A critical role for donor-derived IL-22 in cutaneous chronic GVHD.

Graft-versus-host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end-organ dysfunction and opportunistic infection. The role of interleukin (IL)-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD and that IL-22 is produced by highly inflammatory donor CD4+ T cells posttransplantation. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL-22+ Th17 cells. Donor Th22 and IL-22+ Th17 cells share a similar IL-6-dependent developmental pathway, and while Th22 cells arise independently of the IL-22+ Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of patients with GVHD after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.

A Controversial Relationship Between Crohn's Disease and Hidradenitis Suppurativa: A Case Series and Literature Review.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) with major extraintestinal manifestations. Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that has previously been described to have a strong association with CD. Though the pathophysiology remains uncertain, this case series highlights the different aspects of disease presentation, similarities, severity, current treatment modalities, and the relational conflict between HS as a paradoxical side effect of biologic agents (BA) that is not well established. We identified a total of three patients with CD and HS and described their clinical presentation and management. A systematic search of the literature with PubMed and Ovid MEDLINE was done in 2021. Two patients were initially diagnosed with CD prior to developing skin manifestations. The third patient was diagnosed with HS first, then was found to have gastrointestinal symptoms. All patients had HS requiring surgical intervention. One patient failed a biological agent but responded to another. The second patient was treated with cytotoxic agents with acceptable results. The third patient was managed without the use of biologics. One of three patients' clinical courses may suggest a paradoxical side effect of BA.  The relationship between CD and HS is based on several case reports. A prospective study will help establish the relationship as well as shed light on the treatment of both conditions simultaneously. In addition, further evaluation of the causal relationship between BA, specifically adalimumab and infliximab as treatment for CD and HS are warranted to effectively manage Crohn's disease, evaluate paradoxical HS, and improve outcomes of both HS and CD. CD and HS impact a patient's quality of life and physicians should therefore have a high degree of awareness upon diagnosis.

Whipple's disease review, prevalence, mortality, and characteristics in the United States: A cross-sectional national inpatient study.

Whipple's disease is a rare multiorgan systemic disease caused by Tropheryma whipplei infection that may present with a wide range of signs and symptoms. This study aim to comprehensively review and determine the inpatient prevalence, mortality, risk factors, and reasons for hospitalization of patients with Whipple's disease. ICD-10 codes were used to identify admissions with Whipple's disease during the years 2016 to 2018. Characteristics of admissions with and without Whipple's disease were compared. The most common reasons for hospitalization were identified in admissions with Whipple's disease. The prevalence of Whipple's disease was 4.6 per 1 million hospitalizations during the study period. Whipple's disease admissions were significantly older than other hospitalizations, with a mean age of 60.2 ±â€…1.6 years compared to 50.0 ±â€…0.1. Males were more likely to have Whipple's disease and represented approximately two-thirds of hospitalizations. A disproportionate number of admissions occurred in the Midwest. Patients with Whipple's disease were most commonly admitted for gastrointestinal disease, followed by systemic infection, cardiovascular/circulatory disease, musculoskeletal disease, respiratory disease, and neurological disease. High mortality was seen in admissions for central nervous system (CNS) disease. Whipple's disease has heterogeneous presentations for inpatient admissions, and disproportionately affects older males. High hospitalization rates in the Midwest support environmental and occupational disease transmission likely from the soil. Hospitalists should be aware of the various acute, subacute, and chronic presentations of this disease, and that acute presentations may be more common in the inpatient setting.

Predictors of colorectal carcinoma and inflammatory bowel disease in patients with colonic wall thickening.

Background and Aim: Colonic wall thickening (CWT) is commonly associated with clinically significant pathologies, but predictive factors of such pathologies are not well known. This study aims to identify the predictors of clinically significant pathologies, such as colorectal carcinoma (CRC) and inflammatory bowel disease (IBD), in patients with CWT. Methods: Subjects with an abnormal abdominal computed tomography (CT) and a follow-up colonoscopy between 2010 and 2020 were retrospectively reviewed. Patients with CWT in the CT were included and examined in this study. A multivariable logistic regression analysis was performed to assess for factors independently associated with CRC or IBD in these subjects. Receiver operating characteristic (ROC) curve analysis was used to further examine significant parameters in multivariable logistic regression analysis. Results: Among 403 patients with CWT on CT scans who underwent a colonoscopy, 269 subjects who met the inclusion criteria were identified and studied. On multivariable logistic regression models, elevated platelet count, low hematocrit, and localized CWT were found to be independently associated with CRC, while elevated platelet count and younger age were independently associated with IBD. On ROC curve analysis for CRC, area under the curve (AUC) for hematocrit, platelets, and localized CWT was 0.76, 0.75, and 0.61, respectively. On ROC curve analysis for IBD, AUC for age and platelets was 0.90 and 0.69, respectively. Conclusion: Elevated platelet count, low hematocrit, and localized CWT can be potentially used as predictors of CRC in patients with CWT. Elevated platelet count and young age can be used to predict IBD in these patients.

Candida-Induced Emphysematous Gastritis in a Multiple Myeloma Patient: Conservative Management With Favorable Outcome.

Emphysematous gastritis is a rare, and often fatal, infection with unclear recommendations on management. We report the first documented case of emphysematous gastritis caused by Candida species in a patient on chemotherapy for multiple myeloma. Our patient, who presented with gastrointestinal symptoms was found to have gas in the stomach wall, peri-gastric, and portal veins on CT scan. Nasogastric tube cultures grew Candida albicans and Candida glabrata and the patient was treated with antibiotics and antifungals. Prompt recognition and conservative management led to a favorable outcome.

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma.

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL). METHODS: We conducted 2 parallel phase I/II studies (ClinicalTrials.gov identifiers: NCT02690545 and NCT02917083) at 2 independent centers involving patients with relapsed or refractory HL and administered CD30.CAR-Ts after lymphodepletion with either bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. The primary end point was safety. RESULTS: Forty-one patients received CD30.CAR-Ts. Treated patients had a median of 7 prior lines of therapy (range, 2-23), including brentuximab vedotin, checkpoint inhibitors, and autologous or allogeneic stem cell transplantation. The most common toxicities were grade 3 or higher hematologic adverse events. Cytokine release syndrome was observed in 10 patients, all of which were grade 1. No neurologic toxicity was observed. The overall response rate in the 32 patients with active disease who received fludarabine-based lymphodepletion was 72%, including 19 patients (59%) with complete response. With a median follow-up of 533 days, the 1-year progression-free survival and overall survival for all evaluable patients were 36% (95% CI, 21% to 51%) and 94% (95% CI, 79% to 99%), respectively. CAR-T cell expansion in vivo was cell dose dependent. CONCLUSION: Heavily pretreated patients with relapsed or refractory HL who received fludarabine-based lymphodepletion followed by CD30.CAR-Ts had a high rate of durable responses with an excellent safety profile, highlighting the feasibility of extending CAR-T cell therapies beyond canonical B-cell malignancies.