Background: The adult mammalian heart has limited regenerative capacity, mostly attributable to postnatal cardiomyocyte cell cycle arrest. In the last 2 decades, numerous studies have explored cardiomyocyte cell cycle regulatory mechanisms to enhance myocardial regeneration after myocardial infarction. Pkm2 (Pyruvate kinase muscle isoenzyme 2) is an isoenzyme of the glycolytic enzyme pyruvate kinase. The role of Pkm2 in cardiomyocyte proliferation, heart development, and cardiac regeneration is unknown. Methods: We investigated the effect of Pkm2 in cardiomyocytes through models of loss (cardiomyocyte-specific Pkm2 deletion during cardiac development) or gain using cardiomyocyte-specific Pkm2 modified mRNA to evaluate Pkm2 function and regenerative affects after acute or chronic myocardial infarction in mice. Results: Here, we identify Pkm2 as an important regulator of the cardiomyocyte cell cycle. We show that Pkm2 is expressed in cardiomyocytes during development and immediately after birth but not during adulthood. Loss of function studies show that cardiomyocyte-specific Pkm2 deletion during cardiac development resulted in significantly reduced cardiomyocyte cell cycle, cardiomyocyte numbers, and myocardial size. In addition, using cardiomyocyte-specific Pkm2 modified RNA, our novel cardiomyocyte-targeted strategy, after acute or chronic myocardial infarction, resulted in increased cardiomyocyte cell division, enhanced cardiac function, and improved long-term survival. We mechanistically show that Pkm2 regulates the cardiomyocyte cell cycle and reduces oxidative stress damage through anabolic pathways and β-catenin. Conclusions: We demonstrate that Pkm2 is an important intrinsic regulator of the cardiomyocyte cell cycle and oxidative stress, and highlight its therapeutic potential using cardiomyocyte-specific Pkm2 modified RNA as a gene delivery platform.

Background: Obesity is a growing pandemic that is associated with multiple cardiovascular disease (CVD) risk factors such as hypertension, diabetes, dyslipidemia and obstructive sleep apnea. With the increase in obesity rates where nearly two thirds of Americans are either obese or overweight, there has been an increase in the use of pharmacological therapy weight loss. While these therapies have shown benefit in weight reduction, the clinical impact these pharmacological agents on overall CVD outcomes has yet to be determined. Aim: We aimed to assess the effect of pharmacological agents used for weight reduction on CVD risk and all-cause mortality. Methods: We conducted a meta-analysis of peer-reviewed literature that evaluated the impact of anti-obesity drugs on cardiovascular outcomes. Key words used included: “orlistat”, “lorcaserin”, “phentermine/topiramate” or “naltrexone/bupropion” and “cardiovascular outcomes” among others. We reviewed 791 articles, only 47 studies were randomized controlled trials and only 7 studies fulfilled all the inclusion criteria including, quantitative data on cardiovascular risk factors such as, Hemoglobin A1C (A1C), changes in body mass index (BMI), blood pressure and CVD morbidity and mortality. Data was retrieved from these studies and evaluated with comprehensive meta-analysis software® to assess pooled effects for medical management versus placebo. Results: There were 7 studies included in the final analysis, with a total of 18,598 subjects, of which 8,685 were in the intervention (INT) group and 9,913 in the control (CTRL) group. For all cause mortality, there were 45 events in the INT and 55 in the CTRL groups, suggesting no significant difference between the two groups (OR: 0.843, 95%CI: 0.571–1.244, Z: −0.860, P: 0.390). For CVD mortality, there were 17 events in the INT and 36 events in the CTRL groups suggesting a significant mortality benefit in the INT group (OR:0.496, 95% CI: 0.282–0.873, Z: −2.433, P: 0.015). There was a significant absolute reduction in A1C in the INT group (Hg: −0.238, 95%CI: −0.291 to −0.186, Z: −8.937, P< 0.001). The percentage weight reduction was significantly higher for the INT group compared to the CTRL group (Hg: −0.431, 95%CI: −0.477 to −0.385, Z: −18.472, P< 0.001) and the blood pressure reduction was higher for the INT group compared to the CTRL group. (Hg: −0.052, 95%CI: −0.101- −0.003, Z: −2.086, P: 0.037). The heterogeneity observed for our meta analysis is Q: 1.884, df: 6, P: 0.930. Conclusions: Our study demonstrated the favorable and significant effect of pharmacological weight reduction strategies on weight loss, blood pressure reduction, glycemic control (A1C reduction), and CVD mortality. While weight loss without pharmacological means has been shown to reduce CVD risk, the mechanism by which weight loss medications impact CVD risk reduction could be a direct effect of these agents or merely an effect of weight reduction itself. Weight loss has been noted to modify risk factors via improving insulin sensitivity, reduci...

Thyrotoxic periodic paralysis is a sporadic entity characterized by hypokalemia and paralysis in the setting of hyperthyroidism. TPP is most commonly described in young Asian males. Studies have shown an association with mutations affecting inward rectifying potassium channels. The pathophysiology involves Na + -K + - ATPase channel causing an increased intracellular shift of potassium ions in the hyperthyroid state and in the presence of another precipitating condition. Most cases of thyrotoxic periodic paralysis are defined in young Asian males of 20–40 years of age, here we present an interesting case of thyrotoxic periodic paralysis in 32-year-old African American male, who presented with sudden onset weakness in the bilateral lower extremity and left upper extremity. Interestingly, the patient also has sensory deficits, a feature not known to be associated with thyrotoxic periodic paralysis.

Background Lupus myelitis is a rare but disastrous complication of systemic lupus erythematosus (SLE). The transverse myelitis (TM) may involve three or more contiguous spinal cord segments and as such is designated longitudinally extensive transverse myelitis (LETM). The neurological presentation may vary based on the location of the pathology and may consist of a combination of sensory and motor deficits. TM could be the presenting feature of SLE or present after 10 years of disease, while SLE was considered to be in remission. Case presentation 26-year-old Black man with history of biopsy proven-lupus nephritis that had progressed to ESRD, presented with sudden onset quadriplegia that resolved upon arrival to the hospital. On exam, the temperature was 101.8°F and the neurological exam was consistent with residual weakness on the left sided-upper and lower extremities. Leukopenia, lymphopenia and thrombocytopenia, along with low complements were noted. Brain MRI was normal however, the spine MRI was suspicious for an epidural process (C2-T4) and intravenous antibiotics were commenced. After five days, neurological improvement was nil and new spine MRI revealed spinal cord edema secondary to myelitis at several spinal cord levels (C2-T4). Laboratory data was consistent with a SLE flare complicated with longitudinal extensive transverse myelitis. Pulse steroids and plasma exchange were initiated. Two weeks after admission, MRI demonstrated resolution of the epidural spinal lesion and marked improvement in spinal cord edema. Conclusion TM can be the presenting feature of SLE or appear later on during the course of their disease. LETM is the most frequently type of TM found among SLE patients. Given the grave nature of the disease, it is of paramount importance that clinical features of TM be promptly recognized among SLE patients, to prevent catastrophic or even life-threatening outcomes.

Acute viral myositis is a rare condition that is commonly defined with influenza A, B, and enterovirus in the United States of America. Viral myositis complicated by rhabdomyolysis is even less common but requires prompt attention and diagnosis to prevent complications. We describe the occurrence of acute viral myositis complicated by rhabdomyolysis in a young 43-year-old man that lead to acute renal failure. It also highlights that clinicians should keep in mind that viral upper respiratory infections can be complicated with various clinical manifestations that could extend beyond respiratory symptoms.