Patient Outcomes of Definitive Diverticular Hemorrhage After Colonoscopic, Medical, Surgical, or Embolization Treatment.

BACKGROUND: There are few reports of clinical outcomes or the natural history of definitive diverticular hemorrhage (DDH). AIMS: To describe 1-year clinical outcomes of patients with documented DDH treated with colonoscopic hemostasis, angioembolization, surgery, or medical treatment. METHODS: DDH was diagnosed when active bleeding or other stigmata of hemorrhage were found in a colonic diverticulum during urgent colonoscopy or extravasation on angiography or red blood cell (RBC) scanning. This was a retrospective analysis of prospectively collected data of DDH patients from two referral centers between 1993 and 2022. Outcomes were compared for the four treatment groups. The Kaplan-Meier analysis was for time-to-first diverticular rebleed. RESULTS: 162 patients with DDH were stratified based on their final treatment before discharge-104 colonoscopic hemostasis, 24 medical treatment alone, 19 colon surgery, and 15 angioembolization. There were no differences in baseline characteristics, except for a higher Glasgow-Blatchford score in the angioembolization group vs. the colonoscopic group. Post-treatment, the colonoscopic hemostasis group had the lowest rate of RBC transfusions and fewer hospital and ICU days compared to surgical and embolization groups. The medical group had significantly higher rates of rebleeding and reintervention. The surgical group had the highest postoperative complications. CONCLUSIONS: Medically treated DDH patients had significantly higher 1-year rebleed and reintervention rates than the three other treatments. Those with colonoscopic hemostasis had significantly better clinical outcomes during the index hospitalization. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments.

Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome.

Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)-a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component ("naked granulomas"), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously.

miR-130b/301b Is a Negative Regulator of Beige Adipogenesis and Energy Metabolism In Vitro and In Vivo.

Thermogenic brown or beige adipocytes dissipate energy in the form of heat and thereby counteract obesity and related metabolic complications. The miRNA cluster miR-130b/301b is highly expressed in adipose tissues and has been implicated in metabolic diseases as a posttranscriptional regulator of mitochondrial biogenesis and lipid metabolism. We investigated the roles of miR-130b/301b in regulating beige adipogenesis in vivo and in vitro. miR-130b/301b declined in adipose progenitor cells during beige adipogenesis, while forced overexpression of miR-130b-3p or miR-301b-3p suppressed uncoupling protein 1 (UCP1) and mitochondrial respiration, suggesting that a decline in miR-130b-3p or miR-301b-3p is required for adipocyte precursors to develop the beige phenotype. Mechanistically, miR-130b/301b directly targeted AMP-activated protein kinase (AMPKα1) and suppressed peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α), key regulators of brown adipogenesis and mitochondrial biogenesis. Mice lacking the miR-130b/301b miRNA cluster showed reduced visceral adiposity and less weight gain. miR-130b/301b null mice exhibited improved glucose tolerance, increased UCP1 and AMPK activation in subcutaneous fat (inguinal white adipose tissue [iWAT]), and increased response to cold-induced energy expenditure. Together, these data identify the miR-130b/301b cluster as a new regulator that suppresses beige adipogenesis involving PGC-1α and AMPK signaling in iWAT and is therefore a potential therapeutic target against obesity and related metabolic disorders.

Outcomes of patients with ischemic colitis causing severe hematochezia managed medically or surgically.

PURPOSE: To compare short- and long-term outcomes of hospitalized patients with ischemic colitis (IC) presenting with severe hematochezia and treated medically or colectomy and also those with inpatient vs. outpatient start of hematochezia. METHODS: A retrospective analysis of prospectively collected data for IC patients hospitalized for severe hematochezia from two teaching hospitals was done from 1994 to 2020, with the diagnosis of IC made colonoscopically and confirmed histologically. RESULTS: Ninety-seven patients initially all had medical management for IC. Seventy-two (74.2%) were stable and had no further bleeding; 17 (17.5%) had colon resection; and 8 were critically ill and not surgical candidates. Surgical patients and non-surgical candidate had higher comorbidity scores; received more red blood cell (RBC) transfusion (median (IQR) 5 (3-10) vs. 4.5 (3-6.5) vs. 1 (0-4) units, p < 0.001); had significantly longer hospital and ICU days; had higher severe complication rates (35.3% vs. 100%. vs. 5.6%, p < 0.001); and had higher 30-day all-cause mortality rates (23.5% vs. 87.5% vs. 0, p < 0.001). Inpatients developing IC hemorrhage had more RBC transfusions, more complications, longer hospital stays, and higher mortality than patients whose IC bleeding started as outpatients. CONCLUSIONS: The majority of IC patients hospitalized for severe hematochezia were successfully treated medically. Patients who were not surgical candidate had the highest rates of severe complications and mortality. Surgical patients and those who were not surgical candidate had worse outcomes than the medical group. Patients with inpatient start of bleeding from IC had significantly worse outcomes than those with outpatient start of bleeding.

Severe Upper Gastrointestinal Hemorrhage Caused by Reflux Esophagitis.

BACKGROUND: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB). AIMS: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH). METHODS: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed. RESULTS: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH. CONCLUSIONS: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically.

Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots.

BACKGROUND & AIMS: Treatment of high-risk patients with nonbleeding adherent clots on ulcers is controversial. In a previous randomized trial, there was no benefit to endoscopic therapies compared with medical therapy for prevention of ulcer rebleeding. Our purpose was to test the hypothesis that patients treated with combination endoscopic therapy would have significantly lower rebleeding rates than those treated with medical therapy. METHODS: In this randomized, controlled trial, 32 high-risk patients with severe ulcer hemorrhage and nonbleeding adherent clots resistant to target irrigation were randomized to medical therapy or to combination endoscopic therapy (with epinephrine injection, shaving down the clot with cold guillotining, and bipolar coagulation on the underlying stigmata). Physicians blinded to the endoscopic therapy managed all patients. RESULTS: Patients were similar at study entry, except for older age in the medical group and lower platelet count in the endoscopic group. By hospital discharge, significantly more medically treated patients (6/17; 35.3%) than endoscopically treated patients (0/15; 0%) rebled (P = 0.011). There were no complications of endoscopic treatment. CONCLUSIONS: Combination endoscopic therapy of nonbleeding adherent clots significantly reduced early ulcer rebleeding rates in high-risk patients compared with medical therapy alone. This endoscopic treatment was safe.