Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.

A case of type 2 diabetes mellitus with weight gain and worsening of glycemic management after tezepelumab administration for severe bronchial asthma.

Some cases of bronchial asthma are refractory to conventional therapies. As the pathogenesis of bronchial asthma has been clarified, new treatments, such as bronchial thermoplasty and biological drugs, have been developed. Tezepelumab, an anti-thymic stromal lymphopoietin antibody, has been reported to inhibit the exacerbation of severe asthma; however, its adverse effects on glucose metabolism have not yet been reported. We encountered a case of weight gain and worsening glycemic management in a patient with type 2 diabetes and refractory bronchial asthma after the initiation of tezepelumab treatment. It has been reported that the overexpression of thymic stromal lymphopoietin in mice resulted in an enhanced release of free fatty acids from adipose tissues and the liver; thus, the administration of anti-thymic stromal lymphopoietin antibodies in the present case might have caused obesity, fatty liver and lower glucose tolerance.

Lung abscess as a secondary infection of COVID-19: A case report and literature review.

A 16-year-old male was admitted with persistent fever, diarrhea, and anorexia 8 days after the diagnosis of coronavirus disease-2019 (COVID-19). Radiological examination of the lungs showed a cavitary lesion with an air-fluid level, but no apparent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. The lesion was diagnosed as a lung abscess after COVID-19. Treatment with antimicrobials was initiated, which attenuated symptoms and the lung lesion. Specific pathogens were not detected despite repeated sputum cultures, which suggested that lung abscess was caused by oral bacteria as a secondary infection of COVID-19. To date, several cases of lung abscess as a complication of COVID-19 have been reported. However, the majority of cases occurred after intubation to treat COVID-19, and there have been no cases involving young adults. This healthy young patient may have developed lung abscess due to COVID-19.

Impact of newly diagnosed diabetes on coronavirus disease 2019 severity and hyperglycemia.

AIMS/INTRODUCTION: Diabetes is associated with poor clinical outcomes of coronavirus disease 2019 (COVID-19). However, the impact of newly diagnosed diabetes on prognosis has not been clarified. The objective of this study was to show the features and outcome of COVID-19 patients with newly diagnosed diabetes in Japan. MATERIALS AND METHODS: We retrospectively analyzed 62 patients with diabetes hospitalized for COVID-19 between 1 April and 18 August 2021 at the National Center for Global Health and Medicine in Tokyo, Japan. We evaluated the worst severity of COVID-19 and plasma blood glucose levels in patients with newly diagnosed diabetes or pre-existing diabetes. RESULTS: This study included 62 confirmed COVID-19 patients with diabetes, including 19 (30.6%) patients with newly diagnosed diabetes and 43 (69.4%) patients with pre-existing diabetes. Patients with newly diagnosed diabetes significantly progressed to a critical condition more frequently during hospitalization than patients with pre-existing diabetes (52.6% vs 20.9%, P = 0.018). In addition, patients with newly diagnosed diabetes had significantly higher average plasma blood glucose levels for the first 3 days after admission than those with pre-existing diabetes. CONCLUSIONS: Our study suggests that the proportion of COVID-19 patients who are newly diagnosed with diabetes is high, and they have an increased risk of developing severe disease than those with pre-existing diabetes. It might be advisable that at the point of COVID-19 diagnosis, blood glucose and glycated hemoglobin levels be assessed in all patients.

Glycemic control using intermittently scanned continuous glucose monitoring in patients with diabetes requiring methylprednisolone therapy for severe COVID-19.

In patients with severe coronavirus disease 2019 (COVID-19) with diabetes, glycemic control is essential for a better outcome, however, we face difficulty controlling hyperglycemia induced by high-dose glucocorticoids. We report five cases of severe COVID-19 patients with diabetes, whose glycemic control was managed using an intermittently scanned continuous glucose monitoring (isCGM) system during methylprednisolone therapy. Patients using isCGM showed significantly lower average blood glucose levels and significantly higher total daily insulin dose during the methylprednisolone therapy, compared to patients under regular blood glucose monitoring. The use of isCGM enables remote glucose monitoring, and this can reduce the risks of healthcare workers who have frequent contact with the patients. Thus, we suggest that using isCGM should be considered in hospitalized patients with diabetes under the COVID-19 pandemic to achieve better glycemic control and to minimize the possible risks of healthcare workers.