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BACKGROUND: An unannounced balance loss during walking, i.e., balance perturbation, is a stressful event that changes the activity of the Sympathetic Nervous System (SNS). We examined SNS response to unannounced balance perturbation during walking, simulating real-life conditions of balance loss. RESEARCH QUESTION: Do laboratory-induced unannounced balance losses during walking cause a sympathetic response, and if so - does it habituate after a series of perturbations? METHODS: 34 young adults underwent a series of six successive unannounced balance perturbations while walking on a treadmill. Sympathetic activity was monitored continuously using Electrodermal Activity and compared before and immediately after each unannounced perturbation. RESULTS: All perturbations elicited a significant increase in Electrodermal Activity (p<0.001), indicating a phasic increase in the sympathetic drive. The relative phasic increase of Electrodermal Activity caused by the first perturbation was significantly higher than the last perturbation (p<0.05). Three types of Electrodermal Activity behavior were observed: Steady level tonic SNS activity, increased SNS activity, and decreased SNS activity. SIGNIFICANCE: Balance loss during walking triggers phasic SNS response, this response habituates after a series of unannounced balance perturbations. In addition, three distinct patterns of tonic sympathetic activity may imply variations in the ability of the SNS response to habituate across individuals.
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A tiling array yields a series of abundance measurements across the genome using evenly spaced probes. These data can be used for detecting sequences that exhibit a particular behavior. Scanning window statistics are often employed for testing each probe while accounting for local correlation and smoothing noisy measurements. However, window testing may yield false probe discoveries around the sequences and false non-discoveries within the sequences, resulting in biased predicted intervals. We propose to avoid this problem by stipulating that a sequence of interest can appear at most once within a defined region, such as a gene; thus, only one window statistic is considered per region. This substantially reduces the number of tests and hence, is potentially more powerful. We compare this approach to a genome-wise scan that does not require pre-defined search regions, but considers clumps of adjacent probe discoveries. Simulations show that the gene-wise search maintains the nominal FDR level, while the genome-wise scan yields FDR that exceeds the nominal level for low interval effects, and achieves slightly less power. Using arrays to map introns in yeast, we identified 71% of the previously published introns, detected nine previously undiscovered introns, and observed no false intron discoveries by either method.
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Genoma , Intrones/genética , Meiosis/genética , Algoritmos , Biología Computacional , Modelos Teóricos , Saccharomyces cerevisiae/genéticaRESUMEN
BACKGROUND: Primary care physicians played an important role in the global response during the COVID-19 pandemic, but with the absence of laboratory and diagnostics services, the move to telehealth and the focus on respiratory assessment, they faced increased uncertainty when making clinical decisions. OBJECTIVES: This paper aims to examine the impact of the pandemic on decisions made by primary care physicians, as measured by referrals to chest X-ray and laboratory tests and by prescriptions of antibiotics. METHODS: We conducted a retrospective study of all visits recorded with fever or cough, presenting to 209 community clinics in Southern Israel during the years 2018-2022. We describe changes in outcome rates across time and use multivariate generalised linear mixed effects model to compare the odds of referrals and prescriptions between periods, while accounting for gender, age, clinic sector, visit type, diagnosis, and season. RESULTS: In total, 609,823 visits to primary care physicians complied with the cohort definitions. Social restrictions were associated with a decline in all measured outcomes for primary care physician decisions, most prominently among ages 20-59, for throat culture referral during the first lockdown (OR = 0.46) and for cephalosporine prescription during the second lockdown (OR = 0.55). This trend persisted following the cancellation of the restrictions. CONCLUSIONS: Despite higher uncertainty during the COVID-19 social restrictions, the overall course of clinical decision-making processes was maintained, and was associated with a reduction in the use of auxiliary resources, which can improve the quality of patient care by lowering costs and supporting prevention of future antibiotics resistance.
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COVID-19 , Médicos de Atención Primaria , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Israel/epidemiología , Adulto Joven , Anciano , SARS-CoV-2 , Derivación y Consulta/estadística & datos numéricos , Toma de Decisiones Clínicas , Adolescente , Antibacterianos/uso terapéutico , Lactante , Preescolar , Niño , Tos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Fiebre/tratamiento farmacológico , Atención Primaria de SaludRESUMEN
AIMS: Angiotensin receptor neprilysin inhibitor (ARNI) therapy is a cornerstone in the treatment of heart failure with reduced ejection fraction (HFrEF), with significant improvement in mortality as well as morbidity and quality of life. However, maximal ARNI doses often result in hypotension. Recent studies with 'real world' experience suggest that lower doses of ARNI are as effective as higher doses.In order to evaluate the symptomatic effect of low-dose ARNI in HFrEF patients, we analyzed physical activity data obtained via home monitoring of patients with cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analyzed physical activity data obtained from HFrEF patients with CIED-active home monitoring during the years 2021-2022. Patients with ARNI therapy were further divided into subgroups according to the administered dose. Low-dose ARNI included doses of up to 24/26âmg sacubitril/valsartan daily. Intermediate dose and high dose included doses of 72/78-120/130âmg/day, and 144/156-194/206âmg/day, respectively. RESULTS: A total of 122 patients had home monitoring-compatible CIEDs and HFrEF during the study period. Sixty-four of these patients were treated with ARNI. Administration of low-dose ARNI resulted in a 20% increase in daily activity when compared with patients without ARNI treatment ( P â=â0.038). Change in physical activity of patients in the intermediate-dose and high-dose groups was not significant. Younger patients, patients with cardiac resynchronization therapy, and patients without diabetes mellitus were more physically active. CONCLUSION: Low-dose ARNI had a beneficial effect on physical activity in HFrEF patients. MH via CIED provided real-life objective data for patients' follow-up.
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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Neprilisina , Volumen Sistólico , Tetrazoles/efectos adversos , Calidad de Vida , Estudios Retrospectivos , Antagonistas de Receptores de Angiotensina/efectos adversos , Valsartán/efectos adversos , Combinación de Medicamentos , Receptores de AngiotensinaRESUMEN
BACKGROUND: Sperm quality has decreased over the last decades worldwide. It is affected, among others, by season and heat. This study aimed to address the association between ambient temperature and sperm quality by assessing its shape using flexible multivariate models and identifying distinct time-dynamic patterns of temperature change based on unsupervised analysis. MATERIAL AND METHODS: A retrospective population-based study has been conducted, including all samples of males attending the Fertility and In-Vitro-Fertilization unit at a single medical center during 2016-2022. Flexible generalized models were fitted to characterize the relations between sperm quality and temperature while accounting for patients characteristics, and to identify temperature levels that correspond with the optimal sperm quality. This information was then used to estimate adjusted slope coefficients at specified time-windows. RESULTS: In total, 4555 sperm samples were provided by 3229 individuals. Sperm concentration, motility and progressive motility were higher by 8 %, 11 % and 16 %, respectively, during the spring versus the fall season. Furthermore, their quality during early spermatogenesis improved with temperature, until a certain optimum around 23 °C-24 °C. Increasing temperature at later developmental stages was associated with lower sperm concentration and higher motility. Sperm concentration and motility were highest following a period of moderate gradual warming. Motility was higher and sperm concentration was lower, following a period with heatwaves or summer. CONCLUSIONS: This study assessed temperature role in sperm production quality by considering both average and time-dynamic temperatures. It identified several temperature change patterns over time and stratified the analysis by them. The differences in the relations across stages of spermatogenesis were addressed. Several mechanisms may explain the associations found, including heat-induced apoptosis of the sperm cells, and destruction of sperm cells DNA integrity by over-production of reactive oxygen species. The gradual global warming necessitates exploration of individual response to outdoor temperature in relations to genetic predisposition, lifestyle, and other health characteristics.
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Análisis de Semen , Temperatura , Masculino , Estudios Retrospectivos , Humanos , Estaciones del Año , Espermatozoides/fisiología , Motilidad Espermática , Adulto , Recuento de EspermatozoidesRESUMEN
BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard test for the diagnosis of left atrial appendage (LAA) thrombus. Nonetheless, computerized tomography angiography (CTA) is readily used to exclude LAA thrombus before pulmonary vein isolation (PVI) and LAA closure procedures. We aimed to assess the comparability of LAA thrombus diagnosis using chest CTA scans in patients with atrial fibrillation who underwent TEE. METHODS: Retrospective collection of consecutive patients with atrial fibrillation who underwent TEE and chest CTA within 30âdays and had evidence of spontaneous echo contrast (SEC) or LAA thrombus on TEE. Clinical, demographic, and echo data were collected. Prospective analysis of the CTA for evidence of LAA thrombus in the same group of patients was performed. We compared the findings of the two modalities. RESULTS: Out of 1550 patients with atrial fibrillation who underwent TEE examinations in the study period, 63 patients underwent TEE within 30âdays of a chest CTA scan. Twenty-three patients had LAA thrombus and 40 had some degree of SEC according to TEE. On CTA, 11 were interpreted as positive with a high level of suspicion for the presence of an LAA thrombus. Six patients (26.1%) had LAA thrombus according to both CT and TEE. Therefore, low concordance was found between test results (chi-squared continuity correctionâ=â5.5, df â=â1, and P -valueâ=â0.01902). CONCLUSION: The discrepancy between CTA and TEE results suggests these examinations might be more suitable as complementary examinations to exclude LAA thrombus.
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Apéndice Atrial , Fibrilación Atrial , Cardiopatías , Trombosis , Humanos , Ecocardiografía Transesofágica/métodos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Apéndice Atrial/diagnóstico por imagen , Estudios Retrospectivos , Angiografía por Tomografía Computarizada , Trombosis/diagnóstico por imagen , Trombosis/etiología , Cardiopatías/diagnóstico , AngiografíaRESUMEN
(1) Background: COVID-19 presented many challenges to effective treatments, such as managing cardiovascular insufficiency while mitigating risks to healthcare providers. This study utilized NICaS, a non-invasive hemodynamic monitor that provides advanced data via whole-body impedance analysis. We investigated the associated trends in hemodynamic parameters obtained by the NICaS device and their correlation with in-hospital all-cause mortality during COVID-19 hospitalization in the intensive care unit. (2) Methods: Data from 29 patients with COVID-19 admitted to the intensive care unit and monitored with NICaS between April 2020 and February 2021 were analyzed retrospectively. (3) Results: Decreasing cardiac output and cardiac power were significantly associated with death. Total peripheral resistance was significantly increasing in non-survivors as was total body water percentage. Those admitted with a heart rate above 90 beats per minute had a significantly reduced survival. (4) Conclusions: Non-invasive hemodynamic monitoring via the NICaS device is simple and effective in evaluating critically ill patients with COVID-19 and may help guide clinical management via remote monitoring. Controlling tachycardia may help ensure adequate oxygen supply-demand ratio. A hint toward a beneficiary effect of a restrictive fluid balance may be observed.
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INTRODUCTION: Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. METHODS: Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. RESULTS: Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPFâ ≥â 4.2% had significantly higher peak troponin levels ( P â =â 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients ( P â =â 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. CONCLUSION: This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.
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Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Infarto del Miocardio con Elevación del ST , Humanos , Troponina , Infarto del Miocardio sin Elevación del ST/diagnóstico , BiomarcadoresRESUMEN
PURPOSE: Immune Checkpoint Inhibitor (ICI) regimens are approved for first-line treatment of metastatic nononcogene-driven NSCLC. Guidelines do not differentiate which patients with PD-L1 ≥ 50% should receive ICI monotherapy. The clinically validated PROphet NSCLC plasma proteomic-based test is designed to inform this therapeutic decision. METHODS: One hundred oncologists were presented with 3 "virtual" metastatic NSCLC cases with PD-L1 scores and asked to recommend an approved first-line regimen. They then watched an online educational webinar on the PROphetNSCLC test. Postwebinar, the same cases were represented with the addition of a PROphet result, and oncologists again recommended a first-line regimen. Responses were compared to assess the impact on first-line treatment selection. RESULTS: Treatment recommendation changed in 39.6% of PROphet-tested cases, with 93% of physicians changing at least 1 case. In the PD-L1 ≥ 50% group, 89% of physicians changed their recommendation, followed by 77%, in PD-L1 < 1%, and 36% in PD-L1 1% to 49%. âIn the PD-L1 ≥ 50%, PROphet POSITIVE group, the recommendation for ICI monotherapy increased from 60% to 89%. âFor the PD-L1 ≥ 50%, PROphet NEGATIVE group, the recommendation for monotherapy dropped from 60% to 9%. In the PD-L1 < 1%, PROphet NEGATIVE group, 35% of patients were spared toxicity from ICI compared to 11% in PROphet untested cases. CONCLUSION: Adding PROphet to PD-L1 expression impacted therapeutic decision making in first-line NSCLC. PROphet identifies those predicted to have an overall survival benefit from ICI monotherapy versus combination versus chemotherapy, improving the probability of efficacy and reducing toxicity for some patients.
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PURPOSE: Current guidelines for the management of metastatic non-small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions. PATIENTS AND METHODS: We conducted a multicenter observational trial (ClinicalTrials.gov identifier: NCT04056247) of patients undergoing PD-1/PD-L1 inhibitor-based therapy (n = 540) and an additional patient cohort receiving chemotherapy (n = 85) who consented to pretreatment plasma and clinical data collection. Plasma proteome profiling was performed using SomaScan Assay v4.1. RESULTS: Our test demonstrates a strong association between model output and clinical benefit (CB) from PD-1/PD-L1 inhibitor-based treatments, evidenced by high concordance between predicted and observed CB (R2 = 0.98, P < .001). The test categorizes patients as either PROphet-positive or PROphet-negative and further stratifies patient outcomes beyond PD-L1 expression levels. The test successfully differentiates between PROphet-negative patients exhibiting high tumor PD-L1 levels (≥50%) who have enhanced overall survival when treated with a combination of immunotherapy and chemotherapy compared with immunotherapy alone (hazard ratio [HR], 0.23 [95% CI, 0.1 to 0.51], P = .0003). By contrast, PROphet-positive patients show comparable outcomes when treated with immunotherapy alone or in combination with chemotherapy (HR, 0.78 [95% CI, 0.42 to 1.44], P = .424). CONCLUSION: Plasma proteome-based testing of individual patients, in combination with standard PD-L1 testing, distinguishes patient subsets with distinct differences in outcomes from PD-1/PD-L1 inhibitor-based therapies. These data suggest that this approach can improve the precision of first-line treatment for metastatic NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptor de Muerte Celular Programada 1/uso terapéutico , Proteoma , ProteómicaRESUMEN
Most human genes code for more than one transcript. Different ratios of transcripts of the same gene can be found in different cell types or states, indicating differential use of transcription start sites or differential splicing. Such differential transcript use (DTUs) events provide an additional layer of regulation and protein diversity. With the exceptions of PTPRC and CIITA, there are very few reported cases of DTU events in the immune system. To rigorously map DTUs between different human immune cell types, we leveraged four publicly available RNA sequencing datasets. We identified 282 DTU events between five human healthy immune cell types that appear in at least two datasets. The patterns of the DTU events were mostly cell-type-specific or lineage-specific, in the context of the five cell types tested. DTUs correlated with the expression pattern of potential regulators, namely, splicing factors and transcription factors. Of the several immune related conditions studied, only sepsis affected the splicing of more than a few genes and only in innate immune cells. Taken together, we map the DTUs landscape in human peripheral blood immune cell types, and present hundreds of genes whose transcript use changes between cell types or upon activation.
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Sistema Inmunológico , Empalme del ARN , Humanos , Tipificación y Pruebas Cruzadas Sanguíneas , Estado de Salud , Factores de Empalme de ARNRESUMEN
Non-invasive oxygen saturation (SpO2) is a central vital sign used to shape the management of COVID-19 patients. Yet, there have been no report quantitatively describing SpO2 dynamics and patterns in COVID-19 patients using continuous SpO2 recordings. We performed a retrospective observational analysis of the clinical information and 27 K hours of continuous SpO2 high-resolution (1 Hz) recordings of 367 critical and non-critical COVID-19 patients hospitalised at the Rambam Health Care Campus, Haifa, Israel. An absolute SpO2 threshold of 93% most efficiently discriminated between critical and non-critical patients, regardless of oxygen support. Oximetry-derived digital biomarker (OBMs) computed per 1 h monitoring window showed significant differences between groups, notably the cumulative time below 93% SpO2 (CT93). Patients with CT93 above 60% during the first hour of monitoring, were more likely to require oxygen support. Mechanical ventilation exhibited a strong effect on SpO2 dynamics by significantly reducing the frequency and depth of desaturations. OBMs related to periodicity and hypoxic burden were markedly affected, up to several hours before the initiation of the mechanical ventilation. In summary, OBMs, traditionally used in the field of sleep medicine research, are informative for continuous assessment of disease severity and response to respiratory support of hospitalised COVID-19 patients. In conclusion, OBMs may improve risk stratification and therapy management of critical care patients with respiratory impairment.
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COVID-19 , Humanos , COVID-19/terapia , Estudios Retrospectivos , Oximetría , Oxígeno , Frecuencia RespiratoriaRESUMEN
BACKGROUND: Increased levels of bone marrow adipose tissue (BMAT) are negatively associated with skeletal health and hematopoiesis. BMAT is known to increase with age; however, the effect of long-term weight loss on BMAT is still unknown. OBJECTIVE: In this study, we examined BMAT response to lifestyle-induced weight loss in 138 participants (mean age 48 y; mean body mass index 31 kg/m2), who participated in the CENTRAL-MRI trial. METHODS: Participants were randomized for dietary intervention of low-fat or low-carb, with or without physical activity. Magnetic resonance imaging (MRI) was used to quantify BMAT and other fat depots at baseline, six and eighteen months of intervention. Blood biomarkers were also measured at the same time points. RESULTS: At baseline, the L3 vertebrae BMAT is positively associated with age, HDL cholesterol, HbA1c and adiponectin; but not with other fat depots or other metabolic markers tested. Following six months of dietary intervention, the L3 BMAT declined by an average of 3.1 %, followed by a return to baseline after eighteen months (p < 0.001 and p = 0.189 compared to baseline, respectively). The decrease of BMAT during the first six months was associated with a decrease in waist circumference, cholesterol, proximal-femur BMAT, and superficial subcutaneous adipose tissue (SAT), as well as with younger age. Nevertheless, BMAT changes did not correlate with changes in other fat depots. CONCLUSIONS: We conclude that physiological weight loss can transiently reduce BMAT in adults, and this effect is more prominent in younger adults. Our findings suggest that BMAT storage and dynamics are largely independent of other fat depots or cardio-metabolic risk markers, highlighting its unique functions.
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Tejido Adiposo , Médula Ósea , Adulto , Humanos , Persona de Mediana Edad , Médula Ósea/patología , Tejido Adiposo/metabolismo , Vértebras Lumbares , Imagen por Resonancia Magnética , Pérdida de PesoRESUMEN
OBJECTIVES: This study examines relationships between door to balloon (D2B) time and subsequent admissions due to heart failure (HF), acute coronary syndrome (ACS), and mortality for up to 1 year. BACKGROUND: Current guidelines set 90-min for D2B time for primary percutaneous coronary intervention (PPCI) as a goal, which has been shown to reduce mortality and adverse events. METHODS: Using the MDclone ADAMS system integrated with our electronic medical records, we conducted retrospective analysis of all patients admitted due to ST-elevation myocardial infarction from home, without any history of HF or coronary disease, and who underwent PPCI during 2013-2019. Data on D2B time, baseline clinical and demographic characteristics, and outcomes of HF, ACS and mortality were collected. Adjusted HR for each of the outcomes was calculated by multivariate Cox model. RESULTS: A total of 826 patients were included in the final analysis. D2B had no significant effect on incidence of heart failure admissions for up to 1-year follow-up. D2B had a significant effect on mortality at 180 days, showing a 30% increase for each 30-min increase (HR 1.308; CI, 1.046-1.635) as for ACS at 90 days (HR 1.307; 1.025-1.638). The 30-min D2B cutoff showed a significant increase in ACS recurrence throughout the follow-up period at 90 days (HR 2.871, 1.239-6.648), 180 days (HR 2.607, 1.255-5.413), and 1 year (HR 1.886, 1.073-3.317). CONCLUSIONS: Patients with shorter D2B times had significantly reduced mortality and recurrence of ACS, with no effect on heart failure admission incidence.
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Angioplastia Coronaria con Balón , Insuficiencia Cardíaca , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Angioplastia Coronaria con Balón/efectos adversos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/cirugía , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) crisis and consequent changes in medical practice have engendered feelings of distress in diverse populations, potentially adversely affecting the psychological well-being of cancer patients. AIM: The purpose of this observational longitudinal study was to evaluate psychosocial perspectives among patients with cancer on intravenous treatment during the COVID-19 pandemic. METHODS AND RESULTS: The study recruited 164 cancer patients undergoing intravenous anti-neoplastic therapy in a tertiary cancer center. Psychosocial indices were assessed at two points in time, corresponding with the beginning of the first wave of COVID-19 pandemic in Israel (March 2020) and the time of easing of restrictions implemented to curtail spread of infection (May 2020). At Time 1 (T1), elevated COVID-19 distress levels (score 1 and 2 on 5-point scale) were observed in 44% of patients, and associated with pre-existing hypertension and lung disease in multivariate analyses but no demographic or cancer related factors. At Time 2 (T2), 10% had elevated anxiety and 24% depression as indicated by Hospital Anxiety and Depression Scale (HADS-A/D). COVID-19 distress at T1 was related to higher levels of HADS-A at T2 (Spearman 0.33 p < .01), but not HADS-D. Patients with breast cancer expressed greater COVID-19 distress compared with other cancer types (p < .01), while both HADS-A and HADS-D were highest for patients with GI cancer. Patient report of loneliness and decreased support from relatives were factors associated with HADS-A (p = .03 and p < .01, respectively), while HADS-D was not similarly related to the factors evaluated. CONCLUSION: Patients with cancer undergoing intravenous treatment may be vulnerable to acute adverse psychological ramifications of COVID-19, specifically exhibiting high levels of anxiety. These appear unrelated to patient age or disease stage. Those with underlying comorbidities, breast cancer or reduced social support may be at higher risk.
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Neoplasias de la Mama , COVID-19 , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , COVID-19/epidemiología , Depresión/epidemiología , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Estudios Longitudinales , Pandemias , SARS-CoV-2RESUMEN
Background: COVID-19 is a newly recognized illness with a predominantly respiratory presentation. It is important to characterize the differences in disease presentation and trajectory between COVID-19 patients and other patients with common respiratory illnesses. These differences can enhance knowledge of pathogenesis and help in guiding treatment. Methods: Data from electronic medical records were obtained from individuals admitted with respiratory illnesses to Rambam Health Care Campus, Haifa, Israel, between October 1st, 2014 and October 1st, 2020. Four groups of patients were defined: COVID-19 (693), influenza (1,612), severe acute respiratory infection (SARI) (2,292), and Others (4,054). The variable analyzed include demographics (7), vital signs (8), lab tests (38), and comorbidities (15) from a total of 8,651 hospitalized adult patients. Statistical analysis was performed on biomarkers measured at admission and for their disease trajectory in the first 48 h of hospitalization, and on comorobidity prevalence. Results: COVID-19 patients were overall younger in age and had higher body mass index, compared to influenza and SARI. Comorbidity burden was lower in the COVID-19 group compared to influenza and SARI. Severely- and moderately-ill COVID-19 patients older than 65 years of age suffered higher rate of in-hospital mortality compared to hospitalized influenza patients. At admission, white blood cells and neutrophils were lower among COVID-19 patients compared to influenza and SARI patients, while pulse rate and lymphoctye percentage were higher. Trajectories of variables during the first 2 days of hospitalization revealed that white blood count, neutrophils percentage and glucose in blood increased among COVID-19 patients, while decreasing among other patients. Conclusions: The intrinsic virulence of COVID-19 appeared higher than influenza. In addition, several critical functions, such as immune response, coagulation, heart and respiratory function, and metabolism were uniquely affected by COVID-19.
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We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. SIGNIFICANCE: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population.This article is highlighted in the In This Issue feature, p. 2355.
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Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/farmacología , Neoplasias , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BNT162 , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Personal de Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neutropenia/inducido químicamente , Trombocitopenia/inducido químicamente , Tiempo de Tratamiento , VacunaciónRESUMEN
Importance: The efficacy and safety profile of SARS-CoV-2 vaccines have been acquired from phase 3 studies; however, patients with cancer were not represented in these trials. Owing to the recommendation to prioritize high-risk populations for vaccination, further data are warranted. Objective: To evaluate the use and safety of the BNT162b2 vaccine in patients undergoing treatment for cancer. Design, Setting, and Participants: In January 2021, mass SARS-CoV-2 vaccination of high-risk populations, including patients with cancer, was initiated in Israel. This cohort study prospectively enrolled and followed up patients with cancer and healthy participants between January 15 and March 14, 2021. The study was conducted at the Division of Oncology of Rambam Health Care Campus, the major tertiary (referral) medical center of northern Israel. Participants included 232 patients with cancer who were receiving active treatment after the first and second doses of the BNT162b2 vaccine and 261 healthy, age-matched health care workers who served as controls. Exposures: Serum samples were collected after each vaccine dose and in cases of seronegativity. Questionnaires regarding sociodemographic characteristics and adverse reactions were administered at serum collection. A regulatory agencies-approved assay was used to assess IgG at all time points. Patients' electronic medical records were reviewed for documentation of COVID-19 infection and results of blood cell counts, liver enzyme levels, and imaging studies. Main Outcomes and Measures: Seroconversion rate after the first and second doses of the BNT162b2 vaccine and documented COVID-19 infection. Results: Of the 232 patients undergoing treatment for cancer, 132 were men (57%); mean (SD) age was 66 (12.09) years. After the first dose of BNT162b2 vaccine, 29% (n = 25) patients were seropositive compared with 84% (n = 220) of the controls (P < .001). After the second dose, the seropositive rate reached 86% (n = 187) in the patients. Testing rate ratios per 1000 person-days after the first dose were 12.5 (95% CI, 3.4-45.7) for the patients and 48.5 (95% CI, 37.2-63.2) for the controls. Patients undergoing chemotherapy showed reduced immunogenicity (odds ratio, 0.41; 95% CI, 0.17-0.98). In seronegative patients, the rate of documented absolute leukopenia reached 39%. No COVID-19 cases were documented throughout the study period; however, 2 cases in the patient cohort were noted immediately after the first dose. Reported adverse events were similar to data in former trials comprising mostly healthy individuals. Conclusions and Relevance: In this cohort study, the SARS-CoV-2 BNT162b2 vaccine appeared to be safe and achieve satisfactory serologic status in patients with cancer. There was a pronounced lag in antibody production compared with the rate in noncancer controls; however, seroconversion occurred in most patients after the second dose. Future real-world data are warranted to determine the long-term efficacy of the vaccine with regard to type of anticancer treatment.
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Anticuerpos Antivirales/sangre , Antineoplásicos/uso terapéutico , Vacunas contra la COVID-19/inmunología , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BNT162 , Vacunas contra la COVID-19/efectos adversos , Estudios de Casos y Controles , Humanos , Inmunoglobulina G/sangre , Israel , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/inmunología , Estudios Prospectivos , Seroconversión , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
RESUMEN
BACKGROUND: Privacy restrictions limit access to protected patient-derived health information for research purposes. Consequently, data anonymization is required to allow researchers data access for initial analysis before granting institutional review board approval. A system installed and activated at our institution enables synthetic data generation that mimics data from real electronic medical records, wherein only fictitious patients are listed. OBJECTIVE: This paper aimed to validate the results obtained when analyzing synthetic structured data for medical research. A comprehensive validation process concerning meaningful clinical questions and various types of data was conducted to assess the accuracy and precision of statistical estimates derived from synthetic patient data. METHODS: A cross-hospital project was conducted to validate results obtained from synthetic data produced for five contemporary studies on various topics. For each study, results derived from synthetic data were compared with those based on real data. In addition, repeatedly generated synthetic datasets were used to estimate the bias and stability of results obtained from synthetic data. RESULTS: This study demonstrated that results derived from synthetic data were predictive of results from real data. When the number of patients was large relative to the number of variables used, highly accurate and strongly consistent results were observed between synthetic and real data. For studies based on smaller populations that accounted for confounders and modifiers by multivariate models, predictions were of moderate accuracy, yet clear trends were correctly observed. CONCLUSIONS: The use of synthetic structured data provides a close estimate to real data results and is thus a powerful tool in shaping research hypotheses and accessing estimated analyses, without risking patient privacy. Synthetic data enable broad access to data (eg, for out-of-organization researchers), and rapid, safe, and repeatable analysis of data in hospitals or other health organizations where patient privacy is a primary value.