Improvement of Recalcitrant Dissecting Cellulitis of the Scalp After a Trial of Upadacitinib.

Dissecting cellulitis of the scalp (DCS) is a rare condition characterized by painful inflammatory nodules and abscesses on the scalp, often leading to sinus tracts and scarring alopecia. We present a case of DCS in a 26-year-old male who experienced significant clinical improvement following a short course of upadacitinib, a Janus kinase (JAK) inhibitor. The patient received multiple standard treatments such as topical antimicrobials, oral antibiotics, corticosteroids, and intralesional triamcinolone injections, with limited success. However, following the initiation of upadacitinib, the patient reported reduced pain, pustular draining, and bleeding, with significantly improved quality of life. To our knowledge, there is currently a paucity of literature documenting the use of JAK inhibitors for DCS. This case aims to highlight the potential of JAK inhibitors as a therapy for refractory DCS, a condition with limited treatment options.

Evaluating the efficacy of combination and single-agent immunotherapies in real-world patterns of disease progression and survival of metastatic melanoma patients.

The objective of this study is to describe survival outcomes in patients with metastatic melanoma in a real-world setting receiving combination and single-agent immunotherapy outside the clinical trial context. We conducted a retrospective single-institution study of patients with metastatic melanoma in a real-world setting. Survival was calculated using log-rank test. Contingency tables were analyzed using Fisher's Exact test. CD8 + T-cell densities were measured using quantitative immunofluorescence and analyzed using Mann-Whitney U test. The median overall survival (OS) for 132 patients was 45.3 months. Brain metastasis did not confer a higher risk of death relative to liver and/or bone disease (39.53 versus 30.00 months, respectively; P  = 0.687). Anti-PD-1 monotherapy was the most common first-line treatment, received by 49.2% of patients. There was no significant difference in OS between patients receiving single-agent anti-PD-1 and combination anti-PD-1 plus CTLA-4 (39.4 months versus undefined; P  = 0.643). Patients treated with combination therapy were more likely to be alive without progression at the last follow-up than those who received monotherapy (70.4% versus 49.2%; P  = 0.0408). Median OS was 21.8 months after initiation of second-line therapy after anti-PD-1 monotherapy. CD8+ T-cell densities were higher in patients who achieved disease control on first-line immunotherapy ( P  = 0.013). In a real-world setting, patients with metastatic melanoma have excellent survival rates, and treatment benefit can be achieved even after progression on first-line therapy. Combination immunotherapy may produce more favorable long-term outcomes in a real-world setting. High pretreatment CD8+ T-cell infiltration correlates with immunotherapy efficacy.

Pancreatic Panniculitis: A Case Associated With Acute Pancreatic Allograft Rejection.

We present a unique case of pancreatic panniculitis (PP) in a 42-year-old male with a history of pancreas-after-kidney (PAK) transplant. The patient developed PP due to acute pancreas allograft rejection. Clinical manifestations included fevers, myalgias, arthralgias, and tender erythematous subcutaneous nodules on the lower extremities. A recent hospital admission was noted for acute pancreas allograft rejection related to low tacrolimus levels. Rheumatological and infectious disease workups were negative. Skin nodule punch biopsy confirmed PP with lobular panniculitis, necrotic adipocytes, basophilic debris, and calcification. Pancreatic biopsy showed evidence of parenchymal acute cellular rejection. Lipase and amylase levels were elevated (1781 U/L and 881 U/L, respectively). Treatment involved pulse solumedrol and thymoglobulin for pancreatic rejection, alongside adjustments to immunosuppressive medications. This case highlights the rarity of PP in a PAK recipient and its association with acute pancreas allograft rejection. Importantly, it is the first reported case of PP occurring solely in the context of pancreas transplant rejection, without concurrent kidney damage or rejection. Prompt diagnosis and management led to the resolution of skin and systemic symptoms. In conclusion, this report presents a clinically relevant and unique case of PP resulting from acute pancreas allograft rejection in a PAK transplant recipient. The findings underscore the importance of early diagnosis and management for positive patient outcomes, serving as a reminder to consider underlying pancreatic pathology when encountering PP in transplant recipients.

The Pivotal Role of Adipocyte-Na K peptide in Reversing Systemic Inflammation in Obesity and COVID-19 in the Development of Heart Failure.

This review summarizes data from several laboratories that have demonstrated a role of the Na/K-ATPase, specifically its α1 subunit, in the generation of reactive oxygen species (ROS) via the negative regulator of Src. Together with Src and other signaling proteins, the Na/K-ATPase forms an oxidant amplification loop (NKAL), amplifies ROS, and participates in cytokines storm in obesity. The development of a peptide fragment of the α1 subunit, NaKtide, has been shown to negatively regulate Src. Several groups showed that the systemic administration of the cell permeable modification of NaKtide (pNaKtide) or its selective delivery to fat tissue-adipocyte specific expression of NaKtide-ameliorate the systemic elevation of inflammatory cytokines seen in chronic obesity. Severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), the RNA Coronavirus responsible for the COVID-19 global pandemic, invades cells via the angiotensin converting enzyme 2 (ACE-2) receptor (ACE2R) that is appended in inflamed fat tissue and exacerbates the formation of the cytokines storm. Both obesity and heart and renal failure are well known risks for adverse outcomes in patients infected with COVID-19. White adipocytes express ACE-2 receptors in high concentration, especially in obese patients. Once the virus invades the white adipocyte cell, it creates a COVID19-porphyrin complex which degrades and produces free porphyrin and iron and increases ROS. The increased formation of ROS and activation of the NKAL results in a further potentiated formation of ROS production, and ultimately, adipocyte generation of more inflammatory mediators, leading to systemic cytokines storm and heart failure. Moreover, chronic obesity also results in the reduction of antioxidant genes such as heme oxygenase-1 (HO-1), increasing adipocyte susceptibility to ROS and cytokines. It is the systemic inflammation and cytokine storm which is responsible for many of the adverse outcomes seen with COVID-19 infections in obese subjects, leading to heart failure and death. This review will also describe the potential antioxidant drugs and role of NaKtide and their demonstrated antioxidant effect used as a major strategy for improving obesity and epicardial fat mediated heart failure in the context of the COVID pandemic.