Head and Neck Diseases by Alexandros G.Sfakianakis: 01/29/16

Παρασκευή 29 Ιανουαρίου 2016

IJMS, Vol. 17, Pages 184: Enhancement of Alkaline Protease Activity and Stability via Covalent Immobilization onto Hollow Core-Mesoporous Shell Silica Nanospheres

The stability and reusability of soluble enzymes are of major concerns, which limit their industrial applications. Herein, alkaline protease from Bacillus sp. NPST-AK15 was immobilized onto hollow core-mesoporous shell silica (HCMSS) nanospheres. Subsequently, the properties of immobilized proteases were evaluated. Non-, ethane- and amino-functionalized HCMSS nanospheres were synthesized and characterized. NPST-AK15 was immobilized onto the synthesized nano-supports by physical and covalent immobilization approaches. However, protease immobilization by covalent attachment onto the activated HCMSS–NH2 nanospheres showed highest immobilization yield (75.6%) and loading capacity (88.1 μg protein/mg carrier) and was applied in the further studies. In comparison to free enzyme, the covalently immobilized protease exhibited a slight shift in the optimal pH from 10.5 to 11.0, respectively. The optimum temperature for catalytic activity of both free and immobilized enzyme was seen at 60 °C. However, while the free enzyme was completely inactivated when treated at 60 °C for 1 h the immobilized enzyme still retained 63.6% of its initial activity. The immobilized protease showed higher Vmax, kcat and kcat/Km, than soluble enzyme by 1.6-, 1.6- and 2.4-fold, respectively. In addition, the immobilized protease affinity to the substrate increased by about 1.5-fold. Furthermore, the enzyme stability in various organic solvents was significantly enhanced upon immobilization. Interestingly, the immobilized enzyme exhibited much higher stability in several commercial detergents including OMO, Tide, Ariel, Bonux and Xra by up to 5.2-fold. Finally, the immobilized protease maintained significant catalytic efficiency for twelve consecutive reaction cycles. These results suggest the effectiveness of the developed nanobiocatalyst as a candidate for detergent formulation and peptide synthesis in non-aqueous media.

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Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical challenge.

http:--linkinghub.elsevier.com-ihub-imag

Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical challenge.

Int J Surg. 2015 Jul;19:22-6

Authors: Tan QT, Chuwa EW, Chew SH, Lim-Tan SK, Lim SH

Abstract
Adenosquamous carcinoma of the breast (ASBC) is a rare variant of metaplastic breast cancer with both glandular as well as squamous differentiation. Their lack of distinct imaging characteristics, sometimes subtle histological characteristics and overlapping features with other benign lesions pose a diagnostic challenge. Unlike other forms of metaplastic breast cancer, low-grade adenosquamous carcinoma (LGAC) tends to follow an indolent course with favourable prognosis. We reviewed eight cases of LGAC in our institution from June 2005 to March 2014. In six cases, LGAC was only found after excisional biopsy. In our patients, LGAC frequently co-existed with other forms of breast pathology. Two patients had incidental findings of LGAC alongside their primary malignant tumour (adenoid cystic carcinoma and invasive ductal carcinoma in one, four foci between 0.5 and 4.0 mm within a radial sclerosing lesion adjacent to a malignant phyllodes tumour in the other). A further four patients had LGAC within a complex sclerosing lesion. One patient had a focus of LGAC within a fibroadenoma. One had a focus of LGAC within a benign phyllodes tumour. None of the patients had evidence of nodal involvement. A high degree of suspicion is recommended as such lesions tend to be incidental histological findings within benign tumours or within complex sclerosing lesions. Although the risk of nodal and distant metastasis is low, the potential for local recurrence necessitates aggressive local excision with margin clearance. The role of axillary dissection has yet to be defined and routine sentinel node biopsy and axillary clearance may not be necessary in view of rarity of nodal metastasis in literature. Benefit from adjuvant radiotherapy or chemotherapy is not clearly defined. All eight patients in our study have shown no evidence of recurrence after definitive surgery but longer periods of surveillance is required.

PMID: 25986061 [PubMed - indexed for MEDLINE]

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IJMS, Vol. 17, Pages 186: Liensinine- and Neferine-Induced Cardiotoxicity in Primary Neonatal Rat Cardiomyocytes and Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Due to drug-induced potential congestive heart failure and irreversible dilated cardiomyopathies, preclinical evaluation of cardiac dysfunction is important to assess the safety of traditional or novel treatments. The embryos of Nelumbo nucifera Gaertner seeds are a homology of traditional Chinese medicine and food. In this study, we applied the real time cellular analysis (RTCA) Cardio system, which can real-time monitor the contractility of cardiomyocytes (CMs), to evaluate drug safety in rat neonatal CMs and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). This study showed detailed biomechanical CM contractility in vitro, and provided insights into the cardiac dysfunctions associated with liensinine and neferine treatment. These effects exhibited dose and time-dependent recovery. Neferine showed stronger blocking effect in rat neonatal CMs than liensinine. In addition, the effects of liensinine and neferine were further evaluated on hiPS-CMs. Our study also indicated that both liensinine and neferine can cause disruption of calcium homeostasis. For the first time, we demonstrated the potential cardiac side effects of liensinine or neferine. While the same inhibition was observed on hiPS-CMs, more importantly, this study introduced an efficient and effective approach to evaluate the cardiotoxicity of the existing and novel drug candidates.

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IJMS, Vol. 17, Pages 181: Identification of Powdery Mildew Responsive Genes in Hevea brasiliensis through mRNA Differential Display

Powdery mildew is an important disease of rubber trees caused by Oidium heveae B. A. Steinmann. As far as we know, none of the resistance genes related to powdery mildew have been isolated from the rubber tree. There is little information available at the molecular level regarding how a rubber tree develops defense mechanisms against this pathogen. We have studied rubber tree mRNA transcripts from the resistant RRIC52 cultivar by differential display analysis. Leaves inoculated with the spores of O. heveae were collected from 0 to 120 hpi in order to identify pathogen-regulated genes at different infection stages. We identified 78 rubber tree genes that were differentially expressed during the plant–pathogen interaction. BLAST analysis for these 78 ESTs classified them into seven functional groups: cell wall and membrane pathways, transcription factor and regulatory proteins, transporters, signal transduction, phytoalexin biosynthesis, other metabolism functions, and unknown functions. The gene expression for eight of these genes was validated by qRT-PCR in both RRIC52 and the partially susceptible Reyan 7-33-97 cultivars, revealing the similar or differential changes of gene expressions between these two cultivars. This study has improved our overall understanding of the molecular mechanisms of rubber tree resistance to powdery mildew.

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IJMS, Vol. 17, Pages 183: Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice

Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice.

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Bacteremia secondary to Alloscardovia omnicolens urinary tract infection

Publication date: Available online 28 January 2016
Source:Journal of Infection and Chemotherapy
Author(s): Yoshihiko Ogawa, Akira Koizumi, Kei Kasahara, Sang-Tae Lee, Yuki Yamada, Ryuichi Nakano, Hisakazu Yano, Keiichi Mikasa
A 70-year-old woman was admitted to our hospital with malaise, bilateral leg edema, and oliguria. She had a history of advanced uterine cancer. Bilateral double-J catheters were inserted because growth of intra-abdominal metastases led to bilateral ureteral stricture and hydronephrosis. Two days later, she suddenly developed high fever. Thin gram-positive bacilli of moderate length were detected in the anaerobic blood culture bottles. We performed 16S ribosomal RNA analysis of the isolate and it showed 100% match with Alloscardovia omnicolens DSM 21503T. She was successfully treated with cefmetazole in addition to percutaneous nephrostomy.

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Distribution of virulence associated traits among urine Escherichia coli isolates from patients in onco-hematology

Publication date: Available online 28 January 2016
Source:Journal of Infection and Chemotherapy
Author(s): Mariem Safi, Wafa Achour, Rekaya Baaboura, Rym El Fatmi, Tarek Ben othmen, Assia Ben Hassen
Escherchia coli is the most common etiological agent of urinary tract infections. In this study we had two goals: First of all, to find out if urine stains isolated from our patients – having the particularity of being immunocompromised – would have a virulence genes distribution different from the one observed in strains isolated from ordinary patients. Second, we wanted to identify a common virulence profile associated to these particular strains. The prevalence of virulence factors (VF)-encoding genes was analyzed by PCR. Of the tested VF-encoding genes, malX (80%), ompT (79%), fyuA (74%), usp (67%), chuA (66%), iroN (59%), iutA (56%), papC (36%), pap AH (30%), papEF (28%), hlyA (28%), papG allele II (25%), cnf1 (21%), focG (20%),cvaC (20%) and papG allele III (7%) were significantly associated to urinary strains. Virulence genes distribution of urinary strains isolated from onco-hematology patients and the one observed in strains isolated from ordinary patients are almost the same. The virulence profiles containing adhesins type 1, S and F1C fimbriae, siderophore genes and three individual genes ompT, usp and malX were present in half of the urinary strains and were significantly associated to them. Two virulence signatures occurred significantly in UTI-causing strains (12%). These findings provide first insight into the virulence of UTI-causing E. coli strains isolated in onco-hematology patients.

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Perivascular epithelioid cell neoplasm (PEComa) of the uterus: A systematic review.

Perivascular epithelioid cell neoplasm (PEComa) of the uterus: A systematic review.

Int J Surg. 2015 Jul;19:1-5

Authors: Musella A, De Felice F, Kyriacou AK, Barletta F, Di Matteo FM, Marchetti C, Izzo L, Monti M, Benedetti Panici P, Redler A, D'Andrea V

Abstract
BACKGROUND: Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal tumor. Gynecological PEComas account for just over one-fourth of the overall PEComa cases reported in the literature. Surgery is the most recommended primary treatment while adjuvant therapy is generally reserved for high-risk cases. However, the best management of this neoplasia has not been well established, primarily because of the paucity of cases described to date.
OBJECTIVES: The aim of this systematic review is to summarize what is known thus far regarding the etiopathogenesis, clinical and pathologic features of PEComas, focusing also on the most valid treatment options for uterine cases.
DATA SOURCES: Pubmed articles on PEComas published in various journals over the past 70 years were analyzed.
CONCLUSIONS AND KEY FINDINGS: Although the optimal treatment of gynecological PEComas is controversial, surgical resection remains the cornerstone. The use of adjuvant treatment is warranted in high risk patients to increase disease control. A multidisciplinary approach should be key in treatment decision-making regarding gynecological PEComas.

PMID: 25981307 [PubMed - indexed for MEDLINE]

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[Merkel cell carcinoma of the ear lobe complicated with nephrosis syndrome and malignant lymphoma: a case report].

[Merkel cell carcinoma of the ear lobe complicated with nephrosis syndrome and malignant lymphoma: a case report].

Nihon Jinzo Gakkai Shi. 2015;57(8):1369-75

Authors: Okuno A, Arao M, Aoki K, Yonemoto S, Hayashi D, Fujii N, Oka K

Abstract
Here we report a rare case of Merkel cell carcinoma complicated with nephrosis and malignant lymphoma. A 79-year-old male, who had undergone rectectomy due to colorectal cancer about 10 years previously, was diagnosed as Merkel cell carcinoma of the left ear lobe with lymph node metastases. Tumor resection and lymph node dissection were performed. A year later, follow-up PET-CT revealed a small hot spot at the ileocecum without apparent tumor formation based on examination by colonoscopy. The patient received 56 Gy of radiation. Two months later, he developed new-onset nephrosis followed by renal failure, and was referred to our hospital (Cr 4.26 mg/dL, UA 13.5 mg/dL, Alb 2.1 g/dL). Further examination negated the possibility of vasculitis, collagen disease, or myeloma kidney. Since his renal function continued to decline, causing uremic symptoms, he was hospitalized and underwent hemodialysis soon after referral. Abdominal CT scan revealed an ileocecal mass with multiple abdominal lymphadenopathy, which was later diagnosed as diffuse large B-cell lymphoma (stage IV) by tumor biopsy. Corticosteroid therapy (prednisolone 60 mg/day) was soon initiated with no response. Local skin redness and blister formation at the left shoulder emerged gradually, which strongly suggested a local recurrence of Merkel cell carcinoma. Despite the use of rituximab, the patient's general condition deteriorated without any sign of recovery. Three months after the start of dialysis, we discontinued dialysis therapy due to his poor health status, and eventually he died of cachexia. Autopsy revealed triple cancers: rectal cancer, Merkel cell carcinoma, and malignant lymphoma. In addition to the case report, we will summarize and discuss former similar case reports in the literature.

PMID: 26817168 [PubMed - in process]

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Medoidshift clustering applied to genomic bulk tumor data.

Medoidshift clustering applied to genomic bulk tumor data.

BMC Genomics. 2016;17 Suppl 1:6

Authors: Roman T, Xie L, Schwartz R

Abstract
Despite the enormous medical impact of cancers and intensive study of their biology, detailed characterization of tumor growth and development remains elusive. This difficulty occurs in large part because of enormous heterogeneity in the molecular mechanisms of cancer progression, both tumor-to-tumor and cell-to-cell in single tumors. Advances in genomic technologies, especially at the single-cell level, are improving the situation, but these approaches are held back by limitations of the biotechnologies for gathering genomic data from heterogeneous cell populations and the computational methods for making sense of those data. One popular way to gain the advantages of whole-genome methods without the cost of single-cell genomics has been the use of computational deconvolution (unmixing) methods to reconstruct clonal heterogeneity from bulk genomic data. These methods, too, are limited by the difficulty of inferring genomic profiles of rare or subtly varying clonal subpopulations from bulk data, a problem that can be computationally reduced to that of reconstructing the geometry of point clouds of tumor samples in a genome space. Here, we present a new method to improve that reconstruction by better identifying subspaces corresponding to tumors produced from mixtures of distinct combinations of clonal subpopulations. We develop a nonparametric clustering method based on medoidshift clustering for identifying subgroups of tumors expected to correspond to distinct trajectories of evolutionary progression. We show on synthetic and real tumor copy-number data that this new method substantially improves our ability to resolve discrete tumor subgroups, a key step in the process of accurately deconvolving tumor genomic data and inferring clonal heterogeneity from bulk data.

PMID: 26817708 [PubMed - in process]

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Characterization of familial breast cancer in Saudi Arabia.

Characterization of familial breast cancer in Saudi Arabia.

BMC Genomics. 2015;16 Suppl 1:S3

Authors: Merdad A, Gari MA, Hussein S, Al-Khayat S, Tashkandi H, Al-Maghrabi J, Al-Thubaiti F, Hussein IR, Koumosani T, Shaer N, Chaudhary AG, Abuzenadah AM, Al-Qahtani MH, Dallol A

Abstract
BACKGROUND: The contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease. The advent of whole-exome sequencing is offering a unique opportunity to identify the breast cancer susceptibility genes in each family of sufferers. The polymorphisms/mutations identified will then allow for personalizing the genetic screening tests accordingly. To this end, we have performed whole-exome sequencing of seven breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform.
RESULTS: We have identified several coding single nucleotide variations that were either novel or rare affecting genes controlling DNA repair in the BRCA1/2 pathway.
CONCLUSION: The disruption of DNA repair pathways is very likely to contribute to breast cancer susceptibility in the Saudi population.

PMID: 25923920 [PubMed - indexed for MEDLINE]

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Efficacy of pazopanib monotherapy in patients who had been heavily pretreated for metastatic soft tissue sarcoma: a retrospective case series.

Efficacy of pazopanib monotherapy in patients who had been heavily pretreated for metastatic soft tissue sarcoma: a retrospective case series.

BMC Cancer. 2015;15:154

Authors: Yoo KH, Kim HS, Lee SJ, Park SH, Kim SJ, Kim SH, La Choi Y, Shin KH, Cho YJ, Lee J, Rha SY

Abstract
BACKGROUND: We retrospectively reviewed outcomes of treatment with pazopanib, an oral multi-tyrosine kinase angiogenesis inhibitor, in patients with advanced soft tissue sarcoma, a rare and heterogeneous tumor group with limited treatment options.
METHODS: Between 2009 and 2013, 43 patients with metastatic soft tissue sarcoma received pazopanib as salvage chemotherapy after one or more cytotoxic regimens. Response rate, progression-free survival, and overall survival were analyzed according to histological subtype, Eastern Cooperative Oncology Group performance status, and metastatic site.
RESULTS: Common histological subtypes included leiomyosarcoma (n = 9), angiosarcoma (n = 6), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (MFH/UPS, n = 5), malignant peripheral nerve sheath tumor (MPNST, n = 5), and synovial sarcoma (n = 4). Nineteen patients (44.2%) received more than two chemotherapy regimens before pazopanib. At the time of analysis, 208 treatment cycles of pazopanib had been administered (median, 4.8 cycles per patient), and no treatment-related mortality occurred. The disease control rate was 61.0% (95% confidence interval [CI], 46.1-75.9%), and the overall response rate was 17.1% (partial response, n = 7; complete response, n = 0). Partial response was achieved in two patients with synovial sarcoma, two with MFH/UPS, one with MPNST, one with leiomyosarcoma, and one with angiosarcoma. The median lengths of progression-free survival and overall survival were 5.0 months (95% CI, 3.6-6.4 months) and 8.2 months (95% CI, 5.8-10.6 months), respectively. Progression-free survival was shorter in the patients with liposarcoma and rhabdomyosarcoma (1.3 and 0.9 months, respectively) than in those with leiomyosarcoma, MPNST, MFH/UPS, and synovial sarcoma (5.6, 6.5, 7.1, and 7.7 months, respectively).
CONCLUSIONS: Pazopanib demonstrated acceptable antitumor activity in the Asian patients who had been heavily pretreated for sarcoma, with seemingly more favorable results in the patients with leiomyosarcoma, MPNST, MFH/UPS, and synovial sarcoma than in those with liposarcoma and rhabdomyosarcoma.

PMID: 25885855 [PubMed - indexed for MEDLINE]

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Superficial acral fibromyxoma.

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Superficial acral fibromyxoma.

Int J Dermatol. 2015;54(5):499-508

Authors: Sawaya JL, Khachemoune A

Abstract
Superficial acral fibromyxoma (SAF), also known as digital fibromyxoma, is a rare soft tissue tumor with a predilection for acral surfaces. Superficial acral fibromyxoma classically presents as a pink to flesh-colored nodule located on the subungual or periungual region of the hands or feet. It is typically slow-growing and asymptomatic, which, coupled with its nonspecific clinical appearance, presents a diagnostic dilemma to the dermatologist. As these features overlap with those of a multitude of differential diagnoses, it is imperative to have a good understanding of the characteristics on which the diagnosis of SAF is based. Superficial acral fibromyxoma was initially described in 2001, since when several case reports and literature reviews have contributed to our current understanding of these tumors. In this article, we will review the history, clinical features, diagnosis, and management of SAF. It is our hope that this systematic approach will help to facilitate the recognition and management of this distinct dermatologic entity.

PMID: 25772615 [PubMed - indexed for MEDLINE]

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Efficacy and outcome of allogeneic transplantation in IgD and nonsecretory myeloma. A report on behalf of the Myeloma Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation.

Efficacy and outcome of allogeneic transplantation in IgD and nonsecretory myeloma. A report on behalf of the Myeloma Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation.

Biol Blood Marrow Transplant. 2015 Jun;21(6):1054-8

Authors: Morris C, Iacobelli S, Gahrton G, van Biezen A, Drake M, Garderet L, Potter M, Schattenberg AV, Cornelissen JJ, Hamladji RM, Martelli M, Petersen E, Rovira M, Bandini G, Kroger N, de Witte T

Abstract
We have recently reported on the outcome of autologous transplantation in the rare myelomas (IgD, IgE, IgM, and nonsecretory [NS]) but there is no real information on the outcome of these conditions after allogeneic transplantation. We used the European Group for Blood and Marrow Transplantation myeloma database to compare the outcomes after allogeneic transplantation of 1354 common myelomas (IgG, IgA, and light chain myeloma) with the outcome in 26 IgD myelomas and 52 NS myelomas. There was little difference between common and the IgD and NS myeloma patients with respect to prognostic factors although the IgD group had a higher beta 2 microglobulin at diagnosis, shorter time to transplantation, and more T cell depletion. IgD and NS patients had a significantly greater achievement of complete remission at conditioning but this did not translate into equivalent progression-free survival and overall survival for the IgD patients although the NS outcome was very similar to that of common myeloma. The PFS and OS of IgD, common, and NS myelomas appear similar after allogeneic transplantation, despite a tendency for higher early relapse rate in IgD myeloma. Allogeneic transplantation may, therefore, be an option to investigate in prospective observational studies.

PMID: 25708221 [PubMed - indexed for MEDLINE]

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Radiation myelitis after hypofractionated radiotherapy with concomitant gefitinib.

Radiation myelitis after hypofractionated radiotherapy with concomitant gefitinib.

Radiat Oncol. 2015;10:29

Authors: Lewitzki V, Andratschke N, Kuhnt T, Hildebrandt G

Abstract
We describe the case of a 71-year-old Caucasian female with primary disseminated non-small cell cancer of the lung, presented for palliative radiotherapy of metastatic spread to the 9th and 11th thoracic vertebrae without intramedullary growth. Palliative radiotherapy with daily fractions of 3 Gy and a cumulative dose of 36 Gy to thoracic vertebrae 8-12 was performed. The patient received concomitantly 250 mg gefitinib daily. After a latent period of 16 months, the patient developed symptoms of myelitis. Magnetic resonance imaging (MRI) did not reveal any bony or intraspinal tumor progression, but spinal cord signal alteration. No response to steroids was achieved. The neurological symptoms were progressive in August 2013 with the right leg being completely plegic. The left leg was incompletely paralyzed. Deep and superficial sensitivity was also diminished bilaterally. The patient was completely urinary and anally incontinent. Contrary to the clinical findings, a follow-up MRI (July 2013) showed amelioration of the former signal alterations in the spinal cord. The diagnosis of paraneoplastic myelopathy was refuted by a negative test for autologous antibodies. At the last clinical visit in May 2014, the neurological symptoms were stable. The last tumor-specific treatment the patient is receiving is erlotinib 125 mg/d.We reviewed the literature and found no reported cases of radiation myelopathy after the treatment in such a setting. The calculated probability of such complication after radiotherapy alone is statistically measurable at the level of 0.02%. We suppose that gefitinib could also play a role in the development of this rare complication.

PMID: 25631068 [PubMed - indexed for MEDLINE]

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Clinical features of vestibular schwannomas in patients who experience hearing improvement after surgery.

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Clinical features of vestibular schwannomas in patients who experience hearing improvement after surgery.

Neurosurg Rev. 2015 Apr;38(2):331-41; discussion 341

Authors: Kohno M, Sora S, Sato H, Shinogami M, Yoneyama H

Abstract
Postoperative improvements in hearing in patients with vestibular schwannoma are extremely rare. We reviewed nine cases retrospectively to investigate the clinical features of these cases. Hearing improvement was defined as an improvement in hearing class according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria. The nine patients comprised five men and four women with a mean age of 40.4 years. Of the nine tumors, three were solid and six cystic; mean tumor size was 29.7 mm. Mean pure tone average (PTA) and mean speech discrimination scores (SDS) were 47.5 dB and 22.8%, respectively, preoperatively and 29.6 dB and 83.9%, respectively, postoperatively. AAO-HNS class distribution was class B:1 and D:8, preoperatively, and class A: 5 and B:4, postoperatively. A lateral suboccipital retrosigmoid approach with a lateral (park bench) position was used in all nine patients. Clinical features of these vestibular schwannomas included (1) large cystic tumors, (2) sudden onset hearing loss, (3) the presence of a valley shape in the middle-pitch area on preoperative audiograms, (4) almost intact preoperative inner ear function, (5) a low SDS relative to PTA preoperatively, (6) surgical treatment via a lateral suboccipital approach within 6 months of the most recent exacerbation of hearing loss, (7) observation of I waves in preoperative, intraoperative, and postoperative auditory brainstem response (ABR) recordings, and (8) postoperative improvement in mainly the middle-pitch range and SDS. For surgical treatment of vestibular schwannomas with the above clinical features, a translabyrinthine approach and cochlear nerve section (unless the I wave on the intraoperative ABR trace disappears) should be avoided, regardless of the patient's preoperative hearing level, if a surgeon hopes to maximize the chances of preserving or improving hearing.

PMID: 25528569 [PubMed - indexed for MEDLINE]

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Giant pedunculated pilomatrix carcinoma on the upper limb: A rare clinical appearance.

Giant pedunculated pilomatrix carcinoma on the upper limb: A rare clinical appearance.

Eur J Dermatol. 2015 Jan-Feb;25(1):91-2

Authors: Sato S, Nakamura Y, Shimizu M, Yamada K, Teramoto Y, Yamazaki N, Yamamoto A

PMID: 25464929 [PubMed - indexed for MEDLINE]

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Bacteremia secondary to Alloscardovia omnicolens urinary tract infection

Publication date: Available online 28 January 2016
Source:Journal of Infection and Chemotherapy
Author(s): Yoshihiko Ogawa, Akira Koizumi, Kei Kasahara, Sang-Tae Lee, Yuki Yamada, Ryuichi Nakano, Hisakazu Yano, Keiichi Mikasa
A 70-year-old woman was admitted to our hospital with malaise, bilateral leg edema, and oliguria. She had a history of advanced uterine cancer. Bilateral double-J catheters were inserted because growth of intra-abdominal metastases led to bilateral ureteral stricture and hydronephrosis. Two days later, she suddenly developed high fever. Thin gram-positive bacilli of moderate length were detected in the anaerobic blood culture bottles. We performed 16S ribosomal RNA analysis of the isolate and it showed 100% match with Alloscardovia omnicolens DSM 21503^T. She was successfully treated with cefmetazole in addition to percutaneous nephrostomy.

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Immediate disappearance of hemifacial spasm after partial removal of ponto-medullary junction anaplastic astrocytoma: case report.

Immediate disappearance of hemifacial spasm after partial removal of ponto-medullary junction anaplastic astrocytoma: case report.

Neurosurg Rev. 2015 Apr;38(2):385-90; discussion 390

Authors: Castiglione M, Broggi M, Cordella R, Acerbi F, Ferroli P

Abstract
Hemifacial spasm (HFS) is generally caused by a neurovascular conflict (NC) at the root exit zone (REZ) of the facial nerve at the brainstem. Although a direct compression to the seventh cranial nerve (CN) by the anterior inferior cerebellar artery (AICA) is generally the most frequent cause, secondary HFS may be related to other pathological conditions. HFS due to an intracranial mass lesion is exceptionally rare and it has been reported in very few cases. The online database was searched for English-language articles reporting cases of HFS due to brainstem mass lesions and the possible pathophysiological mechanisms involved in its genesis. A 47-year-old man affected by an anaplastic astrocytoma of the brainstem at the level of the ponto-medullary junction developed right HFS. He underwent a subtotal surgical removal of the tumor with complete resolution of the HFS. This is the ninth reported case of HFS caused by an intrinsic brainstem tumor. The exceptional rarity of the relationship between intra-axial tumors and peripheral HFS was analyzed.

PMID: 25382264 [PubMed - indexed for MEDLINE]

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Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis.

Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis.

Radiat Oncol. 2014;9:226

Authors: Guckenberger M, Mantel F, Gerszten PC, Flickinger JC, Sahgal A, Létourneau D, Grills IS, Jawad M, Fahim DK, Shin JH, Winey B, Sheehan J, Kersh R

Abstract
PURPOSE: To evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases.
MATERIALS AND METHODS: Eight centers from the United States (n=5), Canada (n=2) and Germany (n=1) participated in the retrospective study and analyzed 301 patients with 387 vertebral metastases. No patient had been exposed to prior radiation at the treatment site. All patients were treated with linac-based SBRT using cone-beam CT image-guidance and online correction of set-up errors in six degrees of freedom.
RESULTS: 387 spinal metastases were treated and the median follow-up was 11.8 months. The median number of consecutive vertebrae treated in a single volume was one (range, 1-6), and the median total dose was 24 Gy (range 8-60 Gy) in 3 fractions (range 1-20). The median EQD210 was 38 Gy (range 12-81 Gy). Median overall survival (OS) was 19.5 months and local tumor control (LC) at two years was 83.9%. On multivariate analysis for OS, male sex (p<0.001; HR=0.44), performance status <90 (p<0.001; HR=0.46), presence of visceral metastases (p=0.007; HR=0.50), uncontrolled systemic disease (p=0.007; HR=0.45), >1 vertebra treated with SBRT (p=0.04; HR=0.62) were correlated with worse outcomes. For LC, an interval between primary diagnosis of cancer and SBRT of ≤ 30 months (p=0.01; HR=0.27) and histology of primary disease (NSCLC, renal cell cancer, melanoma, other) (p=0.01; HR=0.21) were correlated with worse LC. Vertebral compression fractures progressed and developed de novo in 4.1% and 3.6%, respectively. Other adverse events were rare and no radiation induced myelopathy reported.
CONCLUSIONS: This multi-institutional cohort study reports high rates of efficacy with spine SBRT. At this time the optimal fractionation within high dose practice is unknown.

PMID: 25319530 [PubMed - indexed for MEDLINE]

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Oksidativt stress hemmer metastaser

Reaktive oksygenderivater kan hemme metastasering ved malignt melanom.

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Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus

Abstract

Insulin glargine 300 U/mL (Toujeo^®) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus^®), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

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Editorial Board

Publication date: February 2016
Source:Cancer Treatment Reviews, Volume 43

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HSMNR belongs to the most frequent types of hereditary neuropathy in the Czech Republic and is twice more frequent than HMSNL

Abstract

Hereditary motor and sensory neuropathy type Russe (HMSNR), also called CMT4G is an autosomal recessive inherited peripheral neuropathy (IPN) caused by a founder mutation in the HK1 gene. HMSNR affects only patients with Roma origin, similar to the better known HMSN type Lom clarified earlier. By testing IPN patients with Roma origin we realized that HMSNR affects surprisingly many patients in the Czech Republic. HMSNR is one of the most frequent types of IPN in this country and seems to be twice more frequent than HMSNL. Pronounced lower limb atrophies and severe deformities often lead to walking inability in even young patients, but hands are usually only mildly affected even after many years of disease duration. The group of 20 patients with HMSNR presented here is the first report about the prevalence of HMSNR from central Europe.

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Next-generation sequencing confirms the implication of SLC24A1 in autosomal-recessive congenital stationary night blindness (CSNB)

Abstract

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs-electroretinogram (ERG) while patients with a signal transmission defect show a Schubert-Bornschein-ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs-ERG and only one family with a disease causing variant in SLC24A1 have been reported. Whole-exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SLC24A1. Indeed, reinvestigation of the clinical data corrected the diagnosis to Riggs-form of CSNB. Targeted next-generation sequencing (NGS) identified compound heterozygous deletions and a homozygous missense variant in SLC24A1 in two other patients, respectively. ERG abnormalities varied in these three cases but all patients had normal visual acuity, no myopia or nystagmus, unlike in Schubert-Bornschein-type of CSNB. This confirms that SLC24A1 defects lead to CSNB, and outlines phenotype/genotype correlations in CSNB subtypes. In case of unclear clinical characteristics, NGS techniques are helpful to clarify the diagnosis.

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New Sections for the New Year

Horm Res Paediatr 2016;85:1

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Use of two gene panels for prostate cancer diagnosis and patient risk stratification

Abstract

Currently, no ideal prostate cancer (PCa) diagnostic or prognostic test is available due to the lack of biomarkers with high sensitivity and specificity. There is an unmet medical need to develop combinations of multiple biomarkers which may have higher accuracy in detection of PCa and stratification of aggressive and indolent cancer patients. The aim of this study was to test two biomarker gene panels in distinguishing PCa from benign prostate and high-risk, aggressive PCa from low-risk, indolent PCa, respectively. We identified a five-gene panel that can be used to distinguish PCa from benign prostate. The messenger RNA (mRNA) expression signature of the five genes was determined in 144 PCa and benign prostate specimens from prostatectomy. We showed that the five-gene panel distinguished PCa from benign prostate with sensitivity of 96.59 %, specificity of 92.86 %, and area under the curve (AUC) of 0.992 (p < 0.0001). The five-gene panel was further validated in a 137 specimen cohort and showed sensitivity of 84.62 %, specificity of 91.84 %, and AUC of 0.942 (p < 0.0001). To define subtypes of PCa for treatment guidance, we examined mRNA expression signature of an eight-gene panel in 87 PCa specimens from prostatectomy. The signature of the eight-gene panel was able to distinguish aggressive PCa (Gleason score >6) from indolent PCa (Gleason score ≤6) with sensitivity of 90.28 %, specificity of 80.00 %, and AUC of 0.967 (p < 0.0001). This panel was further validated in a 158 specimen cohort and showed significant difference between aggressive PCa and indolent PCa with sensitivity of 92.57 %, specificity of 70.00 %, and AUC of 0.962 (p < 0.0001). Our findings in assessing multiple biomarkers in combination may provide new tools to detect PCa and distinguish aggressive and indolent PCa for precision and personalized treatment. The two biomarker panels may be used in clinical settings for accurate PCa diagnosis and patient risk stratification for biomarker-guided treatment.

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The prognostic implication of SRSF2 mutations in Chinese patients with acute myeloid leukemia

Abstract

Recently, somatic mutations in SRSF2 gene have been discovered in a proportion of hematologic malignancies including acute myeloid leukemia (AML). This study was aimed to investigate SRSF2 mutations in Chinese AML patients. High-resolution melting analysis (HRMA) was developed to screen SRSF2 mutations in 249 cases with AML, and then direct DNA sequencing was used to verify the results of HRMA. In this study, 3.6 % (9/249) of Chinese AML patients were found with heterozygous SRSF2 mutations. Patients with SRSF2 mutations were older than those with wild-type SRSF2 (P = 0.014). No differences in the sex, blood parameters, French–American–British classification (FAB) subtypes, and karyotypes were observed between AML patients with and without SRSF2 mutations. Although the overall survival (OS) of SRSF2-mutated patients was inferior to those without mutations in both whole AML patients (median 4 vs. 11 months, respectively; P = 0.006) and cytogenetically normal patients (median 2 vs. 12 months, respectively; P = 0.008), multiple analysis disclosed that SRSF2 mutation was not an independent prognostic factor in AML patients. These results suggest that SRSF2 mutation occurs at a low frequency in aged AML patients and might not be associated with adverse prognosis in Chinese AML patients.

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A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel

Abstract

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

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Long non-coding RNA AK027294 involves in the process of proliferation, migration, and apoptosis of colorectal cancer cells

Abstract

This study is aimed to investigate the differentially expressed long non-coding RNAs (lncRNAs) in colorectal cancer and its potential biological function. Colorectal adenoma is the precancerous lesions of colorectal cancer, so in this study, we used colorectal adenoma as negative control. The global lncRNA expression profile in colorectal cancer and adenoma was evaluated by bioinformatics. The biological functions and potential mechanism of AK027294 were investigated in HCT116, HCT8, and SW480 colorectal cancer cells. A total of 135 lncRNAs were found to be differentially expressed in colorectal cancer and adenoma tissues. Among them, 71 lncRNAs were up-regulated and 64 lncRNAs were down-regulated. Especially, AK027294 was found to be highly expressed in colorectal cancer tissues compared with colorectal adenoma tissues (fold change is 184.5). Our results indicated that AK027294 down-regulation significantly inhibited colorectal cancer cells proliferation and migration, but promoted cell apoptosis (P < 0.05). The potential mechanism of AK027294 might be associated with the regulation of caspase-3, caspase-8, Bcl-2, MMP12, MMP9, and TWIST. The lncRNA expression profile in colorectal cancer suggests lncRNAs may play important roles in the occurrence and progression of colorectal cancer. AK027294 is highly expressed in colorectal cancer and closely correlates with colorectal cells proliferation, migration, and apoptosis.

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Atmosphere, Vol. 7, Pages 18: Solar Forecasting in a Challenging Insular Context

This paper aims at assessing the accuracy of different solar forecasting methods in the case of an insular context. Two sites of La Réunion Island, Le Tampon and Saint-Pierre, are chosen to do the benchmarking exercise. Réunion Island is a tropical island with a complex orography where cloud processes are mainly governed by local dynamics. As a consequence, Réunion Island exhibits numerous micro-climates. The two aforementioned sites are quite representative of the challenging character of solar forecasting in the case of a tropical island with complex orography. Hence, although distant from only 10 km, these two sites exhibit very different sky conditions. This work focuses on day-ahead and intra-day solar forecasting. Day-ahead solar forecasts are provided by the European Center for Medium-Range Weather Forecast (ECMWF). This organization maintains and runs the Numerical Weather Prediction (NWP) model named Integrated Forecast System (IFS). In this work, post-processing techniques are applied to refine the output of the IFS model for day-ahead forecasting. Statistical models like a recursive linear model or a nonlinear model such as an artificial neural network are used to produce the intra-day solar forecasts. It is shown that a combination of the IFS model and the neural network model further improves the accuracy of the forecasts.

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Langerhans Cell Histiocytosis of the Rib in an Adult: A Case Report

Single-site, single-system Langerhans cell histiocytosis (LCH) of the rib is one of the rarest causes of bone tumor in adults. Herein, we report a case of a healthy 35-year-old male who presented with upper back pain that was attributed to a solitary osteolytic lesion at the posterolateral aspect of his sixth rib. For diagnostic confirmation and treatment, partial resection of the sixth rib was performed and pathologic finding was consistent with LCH. At the final follow-up after 2 years, no local recurrence or metastasis was observed.
Case Rep Oncol 2016;9:83-88

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Simultaneous thoraco-laparoscopic repair of giant hiatal hernias: an alternative approach

Summary

Laparoscopic repair of giant hiatal hernias with intrathoracic displacement of organs is recommended to relieve troublesome symptoms in patients. During this procedure, incomplete excision of the hernia sac from the mediastinum and omission of creating a 'non-tension-free position' of the cardio-esophageal junction into the abdominal cavity are associated with hiatal hernia recurrence. Giant hiatal hernias therefore often require a thoracotomy or thoracoscopy, to free dense adhesions higher up the chest. These procedures may increase the risk of perioperative morbidity due to lengthy operating times. We developed an operation procedure for giant hiatal hernia repair containing all the benefits of minimal invasive surgery, with overview of both thoracic and abdominal herniated structures. Three patients with a giant hiatal hernia were treated by a simultaneous thoraco-laparoscopic approach, which proved to be technically feasible and safe. Simultaneous thoraco-laparoscopic hernia repair can be considered a reasonable treatment option in selected cases such as type IV hernias, hernia recurrence or traumatic diaphragmatic herniation.

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Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial

Summary

Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40–50% of patients. Cannabinoid receptors 1 (CB1) and 2 (CB2) modulate release of neurotransmitters; CB1 is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity. We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP. Subjects with FCP received dronabinol (5 mg, twice daily; n = 7; average age, 44 years; mean body mass index, 26.7) or placebo (n = 6; average age, 42 years; mean body mass index, 25.9) for 28 days (4 weeks). Chest pain, general health, and anxiety/depression questionnaires were assessed at baseline and at 4 weeks. Subjects underwent an esophageal balloon distention test prior to treatment and on last day of the study. Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04). Depression and anxiety scores did not differ between the groups at baseline or after treatment. No significant adverse effects were observed. In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings.

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Most children with eosinophilic esophagitis have a favorable outcome as young adults

Summary

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0–100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4–17) and mean duration of follow-up was 8.3 years (2–16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0–30) and 14.1 (0–50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97–10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85–21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare.

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Prevalence rate and clinical characteristics of esophageal ectopic sebaceous glands in asymptomatic health screen examinees

Summary

Ectopic sebaceous glands in the esophagus have rarely been reported and, thus, represent an obscure medical condition. The aim of this study is to identify the prevalence rate and clinical characteristics of this lesion in an asymptomatic population. We prospectively enrolled health screen examinees who underwent esophagogastroduodenoscopy for gastric cancer screening. An esophageal biopsy was performed in the cases in which esophageal ectopic sebaceous glands were suspected. The general characteristics of the examinees were analyzed based on their medical records. A total of 9989 examinees were enrolled, and five examinees were diagnosed with esophageal ectopic sebaceous glands between December 2012 and June 2014. The endoscopic findings of the esophageal ectopic sebaceous glands indicated multiple yellowish patches or papules, which varied in size. The histopathological findings indicated several lobulated sebaceous glands in the squamous epithelium with inflammatory infiltration. The follow-up endoscopic findings indicated that there was no grossly discernible change. In conclusion, esophageal ectopic sebaceous glands are present in 0.05% of asymptomatic subjects. This lesion is thought to be benign and is not related to clinical symptoms. Therefore, esophageal ectopic sebaceous glands do not require further treatment or follow-up, which makes endoscopists free from active efforts for differential diagnosis with other malignant diseases.

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Polymorphisms of the FOXF1 and MHC locus genes in individuals undergoing esophageal acid reflux assessments

Summary

Gastroesophageal reflux disease (GERD) may lead to Barrett's esophagus (BE). Previously, a large genome-wide association study found two germline markers to be associated with BE, FOXF1 rs9936833 (C allele) and MHC rs9257809 (A allele). This study evaluated whether these two polymorphisms are associated with gastroesphageal acid reflux as measured by 24-hour pH testing. Patients with acid reflux symptoms referred for esophageal manometry and 24-hour pH monitoring at University Health Network (Toronto, ON) were enrolled. DNA extracted from blood was genotyped using a Taqman Polymerase Chain Reaction (PCR) assay. DeMeester scores of ≥14.7 or prior evidence of reflux esophagitis on endoscopy defined individuals with esophageal acid reflux. Logistic regression analysis, adjusted for clinical risk factors, was used to calculate odds ratios with 95% confidence intervals for each polymorphism in relation to the presence of acid reflux. Of 182 patients, the median age was 50 years and 62% were female; 95 (52%) met the definition of GERD. In the multivariable analysis, both FOXF1 rs9936833 (OR = 1.82; 95%CI: 1.12–2.96; P = 0.02) and MHC rs9257809 (OR = 9.36; 95%CI: 2.92–29.99; P < 0.001) remained significantly associated with presence of acid reflux. When both polymorphisms were placed in the same model, the adjusted ORs were 2.10 (95%CI: 1.24–3.53; P = 0.005) and 10.95 (95%CI: 3.32–36.09; P < 0.001), respectively. The association for risk allele C in FOXF1 rs9936833 and risk allele A in MHC rs9257809 with the presence of acid reflux suggests a potential pathophysiologic mechanism for the role of genetic influences in BE development.

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Is rigid endoscopy necessary with childhood corrosive ingestion? a retrospective comparative analysis of 458 cases

Summary

The aim of this study was to determine the necessity of endoscopy in cases in which a corrosive substance was ingested and to find a practical way to avoid unnecessary endoscopies for similar cases in the future. The clinical records of 458 hospitalized cases with clinical histories of corrosive substance ingestion between January 2007 and December 2013 were retrospectively reviewed. The demographics of the cases, the ingested substances, and the rigid endoscopy findings were evaluated. The three most commonly ingested corrosive agents were household bleach (22.9%), household degreaser (15.9%), and drain cleaner (13.1%). Rigid esophagoscopy was performed in 367 of the 458 cases. Corrosive agents were grouped according to their purpose of household use; eight groups were created. The degree of corrosive injury observed in the different groups was compared with the degree of injury caused by household bleach. Among the corrosive agent groups, dishwashing machine products (Gr.1), laundry products (Gr.2), liquid cleaners (Gr.3), and household bleach (Gr.4) did not cause high-grade injuries. The resulting injuries and esophagoscopy results among the above groups, whether symptomatic or not, did not differ from one another. Corrosive agents such as drain cleaner (Gr.6), household degreaser (Gr.7), and several other acidic products (Gr.8) caused high-grade injuries in the esophagus; however, lime remover/HCl (Gr.5) did not. Thus, hospitalization and rigid endoscopy seem unnecessary to assess esophageal injury in most cases, if the ingested corrosive agent fits into group 1, 2, 3, or 4 and if the patient can be easily fed. Esophagoscopy is useful to shorten the hospitalization times in cases where strong corrosive agents were ingested, such as those in groups 5, 6, 7, and 8.

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HLA-B*59:01: a marker for Stevens–Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese

HLA-B*59:01: a marker for Stevens–Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese

The Pharmacogenomics Journal 16, 83 (February 2016). doi:10.1038/tpj.2015.25

Authors: F Yang, J Xuan, J Chen, H Zhong, H Luo, P Zhou, X Sun, L He, S Chen, Z Cao, X Luo & Q Xing

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Segmental Basal cell nevus syndrome caused by an activating mutation in Smoothened

Abstract

Aberrant sonic hedgehog signaling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in Basal Cell Nevus Syndrome (BCNS). Mutations in Smoothened (SMO) encoding a receptor for sonic hedgehog, have been reported in sporadic BCCs but not in BCNS.

We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in 3 BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in an increased SMO transactivating activity, and the patient responded to vismodegib therapy.

Activating mutations in SMO may also cause BCNS. The identification of a gain-of-function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumors, whether sporadic or inherited.

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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

Publication date: Available online 28 January 2016
Source:Cancer Cell
Author(s): Eric R. Lechman, Bernhard Gentner, Stanley W.K. Ng, Erwin M. Schoof, Peter van Galen, James A. Kennedy, Silvia Nucera, Fabio Ciceri, Kerstin B. Kaufmann, Naoya Takayama, Stephanie M. Dobson, Aaron Trotman-Grant, Gabriela Krivdova, Janneke Elzinga, Amanda Mitchell, Björn Nilsson, Karin G. Hermans, Kolja Eppert, Rene Marke, Ruth Isserlin, Veronique Voisin, Gary D. Bader, Peter W. Zandstra, Todd R. Golub, Benjamin L. Ebert, Jun Lu, Mark Minden, Jean C.Y. Wang, Luigi Naldini, John E. Dick
To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.

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Lechman et al. show that miR-126 targets the PI3K/AKT/MTOR signaling pathway to preserve quiescence, increase self-renewal, and promote chemotherapy resistance of acute myeloid leukemia stem cells (LSC). Reducing the miR-126 level impairs LSC maintenance in contrast to expanding normal hematopoietic stem cells.

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Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and manifestation of toxicities from sunitinib in Asian patients

Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and manifestation of toxicities from sunitinib in Asian patients

The Pharmacogenomics Journal 16, 47 (February 2016). doi:10.1038/tpj.2015.13

Authors: Y L Teo, H L Wee, X P Chue, N M Chau, M-H Tan, R Kanesvaran, H L Wee, H K Ho & A Chan

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Using the Retrograde Internal Mammary System for Stacked Perforator Flap Breast Reconstruction: 71 Breast Reconstructions in 53 Consecutive Patients

Background: Abdominal tissue is the preferred donor source for autologous breast reconstruction, but in select patients with inadequate tissue, additional volume must be recruited to achieve optimal outcomes. Stacked flaps are an effective approach in these cases, but can be limited by the need for adequate recipient vessels. This article reports outcomes for the use of the retrograde internal mammary system for stacked flap breast reconstruction in a large number of consecutive patients. Methods: Fifty-three patients underwent stacked autologous tissue breast reconstruction with a total of 142 free flaps. Thirty patients underwent unilateral stacked deep inferior epigastric perforator (DIEP) flap reconstruction, five had unilateral stacked profunda artery perforator flap reconstruction, one had bilateral stacked DIEP/superior gluteal artery perforator flap reconstruction, and 17 underwent bilateral stacked DIEP/profunda artery perforator flap reconstruction. In all cases, the antegrade and retrograde internal mammary vessels were used for anastomoses. In situ manometry studies were also conducted comparing the retrograde internal mammary arteries in 10 patients to the corresponding systemic pressures. Results: There were three total flap losses (97.9 percent flap survival rate), two partial flap losses, four reexplorations for venous congestion, and three patients with operable fat necrosis. The mean weight of the stacked flaps for each reconstructed breast was 622.8 g. The retrograde internal mammary mean arterial pressures were on average 76.6 percent of the systemic mean arterial pressures. Conclusions: The results demonstrate that the retrograde internal mammary system is capable of independently supporting free tissue transfer. These vessels provide for convenient dissection and improved efficiency of these cases, with successful postsurgical outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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The role of Toll-like receptor 4 polymorphisms in vaccine immune response

The role of Toll-like receptor 4 polymorphisms in vaccine immune response

The Pharmacogenomics Journal 16, 96 (February 2016). doi:10.1038/tpj.2015.21

Authors: P Pellegrino, F S Falvella, S Cheli, C Perrotta, E Clementi & S Radice

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Using local multiplicity to improve effect estimation from a hypothesis-generating pharmacogenetics study

Using local multiplicity to improve effect estimation from a hypothesis-generating pharmacogenetics study

The Pharmacogenomics Journal 16, 107 (February 2016). doi:10.1038/tpj.2015.19

Authors: W Zou & H Ouyang

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A Comparison of Methods to Assess Mastectomy Flap Viability in Skin-Sparing Mastectomy and Immediate Reconstruction: A Prospective Cohort Study

Background: Skin-sparing mastectomy with immediate reconstruction can yield excellent aesthetic results, but high rates of mastectomy flap necrosis have been reported. A prospective cohort study was undertaken to compare three methods of assessing mastectomy flap viability following skin-sparing mastectomy and immediate reconstruction to determine which is most effective in reducing mastectomy flap necrosis. Methods: The study group included 60 consecutive patients (99 breasts) undergoing skin-sparing mastectomy and immediate reconstruction with either tissue expanders (n = 39) or transverse rectus abdominis musculocutaneous flaps (n = 21). Mastectomy flap viability was assessed either visually (n = 20), with fluorescein dye and Wood's lamp imaging (n = 20), or by indocyanine green angiography (n = 20). Variation across groups was analyzed using analysis of variance for continuous variables and chi-square test for dichotomous variables. Results: The mean follow-up was 10 months. There were no significant differences in mean age, body mass index, medical history, smoking history, pathologic diagnosis, chemotherapy, or reconstruction type. Mastectomy flap necrosis was observed in eight of 30 breasts in the direct visualization group (27 percent), compared with 14 percent in the indocyanine green angiography group and 3 percent in the fluorescein group (p = 0.03). The reoperation rate in the direct visualization group was 20 percent, compared with 15 percent in the indocyanine green angiography group and 0 percent in the fluorescein group. Conclusions: Fluorescein dye was associated with the lowest rate of complications after skin-sparing mastectomy, but indocyanine green angiography was also shown to reduce mastectomy flap necrosis compared with direct visualization. Routine imaging of mastectomy flap perfusion seems to be beneficial in skin-sparing mastectomy, but intravenous fluorescein may be as effective as more expensive modalities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

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Validation of database search strategies for the epidemiological study of eczema herpeticum

Abstract

Eczema herpeticum (EH) is characterized by viral infection of a preexisting inflammatory dermatosis. EH is associated with considerable morbidity and even mortality. It is important to study EH, in order to identify risk factors and burden of disease. Yet, the epidemiology of EH has not been well defined. To our knowledge, large-scale population-based studies that examined the epidemiology of EH have not been reported. Previous studies of risk factors for EH have been mostly limited to single centers and small cohorts. Self-reported history of EH using survey-based research is likely not a feasible epidemiological approach given the low incidence of disease. Evaluation of large-scale clinical datasets that are representative of the broader population is needed in order to capture meaningful epidemiological data from a sufficient number of EH cases.

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Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study

Abstract

Background

Epidermal barrier impairment and altered immune system in atopic dermatitis (AD) may predispose to ultraviolet induced DNA damage.

Objective

To study the association between atopic dermatitis and actinic keratosis (AK) in a population-based cross-sectional study.

Methods

AD was defined by modified criteria of the U.K. working party's diagnostic criteria. The AKs were diagnosed by physicians during a full-body skin examination and keratinocyte cancers were identified via linking to the national pathology database. The results were analysed in adjusted multivariable and multinomial models.

Results

Lower proportion of subjects with AD had AKs than without AD (16% vs 24%, p=0.002; unadjusted OR 0.60; 95% CI, 0.42-0.83, adjusted 0.74; 95% CI, 0.51-1.05, fully adjusted 0.69; 95 CI, (0.47-1.07)). In a multinomial model AD patients were less likely to have 10 or more AKs (adjusted OR 0.28; 95% CI, 0.09-0.90). No effect of AD on BCC and SCC was found (adjusted OR 0.71; 95% CI, 0.41-1.24 and adjusted OR 1.54; 95% CI, 0.66-3.62).

Conclusion

AD in community dwelling patients is not associated with AK.

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PRC1 coordinates timing of sexual differentiation of female primordial germ cells

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Ausgewählte Aufsätze zur europäischen Kunstgeschichte

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Αρχειοθήκη ιστολογίου

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Η λίστα ιστολογίων μου

Παρασκευή 29 Ιανουαρίου 2016

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Αρχειοθήκη ιστολογίου