Successful treatment of oral linear IgA disease using mycophenolate

Linear IgA disease (LAD) is a rare acquired autoimmune bullous disorder, characterized by linear deposition of IgA along the dermoepidermal basement membrane zone. The clinical presentation of LAD consists of vesiculobullous lesions affecting the skin and mucosal surfaces. The present case report presents a rare presentation of this vesiculobullous disorder. Although more than 50% of LAD patients present with oral lesions, there are few reported cases of involvement of the mouth as the sole manifestation. A 79-year-old female presented with a sore mouth and erosions affecting the palate. The symptoms resolved following the provision of mycophenolate, an antiproliferative immunosuppressant which has not previously appeared to have been reported in the long-term successful management of linear IgA disease limited to the mouth. We found that mycophenolate is a useful adjunct to the successful treatment of oral linear IgA when the uses of other immunosuppressants are contraindicated.     

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N_females = 130; N_males = 81) and 567 age-matched controls (N_females = 317; N_males = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020     

Identification of Subgroups of Schizophrenia Patients With Changes in Either Immune or Growth Factor and Hormonal Pathways

Schizophrenia is a heterogeneous disorder normally diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. However, these criteria do not necessarily reflect differences in underlying molecular abnormalities of the disorder. Here, we have used multiplexed immunoassay analyses to measure immune molecules, growth factors, and hormones important to schizophrenia in acutely ill antipsychotic-naive patients (n = 180) and matched controls (n = 398). We found that using the resulting molecular profiles, we were capable of separating schizophrenia patients into 2 significantly distinct subgroups with predominant molecular abnormalities in either immune molecules or growth factors and hormones. These molecular profiles were tested using an independent cohort, and this showed the same separation into 2 subgroups. This suggests that distinct abnormalities occur in specific molecular pathways in schizophrenia patients. This may be of relevance for intervention studies that specifically target particular molecular mechanisms and could be a first step to further define the complex schizophrenia syndrome based on molecular profiles.Key words: schizophrenia, subtypes, diagnosis, molecular profiling, immune factors, growth factors     

Carvedilol induces greater control of β2- than β1-adrenoceptor-mediated inotropic and lusitropic effects by PDE3, while PDE4 has no effect in human failing myocardium

The β-blockers carvedilol and metoprolol provide important therapeutic strategies for heart failure treatment. Therapy with metoprolol facilitates the control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of catecholamines in human failing ventricle. However, it is not known whether carvedilol has the same effect. We investigated whether the PDE3-selective inhibitor cilostamide (0.3 μM) or PDE4-selective inhibitor rolipram (1 μM) modified the positive inotropic and lusitropic effects of catecholamines in ventricular myocardium of heart failure patients treated with carvedilol. Right ventricular trabeculae from explanted hearts of nine carvedilol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β₁-adrenoceptors (β₂-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β₂-adrenoceptors (β₁-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of the PDE inhibitors. The inotropic potency, estimated from –logEC₅₀s, was unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in carvedilol-treated compared to non-β-blocker-treated patients, consistent with the previously reported β₂-adrenoceptor-selectivity of carvedilol. Cilostamide caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in trabeculae from carvedilol-treated patients. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline. Treatment of heart failure patients with carvedilol induces PDE3 to selectively control the positive inotropic and lusitropic effects mediated through ventricular β₂-adrenoceptors compared to β₁-adrenoceptors. The β₂-adrenoceptor-selectivity of carvedilol may provide protection against β₂-adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated patients. PDE4 does not control β₁- and β₂-adrenoceptor-mediated inotropic and lusitropic effects in carvedilol-treated patients.     

Perioperative complications of robotic sacrocolpopexy for post-hysterectomy vaginal vault prolapse

Introduction and hypothesis

Open abdominal sacrocolpopexy has been the preferred treatment for post-hysterectomy vaginal vault prolapse. In light of the rise in popularity of less invasive robotic sacrocolpopexy, our objective was to compare perioperative complications of robotic vs open sacrocolpopexy.

Methods

This was a single-institution, retrospective cohort study of robotic and open sacrocolpopexies. Robotic sacrocolpopexies performed between 1 January 2007 and 31 December 2009 were compared with open cases performed between 1 January 2002 and 31 December 2006. Baseline and intraoperative variables of the groups were compared. Complications were compared univariately and in a multivariable logistic regression model to adjust for prior transabdominal surgery.

Results

A total of 50 robotic and 87 open sacrocolpopexies were analyzed. Baseline characteristics were similar, but patients in the open group had more prior transabdominal surgeries. The robotically assisted group had decreased estimated blood loss (median, 100 mL vs 150 mL; P?=?0.002) and hospital stay (median, 2 days vs 3 days; P?P?P?=?0.02), and vaginotomy (24.0 % [12 out of 50] vs 5.7 % [5 out of 87]; P?=?0.003). Two patients in the robotically assisted group had postoperative hernia. There were no differences in rates of ureteral or bowel injury, urinary tract infection, ileus, bowel obstruction, or overall complications.

Conclusions

Overall complication rates of robotic and open sacrocolpopexy were not significantly different. The robotically assisted group experienced shorter hospital stay but increased operative times and increased incidence of cystotomy and vaginotomy, possibly reflecting the learning curve of robotic sacrocolpopexy.