Identifying cellular mechanisms of zinc-induced relaxation in isolated cardiomyocytes.

We tested several molecular and cellular mechanisms of cardiomyocyte contraction-relaxation function that could account for the reduced systolic and enhanced diastolic function observed with exposure to extracellular Zn(2+). Contraction-relaxation function was monitored in isolated rat and mouse cardiomyocytes maintained at 37°C, stimulated at 2 or 6 Hz, and exposed to 32 µM Zn(2+) or vehicle. Intracellular Zn(2+) detected using FluoZin-3 rose to a concentration of ∼13 nM in 3-5 min. Peak sarcomere shortening was significantly reduced and diastolic sarcomere length was elongated after Zn(2+) exposure. Peak intracellular Ca(2+) detected by Fura-2FF was reduced after Zn(2+) exposure. However, the rate of cytosolic Ca(2+) decline reflecting sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) activity and the rate of Na(+)/Ca(2+) exchanger activity evaluated by rapid Na(+)-induced Ca(2+) efflux were unchanged by Zn(2+) exposure. SR Ca(2+) load evaluated by rapid caffeine exposure was reduced by ∼50%, and L-type calcium channel inward current measured by whole cell patch clamp was reduced by ∼70% in cardiomyocytes exposed to Zn(2+). Furthermore, ryanodine receptor (RyR) S2808 and phospholamban (PLB) S16/T17 were markedly dephosphorylated after perfusing hearts with 50 µM Zn(2+). Maximum tension development and thin-filament Ca(2+) sensitivity in chemically skinned cardiac muscle strips were not affected by Zn(2+) exposure. These findings suggest that Zn(2+) suppresses cardiomyocyte systolic function and enhances relaxation function by lowering systolic and diastolic intracellular Ca(2+) concentrations due to a combination of competitive inhibition of Ca(2+) influx through the L-type calcium channel, reduction of SR Ca(2+) load resulting from phospholamban dephosphorylation, and lowered SR Ca(2+) leak via RyR dephosphorylation. The use of the low-Ca(2+)-affinity Fura-2FF likely prevented the detection of changes in diastolic Ca(2+) and SERCA2a function. Other strategies to detect diastolic Ca(2+) in the presence of Zn(2+) are essential for future work.

A Gut Feeling: Isolated Small Bowel Angioedema due to Angiotensin-Converting Enzyme Inhibitor.

Isolated angioedema of the small intestine is a rare adverse event in patients taking angiotensin-converting enzyme inhibitors. Here, we present a case of visceral angioedema in a 32-year-old woman who presented with left upper quadrant pain, nausea, vomiting, diarrhea, and characteristic radiographic signs of small bowel angio-edema, six months after starting lisinopril. Her symptoms improved within 48 hours of withholding the offending agent and with supportive care. We discuss the epidemiology, pathophysiology, diagnosis, and management of angiotensin-converting enzyme inhibitor- induced angioedema.

Diagnosing Lemierre's Syndrome as the Cause of Multifocal Pneumonia During the COVID-19 Pandemic.

A 21-year-old male with no past medical history presented with a sore throat, cough, and shortness of breath after attending a party days earlier. He was initially treated for community-acquired pneumonia, but subsequently developed a new oxygen requirement. CT imaging of the chest showed multifocal airspace disease, concerning for COVID-19. Testing for SARS-CoV-2 was negative by RT-PCR and antibody testing. Blood cultures subsequently grew Streptococcus anginosus. A CT scan of his neck demonstrated a right peritonsillar abscess and right internal-jugular thrombus, consistent with Lemierre's syndrome. He underwent incision and drainage of the peritonsillar abscess and completed 4 weeks of IV antibiotics, which improved his symptoms. It is important to recognize that the differential diagnosis of multifocal pneumonia is broad and includes Lemierre's syndrome. The COVID-19 pandemic presents challenges with regards to anchoring bias for multifocal pneumonia.

Overuse of Tuberculosis Surveillance Testing in Patients With Inflammatory Bowel Disease Compared to Non-IBD Patients on Biologic Therapy.

Background: Biologic treatment for moderate to severe inflammatory bowel disease (IBD) places patients at risk for infectious complications. Tuberculosis (TB) infection and reactivation can lead to serious morbidity and mortality for immunosuppressed patients. As a result, guidelines recommend screening for TB before starting biologic treatment, but a paucity of data remains on the utility of surveillance testing. Methods: We performed a retrospective chart review at a single academic center evaluating both IBD and non-IBD patients on biologic therapy. The primary outcome was to determine the number of subsequent surveillance tests performed after initial screening for latent TB in both patient groups. Results: A total of 188 patients (147 IBD and 41 non-IBD patients) on biologic therapy were included. Screening for TB before biologic treatment was performed in 56% of non-IBD patients versus 83% for patients with IBD (P = 0.0003). Of the total cohort, 65% had at least 2 follow-up surveillance tests for TB. Three or more surveillance tests were performed in 40% of patients with IBD versus only 13% for non-IBD patients (P = 0.0132). A total of 7 patients (4%) had an abnormal surveillance test. No patients were confirmed to have a diagnosis of TB or underwent treatment. Conclusions: Patients on biologic therapy unnecessarily undergo surveillance testing for TB. Patients with IBD on biologic therapy are screened annually for TB at a higher rate compared to non-IBD patients. Standardization of care among patients on biologic therapy is necessary to avoid excessive testing in areas with a low incidence of TB.

Cognitive Biases in the Era of COVID-19 : A Case of Clostridium sporogenes Bacteremia in a Patient with Small Bowel Obstruction.

Clostridium sporogenes bacteremia in immunocompetent patients is rare with very few reported cases in the literature. We present a case of Clostridium sporogenes bacteremia in an 81-year-old immunocompetent man with small bowel obstruction and hypoxemia during the COVID-19 pandemic. Routine monitoring of prognostic inflammatory markers for COVID-19 created a unique challenge in the management of our patient who developed sepsis with respiratory symptoms. Upon review, bacteremia from Clostridium sporogenes was associated with high mortality rates and could produce similar elevations in the inflammatory markers observed in COVID-19 pneumonia. Further, we reviewed the cognitive biases encountered when monitoring these inflammatory markers during the management of our patient with Clostridium sporogenes bacteremia, who was initially thought to have COVID-19 disease. While our patient ultimately tested negative for COVID-19, early administration of empiric antimicrobial therapy without source control failed to prevent clinical decompensation.

Total laparoscopic management of spontaneous biliary perforation.

Spontaneous biliary perforation (SBP) in pediatrics is rare and historically has been treated with laparotomy for attempted repair and cholecystectomy. In recent years, management has evolved into a conservative approach, opting for cholecystostomy and peritoneal drainage over cholecystectomy. In this case, we report the first successful conservative management of SBP using an exclusively laparoscopic approach without cholecystectomy in a pediatric patient.