Disease Severity Research Articles

Positive experience in treating patients with Duchenne muscular dystrophy caused by a nonsense mutation: family clinical case

Duchenne muscular dystrophy is a severe genetic disease caused by mutations in the dystrophin gene (DMD), which lead to a significant decrease or complete absence of the protein of the same name in muscle fibers. The disease manifests itself in boys from the age of 2–5 years in the form of progressive muscular weakness, cardiomyopathy and respiratory failure. As a result of progression, patients lose the ability to move by adolescence and die in the third decade from cardiopulmonary complications. However, timely pathogenetic therapy for Duchenne muscular dystrophy can prolong the life of patients and improve its quality. In this regard, early diagnosis of the disease and early initiation of pathogenetic therapy are very important.The article describes two clinical cases of the disease in siblings with onset at 2 years of age and different ages of diagnosis. Pathogenetic therapy in the first case made it possible to prolong the patient’s outpatient stay and improve the quality of life, and early diagnosis and initiation of pathogenetic therapy in the second case avoided disease progression and contributed to the development of new motor skills. The presented clinical case demonstrates the need for early diagnosis of the disease even before the onset of clinical manifestations.

Metastatic cholangiocarcinoma in a cow presenting as suspect bovine tuberculosis in Ireland

AbstractCholangiocarcinoma is a malignant tumour of bile duct epithelial cells, an uncommon primary hepatic neoplasm in cattle. A 9‐year‐old Simmental cow presented with watery diarrhoea, crusty skin lesions, loss of appetite and hepatomegaly. Suspecting severe liver disease, the cow was euthanased due to poor prognosis. During gross postmortem examination, large numbers of multifocal to coalescing nodules often with soft necrotic centres ranging from miliary to 7 cm in size were present in the liver, lung, mesentery, peritoneum and lymph nodes. These features were suggestive of bovine tuberculosis. However, direct tissue smears stained by Ziehl Neelsen stain were negative for the presence of acid‐fast bacteria, and subsequent histopathological and immunohistochemical investigations confirmed the presence of metastasizing cholangiocarcinoma. This case reminds clinicians and pathologists to keep an open mind during the diagnostic process and serves to highlight the value of histopathology in diagnosing seemingly characteristic gross lesions.

Self-reported body function and daily life activities 18 months after Covid-19: A nationwide cohort study.

This study aimed to investigate body function and daily life activities 18 months after Covid-19 infection, depending on the initial severity of disease and according to sex. All 11,955 individuals on sick leave due to Covid-19 during the first wave of the pandemic in Sweden were invited to answer a questionnaire regarding experiencing negative changes in body function and daily life activities approximately 18 months after the start of sick leave. The analysis of data included descriptive statistics, group comparisons and multivariable binary logistic regressions (two groups). Of 5464 responders (45.7%), 4676 (85.6%) reported experiencing at least one problem with body function, and the reported prevalence of problems with daily life activities was 46%. The most frequently reported problems were fatigue (66.3%), cognition, sleep and movement. In general, women and those initially hospitalised reported more problems. In the regression analyses, problems with body function could partly explain whether individuals experienced problems with daily life activities. However, only fatigue and movement significantly contributed throughout all groups (p<0.001). Furthermore, the odds ratios for fatigue were larger in regressions for women than for men. In this nationwide study, more than 8 out of 10 individuals experienced problems with body function 18 months after being on sick leave due to Covid-19, with women and those initially hospitalised reporting more problems. Problems with body function, such as fatigue, could partly explain problems with daily life activities. However, the mechanisms behind the consequences are not yet clear and need to be further investigated.

WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD

Recent advancements highlight the intricate interplay between the extracellular matrix (ECM) and immune responses, notably in respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). The ECM, a dynamic structural framework within tissues, orches-trates a plethora of cellular processes, including immune cell behavior and tissue repair mecha-nisms. WNT1-inducible-signaling pathway protein 1 (WISP1), a key ECM regulator, controls immune cell behavior, cytokine production, and tissue repair by modulating integrins, PI3K, Akt, β-catenin, and mTOR signaling pathways. WISP1 also induces macrophage migration inhibitory factor (MIF) expression via Src kinases and epidermal growth factor receptor (EGFR) activation. MIF, through its wide range of activities, enhances inflammation and tissue restructuring. Rec-ognized for its versatile roles in regulating the immune system, MIF interacts with multiple immune components, such as the NLRP3 inflammasome, thereby sustaining inflammatory pro-cesses. The WISP1–MIF axis potentially unveils complex molecular mechanisms governing im-mune responses and inflammation. Understanding the intricate roles of WISP1 and MIF in the pathogenesis of chronic respiratory diseases such as asthma and COPD could lead to the identi-fication of novel targets for therapeutic intervention to alleviate disease severity and enhance patient outcomes.

EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells.

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

Advances in the Computational Assessment of Disturbed Coronary Flow and Wall Shear Stress: A Contemporary Review.

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid-structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-reactive CD3+CD4+CD154+ T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4+ T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4+ T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2-reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Patient-Reported Racial and Ethnic Disparities in Patients with Ulcerative Colitis: Results from the National Health and Wellness Survey

Abstract Background Ulcerative colitis (UC) is an inflammatory condition characterized by chronic, disabling gastrointestinal symptoms that can have detrimental effects on psychological, social, and professional quality of life. Few studies have examined patient-reported outcomes (PROs) and economic outcomes among individuals with varying UC severity and across different racial/ethnic groups. Methods This cross-sectional study assessed sociodemographic data, PROs, and economic outcomes for participants from the National Health and Wellness Survey (2018, 2019, and 2020) with UC. Multivariable analyses were used to assess the association of self-reported UC severity and race/ethnicity with health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HCRU), and medical costs. Results This study included 1,500 participants with UC (1,150 non-Hispanic White, 99 non-Hispanic Black, and 251 Hispanic). Moderate/severe disease was associated with significantly worse HRQoL and WPAI, greater HCRU, and higher direct medical costs than mild UC. Compared with non-Hispanic White participants, non-Hispanic Black participants reported better HRQoL, whereas Hispanic participants reported more HCRU and higher medical costs. Race/ethnicity significantly interacted with UC severity level in predicting labor force participation. Conclusions Participants with moderate/severe disease had worse outcomes than those with mild UC. Additionally, racial/ethnic differences were found in HRQoL, employment, WPAI, HCRU, and direct medical costs. Notably, Hispanic participants showed distinct patterns, particularly in how disease severity influenced employment outcomes. Further research is needed to better understand the differential burden among patients across racial/ethnic groups.

Sepsis-associated acute kidney injury in patients with chronic kidney disease: Patient characteristics, prevalence, timing, trajectory, treatment and associated outcomes.

The features and outcomes of sepsis-associated acute kidney injury (SA-AKI) may be affected by chronic kidney disease (CKD). Accordingly, we aimed to compare SA-AKI in patients with or without CKD. Retrospective cohort study in 12 intensive care units (ICU). We studied the prevalence, patient characteristics, timing, trajectory, treatment and outcomes of SA-AKI with and without CKD. Of 84 240 admissions, 7255 (8.6%) involved patients with CKD. SA-AKI was more common in patients with CKD (21% vs 14%; p < .001). CKD patients were older (70 vs. 60 years; p < .001), had a higher median Charlson co-morbidity index (5 vs. 3; p < .001) and acute physiology and chronic health evaluation (APACHE) III score (78 vs. 60; p < .001) and were more likely to receive renal replacement therapy (RRT) (25% vs. 17%; p < .001). They had less complete return to baseline function at ICU discharge (48% vs. 60%; p < .001), higher major adverse kidney events at day 30 (MAKE-30) (38% vs. 27%; p < .001), and higher hospital and 90-day mortality (21% vs. 13%; p < .001, and 27% vs. 16%; p < .001, respectively). After adjustment for patient characteristics and severity of illness, however, CKD was not an independent risk factor for increased 90-day mortality (OR 0.88; 95% CI 0.76-1.02; p = .08) or MAKE-30 (OR 0.98; 95% CI 0.80-1.09; p = .4). SA-AKI is more common in patients with CKD. Such patients are older, more co-morbid, have higher disease severity, receive different ICU therapies and have different trajectories of renal recovery and greater unadjusted mortality. However, after adjustment day-90 mortality and MAKE-30 risk were not increased by CKD.

Polymorphism in the Drug Transporter Gene ABCB1 as a Potential Disease Modifier in Cortisol-Producing Adrenal Adenomas.

Endogenous hypercortisolism presents with variable phenotypes. Etiological factors accounting for the level of hypercortisolism or varying severity of associated comorbidities are lacking. Recently, the adrenal ATP-binding cassette B1 (ABCB1) gene was identified as a modulator of glucocorticoid secretion. To evaluate the effect of ABCB1 polymorphism rs2032582 on steroid metabolome and clinical phenotypes in patients with endogenous hypercortisolism. In this cross-sectional cohort study, 137 patients prospectively enrolled in the German Cushing's registry were included (41 with ACTH-producing pituitary adenoma, 21 with cortisol-producing adrenal adenoma, and 75 with excluded hypercortisolism). In all patients, ABCB1 polymorphism was analyzed using a TaqMan genotyping assay, glucocorticoid metabolite excretion in 24-hour urine samples was analyzed by gas chromatography-mass spectrometry, and the clinical phenotype was assessed systematically. In patients with cortisol-producing adrenal adenomas, but not in patients with ACTH-producing pituitary adenomas, homozygous major allele GG of ABCB1 polymorphism rs2032582 was associated with higher overall cortisol metabolite secretion (median 13515 [IQR 10347; 25669] µg/24h vs. 9645 [6146; 10732] µg/24h in minor homo- and heterozygotes, p=0.036) and elevated major cortisol metabolites αTHF, THF and THE (9339 [6929; 17789] µg/24h vs. 6288 [4184; 7455] µg/24h, p=0.045). Moreover, these patients showed higher mean arterial pressure (116 [111; 131] mmHg in major homozygotes vs. 105 [96; 112] mmHg in minor homo- and heterozygotes, p=0.036). The genotype of drug transporter gene ABCB1 rs2032582 polymorphism is associated with the degree of cortisol metabolite secretion in cortisol-producing adrenal adenomas and could, therefore, represent a modifier of disease severity in this context.

Association between dietary inflammatory index and disease activity in patients with ulcerative colitis

Considering the influence of dietary factors on inflammatory markers that may affect the disease course in patients with ulcerative colitis (UC), this study aimed to assess the association between dietary inflammatory index (DII) score and disease activity in patients with ulcerative colitis. This cross-sectional study included 158 patients with UC. The Mayo Clinic score was used to determine the disease severity. A food frequency questionnaire was applied to gather the dietary information, then the Shivappa et al. method was used for the calculation of DII. An association between disease severity (dependent factor) and DII score quartiles (independent factors) was conducted by a logistic regression adjusted to different covariates. In this study, 53.8% of participants were in remission or had mild disease activity. The mean DII score was − 0.24 ± 0.66. The mean DII score was significantly lower in patients with remission (-0.34 ± 0.71) compared with patients who were in the active phase (-0.1 ± 0.57) of UC (P = 0.02). The results of the logistic regression analysis showed that after adjusting for confounding factors, the odds of severe disease were 3.33 times higher among patients who had a more pro-inflammatory diet compared with patients who had an anti-inflammatory diet [OR: 3.33 (95%CI: 1.13, 9.76), p = 0.02]. In conclusion, there was a significant association between higher intake of a pro-inflammatory diet and UC severity. So, from a clinical point of view, there is a need to apply an anti-inflammatory diet to decrease disease severity in patients with ulcerative colitis.

Determining the optimal ratio of resistant to susceptible bentgrass cultivars to reduce dollar spot severity

AbstractDollar spot, caused by Clarireedia spp., is the most prevalent disease on creeping bentgrass golf fairways. Interseeding newer dollar spot‐resistant cultivars into susceptible bentgrass stands could reduce dollar spot severity and the need for resultant fungicide use. This study was conducted to determine the optimal ratio of resistant to susceptible cultivars in a blend that will result in dollar spot reduction. Greenhouse experiments were conducted on cultivar blend ratios (0%, 10%, 25%, 50%, 75%, 90%, 100%) of dollar spot‐resistant (Pure Select, 007XL, Coho) and susceptible (Penncross) bentgrass challenged with inoculation of two Clarireedia spp. isolates. Disease severity was determined using visual estimates and digital image analysis. Dollar spot severity was significantly influenced by the Clarireedia isolate, with a fungicide‐resistant isolate being more aggressive and producing more disease than a sensitive one. Dollar spot severity was highest on Penncross alone, with no statistical differences observed among the resistant cultivar monostands. Mean disease severity of the blended cultivar ratios was divided into three statistically different groups—low resistance (10% and 25%), medium resistance (50% and 75%), and high resistance (90% and 100%). Compared to Penncross, blending a 10% resistant cultivar reduced AUDPC (area under the disease progress curve) values by 2% and 3% in Experiments 1 and 2, respectively, while blending a 90% resistant cultivar yielded 20% and 32% reductions. These results indicate dollar spot severity decreases as the ratio of the resistant cultivar in a stand increases, and blending resistant cultivars into susceptible has the potential for reducing disease.

Podoplanin expressing macrophages and their involvement in tertiary lymphoid structures in mouse models of Sjögren’s disease

Tertiary lymphoid structures (TLSs) are formed in tissues targeted by chronic inflammation processes, such as infection and autoimmunity. In Sjögren’s disease, the organization of immune cells into TLS is an important part of disease progression. Here, we investigated the dynamics of tissue resident macrophages in the induction and expansion of salivary gland TLS. We induced Sjögren’s disease by cannulation of the submandibular glands of C57BL/6J mice with LucAdV5. In salivary gland tissues from these mice, we analyzed the different macrophage populations prior to cannulation on day 0 and on day 2, 5, 8, 16 and 23 post-infection using multicolored flow cytometry, mRNA gene analysis, and histological evaluation of tissue specific macrophages. The histological localization of macrophages in the LucAdV5 induced inflamed salivary glands was compared to salivary glands of NZBW/F1 lupus prone mice, a spontaneous mouse model of Sjögren’s disease. The evaluation of the dynamics and changes in macrophage phenotype revealed that the podoplanin (PDPN) expressing CX3CR1+ macrophage population was increased in the salivary gland tissue during LucAdV5 induced inflammation. This PDPN+ CX3CR1+ macrophage population was, together with PDPN+CD206+ macrophages, observed to be localized in the parenchyma during the acute inflammation phase as well as surrounding the TLS structure in the later stages of inflammation. This suggests a dual role of tissue resident macrophages, contributing to both proinflammatory and anti-inflammatory processes, as well as their possible interactions with other immune cells within the inflamed tissue. These macrophages may be involved with lymphoid neogenesis, which is associated with disease severity and progression. In conclusion, our study substantiates the involvement of proinflammatory and regulatory macrophages in autoimmune pathology and underlines the possible multifaceted functions of macrophages in lymphoid cell organization.

Serum Interleukin (IL)-6, Lipid Profile, and Association With Disease Severity in Patients With Psoriasis: A Cross-Sectional Study

Serum Interleukin (IL)-6, Lipid Profile, and Association With Disease Severity in Patients With Psoriasis: A Cross-Sectional Study

Agonist antibody to MuSK protects mice from MuSK myasthenia gravis

Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). MuSK, a master regulator of NMJ development, associates with the low-density lipoprotein-related receptor 4 (Lrp4) to form the signaling receptor for neuronal Agrin, a nerve-derived synaptic organizer. Pathogenic antibodies to MuSK interfere with binding between MuSK and Lrp4, inhibiting the differentiation and maintenance of the NMJ. MuSK MG can be debilitating and refractory to treatments that are effective for AChR MG. We show here that recombinant antibodies, derived from MuSK MG patients, cause severe neuromuscular disease in mice. The disease can be prevented by a MuSK agonist antibody, presented either prophylactically or after disease onset. These findings suggest a therapeutic alternative to generalized immunosuppression for treating MuSK MG by selectively and directly targeting the disease mechanism.

Risk Factors Associated with Angiographic Severity of Coronary Artery Disease Based on Serum Uric Acid: A Study in a Tertiary Care Hospital, Chattogram, Bangladesh

Background: Coronary Artery Disease (CAD) is a leading cause of death worldwide, identifying risk factors and severity is crucial for management and prevention. Serum Uric Acid (SUA) has been proposed as a potential marker for the severity of CAD. Elevated SUA levels are associated with endothelial dysfunction, oxidative stress, and inflammation, all of which contribute to the development and progression of atherosclerosis. This study aims to determine the association of risk factors with the severity of CAD using SUA levels. Materials and methods: This was a cross-sectional observational study conducted in the Department of Cardiology at CMCH in Chattogram over one year from October 2020 to September 2021. After case selection demographic data were collected and transthoracic echocardiography was performed on study patients. Results: The study analyzed the association between SUA level and CAD severity in 130 patients undergoing coronary angiography. The mean SUA level was 5.06 mg/dl and was significantly associated with the presence of CAD, number of vessel involvement and severity of CAD assessed by the Gensini score. The mean SUA level in cases with CAD was significantly higher (5.26 ± 1.32 mg/dl) than in cases without CAD (4.22 ± 1.03 mg/dl). Conclusion: This study concluded that demographic variables and risk factors are associated with the severity of CAD. The severity of CAD was higher in elderly and male patients. The study suggests that when assessing the risk in a CAD patient, hyperuricemia should be considered. IAHS Medical Journal Volume 6(2) December 2023; 48-52

Design of a Phase 3, Global, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab is a neonatal fragment crystallizable (Fc) receptor (FcRn)-blocking monoclonal antibody that inhibits placental immunoglobulin G (IgG) transfer and lowers circulating maternal IgG levels. In an open-label, single-arm, phase 2 study, nipocalimab demonstrated evidence of safety and efficacy that support further investigation in a pivotal phase 3 trial of recurrent hemolytic disease of the fetus and newborn (HDFN). The phase 3 AZALEA study aims to evaluate the efficacy and safety of nipocalimab in a larger population at risk for severe HDFN, defined as HDFN associated with poor fetal outcomes or neonatal death. AZALEA is a multicenter, randomized, placebo-controlled, double-blind, phase 3 study enrolling alloimmunized pregnant individuals (N ≈ 120) at risk for severe HDFN based on obstetric history. Participants are randomized 2:1 to receive intravenous 45 mg/kg nipocalimab or placebo weekly from 13-16 to 35 weeks gestational age (GA). During the double-blind treatment period, participants receive standard-of-care weekly monitoring for fetal anemia until planned delivery at 37 to 38 weeks of GA. Postnatal follow-up periods are 24 weeks for maternal participants and 104 weeks for neonates/infants. The primary endpoint is the proportion of pregnancies that do not result in intrauterine transfusion (IUT), hydrops fetalis, or fetal loss/neonatal death from all causes. Key secondary endpoints include the severity of HDFN as measured by a composite HDFN severity index, the earliest time to occurrence of IUT or hydrops fetalis, the modified neonatal mortality and morbidity index in liveborn neonates, and the number of IUTs received. Other endpoints are safety, patient- and caregiver-reported outcomes, pharmacokinetics, pharmacodynamics (e.g., IgG, FcRn receptor occupancy), and immunogenicity of nipocalimab. AZALEA, the first placebo-controlled, randomized, multicenter, prospective trial in severe HDFN, is designed to evaluate the safety and efficacy of nipocalimab, a potential preventive and noninvasive intervention, in at-risk HDFN pregnancies. · Severe HDFN leads to poor fetal/neonatal outcomes.. · IUTs are associated with complications and fetal loss.. · Nipocalimab blocks IgG recycling and placental transfer.. · Nipocalimab reduces fetal anemia and IUTs in early-onset severe HDFN.. · The phase 3 AZALEA study evaluates nipocalimab in severe HDFN..

Immediate Effect of Continuous Positive Airway Pressure Therapy on Sleep and Respiration in Patients with Multiple System Atrophy and Sleep-Disordered Breathing.

Sleep-disordered breathing (SDB; including stridor and sleep apnea syndromes) is frequent in multiple system atrophy (MSA), but the immediate effect of continuous positive airway pressure (CPAP) therapy is incompletely determined. We sought to evaluate the acute effect and safety of CPAP therapy on SDB and sleep architecture, as well as the clinical characteristics of nonresponders to CPAP therapy. The measures of 63 consecutive patients with MSA who underwent a video-polysomnography during two consecutive nights (a first night in ambient air, a second night with or without CPAP, depending on the presence of SDB and availability of CPAP) in routine care were retrospectively collected. Linear mixed models assessed the two-night change in sleep and respiratory measures, comparing those with and without the CPAP therapy on the second night. SDB was frequent and mainly associated with the cerebellar phenotype. The introduction of CPAP had immediate benefits, including the normalization of the apnea-hypopnea index and a resolution of stridor in more than two-thirds of the cases, decreased arousal index, and increased rapid eye movement sleep. CPAP therapy was well tolerated, and only two patients had emergent central apneas. Nonresponse to CPAP was generally associated with more severe motor disease. CPAP seems a well-tolerated and effective therapy in patients with MSA and SDB in the short term. This treatment shows remarkable immediate benefits by objectively improving both respiratory disturbances and sleep architecture. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Drug-Induced Hypouricemia.

Hypouricemia is defined as a serum uric acid concentration of ≤ 2.0mg/dL or 119μmol/L. Hypouricemia may occur secondarily to a number of underlying conditions, including severe hepatocellular disease, neoplasia, defective renal tubular reabsorption of uric acid, inherited metabolic defect in purine metabolism, and drugs. Medications are an important cause of hypouricemia. They can cause hypouricemia by a variety of mechanisms. Drug-induced hypouricemia mostly occurs as overtreatment of hyperuricemia by urate-lowering therapies including xanthine oxidase inhibitors, uricosuric agents and uricases. Drugs not used in the treatment of gout may also lead to a decrease of uric acid levels. In this literature review, medications leading to hypouricemia are summarized with regard to their mechanism of action and clinical significance.

Epidemiology and Regional Variation in Additional Surgical Interventions for Children with Congenital Diaphragmatic Hernia: A Multi-institutional Analysis.

To determine practice variation in surgical management of co-morbidities in pediatric patients with Congenital Diaphragmatic Hernia (CDH). A higher percentage of CDH patients are surviving to discharge, accompanied by an increase in morbidity requiring surgical interventions such as tracheostomy and gastrostomy tube insertion. The frequency, trends, and regional variations in operative management of these co-morbidities in this population are unclear. Neonates who underwent CDH repair between 2012-2022 in the United States Pediatric Health Information System database were identified. Multivariable regression identified predictive factors for additional surgical morbidity after CDH repair, defined by an additional surgical intervention during index hospitalization or within one year after discharge. To narrow the spectrum of severity of disease, only patients with an intensive care unit admission on index hospitalization were included. Secondary analysis compared frequency of operations and hospital resource utilization by region. 4003 patients underwent CDH repair and were discharged from their index hospitalization. 1939 (48%) underwent at least one additional surgical procedure after the index CDH repair. Most performed surgeries were gastrostomy tube (28%), fundoplication (13%), and tracheostomy (5%). Covariates associated with additional surgical morbidity included: prematurity (OR 1.38; 95% CI: 1.20-1.59), cardiac co-morbidity (OR 1.31; 95% CI: 1.14-1.49), and chromosomal anomalies (OR 1.76, 95% CI: 1.30-2.40). Northeast (OR: 2.43; CI 1.42-3.52), Midwest (OR 2.11; 95% CI: 1.45-3.07), and South (OR 1.45, 95% CI 1.02-2.12) regions were associated with additional surgical morbidity. Patients who required additional surgical procedures had longer initial inpatient length of stays (71 versus 31d) and higher associated costs ($357,000 versus $161,000). Surgical morbidity exists in CDH patients after initial CDH repair. Counseling families on these outcomes is important in establishing expectations for management. Establishing guidelines for optimal surgical management will require continued reporting from multi-institutional studies.