Myocarditis Following Immune Checkpoint Inhibition With Pembrolizumab: Management in a Context of Steroid Intolerance.

Immune checkpoint inhibitors (ICIs) are a major advance in oncology and have become first- or second-line therapy for over 50% of oncology patients. ICI-associated myocarditis is a complication that, although rare, has a high mortality rate. We present a case of ICI-associated myocarditis presenting as complete heart block. Traditional treatment with high-dose steroids was abandoned in this case, owing to steroid-induced psychosis. Alternative treatment with immunomodulators was initiated with a good response. This case highlights the variable presentation of ICI-associated myocarditis. As use of ICIs continues to expand, an understanding of their adverse reactions and best treatments will be needed.

Les inhibiteurs des points de contrôle immunitaire (IPCI) constituent un progrès majeur dans le domaine de l'oncologie, et sont maintenant utilisés comme traitement de première ou de deuxième intention pour plus de 50 % des patients en oncologie. La myocardite associée aux IPCI est une complication rare, mais dont le taux de mortalité est élevé. Nous présentons ici un cas de myocardite associée aux IPCI caractérisé par un bloc cardiaque complet. Le traitement classique par doses élevées de stéroïdes a dû être abandonné en raison d'une psychose provoquée par les stéroïdes. Un autre traitement par des immunomodulateurs a été amorcé et a produit une réponse satisfaisante. Ce cas permet de souligner la variété des tableaux cliniques des myocardites associées aux IPCI. Alors que l'utilisation des IPCI continue d'augmenter, une meilleure compréhension des réactions indésirables et des options pour leur prise en charge seront nécessaires.

Myocarditis in the Setting of Recent COVID-19 Vaccination.

We report three patients who presented with chest pain after receiving either the BNT162b2 Pfizer/BioNTech or mRNA-1273 Moderna/NIH vaccine. Clinical presentation, biomarker, and cardiac MRI supported myocarditis. It is imperative that potential side effects of COVID-19 vaccine are reported to improve our knowledge about COVID-19 and mRNA vaccines.

Medical Management of Recurrent Left Ventricular Assist Device Thrombosis in a Patient With Biventricular Assist Devices.

Ventricular assist device (VAD) pump thrombosis is a known complication and while the preferred standard treatment is surgical pump exchange this procedure is not without risk and for some patients the risks are prohibitive. This is a case of a 68-year-old female with bilateral HeartWare ventricular assist devices (HVAD) implanted as destination therapy who presented with signs of recurrent pump thrombosis. Surgical pump exchange was deemed to confer prohibitive risk due to her underlying medical co-morbidities and therefore not an option for treatment. After careful consideration of possible options for treatment, she received systemic thrombolysis (Alteplase 5 mg IV bolus followed by 3 mg/hour infusion for 10 hours through a central line) which was successful. This case highlights, not only the rarity of bilateral VADs as destination therapy, but also demonstrates the safety and efficacy of using systemic thrombolytics in patients with bilateral HVADs for treatment of pump thrombosis.

Cardiovascular Risk in Survivors of Cancer.

PURPOSE OF REVIEW: Survivors of childhood and adult cancers face increased risk of cardiovascular disease. We review the current evidence base and guidelines for this rapidly growing population. RECENT FINDINGS: Research continues to show that cardiovascular disease is an important cause of morbidity and mortality in cancer survivors. Cardiotoxicity related to chemotherapy and radiotherapy accounts for part of this increased risk. There is emerging evidence that cancer and cardiovascular disease share a similar biology and risk factors. At present, there are several guidelines and consensus recommendations for the management of cardiovascular risk in cancer survivors. The evidence base is accumulating though additional research is necessary to demonstrate improved outcomes and comparative effectiveness.

Treatment of articular fractures with continuous passive motion.

This article presents a review of the basic science and current research on the use of continuous passive motion therapy after surgery for an intra-articular fracture. This information is useful for surgeons in the postoperative management of intra-articular fractures in determining the best course of treatment to reduce complications and facilitate quicker recovery.

C-terminal methylation of truncated neuropeptides: an enzyme-assisted extraction artifact involving methanol.

Neuropeptides are the largest class of signaling molecules used by nervous systems. Today, neuropeptide discovery commonly involves chemical extraction from a tissue source followed by mass spectrometric characterization. Ideally, the extraction procedure accurately preserves the sequence and any inherent modifications of the native peptides. Here, we present data showing that this is not always true. Specifically, we present evidence showing that, in the lobster Homarus americanus, the orcokinin family members, NFDEIDRSGFG-OMe and SSEDMDRLGFG-OMe, are non-native peptides generated from full-length orcokinin precursors as the result of a highly selective peptide modification (peptide truncation with C-terminal methylation) that occurs during extraction. These peptides were observed by MALDI-FTMS and LC-Q-TOFMS analyses when eyestalk ganglia were extracted in a methanolic solvent, but not when tissues were dissected, co-crystallized with matrix, and analyzed directly with methanol excluded from the sample preparation. The identity of NFDEIDRSGFG-OMe was established using MALDI-FTMS/SORI-CID, LC-Q-TOFMS/MS, and comparison with a peptide standard. Extraction substituting deuterated methanol for methanol confirmed that the latter is the source of the C-terminal methyl group, and MS/MS confirmed the C-terminal localization of the added CD3. Surprisingly, NFDEIDRSGFG-OMe is not produced via a chemical acid-catalyzed esterification. Instead, the methylated peptide appears to result from proteolytic truncation in the presence of methanol, as evidenced by a reduction in conversion with the addition of a protease-inhibitor cocktail; heat effectively eliminated the conversion. This unusual and highly specific extraction-derived peptide conversion exemplifies the need to consider both chemical and biochemical processes that may modify the structure of endogenous neuropeptides.