Background The presence of a hypercoagulable disorder such as heparin‐induced thrombocytopenia (HIT) may protect against anticoagulant‐associated bleeding. Objectives To determine the incidence of major bleeding in patients with suspected HIT. Methods We performed a retrospective analysis of 310 patients suspected of having HIT from the Hospital of the University of Pennsylvania and an affiliated community hospital. We compared the cumulative incidence of major bleeding following suspicion for HIT by ultimate HIT status (HIT+ or HIT−) and exposure to an alternative anticoagulant (Tx+ or Tx−). Secondary outcomes included the incidence of new/progressive thrombosis and 30‐day mortality. Results The incidence of major bleeding was high in the HIT+Tx+, HIT− Tx+, and HIT−Tx− groups (35.7%, 44.0%, and 37.3%, respectively). The time to first major bleeding event did not differ between groups (P = .24). Factors associated with increased risk of major bleeding included intensive care unit admission (HR 2.24, 95% CI 1.44‐3.47), platelet count < 25 × 109/L (HR 2.13, 1.10‐4.12), and renal dysfunction (HR 1.56, 1.06‐2.27); 35.7% of HIT+Tx+, 13.8% HIT−Tx+, and 9.3% of HIT−Tx− patients experienced new or progressive thrombosis. Mortality was similar among the three groups (26.2% HIT+Tx+, 34.5% HIT−Tx+, and 26.7% of HIT−Tx− [P = .34]). Conclusions Among patients with suspected HIT, major bleeding was common regardless of HIT status. Contrary to our hypothesis, HIT+ patients were not protected from major bleeding. A better understanding of bleeding risk is needed to inform management decisions in patients with suspected HIT.

The HIT Expert Probability (HEP) score compared favorably with the 4Ts score in a retrospective study. We assessed the diagnostic accuracy of the HEP score compared with the 4Ts score in a prospective cohort of 310 patients with suspected heparin-induced thrombocytopenia (HIT). A member of the clinical team calculated the HEP score and 4Ts score. An independent panel adjudicated HIT status based on a clinical summary as well as the results of HIT laboratory testing. The prevalence of HIT in the study population was 14.7%. At a cutoff of ≥3, the HEP score was 95.3% sensitive (95% confidence interval [CI], 84.2-99.4) and 35.7% specific (95% CI, 29.8-42.0) for HIT. A 4Ts score of ≥4 had a sensitivity of 97.7% (95% CI, 86.2-99.8) and specificity of 32.9% (95% CI, 27.2-39.1). The areas under the receiver operating characteristic (ROC) curves (AUCs) for the HEP score and 4Ts score were similar (0.81 [95% CI, 0.74-0.87] vs 0.76 [95% CI, 0.69-0.83]; P = .12). The HEP score exhibited a significantly higher AUC than the 4Ts score in patients in the intensive care unit (ICU) (0.86 vs 0.79; P = .03). Among trainee scorers, the HEP score performed significantly better than the 4Ts score (AUC, 0.80 vs 0.73; P = .03). Our data suggest that either the 4Ts score or the HEP score may be used in clinical practice. The HEP score may be preferable in ICU patients and among less experienced clinicians.

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P &lt; .001). An sGPVI level &gt;43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT.

Rosai–Dorfman disease (RDD) is a rare, nonmalignant disorder of histiocyte proliferation typically involving the cervical lymph nodes. However, a subset of patients with RDD will display extranodal manifestations that are highly variable in presentation, more challenging to diagnose, and less likely to spontaneously regress compared to nodal disease. While case reports of extranodal involvement in nearly every organ system exist, documented instances of mediastinal and pulmonary artery involvement are particularly rare. This study describes the case of a middle-aged woman presenting with new onset right heart failure who was found to have extranodal RDD in the form of a large mediastinal mass with invasion and occlusion of the main pulmonary arteries.

Background: Most patients with suspected heparin-induced thrombocytopenia (HIT) and an intermediate probability 4Ts score do not have HIT. We aimed to develop a metric based on the rate of platelet count fall to aid in discriminating HIT status among patients with an intermediate 4Ts score. Methods:We derived a measure of the maximum 24-hour percentage decrease in platelet count (Fall max ) in a cohort of patients with suspected HIT and an intermediate 4Ts score at the University of Pennsylvania. We validated this metric in a prospectively collected cohort of patients with suspected HIT and an intermediate 4Ts score from four hospitals in Hamilton, Ontario.Results: One hundred fifty-eight and 139 patients were included in the analysis from the derivation and validation cohorts, respectively. Fall max was significantly higher in HIT-positive patients in the derivation cohort (49.6% versus 38.6%, P = .009) and validation cohort (43.5% versus 29.3%, P = .027). The area under the receiver operating characteristic curve was 0.68 (95% confidence interval [CI] 0.57-0.78) and 0.71 (0.59-0.83) in the two cohorts, respectively. At Fall max ≥ 30%, sensitivity and specificity were 95.5% and 29.4% in the derivation cohort and 80.0% and 52.7% in the validation cohort.Conclusions: Among patients with suspected HIT and an intermediate 4Ts score, Fall max aided in discriminating HIT-negative from HIT-positive patients. Using a measure that accounts for the rate of platelet count fall may help to avoid unnecessary suspension of heparin and treatment with an alternative anticoagulant in HIT-negative patients with an intermediate probability 4Ts score, though further evaluation is warranted.

Background: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. Method: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. Results: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. Conclusion: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI.

The hands-on laboratory experiments are frequently what spark students' interest in science. Students who are blind or have low vision (BLV) typically do not get the same experience while participating in hands-on activities due to accessibility. Over the course of approximately nine months, common chemistry laboratory experiments were adapted and field tested for use in a residential school for the blind. These adaptations most commonly used a SciVoice Talking LabQuest and associated sensors, as well as other tactile methods.

Cholangiocarcinoma is a highly morbid gastrointestinal malignancy for which available therapies are limited. Standard of care includes cytotoxic chemotherapies such as gemcitabine, platinum agents, nab-paclitaxel, and fluoropyrimidine analogues. However, tolerability of these regimens varies, and patients who do not tolerate chemotherapy have limited targeted therapies and immunotherapy options. In cholangiocarcinoma, mesenchymal–epithelial transition factor ( MET) amplification may present an additional opportunity for a targeted therapeutic approach, especially considering emerging data in non-small cell lung cancer. In this case, we present a metastatic cholangiocarcinoma patient with high-level MET gene amplification for whom capmatinib, a tyrosine kinase inhibitor with activity against c-MET, provided a partial response after cessation of chemotherapy.