Dapagliflozin (DAPA), a sodium–glucose cotransporter 2 inhibitor, is approved for treatments of patients with diabetes. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial disclosed DAPA’s benefits in symptomatic heart failure, but the underlying mechanism remains largely unknown. In this longitudinal and prospective study, we investigated changes of left ventricular functions including speckle tracking in patients with diabetes who were free from symptomatic heart failure post–DAPA treatment. Using a rat model with streptozotocin-induced diabetes, we measured the effects of DAPA on myocardial function. In patients with diabetes, following 6 months of DAPA treatment, despite no significant changes in left ventricular ejection fraction, the diastolic function and longitudinal strain improved. Likewise, compared with control, the diabetic rat heart developed pronounced fibrosis and a decline in strain and overall hemodynamics, all of which were mitigated by DAPA treatment. In contrast, despite insulin exerting a glucose-lowering effect, it failed to improve myocardial function and fibrosis. In our in vitro study, under high glucose cardiomyocytes showed significant activations of apoptosis, reactive oxygen species, and endoplasmic reticulum (ER) stress–associated proteins, which were attenuated by the coincubation of DAPA. Mechanistically, DAPA suppressed ER stress, reduced myocardial fibrosis, and improved overall function. The results can lead to further improvement in management of left ventricular function in patients with diabetes.

Poorly differentiated pancreatic neuroendocrine carcinomas (NECs) are rare and aggressive malignancies with rapid disease progression and early widespread metastasis. Given histology similarity, they are commonly treated with platinum-based chemotherapy as small cell lung cancer (SCLC). However, no standard treatment has been established for recurrent or progressive disease. We present an Asian patient with recurrent poorly differentiated pancreatic NEC after curative surgery and adjuvant chemotherapy with cisplatin and etoposide. The tumor mutational burden (TMB) was high. The patient received chemotherapy combined with maintenance immunotherapy with nivolumab and achieved promising and durable response, suggesting TMB could be a biomarker to identify NEC patients for immune checkpoint inhibitor (ICI) treatment.

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma (NEC) of the skin. As compared to pure MCCs, combined MCCs are aggressive and exhibit a higher probability of metastasis. A correct diagnosis might be missed, especially when the biopsy sample is too small or too superficial. We report a 79-year-old Taiwanese male who presented with lymphadenopathy suspicious for lymphoma. A nodal biopsy showed metastatic NEC. A skin tumor in the lower back was identified, and an incisional biopsy showed only squamous cell carcinoma (SCC). A subsequent excisional biopsy was performed based on the advice of the senior pathologist because of the presence of metastatic nodal NEC. Finally, a diagnosis of combined MCC and SCC was confirmed. Our literature review identified 13 cases of combined MCC with nodal metastasis as initial presentations, all with an aggressive clinical course. Both the MCC and non-MCC components could be present in the metastatic nodes. Metastases of pure MCC cells were observed in three combined MCCs in sun-protected areas, probably pointing to a distinct pathogenesis. Excision or punch biopsy to include the deep dermal NEC component is recommended as timely diagnosis is mandatory for appropriate management of patients with this rare skin cancer.

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