SRF Expression in Excess Permits a Dual Contractile-Proliferative Phenotype of Airway Smooth Muscle.

The transcription factors (TFs) myocardin (MyoCD) and ETS Like-1 protein (Elk-1) competitively bind to serum response factor (SRF) and control myogenic- and mitogenic-related gene expression in smooth muscle, respectively. Their functions are therefore mutually inhibitory, which result in a contractile versus proliferative phenotype dichotomy. Airway smooth muscle cell (ASMC) phenotype alterations occur in various inflammatory airway diseases, promoting pathological remodelling and contributing to airflow obstruction. We characterized MyoCD and Elk-1 interactions and their roles in phenotype determination in human ASMCs. MyoCD overexpression in ASMCs increased smooth muscle gene expression, force generation, and partially restored the loss of smooth muscle protein associated with prolonged culturing, while inhibiting Elk-1 transcriptional activities and proliferation induced by epidermal growth factor (EGF). However, MyoCD overexpression failed to suppress these responses induced by fetal bovine serum (FBS) as FBS also upregulated SRF expression to a degree that allowed unopposed function of both TFs. Inhibition of the RhoA pathway reversed said SRF changes, allowing inhibition of Elk-1 by MyoCD overexpression and suppressing FBS-mediated contractile protein gene upregulation. Our study confirmed that MyoCD in increased abundance can competitively inhibit Elk-1 function. However, SRF upregulation permits a dual contractile-proliferative ASMC phenotype, anticipated to exacerbate pathological alterations, whereas therapies targeting SRF may inhibit both pathological ASMC proliferation and contractile protein gene expression.

Lessons Learned From Clinical Studies in Centronuclear Myopathies: The Patient Perspective-A Qualitative Study.

BACKGROUND: Since 2014, several clinical studies focusing on centronuclear myopathies have been conducted, including a prospective natural history study, a gene transfer clinical trial and a clinical trial using an antisense oligonucleotide. Dedicated patient organizations have played an important role in this process. The experience of members of these organizations, either as a study participant, parent or as a patient organization member communicating with the sponsors are potentially very informative for future trial design. METHODS: We investigated the burden of and the lessons learned from the first natural history studies and clinical trials from a patient perspective using a qualitative approach. We arranged 4 focus groups with a total of 37 participants from 3 large international patient organizations: ZNM-ZusammenStark!, the Myotubular Trust, and the MTM-CNM Family Connection. 4 themes, based on a systematic literature search were discussed: Expectations and preparation, Clinical study participation, Communication and Recommendations for future clinical trials. The focus group recordings were transcribed, anonymized, and uploaded to Atlas-ti version 8.1 software. The data were analyzed using a thematic content analysis. RESULTS: Overall, participants were realistic in their expectations, hoping for small improvements of function and quality of life. The realization that trial participation does not equate to a treatment was challenging. Participating in a clinical study had a huge impact on many aspects of daily life, both for patients and their immediate families. First-hand insights into the burden of the design and its possible effect on performance were provided, resulting in numerous compelling recommendations for future clinical studies. Furthermore, participants stressed the importance of clear communication, which was considered to be especially vital in cases of severe adverse events. Finally, while patients were understanding of the importance of adhering to the regulations of good clinical practice, they indicated that they would strongly appreciate a greater understanding and/or acknowledgment of the patient perspective and a reflection of this perspective in future clinical trial design. CONCLUSION: The acknowledgment and inclusion of patients' perspectives and efficient and effective communication is expected to improve patient recruitment and retention in future clinical studies, as well as more accurate assessment of the patient performance related to suitable planning of the study visits.

Impact of Regional Metastasis on Survival for Patients with Nonfunctional Pancreatic Neuroendocrine Tumors: A Systematic Review.

BACKGROUND: Controversy exists regarding the benefit of lymphadenectomy for nonfunctional pancreatic neuroendocrine tumors (NF-PNET). PATIENTS AND METHODS: MEDLINE/PubMed, EMBASE, and the Cochrane Library were searched for studies of pancreatic neuroendocrine tumors (PNET) published between 1990 and 2021. Studies of functional PNET were excluded. Reported incidence of lymph node metastasis (LNM) and survival analysis of either disease-free survival (DFS) or overall survival (OS) were required for inclusion. RESULTS: Overall, 52 studies analyzing 24,608 PNET met the inclusion criteria. The reported LNM rate for NF-PNET ranged from 7 to 64 % (median 24.5%). Reported LNM rates ranged from 7 to 51% (median 11%) for NF-PNET< 2 cm in 14 studies and 29-47% (median 38%) in NF-PNET > 2 cm. In total, 19 studies (66%) reported LNM to have a negative impact on DFS. Additionally, 21 studies (60%) reported LNM to have a negative impact on OS. Two studies investigating the impact of lymphadenectomy (LND) found LND had the greatest impact for large, high-grade tumors. The overall quality of available evidence was low as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation System. CONCLUSIONS: Published literature evaluating the impact of regional LNM and LND in PNET is confounded by heterogeneity in practice patterns and the retrospective nature of these cohort studies. Most studies suggest high rates of LNM in NF-PNET that negatively impact DFS and OS. Given the high rate of LNM in NF-PNET and its potential detrimental effect on DFS and OS, we recommend lymphadenectomy be completed for NF-PNET > 2 cm and strongly considered for NF-PNET < 2 cm.

Inactivated Poliovirus Vaccine Booster Reduces the Likelihood of COVID-19 Outcomes in Individuals Primed with Oral Poliovirus Vaccination.

Introduction: Prior research explores whether seasonal and childhood vaccines mitigate the risk of SARS-CoV-2 infection. Although there are trials investigating COVID-19 infection in response to the effects of the oral poliovirus vaccine (OPV), there has been no prior research assessing COVID-19 outcomes in recently immunized adults with the inactivated poliovirus vaccine (IPV). Methods: SARS-CoV-2 infection and COVID-19 symptoms were analyzed across a cohort of 282 adults who received an IPV booster. Bivariate and multivariate regression models explored associations among variables related to vaccination histories and COVID-19 outcomes. Results: One year post-IPV inoculation, participants who had never received OPV were more likely to test positive for SARS-CoV-2 and experience COVID-19 symptoms, compared to those who had previously received OPV (OR = 3.92, 95%CI 2.22-7.03, p < 0.001; OR = 4.45, 95%CI 2.48-8.17, p < 0.001, respectively). Those who had never received OPV experienced COVID-19 symptoms for 6.17 days longer than participants who had previously received OPV (95%CI 3.68-8.67, p < 0.001). Multivariate regression modeling indicated COVID-19 vaccination did not impact SARS-CoV-2 infection or COVID-19 symptoms in this sample of adults who had recently received IPV. Discussion: Findings suggest IPV may boost mucosal immunity among OPV-primed individuals, and COVID-19 vaccination may not provide additional protection among those who had received IPV. Future, larger-scale studies should measure the extent of protective effects against COVID-19 to inform public health policies in resource-deficient settings.

Advice to Clinicians From Expectant Parents at Extreme Prematurity: A Multimethod Study.

BACKGROUND AND OBJECTIVES: Despite recommendations for patient-centered counseling on extreme prematurity, clinicians often miss opportunities to communicate in a way that facilitates parental knowledge, decision-making, and emotional support. In this study, we aimed to determine empirical, parent-derived recommendations and advice for clinicians counseling on extreme prematurity. METHODS: Pregnant women (and their partners) admitted at 22 0/7 to 25 6/7 weeks' estimated gestation participated in postantenatal counseling semi-structured interviews or questionnaires to explore parental preferences in the counseling process, including advice to clinicians. Thematic analysis was performed. RESULTS: A total of 39 interviews and 47 questionnaires, representing 62 total prenatal consultations, were completed. Thematic analysis of participants' advice to clinicians from both interview and questionnaire data resulted in 14 parent-derived recommendations to clinicians who counsel expectant parents at extreme prematurity. Parental recommendations related to compassionately engaging, supporting, and communicating with families, as well as aligning teams and following up. CONCLUSIONS: We present an empirical parent-derived, family-centered, and practical approach for clinicians counseling on extreme prematurity. Future studies should include a more diverse patient population and assess the impact of these recommendations on the counseling process and outcomes.

Median arcuate ligament release at the time of pancreaticoduodenectomy or total pancreatectomy.

BACKGROUND: Celiac artery compression can complicate the performance of pancreaticoduodenectomy or total pancreatectomy due to the need for ligation of the gastroduodenal artery. Median arcuate ligament release restores normal arterial flow to the liver, spleen, and stomach and may avoid complications related to poor perfusion of the foregut. METHODS: All patients who underwent median arcuate ligament release for celiac artery compression at the time of pancreatectomy between 2009 and 2023 were reviewed. Pre- and postoperative computed tomography was used to categorize celiac artery compression by the extent of compression (types A [<50%], B [50%-80%], and C [>80%]). RESULTS: Of 695 patients who underwent pancreatectomy, 22 (3%) had celiac artery compression, and a majority (17) were identified on preoperative imaging. Median celiac artery compression was 52% (interquartile range = 18); 8 (36%) patients had type A and 14 (64%) had type B compression with a median celiac artery compression of 39% (interquartile range = 18) and 59% (interquartile range = 14), respectively (P < .001). Postoperative imaging was available for 20 (90%) patients, and a reduction in the median celiac artery compression occurred in all patients: type A, 14%, and type B, 31%. Complications included 1 (5%) death after hospital discharge, 1 (5%) pancreatic fistula, 1 (5%) delayed gastric emptying, and 4 (18%) readmissions. No patient had evidence of a biliary leak or liver dysfunction. CONCLUSION: Preoperative computed tomography allows accurate identification of celiac artery compression. Ligation of the gastroduodenal artery during pancreaticoduodenectomy or total pancreatectomy in the setting of celiac artery compression requires median arcuate ligament release to restore normal arterial flow to the foregut and avoid preventable complications.

Vitamin D Supplementation and Prior Oral Poliovirus Vaccination Decrease Odds of COVID-19 Outcomes among Adults Recently Inoculated with Inactivated Poliovirus Vaccine.

BACKGROUND: Structural and functional commonalities between poliovirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest that poliovirus inoculation may induce antibodies that mitigate the coronavirus disease (COVID-19). No known studies have evaluated COVID-19 risk factors in adults recently vaccinated against poliovirus. STUDY OBJECTIVE: Among adults with no history of COVID-19 infection or vaccination, who recently received an inactivated poliovirus vaccine (IPV), we sought to determine which biological factors and social determinants of health (SDOH) may be associated with (1) testing positive for SARS-CoV-2, (2) experiencing COVID-19 symptoms, and (3) a longer duration of COVID-19 symptoms. METHODS: The influence of biological factors and SDOH on SARS-CoV-2 infection and COVID-19 symptoms were evaluated among 282 adults recently inoculated with IPV. Participant-reported surveys were analyzed over 12 months post-enrollment. Bivariate and multivariate linear and logistic regression models identified associations between variables and COVID-19 outcomes. RESULTS: Adjusting for COVID-19 vaccinations, variants, and other SDOH, secondary analyses revealed that underlying conditions, employment, vitamin D, education, and the oral poliovirus vaccination (OPV) were associated with COVID-19 outcomes. The odds of testing positive for SARS-CoV-2 and experiencing symptoms were significantly reduced among participants who took vitamin D (OR 0.12 and OR 0.09, respectively). Unemployed or part-time working participants were 72% less likely to test positive compared with full-time workers. No prior dose of OPV was one of the strongest predictors of SARS-CoV-2 infection (OR 4.36) and COVID-19 symptoms (OR 6.95). CONCLUSIONS: Findings suggest that prophylactic measures and mucosal immunity may mitigate the risk and severity of COVID-19 outcomes. Larger-scale studies may inform future policies.

The experience of clinical study and trial participation in rare diseases: A scoping review of centronuclear myopathy and other neuromuscular disorders.

The design of a clinical trial for a rare disease can be challenging. An optimal study design is required to effectively study the clinical outcomes for possible therapies for these types of disorders. Understanding the study participants' experiences as well as barriers and facilitators of participation are important to optimize future research and to inform clinical trial management. Centronuclear myopathies (CNMs) including X-linked myotubular myopathy (XLMTM) are a group of rare congenital myopathies for which there is no cure currently. Since 2014, a number of natural history studies and clinical trials have been conducted in CNMs. Two trials have been prematurely terminated because of severe adverse events. Since no research has been conducted regarding trial experience in CNM, we performed a scoping literature research on clinical trial experience of patients with neuromuscular disorders in general. The most common barriers to trial participation of patients comprise concerns about potential harmful effects, opportunity loss and the expected burden on daily life. The most common facilitators were an expected benefit on the disease course, altruism and collateral benefit. While several results are in line with trial experiences of other types of patients, for example oncological patients, distinctions can be made for patients with CNM and other neuromuscular disorders. However, the limited availability of relevant literature suggests that future (qualitative) research should focus on trial experiences in CNM patients.

The Functional Implications of Broad Spectrum Bioactive Compounds Targeting RNA-Dependent RNA Polymerase (RdRp) in the Context of the COVID-19 Pandemic.

BACKGROUND: As long as COVID-19 endures, viral surface proteins will keep changing and new viral strains will emerge, rendering prior vaccines and treatments decreasingly effective. To provide durable targets for preventive and therapeutic agents, there is increasing interest in slowly mutating viral proteins, including non-surface proteins like RdRp. METHODS: A scoping review of studies was conducted describing RdRp in the context of COVID-19 through MEDLINE/PubMed and EMBASE. An iterative approach was used with input from content experts and three independent reviewers, focused on studies related to either RdRp activity inhibition or RdRp mechanisms against SARS-CoV-2. RESULTS: Of the 205 records screened, 43 studies were included in the review. Twenty-five evaluated RdRp activity inhibition, and eighteen described RdRp mechanisms of existing drugs or compounds against SARS-CoV-2. In silico experiments suggested that RdRp inhibitors developed for other RNA viruses may be effective in disrupting SARS-CoV-2 replication, indicating a possible reduction of disease progression from current and future variants. In vitro, in vivo, and human clinical trial studies were largely consistent with these findings. CONCLUSIONS: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins.

Development of an Online Training to Engage Home Visitors as Research Stakeholders.

BACKGROUND: Home visiting (HV) has demonstrated positive impacts across family well-being domains. Home visitors receive training in HV model requirements as well as to develop knowledge and various skills. Despite growth in HV research, we are not aware of existing training or required competencies in research design, research methods, or dissemination of research findings for home visitors. OBJECTIVES: Via ongoing collaboration with an Advisory Board of key HV stakeholders, we developed a three-module online training that incorporated examples from HV research and practice to address the gap in research training for home visitors and to promote home visitors' engagement as research stakeholders. METHODS: A convenience sample of home visitors (n = 176) was surveyed on research knowledge, research self-efficacy, and priority training topics, with results used to create a beta version of the training completed by six home visitors. Home visitor feedback on the beta version, coupled with Advisory Board recommendations, led to creation of the final online training. Forty home visitors viewed the final training and completed pre- and post-training surveys to assess changes in research knowledge and self-efficacy. Twelve home visitors also completed a semi-structured qualitative interview. Home visitors demonstrated improvements in research knowledge and self-efficacy and found the training easy to understand and useful. CONCLUSIONS: Guidance from stakeholders led to development of an online training that was effective in improving home visitors' research knowledge and self-efficacy. This training can be used by HV researchers and practitioners as a tool to promote home visitors' active engagement as stakeholders in research.

The Ultramarathon of Gene Therapy Development for Rare Diseases: How Can We Cross the Finish Line Together?

The promising developments in gene and cell therapy bring an array of hope to the >7000 rare disease patient communities, of which 90% to 95% are still working toward a treatment. However, the pace of gene and cell therapy development pathways often resembles ultramarathon relay races that potentially span decades. It is a pace that is incongruent to the sprint that most individuals with rare diseases and their families are living and working in pursuit of life-saving treatments. It is also challenging for the medical professionals, academic researchers, and pharmaceutical partners working tirelessly to bring a treatment to reality. Gene and cell therapy development programs can have many parallels to an ultramarathon, including extensive training and preparation leading up to clinical trials, selecting inclusion and exclusion criteria, supporting trial participants, and creating support teams. All aspects of the development course carry the greatest hope that as many treatments as possible can cross the finish line. Drawing on this analogy, perspectives and insights from a patient family member and rare disease advocacy leader in a community that has experienced its first clinical trial of gene therapy is shared. Bringing attention to these experiences, challenges, barriers, and potential learnings from a patient family perspective will likely encourage continued improvements in development of patient-driven gene and cell drug and therapy for the rare disease community.

Predicting the Next-Day Perceived and Physiological Stress of Pregnant Women by Using Machine Learning and Explainability: Algorithm Development and Validation.

BACKGROUND: Cognitive behavioral therapy-based interventions are effective in reducing prenatal stress, which can have severe adverse health effects on mothers and newborns if unaddressed. Predicting next-day physiological or perceived stress can help to inform and enable pre-emptive interventions for a likely physiologically and perceptibly stressful day. Machine learning models are useful tools that can be developed to predict next-day physiological and perceived stress by using data collected from the previous day. Such models can improve our understanding of the specific factors that predict physiological and perceived stress and allow researchers to develop systems that collect selected features for assessment in clinical trials to minimize the burden of data collection. OBJECTIVE: The aim of this study was to build and evaluate a machine-learned model that predicts next-day physiological and perceived stress by using sensor-based, ecological momentary assessment (EMA)-based, and intervention-based features and to explain the prediction results. METHODS: We enrolled pregnant women into a prospective proof-of-concept study and collected electrocardiography, EMA, and cognitive behavioral therapy intervention data over 12 weeks. We used the data to train and evaluate 6 machine learning models to predict next-day physiological and perceived stress. After selecting the best performing model, Shapley Additive Explanations were used to identify the feature importance and explainability of each feature. RESULTS: A total of 16 pregnant women enrolled in the study. Overall, 4157.18 hours of data were collected, and participants answered 2838 EMAs. After applying feature selection, 8 and 10 features were found to positively predict next-day physiological and perceived stress, respectively. A random forest classifier performed the best in predicting next-day physiological stress (F1 score of 0.84) and next-day perceived stress (F1 score of 0.74) by using all features. Although any subset of sensor-based, EMA-based, or intervention-based features could reliably predict next-day physiological stress, EMA-based features were necessary to predict next-day perceived stress. The analysis of explainability metrics showed that the prolonged duration of physiological stress was highly predictive of next-day physiological stress and that physiological stress and perceived stress were temporally divergent. CONCLUSIONS: In this study, we were able to build interpretable machine learning models to predict next-day physiological and perceived stress, and we identified unique features that were highly predictive of next-day stress that can help to reduce the burden of data collection.

Reducing posttraumatic stress disorder symptom severity among depressed women with childhood sexual abuse histories in interpersonal psychotherapy-trauma: The role of improved social functioning.

OBJECTIVE: Childhood sexual abuse (CSA) increases risk for posttraumatic stress disorder (PTSD), and both CSA and PTSD are strongly associated with impaired social functioning. Interpersonal psychotherapy (IPT) has demonstrated promise for adults with PTSD and has been shown to be effective for women with PTSD and histories of CSA, but the mechanisms by which IPT might improve PTSD are unknown. The current secondary analysis tested whether the ameliorative effect of IPT-trauma (IPT-T) on PTSD, demonstrated in a randomized effectiveness trial, was mediated by improved social function. METHOD: The randomized effectiveness trial compared IPT-T to clinic psychotherapy in a publicly funded community mental health center. Women with CSA histories and major depression (n = 162; Mage = 36.3; 54% White, 38% Black, 8% other race) were randomly assigned to IPT-T or CP, and 16 free sessions of IPT-T or CP were offered within a 32-week treatment period. Eighty-eight percent of the sample met diagnostic criteria for PTSD. RESULTS: Mediation models confirmed hypotheses, showing that the effect of IPT-T on improved PTSD symptoms at Week 32 (end of treatment) was partially mediated by better social functioning at Week 16 (middle of treatment period; path c¹: B = 12.25, p = .04, 95% confidence interval [.44, 24.05]). CONCLUSIONS: Findings support that a non-exposure-based therapy can reduce PTSD symptoms via improved social functioning. Given extensive literature showing the importance of social functioning in mental health generally and PTSD specifically, integrating a focus on social functioning (e.g., building social skills, expanding support networks) into treatments, including exposure-based treatments, may enhance outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Amplifying patient voices amid pandemic: Perspectives on tracheostomy care, communication, and connection.

OBJECTIVE: To investigate perspectives of patients, family members, caregivers (PFC), and healthcare professionals (HCP) on tracheostomy care during the COVID-19 pandemic. METHODS: The cross-sectional survey investigating barriers and facilitators to tracheostomy care was collaboratively developed by patients, family members, nurses, speech-language pathologists, respiratory care practitioners, physicians, and surgeons. The survey was distributed to the Global Tracheostomy Collaborative's learning community, and responses were analyzed. RESULTS: Survey respondents (n = 191) from 17 countries included individuals with a tracheostomy (85 [45 %]), families/caregivers (43 [22 %]), and diverse HCP (63 [33.0 %]). Overall, 94 % of respondents reported concern that patients with tracheostomy were at increased risk of critical illness from SARS-CoV-2 infection and COVID-19; 93 % reported fear or anxiety. With respect to prioritization of care, 38 % of PFC versus 16 % of HCP reported concern that patients with tracheostomies might not be valued or prioritized (p = 0.002). Respondents also differed in fear of contracting COVID-19 (69 % PFC vs. 49 % HCP group, p = 0.009); concern for hospitalization (55.5 % PFC vs. 27 % HCP, p < 0.001); access to medical personnel (34 % PFC vs. 14 % HCP, p = 0.005); and concern about canceled appointments (62 % PFC vs. 41 % HCP, p = 0.01). Respondents from both groups reported severe stress and fatigue, sleep deprivation, lack of breaks, and lack of support (70 % PFC vs. 65 % HCP, p = 0.54). Virtual telecare seldom met perceived needs. CONCLUSION: PFC with a tracheostomy perceived most risks more acutely than HCP in this global sample. Broad stakeholder engagement is necessary to achieve creative, patient-driven solutions to maintain connection, communication, and access for patients with a tracheostomy.

Cultural Adaptation of the Mothers and Babies Intervention for Use in Tribal Communities.

OBJECTIVE: While one in five women may experience mood and anxiety disorders during pregnancy and postpartum, Indigenous identity increases that risk by 62%, especially among younger Indigenous women. The need for evidence-based perinatal mental health interventions that provide culturally relevant well-being perspectives and practices is critical to improving maternal, child, and community outcomes for Indigenous peoples, and reducing health inequities. METHODS: Through a collaboration between community maternal and child health professionals, intervention researchers, and a cultural consultant, our workgroup developed cultural adaptations to Mothers and Babies, an evidence-based perinatal depression prevention intervention. Applying a cultural interface model, the workgroup identified existing intervention content for surface adaptations, as well as deep, conceptual adaptations to incorporate traditional teachings into this evidence-based intervention. RESULTS: This collaboration developed a culturally adapted facilitator manual for intervention providers, including guidance for implementation and further adaptation to represent local tribal culture, and a culturally adapted participant workbook for Indigenous perinatal women that reflects cultural teachings and traditional practices to promote well-being for mother and baby. IMPLICATIONS: Committing to a culturally respectful process to adapt Mothers and Babies is likely to increase the reach of the intervention into Indigenous communities, reengage communities with cultural practice, improve health outcomes among parents, children, and the next generation's elders, and reduce disparities among Indigenous groups. Replication of this community-engaged process can further the science and understanding of cultural adaptations to evidence-based interventions, while also further reducing health inequities. Future steps include evaluating implementation of the culturally adapted intervention among tribal home visiting organizations.

Prevalence of hepatitis C in sexual assault survivors presenting to a SANE clinic: A descriptive analysis.

While previous epidemiologic research has demonstrated that sexual assault survivors (SAS) may be at disproportionate risk for exposure to Hepatitis C (HCV), HCV screening in SAS is not addressed in current post-sexual assault testing recommendations. We sought to identify the prevalence of HCV among a SAS cohort along with associated basic demographics. Opt-out HCV antibody screening and RNA confirmatory testing was provided for all SAS at a Sexual Assault Nurse Examiner (SANE) clinic in Birmingham, Alabama, from April 2020 through March 2021. A retrospective chart review was conducted using descriptive statistical and Chi-squared analyses. A total of 293 SAS presented to the clinic during the study timeframe. Two hundred forty-two (82.6%) were screened for HCV and 26 (8.9%) were found to be HCV antibody (Ab) positive [significantly higher than state (<1.0%) and national (1.0%) HCV incidence rates (p < 0.0001)]. SAS age groups 25-34 and 35-44 were more likely to screen HCV Ab-positive (15.2% and 14.9% respectively; p = 0.02). Female SAS were more likely to be tested for HCV then males (p = 0.02), although male SAS were more likely to be found HCV Ab-positive when screened (24.4%, p < 0.0001). Overall, SAS demographics also demonstrate the presence of significant social vulnerabilities, specifically high rates of homelessness (4.4%) and incarceration (5.1%). This data highlight the potential impact of universal HCV screening and risk counselling in a high social risk population and suggests a potential for future focused interventions.

Undifferentiated carcinoma with osteoclast-like giant cells: A pathologic-radiologic correlation of a rare histologic subtype of pancreatic ductal adenocarcinoma.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an exceedingly rare subtype of pancreatic ductal adenocarcinoma. Histologically, UC-OGC is characterized by three cell types namely, a neoplastic mononuclear cell component, non-neoplastic osteoclast-like giant cells, and a non-neoplastic mononuclear histiocytic component. The behavior of this tumor is unpredictable; but many patients survive many years after diagnosis. UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma due to its slower local spread, less aggressive nature, better response to surgical resection and/or chemotherapy, and fewer metastases. Due to likely differences in prognosis and significant impact on patient management, it is important to distinguish this subtype from other types of pancreatic adenocarcinoma. We report a case of a small (<1 cm) undifferentiated carcinoma with osteoclast-like giant cells of the posterior pancreatic body discovered incidentally on magnetic resonance image (MRI) scan of a middle-aged man. The radiologic and pathologic findings are presented along with a discussion of the differential diagnosis of this exceedingly rare entity.

Tracheostomy care and communication during COVID-19: Global interprofessional perspectives.

OBJECTIVE: Investigate healthcare providers, caregivers, and patient perspectives on tracheostomy care barriers during COVID-19. STUDY DESIGN: Cross-sectional anonymous survey SETTING: Global Tracheostomy Collaborative Learning Community METHODS: A 17-item questionnaire was electronically distributed, assessing demographic and occupational data; challenges in ten domains of tracheostomy care; and perceptions regarding knowledge and preparedness for navigating the COVID-19 pandemic. RESULTS: Respondents (n = 115) were from 20 countries, consisting of patients/caregivers (10.4%) and healthcare professionals (87.0%), including primarily otolaryngologists (20.9%), nurses (24.3%), speech-language pathologists (18.3%), respiratory therapists (11.3%), and other physicians (12.2%). The most common tracheostomy care problem was inability to communicate (33.9%), followed by mucus plugging and wound care. Need for information on how to manage cuffs and initiate speech trials was rated highly by most respondents, along with other technical and knowledge areas. Access to care and disposable supplies were also prominent concerns, reflecting competition between community needs for routine tracheostomy supplies and shortages in intensive care units. Integrated teamwork was reported in 40 to 67% of respondents, depending on geography. Forty percent of respondents reported concern regarding personal protective equipment (PPE), and 70% emphasized proper PPE use. CONCLUSION: While safety concerns, centering on personal protective equipment and pandemic resources are prominent concerns in COVID-19 tracheostomy care, patient-centered concerns must also be prioritized. Communication and speech, adequate supplies, and care standards are critical considerations in tracheostomy. Stakeholders in tracheostomy care can partner to identify creative solutions for delays in restoring communication, supply disruptions, and reduced access to tracheostomy care in both inpatient and community settings.

Current Controversies in Neoadjuvant Therapy for Pancreatic Cancer.

Over the last two decades, there have been significant changes in the management of patients with localized pancreatic cancer. The rationale for an evolution toward a neoadjuvant approach and summary of relevant clinical trials is reviewed. Controversies in identifying optimal neoadjuvant therapeutic approaches are discussed.