Examining the Trajectory of Health-Related Quality of Life among Coronavirus Disease Patients.

BACKGROUND: Recent studies have reported a reduction in health-related quality of life (HR-QoL) among post-coronavirus disease 2019 (COVID-19) patients. However, there remains a gap in research examining the heterogeneity and determinants of HR-QoL trajectory in these patients. OBJECTIVE: To describe and identify factors explaining the variability in HR-QoL trajectories among a cohort of patients with history of COVID-19. DESIGN: A prospective study using data from a cohort of COVID-19 patients enrolled into a registry established at a health system in New York City. PARTICIPANTS: Participants were enrolled from July 2020 to June 2022, and completed a baseline evaluation and two follow-up visits at 6 and 12 months. METHODS: We assessed HR-QoL with the 29-item Patient Reported Outcomes Measurement Information System instrument, which was summarized into mental and physical health domains. We performed latent class growth and multinomial logistic regression to examine trajectories of HR-QoL and identify factors associated with specific trajectories. RESULTS: The study included 588 individuals with a median age of 52 years, 65% female, 54% White, 18% Black, and 18% Hispanic. We identified five physical health trajectories and four mental health trajectories. Female gender, having pre-existing hypertension, cardiovascular disease, asthma, and hospitalization for acute COVID-19 were independently associated with lower physical health. In addition, patients with increasing body mass index were more likely to experience lower physical health over time. Female gender, younger age, pre-existing asthma, arthritis and cardiovascular disease were associated with poor mental health. CONCLUSIONS: We found significant heterogeneity of HR-QoL after COVID-19, with women and patients with specific comorbidities at increased risk of lower HR-QoL. Implementation of targeted psychological and physical interventions is crucial for enhancing the quality of life of this patient population.

World Trade Center workers with asthma and post-traumatic stress disorder perceive airflow limitation more accurately.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a major risk factor for increased asthma morbidity among World Trade Center (WTC) workers. OBJECTIVE: To investigate whether differences in perception of airflow limitation mediate the association of PTSD with worse asthma control in WTC workers. METHODS: We collected data from WTC workers on asthma control (Asthma Control Questionnaire and Asthma Quality of Life Questionnaire) and daily peak expiratory flow (PEF) measures over 6 weeks. Perception of airway limitation was assessed by comparing guessed vs actual PEF values. Post-traumatic stress disorder was diagnosed using the Structured Clinical Interview. We used unadjusted and adjusted models to compare PEF and perception measures in WTC workers with PTSD with those of workers without PTSD. RESULTS: Overall, 25% of 224 participants had PTSD. Post-traumatic stress disorder was associated with worse Asthma Control Questionnaire (2.2±0.8 vs 1.1±0.9, P < .001) and Asthma Quality of Life Questionnaire (3.9±1.1 vs 5.4±1.1, P < .001) scores. Adjusted analyses showed no significant differences in PEF between WTC workers with (351.9±143.3 L/min) and those without PTSD (364.6±131.6 L/min, P = .55). World Trade Center workers with PTSD vs those without PTSD had increased proportion of accurate perception (67.0±37.2% vs 53.5±38.1%, P = .01) and decreased underperception (23.3.0±32.1% vs 38.9±37.5%, P = .004) of airflow limitation during periods of limitation. Similar results were obtained in adjusted analyses. CONCLUSION: This study indicates that differences in perception of airflow limitation may mediate the relationship of PTSD and increased asthma symptoms, given WTC workers with PTSD have worse self-reported asthma control, an increased proportion of accurate perception, and decreased underperception, despite no differences in daily PEF measures.

Improving Asthma Control Test completion rates across a multi-site pediatric pulmonary clinic network: a quality improvement initiative.

OBJECTIVE: Assessing asthma control is an essential part of the outpatient management of children with asthma and can be performed through validated questionnaires such as the Asthma Control Test (ACT). Systematic approaches to incorporating the ACT in outpatient visits are often lacking, contributing to inconsistent completion rates. We conducted a quality improvement initiative to increase the proportion of visits where the ACT is completed for children with asthma in our multi-site pediatric pulmonary clinic network. METHODS: We developed an intervention of sending the ACT questionnaire to patients and caregivers through the electronic patient portal to complete prior to their visits. This strategy was first piloted at one clinic beginning in July 2020 and then expanded to 5 other clinics in the network in October 2020. Our outcome measure was average monthly proportion of visits with a completed ACT, tracked using statistical process control charts. The process measure was method of ACT completion tracked using run charts. RESULTS: At the pilot clinic, average monthly completion rate rose within 3 months of the intervention from 27% to 72% and was sustained more than 22 months. Completion across all clinics increased from 57% pre-intervention to 76% post-intervention. Importantly, the intervention did not rely on clinic staff to administer the questionnaire and did not interfere with existing clinic flow. CONCLUSION: An intervention of delivering the ACT electronically to patients and caregivers for completion prior to visits led to a rapid and sustained improvement in ACT completion rates across a large, pediatric pulmonary clinic network.

Assessing the interrelationship between asthma and obesity self-management behaviors.

Asthma and obesity are common coexisting conditions with increasing prevalence and substantial morbidity. This study examines the inter-relationship between illness and treatment beliefs in asthma and obesity and how they influence self-management behaviors. Overweight and obese adults ≥ 18 years with asthma were recruited from primary care and pulmonary practices in New York, NY and Denver, CO (n = 219). Path analysis was used to examine the relationship between asthma, weight and exercise-related illness and medication beliefs and SMB. Necessity beliefs about asthma medications and diet were associated with better medication adherence and healthier dietary behaviors (ß = 0.276, p = < 0.001, ß = 0.148, p = 0.018 respectively) whereas concerns about these self-care activities were associated with poorer adherence and worse dietary behaviors (ß = - 0.282, p < 0.001, ß = - 0.188, p = 0.003 respectively). We found no statistically significant association of exercise behaviors with any other weight or asthma illness or treatment beliefs. Our study demonstrates that necessity and concerns about treatment are associated with adherence in asthma and obesity. The lack of association of exercise behaviors with any asthma or weight related beliefs may reflect limited awareness of the impact of weight on asthma and warrants additional research.

Racial and ethnic differences in post-traumatic stress trajectories in breast cancer survivors.

PURPOSE: To describe differences in post-traumatic stress (PTS) symptoms over time among racial and ethnic minoritized breast cancer survivors (BCS) with comorbid diabetes. DESIGN: In a multisite longitudinal study, post-traumatic stress was evaluated at baseline, 6 and 12 months through self-reported questionnaires (Impact of Events Scale-Revised [IES-R]). PARTICIPANTS: One hundred and seventy-eight post-treatment BCS with diabetes were recruited from three tertiary medical centers. FINDINGS: Relative to non-Hispanic White women, minoritized women reported higher total IES-R scores at all time points. In the adjusted model, Latina women reported persistently higher IES-R total scores and Latina, and 'Other' women reported higher avoidance scores. CONCLUSIONS: Minoritized BCS with comorbid diabetes report higher rates of cancer related PTS that persist over 12 months. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Post diagnosis PTS evaluation and support is important in survivorship and primary care practices. Linkage to socially and culturally sensitive community support may be warranted.

Geographic Variation in Colorectal Cancer Incidence Among Asian Americans: A Population-Based Analysis 2006-2016.

Among Asian Americans, cancer is the leading cause of death and colorectal cancer (CRC) is the second most common cancer.1 The uptake of CRC screening influences incidence and mortality trends; however, the most recent American Cancer Society CRC statistics reveals ongoing disparities in screening based on race and ethnicity, with people of Asian descent demonstrating the lowest CRC screening rates despite being the fastest growing racial or ethnic group in the United States.2,3.

Telemedicine Impact on the Patient-Provider Relationship in Primary Care During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has necessitated a rapid uptake of telemedicine in primary care requiring both patients and providers to learn how to navigate care remotely. This change can impact the patient-provider relationship that often defines care, especially in primary care. OBJECTIVE: This study aims to provide insight into the experiences of patients and providers with telemedicine during the pandemic, and the impact it had on their relationship. RESEARCH DESIGN: A qualitative study using thematic analysis of semistructured interviews. SUBJECTS: Primary care providers (n=21) and adult patients (n=65) with chronic disease across primary care practices in 3 National Patient-centered Clinical Research Network sites in New York City, North Carolina, and Florida. MEASURES: Experiences with telemedicine during the COVID-19 pandemic in primary care. Codes related to the patient-provider relationship were analyzed for this study. RESULTS: A recurrent theme was the challenge telemedicine posed on rapport building and alliance. Patients felt that telemedicine affected provider's attentiveness in varying ways, whereas providers appreciated that telemedicine provided unique insight into patients' lives and living situations. Finally, both patients and providers described communication challenges. CONCLUSIONS: Telemedicine has altered structure and process aspects of primary health care such as the physical spaces of encounters, creating a new setting to which both patients and providers must adjust. It is important to recognize the opportunities and limits that this new technology has to help providers maintain the type of one-on-one attention that patients expect and that contributes to relationship building.

ß1 integrin monoclonal antibody treatment ameliorates cerebral cavernous malformations.

ß1 integrins are important in blood vessel formation and function, finely tuning the adhesion of endothelial cells to each other and to the extracellular matrix. The role of integrins in the vascular disease, cerebral cavernous malformation (CCM) has yet to be explored in vivo. Endothelial loss of the gene KRIT1 leads to brain microvascular defects, resulting in debilitating and often fatal consequences. We tested administration of a monoclonal antibody that enforces the active ß1 integrin conformation, (clone 9EG7), on a murine neonatal CCM mouse model, Krit1flox/flox ;Pdgfb-iCreERT2 (Krit1ECKO ), and on KRIT1-silenced human umbilical vein endothelial cells (HUVECs). In addition, endothelial deletion of the master regulator of integrin activation, Talin 1 (Tln1), in Krit1ECKO mice was performed to assess the effect of completely blocking endothelial integrin activation on CCM. Treatment with 9EG7 reduced lesion burden in the Krit1ECKO model and was accompanied by a strong reduction in the phosphorylation of the ROCK substrate, myosin light chain (pMLC), in both retina and brain endothelial cells. Treatment of KRIT1-silenced HUVECs with 9EG7 in vitro stabilized cell-cell junctions. Overnight treatment of HUVECs with 9EG7 resulted in significantly reduced total surface expression of ß1 integrin, which was associated with reduced pMLC levels, supporting our in vivo findings. Genetic blockade of integrin activation by Tln1ECKO enhanced bleeding and did not reduce CCM lesion burden in Krit1ECKO mice. In sum, targeting ß1 integrin with an activated-specific antibody reduces acute murine CCM lesion development, which we found to be associated with suppression of endothelial ROCK activity.

Greater executive dysfunction in patients post-COVID-19 compared to those not infected.

BACKGROUND: A number of patients post-coronavirus disease-19 (COVID-19) report cognitive impairment (CI), even months after acute infection. We aimed to assess if COVID-19 is associated with increased incidence of CI in comparison to controls. METHODS: We analyzed data from the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort of patients post-COVID-19 ≥18 years of age and non-infected controls. CI was defined by scores ≥ 1.0 standard deviation below population norms, and was assessed using well-validated measures of attention, working memory, processing speed, executive functioning/cognitive flexibility, language, learning, and memory. Logistic regression models assessed odds for CI in each domain in patients post-COVID-19 vs. controls after adjusting for potential confounders. In exploratory analyses, we assessed odds for CI by site of acute COVID-19 care as a proxy for disease severity. FINDINGS: 417 patients post-COVID-19 and 151 controls (mean age 49 years, 63% female, 21% Black, 17% Latinx) were included. In adjusted analyses, patients were significantly more likely than controls to have CI in executive functioning (odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.03 to 4.67), particularly those treated in outpatient (OR: 2.22; 95% CI: 1.02 to 4.82) and inpatient hospital (OR: 3.59; 95% CI: 1.27 to 10.16) settings. There were no significant associations between CI in other domains and history of COVID-19 or site of acute care. INTERPRETATION: Patients post-COVID-19 have greater odds of executive dysfunction, suggesting that focused cognitive screening may be prudent, even in those with mild to moderate disease. Studies should explore the pathophysiology and potential treatments for CI in this population. FUNDING: This work was funded by the Icahn School of Medicine at Mount Sinai.

Patient perspectives on risk-reducing salpingectomy with delayed oophorectomy for ovarian cancer risk-reduction: A systematic review of the literature.

OBJECTIVE: Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating salpingectomy with delayed oophorectomy (RRSDO) for ovarian cancer risk reduction and patients are beginning to ask their clinicians about this surgical option. This study sought to systematically review the available literature examining patient preferences regarding RRSDO and risk-reducing salpingo-oophorectomy (RRSO) to provide clinicians with an understanding of patient values, concerns, and priorities surrounding ovarian cancer risk-reducing surgery. METHODS: We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42023400690). We searched key electronic databases to identify studies evaluating acceptance and surgical decision-making regarding RRSO and RRSDO among patients with an increased risk of ovarian cancer. RESULTS: The search yielded 239 results, among which six publications met the systematic review inclusion criteria. Acceptance of RRSDO was evaluated in all studies and ranged from 34% to 71%. Factors positively impacting patients' acceptance of RRSDO included: avoidance of surgical menopause, preservation of fertility, concerns about sexual dysfunction, family history of breast cancer, and avoidance of hormone replacement therapy. Factors limiting this acceptance reported by patients included concerns regarding oncologic safety, surgical timing, and surgical complications. CONCLUSION: To date, few studies have explored patient perspectives surrounding RRSDO. Collectively, the limited data available indicate a high level of acceptance among BRCA1/2 carriers, and provides insight regarding both facilitating and limiting factors associated with patient preferences to better equip clinicians in the counseling and support of their patients.

Web-based tool for cancer family history collection: A prospective randomized controlled trial.

OBJECTIVES: Approximately 1% of individuals have a hereditary cancer predisposition syndrome, however, the majority are not aware. Collecting a cancer family history (CFH) can triage patients to receive genetic testing. To rigorously assess different methods of CFH collection, we compared a web-based tool (WBT) to usual care (clinician collects CFH) in a randomized controlled trial. METHODS: New gynecologic oncology patients (seen 9/2019-9/2021) were randomized to one of three arms in a 2:2:1 allocation ratio: 1) usual care clinician CFH collection, 2) WBT completed at home, or 3) WBT completed in office. The WBT generated a cancer-focused pedigree and scores on eight validated cancer risk models. The primary outcome was collection of an adequate CFH (based on established guidelines) with usual care versus the WBT. RESULTS: We enrolled 250 participants (usual care - 110; WBT home - 105; WBT office - 35 [closed early due to COVID-19]). Within WBT arms, 109 (78%) participants completed the tool, with higher completion for office versus home (33 [94%] vs. 76 [72%], P = 0.008). Among participants completing the WBT, 63 (58%) had an adequate CFH versus 5 (5%) for usual care (P < 0.001). Participants completing the WBT were significantly more likely to complete genetic counseling (34 [31%] vs. 15 [14%], P = 0.002) and genetic testing (20 [18%] vs. 9 [8%], P = 0.029). Participant and provider WBT experience was favorable. CONCLUSIONS: WBTs for CFH collection are a promising application of health information technology, resulting in more comprehensive CFH and a significantly greater percentage of participants completing genetic counseling and testing.

The Telemedicine Experience in Primary Care Practices in the United States: Insights From Practice Leaders.

PURPOSE: The need to rapidly implement telemedicine in primary care during the coronavirus disease 2019 (COVID-19) pandemic was addressed differently by various practices. Using qualitative data from semistructured interviews with primary care practice leaders, we aimed to report commonly shared experiences and unique perspectives regarding telemedicine implementation and evolution/maturation since March 2020. METHODS: We administered a semistructured, 25-minute, virtual interview with 25 primary care practice leaders from 2 health systems in 2 states (New York and Florida) included in PCORnet, the Patient-Centered Outcomes Research Institute clinical research network. Questions were guided by 3 frameworks (health information technology evaluation, access to care, and health information technology life cycle) and involved practice leaders' perspectives on the process of telemedicine implementation in their practice, with a specific focus on the process of maturation and facilitators/barriers. Two researchers conducted inductive coding of qualitative data open-ended questions to identify common themes. Transcripts were electronically generated by virtual platform software. RESULTS: Twenty-five interviews were administered for practice leaders representing 87 primary care practices in 2 states. We identified the following 4 major themes: (1) the ease of telemedicine adoption depended on both patients' and clinicians' prior experience using virtual health platforms, (2) regulation of telemedicine varied across states and differentially affected the rollout processes, (3) visit triage rules were unclear, and (4) there were positive and negative effects of telemedicine on clinicians and patients. CONCLUSIONS: Practice leaders identified several challenges to telemedicine implementation and highlighted 2 areas, including telemedicine visit triage guidelines and telemedicine-specific staffing and scheduling protocols, for improvement.

Development of a novel instrument to characterize telemedicine programs in primary care.

BACKGROUND: Given the rapid deployment of telemedicine at the onset of the COVID - 19 pandemic, updated assessment methods are needed to study and characterize telemedicine programs. We developed a novel semi - structured survey instrument to systematically describe the characteristics and implementation processes of telemedicine programs in primary care. METHODS: In the context of a larger study aiming to describe telemedicine programs in primary care, a survey was developed in 3 iterative steps: 1) literature review to obtain a list of telemedicine features, facilitators, and barriers; 2) application of three evaluation frameworks; and 3) stakeholder engagement through a 2-stage feedback process. During survey refinement, items were tested against the evaluation frameworks while ensuring it could be completed within 20-25 min. Data reduction techniques were applied to explore opportunity for condensed variables/items. RESULTS: Sixty initially identified telemedicine features were reduced to 32 items / questions after stakeholder feedback. Per the life cycle framework, respondents are asked to report a month in which their telemedicine program reached a steady state, i.e., "maturation". Subsequent questions on telemedicine features are then stratified by telemedicine services offered at the pandemic onset and the reported point of maturation. Several open - ended questions allow for additional telemedicine experiences to be captured. Data reduction techniques revealed no indication for data reduction. CONCLUSION: This 32-item semi-structured survey standardizes the description of primary care telemedicine programs in terms of features as well as maturation process. This tool will facilitate evaluation of and comparisons between telemedicine programs across the United States, particularly those that were deployed at the pandemic onset.

Transcutaneous and Direct Electrical Stimulation of Mouse Sciatic Nerve Accelerates Functional Recovery After Nerve Transection and Immediate Repair.

BACKGROUND: Electrical stimulation can accelerate peripheral nerve regeneration after injury and repair. Clinically, direct electrical stimulation (DES) may involve longer operating times, increasing risks of perioperative complications. Transcutaneous electrical stimulation (TCES) is a noninvasive alternative. In this study, we investigate how transcutaneous and DES compare for accelerating functional nerve recovery in a mouse sciatic nerve model. METHODS: Twenty-eight mice were divided into sham (n = 4), axotomy (n = 8), DES (n = 8), and TCES (n = 8) groups. After sciatic nerve transection and repair, the proximal nerve was subjected to DES or TCES at 20 Hz for 1 hour. Sciatic functional index was measured before the injury, and at weeks 1, 2, 4, 6, 8, 10, and 12 by walking-track analysis. Electrophysiological measures were taken at week 12. RESULTS: Kinematic studies showed significant improvement from the 8th week to the 12th week for both electrical stimulation groups compared with the axotomy group (P < 0.05), with no difference between the electrical stimulation groups. At the 12th week, both DES and TCES groups had significantly faster average conduction velocity than the axotomy group. CONCLUSIONS: Functional recovery was significantly better from 8 weeks onward in mice receiving either DES or TCES stimulation when compared with axotomy and repair alone. Transcutaneous electrical stimulation is a minimally invasive alternative treatment for accelerating functional recovery after peripheral nerve injury.

The TCI Clinical Encounter Program for PhD Students in Cancer Biology: a Feasibility Pilot.

Clinical rotations are often not included in graduate-level cancer biology curricula; however, basic insight into clinical oncology is often crucial for developing translational research that addresses unmet needs with the potential to benefit cancer patients. We describe a needs assessment, design, implementation, and descriptive evaluation of an oncology-specific pilot clinical encounter program developed for PhD students in the Cancer Biology Training Area (CAB) in the Graduate School of Biomedical Sciences (GSBS) and Tisch Cancer Institute (TCI) at the Icahn School of Medicine at Mount Sinai (ISMMS). Prior to the development of this pilot program, CAB students, in years 2-5 + , were surveyed to determine their interest in a structured clinical experience. Seventeen out of thirty-one students responded (55%) to the survey. Of those seventeen respondents, fifteen (88.2%) expressed that exposure to cancer patients in the clinical setting would be useful for their pre-doctoral biomedical science and cancer biology training and indicated an interest in participating in the clinical encounter program. Based on these responses, a three-session clinical encounter pilot program was designed. Two separate cohorts of 5 students participated in this pilot program. During a formal debrief, following the clinical experience, students commented on the resilience of patients and the importance of research on clinical decision making, and reported that they found the experience motivational. Five out of 10 students responded (50%) to a post-program assessment survey; all five respondents answered that they would recommend the clinical encounter program to their peers. While limited in size and scope, this pilot TCI Clinical Encounter Program proved feasible and has the potential to enrich and inform the experience of PhD students pursing advanced degrees in a cancer biology.

Chronic canaliculitis with canaliculoliths due to Providencia stuartii infection.

Canaliculitis, inflammation of the lacrimal canaliculi, can be caused by numerous pathogens, most commonly bacteria from the genera Actinomyces, Streptococcus, and Staphylococcus. Primary canaliculitis often requires surgical canaliculolith removal and appropriate antibiotic coverage. The authors report a case of a 77-year-old woman with a history of punctal plugs who presented with chronic canaliculitis with canaliculoliths that grew Providencia stuartii. P. stuartii has not previously been described as a cause of primary canaliculitis. This case highlights a new organism that causes canaliculitis with canaliculoliths and stresses the importance of speciation and antibiotic sensitivity testing following canaliculotomy and curettage. P. stuartii should be considered in the differential for bacterial canaliculitis with canaliculoliths, especially in patients with persistent symptoms on topical antibiotic therapy without canaliculotomy.

What happens in the long term: Uptake of cancer surveillance and prevention strategies among at-risk relatives with pathogenic variants detected via cascade testing.

BACKGROUND: Cascade genetic testing for hereditary cancer syndromes offers affected relatives the opportunity to pursue cancer screening and risk-reducing surgery and thus reduces morbidity and mortality. The purpose of this study was to measure the long-term utilization of targeted cancer prevention and quality of life among at-risk relatives offered clinician-facilitated cascade genetic testing. METHODS: In a pilot study, at-risk relatives of patients with a hereditary cancer syndrome were contacted directly by the clinical team and offered telephone genetic counseling and genetic testing via an at-home, mailed saliva kit. Two-year follow-up results evaluating the use of targeted cancer prevention strategies and the quality of life for enrolled relatives were reported. Quality-of-life was measured with validated surveys, and scores were compared to the time of initial contact by the Wilcoxon signed-rank test. RESULTS: Ninety-five at-risk relatives were enrolled in the initial pilot study, and 72 (76%) participated in the 2-year follow-up; 57 of these (79%) had completed genetic testing. Twenty-five of those 57 relatives (44%) were found to harbor an inherited pathogenic variant. Guideline-based cancer surveillance was recommended to 18 relatives; 13 (72%) completed at least one recommended screening, and six (33%) completed all recommended screenings. Risk-reducing surgery was recommended to 10 relatives; four (40%) completed a total of eight procedures. Quality-of-life surveys demonstrated low levels of anxiety, depression, distress, and uncertainty. CONCLUSIONS: The 2-year follow-up of the original pilot study revealed that clinician-facilitated cascade testing resulted in genetically targeted cancer screening and prevention with preserved quality of life. These results, to be confirmed by larger randomized controlled trials, suggest that medical systems should consider supporting clinician-facilitated cascade testing programs.

Talin-1 is the principal platelet Rap1 effector of integrin activation.

Ras-related protein 1 (Rap1) is a major convergence point of the platelet-signaling pathways that result in talin-1 binding to the integrin ß cytoplasmic domain and consequent integrin activation, platelet aggregation, and effective hemostasis. The nature of the connection between Rap1 and talin-1 in integrin activation is an important remaining gap in our understanding of this process. Previous work identified a low-affinity Rap1-binding site in the talin-1 F0 domain that makes a small contribution to integrin activation in platelets. We recently identified an additional Rap1-binding site in the talin-1 F1 domain that makes a greater contribution than F0 in model systems. Here we generated mice bearing point mutations, which block Rap1 binding without affecting talin-1 expression, in either the talin-1 F1 domain (R118E) alone, which were viable, or in both the F0 and F1 domains (R35E,R118E), which were embryonic lethal. Loss of the Rap1-talin-1 F1 interaction in platelets markedly decreases talin-1-mediated activation of platelet ß1- and ß3-integrins. Integrin activation and platelet aggregation in mice whose platelets express only talin-1(R35E, R118E) are even more impaired, resembling the defect seen in platelets lacking both Rap1a and Rap1b. Although Rap1 is important in thrombopoiesis, platelet secretion, and surface exposure of phosphatidylserine, loss of the Rap1-talin-1 interaction in talin-1(R35E, R118E) platelets had little effect on these processes. These findings show that talin-1 is the principal direct effector of Rap1 GTPases that regulates platelet integrin activation in hemostasis.

Association of Vaccination with the Persistence of Post-COVID Symptoms.

BACKGROUND: Patients who have had COVID-19 often report persistent symptoms after resolution of their acute illness. Recent reports suggest that vaccination may be associated with improvement in post-acute symptoms. We used data from a prospective cohort to assess differences in post-acute sequelae of COVID (PASC) among vaccinated vs. unvaccinated patients. METHODS: We used data from a cohort of COVID-19 patients enrolled into a prospective registry established at a tertiary care health system in New York City. Participants underwent a baseline evaluation before COVID-19 vaccines were available and were followed 6 months later. We compared unadjusted and propensity score-adjusted baseline to 6-month change for several PASC-related symptoms and measures: anosmia, respiratory (cough, dyspnea, phlegm, wheezing), depression, anxiety, post-traumatic stress disorder (PTSD; COVID-19-related and other trauma), and quality-of-life domains among participants who received vs. those who did not receive COVID-19 vaccination. RESULTS: The study included 453 COVID-19 patients with PASC, of which 324 (72%) were vaccinated between the baseline and 6-month visit. Unadjusted analyses did not show significant differences in the baseline to 6-month change in anosmia, respiratory symptoms, depression, anxiety, PTSD, or quality of life (p > 0.05 for all comparisons) among vaccinated vs. unvaccinated patients. Similar results were found in propensity-adjusted comparisons and in secondary analyses based on the number of vaccine doses received. CONCLUSIONS: Our findings suggest that COVID vaccination is not associated with improvement in PASC. Additional studies are needed to better understand the mechanisms underlying PASC and to develop effective treatments.

Tisch Cancer Institute Scholars Program: Mentored Cancer Research Training Pipeline for Medical Students.

Cancer research has led to unprecedented advances in treatment in recent decades. Physician-scientists have played a crucial role in these advances given their unique perspective at the intersection between basic research and clinical care, though their representation in cancer research has been in progressive decline. Cancer research programs that feature strong mentorship at the medical student level are associated with increased likelihood of alumni choosing a cancer research career path. In an effort to increase the cancer research medical student training pipeline, senior research faculty from the Tisch Cancer Institute (TCI) at the Icahn School of Medicine at Mount Sinai (ISMMS) developed the TCI Scholars Program, a rigorous mentored research training program funding medical students' summer research. This program is currently in its third year and has garnered significant interest among mentors and students alike from all four TCI Cancer Center Support Grant (CCSG)-funded research programs. Herein, we describe the development, implementation, evaluation, and major outcomes of this program.