A Rare Complication of Pneumopericardium, Spontaneous Pneumothorax, and Subcutaneous Emphysema in a COVID-19 Pneumonia Patient Treated With High Flow Nasal Cannula.

Spontaneous pneumomediastinum (SPM), unrelated to mechanical ventilation, has been newly described as a complication of patients with coronavirus disease (COVID-19) pneumonia without the associated risk factors. The main objective of presenting this case is to highlight a rare but important complication among patients with COVID-19 pneumonia treated only with a high-flow nasal cannula (HFNC). We aim to study the possible underlying pathophysiology of this phenomenon.

Beriberi: A Reversible Cause of Acute Severe Pulmonary Hypertension.

Thiamine, also known as vitamin B1, plays a fundamental role in energy metabolism. The organs most sensitive to thiamine deficiency are the cardiovascular and nervous systems. The usual presentations include Wernicke's encephalopathy, polyneuropathy (known as "dry beriberi"), and the cardiovascular form (known as "wet beriberi"). Wet beriberi-induced acute severe pulmonary hypertension has rarely been previously described. Here we present a case of wet beriberi with severe right heart failure due to acute pulmonary hypertension. The underlying physiologic derangements dramatically improved after thiamine treatment. No other possible causes of pulmonary hypertension could be identified, with the exception of thiamine deficiency. This case illustrates the importance of considering wet beriberi as a possible cause of acute pulmonary hypertension with right heart failure.

The potential role of free chitosan in bone trauma and bone cancer management.

Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management.

The performance of doxorubicin encapsulated in chitosan-dextran sulphate microparticles in an osteosarcoma model.

Osteosarcoma (OS) is the most common primary bone cancer affecting children and adolescents. It is potentially debilitating and fatal due to pulmonary metastasis. A common management strategy, chemotherapy, has a 10-year disease-free survival of approximately 60%. However, a targeted approach to OS tumor inhibition is still lacking, calling for improved management strategies. A frontline drug for OS, doxorubicin (DOX), causes multiple side-effects (example myelosuppression, heart failure, hepatic toxicity, alopecia) in patients, especially in high doses required to control tumor growth. A drug delivery system (DDS) was developed to deliver DOX specifically to tumor sites. Through DOX encapsulation into chitosan DDS via the complex coacervation method with dextran sulphate, novel DOX microparticles (DMPs), with a DOX loading content of more than 99%, were formed. Multiple optimisation steps produced DMPs which caused OS cell death through apoptosis, necrosis and autophagic cell death. Treatment of mice bearing orthotopic OS with DMP decreased tumor volume, decreased bone lysis, and reduced secondary metastasis to the lungs. DMP-treated mice also maintained their weight and did not appear to suffer from any visible side-effects such as heart failure or dry skin. Thus, DMP may prove to be a useful DDS platform clinically provided further studies are performed to rigorously validate this technology.