Co-occurrence Of Disease Research Articles

Bidirectional association between inflammatory bowel disease and type 1 diabetes: a nationwide matched cohort and case-control study

Co-occurrence of inflammatory bowel disease (IBD) and type 1 diabetes (T1D) has been linked to poor clinical outcomes, but evidence on their bidirectional associations remain scarce. This study aims to investigate their bidirectional associations. A nationwide matched cohort and case-control study with IBD patients identified between 1987 and 2017. The cohort study included 20,314 IBD patients (≤28 years; Crohn's disease [CD, n=7277], ulcerative colitis [UC, n=10,112], and IBD-unclassified [IBD-U, n=2925]) and 99,200 individually matched reference individuals, with a follow-up until December 2021. The case-control study enrolled 87,001 IBD patients (no age restriction) and 431,054 matched controls. We estimated adjusted hazard ratio (aHR) of incident T1D in the cohort study with flexible parametric survival model and adjusted odds ratio (aOR) of having a prior T1D in the case-control study with conditional logistic regression model, with 95% confidence intervals (CI). During a median follow-up of 14 years, 116 IBD patients and 353 reference individuals developed T1D. Patients with IBD had a higher hazard of developing T1D (aHR=1.58 [95% CI=1.27-1.95]). The hazard was increased in UC (aHR=2.02 [1.51-2.70]) but not in CD or IBD-U. In the case-control study, a total of 1018 (1.2%) IBD patients and 3496 (0.8%) controls had been previously diagnosed with T1D. IBD patients had higher odds of having prior T1D (aOR=1.36 [1.26-1.46]). Such positive association was observed in all IBD subtypes. The sibling comparison analyses showed similar associations between IBD and T1D (aHR=1.44 [0.97-2.15] and aOR=1.32 [1.18-1.49]). Patients with IBD had a moderately increased hazard of developing T1D and higher odds of having prior T1D. Their bidirectional associations may be partially independent of shared familial factors. European Crohn's and Colitis Organisation, Stiftelsen Professor Nanna Svartz Fond, SSMF (project#: PG-23-0315-H-02), Ruth and Richard Julin Foundation; and FORTE (project#: 2016-00424).

Association between vulvar lichen sclerosus and celiac disease in woman.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory condition involving mainly the genital area with an undetermined aetiology. Recent studies show that in up to 34% of cases in adult women, VLS coexists with allergies or autoimmune diseases like celiac disease (CD), among others. However, literature data relating strictly to the co-occurrence of celiac disease and Duhring's disease (DH) in patients with VLS are very limited. In our study, we sought to clarify the possible relationship between vulvar lichen sclerosus in adult women and celiac disease in its cutaneous form. The aim of the study was to demonstrate the presence of celiac disease-specific antibodies in women with VLS. The control group consisted of 41 healthy women, and the study group consisted of 50 women aged 24-83 years with diagnosed vulvar lichen sclerosus who were hospitalized in the Department of Gynaecology, Obstetrics and Gynaecologic Oncology of the Bonifraters Medical Centre in Katowice. There were no significant differences in blood serum levels of CD-specific antibodies between both groups. The study conducted did not confirm the association between vulvar lichen sclerosus and celiac disease or Duhring's disease. The main limitation of the research was the small size of the study and control groups. Further studies on a larger group of patients are needed. They could clarify the possible mechanisms behind the co-occurrence of these two conditions. Earlier diagnostic will help prevent the development of severe and irreversible complications.

XAI-Augmented Voting Ensemble Models for Heart Disease Prediction: A SHAP and LIME-Based Approach.

Ensemble Learning (EL) has been used for almost ten years to classify heart diseases, but it is still difficult to grasp how the "black boxes", or non-interpretable models, behave inside. Predicting heart disease is crucial to healthcare, since it allows for prompt diagnosis and treatment of the patient's true state. Nonetheless, it is still difficult to forecast illness with any degree of accuracy. In this study, we have suggested a framework for the prediction of heart disease based on Explainable artificial intelligence (XAI)-based hybrid Ensemble Learning (EL) models, such as LightBoost and XGBoost algorithms. The main goals are to build predictive models and apply SHAP (SHapley Additive expPlanations) and LIME (Local Interpretable Model-agnostic Explanations) analysis to improve the interpretability of the models. We carefully construct our systems and test different hybrid ensemble learning algorithms to determine which model is best for heart disease prediction (HDP). The approach promotes interpretability and transparency when examining these widespread health issues. By combining hybrid Ensemble learning models with XAI, the important factors and risk signals that underpin the co-occurrence of heart disease are made visible. The accuracy, precision, and recall of such models were used to evaluate their efficacy. This study highlights how crucial it is for healthcare models to be transparent and recommends the inclusion of XAI to improve interpretability and medical decisionmaking.

Plasma Proteomic Biomarkers in Alzheimer's Disease and Cardiovascular Disease: A Longitudinal Study.

The co-occurrence of Alzheimer's disease (AD) and cardiovascular diseases (CVDs) in older adults highlights the necessity for the exploration of potential shared risk factors. A total of 566 adults were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 111 individuals with AD, 383 with mild cognitive impairment (MCI), and 410 with CVD. The multivariable linear mixed model (LMM) was used to investigate the associations of AD and CVD with longitudinal changes in 146 plasma proteomic biomarkers (measured at baseline and the 12-month follow-up). The LMM showed that 48 biomarkers were linked to AD and 46 to CVD (p < 0.05). Both AD and CVD were associated with longitudinal changes in 14 biomarkers (α1Micro, ApoH, β2M, BNP, complement C3, cystatin C, KIM1, NGAL, PPP, TIM1, THP, TFF3, TM, and VEGF), and both MCI and CVD were associated with 12 biomarkers (ApoD, AXL, BNP, Calcitonin, CD40, C-peptide, pM, PPP, THP, TNFR2, TTR, and VEGF), suggesting intricate connections between cognitive decline and cardiovascular health. Among these, the Tamm Horsfall Protein (THP) was associated with AD, MCI, CVD, and APOE-ε4. This study provides valuable insights into shared and distinct biological markers and mechanisms underlying AD and CVD.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients

ObjectivesElectroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines.MethodsIn this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests.ResultsWe identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT.ConclusionEven if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Double Trouble: Co-occurrence of Langerhans Cell Histiocytosis and Rosai Dorfman Disease in a Toddler

The coexistence of Rosai-Dorfman disease (RDD) with Langerhans cell histiocytosis (LCH) is very rare, as to date only a handful of cases have been reported. Though both the entities come under the spectrum of histiocytic disorders, the patient outcomes are very different for each one of them. RDD is a benign disorder with often a self-limiting course; whereas LCH has a more aggressive outcome. The pathobiology of this rare co-occurrence is still unknown and the topic of several theories. Case presentation: We report a case of a 2-year-old female patient who presented with fever, pallor, lymphadenopathy and neck pain. X-ray radiograph and Computed Tomography (CT) scan chest showed multiple lytic lesions on vertebra. The biopsy finding of lymph node and bone marrow were consistent with a combined RDD-LCH disease. Conclusion: Combined RDD-LCH presentation is very rare and it’s pathophysiology is still elusive and a topic of numerous conjectures.

Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder

Editor’s Pick: Genetics and Pathophysiology of Co-occurrence of Congenital Heart Disease and Autism Spectrum Disorder

Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients.

The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients. We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model. For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR. Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.

Vascular function and skeletal fragility: a study of tonometry, brachial hemodynamics, and bone microarchitecture.

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these 2 common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by HR-pQCT, in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude, and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: -0.21 [-0.26, -0.15] standardized beta [95% CI], radius: -0.20 [-0.26, -0.15]), lower cortical thickness (tibia: -0.09 [-0.15, -0.04], radius: -0.07 [-0.12, -0.01]) and increased cortical porosity (tibia: 0.20 [0.15, 0.25], radius: 0.21 [0.15, 0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health.

TLR7-dependent eosinophil degranulation links psoriatic skin inflammation to small intestinal inflammatory changes in mice

Recent evidence of gut microbiota dysbiosis in the context of psoriasis and the increased cooccurrence of inflammatory bowel disease and psoriasis suggest a close relationship between skin and gut immune responses. Using a mouse model of psoriasis induced by the Toll-like receptor (TLR) 7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by inflammatory changes in the small intestine associated with eosinophil degranulation, which impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were increased in mice prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells were treated with media containing eosinophil granule proteins and exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by the transfer of eosinophils. Imiquimod levels and the distribution of eosinophils were positively correlated in the intestine. TLR7-deficient mice did not exhibit intestinal eosinophil degranulation but did exhibit attenuated inflammation in the skin and small intestine following imiquimod administration. These results suggest that TLR7-dependent bidirectional skin-to-gut communication occurs in psoriatic inflammation and that inflammatory changes in the intestine can accelerate psoriasis.

Prediction of Co-Occurrence of Lewy Body Disease with Alzheimer's Disease.

Identifying the coexistence of Lewy body (LB) pathology with Alzheimer's disease (AD) in clinical practice is important in the era of anti-amyloid-β antibody therapy. However, few studies have predicted the presence of comorbid LB pathology with AD using indicative biomarkers of dementia with Lewy bodies or by collecting detailed clinical symptoms. We report the clinical progression of a 67-year-old patient diagnosed with AD who developed rapid eye movement sleep disorder-like symptoms and transient visual hallucinations 10 years after AD onset and was considered to have comorbid LB pathology based on imaging indicative biomarkers of dementia with Lewy bodies.

Case report: Multiple autoimmune syndrome

This is a case of multiple autoimmune syndrome with the co-occurrence of vitiligo, pernicious anemia, celiac disease and autoimmune hepatitis is extremely rare. We are presenting a case is a 40-year-old woman with autoimmune hepatitis who is suffering from poor appetite, weight loss and skin lesions. Laboratory investigation shows hypochromic microcytic anemia, B12, and iron deficiency. The testing for parietal cell antibody was positive so pernicious anemia was diagnosed with positive Tissue transglutaminase antibody IgA so the diagnosis of celiac disease was confirmed.

A Cross-Sectional Study Evaluating the Association of Brachial Artery Flow Mediated Vasodilation with Physical Activity Measured by Accelerometry in Patients with the Overlap of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Overlap Syndrome (OS), the co-occurrence of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease. Clustering of patients in subgroups with similar pre-clinical manifestations (ie, endothelial dysfunction) may identify relevant therapeutic phenotype categories for patients with OS who are at high risk of CVD. We therefore conducted a cross-sectional pilot study of endothelial function in 7 patients with OS (Forced Expiratory Volume in 1 second/Forced Vital Capacity < 0.7) on continuous positive airway pressure therapy (n = 7) to assess the relationship between FMD and physical activity. We found a strong association between FMD and step counts (rho = 0.77, p = 0.04); and FMD and moderate physical activity (rho = 0.9, p = 0.005). Further, larger studies are needed to confirm that FMD may identify patients with OS at high risk of CVD who benefit from increased physical activity.

Autoimmune thyroid disease and rheumatoid arthritis: where the twain meet.

Autoimmune thyroid disease (AITD) is the most prevalent autoimmune disease. It shares multiple genetic, clinical, and serologic characteristics with rheumatoid arthritis (RA). Although frequently described as a classic form of single-organ autoimmunity, the AITD disease burden in a subset of patients extends well beyond the thyroid gland. This review explores the complex interaction between the two diseases and the clinical consequences when they overlap. Beyond the well-known effects of AITD on thyroid function in RA, there is mounting evidence of the association of both conditions impacting the presentation and outcomes of diabetes, metabolic syndrome, and cardiovascular disease. An increasing number of studies suggest that there are negative effects of AITD on RA disease activity both in the presence and in the absence of thyroid dysfunction. Recent evidence suggests that AITD may not only worsen the cumulative damage of RA through higher disease activity but may also worsen secondary osteoarthritis changes. Less well-known is the significant association between AITD and chronic widespread pain syndromes including fibromyalgia. Importantly, the presence of fibromyalgia, which is increased in RA patients, appears to be further increased when it overlaps with AITD. Lastly, we probe the possible influence of AITD interacting with RA on fertility and clinical depression. Key Points • Autoimmune thyroid disease is the most common autoimmune disease and is frequently associated with rheumatoid arthritis. • Autoimmune thyroid disease can present with osteoarthritis, inflammatory arthritis, and chronic widespread pain syndromes. • The co-occurrence of autoimmune thyroid disease and rheumatoid arthritis may worsen disease activity and exacerbate other disease manifestations including cardiovascular disease, fertility, and depression. • The overlap of rheumatoid arthritis with autoimmune thyroid disease needs further research and should be sought in general clinical practice.

Co-occurrence of dental caries and periodontitis: multilevel modelling approach

BackgroundPrevious studies reported varyingly positive, negative, or no relationships between caries and periodontitis. Therefore, the aim was to assess the potential co-occurrence of caries experience and periodontal inflammation on the same teeth.MethodsThis cross-sectional study used data from the Lithuanian National Oral Health Survey. The study included a stratified random sample of 1405 individuals aged 34–78, recruited from 5 Lithuanian cities and 10 peri-urban/rural areas (response rate 52%). Information about sociodemographic (age, sex, education, residence), behavioral (sugar-containing diet, tooth brushing frequency, use of interdental care products, last dental visit, smoking) and biological (systemic disease, use of medication and xerostomia) determinants was collected using the World Health Organization (WHO) Oral Health Questionnaire for Adults supplemented with additional questions. Clinical data were recorded using the WHO criteria and collected by one trained and calibrated examiner. Dental caries status was recorded as sound, decayed, missing, filled surfaces. Subsequently for the analyses, status was recorded at a tooth-level as decayed- and filled-teeth (DT and FT) including proximal, buccal, and oral surfaces. Two measures were used for periodontal status. The probing pocket depth (PPD) was measured at six sites and recorded at a tooth level into the absence of PPD or presence of PPD ≥ 4 mm. Bleeding on probing (BOP) was measured at the same six sites and was recorded as either present or absent at a tooth-level. Univariable and multivariable 2-level random intercept binary logistic regression analyses were utilized.ResultsPositive associations were found between DT and BOP (OR 1.42, 95% CI 1.20–1.67), FT and BOP (OR 2.07, 95% CI 1.82–2.23), DT and PPD (OR 1.38, 95% CI 1.15–1.67) and FT and PPD (OR 2.01, 95% CI 1.83–2.20).ConclusionsOur findings add evidence for the co-occurrence of periodontal inflammation and caries on the same teeth. This suggests the need for increased emphasis on a transdisciplinary approach in designing oral health interventions that target dental caries and periodontal disease simultaneously. In addition, longitudinal studies exploring the co-occurrence of caries and periodontal disease at the same sites, taking into consideration the levels of both conditions and genetic variation, are warranted.

Co-occurrence of Neuromyelitis Optica Spectrum Disorder and Behcets Disease

Co-occurrence of Neuromyelitis Optica Spectrum Disorder and Behcets Disease

Chronic disease prevalence in a population with structural hemoglobin disorders undergoing diabetes diagnosis: A bayesian approach

BackgroundStructural disorders of hemoglobin are a group of rare and fatal genetic diseases that disrupt the transport and exchange of oxygen in the blood, causing tissue damage and ultimately leading to chronic conditions. The hemoglobin (Hb) S variant predominantly impacts individuals of Afro-descendant heritage. A significant concentration of the Afro-descendant population in Colombia, notably 12.5 %, is found in the city of Cali. Previous research has identified this city's structural hemoglobin disorders prevalence rate of 3.78 %. The aim of this study was to determine the prevalence of HbC, HbS, HbF, and HbA2 variants within a population who underwent HbA1c testing, as well as the prevalence of chronic diseases among patients with these hemoglobin alterations, at a high-complexity hospital in the city of Cali from 2015 to 2019. MethodsA descriptive observational study was conducted, involving a study population that comprised patients with both suspected and monitored diagnoses of diabetes. The cohort was selected from a high-complexity hospital in Cali. A total of 15,608 patients were included in the analysis, all of whom underwent HbA1C measurement through capillary electrophoresis, which also offers an indirect diagnosis of certain structural disorders of hemoglobin. Bayesian methods were employed for frequency analysis. ResultsAmong the 15,608 patients assessed, 63.6 % (n = 9920) were women. The overall prevalence of structural hemoglobin disorders was 1.98 % (n = 287, 95 % CI = 1.77 %–2.21 %). The co-occurrence of diabetes and kidney disease emerged as the most prevalent combination of pathologies observed in individuals with HbC, for both men and women across various age groups: 18–42 (58.3 % and 50.0 % respectively), 43–55 (50.0 % for both), 56–65 (50.0 % and 37.5 % respectively), and >65 years (66.7 % and 57.1 % respectively). ConclusionsThe observed prevalence of the studied variants exceeded 1 %, a threshold underscored by the World Health Organization (WHO) as epidemiologically significant. Among HbC and HbS-positive patients, the elevated prevalence of diabetes and kidney disease is a guiding factor in developing proactive prevention strategies.

Novel Diabetic Nephropathy-Based Hypertension Treatment for Type-2 Diabetes Mellitus and CKD Patients: A Mini Review

Diabetes mellitus is known to result in persistent renal impairment among individuals with the condition and is presently the primary aetiology of terminal-stage renal disease, with more than fifty percent of dialysis patients being affected. The prevalence of diabetes continues to rise, resulting in a decline in individuals' health status and imposing significant financial burdens on healthcare systems. Accurately distinguishing between the various types of diabetes is crucial in order to provide appropriate treatment that mitigates the severity of associated complications and their significant consequences. The co-occurrence of diabetes and renal disease has been found to be linked with a significant fourfold rise in both the frequency and fatality of cardiovascular disease. Pharmacological interventions aimed at reducing blood pressure have been a crucial component in the management of diabetic nephropathy for several decades. The past decade has witnessed a decline in the occurrence of end-stage renal disease, owing to enhanced care measures such as the administration of hypertension medication. It is assumed in clinical practice recommendations that angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists hold an equivalent status. The efficacy of low doses of ACEI and ARB in reducing proteinuria was found to be superior to that of high doses. The co-administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has been observed to elicit a more pronounced reduction in 24-hour proteinuria and urinary albumin excretion rate (UAER) in comparison to the singular administration of either ACEI or ARB.

Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

The use of continuous positive airway pressure in COPD-OSA overlap syndrome: A systematic review

BackgroundThe co-occurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), known as COPD-OSA overlap syndrome, increases morbidity and mortality. The effectiveness of continuous positive airway pressure (CPAP) therapy, a commonly used treatment for OSA, in this patient population remains uncertain. Therefore, we conducted a systematic review to evaluate the efficacy of CPAP therapy in improving clinical outcomes. MethodsWe conducted a comprehensive systematic review to identify studies that evaluated the impact of CPAP therapy on COPD exacerbation, hospitalization, and mortality in patients with COPD-OSA overlap syndrome. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Statement and assessed the quality of each study using the Newcastle-Ottawa quality scale. ResultsFrom the initial 3184 articles identified, we reviewed 365 and included five in the systematic review. Our findings revealed that CPAP therapy improved clinical outcomes, including COPD exacerbation, COPD related hospitalization, and mortality in patients with COPD-OSA overlap syndrome. However, the definition of COPD and OSA varied across studies, and the definition of CPAP usage was not consistent. ConclusionOur systematic review suggests that CPAP therapy is effective in improving outcomes in patients with COPD-OSA overlap syndrome. Nonetheless, further research is required to establish the efficacy of CPAP therapy by standardizing the definition of COPD, OSA, and CPAP usage.