CPAP interface selection.

Development of a smart-fit system for CPAP interface selection.:

Development of a smart-fit system for CPAP interface selection.

Proc Inst Mech Eng H. 2020 Sep 28;:954411920959879

Authors: Ma Z, Hyde P, Drinnan M, Munguia J

Abstract

Continuous Positive Airway Pressure (CPAP) therapy is commonly prescribed for longstanding, acute cases of Obstructive Sleep Apnea (OSA) during which patients must wear a tight-fitting breathing mask overnight for the duration of the treatment. Because this condition frequently leads to the permanent use of CPAP masks, interface selection is a crucial factor influencing the treatment quality and effectiveness. Masks/interface selection is normally performed on a trial an error basis with clinicians informing their selection based on OSA-related factors with basic fitting feedback from patients. However, it is not uncommon for patients to abandon the treatment or request additional consultations due to ill-fitting CPAP mask with the main sources of discomfort being perceived air leakage and mask/strap overtightening leading to skin damage. This work introduces a novel system (Smart-Fit), for CPAP interface selection using advanced digital technologies, such as Reverse Engineering and Computational Modeling (Finite Element Analysis) which are paired to evaluate and determine the best fitting interface for each clinical case. The model simplifies the number of 3D facial landmarks to 12 and established that a 2 mm scan resolution is enough for accurate scans. The Von Mises stress map in ANSYS serves as an indicator of potential high-pressure areas, triggering the need for a chance of mask size. Current results indicate the Smart Fit System can enable a "best fit CPAP interface" to be selected considering individual's physical characteristics and existing CPAP interface configurations. The development of the Smart Fit System is an evolution compared to traditional CPAP interface selection approach, which optimizes the CPAP interface selection process.



PMID: 32988316 [PubMed - as supplied by publisher]

Polysomnographic Outcomes After Observation for Mild Obstructive Sleep Apnea in Children Younger Than 3 Years.

Polysomnographic Outcomes After Observation for Mild Obstructive Sleep Apnea in Children Younger Than 3 Years.:

Polysomnographic Outcomes After Observation for Mild Obstructive Sleep Apnea in Children Younger Than 3 Years.

Otolaryngol Head Neck Surg. 2020 Sep 29;:194599820954383

Authors: Sarber KM, von Allmen DC, Tikhtman R, Howard J, Simakajornboon N, Yu W, Smith DF, Ishman SL

Abstract

OBJECTIVE: Mild obstructive sleep apnea (OSA), particularly in young children, is often treated with observation. However, there is little evidence regarding the outcomes with this approach. Our aim was to assess the impact of observation on sleep for children aged <3 years with mild OSA.

STUDY DESIGN: Case-control study.

SETTING: Pediatric tertiary care center.

METHODS: We reviewed cases of children (<3 years old) diagnosed with mild OSA (obstructive apnea-hypopnea index, 1-5 events/h) who were treated with observation between 2012 and 2017 and had at least 2 polysomnograms performed 3 to 12 months apart. Demographic data and comorbid diagnoses were collected.

RESULTS: Twenty-six children met inclusion criteria; their median age was 7.2 months (95% CI, 1.2-22.8). Nine (35%) were female and 24 (92%) were White. Their median body mass index percentile was 39 (95% CI, 1-76). Comorbidities included cardiac disease (42.3%), laryngomalacia (42.3%), allergies (34.6%), reactive airway disease (23.1%), and prematurity (7.7%). The obstructive apnea-hypopnea index significantly decreased from 2.7 events/h (95% CI, 1-4.5) to 1.3 (95% CI, 0-4.5; P = .013). There was no significant improvement in median saturation nadir (baseline, 86%; P = .76) or median time with end-tidal carbon dioxide >50 mm Hg (baseline, 0 minutes; P = .34). OSA resolved in 8 patients (31%) and worsened in 1 (3.8%). Only race was a significant predictor of resolution per regression analysis; however, only 2 non-White children were included.

CONCLUSION: In our cohort, resolution of mild OSA occurred in 31% of patients treated with 3 to 12 months of observation. The presence of laryngomalacia, asthma, and allergies did not affect resolution. Larger studies are needed to better identify factors (including race) associated with persistent OSA and optimal timing of intervention for these children.

LEVEL OF EVIDENCE: 4.



PMID: 32988267 [PubMed - as supplied by publisher]

Patent foramen ovale in various cerebrovascular diseases caused by obstructive sleep apnea

[The role of patent foramen ovale in various cerebrovascular diseases caused by obstructive sleep apnea].:

[The role of patent foramen ovale in various cerebrovascular diseases caused by obstructive sleep apnea].

Zhonghua Yi Xue Za Zhi. 2020 Sep 29;100(36):2808-2812

Authors: He QY

PMID: 32988140 [PubMed - in process]



Patent Foramen Ovale (PFO)

Adapted from "Holes in the Heart," Stroke Connection Magazine, January/February 2011

https://www.heart.org/en/health-topics/congenital-heart-defects/about-congenital-heart-defects/patent-foramen-ovale-pfo

A hole in your heart would seem to be the very definition of a "problem." Yet more than a quarter of the population has one, and for most it causes no adverse health effects. In fact, the vast majority of those affected don't even know it.



There are two kinds of holes in the heart. One is called an atrial septal defect (ASD), and the other is a patent foramen ovale (PFO). Although both are holes in the wall of tissue (septum) between the left and right upper chambers of the heart (atria), their causes are quite different. An ASD is a failure of the septal tissue to form between the atria, and as such it is considered a congenital heart defect, something that you are born with. Generally an ASD hole is larger than that of a PFO. The larger the hole, the more likely there are to be symptoms.



PFOs, on the other hand, can only occur after birth when the foramen ovale fails to close. The foramen ovale is a hole in the wall between the left and right atria of every human fetus. This hole allows blood to bypass the fetal lungs, which cannot work until they are exposed to air. When a newborn enters the world and takes its first breath, the foramen ovale closes, and within a few months it has sealed completely in about 75 percent of us. When it remains open, it is called a patent foramen ovale, patent meaning open. For the vast majority of the millions of people with a PFO, it is not a problem, even though blood is leaking from the right atrium to the left. Problems can arise when that blood contains a blood clot.



A simplified view of a PFO



"Blood clots form in our veins all the time," said Dr. David Thaler, associate professor of neurology at Tufts University School of Medicine and director of the Comprehensive Stroke Center at Tufts Medical Center in Boston. "These are tiny blood clots of just a few millimeters that travel from all over the body into the vena cava where they enter the right upper chamber of the heart." From there they are pumped into the right ventricle, from where they enter the lungs. These tiny blood clots (individually called a venous thrombus) get filtered by the tiny capillaries in the lungs, after which the freshly oxygenated blood enters the left atrium, then the left ventricle. From the left ventricle, the blood is pumped out into the miles of blood vessels that feed oxygen and nutrients to every cell in our bodies. "Our lungs normally filter out these tiny clots, but a 2mm thrombus in the brain can cause real havoc," Dr. Thaler said.



That can happen when someone has a PFO or ASD. "PFOs don't actually cause strokes, but they provide a portal through which a thrombus might pass from the right to the left side of the circulation," said Dr. Patrick O'Gara, professor of medicine at Harvard Medical School and executive director of the Shapiro Cardiovascular Center. Depending on whether the clot takes a right or left turn as it exits the heart, it can travel to the brain and cause stroke or TIA. Statistically speaking, the odds of this happening are low, but it can happen.



How would you know?

Finding out whether you have a PFO is not easy, and it's something that isn't usually investigated unless a patient is having symptoms like severe migraines, TIA or stroke. Although the prevalence of PFO is about 25 percent in the general population, this increases to about 40 to 50 percent in patients who have stroke of unknown cause, referred to as cryptogenic stroke. This is especially true in patients who have had a stroke before age 55. In some cases, the PFO combines with another condition, such as atrial fibrillation, to increase the risk of stroke.



For survivors who don't have a definitive cause of their stroke, Dr. O'Gara suggests meeting with their neurologist to discuss the possibility of PFO. "There are many causes of stroke and having a PFO accounts for only a very small number," Dr. O'Gara said. PFO is diagnosed with an echocardiogram. An echocardiogram, also called a cardiac echo, creates an image of the heart using ultrasound.



What's to be done?

"The greatest myth about PFOs is that they must be closed. The vast majority of them require no treatment," Dr. O'Gara said. "If someone has one that is related to symptoms, they can be treated with aspirin, warfarin or catheter closure, depending on the circumstances."



Of course, drugs don't close the hole, "so the aim of drug treatment is to prevent a clot from forming in the first place," Dr. Thaler said. Nothing will close it except open-heart surgery or a closure device placed by a catheter threaded from the groin through the veins to the heart. Until recently, there were no approved catheter-closure devices designed for PFOs. The FDA has approved a device for patients who've had a stroke believed to be caused by a PFO, which reduces the risk of another stroke.

Clinical FLASH Radiotherapy System: Pediatric Whole Brain Irradiation with 40 MeV Electrons at FLASH Dose Rates.

Initial Steps Towards a Clinical FLASH Radiotherapy System: Pediatric Whole Brain Irradiation with 40 MeV Electrons at FLASH Dose Rates.:

Initial Steps Towards a Clinical FLASH Radiotherapy System: Pediatric Whole Brain Irradiation with 40 MeV Electrons at FLASH Dose Rates.

Radiat Res. 2020 Sep 29;:

Authors: Breitkreutz DY, Shumail M, Bush KK, Tantawi SG, Maxim PG, Loo BW

Abstract

In this work, we investigated the delivery of a clinically acceptable pediatric whole brain radiotherapy plan at FLASH dose rates using two lateral opposing 40-MeV electron beams produced by a practically realizable linear accelerator system. The EGSnrc Monte Carlo software modules, BEAMnrc and DOSXYZnrc, were used to generate whole brain radiotherapy plans for a pediatric patient using two lateral opposing 40-MeV electron beams. Electron beam phase space files were simulated using a model of a diverging beam with a diameter of 10 cm at 50 cm SAD (defined at brain midline). The electron beams were collimated using a 10-cm-thick block composed of 5 cm of aluminum oxide and 5 cm of tungsten. For comparison, a 6-MV photon plan was calculated with the Varian AAA algorithm. Electron beam parameters were based on a novel linear accelerator designed for the PHASER system and powered by a commercial 6-MW klystron. Calculations of the linear accelerator's performance indicated an average beam current of at least 6.25 μA, providing a dose rate of 115 Gy/s at isocenter, high enough for cognition-sparing FLASH effects. The electron plan was less homogenous with a homogeneity index of 0.133 compared to the photon plan's index of 0.087. Overall, the dosimetric characteristics of the 40-MeV electron plan were suitable for treatment. In conclusion, Monte Carlo simulations performed in this work indicate that two lateral opposing 40-MeV electron beams can be used for pediatric whole brain irradiation at FLASH dose rates of 115 Gy/s and serve as motivation for a practical clinical FLASH radiotherapy system, which can be implemented in the near future.



PMID: 32991725 [PubMed - as supplied by publisher]

Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors-is it time for a paradigm shift?

Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors-is it time for a paradigm shift?:

Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors-is it time for a paradigm shift?

Clin Rheumatol. 2020 Sep 28;:

Authors: Chatzidionysiou K, Liapi M, Tsakonas G, Gunnarsson I, Catrina A

Abstract

Immunotherapy has revolutionized cancer treatment during the last years. Several monoclonal antibodies that are specific for regulatory checkpoint molecules, that is, immune checkpoint inhibitors (ICIs), have been approved and are currently in use for various types of cancer in different lines of treatment. Cancer immunotherapy aims for enhancing the immune response against cancer cells. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events of autoimmune origin, often referred to as immune-related adverse events (irAEs), which limit the utility of these drugs. These irAEs are quite common and can affect almost every organ. The grade of toxicity varies from very mild to life-threatening. The pathophysiological mechanisms behind these events are not fully understood. In this review, we will summarize current evidence specifically regarding the rheumatic irAEs and we will focus on current and future treatment strategies. Treatment guidelines largely support the use of glucocorticoids as first-line therapy, when symptomatic therapy is not efficient, and for more persistent and/or moderate/severe degree of inflammation. Targeted therapies are higher up in the treatment pyramid, after inadequate response to glucocorticoids and conventional, broad immunosuppressive agents, and for severe forms of irAEs. However, preclinical data provide evidence that raise concerns regarding the potential risk of impaired antitumoral effect. This potential risk of glucocorticoids, together with the high efficacy and potential synergistic effect of newer, targeted immunomodulation, such as tumor necrosis factor and interleukin-6 blockade, could support a paradigm shift, where more targeted treatments are considered earlier in the treatment sequence.



PMID: 32989505 [PubMed - as supplied by publisher]

Triapine.

In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine.:

In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine.

Cancer Chemother Pharmacol. 2020 Sep 28;:

Authors: Joshi A, Kiesel BF, Chaphekar N, Jones R, Guo J, Kunos CA, Taylor S, Chu E, Venkataramanan R, Beumer JH

Abstract

PURPOSE: To investigate the metabolic pathways of triapine in primary cultures of human hepatocytes and human hepatic subcellular fractions; to investigate interactions of triapine with tenofovir and emtricitabine; and to evaluate triapine as a perpetrator of drug interactions. The results will better inform future clinical studies of triapine, a radiation sensitizer currently being studied in a phase III study.

METHODS: Triapine was incubated with human hepatocytes and subcellular fractions in the presence of a number of inhibitors of drug metabolizing enzymes. Triapine depletion was monitored by LC-MS/MS. Tenofovir and emtricitabine were co-incubated with triapine in primary cultures of human hepatocytes. Triapine was incubated with a CYP probe cocktail and human liver microsomes, followed by LC-MS/MS monitoring of CYP specific metabolite formation.

RESULTS: Triapine was not metabolized by FMO, AO/XO, MAO-A/B, or NAT-1/2, but was metabolized by CYP450s. CYP1A2 accounted for most of the depletion of triapine. Tenofovir and emtricitabine did not alter triapine depletion. Triapine reduced CYP1A2 activity and increased CYP2C19 activity.

CONCLUSION: CYP1A2 metabolism is the major metabolic pathway for triapine. Triapine may be evaluated in cancer patients in the setting of HIV with emtricitabine or tenofovir treatment. Confirmatory clinical trials may further define the in vivo triapine metabolic fate and quantify any drug-drug interactions.



PMID: 32989483 [PubMed - as supplied by publisher]

Localized Extra-pulmonary Small Cell Carcinoma (EPSC) of the Esophagus

First Reported Case of Localized Extra-pulmonary Small Cell Carcinoma (EPSC) of the Esophagus Treated With Triple Therapy.:

First Reported Case of Localized Extra-pulmonary Small Cell Carcinoma (EPSC) of the Esophagus Treated With Triple Therapy.

Anticancer Res. 2020 Oct;40(10):5919-5923

Authors: Haag A, Jayakrishnan T, Shah D, Sandhu A, Monga D

Abstract

BACKGROUND/AIM: Early stage extra-pulmonary small cell carcinoma (EPSC) of the esophagus is very rare and is usually treated with chemo-radiation or surgical resection.

CASE REPORT: A case of early stage small cell carcinoma of the esophagus that was treated with all three current modalities of chemotherapy, radiation, and surgery. To our best knowledge this is the first case treated with triple therapy. The patient is a 64-year-old male with increasing gastroesophageal reflux disease (GERD) symptoms. EGD biopsy of the mass showed small cell carcinoma. Metastatic work up was negative. Patient was treated with 6 cycles of a platinum-based agents and Etoposide along with radiation. Patient underwent distal esophagectomy. Patient is alive without evidence of recurrent disease at 20 months follow up.

CONCLUSION: Currently there are no definite treatment recommendations, but we present a possible future option with good outcomes in patients who can tolerate triple therapy.



PMID: 32988923 [PubMed - in process]

Obesity on voriconazole pharmacokinetics

Impact of obesity on voriconazole pharmacokinetics among pediatric hematopoietic cell transplant recipients.:

Impact of obesity on voriconazole pharmacokinetics among pediatric hematopoietic cell transplant recipients.

Antimicrob Agents Chemother. 2020 Sep 28;:

Authors: Takahashi T, Smith AR, Jacobson PA, Fisher J, Rubin NT, Kirstein MN

Abstract

BACKGROUND: Voriconazole (VCZ) is an antifungal agent with wide inter- and intra- patient pharmacokinetic (PK) variability and narrow therapeutic index. Although obesity was associated with higher VCZ trough concentrations in adults, the impact of obesity is yet to be studied in children. We characterized the PK of VCZ in obese accounting for age and CYP2C19 phenotype.

METHODS: We conducted intensive PK studies of VCZ and VCZ N-oxide metabolite in 44 hematopoietic stem cell transplant (HSCT) recipients aged 2-21 years who received prophylactic intravenous VCZ q12h. Blood samples were collected at 5 and 30 minutes; 1, 3, 6 and 9 hours after infusion completion; and immediately before the next infusion start. We estimated PK parameters with non-compartmental analysis and evaluated for association with obesity by multiple linear regression analysis.

RESULTS: The 44 participants included 9 (20%) with obesity. CYP2C19 metabolism phenotypes were identified as normal in 22 (50%), poor/intermediate in 13 (30%), and rapid/ultra-rapid in 9 patients (21%). Obesity status significantly affects VCZ Cmin (higher by 1.4 mg/L, 95%CI: 0.0-2.8, p = 0.047) and VCZ AUCRATIO (higher by 0.4; 95%CI: 0.0-0.7; p=0.03) while no association was observed with VCZ AUC (p=0.09) after adjusting for clinical factors. A younger age and a CYP2C19 phenotype were associated with lower VCZ AUC.

CONCLUSION: Obesity was associated with decreased metabolism of VCZ to its inactive N-oxide metabolite and, concurrently, increased VCZ Cmin, which is deemed clinically meaningful. Future research should aim to further characterize its effects and determine a proper dosing regimen for the obese.



PMID: 32988816 [PubMed - as supplied by publisher]

Investigate coagulation disturbance with viscoelastic monitoring (VEM)

New Uses for Thromboelastography and Other Forms of Viscoelastic Monitoring in the Emergency Department: A Narrative Review.:

New Uses for Thromboelastography and Other Forms of Viscoelastic Monitoring in the Emergency Department: A Narrative Review.

Ann Emerg Med. 2020 Sep 25;:

Authors: Tyler PD, Yang LM, Snider SB, Lerner AB, Aird WC, Shapiro NI

Abstract

Patients frequently visit the emergency department with conditions that place them at risk of worse outcomes when accompanied by coagulopathy. Routine tests of coagulation-prothrombin time, partial thromboplastin time, platelets, and fibrinogen-have shortcomings that limit their use in providing emergency care. One alternative is to investigate coagulation disturbance with viscoelastic monitoring (VEM), a coagulation test that measures the timing and strength of blood clot development in real time. VEM is widely used and studied in cardiac surgery, liver transplant surgery, anesthesia, and trauma. In this article, we review the technique of VEM and the biologic rationale of using it in addition to routine tests of coagulation in emergency clinical situations. Then, we review the evidence (or lack thereof) for using VEM in the diagnosis and treatment of specific conditions. Finally, we describe the limitations of the test and future directions for clinical use and research in emergency medicine.



PMID: 32988649 [PubMed - as supplied by publisher]

Nodal recurrences after stereotactic body radiotherapy for early stage non-small-cell lung cancer.

Nodal recurrences after stereotactic body radiotherapy for early stage non-small-cell lung cancer.:

Nodal recurrences after stereotactic body radiotherapy for early stage non-small-cell lung cancer.

Curr Probl Cancer. 2020 Sep 22;:100653

Authors: Tibdewal A, Pathak RS, Agarwal JP, Hoskote S, Mummudi N, Iyer V, Nair AG

Abstract

Lobectomy is considered the standard of care for early stage non-small-cell lung cancer. However, for those patients who remain unfit to undergo surgery due to advanced age, poor performance status, comorbidities, poor pulmonary reserve or a combination of these are now treated with stereotactic body radiation therapy (SBRT). Due to its noninvasive nature, lower cost, lower toxicity, reduced recovery time and equivalent efficacy, even medically operable patients are attracted to the option of SBRT despite the lack of level I evidence. Thus, studying the incidence and patterns of recurrence after SBRT help in understanding the magnitude of the problem, risk factors associated with the different patterns of recurrence, and aid in devising strategies to prevent them in future. Nodal recurrences are not uncommon after SBRT and can potentially lead to further seeding for distant metastases and ultimately poor survival. This review is aimed at reviewing the published data on the incidence of nodal recurrences after SBRT and compare it to surgery, identify potential risk factors for recurrence, salvage treatment options and prevention strategies.



PMID: 32988628 [PubMed - as supplied by publisher]

Liquid biopsy for ALK-positive early non-small-cell lung cancer predicts disease relapse.

Liquid biopsy for ALK-positive early non-small-cell lung cancer predicts disease relapse.:

Liquid biopsy for ALK-positive early non-small-cell lung cancer predicts disease relapse.

Future Oncol. 2020 Sep 29;:

Authors: Li J, Dong W, Liu LN, Huang YJ, Xiao MF

Abstract

Background: We aimed to determine whether circulating tumor cells (CTCs) and cell-free DNA (cfDNA) aids in prognosis of relapse-free survival (RFS). Methods: Non-small cell lung cancer patients with ALK mutations were recruited prospectively. CTCs and cfDNA were quantified at different time points. RFS was estimated and correlated. Results: Baseline median CTCs and cfDNA were 16 cells and 57 ng/mL and declined to nine cells and 30 ng/mL, respectively, postsurgery in 150 patients. Interestingly, patients without detectable CTCs postsurgery fared better for RFS. cfDNA monitoring showed deviations within 7 months of surgery that were significant predictors for RFS. Conclusion: Short-term monitoring of CTCs and cfDNA variations shows promise for early risk detection and may aid in better disease control.



PMID: 32988235 [PubMed - as supplied by publisher]

Immune checkpoint inhibitors in clinical diagnosis and treatment of non-small cell lung cancer

[Research progress of immune checkpoint inhibitors in clinical diagnosis and treatment of non-small cell lung cancer].:

[Research progress of immune checkpoint inhibitors in clinical diagnosis and treatment of non-small cell lung cancer].

Zhonghua Zhong Liu Za Zhi. 2020 Sep 23;42(9):713-717

Authors: Huang Y, Xu K, Wang W, Cui F, Zeng Y, Hao ZX, Cai WP, He JX, Liu J

Abstract

Lung cancer is currently the malignant tumor with the highest morbidity and mortality in the world, and the main type is non-small cell lung cancer. Immune checkpoint inhibitor is a landmark discovery in the history of cancer treatment, which rewrites the history of cancer treatment, and improves the medical treatment of advanced tumors by a big step forward. The article summarizes the research progress of therapeutic drugs against anti-programmed cell death protein and programmed cell death protein ligand antibodies in the clinical diagnosis and treatment of non-small cell lung cancer. The principle of drug action, the differences in the diagnosis and treatment of non-small cell lung cancer in different clinical stages, and future research directions are discussed to provide the usage guidelines of immune checkpoint inhibitors for clinical oncologists.



PMID: 32988151 [PubMed - in process]

Childhood Anaplastic Large Cell Lymphoma

Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial.:

Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial.

Cancers (Basel). 2020 Sep 24;12(10):

Authors: Mussolin L, Le Deley MC, Carraro E, Damm-Welk C, Attarbaschi A, Williams D, Burke A, Horibe K, Nakazawa A, Wrobel G, Mann G, Csóka M, Uyttebroeck A, Fernández-Delgado Cerdá RF, Beishuizen A, Mellgren K, Burkhardt B, Klapper W, Turner SD, D'Amore ESG, Lamant L, Reiter A, Woessmann W, Brugières L, Pillon MPOBOTEIFCNL

Abstract

With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). Analysis of minimal disseminated disease (MDD), available for 162 patients, showed that both SC/LH pattern (hazard ratio = 2.4) and MDD positivity (hazard ratio = 2.15) were significantly associated with risk of failure in multivariate analysis. Considering MDD and SC/LH results, patients were separated into three biological/pathological (bp) risk groups: a high-risk group (bpHR) including MDD-positive patients with SC/LH pattern; a low-risk group (bpLR) including MDD-negative patients without SC/LH pattern; and an intermediate-risk group (bpIR) including remaining patients. The 10-year PFS was 40%, 75% and 86% for bpHR, bpIR and bpLR, respectively (p < 0.0001). These results should be considered in the design of future ALCL trials to tailor individual treatments.



PMID: 32987765 [PubMed]

Injection laryngoplasty for treatment of congenital type 1 laryngeal clefts.

Side effects and complications of injection laryngoplasty for treatment of congenital type 1 laryngeal clefts.:

Related Articles

Side effects and complications of injection laryngoplasty for treatment of congenital type 1 laryngeal clefts.

Int J Pediatr Otorhinolaryngol. 2020 Apr;131:109886

Authors: Ramazani F, Isaac A, Johannsen W, El-Hakim H

Abstract

INTRODUCTION: Injection laryngoplasty (IL) is a brief, minimally invasive procedure involving injection of agents to augment the interarytenoid space. It was initially described as a diagnostic and temporizing measure for management of type one laryngeal clefts (LC1) and associated swallowing dysfunction (SwD), but more gradually it is being proposed as a definitive treatment modality. However, the morbidity of this treatment for LC1 remains under-investigated. This study sought to determine the morbidities associated with IL as a treatment modality for LC1 and associated SwD.

METHOD: Single centre retrospective review of a prospective surgical database of one Pediatric Otolaryngologist at a tertiary care center. Participants included pediatric patients with an endoscopic diagnosis of LC1, treated with IL between 2000 and 2018-excluding those with concurrent upper airway anomalies. Patient charts were reviewed for demographic information, immediate post-op complications (within the first 14 days following IL), and subsequent management.

RESULTS: Out of 85 consecutive, eligible patients, 12 were excluded (5 subglottic stenosis, 6 laryngomalacia, and one tracheomalacia). Of the 73 included patients, 42 were male and 31 females. The median age at IL was 29 months (range 1-132, interquartile range of 38 months). All IL procedures in this study utilized hyaluronic acid derivatives. From this series, 13 patients experienced post-operative complications. The complications encountered were respiratory distress (N = 5), croup-like cough (N = 6), and stridor (N = 6). These complications were either self-limiting (N=9), managed by systemic or inhaled steroids (N = 4), or admitted to hospital for monitoring (N=3). One case (augmented with dextranomer and hyaluronic acid) required intubation, repeat endoscopy, and drainage of seroma.

CONCLUSION: IL was followed by respiratory morbidity in nearly two in ten of this series of consecutive patients. All the morbidities occurred in association with one injection product. Parents should be counselled appropriately about potential morbidities associated with this procedure.



PMID: 31968273 [PubMed - indexed for MEDLINE]

TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells.

TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells.:

TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells.

J Exp Med. 2021 Jan 04;218(1):

Authors: Mishra S, Liao W, Liu Y, Yang M, Ma C, Wu H, Zhao M, Zhang X, Qiu Y, Lu Q, Zhang N

Abstract

In addition to Foxp3+ CD4+ regulatory T cells (CD4+ T reg cells), Foxp3- CD8+ regulatory T cells (CD8+ T reg cells) are critical to maintain immune tolerance. However, the molecular programs that specifically control CD8+ but not CD4+ T reg cells are largely unknown. Here, we demonstrate that simultaneous disruption of both TGF-β receptor and transcription factor Eomesodermin (Eomes) in T cells results in lethal autoimmunity due to a specific defect in CD8+ but not CD4+ T reg cells. Further, TGF-β signal maintains the regulatory identity, while Eomes controls the follicular location of CD8+ T reg cells. Both TGF-β signal and Eomes coordinate to promote the homeostasis of CD8+ T reg cells. Together, we have identified a unique molecular program designed for CD8+ T reg cells.



PMID: 32991667 [PubMed - as supplied by publisher]

Cell Cycle

 

miR-138-5p suppresses glioblastoma cell viability and leads to cell cycle arrest by targeting cyclin D3.

miR-138-5p suppresses glioblastoma cell viability and leads to cell cycle arrest by targeting cyclin D3. Oncol Lett. 2020 Nov;20(5):264 Authors: Wu H, Wang C, Liu Y, Yang C, Liang X, Zhang X, Li X Abstract Although malignant glioblastoma (GBM) treatment has significantly improved in the past few decades, the prognosis of GBM remains unsatisfactory. MicroRNA (miR)-138-5p has been reported as a tumor suppressor in several types of human cancer;...

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells.

Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells. Clin Transl Oncol. 2020 Sep 28;: Authors: Huang XF, Chen PT, Lin YL, Lee MS, Chang KF, Liao KW, Sheu GT, Hsieh MC, Tsai NM Abstract PURPOSE: The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing...

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

[Epigallocatechin gallate induces CHD5 gene demethylation to promote acute myeloid leukemia cell apoptosis in vitro by regulating p19Arf-p53-p21Cip1 signaling pathway].

[Epigallocatechin gallate induces CHD5 gene demethylation to promote acute myeloid leukemia cell apoptosis in vitro by regulating p19Arf-p53-p21Cip1 signaling pathway]. Nan Fang Yi Ke Da Xue Xue Bao. 2020 Sep 30;40(9):1230-1238 Authors: Wu M, Jiang M, Xue M, Li Q, Cheng B, Huang M, Xu L, Zhang Y Abstract OBJECTIVE: To investigate the mechanism by which epigallocatechin gallate (EGCG) induces CHD5 gene demethylation and promotes the apoptosis...

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

Inflammaging of Female Reproductive System: a Molecular Landscape.

Inflammaging of Female Reproductive System: a Molecular Landscape. Curr Aging Sci. 2020 Sep 29;: Authors: Rodichkina V, Kvetnoy I, Polyakova V, Arutjunyan A, Nasyrov R, Ivanov D Abstract Aging is a complex biological process, a major aspect of which is the accumulation of somatic changes throughout the life. Cellular senescence is a condition in which cells undergo an irreversible cell cycle arrest in response to various cellular stresses....

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

Bacterial cell proliferation: from molecules to cells.

Bacterial cell proliferation: from molecules to cells. FEMS Microbiol Rev. 2020 Sep 29;: Authors: Meunier A, Cornet F, Campos M Abstract Bacterial cell proliferation is highly efficient, both because bacteria grow fast and multiply with a low failure rate. This efficiency is underpinned by the robustness of the cell cycle and its synchronization with cell growth and cytokinesis. Recent advances in bacterial cell biology brought about by single...

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

Developmentally-programmed cellular senescence is conserved and widespread in zebrafish.

Developmentally-programmed cellular senescence is conserved and widespread in zebrafish. Aging (Albany NY). 2020 Sep 29;12: Authors: Da Silva-Álvarez S, Guerra-Varela J, Sobrido-Cameán D, Quelle A, Barreiro-Iglesias A, Sánchez L, Collado M Abstract Cellular senescence is considered a stress response imposing a stable cell cycle arrest to restrict the growth of damaged cells. More recently however, cellular senescence was identified during mouse...

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer.

Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer. Bioorg Med Chem. 2020 Sep 12;28(23):115763 Authors: Hou Q, Lin X, Lu X, Bai C, Wei H, Luo G, Xiang H Abstract A series of novel steroidal-chalcone derivates were designed and synthesized based on the molecular hybridization strategy and further evaluated for their growth inhibitory activity against three human cancer cell...

pubmed: cell cycle arrest

Wed Sep 30, 2020 13:10

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.:

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.

Cancer Discov. 2020 Sep 28;:

Authors: Sakuma S, Raices M, Borlido J, Guglielmi V, Zhu EYS, D'Angelo MA

Abstract

Nuclear pore complexes (NPCs) are the central mediators of nucleocytoplasmic transport. Increasing evidence shows that many cancer cells have increased numbers of NPCs and become addicted to the nuclear transport machinery. How reducing NPC numbers affects the physiology of normal and cancer cells and if it could be exploited for cancer therapies has not been investigated. We report that inhibition of NPC formation, a process mostly restricted to proliferating cells, causes selective cancer cell death, prevents tumor growth and induces tumor regression. While cancer cells die in response to NPC assembly inhibition, normal cells undergo a reversible cell cycle arrest that allows them to survive. Mechanistically, reducing NPC numbers results in multiple alterations contributing to cancer cell death including abnormalities in nuclear transport, catastrophic alterations in gene expression, and the selective accumulation of DNA damage. Our findings uncover the NPC formation process as a novel targetable pathway in cancer cells.



PMID: 32988961 [PubMed - as supplied by publisher]

Azidothymidine (AZT) Inhibits Proliferation of Human Ovarian Cancer Cells by Regulating Cell Cycle Progression.

Azidothymidine (AZT) Inhibits Proliferation of Human Ovarian Cancer Cells by Regulating Cell Cycle Progression.:

Azidothymidine (AZT) Inhibits Proliferation of Human Ovarian Cancer Cells by Regulating Cell Cycle Progression.

Anticancer Res. 2020 Oct;40(10):5517-5527

Authors: Hsieh Y, Tseng JJ

Abstract

BACKGROUND/AIM: Drug resistance is a significant cause of high mortality in ovarian cancer (OC) patients. The reverse transcriptase inhibitor azidothymidine (AZT) has been utilized as a treatment for tumors, but its role in OC treatment has not been revealed. The aim of the present in vitro study was to examine the influence of AZT on the growth of human OC cells and the involved proteins.

MATERIALS AND METHODS: The proliferation, cell cycle distribution, extent of apoptosis, mitotic index, and terminal restriction fragment length were examined in three OC cell lines, CaOV3, TOV112D, and TOV21G, treated with AZT.

RESULTS: AZT inhibited growth of the TOV21G and CaOV3 cell lines by regulating cell cycle distribution. Specifically, AZT caused G2/M phase arrest on TOV21G cells and S phase arrest on CaOV3 cells. In addition, AZT treatment induced up-regulation of p21 and p16 in the TOV21G and CaOV3 cell line, respectively.

CONCLUSION: AZT inhibited cell proliferation in serous and clear cell OC via the regulation of cell cycle distribution.



PMID: 32988875 [PubMed - in process]

Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma.

Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma.:

Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma.

Cancers (Basel). 2020 Sep 24;12(10):

Authors: Paíno T, González-Méndez L, San-Segundo L, Corchete LA, Hernández-García S, Díaz-Tejedor A, Algarín EM, Mogollón P, Martín-Sánchez M, Gutiérrez NC, Mateos MV, Garayoa M, Ocio EM

Abstract

BACKGROUND: Proviral Insertion site for Moloney murine leukemia virus (PIM) kinases are overexpressed in hematologic malignancies, including multiple myeloma. Previous preclinical data from our group demonstrated the anti-myeloma effect of the pan-PIM kinase inhibitor PIM447.

METHODS: Based on those data, we evaluate here, by in vitro and in vivo studies, the activity of the triple combination of PIM447 + pomalidomide + dexamethasone (PIM-Pd) in multiple myeloma.

RESULTS: Our results show that the PIM-Pd combination exerts a potent anti-myeloma effect in vitro and in vivo, where it markedly delays tumor growth and prolongs survival of treated mice. Mechanism of action studies performed in vitro and on mice tumor samples suggest that the combination PIM-Pd inhibits protein translation processes through the convergent inhibition of c-Myc and mTORC1, which subsequently disrupts the function of eIF4E. Interestingly the MM pro-survival factor IRF4 is also downregulated after PIM-Pd treatment. As a whole, all these molecular changes would promote cell cycle arrest and deregulation of metabolic pathways, including glycolysis and lipid biosynthesis, leading to inhibition of myeloma cell proliferation.

CONCLUSIONS: Altogether, our data support the clinical evaluation of the triple combination PIM-Pd for the treatment of patients with multiple myeloma.



PMID: 32987735 [PubMed]

Polyploid giant cancer cells (PGCC)

Giants and monsters: Unexpected characters in the story of cancer recurrence.:

Related Articles

Giants and monsters: Unexpected characters in the story of cancer recurrence.

Adv Cancer Res. 2020;148:201-232

Authors: White-Gilbertson S, Voelkel-Johnson C

Abstract

Polyploid giant cancer cells (PGCC) constitute a dangerous subpopulation of cancer cells and are a driving force in cancer recurrence. These unique cells arise from diploid tumor cells in response to stress encountered in the tumor microenvironment or during cancer therapy. PGCC are greatly dedifferentiated, acquire pluripotency, and are able to replicate through a form of asymmetric division called neosis, which results in new populations that are themselves able to differentiate into new cell types or to re-establish tumors. Progeny tend to be more genetically unstable than the founding population due to the dysregulation required to transition through a PGCC state. Therefore, cancers that escape stressors through this mechanism tend to re-emerge with a more aggressive phenotype that is therapy resistant. This review focuses on the clinical significance of PGCC, the need for standardized nomenclature and molecular markers, as well as possible avenues to develop therapies aimed at PGCC and the process of neosis. The biology underlying the development of PGCC including cell cycle checkpoint dysregulation, stress responses, dedifferentiation, stemness and epithelial-mesenchymal transition is discussed.



PMID: 32723564 [PubMed - indexed for MEDLINE]

Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest.

Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest.:

Related Articles

Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest.

Hum Reprod. 2019 11 01;34(11):2112-2119

Authors: van der Bijl N, Röpke A, Biswas U, Wöste M, Jessberger R, Kliesch S, Friedrich C, Tüttelmann F

Abstract

STUDY QUESTION: Are sequence variants in the stromal antigen 3 (STAG3) gene a cause for non-obstructive azoospermia (NOA) in infertile human males?

SUMMARY ANSWER: Sequence variants affecting protein function of STAG3 cause male infertility due to meiotic arrest.

WHAT IS KNOWN ALREADY: In both women and men, STAG3 encodes for a meiosis-specific protein that is crucial for the functionality of meiotic cohesin complexes. Sequence variants in STAG3 have been reported to cause meiotic arrest in male and female mice and premature ovarian failure in human females, but not in infertile human males so far.

STUDY DESIGN, SIZE, DURATION: The full coding region of STAG3 was sequenced directly in a cohort of 28 men with NOA due to meiotic arrest. In addition, a larger group of 275 infertile men that underwent whole-exome sequencing (WES) was screened for potential STAG3 sequence variants. Furthermore, meiotic spreads, immunohistochemistry, WES and population sampling probability (PSAP) have been conducted in the index case.

PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 28 infertile but otherwise healthy human males who underwent Sanger sequencing of the full coding region of STAG3. Additionally, WES data of 275 infertile human males with different infertility phenotypes have been screened for relevant STAG3 variants. All participants underwent karyotype analysis and azoospermia factor (AZF) screening in advance. In the index patient, segregation analysis, WES data, PSAP, lab parameters, testis histology and nuclear spreads have been added to suplort the findings.

MAIN RESULTS AND THE ROLE OF CHANCE: Two compound-heterozygous variants in STAG3 (c.[1262T>G];[1312C>T], p.[(Leu421Arg)];[(Arg438Ter)]) have been found to cause male infertility due to complete bilateral meiotic arrest in an otherwise healthy human male. Compound heterozygosity was confirmed by Sanger sequencing of the parents and the patient's brother. Other variants which may affect spermatogenesis have been ruled out through analysis of the patient's WES data and application of the PSAP pipeline. As expected from Stag3 knockout-mice meiotic spreads, germ cells did not develop further than zygotene and showed drastic chromosome aberrations. No rare variants in STAG3 were found in the 275 infertile males with other phenotypes. Our results indicate that STAG3 variants that negatively affect its protein function are a rare cause of NOA (<1% of cases).

LIMITATIONS, REASONS FOR CAUTION: We identified only one patient with compound-heterozygous variants in STAG3 causing NOA due to meiotic arrest. Future studies should evaluate STAG3 variants in larger cohorts to support this finding.

WIDER IMPLICATIONS OF THE FINDINGS: Identification of STAG3 sequence variants in infertile human males should improve genetic counselling as well as diagnostics and treatment. Especially before testicular sperm extraction (TESE) for ICSI, STAG3 variants should be ruled out to prevent unnecessary interventions with frustrating outcomes for both patients and clinicians.

STUDY FUNDING/COMPETING INTEREST(S): This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit 'Male Germ Cells: from Genes to Function' (CRU326). Work in the laboratory of R.J. is supported by a grant of the European Union H2020 program GermAge. The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER: Not applicable.



PMID: 31682730 [PubMed - indexed for MEDLINE]

Low C6orf141 Expression in Oral Cancer.

Low C6orf141 Expression is Significantly Associated with a Poor Prognosis in Patients with Oral Cancer.:

Related Articles

Low C6orf141 Expression is Significantly Associated with a Poor Prognosis in Patients with Oral Cancer.

Sci Rep. 2019 03 14;9(1):4520

Authors: Yang CM, Chang HS, Chen HC, You JJ, Liou HH, Ting SC, Ger LP, Li SC, Tsai KW

Abstract

C6orf141 (Chromosome 6 open reading frame 141) is a novel gene, and its role in oral cancer progression remains unclear. C6orf141 expression in oral squamous cell carcinoma (OSCC) and adjacent normal tissues from 428 patients was examined through immunohistochemistry (IHC). Our results revealed that C6orf141 expression was significantly reduced in OSCC compared with adjacent normal tissues. Low C6orf141 expression was significantly associated with a poor American Joint Committee on Cancer pathological stage (P < 0.001), T classification (P = 0.002), and pN stage (P = 0.032). Kaplan-Meier curves revealed that low C6orf141 expression was significantly associated with shorter disease-specific survival (DSS) in patients with OSCC (log-rank P = 0.007). Multivariate analysis indicated that low C6orf141 expression was an independent prognostic biomarker for DSS (adjusted hazard ratio = 1.34; 95% confidence interval = 1.10-1.81; P = 0.05). Additionally, ectopic C6orf141 expression could significantly suppress oral cancer cell proliferation, colony formation, and migratory and invasive abilities. Xenograft tumor growth assay revealed that C6orf141 could significantly suppress oral tumor growth in vivo. Our results suggest that C6orf141 plays a novel tumor-suppressive role in oral cancer cell growth and motility. Furthermore, C6orf141 dysfunction could be a potential prognostic biomarker for OSCC and provide new therapeutic strategies in the future.



PMID: 30872783 [PubMed - indexed for MEDLINE]

Therapy change in metastatic renal cell carcinoma treated with cytoreductive nephrectomy.

Prognostic impact of systemic therapy change in metastatic renal cell carcinoma treated with cytoreductive nephrectomy.:

Prognostic impact of systemic therapy change in metastatic renal cell carcinoma treated with cytoreductive nephrectomy.

Jpn J Clin Oncol. 2020 Sep 29;:

Authors: Ishihara H, Takagi T, Kondo T, Fukuda H, Tachibana H, Yoshida K, Iizuka J, Kobayashi H, Okumi M, Ishida H, Tanabe K

Abstract

OBJECTIVE: Limited data are available regarding the effect of systemic therapy change in the post-cytokine era on survival of metastatic renal cell carcinoma (mRCC) patients undergoing cytoreductive nephrectomy (CN).

METHODS: Overall, 161 patients with synchronously mRCC were retrospectively evaluated. The patients were classified into three groups based on the time of diagnosis: (i) early molecular-targeted therapy (mTT) (2008-2011), (ii) late mTT (2012-8/2016) and (iii) immune checkpoint inhibitor (ICI) eras (9/2016-2018). Overall survival (OS) after the diagnosis was compared among the eras.

RESULTS: Of the 161 patients, 52 (32%), 75 (46%), and 34 patients (21%) were classified into the early mTT, late mTT and ICI eras, respectively. OS was significantly longer in the ICI and late mTT eras than that in the early mTT era (P = 0.0065 and P = 0.0010, respectively) but did not significantly differ between the ICI and late mTT eras (P = 0.389). In 112 patients undergoing CN and systemic therapy, OS was significantly longer in the ICI and late mTT eras than that in the early mTT era (P = 0.0432 and P = 0.0498, respectively) but did not significantly differ between the ICI and late mTT eras (P = 0.320). Multivariate analysis of OS in the 161 synchronous mRCC patients revealed that the era was an independent factor (P < 0.0001), together with the histopathological type (P = 0.0130), CN status (P = 0.0010), International Metastatic Renal Cell Carcinoma Database Consortium risk (P = 0.0002) and liver metastasis status (P = 0.0124).

CONCLUSION: This retrospective analysis showed that systemic therapy change in the post-cytokine era improved OS of mRCC patients undergoing CN.



PMID: 32989464 [PubMed - as supplied by publisher]

Cytokine Storm Syndromes..............familiar hemophagocytic lymphohistiocytosis, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis

Highways to hell: mechanism based management of Cytokine Storm Syndromes:



Publication date: Available online 29 September 2020

Source: Journal of Allergy and Clinical Immunology

Author(s): Scott W. Canna, Randy Q. Cron

Cytokine storm

From Wikipedia, the free encyclopedia

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Not to be confused with Cytokine release syndrome.

A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Normally, cytokines are part of the body's immune response to infection, but their sudden release in large quantities can cause multisystem organ failure and death.^[1] Cytokine storms can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza, SARS-CoV-1,^[2][3] and SARS-CoV-2 (COVID-19 agent). Other causative agents include the Epstein-Barr virus, cytomegalovirus, and group A streptococcus, and non-infectious conditions such as graft-versus-host disease.^[4]

Cytokine storm syndrome is diverse set of conditions that can result in cytokine storm. Cytokine storm syndromes include familiar hemophagocytic lymphohistiocytosis, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis.^[5]

Contents

• 1Cytokine storms versus cytokine release syndrome
• 2Research
• 3History
• 4References

Cytokine storms versus cytokine release syndrome[edit]

The term "cytokine storm" is often loosely used interchangeably with cytokine release syndrome (CRS) but is more precisely a differentiable syndrome that may represent a severe episode of cytokine release syndrome or a component of another disease entity, such as macrophage activation syndrome. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset (fulminant) CRS appears to be a cytokine storm.^[6]

Research[edit]

Nicotinamide (Vitamin B3) is a potent inhibitor of proinflammatory cytokines.^[7][8]

Magnesium decreases inflammatory cytokine production by modulation of the immune system.^[9][10]

History[edit]

The first reference to the term cytokine storm in the published medical literature appears to be by Ferrara et al. in 1993 in a discussion of graft vs. host disease; a condition in which the role of excessive and self-perpetuating cytokine release had already been under discussion for many years.^[11][12] The term next appeared in a discussion of pancreatitis in 2002, and in 2003 it was first used in reference to a reaction to an infection.^[11]

It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, which killed 17 to 50 million people. In this case, a healthy immune system may have been a liability rather than an asset.^[13] Preliminary research results from Taiwan also indicated this as the probable reason for many deaths during the SARS epidemic in 2003.^[14] Human deaths from the bird flu H5N1 usually involve cytokine storms as well.^[15] Cytokine storm has also been implicated in hantavirus pulmonary syndrome.^[16]

In 2006, a study at Northwick Park Hospital in England resulted in all 6 of the volunteers given the drug theralizumab becoming critically ill, with multiple organ failure, high fever, and a systemic inflammatory response.^[17] Parexel, a company conducting trials for pharmaceutical companies, in one of its documents, wrote about the trial and said theralizumab could cause a cytokine storm—the dangerous reaction the men experienced.^[18]

During the COVID-19 pandemic, some doctors attributed many deaths to cytokine storms.^[19][20]

References[edit]

1. ^ Farsalinos, Konstantinos; Barbouni, Anastasia; Niaura, Raymond (2020). "Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: Could nicotine be a therapeutic option?". Internal and Emergency Medicine. 15 (5): 845–852. doi:10.1007/s11739-020-02355-7. PMC 7210099. PMID 32385628.
2. ^ Wong, Jonathan P.; Viswanathan, Satya; Wang, Ming; Sun, Lun-Quan; Clark, Graeme C.; D'Elia, Riccardo V. (February 2017). "Current and future developments in the treatment of virus-induced hypercytokinemia". Future Medicinal Chemistry. 9 (2): 169–178. doi:10.4155/fmc-2016-0181. ISSN 1756-8927. PMC 7079716. PMID 28128003.
3. ^ Liu, Qiang; Zhou, Yuan-hong; Yang, Zhan-qiu (January 2016). "The cytokine storm of severe influenza and development of immunomodulatory therapy". Cellular & Molecular Immunology. 13(1): 3–10. doi:10.1038/cmi.2015.74. ISSN 2042-0226. PMC 4711683. PMID 26189369.
4. ^ Tisoncik, Jennifer R.; Korth, Marcus J.; Simmons, Cameron P.; Farrar, Jeremy; Martin, Thomas R.; Katze, Michael G. (2012). "Into the Eye of the Cytokine Storm". Microbiology and Molecular Biology Reviews. 76 (1): 16–32. doi:10.1128/MMBR.05015-11. ISSN 1092-2172. PMC 3294426. PMID 22390970.
5. ^ Behrens, Edward M.; Koretzky, Gary A. (2017). "Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era". Arthritis & Rheumatology. 69 (6): 1135–1143. doi:10.1002/art.40071. ISSN 2326-5205. PMID 28217930.
6. ^ Porter D, Frey N, Wood PA, Weng Y, Grupp SA (March 2018). "Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel". Journal of Hematology & Oncology. 11 (1): 35. doi:10.1186/s13045-018-0571-y. PMC 5833070. PMID 29499750.
7. ^ Ungerstedt JS, Blömback M, Söderström T (2003). "Nicotinamide is a potent inhibitor of proinflammatory cytokines". Clin Exp Immunol. 131(1): 48–52. doi:10.1046/j.1365-2249.2003.02031.x. PMC 1808598. PMID 12519385.
8. ^ Yanez M, Jhanji M, Murphy K, Gower RM, Sajish M, Jabbarzadeh E (2019). "Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation". Sci Rep. 9 (1): 10219. doi:10.1038/s41598-019-46678-8. PMC 6629694. PMID 31308445.
9. ^ Sugimoto J, Romani AM, Valentin-Torres AM, Luciano AA, Ramirez Kitchen CM, Funderburg N; et al. (2012). "Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism". J Immunol. 188 (12): 6338–46. doi:10.4049/jimmunol.1101765. PMC 3884513. PMID 22611240.
10. ^ Nielsen FH (2018). "Magnesium deficiency and increased inflammation: current perspectives". J Inflamm Res. 11: 25–34. doi:10.2147/JIR.S136742. PMC 5783146. PMID 29403302.
11. ^ Jump up to:^a b Clark IA (June 2007). "The advent of the cytokine storm". Immunology and Cell Biology. 85 (4): 271–3. doi:10.1038/sj.icb.7100062. PMID 17551531. Archived from the original on 2017-05-05. Retrieved 2017-10-16.
12. ^ Ferrara JL, Abhyankar S, Gilliland DG (February 1993). "Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1". Transplantation Proceedings. 25 (1 Pt 2): 1216–7. PMID 8442093.
13. ^ Osterholm MT (May 2005). "Preparing for the next pandemic". The New England Journal of Medicine. 352 (18): 1839–42. CiteSeerX 10.1.1.608.6200. doi:10.1056/NEJMp058068. PMID 15872196.
14. ^ Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, Lei HY (February 2005). "An interferon-gamma-related cytokine storm in SARS patients". Journal of Medical Virology. 75 (2): 185–94. doi:10.1002/jmv.20255. PMC 7166886. PMID 15602737.
15. ^ Haque A, Hober D, Kasper LH (October 2007). "Confronting potential influenza A (H5N1) pandemic with better vaccines". Emerging Infectious Diseases. 13 (10): 1512–8. doi:10.3201/eid1310.061262. PMC 2851514. PMID 18258000.
16. ^ Mori M, Rothman AL, Kurane I, Montoya JM, Nolte KB, Norman JE, et al. (February 1999). "High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome". The Journal of Infectious Diseases. 179 (2): 295–302. doi:10.1086/314597. PMID 9878011.
17. ^ The Lancet Oncology (February 2007). "High stakes, high risks". The Lancet. Oncology. 8 (2): 85. doi:10.1016/S1470-2045(07)70004-9. PMID 17267317.
18. ^ Coghlan A (2006-08-14). "Mystery over drug trial debacle deepens". Health. New Scientist. Retrieved 2009-04-29.
19. ^ Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ (March 2020). "COVID-19: consider cytokine storm syndromes and immunosuppression". Lancet. 395 (10229): 1033–1034. doi:10.1016/S0140-6736(20)30628-0. PMC 7270045. PMID 32192578.
20. ^ Ruan Q, Yang K, Wang W, Jiang L, Song J (March 2020). "Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China". Intensive Care Medicine. 46 (5): 846–848. doi:10.1007/s00134-020-05991-x. PMC 7080116. PMID 32125452.

Categories: 

• Immunology
• Endocrine system
• Cytokines