On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of ...resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness.
Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore's Institute for Reproductive Medicine and Health in NY). Data from multiple choice and open response questions collected demographic, reproductive history, experience and attitudes about Covid-19, prior infertility treatment, sense of hopefulness and stress, coping strategies for mitigating stress and two validated psychological surveys to assess anxiety (six-item short-form State Trait Anxiety Inventory (STAl-6)) and resilience (10-item Connor-Davidson Resilience Scale, (CD-RISC-10).
Seven hundred thirty-four patients were sent invitations to participate. Two hundred fourteen of 734 (29.2%) completed the survey. Patients reported their fertility journey had been delayed a mean of 10 weeks while 60% had been actively trying to conceive > 1.5 years. The top 5 ranked coping skills from a choice of 19 were establishing a daily routine, going outside regularly, exercising, maintaining social connection via phone, social media or Zoom and continuing to work. Having a history of anxiety (p < 0.0001) and having received oral medication as prior infertility treatment (p < 0.0001) were associated with lower resilience. Increased hopefulness about having a child at the time of completing the survey (p < 0.0001) and higher resilience scores (p < 0.0001) were associated with decreased anxiety. Higher reported stress scores (p < 0.0001) were associated with increased anxiety. Multiple multivariate regression showed being non-Hispanic black (p = 0.035) to be predictive of more resilience while variables predictive of less resilience were being a full-time homemaker (p = 0.03), having received oral medication as prior infertility treatment (p = 0.003) and having higher scores on the STAI-6 (< 0.0001).
Prior to and in anticipation of further pauses in treatment the clinical staff should consider pretreatment screening for psychological distress and provide referral sources. In addition, utilization of a patient centered approach to care should be employed.
Phenotyping of immune cell subsets in clinical trials is limited to well-defined phenotypes, due to technological limitations of reporting flow cytometry multi-dimensional phenotyping data. We ...developed a multi-dimensional phenotyping analysis tool and applied it to detect nitric oxide (NO) levels in peripheral blood immune cells before and after adjuvant ipilimumab co-administration with a peptide vaccine in melanoma patients. We analyzed inhibitory and stimulatory markers for immune cell phenotypes that were felt to be important in the NO analysis. The pipeline allows visualization of immune cell phenotypes without knowledge of clustering techniques and to categorize cells by association with relapse-free survival (RFS). Using this analysis, we uncovered the potential for a dichotomous role of NO as a pro- and anti-melanoma factor. NO was found in subsets of immune-suppressor cells associated with shorter-term (≤ 1 year) RFS, whereas NO was also present in immune-stimulatory effector cells obtained from patients with significant longer-term (> 1 year) RFS. These studies provide insights into the cell-specific immunomodulatory role of NO. The methods presented herein can be applied to monitor the pro- and anti-tumor effects of a variety of immune-based therapeutics in cancer patients.
NCT00084656 (https://clinicaltrials.gov/ct2/show/NCT00084656).
Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute-Onset Neuropsychiatric syndrome (PANS) are presumed autoimmune complications of ...infection or other instigating events. To determine the incidence of these disorders, we performed a retrospective review for the years 2017-2019 at three academic medical centers.
We identified the population of children receiving well-child care at each institution. Potential cases of PANS and PANDAS were identified by including children age 3-12 years at the time they received one of five new diagnoses: avoidant/restrictive food intake disorder, other specified eating disorder, separation anxiety disorder of childhood, obsessive-compulsive disorder, or other specified disorders involving an immune mechanism, not elsewhere classified. Tic disorders was not used as a diagnostic code to identify cases. Data were abstracted; cases were classified as PANDAS or PANS if standard definitions were met.
The combined study population consisted of 95,498 individuals. The majority were non-Hispanic Caucasian (85%), 48% were female and the mean age was 7.1 (SD 3.1) years. Of 357 potential cases, there were 13 actual cases mean age was 6.0 (SD 1.8) years, 46% female and 100% non-Hispanic Caucasian. The estimated annual incidence of PANDAS/PANS was 1/11,765 for children between 3 and 12 years with some variation between different geographic areas.
Our results indicate that PANDAS/PANS is a rare disorder with substantial heterogeneity across geography and time. A prospective investigation of the same question is warranted.
Objective
To characterize the accrual of long‐term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and magnetic resonance imaging (MRI) data ...used in clinical trials have long‐term prognostic value.
Methods
This is a prospective study of 517 actively managed MS patients enrolled at a single center.
Results
More than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Scale (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first 2 years had long‐term outcomes that were no different from those of the cohort as a whole. 25‐OH vitamin D serum levels were inversely associated with short‐term MS disease activity; however, these levels had no association with long‐term disability. At a median time of 16.8 years after disease onset, 10.7% (95% confidence interval CI = 7.2–14%) of patients reached an EDSS ≥ 6, and 18.1% (95% CI = 13.5–22.5%) evolved from relapsing MS to secondary progressive MS (SPMS).
Interpretation
Rates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2‐year endpoint was not a predictor of long‐term stability. Finally, the data call into question the utility of annual MRI assessments as a treat‐to‐target approach for MS care. Ann Neurol 2016;80:499–510
Abstract Modern clinical research takes advantage of multicentric cohorts to increase sample size and gain in statistical power. However, combining individuals from different recruitment centers ...provides heterogeneity in the dataset that needs to be accounted for to obtain robust results. Sophisticated statistical multivariate models adjusting for center effect can be implemented, but they can become unstable and can be complex to interpret with the increasing number of covariates to consider. Here, we present a multidimensional reduction technique to identify heterogeneity in a French multicentric cohort of hematopoietic stem cell transplantations and characterize a homogeneous subgroup prior to performing simple statistical univariate analyses. The exclusion of outliers allowed the identification of two genetic factors associated with post-transplantation overall survival. We therefore provide proof-of-concept that a sample size reduction method can efficiently account for heterogeneity and center effect in multicentric cohorts while increasing statistical power and robustness for discovery of new association signals.
Introduction: The need for a new biometric system is gaining importance. Tongue print is also getting acceptance as a system for biometric authentication. The tongue is an extremely muscular organ ...used for communication, taste, and deglutition. Studies have shown variations in the morphology of the tongue. Studies pertaining to the morphology of the tongue is lagging in Nepal. Hence this study was carried out to assess the various morphological variations of the tongue such as shapes, borders, and color among the bachelor level students in a tertiary care center in Nepal Methods: A descriptive cross-sectional study was conducted among 312 bachelor-level students of Chitwan Medical College. The convenience sampling method was used to collect the data. All the data was recorded in a proforma. The sociodemographic details of the participants were recorded. The borders, colors, fissures, and shapes of the tongue’s morphology were documented. The collected data were entered into Microsoft excel 2019 and transported into Statistical Package for Social Science (SPSS) version 16. The data was then analyzed using descriptive statistical methods. The data was also calculated in form of frequency and percentage and later on, they were presented in form of a table. Results: Among 312 students who took part in the study, 126 (40.4 %) of the participants were male and 186 (59.6 %) of them were female. The mean age of participants was 22.38 ±2.008 years. U-shaped tongue was prevalent followed by V-Shape tongue and bifid tongue. More than half of the participants 180 (57.7 %) had partially scalloped tongues. While comparing gender wise U-shaped tongue was more common in both males and females. The bifid tongue was observed more in males 11 (8.7 %) while the V-shaped tongue was more in females 52 (28 %). Conclusions:
The pestilential pathogen SARS-CoV-2 has led to a seemingly ceaseless pandemic of COVID-19. The healthcare sector is under a tremendous burden, thus necessitating the prognosis of COVID-19 severity. ...This in-depth study of plasma proteome alteration provides insights into the host physiological response towards the infection and also reveals the potential prognostic markers of the disease. Using label-free quantitative proteomics, we performed deep plasma proteome analysis in a cohort of 71 patients (20 COVID-19 negative, 18 COVID-19 non-severe, and 33 severe) to understand the disease dynamics. Of the 1200 proteins detected in the patient plasma, 38 proteins were identified to be differentially expressed between non-severe and severe groups. The altered plasma proteome revealed significant dysregulation in the pathways related to peptidase activity, regulated exocytosis, blood coagulation, complement activation, leukocyte activation involved in immune response, and response to glucocorticoid biological processes in severe cases of SARS-CoV-2 infection. Furthermore, we employed supervised machine learning (ML) approaches using a linear support vector machine model to identify the classifiers of patients with non-severe and severe COVID-19. The model used a selected panel of 20 proteins and classified the samples based on the severity with a classification accuracy of 0.84. Putative biomarkers such as angiotensinogen and SERPING1 and ML-derived classifiers including the apolipoprotein B, SERPINA3, and fibrinogen gamma chain were validated by targeted mass spectrometry-based multiple reaction monitoring (MRM) assays. We also employed an
screening approach against the identified target proteins for the therapeutic management of COVID-19. We shortlisted two FDA-approved drugs, namely, selinexor and ponatinib, which showed the potential of being repurposed for COVID-19 therapeutics. Overall, this is the first most comprehensive plasma proteome investigation of COVID-19 patients from the Indian population, and provides a set of potential biomarkers for the disease severity progression and targets for therapeutic interventions.
Severe coronavirus disease 2019 (COVID-19) infection may lead to lung injury, multi-organ failure, and eventually death. Cytokine storm due to excess cytokine production has been associated with ...fatality in severe infections. However, the specific molecular signatures associated with the elevated immune response are yet to be elucidated. We performed a mass-spectrometry-based proteomic and metabolomic analysis of COVID-19 plasma samples collected at two time points. Using Orbitrap Fusion LC–MS/MS-based label-free proteomic analysis, we identified around 10 significant proteins, 32 significant peptides, and 5 metabolites that were dysregulated at the severe time points. Few of these proteins identified by quantitative proteomics were validated using the multiple reaction monitoring (MRM) assay. Integrated pathway analysis using distinct proteomic and metabolomic signatures revealed alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism. Further, we highlight the role of leukocyte activation and arginine metabolism in COVID-19 pathogenesis and targeting these pathways for COVID-19 therapeutics.
Awareness of grave complications like ischemic necrosis associated with uterine compression sutures is essential for prompt diagnosis and timely management.
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