Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation.

Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second "salvage" FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.

Antibody-Drug Conjugates: A Review of Approved Drugs and Their Clinical Level of Evidence.

Antibody-drug conjugates (ADCs) are an innovative family of agents assembled through linking cytotoxic drugs (payloads) covalently to monoclonal antibodies (mAbs) to be delivered to tumor tissue that express their particular antigen, with the theoretical advantage of an augmented therapeutic ratio. As of June 2023, eleven ADCs have been approved by the Food and Drug Administration (FDA) and are on the market. These drugs have been added to the therapeutic armamentarium of acute myeloblastic and lymphoblastic leukemias, various types of lymphoma, breast, gastric or gastroesophageal junction, lung, urothelial, cervical, and ovarian cancers. They have proven to deliver more potent and effective anti-tumor activities than standard practice in a wide variety of indications. In addition to targeting antigen-expressing tumor cells, bystander effects have been engineered to extend cytotoxic killing to low-antigen-expressing or negative tumor cells in the heterogenous tumor milieu. Inevitably, myelosuppression is a common side effect with most of the ADCs due to the effects of the cytotoxic payload. Also, other unique side effects are specific to the tissue antigen that is targeted for, such as the cardiac toxicity with Her-2 targeting ADCs, and the hemorrhagic side effects with the tissue factor (TF) targeting Tisotumab vedotin. Further exciting developments are centered in the strategies to improve the tolerability and efficacy of the ADCs to improve the therapeutic window; as well as the development of novel payloads including (1) peptide-drug conjugates (PDCs), with the peptide replacing the monoclonal antibody, rendering greater tumor penetration; (2) immune-stimulating antibody conjugates (ISACs), which upon conjugation of the antigen, cause an influx of pro-inflammatory cytokines to activate dendritic cells and harness an anti-tumor T-cell response; and (3) the use of radioactive isotopes as a payload to enhance cytotoxic activity.

Pneumothorax in Intubated Patients With COVID-19: A Case Series.

Pneumothorax is a rare complication among mechanically ventilated patients since low tidal volumes are used nowadays instead of traditional high tidal volumes, but the incidence is slightly higher in patients with high positive end-expiratory pressure (PEEP). Herein we describe a case series of nine patients who were on mechanical ventilation due to acute respiratory distress syndrome (ARDS) secondary to coronavirus disease 2019 (COVID-19) and developed pneumothorax in due course. A retrospective analysis was done on COVID-19 intubated patients from March 2020 to June 2020 in a community hospital in Central New Jersey, which was one of the early hit states in the United States at the beginning of the pandemic. Outcomes were studied. The demographics of patients like age, gender, and body mass index (BMI); risk factors like smoking, comorbidities especially chronic lung disease, and the treatment they received were compared. We compared the total number of days on the ventilator, the highest PEEP they received, and the ventilator day when pneumothorax developed. All the patients who developed pneumothorax had a chest tube inserted to treat it. The mortality was noted to be 100% indicating that pneumothorax is a life-threatening complication of COVID-19 and COVID-19 by itself is a risk factor for pneumothorax likely due to a change in lung mechanics. There is a need for large-scale studies to confirm that these outcomes are related to COVID-19.

Case report: A rare case of Rosai-Dorfman-Destombes disease after the COVID-19 infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to cause immune dysregulation and, therefore, has varied and often rare presentations. Rosai-Dorfman-Destombes disease (RDD) is an unusual non-Langerhans cell (non-LC) histiocytosis presenting with massive lymphadenopathy and various systemic symptoms. A 55-year-old Asian-American woman with no significant medical history or recent use of new drugs initially presented with cervical lymphadenopathy and urticarial rash 1 week after receiving the COVID-19 messenger RNA (mRNA) vaccine (Moderna, mRNA-1273) against SARS-CoV-2. The biopsy of the skin rash was consistent with a drug reaction. Approximately 2 months later, she developed mild flu-like symptoms and was diagnosed with a COVID-19 infection. Her symptoms were mild and self-resolving. Approximately 3 months later, she developed a generalized patchy erythematous rash on the face and the body that gradually worsened; diffuse lymphadenopathy involving the bilateral cervical, axillary, and inguinal areas; and constitutional symptoms. Laboratory results were consistent with lymphopenia, anemia, and an elevated sedimentation rate. Supraclavicular lymph node biopsy showed Rosai-Dorfman disease with a marked polyclonal plasmacytosis. She was started on a tapering dose of corticosteroids and showed clinical improvements over the next few weeks. Herein, we present a rare case of a histiocytic disorder that developed after contracting the SARS-COV2 infection in the event of receiving a recent mRNA COVID vaccination.

Rapidly Progressing Primary Membranous Nephropathy in a Hispanic Male With Elevated Levels of Anti-phospholipase A2 Receptor Antibodies.

A 49-year-old Hispanic male presented to the Emergency Department with progressively worsening swelling in his extremities for the past two months. Physical examination was significant for diffuse edema, with concomitant initial laboratory tests revealing hypoalbuminemia, hypercholesteremia, and proteinuria. A renal biopsy was performed, and the histopathology confirmed a diagnosis of membranous nephropathy through immunofluorescence and electron microscopy. Anti-phospholipase A2 receptor (anti-PLA2R) antibodies were detected on immunofluorescence, as well as high levels being discovered in the patient's serum, indicating a diagnosis of primary membranous nephropathy. The patient underwent adequate diuresis and was discharged. The patient presented six months later due to severe anasarca with laboratory tests indicating a rapid decline in renal function. He was then started on immunosuppressive therapy. Our rare case of a Hispanic male presenting with rapidly deteriorating renal function secondary to primary membranous nephropathy seeks to highlight the possibility of using anti-PLA2R antibodies as a marker for early initiation of immunosuppressive therapy as well as to encourage additional research on the course of disease progression in the Hispanic population.

Multiple cutaneous and haemorrhagic brain metastases as the sentinel presentation of lung adenocarcinoma.

Skin is a relatively uncommon site of metastasis in lung cancer and is associated with a poor prognosis. Although, lung cancer does not uncommonly metastasise to the brain, haemorrhagic brain metastases are rarely reported. In this report, we present a dramatic presentation of a female smoker with a 3-week history of numerous cutaneous lesions over her body and two episodes of transient memory loss. Work-up demonstrated widely metastatic, poorly differentiated lung adenocarcinoma with haemorrhagic brain metastases. She proceeded with whole brain radiotherapy, but her performance status quickly declined afterwards; she succumbed to her malignancy within 6 weeks of presentation. This case presentation demonstrates that, for patients who present with cutaneous masses, especially those aged more than 60 years, and who have extensive smoking history, metastatic lung cancer should remain on the differential diagnosis. Also, the very poor prognosis of multiple metastases may influence medical and social decisions in the patient's treatment plan.

Acute liver failure masquerading an occult malignancy.

Acute liver failure (ALF) is a rare initial presentation of metastatic liver disease and is associated with high fatality. Our case report describes acute hepatic decompensation from an occult pancreatic malignancy. A 64-year-old man presented with abdominal distension for 2 weeks associated with decreased appetite and a weight loss of 13.6 kg, over the past 8 months. Significant admission labs were serum creatinine: 6.15 mg/dL, serum bilirubin: 27 mg/dL, aspartate aminotransferase (AST): 316 u/L, alanine aminotransferase (ALT): 198 u/L and serum alkaline phosphatase: 2121 u/L. He was admitted to the medical intensive care unit and was started on dialysis for acute renal failure. MRI of the abdomen showed multiple masses in the liver concerning for metastatic disease, cystic lesions in the pancreatic body and ascites. He underwent paracentesis and ascitic fluid analysis was positive for adenocarcinoma. CA 19-9 was 17 828 u/mL. The patient's condition gradually deteriorated, and he died of cardiac arrest.

Hypercalcaemia, Renal Dysfunction, Anaemia, Bone Disease (CRAB Criteria): A Case of Lymphoma.

Calcium elevation, Renal dysfunction, Anaemia and Bone disease (CRAB criteria) are usually seen in multiple myeloma (MM). We report a unique case of lymphoma with all the features of CRAB criteria. We describe a 59-year-old patient who presented with confusion, severe back pain, fatigue and constipation and was found to have hypercalcaemia, kidney dysfunction, anaemia and multiple osteolytic lesions. Physical examination and imaging did not reveal any enlarged lymph nodes. Work-up for MM (serum protein electrophoresis, serum immunofixation, bone marrow biopsy) was negative. The patient was diagnosed with diffuse large B-cell lymphoma based on a pelvic mass biopsy. Hence, our case report suggests that CRAB criteria are not pathognomonic of MM and that in the appropriate clinical scenario, lymphoma is a possible diagnosis. LEARNING POINTS: The CRAB criteria consist of end-organ damage with hypercalcaemia, renal dysfunction, anaemia and bone involvement.The CRAB criteria are not pathognomonic of multiple myeloma, and in the appropriate clinical scenario, lymphoma is a possible diagnosis.Major mechanisms by which hypercalcaemia of malignancy can occur are tumour secretion of parathyroid hormone-related protein (PTHrP), osteolytic metastases with local release of cytokines, or tumour production of 1,25-dihydroxyvitamin D (calcitriol).

Perioperative sildenafil therapy for children with ventricular septal defects and associated pulmonary hypertension undergoing corrective surgery: A randomised clinical trial.

BACKGROUND AND AIMS: Sildenafil is known to reduce pulmonary artery pressure but its role in the perioperative period has not been well studied. We aimed to evaluate the efficacy of sildenafil in controlling post-operative pulmonary hypertension in children with pulmonary hypertension undergoing surgeries for correction of ventricular septal defect. METHODS: The patients were divided randomly into two groups of thirty each. Group 1 (placebo) received pre-operative placebo and post-operative sildenafil (0.5mg/kg every 6 hrs) while Group 2 (sildenafil) received pre- and post-operative sildenafil (0.5mg/kg every 6 hrs). RESULTS: In the Group 1, systolic pulmonary artery pressure reduced from 81.63 (±12.1) mmHg preoperatively to 79.26 (±11.29) mmHg pre-cardiopulmonary bypass (CPB) and 56.76 (±11) mmHg (with 10 minutes post-CPB), whereas in Group 2, it reduced from 83.3 (±12.1) before surgery to 68.9 (±11.3) mmHg pre-CPB and after CPB, to 42.2 (±7.6) mmHg (P = 0.001). The mean pulmonary artery pressure decreased from 60.63 (±10.5) mmHg to 42.13 (±8.3) mmHg in the Group 1 whereas it reduced from 54.36 (±10) mmHg to 31.36 (±6.5) mmHg in Group 2 (P = 0.001). The reductions in pulmonary artery/aortic ratio and Intensive Care Unit stay were statistically significant No adverse effects were recorded. CONCLUSION: The use of perioperative sildenafil has a statistically significant reduction in the mean pulmonary artery pressure without any adverse effects.

Exploring signet-ring cells in pregnant female.

INTRODUCTION: Primary signet-ring cell carcinoma (SRCC) of the colon and rectum are rare form, which present at an advanced stage and have poor prognosis. Different treatment policies of SRCC during different gestational age of pregnancy are explored from the literature. CASE STUDY: A 26-year-old young pregnant female with 10-week gestation presented with constipation and blood in stools and on per rectal examination a tender circumferential stricture was present 2 cm above the anal verge. Magnetic resonant imaging (MRI) pelvis of the patient revealed rectal thickening, the biopsy of which revealed characteristic appearance of "linitis plastica" and diagnosed as poorly differentiated adenocarcinoma with signet ring morphology with wide spread positivity for cytokeratin & p53. With this diagnosis, patient underwent medical termination of pregnancy (MTP). DISCUSSION: SRCC of the colon comprises about only 1% of all cases of colon cancer. When compared with other types of adenocarcinoma, patients with SRCC in the colon are younger and more likely to experience lymph node metastasis. Its incidence in pregnancy is estimated to be less than 0.1%. Certainly, any pregnant patient who reports rectal bleeding or has hemoccult positive stool on examination deserves careful evaluation to rule out cancer. The complex treatment of colorectal cancer in pregnancy is based on the gestational age of the fetus, tumor stage and need for emergent vs. elective management.