Search

Generalized Pustular Psoriasis (GPP) is a dermatological autoinflammatory disease that rarely occurs in children and is associated with complex genetic factors. GPP pathogenesis has been associated with mutations in IL36RN gene, which encodes an interleukin-36 receptor antagonist. GPP usually occurs without a history of psoriasis in the patients or their family members. This case report describes the clinical course of a 3-year-old toddler with GPP. The diagnosis of GPP was confirmed through a comprehensive series of examinations, and genetic testing revealed an IL36RN mutation, providing further insight into the genetic basis of the condition. This case highlights the importance of a genetic perspective for diagnosing GPP, particularly in children.

This study investigated the association between the pre-miRNA146a C>G rs2910164 polymorphism and serum TNF-α in Egyptian patients with IS.

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m 2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cai, Ali, Filler, Bayati, Toma, Zaki, Yaghmour, Ladha, Woan, Tam and Chaudhary.)

Background: Breast cancer (BC) patients have a higher chance of survival if it is diagnosed at an early stage, which is essential for efficient treatment of the condition. The results of an elevated risk of cancer, including BC, previously associated with the ins/del polymorphism rs145204276 in the promoter region of growth arrest-specific 5 (GAS5) are still up for debate. Thus, this study aimed to appraise the frequency of the GAS5 rs145204276 variant with BC risk and demonstrate the potential impact of the sirtuin 1 (SIRT-1), transforming growth factor-beta (TGF-β), and microRNA-182 (miR-182) expression and their diagnostic value in BC., Methods: Blood samples of 155 patients with BC and fibroadenoma and 80 healthy controls were analyzed for GAS5 rs145204276 single nucleotide polymorphism (SNP), SIRT-1, TGF-β, and miRNA-182 expression levels., Results: Ins/ins genotype and ins allele frequencies for GAS5 rs145204276 were considerably higher in BC patients compared with controls. Patients with BC had significantly greater serum levels of TGF-β, miR-182, and SIRT-1 expression., Conclusions: The SIRT-1, TGF-β, and miR-182 genes provide novel, noninvasive diagnostic biomarkers for BC., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The purpose of this study was to determine agreement with the American Academy of Orthopaedic Surgery Appropriate Use Criteria (AUC) for distal radius fractures (DRFs), before and after their adoption, and secondarily determine predictors of operative management., Methods: A single-institution retrospective cohort study comparing patients treated either nonoperatively (115 patients) or operatively (767 patients) for DRFs between May 1, 2008, and May 1, 2018, by 8 hand surgeons was performed. Data included demographics, injury characteristics, DRF radiographic measurements, treatment rendered, and their appropriateness according to the AUC. Statistical testing used the Fisher and χ 2 tests, t test, and multiple variable logistic regression, with a significance level of .05., Results: Overall, there was a significant increase in AUC agreement for operatively treated DRFs (82.7%-89.3%, P = .01), but no difference in agreement for nonoperatively treated DRFs (12.5%-10.7%, P = .77). Age <80 years, AO classes other than B, intra-articular displacement >1 mm, radial inclination <18°, high-energy mechanism of injury, and greater than 1 week to treatment were independent predictors of operative treatment. The area under the curve for the validated regression model using the aforementioned predictors was 0.82., Conclusion: Agreement with AUC for DRFs increased after its adoption for operatively treated, but not for nonoperatively treated, fractures. In addition, a predictive model for operative treatment was developed and validated. Future studies may benefit from further model refinement and testing in other patient cohorts.

Purpose: To assess vitamin D receptor (VDR) gene polymorphisms and bone mineral density and to investigate the possible risk factors of osteoporosis and fracture in rheumatoid arthritis (RA)., Methods: A total of 97 RA patients and 45 matched controls were enrolled. Serum vitamin D level, VDR genotyping, dual-energy X-ray absorptiometry (DEXA) scan, trabecular bone score (TBS), and fracture risk assessment (FRAX) in 10 years were assessed. Disease activity score (DAS28) and modified health assessment questionnaire (MHAQ) were measured., Results: The mean age of the patients was 47.9 ± 8.9 years; 85 females, 12 males (F:M 7.1:1) and mean disease duration 9.4 ± 6.2 years. DAS28 was 4.52 ± 1.04 and MHAQ 0.6 ± 0.4. There was a significant difference between cases and controls as regards DEXA and FRAX (p < 0.0001) but the TBS and VDR genotyping were comparable (p = 0.29 and p = 0.12, respectively). The vitamin D level was comparable with the control (9.3 ± 6.5 vs 10.4 ± 7.5 ng/mL, p = 0.4). None of the patients was receiving anti-osteoporotic therapy or biologic therapy. There was a significant association between the presence of osteoporosis and age, disease duration, menopause, and rheumatoid factor (RF) positivity. The TBS was significantly lower and FRAX higher in patients with positive RF and anti-CCP. FRAX was significantly related and the TBS inversely with the age, disease duration, serum uric acid, alkaline phosphatase, and MHAQ., Conclusions: Reduced BMD and increased tendency to fractures are remarkable in RA patients. Vitamin D level was decreased in patients and control, and VDR gene polymorphisms were not linked to RA. TBS and FRAX are effective tools to assess osteoporotic fractures in RA. Key Points • Reduced bone mineral density (BMD) and increased tendency to fractures are remarkable in rheumatoid arthritis (RA) patients. • Vitamin D level was decreased in patients and control, and VDR gene polymorphisms were not linked to RA. • Trabecular bone score (TBS) and fracture risk assessment (FRAX) in 10 years are effective tools to assess osteoporotic fractures in RA., (© 2022. The Author(s).)

Background  Due to the commonality of distal radius fractures (DRFs), the potential impact of ulnocarpal abutment (UA) on patient outcomes is significant, whether it developed after or prior to injury. It is, therefore, important to consider whether preexisting UA has any impact on outcomes after an acute DRF. Questions/Purpose  The aims of this study were to determine if differences were present in (1) pain at final follow-up, (2) complications, and (3) unintended operations in patients with DRFs and either without or with preexisting radiographic UA. Methods  A single institution retrospective cohort study comparing patients treated either nonoperatively (43 patients) or operatively (473 patients) for DRFs between 5/1/2008 to 5/1/2018 was performed. Data included demographics, prior wrist pain or surgery, ulnar variance, select treatment data, and presence of pain, complication, or unintended operation by final follow-up. Statistical testing used Fisher's exact test and chi-squared test, with a significance level of 0.05. Results  The prevalence of preexisting UA was 14.0 and 15.6% in the nonoperatively- and operatively treated groups, respectively. In nonoperatively treated patients without or with UA, no differences in pain (37.8 vs. 33.3%, p  = 1.00) or complications were seen (13.5 vs. 50.0%, p  = 0.07). A higher unintended operation rate for nonoperatively treated DRFs with UA, compared with those without, UA was seen (5.4 vs. 50.0%, p  = 0.01). No differences in pain, complications, or unintended operations were seen between those without and with UA in the operatively treated group. Conclusion  Preexisting UA is not associated with pain, complications, or unintended operations after operative treatment of DRFs. Prospective studies further evaluating outcomes in nonoperatively treated DRFs with UA may be beneficial., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty-three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype-phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire BCKDHA, BCKDHB and DBT genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen-PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD., (© 2020 Wiley Periodicals LLC.)

Study Design: Retrospective cohort study OBJECTIVE.: To study 30- and 90-day readmission rates, causes, and risk factors after anterior cervical discectomy and fusion (ACDF) and posterior cervical fusion (PCF)., Summary of Background Data: Existing data on readmission after cervical fusion is majorly derived from national databases. Given their inherent limitations in accuracy, follow-up available, and missing data, we intend to add to literature from our institutional analysis., Methods: Patients who underwent ACDF and PCF for degenerative cervical pathology in 2013 and 2014 were identified for the study. Comprehensive chart review was performed to record demographics and clinical patient profile. Hospital readmission within 30 and 90 days was identified, and the causes and management were recorded. Binary logistic regression analysis was done to study risk factors for readmission. ACDF and PCF were studied separately., Results: Our analysis included a total of 549 patients, stratified as 389 ACDFs and 160 PCFs. The 30- and 90-day unplanned readmission rate was 5.1% and 7.7% after ACDF. These rates were 11.2% and 16.9% after PCF. The most common cause of readmission was systemic infection and sepsis after ACDF and PCF (31.4% and 25.8% of readmitted, respectively), followed by pulmonary complications after ACDF (14.3% of readmitted) and wound complications after PCF (19.4% of readmitted). Predictors of readmission after ACDF included heart failure, history of malignancy, history of deep vein thrombosis/pulmonary embolism, and any intraoperative complication. In the PCF cohort, history of ischemic heart disease, increasing number of fusion levels and longer length of stay were independently predictive., Conclusion: The rates, causes, and risk factors of readmission after ACDF and PCF have been identified. There is variation in published data regarding the incidence and risk factors for readmission after cervical fusion; however, majority of readmissions occur due to medical complications and systemic infection., Level of Evidence: 3.

Background:: Little is known about the place of death of patients with cancer in Eastern Mediterranean countries including Egypt, where palliative care is underdeveloped. Identifying the preferred place of death (PPoD) is important for the development of appropriate palliative care models in these countries., Objectives:: To know the PPoD of Egyptian patients with incurable cancer and their family caregivers (FCGs) and to determine the factors that may impact their preferences., Methods:: An observational cross-sectional study that included 301 dyads of patients with incurable cancer and one of their FCGs. A questionnaire was designed to collect data about the characteristics of patients and FCGs as well as their preferences., Results:: The majority of dyads (272/301, 90.4%) answered the PPoD question. Home was the PPoD in 93% of patients and 90.1% of FCGs ( P = .218). The congruence between patients' and FCGs' PPoD was 92.7% (κ = 0.526). In multivariate analysis, poorer performance status (Eastern Cooperative Oncology Group 3 or 4) and full employment of FCGs associated significantly with patients' preference to die in hospital (odds ratio [OR] = 3.015 [95% confidence interval [CI]: 1.004-9.054], P = .049 and OR = 4.402 [95% CI: 1.561-12.417], P = .005, respectively), while poorer performance status and nonreferral to the palliative medicine unit were associated with FCGs' preference of hospital death (OR = 2.705 [95% CI: 1.105-6.626], P = .029 and OR = 2.537 [95% CI: 1.082-5.948], P = .032, respectively)., Conclusions:: The results of the current study suggest that home is the PPoD for the vast majority of Egyptian patients with incurable cancer and their FCGs. Palliative care interventions that promote home death of patients with incurable cancer are needed in Egypt.

While retrograde cargo selection in the Golgi is known to depend on specific signals, it is unknown whether anterograde cargo is sorted, and anterograde signals have not been identified. We suggest here that S-palmitoylation of anterograde cargo at the Golgi membrane interface is an anterograde signal and that it results in concentration in curved regions at the Golgi rims by simple physical chemistry. The rate of transport across the Golgi of two S-palmitoylated membrane proteins is controlled by S-palmitoylation. The bulk of S-palmitoylated proteins in the Golgi behave analogously, as revealed by click chemistry-based fluorescence and electron microscopy. These palmitoylated cargos concentrate in the most highly curved regions of the Golgi membranes, including the fenestrated perimeters of cisternae and associated vesicles. A palmitoylated transmembrane domain behaves similarly in model systems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pseudozyma flocculosa is a fungus very useful and highly efficient as a biocontrol agent against powdery mildew. The reproduction of this fungus occurs exclusively by asexual production of conidia or sporidia that are the most suitable form for agricultural use and seems to be the most resistant to storage conditions. Despite the advantages offered by P. flocculosa in biological control, the use of this fungus use remains largely limited compared to that of chemical fungicides, at least partly due to the difficulty to obtain sporidia resistant to adverse environmental stresses in submerged culture conditions. Under solid-state and submerged-state cultivation, P. flocculosa strain CBS 16788 produced different types of sporidia. The submerged sporidia (SS) appeared relatively uniform in size, which was 15,4 ± 1,6 μm μm long, and 2,8 ± 0.8 μm wide. The aerial sporidia (AS) varied in shape and size, with a mean length of 8,2 ± 3 μm and width of 2,3 ± 0.6 μm. Under scanning and transmission electron microscopy, the cell wall of submerged sporidia was thinner than that of aerial spores, and the surface was smooth in contrast to the aerial sporidia that had a tendency to have verrucous, brittle surface characteristics. The thickness of the aerial sporidia wall is due to the presence of an outer layer rich in melanin. The sporidia germination was compared on YMPD (yeast extract, malt extract, soy peptone, dextrose and agar) coated coverslips. The aerial sporidia did not show germ tubes until 5 h of incubation, while the submerged sporidia showed many germ tubes after the same time. The resistance against the adverse environmental conditions in relation to the type of sporidia of P. flocculosa is discussed., Competing Interests: We confirm that Artechno’s commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).

Background: Infants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age., Results: Nine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (n = 21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age ≥24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious., Conclusion: Sebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011.

Background: With the increasing number of agents active against cancer, advanced cancer patients including metastatic colorectal cancer (mCRC) patients may continue receiving palliative systemic anticancer therapy (PSAT) near the end-of-life. Validated palliative prognostic models, such as the Chuang's prognostic scale (CPS), may be helpful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT., Aim: To test the ability of the CPS to predict the survival of mCRC under treatment with PSAT., Methods: CPS was prospectively assessed in 36 mCRC patients who were receiving PSAT. The scale is based on eight items: ascites, edema, cognitive impairment, liver and lung metastases, performance status, tiredness, and weight loss. The total CPS score ranges from 0 to 8.5 with the higher score indicating worse prognosis., Results: Patients were divided into two groups using a CPS cutoff score of 5, Group 1 with a CPS score ≤5 and Group 2 with a CPS score >5. Using this cutoff value, 3-month mortality was predicted with a positive predictive value of 71%, a negative predictive value of 77%, a sensitivity of 67%, a specificity of 81% and an overall accuracy of 75%. Group 1 patients had a longer median survival of 149 days (95% confidence interval [CI]: 82-216) in comparison to Group 2 patients who had a median survival of 61 days (95% CI: 35-87). The difference in survival was statistically significant (P = 0.01)., Conclusion: CPS may be useful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT.

Purpose: The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy., Methods: Investigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan-Meier survival analyses were conducted for the overall population and for treated and untreated patients., Results: Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months)., Conclusions: These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.Genet Med 18 5, 452-458.