Pustular psoriasis in Malaysia: A review of the Malaysian Psoriasis Registry 2007 – 2018

AlexandrosSfakianakis shared this article with you from Inoreader Pustular psoriasis in Malaysia: A review of the Malaysian Psoriasis Registry 2007 – 2018 via Wiley: Experimental Dermatology: Table of Contents Abstract Background Pustular psoriasis (PP) is an uncommon subtype of psoriasis with distinct genetic features and clinical phenotypes. Patients with PP tend to experience frequent flares and significant morbidity. This study aims to determine the clinical characteristics, comorbidities and treatment of PP patients in Malaysia. Methods This was a cross-sectional study of patients with PP notified to the Malaysian Psoriasis Registry (MPR) between January 2007 to December 2018. Results Of 21,735 psoriasis patients, 148 (0.7%) had pustular psoriasis. Of these, 93 (62.8%) were diagnosed with generalized pustular psoriasis (GPP) and 55 (37.2%) with localized PP (LPP). The mean age for pustular psoriasis onset was 31.71 ± 18.33 years with a male to female ratio of 1:2.1. Patients with PP were more likely to have dyslipidemia (23.6% vs 16.5%, p=0.022), severe disease [Body surface area >10 and/or Dermatology Life Quality Index (DLQI) >10] (64.8% vs 50%, p=0.003) and require systemic therapy (51.4% vs 13.9%, p<0.001) compared to non-PP patients. Patients with PP also suffered greater impairment to their quality of life (DLQI>10, 48.9% vs 40.3%, p=0.046), had more days off school/work (2.06 ± 6.09 vs 0.5 ± 4.91, p=0.004) and a higher mean number of hospitalizations (0.31 ± 0.95 vs 0.05 ± 1.22, p=0.001) in 6 months compared to non-PP patients. Conclusion Overall, 0.7% of psoriasis patients in the MPR had pustular psoriasis. Patients with PP had a higher rate of dyslipidaemia, severe disease, greater impairment of quality of life, and systemic therapy usage compared to other psoriasis subtypes. View on Web

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Nuclear membrane irregularity in high‐grade urothelial carcinoma cells can be measured by using circularity and solidity as morphometric shape definitions in digital image analysis of urinary tract cytology specimens

AlexandrosSfakianakis shared this article with you from Inoreader Nuclear membrane irregularity in high‐grade urothelial carcinoma cells can be measured by using circularity and solidity as morphometric shape definitions in digital image analysis of urinary tract cytology specimens via Cancer Cytopathology Abstract Background The Paris System for Reporting Urine Cytology defines objective (elevated nuclear/cytoplasmic ratio ≥0.7) and subjective (nuclear membrane irregularity, hyperchromicity, and coarse chromatin) cytomorphologic criteria to identify conventional high-grade urothelial carcinoma (HGUC) cells. Digital image analysis allows quantitative and objective measurement of these subjective criteria. In this study, digital image analysis was used to quantitate nuclear membrane irregularity in HGUC cells. Methods Whole-slide images of HGUC urine specimens were acquired, and HGUC nuclei were manually annotated using the open-source bioimage analysis software QuPath. Custom scripts were used to calculate nuclear morphometrics and perform downstream analysis. Results In total, 1395 HGUC cell nuclei were annotated across 24 HGUC specimens (48.1 ± 6.0 nuclei per case) using both pixel-level and smooth annotation approaches. Nuclear membrane irregularity was estimated by calculating nuclear circularity and solidity. Annotating at pixel-level resolution artifactually increases nuclear membrane perimeter, thus smoothing is necessary to better approximate a pathologist's assessment of nuclear membrane irregularity. After smoothing, nuclear circularity and solidity discriminate between HGUC cell nuclei with visually apparent differences in nuclear membrane irregularity. Conclusions Nuclear membrane irregularity defined by The Paris System for Reporting Urine Cytology is inherently subjective. This study identifies nuclear morphometrics that visually correlate with nuclear membrane irregularity. HGUC specimens show intercase variation in nuclear morphometrics, with some nuclei appearing remarkably regular while others show marked irregularity. A small population of irregular nuclei generates most of the intracase variation in nuclear morphometrics. These results highlight nuclear membrane irregularity as an important, but not definitive, cytomorphologic criterion in HGUC diagnosis. View on Web

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Primary tumor resection improves survival of gastrointestinal neuroendocrine carcinoma patients with nonresected liver metastases

AlexandrosSfakianakis shared this article with you from Inoreader Primary tumor resection improves survival of gastrointestinal neuroendocrine carcinoma patients with nonresected liver metastases via Wiley: Journal of Surgical Oncology: Table of Contents Abstract Background The role of primary tumor resection (PTR) in the survival of gastrointestinal neuroendocrine carcinoma (GI-NEC) patients with liver metastases only remains poorly defined. Therefore, we investigated the impact of PTR on the survival of GI-NEC patients with nonresected liver metastases. Methods GI-NEC patients with a liver-confined metastatic disease diagnosed between 2016 and 2018 were identified in the National Cancer Database. Multiple imputations by chained equations were used to account for missing data, and the inverse probability of treatment weighting (IPTW) method was used to eliminate selection bias. Overall survival (OS) was compared by adjusted Kaplan–Meier curves and log-rank test with IPTW. Results A total of 767 GI-NEC patients with nonresected liver metastases were identified. Among all patients, 177 (23.1%) received PTR and had a significantly favorable OS before (median: 43.6 months [interquartile range, IQR, 10.3–64.4] vs. 8.8 months [IQR, 2.1–23.1], p < 0.001 in log-rank test) and after (median: 25.7 months [IQR, 10.0–64.4] vs. 9.3 months [IQR, 2.2–26.4], p < 0.001 in IPTW-adjusted log-rank test) the IPTW adjustment. Additionally, this survival advantage persisted in an adjusted Cox model (IPTW adjusted hazard ratio = 0.431, 95% confidence interval: 0.332–0.560; p < 0.001). The improved survival persisted in subgroups stratified by primary tumor site, tumor grade, and N stage, even in the complete cohort (excluding patients with missing data). Conclusions PTR led to improved survival for GI-NEC patients with nonresected liver metastases regardless of primary tumor site, tumor grade, and N stage. However, the decision for PTR should be made on an individualized basis following multidisciplinary evaluation. View on Web

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Impact of Exercise and Detraining on Signs of Puberty and Selected Inflammatory Markers in Girls with Precocious Puberty

AlexandrosSfakianakis shared this article with you from Inoreader Impact of Exercise and Detraining on Signs of Puberty and Selected Inflammatory Markers in Girls with Precocious Puberty via Medicine & Science in Sports & Exercise - Published Ahead-of-Print Purpose We examined the effects of aerobic exercise and detraining on adiponectin, resistin, tumor necrosis factor alpha (TNF-α), white blood cell, and pubertal signs (uterine length, ovarian volume, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)) in girls with central precocious puberty (CPP). Methods Thirty girls with CPP (aged 7-9) were randomly divided into CPP and CPP + Exercise (EX) groups. 15 Healthy age-matched girls without precocious puberty participated for comparison with CPP. Subjects in the CPP + Ex group attended 12 weeks of aerobic exercise protocol three sessions a week. In the baseline, after completing the exercise protocol and after 4 weeks of detraining, all the parameters were measured. In the CPP and healthy groups, all the parameters were measured in all three stages. To measure adiponectin, resistin, and TNF-α, the ELISA method was used. LH and FSH were measured by electrochemiluminescence immunoassay. WBC counts were analyzed by an automated blood cell counter. Analysis of Variance with repeated measures test was used to analyze the results. Results CPP girls have lower adiponectin (P = 0.01) and higher TNF-α levels (P = 0.001) than healthy girls. In the CPP + EX group, after 12 weeks, body weight and fat mass decreased, adiponectin increased significantly (P = 0.02). Resistin (P = 0.02), TNF-α (P = 0.02), neutrophils (P = 0.01), and signs of puberty significantly (P View on Web

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Complex Ataxia‐Dementia Phenotype in Patients with Digenic TBP/STUB1 Spinocerebellar Ataxia

AlexandrosSfakianakis shared this article with you from Inoreader Complex Ataxia‐Dementia Phenotype in Patients with Digenic TBP/STUB1 Spinocerebellar Ataxia via Movement Disorders Digenic SCA TBP/STUB1 is caused by the concomitant inheritance of an intermediate expansion in TBP gene and a deleterious mutation in STUB1 gene. SCA TBP/STUB1 patients present a complex phenotype including ataxia, chorea, dementia, and diffuse cerebellar and cerebral brain atrophy. Genetic counseling is essential for all family members. ABSTRACT Background and Objectives Spinocerebellar ataxias (SCAs) are autosomal dominant disorders with extensive clinical and genetic heterogeneity. We recently identified a form of SCA transmitted with a digenic pattern of inheritance caused by the concomitant presence of an intermediate-length expansion in TATA-box binding protein gene (TBP 40–46) and a heterozygous pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1). This SCA TBP/STUB1 represents the first example of a cerebellar disorder in which digenic inheritance has been identified. Objectives We studied a large cohort of patients with SCA TBP/STUB1 with the aim of describing specific clinical and neuroimaging features of this distinctive genotype. Methods In this observational study, we recruited 65 affected and unaffected family members from 21 SCA TBP/STUB1 families and from eight families with monogenic SCA17. Their characteristics and phenotypes were compared with those of 33 age-matched controls. Results SCA TBP/STUB1 patients had multi-domain dementia with a more severe impairment in respect to patient carrying only fully expanded SCA17 alleles. Cerebellar volume and thickness of cerebellar cortex were reduced in SCA TBP/STUB1 compared with SCA17 patients (P = 0.03; P = 0.008). Basal ganglia volumes were reduced in both patient groups, as compared with controls, whereas brainstem volumes were significantly reduced in SCA TBP/STUB1 , but not in SCA17 patients. Conclusions The identification of the complex SCA TBP/STUB1 phenotype may impact on diagnosis and genetic counseling in the families with both hereditary and sporadic ataxia. The independent segregation of TBP and STUB1 alleles needs to be considered for recurrence risk and predictive genetic tests. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. View on Web

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LRRK2 Inhibition by BIIB122 in Healthy Participants and Patients with Parkinson's Disease

AlexandrosSfakianakis shared this article with you from Inoreader LRRK2 Inhibition by BIIB122 in Healthy Participants and Patients with Parkinson's Disease via Movement Disorders Abstract Background Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising therapeutic approach for the treatment of Parkinson's disease (PD). Objective The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the potent, selective, CNS-penetrant LRRK2 inhibitor BIIB122 (DNL151) in healthy participants and patients with PD. Methods Two randomized, double-blind, placebo-controlled studies were completed. The phase 1 study (DNLI-C-0001) evaluated single and multiple doses of BIIB122 for up to 28 days in healthy participants. The phase 1b study (DNLI-C-0003) evaluated BIIB122 for 28 days in patients with mild to moderate PD. The primary objectives were to investigate the safety, tolerability, and plasma pharmacokinetics of BIIB122. Pharmacodynamic outcomes included peripheral and central target inhibition and lysosomal pathway engagement biomarkers. Results A total of 186/184 healthy participants (146/145 BIIB122, 40/39 placebo) and 36/36 patients (26/26 BIIB122, 10/10 placebo) were randomized/treated in the phase 1 and phase 1b studies, respectively. In both studies, BIIB122 was generally well tolerated; no serious adverse events were reported, and the majority of treatment-emergent adverse events were mild. BIIB122 cerebrospinal fluid/unbound plasma concentration ratio was ~1 (range, 0.7–1.8). Dose-dependent median reductions from baseline were observed in whole-blood phosphorylated serine 935 LRRK2 (≤98%), peripheral blood mononuclear cell phosphorylated threonine 73 pRab10 (≤93%), cerebrospinal fluid total LRRK2 (≤50%), and urine bis (monoacylglycerol) phosphate (≤74%). Conclusions At generally safe and well-tolerated doses, BIIB122 achieved substantial peripheral LRRK2 kinase inhibition and modulation of lysosomal pathways downstream of LRRK2, with evidence of CNS distribution and target inhibition. These studies support continued investigation of LRRK2 inhibition with BIIB122 for the treatment of PD. © 2023 Denali Therapeutics Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. View on Web

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Spermidine reduced neuropathic pain in chronic constriction injury‐induced peripheral neuropathy in rats

AlexandrosSfakianakis shared this article with you from Inoreader Spermidine reduced neuropathic pain in chronic constriction injury‐induced peripheral neuropathy in rats via Fundamental & Clinical Pharmacology Abstract Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into 3 groups: sham, CCI and CCI+ SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done 4 times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significant ly lower in the CCI group than the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P<0.01, P< 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of SOD, GPx, and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress, improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model. View on Web

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