ABSTRACT
BACKGROUND: Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. METHODS: We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. RESULTS: Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). CONCLUSIONS: NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.
Subject(s)
Feasibility Studies , Graft Survival , Liver Transplantation , Organ Preservation , Perfusion , Humans , Liver Transplantation/methods , Liver Transplantation/adverse effects , Perfusion/methods , Male , Middle Aged , Female , Organ Preservation/methods , Adult , Treatment Outcome , Time Factors , Proof of Concept Study , Aged , Liver/surgery , Liver/blood supply , Retrospective Studies , Postoperative Complications/etiologyABSTRACT
Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575-10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5 year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.
Subject(s)
Liver , Sepsis , Adult , Humans , Retrospective Studies , Reoperation , Risk Factors , Graft SurvivalABSTRACT
International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.
Subject(s)
Genomics , Neoplasms , Humans , Neoplasms/genetics , Neoplasms/therapy , Precision MedicineABSTRACT
BACKGROUND: A majority of women with multiple sclerosis (MS) are diagnosed prior to menopause, yet their experiences during this transition are not well characterized. OBJECTIVES: To explore associations between mental health, sleep, and other quality of life metrics, and vasomotor symptoms (VMSs) in ambulatory, menopausal women with MS. METHODS: A secondary analysis was performed of baseline data from two trials enrolling ambulatory peri/postmenopausal women with MS: NCT02710214 (N = 24, bothersome VMS) and NCT04002934 (ongoing, N = 35, myelin repair). Measures analyzed were 36-Item Short-Form Survey (SF-36) (primary scale: general mental health), subjective sleep quality (Pittsburg Sleep Quality Index), VMS (daily diary, interference), mood (Center for Epidemiologist Studies-Depression Scale (CES-D)), walking impairment (timed 25-foot walk (T25FW)), and global disability (Expanded Disability Status Scale (EDSS)). RESULTS: Participants' characteristics (N = 59) were: mean age 51.8 years (SD = 3.4), mean disease duration 11.3 years (SD = 7.6), median EDSS 3.0 (IQR = 2.0-4.0). Mental health was associated with better sleep quality (rho = -0.41, p = 0.019) and better mood (rho = -0.75, p < 0.001), but not with EDSS or T25FW (rho < 0.20, p > 0.10). Worse sleep quality also correlated with more frequent VMS (rho = 0.41, p = 0.02) and VMS interference (rho = 0.59, p < 0.001). CONCLUSIONS: Findings suggest that optimizing sleep quality, mood, and hot flash quantity/interference could substantially improve mental health in menopausal women with MS-and highlight an important care gap in this population.
Subject(s)
Mental Health , Multiple Sclerosis , Female , Humans , Middle Aged , Quality of Life , Multiple Sclerosis/complications , Depression/epidemiology , MenopauseABSTRACT
INTRODUCTION: Diverticulitis is a common gastrointestinal disease usually presenting with a typical clinical picture depending on the stage of the disease. In complicated cases, the clinical presentation may be untypical, thus delaying diagnosis and treatment. PRESENTATION OF CASE: We present a case of a young patient who was initially treated for obscure intraabdominal abscesses presumably due to gangrenous appendicitis; however, intraoperative exploration revealed a normal appendix and a coloenteric fistula resulting from an unknown and untreated perforated diverticulitis. DISCUSSION: A patient with a perityphlitic abscess was initially managed with primary non-operative management (NOM) in accordance with the current Jerusalem guidelines, but surgery was eventually necessary due to failure of NOM. Intraoperative findings revealed a sigmoido-ileal fistula, a rare but potentially detectable complication of diverticulitis through colonoscopy. This case highlights the challenges in diagnosing and treating common surgical diseases with uncommon clinical presentations, emphasizing the importance of a detailed patient history and not relying solely on imaging studies. CONCLUSION: Intraabdominal abscesses require prompt treatment with non-operative management, while intestinal fistulae associated with diverticulitis are a rare consequence of chronic inflammation, often asymptomatic and often detected incidentally during surgery. In most cases simple fistulous tract resection is usually sufficient as first line therapy.
ABSTRACT
BACKGROUND: Over one-third of multiple sclerosis (MS) patients are post-menopausal women, the primary demographic affected by breast cancer. After breast cancer diagnosis, there is little information about patients' clinical experiences with both diseases. OBJECTIVE: Utilize a case series of MS patients diagnosed with breast cancer to characterize oncologic and MS trajectories, and generate novel insights about clinical considerations using qualitative analysis. METHODS: A single-center retrospective review was performed on medical record data of patients with MS and breast cancer. Thematic analysis was used to characterize experiences with the concurrent diagnoses. RESULTS: For the 43 patients identified, mean age was 56.7 years at cancer diagnosis and MS duration was 16.5 years. Approximately half were treated with MS disease modifying therapy at cancer diagnosis, and half of these subsequently discontinued or changed therapy. Altogether 14% experienced MS relapse(s) during follow-up (with 2 relapses in the first 2 years), with mean annualized relapse rate of 0.03. Cohort Expanded Disability Status Scale (EDSS) scores remained stable during follow-up. Qualitative insights unique to this population were identified regarding immunosuppression use and neurologic symptoms. CONCLUSIONS: MS relapses were infrequent, and there was modest progression during breast cancer treatment. Oncologic outcomes were comparable to non-MS patients with similarly staged cancer.
Subject(s)
Breast Neoplasms , Multiple Sclerosis , Humans , Female , Middle Aged , Multiple Sclerosis/drug therapy , Breast Neoplasms/therapy , Neoplasm Recurrence, Local , Disease Progression , Patient Outcome AssessmentABSTRACT
The current review aims to summarize published research on nutrition transition patterns (depicting changes in dietary consumption) in European populations over the last three decades (1990-2020), with a focus on East-West regional comparisons. Pubmed and Google-Scholar databases were searched for articles providing information on repeated dietary intakes in populations living in countries across Europe, published between January 1990 and July 2021. From the identified 18,031 articles, 62 were found eligible for review (17 from Eastern and 45 from Western European populations). Overall, both in Eastern and Western Europe, there have been pronounced changes in dietary consumption patterns over the last three decades characterized by reductions in average reported intakes of sugar, carbohydrates and saturated fats and increases in reported fruit and vegetable consumption. There has also been a tendency toward a reduction in traditional foods, such as fish, observed in some Mediterranean countries. Overall, these data suggests that European countries have undergone a nutrition transition toward adopting healthier dietary behaviors. These processes occurred already in the period 1990-2000 in many Western European, and in the last decades have been also spreading throughout Eastern European countries. Firm conclusions are hampered by the lack of standardized methodologies depicting changes in dietary intakes over time and the limited coverage of the full variety of European populations. Future studies based on standardized dietary assessment methods and representative for the whole range of populations across Europe are warranted to allow monitoring trends in nutrition transition within and among European countries.
ABSTRACT
Since their approval, immune checkpoint inhibitors (ICIs) have become the standard of care for multiple malignancies. ICIs enhance tumor destruction by blocking important immunomodulatory pathways that regulate T-cell activation. These pathways include programmed cell death protein-1 and its ligands (programmed cell death protein-1 and programmed death ligand-1, respectively) and cytotoxic T-lymphocyte-associated protein 4. While blocking these pathways can enhance tumor destruction, these pathways are critical for the development of maternal tolerance towards the fetus. Therefore, if ICIs disrupt these immunomodulatory pathways, there could be a maternal immune response against the fetus, as was found in animal studies. With few reported cases of human pregnancy exposure to ICIs, the effects of ICIs on human pregnancy remain largely unknown. Here, we review and summarize the 6 cases of maternal exposure to immunotherapy that have been published before the present study. To add to the evidence, we present a case series of 2 patients who have been exposed to immunotherapy in pregnancy.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Animals , Apoptosis Regulatory Proteins , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Neoplasms/drug therapy , Neoplasms/etiology , PregnancyABSTRACT
BACKGROUND: There is limited information on the risk of hospital-acquired coronavirus disease 2019 (COVID-19) among high-risk hospitalized patients after exposure to an infected patient or healthcare worker (HCW) in a nonoutbreak setting. METHODS: This study was conducted at a tertiary care cancer center in New York City from 10 March 2020 until 28 February 2021. In early April 2020, the study institution implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing at admission and retesting every 3 days through the hospital stay. Contact tracing records were reviewed for all exposures to SARS-CoV-2 positive patients and HCWs. RESULTS: From 10 March 2020 to 28 February 2021, 11 348 unique patients who were SARS-CoV-2 polymerase chain reaction (PCR) negative at the time of admission underwent 31 662 postadmission tests during their hospitalization, and 112 tested positive (0.98%). Among these, 49 patients housed in semiprivate rooms during admission resulted in 74 close contacts and 14 secondary infections within 14 days, for an overall attack rate of 18.9%. Among those exposed to a roommate undergoing an aerosol-generating procedure (AGP), the attack rate was 35.7%. Whole genome sequencing (WGS) corroborated transmission in 6/8 evaluated pairs. In addition, three transmission events occurred in 214 patients with significant exposure to 105 COVID-19 positive healthcare workers (1.4%). CONCLUSIONS: The overall risk of hospital-acquired COVID-19 is low for hospitalized cancer patients, even during periods of high community prevalence. However, shared occupancy with an unrecognized case is associated with a high secondary attack rate in exposed roommates.
Subject(s)
COVID-19 , Neoplasms , COVID-19/diagnosis , COVID-19/epidemiology , Contact Tracing , Delivery of Health Care , Health Personnel , Humans , Infectious Disease Transmission, Patient-to-Professional , Neoplasms/epidemiology , SARS-CoV-2ABSTRACT
BACKGROUND: Peripartum depression (PPD) is underexplored in multiple sclerosis (MS). OBJECTIVE: To evaluate prevalence of and risk factors for PPD in women with MS. METHODS: Retrospective single-center analysis of women with MS with a live birth. Prevalence of PPD was estimated with logistic regression with generalized estimating equations (GEE). GEE evaluated predictors of PPD (e.g. age, marital status, parity, pre-pregnancy depression/anxiety, antidepressant discontinuation, sleep disturbance, breastfeeding, relapses, gadolinium-enhancing lesions, and disability). Factors significant in univariable analyses were included in multivariable analysis. RESULTS: We identified 143 live births in 111 women (mean age 33.1 ± 4.7 years). PPD was found in 18/143 pregnancies (12.6%, 95% CI = 7.3-17.8). Factors associated with PPD included older age (OR 1.16, 95% CI = 1.03-1.32 for 1-year increase), primiparity (OR 4.02, CI = 1.14-14.23), pre-pregnancy depression (OR 3.70, CI = 1.27-10.01), sleep disturbance (OR 3.23, CI = 1.17-8.91), and breastfeeding difficulty (OR 3.58, CI = 1.27-10.08). Maternal age (OR 1.17, CI = 1.02-1.34), primiparity (OR 8.10, CI = 1.38-47.40), and pre-pregnancy depression (OR 3.89, CI = 1.04-14.60) remained significant in multivariable analyses. Relapses, MRI activity, and disability were not associated with PPD. CONCLUSION: The prevalence of PPD in MS appeared similar to the general population, but was likely underestimated due to lack of screening. PPD can affect MS self-management and offspring development, and prospective studies are needed.
Subject(s)
Depression, Postpartum , Multiple Sclerosis , Adult , Female , Humans , Male , Pregnancy , Depression/epidemiology , Depression, Postpartum/epidemiology , Multiple Sclerosis/complications , Multiple Sclerosis/epidemiology , Peripartum Period , Recurrence , Retrospective Studies , Risk FactorsABSTRACT
NEED FOR INNOVATION: There is a clear need for physician leaders with expertise in wellness given the high incidence of physician burnout, especially during the COVID-19 pandemic. A fellowship in physician wellness provides structured opportunity for the development of expertise in the science and administration of physician wellness through a tailored curriculum and academic scholarship. BACKGROUND: Currently, limited opportunities exist to pursue formal wellness training in graduate medical education. This lack of specific training may make the path to expertise and leadership in physician wellness difficult. OBJECTIVE: Our objective was to design and implement a physician wellness fellowship in a department of emergency medicine. Completion of this fellowship, with ongoing professional development, will give physicians the skills to fill various leadership roles within the house of medicine, such as chief wellness officer, department, organization, national wellness leader, or wellness consultant. DEVELOPMENT PROCESS: The fellowship curriculum was developed according to Kern's six-step approach with expert consultation. The Stanford WellMDâ¯Model of Professionalâ¯Fulfillment was used as a framework to define the core content. The curriculum has five principal components developed utilizing competency-based education in medicine: dissemination of knowledge (teaching), clinical, educational foundation, implementation (administrative), and critical investigation (research). IMPLEMENTATION PHASE: The physician wellness fellowship was implemented for the academic year 2019-2020. The fellow completed all the required fellowship activities. In addition, the fellow completed the American College of Emergency Physician's teaching fellowship program. The fellowship is budget neutral because the fellow's half-time clinical revenue is sufficient to cover the fellow's salary and education and support for fellowship direction. REFLECTIVE DISCUSSION: Outcomes of this novel program will be measured over time. Although the format of this fellowship is designed for emergency medicine, the skills and content are relevant to and may be adopted in other medical specialties at other institutions.
ABSTRACT
BACKGROUND: Many patients with MS continue to have symptoms of their disease even when inflammatory activity is reduced by DMTs. Although disease activity tends to be reduced during pregnancy - especially in the third trimester - women with MS can experience ongoing symptoms during pregnancy, or new ones in the immediate postpartum period, that degrade quality of life. While many MS-related and postpartum symptoms can be improved with physical therapy (PT), there are currently no guidelines on pregnancy-related rehabilitation in MS. In this analysis, we evaluated the prevalence of PT-amenable symptoms and patterns of PT referrals in a cohort of UCSF MS Clinic patients who became pregnant. METHODS: We extracted electronic medical records (EMR) data for the year before conception, during pregnancy, and year postpartum for women with MS cared for at UCSF between 09-2005 and 08-2019. This included clinical visits, MS therapies and symptoms (as defined by the National MS Society). PT and pelvic floor PT orders and notes were also extracted. RESULTS: We included 142 live birth pregnancies from 118 women. During the course of their pregnancy and within the year postpartum, 107 women (75.4%) reported at least one PT-amenable symptom. A total of 30 (28.0%) referrals were made to PT, with attendance confirmed for 10 (33.3% of referrals). Symptoms most commonly triggering a referral for PT evaluation were numbness and urinary incontinence. Falls were reported after 10 of the pregnancies; 4 resulted in a referral to PT. Forty-one women reported urinary incontinence: 11 (26.8%) were referred to PT, and 2 to pelvic floor PT. Nineteen women experienced a documented relapse during pregnancy and/or postpartum: 11 received a PT referral, and 4 attended PT. CONCLUSIONS: While women with MS recorded at least 1 PT-amenable symptom during or following 75.4% of their pregnancies, only 28% of these were referred to PT - and only a third attended PT. Of significance was the 4.9% referral rate for pelvic floor PT in postpartum women with a record of urinary incontinence. Pelvic floor PT is a mainstay of general postpartum care in many European countries. These data illustrate critical gaps in rehabilitation referral, access and use at the intersection of neurological conditions and pregnancy in a large US-based MS clinic. They lend support for quality improvement efforts to improve care pathways and for telerehabilitation innovations to reduce barriers to access and improve synergistic care between PT, MD and urologic care.
Subject(s)
Fecal Incontinence , Quality of Life , Europe , Exercise Therapy , Female , Humans , Pelvic Floor , Physical Therapy Modalities , PregnancyABSTRACT
BACKGROUND: New York City (NYC) experienced a surge of coronavirus disease 2019 (COVID-19) cases in March and April 2020. Since then, universal polymerase chain reaction (PCR)-based surveillance testing and personal protective equipment (PPE) measures are in wide use in procedural settings. There is limited published experience on the utility and sustainability of PCR-based surveillance testing in areas with receding and consistently low community COVID-19 rates. METHODS: The study was conducted at a tertiary care cancer center in NYC from 22 March to 22 August 2020. Asymptomatic patients underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing before surgeries, interventional radiology procedures, and endoscopy. Contact tracing in procedural areas was done if a patient with an initial negative screen retested positive within 48 hours of the procedure. RESULTS: From March 22 until August 22, 2020, 11 540 unique patients underwent 14 233 tests before surgeries or procedures at Memorial Sloan Kettering Cancer Center. Overall, 65 patients were positive, with a peak rate of 4.3% that fell below 0.3% after April 2020. Among the 65 positive cases, 3 were presymptomatic and 38 were asymptomatic. Among asymptomatic test-positive patients, 76% had PCR cycle threshold >30 at first detection. Five patients tested newly positive in the immediate postoperative period, exposing 82 employees with 1 case of probable transmission (1.2%). CONCLUSIONS: The prevalence of SARS-CoV-2 infection identified on preprocedural surveillance was low in our study, which was conducted in an area with limited community spread at the later stage of the study. Universal PPE is protective in procedural settings. Optimal and flexible diagnostic strategies are needed to accomplish and sustain the goals of comprehensive preprocedure surveillance testing.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , New York City/epidemiology , Personal Protective Equipment , PolicyABSTRACT
Physiologic changes occurring in pregnancy and postpartum can have secondary effects on the maternal nervous system. While most alterations to neurologic function during pregnancy are transient, there is an elevated risk for more serious complication in the peripartum period, such as cerebrovascular events or exacerbation of preexisting neurologic conditions. Due to the morbidity and mortality associated with these neurologic manifestations in some cases, timely diagnostic evaluation is essential. In the pregnant population, the use of diagnostic techniques such as computed tomography (CT) and magnetic resonance imaging (MRI), commonly employed to evaluate emergent neurologic abnormalities, requires special consideration of the potential risks associated with prenatal exposure. This review discusses several neurologic conditions affecting women during pregnancy for which diagnostic imaging may be warranted. Concerns relating to CT and MRI procedures, radiation exposure in utero, and exposure to intravenous contrast by placental transfer and breastfeeding are also reviewed.
Subject(s)
Pregnancy Complications , Radiation Exposure , Female , Humans , Magnetic Resonance Imaging , Neuroimaging , Placenta , Pregnancy , Pregnancy Complications/diagnostic imagingABSTRACT
PURPOSE OF REVIEW: This review summarises previous literature and recent findings on omega-3 fatty acids in cognition and inflammation in humans, comparing the effects of dietary omega-3 with supplemental omega-3. RECENT FINDINGS: Whilst some omega-3 studies, both dietary and supplementation, show positive benefits of omega-3s in cognition, particularly memory function, and supplementation studies show reduction in markers of inflammation, including IL-6 and TNF-α, some studies also show no clear benefits on cognition and inflammation, particularly in healthy populations. Most consistency in beneficial cognition outcomes has been in populations with MCI. Many clinical trials have investigated omega-3 supplements and cognition outcomes in healthy populations across the lifespan; however, omega-3 dietary interventions are limited to studies in children and adolescents. Future studies should compare the effects of dietary omega-3 with omega-3 supplementation before further conclusions can be drawn.
Subject(s)
Cognition/drug effects , Diet , Dietary Supplements , Fatty Acids, Omega-3/pharmacology , Inflammation/prevention & control , Fatty Acids, Omega-3/administration & dosage , HumansABSTRACT
INTRODUCTION: Nutrition transition has emerged as an important concept in health research used to describe shifts in dietary consumption and energy expenditure that coincide with economic, demographic and epidemiological changes at a population level. Better understanding of the shifts in dietary patterns across populations and their drivers could possibly hold the key to prevention of diet-related disease risk. An increasing number of studies have reported on nutrition transition in populations around the world, however, global evidence has not been summarised. OBJECTIVE: This scoping review is aimed to identify, explore and map the literature on nutrition transition with a specific focus on dietary changes in populations across the world. The review would allow better clarification around the concept of nutrition transition, classification of published studies and provide a framework for further research. METHODS AND ANALYSIS: The scoping review will be designed based on the methodology by Arksey and O'Malley, refined by Levac et al. and developed in conjunction with guidance on conducting systematic scoping reviews by Peters et al. The main research question addressed by the scoping review will be: 'What is the evidence on nutrition transition defined based on dietary changes reported in general adult population across the world?' Electronic databases (PubMed, ScienceDirect and Web of Science), grey literature sources and the reference lists of key studies will be searched to identify studies appropriate for inclusion in the review. Two reviewers will independently screen all abstracts and full-text studies for inclusion. Data will be abstracted into tables and logically organised according to items addressed in the specific research questions. ETHICS AND DISSEMINATION: Dissemination of results will be sought through a peer-reviewed publication, conference presentations and stakeholder meetings. The data used are from publicly available secondary sources, so no ethical review would be required for this study.
Subject(s)
Nutritional Requirements , Humans , Global Health , Systematic Reviews as TopicSubject(s)
Coronavirus Infections/epidemiology , Emergency Service, Hospital , Hospitalization/statistics & numerical data , Pneumonia, Viral/epidemiology , Adult , Age Distribution , Aged , Asthma/epidemiology , Betacoronavirus , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , California/epidemiology , Clinical Laboratory Techniques , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Immunocompromised Host , Male , Middle Aged , Neoplasms/epidemiology , Obesity/epidemiology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Public Health , Real-Time Polymerase Chain Reaction , Renal Insufficiency, Chronic/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Sex DistributionABSTRACT
Clonal heterogeneity and evolution of mantle cell lymphoma (MCL) remain unclear despite the progress in our understanding of its biology. Here, we report a 71-yr-old male patient with an aggressive MCL and depict the clonal evolution from initial diagnosis of typical MCL to relapsed blastoid MCL. During the course of the disease, the patient was diagnosed with classic Hodgkin lymphoma (CHL) and received a CHL therapeutic regimen. Molecular analysis by next-generation sequencing of both MCL and CHL demonstrated clonally related CHL with characteristic immunophenotype and PDL1/2 gains. Moreover, our data illustrate the clonal heterogeneity and acquisition of additional genetic aberrations including a rare fusion of SEC22B-NOTCH2 in the process of clonal evolution. Evidence obtained from our comprehensive immunophenotypic and genetic studies indicates that MCL and CHL can originate from a common precursor by divergent clonal evolution, which may pose a therapeutic challenge.
Subject(s)
Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/genetics , Aged , B7-H1 Antigen/genetics , Cell Proliferation/genetics , Clonal Evolution/genetics , High-Throughput Nucleotide Sequencing , Hodgkin Disease/genetics , Hodgkin Disease/pathology , Humans , Lymphoma, Mantle-Cell/pathology , Male , R-SNARE Proteins/genetics , Receptor, Notch2/geneticsABSTRACT
BACKGROUND: Tampons are used by up to 86% of US women and are a rarely considered potential source of pesticide and metal exposure. Tampons may be of particular concern given the likely higher absorption that occurs in the vagina. Our objective was to examine the potential associations between tampon use and metal concentrations, and biomarkers of inflammation and oxidative stress among healthy women. METHODS: We used information from a prospective cohort of 259 regularly menstruating women, aged 18-44, followed for two menstrual cycles. Tampon use was assessed using information provided in participant study diaries. Metal concentrations were measured from a blood sample collected at enrollment. Oxidative stress and inflammation biomarker concentrations were determined from blood samples collected at up to 8 clinic visits for each cycle. Linear regression models were used to estimate associations of tampon use with metal exposure, and linear mixed models to estimate associations of tampon use with inflammation and oxidative stress biomarkers at different times during the menstrual cycle. RESULTS: We observed non-significantly higher mean levels of mercury for tampon users compared to non-tampon users (exp(ß) = 1.25, 95% CI = 0.93, 1.68). We found no evidence of an association between tampon use and inflammation biomarkers. We observed consistently higher isoprostane levels, an oxidative stress biomarker, among tampon users compared to non-tampon users (e.g. exp.(ß) = 1.05, 95%CI = 0.96, 1.16, for the average isoprostane during the menstruating week); however, these results were not statistically significant. CONCLUSIONS: While our results are not statistically significant, we observed suggestive associations between tampon use and elevated levels of mercury and oxidative stress biomarkers. Although our finding should be interpreted in light of our limitations, they indicate that tampons may be a source of exposure to metals and chemicals that have been largely ignored, and any related health effects are an important public health concern.