Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency.

PURPOSE: MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. METHODS: The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. RESULTS: The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). CONCLUSION: This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life.

Spontaneous bladder rupture secondary to warfarin overdose: a case report.

BACKGROUND: Warfarin, a vitamin K antagonist, is a widely used medication for the treatment and prophylaxis of thromboembolic events. Patients with various clinical conditions due to warfarin overdose present to emergency departments. Although there may be serious bleeding due to a warfarin overdose, no bleeding may also be seen in some clinical conditions. Some of these bleedings may be life-threatening and result in death. Warfarin overdose and related cases of spontaneous bladder rupture are not frequently observed in the literature. We present a case of spontaneous bladder rupture due to warfarin overdose that was unexpectedly seen in a patient using warfarin for coronary artery disease and arrhythmia. CASE PRESENTATION: A 77-year-old Caucasian male patient was admitted to the emergency department with abdominal pain, haematuria, and a reduced volume of urine lasting for three days. The patient's amount of urine was reduced, and he came to the hospital for the first time with this complaint. The patient had local bruises on his arms and legs. From the ultrasound, retrograde cystography and computed tomography images, it was thought that there was blood accumulation due to bladder rupture to the intraperitoneal region. Spontaneous bladder rupture secondary to warfarin overdose was considered for this patient who also had an international normalized ratio (INR) level of 13.4. After the INR level was normalized with vitamin K and a prothrombin complex concentrate, the patient underwent surgery. During the operation, a catheter was placed in the bladder, and the bladder mucosa and muscle were closed separately with a primary repair performed by a urologist. The patient was discharged on the 8th postoperative day without any complications. CONCLUSION: In addition to the known findings of warfarin overdose in these patients presenting to the emergency department, we think that the emergency department staff should suspect bladder rupture, which is a fatal complication in the presence of signs such as oliguria, haematuria, anuria, abdominal pain, and syncope.

Comparison of bismuth-containing quadruple and concomitant therapies as a first-line treatment option for Helicobacter pylori.

BACKGROUND/AIMS: Helicobacter pylori eradication rates with standard triple regimens are worsening, and alternative treatments are urgently needed in some populations. The present study aimed to compare the efficacy of bismuth-based quadruple and concomitant regimens. METHODS: Consecutive Helicobacter pylori-positive patients with non-ulcer dyspepsia were randomized to receive one of two regimens: (i) bismuth subsalicylate 300 mg q.i.d., esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., and amoxicillin 1 g b.i.d. (bismuth group) or (ii) esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. (concomitant group) for 14 days. Gastroscopy and 14C-urea breath test were performed before enrollment, and urea breath test was repeated six weeks after the treatment. RESULTS: A total of 200 patients were randomized, and 180 of them completed the protocols. The intention-to-treat and per-protocol eradication rates were 79% (95% confidence interval 71-87) and 89.7% (95% confidence interval 83-95) in the bismuth group and 74% (95% confidence interval 68-81) and 80.4% (95% confidence interval 72-87) in the concomitant group. The bismuth regimen achieved a slightly better eradication rate compared to the concomitant group in both per-protocol and intention-to-treat analysis, but results were not statistically significant (p>0.05). Ten patients (6 in bismuth, 4 in concomitant groups) dropped out of the study because of side effects. CONCLUSIONS: The quadruple regimens with or without bismuth achieved moderate eradication rates as a first-line eradication option of Helicobacter pylori in our population, in which a bismuth-based regimen seems more appropriate. The compliance and side effects are important issues affecting the success of these regimens.