocardial infarction during the angiography. Intravascular ultrasound (IVUS) findings suggested coronary vasospasm. Intracoronary administration of isosorbide dinitrate restored the coronary flow. This case illustrates the essential role IVUS imaging played in establishing the diagnosis of catheter-induced coronary vasospasm.
http://ift.tt/2BUqNWR
Treating patients with brain metastases has evolved: scalp-sparing, hippocampal avoidance whole brain radiotherapy with simultaneous integrated boost
Description
A 43-year-old male with a history of receiving treatment for squamous cell carcinoma (SqCC) of lung 2 years back presented with a complaint of a single episode of self-resolving generalised tonic–clonic seizure 1 day prior. General physical and neurological examinations were unremarkable. An MRI of the brain revealed a well-defined, enhancing, space-occupying lesion (SOL) in the right temporal lobe (figure 1). He was started on oral dexamethasone, oral phenytoin (after an intravenous loading dose) and underwent a whole body 18flourodeoxyglucose positron emission tomography CT (18FDG PET-CT), which revealed increased FDG uptake in the SOL without evidence of metastatic disease elsewhere (figure 1). A diagnosis of oligometastatic SqCC lung (cTx, cNx and cM1b) was made, and the options for management were discussed with the patient.
Figure 1
Pretreatment MRI and positron emission tomography CT (PET-CT) images. (A) T1-weighted contrast-enhanced axial image reveals a well-defined space occupying lesion in...
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Lingual dyskinesia in hyperthyroidism
Description
A 28-year-old female presented to the hospital with a 3-month history of palpitation, weight loss and neck swelling. On examination, she had diffuse soft goitre, warm extremities and fine tremors of hands. In addition, she had an irregular jerky lingual and lip movements suggestive of dyskinesia (see online ). There were no signs of infiltrative ophthalmopathy or dermopathy. Neurological examination was otherwise unremarkable. A clinical diagnosis of Graves' disease was made that was biochemically confirmed by elevated T3 and T4 with suppressed tyroid stimulating hormone (TSH) as well as diffuse increased uptake of technetium in nuclear imaging. Unlike lingual tremors associated with other neurological conditions or adverse effects of drugs, thyrotoxicosis-associated lingual dyskinesia responds very well to beta blockers.1 After 6 months of follow-up on carbimazole and propranolol therapy, her thyrotoxicosis improved, and the abnormal tongue movements had disappeared.
Learning points
Thyrotoxicosis...
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Parental perceptions, attitudes and acceptance of childhood immunization in Saudi Arabia: A cross sectional study
Source:Vaccine, Volume 36, Issue 1
Author(s): Thamir M. Alshammari, Gehad M. Subaiea, Talib Hussain, Afrasim Moin, Kazeem B. Yusuff
ObjectivesThe widespread availability and use of vaccines have tremendously reduced morbidity, mortality and health care costs associated with infectious diseases. However, parental beliefs about vaccination are one of the major factors in achieving high vaccination rates. Thus, this study aims to assess the perceptions and attitudes regarding routine childhood immunization among Saudi parents.MethodsA cross sectional study with a pre-tested 18-item questionnaire was conducted using 467 randomly selected parents from the Hail region of Saudi Arabia in the period between February 1st, 2016, and February 1st, 2017. The validated questionnaire consisted of three sections that collected information on participants' demographics, parents' awareness of vaccine benefits, and parents' practices regarding the immunization of their children.ResultsFemale and male parents comprised 54.5% (255) and 45.5% (212) of the sample, respectively, and the response and completion rates were 97%. The majority of the respondents had received a formal education (94.1%, 439), were gainfully employed (62.9%, 294) and had a regular monthly income (73.3%). The majority of the respondents were aware of childhood vaccinations (78.9%), completed vaccinations mandated for children up to 5 years (86.2%), encouraged other parents to do so (89.9%), and had easy access to vaccines (90.5%). Sixty to ninety percent of the respondents were knowledgeable regarding the health benefits of vaccinations in children, even though 18.4% of their children had experienced vaccination-related minor adverse effects during or after vaccination of which 23.2% required doctor's visits. Health care professionals were the most frequent source of parents' vaccine-related information (65.2%), and vaccination reminder services provided by the Ministry of Health (MOH) via mobile phones were cited by 57.5% of respondents.ConclusionsConfidence in and acceptance of childhood vaccinations, perceptions of vaccine-related health benefits and ease of access to immunizations appeared to be quite good among Saudi parents.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 36, Issue 1
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Assessing the safety of hepatitis B vaccination during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 1990–2016
Source:Vaccine, Volume 36, Issue 1
Author(s): Pedro L. Moro, Yenlik Zheteyeva, Faith Barash, Paige Lewis, Maria Cano
BackgroundThe safety of hepatitis B vaccination during pregnancy has not been well studied.ObjectiveWe characterized adverse events (AEs) after hepatitis B vaccination of pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.MethodsWe searched VAERS for AEs reports involving pregnant women who received hepatitis B vaccine from January 1, 1990–June 30, 2016. All reports and available medical records were reviewed by physicians. Observed AEs were compared to expected AEs and known rates of pregnancy outcomes to assess for any unexpected safety concern.ResultsWe found 192 reports involving pregnant women following hepatitis B vaccination of which 110 (57.3%) described AEs; 12 (6.3%) were classified as serious; one newborn death was identified in a severely premature delivery, and there were no maternal deaths. Eighty-two (42.7%) reports did not describe any AEs. Among pregnancies for which gestational age was reported, most women were vaccinated during the first trimester, 86/115 (74.7%). Among reports describing an AE, the most common pregnancy-specific outcomes included spontaneous abortion in 23 reports, preterm delivery in 7 reports, and elective termination in 5 reports. The most common non-pregnancy specific outcomes were general disorders and administration site conditions, such as injection site and systemic reactions, in 21 reports. Among 22 reports describing an AE among infants born to women vaccinated during pregnancy, 5 described major birth defects each affecting different organ systems.ConclusionOur analysis of VAERS reports involving hepatitis B vaccination during pregnancy did not identify any new or unexpected safety concerns.
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Designing an immunocyte-targeting delivery system by use of beta-glucan
Source:Vaccine, Volume 36, Issue 1
Author(s): Noriko Miyamoto, Shinichi Mochizuki, Kazuo Sakurai
A β-1,3-d-glucan called Schizophyllan (SPG) can form a novel complex with homo oligodeoxynucleotides (ODNs) via the combination of hydrogen bonding and hydrophobic interactions. Dectin-1 is a major receptor involved in the recognition of β-1,3-d-glucans and expressed on antigen presenting cells (APCs) including macrophages, dendritic cells, monocytes, neutrophils, and a subset of T cells. Therefore, the SPG/ODN complex can be used as APCs cell-specific delivery of functional ODNs including unmethylated CpG sequences (CpG-ODNs). In fact, CpG-ODN/SPG complex induced high antibody titers when it was administered to cynomolgus monkeys as adjutant of influenza vaccine. These results indicate that SPG can be an excellent immunocyte-targeting drug delivery system.
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Immunization effects of a communication intervention to promote preteen HPV vaccination in primary care practices
Source:Vaccine, Volume 36, Issue 1
Author(s): Joan R. Cates, Jamie L. Crandell, Sandra J. Diehl, Tamera Coyne-Beasley
ObjectivesHPV vaccination at the recommended ages of 11–12 is highly effective yet has stalled well below the goal of 80% of the population. We evaluated a statewide practice-based communication intervention (tools: brochures, posters, online training for providers and resources for parents, video game for preteens) to persuade parents, preteens and providers to vaccinate against HPV. The 9-month intervention started May 1, 2015.MethodsWe compared vaccine initiation and completion rates over three 9-month periods (baseline, intervention, post-intervention) between practices enrolled in the intervention and a comparable comparison group. All practices reported to the North Carolina Immunization Registry (NCIR) and had at least 100 11- and 12-year-olds who had not completed the HPV vaccine series. Of 175 eligible practices, the 14 intervention practices included 19,398 individuals and the 161 comparison practices included 127,896 individuals. An extended Cox model was used to test the intervention effect.ResultsThe intervention had a significant effect on both initiation and completion during the intervention and post-intervention periods; the estimated hazard ratio (HR) for initiation was 1.17 (p = .004) during the intervention and 1.11 (p = .005) post-intervention. Likewise, completion during the intervention period was 17% higher in intervention practices, after controlling for baseline differences. This effect increased in the post-intervention period to 30% higher (p = .03).ConclusionsIndividuals in the intervention practices were 17% more likely to initiate and complete HPV vaccination than in the comparison practices during the intervention period and the effect was sustained post-intervention. This intervention is promising for increasing rates of HPV vaccination at ages 11–12.
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Association of prior HPV vaccination with reduced preterm birth: A population based study
Source:Vaccine, Volume 36, Issue 1
Author(s): Beverley Lawton, Anna S. Howe, Nikki Turner, Sara Filoche, Tania Slatter, Celia Devenish, Noelyn Anne Hung
BackgroundEmerging evidence suggests that HPV infection is associated with negative pregnancy outcomes such as preterm birth (PTB), and pre-eclampsia. We aimed to determine if prior HPV vaccination reduced adverse pregnancy outcomes.MethodsA New Zealand population-based retrospective study linking first pregnancy outcome data (2008–2014 n = 35,646) with prior quadrivalent HPV vaccination status. Primary outcomes were likelihood (odds ratios, ORs) of PTB, pre-eclampsia, and stillbirth. Exposure groups were based on HPV vaccination. Adjusted ORs were calculated for each outcome, controlling for mother's age at delivery, ethnicity, socioeconomic status, health board region at time of delivery, and body mass index and smoking status at time of registration with maternity care provider.ResultsMother's mean age at delivery was 19 (SD 2.1) years. Of 34,994 the pregnancies included in the final study analyses 62.3% of women were unvaccinated, 11.0% vaccinated with one or two doses and 27.7% vaccinated with three doses prior to pregnancy. PTB (OR: 0.87; CI 0.78, 0.96)) was significantly lower for women who previously received the HPV vaccine. A dose response effect was found with each successive dose received decreasing the likelihood of PTB. No associations between the vaccinated and unvaccinated groups were shown for pre-eclampsia or stillbirth.ConclusionsPrior receipt of the quadrivalent HPV vaccine was associated with a significant reduction in PTB (13%); suggesting that HPV vaccination may be effective in reducing PTB. The potential global public health impact is considerable and there is urgency to undertake further research to replicate and explore these findings.
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The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review
Source:Vaccine, Volume 36, Issue 1
Author(s): Ryan E. Malosh, Emily T. Martin, Justin R. Ortiz, Arnold S. Monto
BackgroundLower respiratory tract infections (LRTI) are a major cause of morbidity and mortality worldwide, particularly in young children and older adults. Influenza is known to cause severe disease but the risk of developing LRTI following influenza virus infection in various populations has not been systematically reviewed. Such data are important for estimating the impact specific influenza vaccine programs would have on LRTI outcomes in a community. We sought to review the published literature to determine the risk of developing LRTI following an influenza virus infection in individuals of any age.Methods and findingsWe conducted a systematic review to identify prospective studies that estimated the incidence of LRTI following laboratory-confirmed influenza virus infection. We searched PubMed, Medline, and Embase databases for relevant literature. We supplemented this search with a narrative review of influenza and LRTI. The systematic review identified two prospective studies that both followed children less than 5 years. We also identified one additional pediatric study from our narrative review meeting the study inclusion criteria. Finally, we summarized recent case-control studies on the etiology of pneumonia in both adults and children.ConclusionsThere is a dearth of prospective studies evaluating the risk of developing LRTI following influenza virus infection. Determining the burden of severe LRTI that is attributable to influenza is necessary to estimate the benefits of influenza vaccine on this important public health outcome. Vaccine probe studies are an efficient way to evaluate these questions and should be encouraged going forward.
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Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study
Source:Vaccine, Volume 36, Issue 1
Author(s): Himal Lal, Airi Poder, Laura Campora, Brecht Geeraerts, Lidia Oostvogels, Carline Vanden Abeele, Thomas C. Heineman
BackgroundIn phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months.MethodsIn this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2.Results346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination.ConclusionsImmune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals.Clinical Trials Registration: Clinicaltrials.gov (NCT01751165).
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U.S. pregnant women’s knowledge and attitudes about behavioral strategies and vaccines to prevent Zika acquisition
Source:Vaccine, Volume 36, Issue 1
Author(s): Lauren Dapena Fraiz, Ariel de Roche, Christine Mauro, Marina Catallozzi, Gregory D. Zimet, Gilla K. Shapiro, Susan L. Rosenthal
IntroductionZika virus infection during pregnancy can cause significant infant morbidity. Little is known about pregnant women's attitudes regarding behavioral strategies and hypothetical vaccination to prevent Zika infections and sequelae.MethodsPregnant women across the United States (N = 362) completed an online questionnaire regarding attitudes about Zika, including six behavioral prevention strategies (i.e., abstaining from sex, using condoms, not traveling to an area with Zika, their partner not traveling into an area with Zika, using mosquito repellant, wearing long pants and sleeves) and vaccination.ResultsMost women (91%) were married/living with the baby's father, 65% were non-Hispanic White, and 71% had been pregnant. Seventy-four percent were worried about Zika, while 30% thought they were knowledgeable about Zika. The mean knowledge score was 5.0 out of 8 (SD = 2.09), and the mean behavioral strategies score was 4.9 out of 12 (SD = 3.7) with a range of 0 (none would be hard to do) to 12 (all would be hard to do). In a multivariable model, having had a sexually transmitted infection, living/traveling in an area with Zika, and worrying about Zika were significantly related to reporting behavioral strategies as hard to do. Seventy-two percent would be willing to be vaccinated. In the multivariable model, living/traveling in an area with Zika, believing they knew a lot about Zika, worrying about Zika, and considering Zika vaccine development as important were significantly associated with willingness to get vaccinated.ConclusionsPregnant women were worried about Zika, yet had gaps in their factual knowledge. Most women reported they would get vaccinated if a vaccine was available. Pregnant women who reported themselves as vulnerable (being worried, having lived in or traveled to a Zika area) were more likely to view behavioral strategies as hard to do and to accept vaccination.
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Comparison of transcanal endoscopic tympanoplasty with sterile acellular dermal allograft to conventional endaural microscopic tympanoplasty with tragal perichondrium
Source:American Journal of Otolaryngology
Author(s): Jia Min, Se-Hyung Kim
ObjectivesThis study aimed to compare the outcome of endoscopic tympanoplasty with sterile acellular dermal allograft (ADA) and conventional endaural microscopic tympanoplasty with tragal perichondrium.MethodsThis was a retrospective comparative study of 53 patients (25 males and 28 females) with tympanic membrane perforation who underwent type I tympanoplasty in the department of otorhinolaryngology at a tertiary medical center from March 2011 to April 2017. The subjects were classified into two groups; transcanal endoscopic tympanoplasty with ADA (TET, n=26), conventional endaural microscopic tympanoplasty with autologous tragal perichondrium (EMT, n=27). Demographic data, perforation size of tympanic membrane at preoperative state, pure tone audiometric results preoperatively and 3months postoperatively, operation time, sequential postoperative pain scale, and postoperative graft failure rate were evaluated.ResultsThe perforation size of the tympanic membrane in TET and EMT group was 22.3±10.9% and 23.5±9.7%, respectively (P=0.143). Mean operation time of EMT (92.3±16.5min) was longer than that of the TET (65.3±20.5min) with a statistical significance (P=0.004). Graft success rate in the TET and EMT group were 92.3% and 96.3%, respectively; the values were not significantly different (P=0.610). Pre- and postoperative audiometric results including bone and air conduction thresholds and air-bone gap were not significantly different between the groups. In all groups, the postoperative air-bone gap was significantly improved compared to the preoperative air-bone gap. Pain in the immediate postoperative and day 1 after surgery were significantly less in the TET group.ConclusionWith human cadaveric ADA, minimal invasive endoscopic tympanoplasty can be achieved with similar postoperative results and less pain.
http://ift.tt/2BghseI
Is an endoscopic or a microscopic approach optimal for management of attic cholesteatoma?
Source:American Journal of Otolaryngology
Author(s): Zhengcai-LouZihan-LouZhenqi-Gong
http://ift.tt/2AluTd9
Calcification of Thoracic and Abdominal Aneurysms is Associated with Mortality and Morbidity
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Mohammed M. Chowdhury, Lukasz P. Zieliński, James J. Sun, Simon Lambracos, Jonathan R. Boyle, Seamus C. Harrison, James H.F. Rudd, Patrick A. Coughlin
IntroductionCardiovascular events are common in people with aortic aneurysms. Arterial calcification is a recognised predictor of cardiovascular outcomes in coronary artery disease. Whether calcification within abdominal and thoracic aneurysm walls is correlated with poor cardiovascular outcomes is not known.Patients and methodsCalcium scores were derived from computed tomography (CT) scans of consecutive patients with either infrarenal (AAA) or descending thoracic aneurysms (TAA) using the modified Agatston score. The primary outcome was subsequent all cause mortality during follow-up. Secondary outcomes were cardiovascular mortality and morbidity.ResultsA total of 319 patients (123 TAA and 196 AAA; median age 77 [71–84] years, 72% male) were included with a median follow-up of 30 months. The primary outcome occurred in 120 (37.6%) patients. In the abdominal aortic aneurysm group, the calcium score was significantly related to both all cause mortality and cardiac mortality (odds ratios (OR) of 2.246 (95% CI 1.591–9.476; p < 0.001) and 1.321 (1.076–2.762; p = 0.003)) respectively. In the thoracic aneurysm group, calcium score was significantly related to all cause mortality (OR 6.444; 95% CI 2.574–6.137; p < 0.001), cardiac mortality (OR 3.456; 95% CI 1.765–4.654; p = 0.042) and cardiac morbidity (OR 2.128; 95% CI 1.973–4.342; p = 0.002).ConclusionsAortic aneurysm calcification, in either the thoracic or the abdominal territory, is significantly associated with both higher overall and cardiovascular mortality. Calcium scoring, rapidly derived from routine CT scans, may help identify high risk patients for treatment to reduce risk.
http://ift.tt/2nIyeNF
Re: “Catheter Foam Sclerotherapy of Great Saphenous Vein, with Peri-saphenous Tumescence Infiltration and Saphenous Irrigation”
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Cavezzi, G. Mosti, F. Campana, L. Tessari, L. Bastiani, S.U. Urso
http://ift.tt/2A4zLiR
A Rare Cause of Critical Limb Ischaemia: An Aneurysmal Persistent Sciatic Artery
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Gabriele Pagliariccio, Luciano Carbonari
http://ift.tt/2nIyegD
Late Open Surgical Conversion after Endovascular Abdominal Aortic Aneurysm Repair
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Vinay Kansal, Sudhir Nagpal, Prasad Jetty
IntroductionLate open surgical conversion following endovascular aneurysm repair (EVAR) may occur more frequently after performing EVAR in anatomy outside the instructions for use (IFU). This study reviews predictors and outcomes of late open surgical conversion for failed EVAR.MethodsThis retrospective cohort study reviewed all EVARs performed at the Ottawa Hospital between January 1999 and May 2015. Open surgical conversions >1 month post EVAR were identified. Variables analysed included indication for conversion, pre-intervention AAA anatomy, endovascular device and configuration, operative technique, re-interventions, complications, and death.ResultsOf 1060 consecutive EVARs performed, 16 required late open surgical conversion. Endografts implanted were Medtronic Talent (8.50.0%), Medtronic Endurant (3.18.8%), Cook Zenith (4.25.0%), and Terumo Anaconda (1.6.2%). Eleven grafts were bifurcated (68.8%), five were aorto-uni-iliac (31.2%). The median time to open surgical conversion was 3.1 (IQR 1.0–5.2) years. There was no significant difference in pre-EVAR rupture status (1.4% elective, 2.1% ruptured, p = .54). Indications for conversion included: Type 1 endoleak with sac expansion (n = 4, 25.0%), Type 2 endoleak with expansion (n = 2, 12.5%), migration (n = 3, 18.8%), sac expansion without endoleak (n = 2, 12.5%), graft infection (n = 3, 18.8%), rupture (n = 2, 12.5%). Nine patients (56.2%) underwent stent graft explantation with in situ surgical graft reconstruction, seven had endograft preserving open surgical intervention. The 30 day mortality was 18.8% (n = 3, all of whom having had endograft preservation). Ten patients (62.5%) suffered major in hospital complications. One patient (6.5%) required post-conversion major surgical re-intervention. IFU adherence during initial EVAR was 43.8%, versus 79.0% (p < .01) among uncomplicated EVARs.ConclusionsOpen surgical conversion following EVAR results in significant morbidity and mortality. IFU adherence of EVARs later requiring open surgical conversion is markedly low. More data are required to elucidate the impact of increasing liberalisation of EVAR outside of IFU.
http://ift.tt/2A1Wzj6
Exendin-4 partly ameliorates of hyperglycemia-mediated tissue damage in lungs of streptozotocin-induced diabetic mice
Publication date: Available online 7 December 2017
Source:Peptides
Author(s): Fusun Oztay, Serap Sancar Bas, Selda Gezginci-Oktayoglu, Merve Ercin, Sehnaz Bolkent
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, and plays anti-inflammatory role in atherosclerosis, and has surfactant-releasing effects in lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin-4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin-4 and STZ. Exendin-4 (3μg/kg) was administered daily by subcutaneous injection for 30days after mice were rendered diabetic with a single dose of STZ (200mg/kg). Structural alterations, oxidative stress, apoptosis, insulin signaling and expressions of prosurfactant-C, alpha-smooth muscle actin, collagen-I and fibronectin were evaluated in lung tissue. Diabetic mice lungs were characterized by induced oxidative stress, apoptosis, edema, and cell proliferation. They had honeycomb-like alveoli, thick alveolar walls, and hypertrophic pneumocytes. Although exendin-4 treatment improved pulmonary edema, apoptosis, oxidative stress, and lung injury, it led to the disrupted insulin signaling and interstitial collagen accumulation in the lungs of diabetic mice. Exendin-4 reduced hyperglycemia-mediated lung damage by reducing glucose, and oxidative stress and stimulating cell proliferation. However, exendin-4 led to increased risk by reducing insulin signaling in the lungs and collagen accumulation around pulmonary vasculature in diabetic mice.
Graphical abstract
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Can breast cancer patients with HER2 dual-equivocal tumours be managed as HER2-negative disease?
Source:European Journal of Cancer, Volume 89
Author(s): Yiwei Tong, Xiaosong Chen, Xiaochun Fei, Lin Lin, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen
BackgroundIncreasing human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual-equivocal breast tumours are reported after the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of this study is to investigate the clinico-pathologic characteristics, treatment patterns and disease outcome of these patients with HER2 dual-equivocal tumours.Patients and methodsPatients with HER2 IHC 2+ and available FISH results were retrospectively analysed from the Comprehensive Breast Health Center, Shanghai Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive, dual-equivocal and -negative groups. Patient characteristics, systemic treatment patterns and survival were compared among these groups. Reverse transcriptase-polymerase chain reaction-based assays were applied to test HER2 mRNA expression level.ResultsAmong 691 patients included, 133 (19.25%) were HER2 positive, 25 (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate and multivariate analyses stated that HER2 dual-equivocal tumours shared more similarity with HER2-negative tumours, whereas HER2-positive tumours had rather different clinico-pathologic features. HER2 dual-equivocal tumours had similar HER2 mRNA levels compared with HER2-negative tumours (P = 0.26), which were much less compared with HER2-positive breast cancer. Besides, adjuvant systemic treatment patterns were comparable between HER2-negative and dual-equivocal tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment. There was no survival difference among these three groups (P = 0.43).ConclusionHER2 dual-equivocal tumours share more similarity with HER2-negative disease in terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic treatment patterns and disease outcome, which deserves further clinical evaluation.
http://ift.tt/2AF2Diy
Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer
Source:European Journal of Cancer, Volume 89
Author(s): Andreas Schneeweiss, Stephen Chia, Tamas Hickish, Vernon Harvey, Alexandru Eniu, Maeve Waldron-Lynch, Jennifer Eng-Wong, Sarah Kirk, Javier Cortés
BackgroundWe report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy.MethodsDescriptive efficacy analyses were conducted in patients randomised to group A (cycles 1–6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1–3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4–6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1–3: FEC, cycles 4–6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1–6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989.ResultsThree-year Kaplan–Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79–95), 88% (80–96) and 90% (82–97) in groups A–C, respectively. Progression-free survival (PFS) rates were 89% (81–96), 89% (81–96) and 87% (80–95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11–0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A–C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%.ConclusionsLong-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.
http://ift.tt/2B19G8c
Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma
Source:European Journal of Cancer, Volume 89
Author(s): Maeve A. Lowery, David P. Kelsen, Marinela Capanu, Sloane C. Smith, Jonathan W. Lee, Zsofia K. Stadler, Malcolm J. Moore, Hedy L. Kindler, Talia Golan, Amiel Segal, Hannah Maynard, Ellen Hollywood, MaryEllen Moynahan, Erin E. Salo-Mullen, Richard Kinh Gian Do, Alice P. Chen, Kenneth H. Yu, Laura H. Tang, Eileen M. O'Reilly
PurposeBRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC).MethodsPatients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1–2 lines of treatment, Eastern Cooperative Oncology Group 0–2, were enrolled. Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400 mg twice-daily (N = 15) days 1–28. The primary end-point was to determine the response rate of veliparib; secondary end-points included progression-free survival (PFS), duration of response, overall survival (OS) and safety.ResultsSixteen patients were enrolled; male N = 8 (50%). Median age was 52 years (range 43–77). Five (31%) had a BRCA1 and 11 (69%) had a BRCA2 mutation. Fourteen (88%) patients had received prior platinum-based therapy. No confirmed partial responses (PRs) were seen: one (6%) unconfirmed PR was observed at 4 months with disease progression (PD) at 6 months; four (25%) had stable disease (SD), whereas 11 (69%) had PD as best response including one with clinical PD. Median PFS was 1.7 months (95% confidence interval [CI] 1.57–1.83) and median OS was 3.1 months (95% CI 1.9–4.1). Six (38%) patients had grade III toxicity, including fatigue (N = 3), haematology (N = 2) and nausea (N = 1).ConclusionsVeliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ≥ 4 months. Additional strategies in this population are needed, and ongoing trials are evaluating PARPis combined with chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195).
http://ift.tt/2AECyjQ
Enlisting the willing: A study of healthcare professional–initiated and opt-in biobanking consent reveals improvement opportunities throughout the registration process
Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Elizabeth A. Fradgley, Shu Er Chong, Martine E. Cox, Christine L. Paul, Craig Gedye
Biobanking consent processes should accord with patients' preferences and be offered in a consistent and systematic manner. However, these aims can be difficult to achieve under healthcare professionals' (HCPs) time-constrained workflows, resulting in low participation rates.This current perspective provides a brief overview of HCP involvement in consent and reports new data on participant attrition at each step of the biobanking consent process as experienced by 113 patients at an Australian tertiary cancer centre. To determine attrition in this HCP-driven consent process, we reviewed medical records for the following events: inclusion of biobanking consent forms; visible patient and HCP signatures; consent status selected (decline or accept) and specimen registration with local biobank. Accessible medical records revealed the following data: 75 of 85 records included viewable forms; 22 of 85 records included patient and 19 of 85 included HCP signatures; 15 of 85 records included signed and completed forms and 3 of 85 had samples banked with annotated clinical data. We compared these data with self-reported experiences of being approached to participate by HCPs. Of the 15 participants (17.6%) who successfully completed consent, only five could recall being asked and providing consent.The low enrolment rate is a considerable lost opportunity because most patients (59%) who were not asked to participate indicated they would have consented if asked. Furthermore, in comparing self-reported experiences with medical records, we believe cancer patients' preferences for participation are mismatched with actual biobanking enrolment, which has considerable attrition at each step in the consent process.
http://ift.tt/2B1VVG2
Are pathological high-risk features in locally advanced rectal cancer a useful selection tool for adjuvant chemotherapy?
Source:European Journal of Cancer, Volume 89
Author(s): Marloes Swets, Peter J.K. Kuppen, Erik J. Blok, Hans Gelderblom, Cornelis J.H. van de Velde, Iris D. Nagtegaal
BackgroundSeveral histological high-risk factors are used as an indication for adjuvant therapy in stage II colon cancer. Those and other factors, including lymphatic invasion, perineural invasion (PNI), venous invasion and tumour budding are associated with decreased outcome. In this study, we evaluated the prognostic and predictive values of these biomarkers in a cohort of rectal cancer patients.Materials and methodsThe trial-based cohort consisted of 221npTNM stage II–III rectal cancer patients, included in the PROCTOR/SCRIPT trial, a multicentre randomised phase III trial. Patients treated with neoadjuvant radiotherapy and TME surgery were randomised between adjuvant chemotherapy or observation. Lymphatic invasion, PNI, extramural venous invasion, intramural venous invasion and tumour budding were determined in standard tissue slides.ResultsThe presence of PNI (HR 3.36; 95% CI 1.82–6.21), extramural vascular invasion (HR 1.93; 95% CI 1.17–3.19) and tumour budding (HR 1.83, 95% CI 1.11–3.03) was associated with a significant worse overall survival. The presence of ≥2 adverse biomarkers resulted in a stronger prediction of adverse outcome in terms of overall survival (HR 2.82; 95% CI 1.66–4.79), disease-free survival (HR 2.27; 95% CI 1.47–3.48), and distant recurrence (HR 2.51; 95% CI 1.56–4.02). None of these markers alone or combined predicted a beneficial effect of adjuvant chemotherapy.DiscussionWe confirmed that several stage-independent biomarkers were significantly associated with a decreased outcome in rectal cancer patients. More importantly, these markers did not have predictive value and are thus not useful to select for adjuvant therapy in rectal cancer.
http://ift.tt/2AF2xYe
Reviewers 2017
Source:European Journal of Cancer
http://ift.tt/2B1AmWg
Eighth American Joint Committee on Cancer (AJCC) melanoma classification: Let us reconsider stage III
Source:European Journal of Cancer
Author(s): Jean Jacques Grob, Dirk Schadendorf, Paul Lorigan, Paolo Ascierto, James Larkin, Paul Nathan, Caroline Robert, Axel Hauschild, Jeffrey Weber, Adil Daud, Omid Hamid, Reinhard Dummer, Johan Hansson, Christoph Hoeller, Jacob Schachter, Alexander C.J. Van Akkooi, Claus Garbe
http://ift.tt/2AF2taW
CO2: Editorial Board/Subscription info.
Source:Progress in Neurobiology, Volume 159
http://ift.tt/2k8jPFy
Light-focusing human micro-lenses derived from zebrafish-like lens cell masses model lens development and drug-induced cataract in vitro [RESEARCH ARTICLE]
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening, and for clinically-relevant toxicity assays.
http://ift.tt/2AF1Ii6
Pollen differentiation as well as pollen tube guidance and discharge are independent of the presence of gametes [RESEARCH ARTICLE]
After meiosis, an unequal cell division generates the male gamete lineage in flowering plants. The generative cell will undergo a second division, giving rise to the two gametes, i.e. the sperm cells. The other cell will develop into the vegetative cell that plays a crucial role in pollen tube formation and sperm delivery. Recently, the vegetative cell has been implicated to be important for programming of the chromatin state in sperm cells and/or the resulting fertilization products. Blocking the initial unequal division genetically, we first highlight that the default differentiation state after male meiosis is a vegetative fate consistent with earlier work. We find that uni-nucleated mutant microspores differentiated as wildtype vegetative cells, including chromatin remodeling and the transcriptional activation of transposable elements. Moreover, live cell imaging revealed that this vegetative cell is sufficient for the correct guidance of the pollen tube to the female gametes. Hence, we conclude that vegetative cell differentiation and function does not depend on the formation or presence of the actual gametes but rather on external signals or a cell autonomous pace keeper.
http://ift.tt/2AZuxZd
ERECTA-family genes coordinate stem cell functions between the epidermal and internal layers of the shoot apical meristem [RESEARCH ARTICLE]
The epidermal cell layer and the tissues that lie underneath have different intrinsic functions during plant development. The stem cells within the shoot apical meristem (SAM) that give rise to aerial structures are located in the epidermal and internal tissue layers. However, our understanding of how the functions of these stem cells are coordinated across tissue layers so stem cells can behave as a single population remains limited. WUSCHEL (WUS) functions as a master regulator of stem cell activity. Here we show that loss of function in the ERECTA (ER)-family receptor kinase genes can rescue the mutant phenotype of wus plants (loss of stem cells), as demonstrated by the reinstated expression of a stem cell marker gene in the SAM epidermis. Localized ER expression in the epidermis can suppress the er-family SAM phenotype. Furthermore, the CLAVATA3- and cytokinin-induced outputs, which contribute to stem cell homeostasis, are dysfunctional in a tissue layer-specific manner in er-family mutants. Collectively, our findings suggest that the ER family plays a role in the coordination of stem cell behavior between different SAM tissue layers.
http://ift.tt/2AEAHLU
Wnt inhibition promotes vascular specification of embryonic cardiac progenitors [RESEARCH ARTICLE]
Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis (Naito et al., 2006; Qyang et al., 2007) and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSC) (Elliott et al., 2011; Iyer et al., 2016; Lian et al., 2012; Paige et al., 2010; Willems et al., 2011; Witty et al., 2014), however, few studies have investigated the role of Wnt signaling in specification of cardiac progenitor cells (CPC) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (EC) that originated from CPCs expressing Nkx2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to play an inhibitory role on Wnt during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs.
http://ift.tt/2B1zTmY
Mapping the distribution of stem/progenitor cells across the middle ear during homeostasis and inflammation [RESEARCH ARTICLE]
The middle ear epithelium is derived from neural crest and endoderm, which line distinct regions of the middle ear cavity. Here we investigate the distribution of putative stem cell markers in the middle ear combined with an analysis of the location of label retaining cells (LRCs) to create a map of the middle ear mucosa. We show that proliferating cells and LRCs were associated with specific regions of the ear epithelium, concentrated in the hypotympanum at the base of the auditory bulla and around the ear drum. Sox2 was widely expressed in the endodermally-derived ciliated pseudostratified epithelium of the hypotympanum. This part of the middle ear showed high levels of Wnt activity, as indicated by the expression of Axin 2, a readout of Wnt signaling. Keratin 5 showed a more restricted expression within the basal cells of this region, with very little overlap between the Sox2 and Keratin 5 positive epithelium, indicating that these genes mark distinct populations. Little expression of Sox2 or Keratin 5 was observed in the neural crest-derived middle ear epithelium that lined the promontory, except in cases of otitis media when this epithelium underwent hyperplasia. This study lays the foundation for further understanding of homeostasis and repair in the middle ear.
http://ift.tt/2AEE0T9
Cellular basis of brain maturation and acquisition of complex behaviors in salamanders [RESEARCH ARTICLE]
The overall bauplan of the tetrapod brain is highly conserved, yet significant variations exist among species in terms of brain size, structural composition and cellular diversity. Understanding processes underlying neural and behavioral development in a wide range of species is important both from an evolutionary developmental perspective as well as for the identification of cell sources with post-developmental neurogenic potential. Here we characterize germinal processes in the brain of Notophthalmus viridescens and Pleurodeles waltl during both development and adulthood. Using a combination of cell tracking tools, including clonal analyses in new transgenic salamander lines we examine the origin of neural stem and progenitor cells found in the adult brain, determine regional variability in cell cycle length of progenitor cells, and show spatio-temporally orchestrated neurogenesis. We analyze how maturation of different brain regions and neuronal subpopulations are linked to the acquisition of complex behaviors, and how these behaviors are altered upon chemical ablation of dopamine neurons. Our data analyzed from an evolutionary perspective reveal both common and species-specific processes in tetrapod brain formation and function.
http://ift.tt/2AZq7Si