A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas.

Signaling through JAK1 and/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1/2 inhibitor ruxolitinib for patients with relapsed/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7). Patients enrolled onto 1 of 3 biomarker-defined cohorts: (1) activating JAK and/or STAT mutations, (2) ≥30% pSTAT3 expression among tumor cells by immunohistochemistry, or (3) neither or insufficient tissue to assess. Patients received ruxolitinib 20 mg PO twice daily until progression and were assessed for response after cycles 2 and 5 and every 3 cycles thereafter. The primary endpoint was clinical benefit rate (CBR), defined as the combination of complete response, partial response (PR), and stable disease lasting at least 6 months. Only 1 of 7 patients with MF had CBR (ongoing PR > 18 months). CBR among the PTCL cases (n = 45) in cohorts 1, 2, and 3 were 53%, 45%, and 13% (cohorts 1 & 2 vs 3, P = .02), respectively. Eight patients had CBR > 12 months (5 ongoing), including 4 of 5 patients with T-cell large granular lymphocytic leukemia. In an exploratory analysis using multiplex immunofluorescence, expression of phosphorylated S6, a marker of PI3 kinase or mitogen-activated protein kinase activation, in <25% of tumor cells was associated with response to ruxolitinib (P = .05). Our findings indicate that ruxolitinib is active across various PTCL subtypes and support a precision therapy approach to JAK/STAT inhibition in patients with PTCL. This trial was registered at www.clincialtrials.gov as #NCT02974647.

Age and political leaning predict COVID-19 vaccination status at a large, multi-campus, public university in Pennsylvania: A cross-sectional survey.

INTRODUCTION: Vaccine hesitancy during the COVID-19 pandemic impacted many higher education institutions. Understanding the factors associated with vaccine hesitancy and uptake is instrumental in directing policies and disseminating reliable information during public health emergencies. OBJECTIVE: This study evaluates associations between age, gender, and political leaning in relationship to COVID-19 vaccination status among a large, multi-campus, public university in Pennsylvania. METHODS: From October 5-November 30, 2021, a 10-minute REDCap survey was available to students, faculty, and staff 18 years of age and older at the Pennsylvania State University (PSU). Recruitment included targeted email, social media, digital advertisements, and university newspapers. 4,231 responses were received. Associations between the selected factors and vaccine hesitancy were made with Chi-square tests and generalized linear regression models using R version 4.3.1 (2023-06-16). RESULTS: Logistic regression approach suggested that age and political leaning have a statistically significant association with vaccine hesitancy at the 5% level. Adjusted for political leaning, odds of being vaccinated is 4 times higher for those aged 56 years or older compared to the ones aged 18 to 20 (OR = 4.35, 95% CI = (2.82, 6.85), p-value < 0.05). The results also showed that adjusted for age, the odds of being vaccinated is about 3 times higher for liberal individuals compared to far-left individuals (OR = 2.85, 95% CI = (1.45, 5.41), p-value = 0.001). CONCLUSIONS: Age and political leaning are key predictors of vaccine uptake among members of the PSU community, knowledge of which may inform campus leadership's public health efforts such as vaccine campaigns and policy decisions.

Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

Regional Technique Provides Complete Surgical Anesthesia for Above-the-Knee Amputation: A Viable Alternative to General Endotracheal Anesthesia in a Time of COVID-19.

In the initial phase of the coronavirus disease 2019 (COVID-19) pandemic, laboratory test shortages made it impossible to definitively identify patients with active COVID-19 infection or asymptomatic carriers. Without diagnostic certainty, it was imperative to proceed with caution when performing aerosol-generating procedures; this meant that anesthesiologists needed to make conscious decisions to avoid airway manipulation for procedures when it was not completely necessary. This case report describes a regional anesthetic technique that was used as the primary anesthetic for an urgent above-the-knee amputation in a patient with a history of respiratory issue of unknown etiology.

Computerized Decision Support for Bladder Cancer Treatment Response Assessment in CT Urography: Effect on Diagnostic Accuracy in Multi-Institution Multi-Specialty Study.

This observer study investigates the effect of computerized artificial intelligence (AI)-based decision support system (CDSS-T) on physicians' diagnostic accuracy in assessing bladder cancer treatment response. The performance of 17 observers was evaluated when assessing bladder cancer treatment response without and with CDSS-T using pre- and post-chemotherapy CTU scans in 123 patients having 157 pre- and post-treatment cancer pairs. The impact of cancer case difficulty, observers' clinical experience, institution affiliation, specialty, and the assessment times on the observers' diagnostic performance with and without using CDSS-T were analyzed. It was found that the average performance of the 17 observers was significantly improved (p = 0.002) when aided by the CDSS-T. The cancer case difficulty, institution affiliation, specialty, and the assessment times influenced the observers' performance without CDSS-T. The AI-based decision support system has the potential to improve the diagnostic accuracy in assessing bladder cancer treatment response and result in more consistent performance among all physicians.

Emergent Management of Clostridium difficle Infection in a Patient With Chronic Inflammatory Bowel Disease.

Clostridium difficle (C. diff) is a well known cause of infectious diarrhea across hospitals in the developed world. An anaerobic, gram positive rod bacteria, C. diff is part of the normal flora of the human colon; however, alterations to the microbiome can promote proliferation leading to pathogenic behavior. Typical symptoms include watery diarrhea in excess of three or more times a day, for at least two days, and abdominal cramping. While most infections do not lead to long term complications, the two complications that are most deleterious to health are toxic megacolon and bowel perforation. Patients with an inflammatory bowel disease are at a higher risk of complications, and thus need to be managed appropriately. This case presents a 39-year-old male, with pertinent medical history of poorly controlled ulcerative colitis, who presented to general surgery with imaging suggesting rectal perforation secondary to a C. diff infection. Due to the free air visualized in the rectum, the patient was urgently transported to the operating room to undergo a total colectomy and end ileostomy surgery. This case discusses the well-known complication of bowel perforation, in order to raise awareness about the management and guidelines. This case is important and significant as it details the appropriate guidelines and structure to follow amongst this unique, and vulnerable to complications, population in order to manage a potentially devastating manifestation of C. diff.

Acute Management of Trimalleolar Fracture.

Extremity trauma is a common emergency department presentation. The authors report a case of an elderly woman who sustained a trimalleolar ankle fracture. Emergency department care includes stabilization of the fracture with a splint, with careful assessment of neurovascular status. Trimalleolar fractures are unstable and thus almost always will require surgical repair. This is true even for elderly patients and those with co-morbidities. Patients who do not get a surgical repair for these fractures are at risk for significant morbidity, including compartment syndrome, arthritis, malunion, and loss of mobility.

Phalangeal Fracture Secondary to Hammering One's Finger.

The authors report the case of a man who smashed his finger while using a hammer, resulting in a fracture-dislocation. The description of this injury type and the emergency management is discussed.