Efficacy of acitretin in the treatment of reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-gamma autoantibody

Reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-γ autoantibody (AOID) are usually associated with concomitant active opportunistic infections. Data focusing on the treatment of these dermatoses with non-immunosuppressive drugs are still lacking. The aim of this study was to assess the efficacy and safety of acitretin treatment of reactive neutrophilic dermatoses in AOID. We conducted a retrospective review of all patients with AOID who had reactive neutrophilic dermatoses and had been treated with acitretin from January 2008 to December 2018. In total, 23 patients had been diagnosed with AOID, with 27 episodes of reactive neutrophilic dermatoses (20 episodes of Sweet syndrome and seven episodes of generalized pustular eruption) and treated with acitretin. The median effective dose of acitretin was 10 mg/day. The mean initial response was 5.6 ± 2.3 days. The rash had almost or completely cleared within 2 weeks in 70.4% of patients. One case had developed a reversible acitretin-induced liver injury with hepatocellular pattern. The median total duration of treatment was 3 months. In conclusion, this study demonstrates the potential role of acitretin as one of the treatments of choice for reactive neutrophilic dermatoses in AOID, attributable to its favorable response and good tolerability.     

A model of modified meta-iodobenzylguanidine conjugated gold nanoparticles for neuroblastoma treatment

Iodine-131 meta-iodobenzylguanidine (¹³¹I-mIBG) has been utilized as a standard treatment to minimize adverse side effects by targeting therapies to bind to the norepinephrine transporter (NET) expressed on 90% of neuroblastoma cells. However, only a minority of patients who receive ¹³¹I-mIBG radiotherapy have clinical responses, and these are usually not curative. In this study, novel ligand-conjugated gold nanoparticles (GNPs) based on mIBG were synthesized and evaluated biologically with neuroblastoma cells in vitro. To induce specific internalization to the tumor cells and utilize it as a model for radioenhancement, ¹²⁷I-modified mIBG was successfully synthesized and grafted covalently to the surface of carboxylated PEG-GNPs. 49.28% of the novel mIBG derivative was grafted on carboxylated PEG-GNPs. The particles were stable and not toxic to the normal fibroblast cell line, L929, even at the highest concentration tested (10¹³ NPs per mL) at 24, 48, and 72 h. Moreover, the cellular uptake of the model was decreased significantly in the presence of a NET inhibitor, suggesting that there was specific internalization into neuroblastoma cells line (SH-SY5Y) via the NET. Therefore, this model provides useful guidance toward the design of gold nanomaterials to enhance the efficiency of ¹³¹I-mIBG treatment in neuroblastoma patients. However, the investigation of radio-therapeutic efficiency after radioisotope ¹³¹I substitution will be further conducted in a radiation safety laboratory using an animal model.

¹²⁷I-modified mIBG was successfully synthesized and grafted covalently to the surface of carboxylated PEG-GNPs. The particles were not toxic to the normal fibroblast cells while specifically internalized into neuroblastoma cells line via NET.     

Typing of Thai clinical isolates of Mycobacterium leprae and analysis of leprosy transmission by polymorphism of tandem repeats

Mycobacterium leprae isolates from Thai leprosy patients were typed for strain differentiation and analysis of leprosy transmission using the six base tandem repeat, GACATC, in rpoT gene and TTC repeat as genetic markers. M. leprae DNA was isolated from skin biopsies of new untreated leprosy patients living in remote areas or in suburban regions of Thailand where leprosy is in low prevalence. In M. leprae strains of 100 patients, TTC alleles exhibited variations in length with 10 to 30, 33 and 35 repeats, the most common alleles being 15, 16, 17 and 19 repeats. All isolates contained three copies of the six base repeat in rpoT gene. Application of TTC repeats in tracking leprosy transmission in two families with multi-cases identified a single (but different) strain of M. leprae in each family.     

The efficacy and safety of a combined multipolar radiofrequency with pulsed electromagnetic field technology for the treatment of vaginal laxity: a double-blinded,randomized, sham-controlled trial

Lasers in Medical Science - Non-invasive vaginal rejuvenation with radiofrequency (RF) and lasers devices have gained popularity, but well-designed studies confirming their effectiveness are...     

Adult-onset immunodeficiency due to anti-interferon-gamma autoantibody-associated Sweet syndrome: A distinctive entity

Sweet syndrome (SS) has been increasingly reported in patients with adult-onset immunodeficiency (AOID) due to anti-interferon-γ autoantibody who also have concomitant opportunistic infections, especially disseminated non-tuberculous mycobacterial infection (dNTMI). A retrospective study retrieving data from 2011 through 2020 was conducted. We compared clinical characteristics of SS with and without AOID and generated the prediction model and examined the interaction between AOID and dNTMI in the occurrence of SS. Lymphadenopathy, pustular lesions, and leukocytosis are the significant predictors for AOID-associated SS. Adjusted risk differences were 0.58 (95% confidence interval [CI], 0.33–0.83), 0.21 (95% CI, 0.02–0.39), and 0.24 (95% CI, 0.01–0.47), respectively. Based on the analysis of aggregated cross-sectional data, both the overall and the direct effect of AOID increased the prevalence of SS. The indirect effect of AOID on the occurrence of SS might also be mediated through dNTMI or other common opportunistic infections. In addition, there was a trend of positive additive interaction between AOID and dNTMI. Although the test of additive interaction did not reveal statistically significant results, a deviation from additivity of isolated effects might suggest potential causal interaction between AOID and dNTMI. The distinctive clinical syndrome comprising lymphadenopathy, pustular lesions, and leukocytosis in patients with SS should raise the awareness of clinicians to the potential of underlying AOID.     

Effect of colpexin sphere on pelvic floor muscle strength in women with pelvic organ prolapse: a randomized controlled trial (a preliminary report)

Objective  

The aim of this study was to assess the effect of Colpexin Sphere with pelvic floor exercise in women with stage I and II pelvic organ prolapse on improving pelvic floor muscle strength compared with the pelvic floor exercise only.     

Outcomes of Transcatheter Closure in Outlet-Type Ventricular Septal Defect after 1 Year

Background: Ventricular septal defect (VSD) is the most common congenital heart disease. Transcatheter VSD closure is an effective treatment for patients with muscular and perimembranous VSD. However, there is a limit data for outlet VSD, especially impact to the aortic valve leaflet after transcatheter closure. This study aims to assess the outcomes of transcatheter closure of the outlet-type ventricular septal defect (OVSD) after 1 postoperative year. Methods: A retrospective study was performed including 50 patients who underwent transcatheter (n = 25) and surgical (n = 25) OVSD closure during the exact time frame at two medical centres. Results: The median age and body weight of patients in the transcatheter group were significantly higher than those of patients in the surgical group (7.0 vs. 2.8 years; 27.0 vs. 11.4 kg; p < 0.01). The defect size in the surgical group was significantly larger than that in the transcatheter group (5.0 vs. 3.0 mm; p < 0.01). All OVSD patients have successful transcatheter closure (100%) as effective as surgical closure. Less than small residual shunt was present 20% and 8% immediately after the procedure in the transcatheter and surgical groups (p = 0.50), which decreased to 12% and 4% at the 1-year follow-up (p = 0.61), respectively. No incidence of complete atrioventricular block and other complications was observed in both groups, and no significant differences were noted in the new onset or worsening of the aortic regurgitation in both groups (p = 1.0). Conclusions: Transcatheter treatment could be effectively and safely achieved for OVSD closure at 1-year follow-up.     

Functional analysis of XRCC4 mutations in reported microcephaly and growth defect patients in terms of radiosensitivity

Non-homologous end joining is one of the main pathways for DNA double-strand break (DSB) repair and is also implicated in V(D)J recombination in immune system. Therefore, mutations in non-homologous end-joining (NHEJ) proteins were found to be associated with immunodeficiency in human as well as in model animals. Several human patients with mutations in XRCC4 were reported to exhibit microcephaly and growth defects, but unexpectedly showed normal immune function. Here, to evaluate the functionality of these disease-associated mutations of XRCC4 in terms of radiosensitivity, we generated stable transfectants expressing these mutants in XRCC4-deficient murine M10 cells and measured their radiosensitivity by colony formation assay. V83_S105del, R225X and D254Mfs^*68 were expressed at a similar level to wild-type XRCC4, while W43R, R161Q and R275X were expressed at even higher level than wild-type XRCC4. The expression levels of DNA ligase IV in the transfectants with these mutants were comparable to that in the wild-type XRCC4 transfectant. The V83S_S105del transfectant and, to a lesser extent, D254Mfs^*68 transfectant, showed substantially increased radiosensitivity compared to the wild-type XRCC4 transfectant. The W43R, R161Q, R225X and R275X transfectants showed a slight but statistically significant increase in radiosensitivity compared to the wild-type XRCC4 transfectant. When expressed as fusion proteins with Green fluorescent protein (GFP), R225X, R275X and D254Mfs^*68 localized to the cytoplasm, whereas other mutants localized to the nucleus. These results collectively indicated that the defects of XRCC4 in patients might be mainly due to insufficiency in protein quantity and impaired functionality, underscoring the importance of XRCC4’s DSB repair function in normal development.     

Effect of Colpexin Sphere on pelvic floor muscle strength and quality of life in women with pelvic organ prolapse stage I/II: a randomized controlled trial

Introduction and hypothesis  

Colpexin Sphere was effective for advanced pelvic organ prolapse. The aim of this study was to assess the effect of Colpexin Sphere in women with pelvic organ prolapse (POP) stage I or II on pelvic floor muscle strength, quality of life, and POP stage.