Delayed Presentation of a Post-infarction Ventricular Septal Rupture.

Ventricular septal rupture, a formidable complication of acute myocardial infarction (AMI), is linked to significant morbidity and mortality. The clinical manifestation typically involves pronounced hemodynamic compromise necessitating prompt surgical intervention. This report outlines the case of a 60-year-old male presenting with acute heart failure 3 weeks post a presumed AMI. On evaluation, a substantial ventricular septal defect with left-to-right shunt was observed. The patient, although hemodynamically stable with mild symptoms, underwent surgical closure of the defect and coronary artery bypass graft for multivessel coronary artery disease. This case contributes to the literature on the delayed presentation of post-myocardial infarction (MI) ventricular septal rupture, a scenario deviating from the anticipated severe hemodynamic instability given the timing of the MI and the extent of the septal defect.

Traumatic Right Atrium Perforation Causing a Pneumothorax and Pneumopericardium, Treated Conservatively.

Pacemaker insertion is a daily occurrence in the United States of America, and it is a relatively common procedure; however, complications can occur. One common complication includes the development of a pneumothorax; however, there are rare instances where patients can develop a pneumopericardium as well. We present a case of a patient who underwent dual chamber pacemaker implantation complicated by a pneumothorax and left-sided pneumopericardium, which is a rare finding. This patient initially presented with syncopal episodes and a dual chamber pacemaker was inserted; however, not long after, the patient developed pericarditis and was found to have a pneumothorax and a pneumopericardium. In these cases, patients can be treated with chest tube insertion, lead extraction, or even conservatively, depending on the patient's clinical status. Various reasons exist for the development of a pneumothorax and pneumopericardium; however, the guidelines on management are still unclear and require further study. In our patient, his pneumothorax and contralateral pneumopericardium were treated conservatively with stable follow-up post-hospitalization.

A Rare Case of Splenic Infarct Secondary to Mobile Cardiac Echodensity.

Lambl's excrescences (LE) are mobile filiform lesions, mostly found on the left-sided heart valves. Histologically, they have a mesenchymal origin with a single endothelial layer. They have the potential to detach, resulting in catastrophic thromboembolic events. Their rarity often leads to them being misdiagnosed as vegetations of endocarditis with patients failing to improve on conventional therapy. A 48-year-old female with a history of hypertension presented to the Emergency Department with a one-week history of sharp left upper quadrant pain. She was vitally stable; the only lab abnormality was revealed to be a mildly elevated white cell count. CT abdomen revealed a splenic infarct involving 25% of the parenchyma. Patients had no history of abdominal trauma, coagulation disorders, exogenous estrogen use or IV drug abuse. Subsequent investigations failed to reveal any cause of hypercoagulability. An extensive cardiac workup revealed no arrhythmias, but transesophageal echocardiogram showed a mobile echo density on the ventricular side of the aortic valve attached at the coaptation zone, approximately 2.7 cm long and 0.1 cm wide, suggesting a very prominent Lambl's excrescence. In the absence of any other findings, the patient's splenic infarct was determined to be secondary to an embolic event from the aortic valve lesion. Rivaroxaban was initiated and the patient subsequently improved. Existing literature describes most LEs as being asymptomatic and discovered incidentally on echocardiograms. This case illustrates the need to develop a criterion for prompt identification of LEs and differentiating them from the vegetations of endocarditis. It also brings forth the question of prophylactic treatment of these lesions while highlighting the lack of guidelines regarding the management of embolic phenomena secondary to LE.

A Case of Stress Cardiomyopathy With Nab-Paclitaxel Infusion.

Stress cardiomyopathy is a transient left ventricular dysfunction caused by physiologic or pathologic stressors. Anaphylaxis is a hypersensitivity disorder that can lead to a rapid life-threatening respiratory collapse. It happens due to exposure to allergens including medications. During anaphylaxis, there is a compensatory release of catecholamines that can lead to stress cardiomyopathy. In this case, nab-paclitaxel infusion led to anaphylaxis with respiratory failure. Echocardiogram showed features of diffuse hypokinesis with preserved basal segment contractility, and cardiac catheterization did not show any evidence of obstructive coronary artery disease. The overall clinical picture suggested stress cardiomyopathy. The patient was treated with guideline-directed medical therapy which resulted in normalization of the ejection fraction with no symptoms of congestive heart failure at any point. The patient was thereafter resumed on a reduced dose of nab-paclitaxel. This case report adds to the spectrum of infusion-related reactions associated with paclitaxel and demonstrates the course of events in the management of anaphylaxis and stress cardiomyopathy in this scenario.

Case of ST-Elevation Myocardial Infarction in a 32-Year-Old Male Receiving Bleomycin, Etoposide, and Cisplatin Chemotherapy for Embryonal Carcinoma.

Myocardial infarction in young individuals has unique risk factors compared to the older population. Along with usual risk factors, one should explore causes such as recreational drug use, medication-induced myocardial infarction, and spontaneous coronary artery dissection. Here, we present the case of a 32-year-old male who presented with chest pain and was found to have complete thrombotic occlusion of the right coronary artery. He recently started receiving chemotherapy with bleomycin, etoposide, and cisplatin (PEB). In the absence of other risk factors and previous reports of similar cardiotoxicity with bleomycin, the patient was deemed to have an adverse effect from the chemotherapy regimen.

Improving the generalizability of protein-ligand binding predictions with AI-Bind.

Identifying novel drug-target interactions is a critical and rate-limiting step in drug discovery. While deep learning models have been proposed to accelerate the identification process, here we show that state-of-the-art models fail to generalize to novel (i.e., never-before-seen) structures. We unveil the mechanisms responsible for this shortcoming, demonstrating how models rely on shortcuts that leverage the topology of the protein-ligand bipartite network, rather than learning the node features. Here we introduce AI-Bind, a pipeline that combines network-based sampling strategies with unsupervised pre-training to improve binding predictions for novel proteins and ligands. We validate AI-Bind predictions via docking simulations and comparison with recent experimental evidence, and step up the process of interpreting machine learning prediction of protein-ligand binding by identifying potential active binding sites on the amino acid sequence. AI-Bind is a high-throughput approach to identify drug-target combinations with the potential of becoming a powerful tool in drug discovery.

The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.

Thyroid dysfunction may be associated with poor outcomes in patients with COVID-19.

BACKGROUND: Coronavirus disease (COVID-19) has resulted in considerable morbidity and mortality worldwide. Thyroid hormones play a key role in modulating metabolism and the immune system. However, the prevalence of thyroid dysfunction (TD) and its association with the prognosis of COVID-19 have not yet been elucidated. In this study, we seek to address this gap and understand the link between TD and COVID-19. METHODS: Herein, we enrolled patients who were hospitalized with COVID-19 and had normal or abnormal thyroid function test results at the West Court of Union Hospital in Wuhan, China, between 29 January and February 26, 2020. We carried out follow up examinations until April 26, 2020. Data on clinical features, treatment strategies, and prognosis were collected and analyzed. TD was defined as an abnormal thyroid function test result, including overt thyrotoxicosis, overt hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroid sick syndrome. RESULTS: A total of 25 and 46 COVID-19 patients with and without TD, respectively, were included in the study. COVID-19 patients with TD had significantly higher neutrophil counts and higher levels of C-reactive protein, procalcitonin, lactate dehydrogenase, serum creatine kinase, aspartate transaminase, and high-sensitive troponin I and a longer activated partial thromboplastin time but lower lymphocyte, platelet, and eosinophil counts. A longitudinal analysis of serum biomarkers showed that patients with TD presented persistently high levels of biomarkers for inflammatory response and cardiac injury. COVID-19 patients with TD were more likely to develop a critical subtype of the disease. Patients with TD had a significantly higher fatality rate than did those without TD during hospitalization (20% vs 0%, P = 0.002). Patients with TD were more likely to stay in the hospital for more than 28 days than were those without TD (80% vs 56.52%, P = 0.048). CONCLUSIONS: Our preliminary findings suggest that TD is associated with poor outcomes in patients with COVID-19.