Clostridioides difficile Infection and Risk of Acute Graft-versus-Host Disease among Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. The relationship between CDI and acute graft-versus-host disease (aGVHD) has been a topic of interest, as these 2 conditions may influence each other. We studied the temporal relationship of CDI to aGVHD in the first 100 days post-transplantation in a large cohort of allo-HSCT recipients. We performed a retrospective cohort study of adult patients undergoing their first allo-HSCT at our tertiary care medical center between January 1, 2010, and December 31, 2016. Patients were followed for CDI diagnosis, development of aGVHD, and vital status up to day +100 post-transplantation. Descriptive statistics and multivariate Cox models with CDI as a time-varying covariate and aGVHD and high-grade aGVHD as outcomes were used for data analyses. A total of 656 allo-HSCT recipients were included in the analysis. Of these, 419 (64%) developed aGVHD, and 111 (17%) were diagnosed with CDI within the first 100 days post-transplantation. CDI developed before the onset of aGVHD in 72 of the 84 allo-HSCT recipients (85%) with both CDI and aGVHD. Fidaxomicin was used in the treatment of 57 of the 111 CDI cases (50%), whereas vancomycin was used in 52 (47%). Most of the CDI cases (88%) were diagnosed in the peritransplantation period (between day -10 and day +10). The median time to the development of CDI and aGVHD was 3.5 days (range, -7 to 95 days) and 33 days (range, 9 to 98 days) post-transplantation, respectively. Using multivariate Cox model, the following predictors were significantly associated with the development of aGVHD: CDI (adjusted hazard ratio [aHR], 1.52; 95% confidence interval [CI], 1.17 to 1.97; P = .0018), transplantation from a matched related donor (MRD) compared with a matched unrelated donor (aHR, 0.68; 95% CI, 0.54 to 0.85; P = .0003), and myeloablative versus nonmyeloablative conditioning (aHR, 2.45; 95% CI, 1.80 to 3.34; P < .0001), adjusting for age, sex, race, underlying disease, cytomegalovirus CMV serostatus, transplant source, and receipt of antithymocyte globulin (ATG). There was no association between CDI and high-grade aGVHD after adjustment for age, underlying disease, transplant type, intensity of conditioning, and receipt of ATG (aHR, 1.59; 95% CI, 0.95 to 2.66; P = .0755). CDI after allo-HSCT is associated with increased risk of GVHD when no CDI prophylaxis was used. Further studies examining CDI preventive measures, including prophylaxis, as well as the preservation or reconstitution of the gastrointestinal microbiome in the setting of HSCT are warranted.

Metastatic Plasmacytoid Bladder Cancer Harboring a CDH-1 Mutation and Producing High Levels of CA 19-9. A Case Report and Literature Review.

BACKGROUND Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive variant of urothelial cancers. Herein, we report a patient with CDH-1 mutated PUC who presented with disseminated peritoneal metastasis and high levels of CA 19-9. CASE REPORT A 65-year-old female presented to the hospital with vomiting, obstructive jaundice, and acute renal failure. Imaging studies showed bilateral hydronephrosis, bladder wall thickening without masses, and dilation of both common bile and pancreatic ducts without pancreatic masses. Carbohydrate antigen (CA) 19-9 was elevated at >17 000 U/mL. Repeated cystoscopies demonstrated no masses within the bladder, but with nodularity and inflamed mucosa, and random biopsies were obtained and showed PUC. Ascitic fluid cytology revealed metastatic PUC. A targeted exome next-generation sequencing (NGS) revealed pathogenic mutations in TP53, CDH-1, RB1, and ARIDA1A. The patient was debilitated, and hospice care was recommended. She passed away after 2 months of her initial presentation. CONCLUSIONS PUC is a rare and aggressive histological variant of bladder cancer. Advanced stage at diagnosis and high relapse rates after treatment with cytotoxic regimens are common. At the molecular level, somatic alterations in cadherin-1 (CDH-1) gene seem to be characteristic. Exploring the molecular sphere of this disease is prudent to identify possible new therapeutic targets.

Vision loss with pembrolizumab treatment: A report of two cases.

BACKGROUND: Vision loss and other ocular toxicities are rare, but detrimental, side effects of immune checkpoint inhibitors. Herein, we report two patients who developed vision loss while on pembrolizumab treatment. CASES PRESENTATION: Case 1 - A 58-year-old man was started on pembrolizumab for advanced melanoma. He was tolerating the treatment well. After receiving 14 cycles of pembrolizumab, he developed acute bilateral vision loss and occipital headaches. An emergent ophthalmologic evaluation revealed bilateral shallow choroidal effusion with bilateral focal exudative retinal detachment. After excluding other possible etiologies, inflammatory process secondary to pembrolizumab was suspected. Pembrolizumab was stopped, and the patient was started on a course of systemic and topical steroids. His vision improved within days and he recovered completely within two months. Calculated Naranjo Nomogram score was 7 indicating a "probable" correlation; Case 2 - A 57-year-old man with stage IIIC melanoma was started on adjuvant pembrolizumab. After a few weeks of treatments, he reported minor bilateral vision changes that progressively worsened over a period of six months. An ophthalmologic evaluation revealed bilateral posterior uveitis with right optic disc edema. Pembrolizumab-related inflammatory changes were suspected, and he was started on systemic and topical steroids. His symptoms improved within a few weeks and steroids were tapered. He was re-challenged with pembrolizumab and his symptoms quickly re-occurred. Pembrolizumab was stopped indefinitely and the patient again treated with systemic and topical steroids. His symptoms resolved and his vision returned to baseline within two months. The Naranjo Nomogram score was 9 indicating a "definite" correlation. CONCLUSIONS: Vision loss is a serious complication that may occur at any point during treatment with PD-1 inhibitors. Vision loss is very distressing to the patients and their families. It is prudent for practitioners to recognize early vision abnormalities in patients receiving PD-1 antagonists to prevent permanent vision loss.

Hydration, methylene blue, and thiamine as a prevention regimen for ifosfamide-induced encephalopathy.

Ifosfamide is an alkylating chemotherapeutic agent used in the treatment of many malignancies. Ifosfamide-induced encephalopathy is one potential side effect that represents a major drawback to ifosfamide therapy and often necessitates discontinuation of chemotherapy. Previous reports demonstrate moderate effectiveness of prophylactic methylene blue at thwarting ifosfamide-induced encephalopathy. This is a report of a 64-year-old female with relapsed double-hit diffuse large B-cell lymphoma who developed severe altered mental status and neurological symptoms after receiving a second dose of ifosfamide as part of her salvage standard dose R-IE (rituximab, ifosfamide, etoposide), in preparation for chimeric antigen receptor T-cell therapy. Ifosfamide was stopped and extensive metabolic and infectious workups, in addition to brain images, were all unremarkable. Her symptoms were attributed to ifosfamide. Prior to initiating cycle 2 of R-IE, she was started on prophylactic oral thiamine 100 mg, once a day, one week prior to her admission, methylene blue 50 mg intravenous every 6 h (for a total of four doses) and intravenous hydration with normal saline starting on day one of admission. Ifosfamide was administered in the standard dose 2000 mg/m2, days 1-3 as continuous intravenous infusion over 24 h. She tolerated the first two days of ifosfamide well and only developed mild encephalopathy during her last dose of ifosfamide. Her symptoms resolved completely without any intervention the following day and she completed all scheduled doses. She eventually received chimeric antigen receptor T-cell therapy. Our report demonstrates the use of hydration, methylene blue, and thiamine as a successful secondary prevention regimen for ifosfamide-induced encephalopathy.

Utilization of 4T score to determine the pretest probability of heparin-induced thrombocytopenia in a community hospital in upstate New York.

BACKGROUND: Thrombocytopenia is common in hospitalized patients. Heparin-induced thrombocytopenia (HIT) is a life-threatening condition which can lead to extensive thrombosis. Diagnosis of HIT relies on clinical suspicion determined by 4T score and immunoassays through testing for anti-PF4/heparin antibodies. Clinical practice guidelines published by the American Society of Hematology in 2013 recommended use of the 4T score before ordering the immunoassays as a measure of pretest probability. The purpose of this study was to evaluate the utilization of 4T score before ordering anti-PF4/heparin antibodies at Unity Hospital. METHODS: We did a retrospective chart review for patients who are 18 years or older, admitted to Unity Hospital between July 1, 2013, and December 31, 2014, and had anti-PF4/heparin antibodies ordered. Subjects who had prior history of HIT or had end-stage renal disease on hemodialysis were excluded. After calculating 4T score retrospectively, we calculated the proportion of patients who had 4T score documented prior to ELISA testing and proportion of ELISA tests, which were not indicated due to a 4T score less than or equal to 3 using Minitab 16. RESULTS: Review of 123 patients, with an average age of 69.4 years, showed that testing was indicated in 18 patients. Six subjects had positive results, and testing was indicated in all of them. 4T score was documented in three patients. This quality improvement study showed that 4T score documentation rate at Unity Hospital is 2.4%. Anti-PF4/heparin antibody testing was indicated in 14.6%. This test is being overused in thrombocytopenia work up at Unity Hospital, costing $9,345. The topic was reviewed for residents. A prompt and calculator for 4T score were added to electronic medical records before ordering the test as a step to improve high value care.