Thrombosis Development After mRNA COVID-19 Vaccine Administration: A Case Series.

The coronavirus disease 2019 (COVID-19) pandemic remains one of the largest global health crises of the last century. Fortunately, COVID-19 vaccines have proven to be one of the most promising options in halting the progression of the pandemic. As more and more people receive COVID-19 vaccines, the medical community has learned a great deal about their efficacy and the occurrence of very rare adverse effects. While the number of thromboembolic events post-adenoviral vaccines has been well-documented in the medical literature, there has been limited information regarding thrombosis development after receiving a messenger RNA (mRNA)-based vaccine. This case series highlights four different patients who received an mRNA-based COVID-19 vaccine and subsequently developed venous thromboembolism. Therefore, we hope that after reviewing this article, physicians will be more aware of thrombosis-related developments following mRNA vaccine administration for COVID-19. Fortunately, with early diagnosis and prompt treatment, patients can still expect full recovery from any vaccine thrombosis-associated complications, and the benefits of receiving an mRNA-based COVID-19 vaccine still outweigh the risks of post-vaccination complications.

Digital ischaemia and necrosis from oxaliplatin.

Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in direct cell cytotoxicity with resultant cell death. The most common side effects often noted are neurotoxicity, nausea, vomiting, diarrhoea, hepatotoxicity and myelosuppression. Oxaliplatin induced digital ischaemia and necrosis is a rare side effect that was observed in our patient. In general, digital ischaemia is a rare vascular disorder that is often associated with autoimmune disease. A patient with digital ischaemia due to oxaliplatin will be described in this case report.

Anaplastic Lymphoma Kinase (ALK)-positive Tumors: Clinical, Radiographic and Molecular Profiles, and Uncommon Sites of Metastases in Patients With Lung Adenocarcinoma.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) gene rearrangements are observed in about 4% to 8% non-small cell lung cancer (NSCLC). ALK+ tumors have been associated with increased pleural and pericardial disease. Our primary objective was to determine the uncommon sites of metastasis of ALK+ NSCLC. Secondary objectives included study of coexisting mutations and factors impacting survival of ALK+ NSCLC. METHODS: All patients with metastatic ALK+ NSCLC at the City of Hope Cancer Center in Duarte, California from 2010 to 2017 were selected for retrospective chart review. The demographic variables were collected. The molecular statuses of patients were evaluated through commercially available platforms for next-generation sequencing. Three-dimensional volumetric images were generated for the primary lesion and different sites of metastasis. RESULTS: Sixty two patients with ALK+ NSCLC were identified from 2010 to 2017. The median age was 59 with 36 (58%) female individuals and only 20 (32%) smokers. Twenty four patients had uncommon sites of metastasis which were thyroid, soft tissue, chest and abdominal wall, spleen, peritoneum, omentum, kidney, and ovary. Common characteristics of the primary lesions were right upper lobe location (N=23 [37%]), oval shape (N=22 [35%]), irregular margins (N=26 [42%]), solid lesions (N=27 [44%]), presence of pleural contact or effusion (N=22 [35%]). Twenty four patients had next-generation sequencing testing which showed coexisting mutations such as TP53 (N=8), EGFR (N=5), KRAS (N=3). Patients with uncommon sites of metastasis had a decreased median survival compared with common sites (39 vs. 82 m, P=0.046). CONCLUSION: In NSCLC, ALK rearrangements may not be mutually exclusive mutations and can present with unique radiographic patterns. Patients with uncommon sites of metastasis may have worse outcomes.

The effect of gut microbiome on tolerance to morphine mediated antinociception in mice.

There is growing appreciation for the importance of gastrointestinal microbiota in many physiological and pathophysiological processes. While morphine and other narcotics are the most widely prescribed therapy for moderate to severe pain clinically, they have been noted to alter microbial composition and promote bacterial translocation to other tissues. Here we examined the pharmacodynamic properties of chronic morphine in mice following bacterial depletion with oral gavage of an antibiotic cocktail (ABX). ABX significantly reduced gut bacteria and prevented chronic morphine induced increases in gut permeability, colonic mucosal destruction, and colonic IL-1ß expression. In addition, ABX prevented the development of antinociceptive tolerance to chronic morphine in both the tail-immersion and acetic acid stretch assays. Morphine tolerance was also reduced by oral vancomycin that has 0% bioavailability. These findings were recapitulated in primary afferent neurons isolated from dorsal root ganglia (DRG) innervating the lower gastrointestinal tract, wherein in-vivo administration of ABX prevented tolerance to morphine-induced hypoexcitability. Finally, though ABX repeatedly demonstrated an ability to prevent tolerance, we show that it did not alter susceptibility to precipitation of withdrawal by naloxone. Collectively, these finding indicate that the gastrointestinal microbiome is an important modulator of physiological responses induced by chronic morphine administration.