Onset Of Type Research Articles

THU013 A Rare Case of Ectopic Cushing’s Syndrome Caused By Metastatic Parotid Gland Carcinoma

Abstract Disclosure: E. Punni: None. I. Goyal: None. Introduction: Ectopic Cushing’s Syndrome (ECS) is a rare condition that accounts for only a small percentage of all Cushing’s syndrome cases. Although rare, the typical tumors associated with ECS are small cell lung carcinomas, bronchial carcinoids, pancreatic neuroendocrine tumors, medullary thyroid carcinomas, thymic carcinoids and pheochromocytomas. Metastatic acinic cell carcinoma (ACC) of the parotid gland has very rarely been associated with ectopic Cushing’s syndrome. Case Presentation: A 67-year-old Caucasian male with a known diagnosis of high grade metastatic ACC of the parotid gland presented to the hospital with progressively worsening proximal muscle weakness and bilateral lower extremity edema of 6 weeks duration. A month prior to presentation, he developed persistent hypokalemia requiring potassium supplementation and was diagnosed with new onset type 2 diabetes mellitus. Laboratory results on admission were remarkable for low potassium at 2.5 mEq/L (N: 3.5-5.3 meq/L), a random cortisol level of 107 mcg/dL (N: 6 - 30 mcg/dL), and an ACTH level of 485 pg/mL (N: 7.2 - 63.3 pg/mL). Subsequently, a 24-hour urine cortisol was > 1600 ug/24 hours (N 5-64 ug/24 hours). A 1 mg dexamethasone suppression test failed to suppress an 8 a.m. cortisol with level of 110.8 mcg/dl (N < 1.8 mcg/dl). Following, an 8 mg dexamethasone suppression test also failed to suppress 8 a.m. cortisol with a value of 100.8 mcg/dl. A MRI of the pituitary with and without contrast showed mild diffuse enlargement of the pituitary gland concerning for pituitary hyperplasia. At the time, ECS was highly suspected given the rapid course of patient’s presentation, known metastatic malignancy, and failed 8 mg dexamethasone suppression test. An inferior petrosal sinus sampling (IPSS) could not be performed given the patient’s guarded condition. Instead, a PET/CT Ga-68 DOTA-TATE scan obtained showed widespread DOTA-TATE avid malignancy concerning for neuroendocrine type tumor. Patient was a poor surgical candidate, therefore bilateral adrenalectomy could not be performed for the rapid treatment of ECS. Patient was started on a steroidogenesis inhibitor ketoconazole. However, he elected to undergo hospice care and passed away shortly after. Conclusion: This case is particularly interesting given that metastatic ACC of the parotid gland causing ECS is rare with only a few cases reported in the literature. This case highlights the importance of maintaining a high degree of suspicion for diagnosing ECS especially when patients present with rapid onset of signs and symptoms of Cushing’s syndrome and a known underlying malignancy. Recognizing less common causes of ECS may prompt early diagnosis and intervention. Presentation: Thursday, June 15, 2023

THU277 Deletion Or inhibition Of Ornithine Decarboxylase Protects Islet β-cell Health And Is Associated With Preserved Residual C-peptide In Persons With Recent Onset Type 1 Diabetes

Abstract Disclosure: B. Hammoud: None. L.A. DiMeglio: None. A. Kulkarni: None. A. Hull: None. S. Woerner: None. S. Cabrera: None. L.D. Mastrandrea: None. F. Ouyang: None. S.N. Perkins: None. C. Evans-Molina: None. T.L. Mastracci: None. S.A. Tersey: None. S. Sarkar: None. E. Nakayasu: None. B. Webb-Robertson: None. E. Gerner: None. R.G. Mirmira: None. E.K. Sims: None. Inhibition of polyamine biosynthesis using α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduces β cell stress and type 1 diabetes (T1D) incidence in preclinical animal models. However, the cellular and molecular mechanisms by which polyamines promote β-cell stress and the tolerability and effectiveness of their depletion by DFMO in humans with T1D remain unknown. We hypothesized that β-cell protection from stress occurs via cell-autonomous effects of polyamine depletion. To test this hypothesis, we generated β-cell specific knockout of ornithine decarboxylase in mice, performed comprehensive proteomics and transcriptomics on human islets treated with DFMO under inflammatory conditions in vitro, and performed a clinical study of DFMO tolerability, safety, and efficacy in persons with new-onset T1D. β-cell-specific deletion of the gene encoding ornithine decarboxylase in mice demonstrated protection of these animals against toxin (streptozotocin)-induced β-cell loss and hyperglycemia, implicating a cell-autonomous role for ornithine decarboxylase in β-cell stress. RNA sequencing and proteomics analyses of human islets exposed to a cytokine mix (1000 U/mL IFNγ + 50 U/mL IL-1β) +/- 5 mM DFMO identified 130 differentially regulated transcripts and 701 differentially regulated proteins. Pathway analysis implicated endosomal transport, vesicle organization and regulation of exocytosis, mRNA processing, and antigen cross presentation as mechanisms underlying DFMO effects on the islet response. To test DFMO in humans, we performed a 3-site randomized, placebo-controlled, double masked dose-ranging study of 3 months daily oral DFMO in persons with recent-onset T1D (<100 days). Dosing at 125, 250, 500, 750 or 1000 mg/m2/day was tested in 41 persons (12-34 y/o, 59% male, mean HbA1c 7.3%), with 6-10 participants/dosing group. Only mild and moderate adverse effects (AEs) were noted. Possible drug-related AEs included mild-moderate gastrointestinal symptoms, headache, upper respiratory infections, a pump site infection, and anemia. Urinary levels of the ODC product putrescine were decreased (p=0.05) in the 1000 mg/m2 dosing group. Compared to placebo, individuals receiving 750 and 1000 mg/m2 doses had significantly higher mixed-meal C-peptide area under the curve values at the 6-month post-randomization visit (p<0.05 vs. placebo). In conclusion, β-cell ODC inhibition protects β-cell health and function in the context of the proinflammatory T1D milieu. A 3-month course of oral DFMO was well tolerated with a favorable AE profile in persons with recent-onset T1D. Higher doses were associated with greater β-function compared to placebo. DFMO may have utility as a β-cell preservation therapy in recent-onset T1D. Presentation: Thursday, June 15, 2023

Incidence of New-onset Hypertension and New-onset Type 2 Diabetes during or after SARS-CoV-2 Infection.

Background: Considering the potential clinical and therapeutic implications, there is a need to determine whether or not COVID infection induces or unmasks new-onset/newly diagnosed hypertension/diabetes during the acute phase and post-COVID-19. Aim: In the current article, we discuss the current data at the intersection of COVID, hypertension, and COVID and diabetes, from prevalence, risk factors, and underlying mechanisms during an acute and post-COVID phase; focusing on new-onset hypertension and new onset type 2 diabetes. Method: We have performed a literature search via online databases such as PubMed/MEDLINE and Google Scholar from December 2019-August 2022. The data from various studies and review articles have been included. Results: Current evidence suggests the occurrence of new-onset hypertension and new onset type 2 diabetes in patients infected with the SARS-CoV-2 virus. Data also indicate a higher risk of negative outcomes in these patients. Conclusions: It is evident that the tenacity of these new-onset diseases post-COVID-19 is likely to have huge implications in terms of unexpected morbidity. Therefore, screening and follow-up of these patients seems reasonable. Clinicians shall have to deal with this evolving challenge and adequately equip themselves to address this facet of COVID-19 as well. Further data from various follow-up studies and registries like the CoviDIAB Project is required to be better equipped to propose exact recommendations for patients with NOD. On the contrary, more evidence is required for incidence and long-term sequelae for patients with new-onset hypertension. How to cite this article: Gupta A, Duggal R. Incidence of New-onset Hypertension and New-onset Type 2 Diabetes during or after SARS-CoV-2 Infection. J Assoc Physicians India 2023;71(10):78-82.

Demographic, social and geographic factors associated with glycaemic control among US Veterans with new onset type 2 diabetes: a retrospective cohort study

ObjectivesThis study evaluated whether a range of demographic, social and geographic factors had an influence on glycaemic control longitudinally after an initial diagnosis of diabetes.Design, setting and participantsWe used the...

Analyzing characteristics of collateral flow to parasylvian cortical arteries by three-dimensional digital subtraction angiography-magnetic resonance angiography fusion imaging in adult moyamoya disease.

The hemodynamic sources of recipient parasylvian cortical arteries (PSCAs) were significantly related to postoperative cerebral hyperperfusion (CHP) after bypass surgery in patients with moyamoya disease (MMD). The present study aimed to introduce a new method to investigate the characteristics of PSCAs hemodynamic sources and their relationships with clinical presentations in adult MMD and to provide preoperative evaluation for recipient vessel selection in MMD bypass surgery. The hemodynamic sources of the PSCAs in 171 symptomatic MMD hemispheres were analyzed by three-dimensional digital subtraction angiography (3D-DSA) combined with magnetic resonance angiography (MRA) fusion imaging. The spatial and temporal characteristics of the hemodynamic sources of the PSCAs and their associations with the patient's demographics, Suzuki stage, and initial onset type were investigated. Six major types of hemodynamic sources in the PSCAs were observed. There was a significant difference between the hemodynamic sources of the PSCAs above and below the SF (P < 0.001). With advancing Suzuki stages, collateral flow to the PSCAs above the SF from the internal carotid arteries (ICAs) significantly decreased, while the non-ICAs increased (P < 0.001). Multivariate analysis revealed that hemodynamic sources of the PSCAs above the SF were significantly associated with patients' initial onset type (P = 0.026). In MMD hemispheres, the hemodynamic sources of the PSCAs above the SF are more varied than those below the SF and present a typical conversion trend from ICAs to non-ICAs with advancing Suzuki stages. Analyzing the hemodynamic sources of the PSCAs can help in understanding the conversion pattern of compensatory vascular systems, predicting episodes in MMD, and preoperatively evaluating suitable recipient vessel selection for bypass surgery to avoid postoperative CHP.

The Incidence Rate, Microbiological Etiology, and Results of Treatments of Prosthetic Joint Infection following Total Knee Arthroplasty.

Periprosthetic joint infection (PJI) remains among the most challenging and costly complications. PJI rates vary from 0.39% to 3.9% after total knee arthroplasty (TKA). This study aimed to identify the causative microorganisms involved and to report our experience of subsequent treatment of PJI following over 7000 TKAs performed over 19 years. A retrospective study was conducted on 4547 patients (7019 cases) from March 2000 to September 2019. The incidence rate of PJI was 0.5%. Gram-positive bacteria accounted for 88.8% (n = 16) of the 18 cases, and S. aureus was the most commonly isolated pathogen (n = 7, 38.8%). There were six cases of MSSA and one case of MRSA. Streptococcus species (n = 7, 38.8%) also showed the same pattern. The CoNS species (n = 2, 11.1%) and Gram-negative bacteria (n = 1, 5.5%) were also reported. Candida species were isolated from 1 patient (5.5%). Successful I&D and implant retention (DAIR procedures) was achieved at the final follow-up in 19 patients (82.6%). The incidence of causative microorganisms was different for each PJI onset type. The overall infection rate of PJI was less than 1%. Although the success rate of DAIR procedures is lower than the two-stage exchange arthroplasty in this study, it is possible to achieve acceptable success rates if DAIR procedures are carefully selected considering the virulence of the microorganism, duration since symptom onset, and early-onset infection.

Assessment of the detection accuracy of SARS-CoV-2 rapid antigen test in children and adolescents: An updated meta-analysis.

Real-time and appropriate antigen tests play a pivotal role in preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, a previous meta-analysis reported that the antigen test had lower sensitivity for the detection of SARS-CoV-2 in children. To provide a comprehensive evaluation of diagnostic efficiency, we performed an updated meta-analysis to assess the detection accuracy of SARS-CoV-2 antigen tests stratified by days after symptom onset and specimen type in children and adolescents. We comprehensively searched for appropriate studies in the PubMed, Embase, and Cochrane Library databases. Studies on the diagnostic accuracy of antigen tests for SARS-CoV-2 in children and adolescents were included. The relevant data of the included studies were extracted to construct a 2 × 2 table on a per-patient basis. The overall sensitivity and specificity of the SARS-CoV-2 antigen tests were estimated using a bivariate random-effects model. Seventeen studies enrolling 10,912 patients were included in the present meta-analysis. For the detection accuracy of SARS-CoV-2 antigen tests, the meta-analysis generated a pooled sensitivity of 77.9% (95% confidence interval (CI): 67.3-85.8%) and a pooled specificity of 99.6% (95% CI: 98.9-99.8%). The subgroup analysis of studies that examined antigen tests in symptomatic participants ≦7 days after symptom onset generated a pooled sensitivity of 79.4% (95% CI: 47.6-94.2%) and a pooled specificity of 99.4% (95% CI: 98.2-99.8%). Another subgroup analysis of studies that evaluated nasal swab specimens demonstrated a pooled sensitivity of 80.1% (95% CI: 65.0-89.7%) and a pooled specificity of 98.5% (95% CI: 97.3-99.2%). Our findings demonstrated that the antigen test performed using nasal swab specimens exhibited high sensitivity for the detection of SARS-CoV-2 within 7 days after symptom onset. Therefore, antigen testing using nasal swabs may be effective in blocking SARS-CoV-2 transmission in children.

Analysis of clinicopathologic characteristics and prognosis of gastric cancer in patients

An increase trend and a bad prognosis toward gastric cancer (GC) in individuals <40 years have been observed over the past few decades. GC in Young adult needs further evaluation to identify clear risk factors for early screening and better prognosis. A total of 126 young adult patients with gastric cancer (individuals <40 years) (YG) were collected in Liaocheng hospital in China from Jan 2003 to Dec 2019. The overall median follow-up was 96.5 months (rang 1-192 months). Survival was determined by the Kaplan-Meier method and the difference in survival among different subgroups were assessed using the log-lank test. Correlations between risk factors and overall survival were assessed by univariate and multivariate Cox proportional hazards regression analysis. Advanced stage cancer at onset and undifferentiated histologic tumor type were the prominent clinicopathological features of YG. The 5-year overall survival of the YG was 31.7%. The 5-year survival of the YG differed from tumor staging and treatment methods. The 5-year survival was 100% in stage I group, 58.8% in stage II group, 22.6% in stage III group, and 8.3% in stage IV group respectively. The 5-year survival was 52.1% in the curative resection group versus 3.8% in the non-curative resection group. Multivariate analysis displayed that tumor staging (P = .002) and treatment method (P = .034) were 2 independent prognostic predictors for survival. GC in young adult patients have unique clinicopathological features. Upper gastrointestinal endoscopy should regularly perform for young adult especially those symptomatic patients. Early diagnosis and then proceed to a successful curative resection are vital for a better prognosis.

The Effect of the SARS-CoV-2 Pandemic on Presentation with Diabetic Ketoacidosis in Children with New Onset Type 1 Diabetes Mellitus

Diabetic ketoacidosis (DKA) is a life-threatening, acute complication of type 1 diabetes mellitus (T1DM). Infection is the most common precipitating factor for DKA, being responsible for more than 50% of such complications. The frequency and severity of DKA in children with T1DM, before and during the coronavirus disease 2019 outbreak were evaluated and compared with pre-pandemic presentation and severity rates. In total, 199 patients younger than 18 years were included in the study. Patients were divided into two groups: the Coronavirus disease-2019 (COVID-19) pandemic group (new onset T1DM presenting from March 2020 to March 2021; the control group included new onset T1DM from March 2016 to March 2020. The rate of DKA at presentation was similar (p=0.393) during the pandemic period (58.3%) compared to the pre-pandemic years (44.8-64.3%). Although the percentage of DKA was similar, the rate of severe DKA in the COVID-19 group was higher than previous years. Although not significant, the duration of diabetes symptoms was longer in the COVID-19 period than the previous years. This study suggests that the rate of severe DKA, but not the overall rate of DKA, has increased during the COVID-19 pandemic compared to the prior four years. This may be due to the behavior of the parents of sick children and the limited access to the healthcare system. Despite this limited access, parental concern may have been sufficiently high to seek medical attention for their children, avoiding an increased frequency of DKA as the first presentation of new-onset T1DM.

A self-management plus mind body intervention for adolescents and young adults with type 2 diabetes: Trial design and methodological report

BackgroundThe onset of type 2 diabetes (T2D) is increasingly common in adolescents and young adults (AYAs). Improving self-management skills and the mental health of this population is important, but understudied. MethodsThe goal of this research was to develop a mind-body intervention which could serve as an adjunctive therapy to support AYAs with T2D (INTEND intervention). Toward that end, we used an iterative process, including use of focus groups, advisory board, and cognitive semi-structured interviews with patients, parents of patient and clinical providers, to understand the gaps in the current information provided to AYAs with T2D. Based on the data gathered from the focus groups and interviews, we enhanced an existing self-management intervention for adults with T2D to include an additional mind body intervention for AYAs with T2D. The INTEND intervention will be piloted in a group of AYAs with T2D. ResultsThis report describes the methodology and design of the InterveNTion for Early oNset type 2 Diabetes (INTEND) study. The details of this single arm pre-post pilot feasibility trial are described. DiscussionIf successful, the INTEND approach has the potential to advance care for vulnerable youth with T2D.

Typing myalgic encephalomyelitis by infection at onset: A DecodeME study.

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Detailed questionnaire responses from UK-based participants who all reported being diagnosed with ME/CFS by a health professional provided an unparalleled opportunity to investigate, using logistic regression, whether ME/CFS severity or onset type is significantly associated with sex, age, illness duration, comorbid conditions or symptoms. The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females tend to have more comorbidities than males. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia. DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.

Is COVID-19 incriminated in new onset type 2 diabetes mellitus in Lebanese adults?

BackgroundThe effects of COVID-19 on the organism are still being investigated, especially after the transformation of this virus from a respiratory disease in its first appearance to a multi-organ disease that can affect nearly all systems and organs including the endocrinological system. The objective of the study was to find an association between COVID-19 infection and new onset type 2 diabetes in Lebanese adults.MethodsA retrospective case–control study (2019–2022) included 200 subjects, 100 cases with new onset diabetes and 100 controls recruited from endocrinology clinics in rural and suburban located regions of Lebanon. Univariate and multivariate logistic regression were performed.ResultsOlder age (aOR = 1.07; 95% CI 1.03–1.12), higher BMI (aOR = 1.32; 95% CI 1.17–1.48), having been infected with COVID-19 (aOR = 2.38; 95% CI 1.001–5.68) and having a family history of diabetes (aOR = 11.80; 95% CI 4.23–32.87) were significantly associated with higher odds of having new onset type 2 diabetes after adjusting for multiple risk factors.ConclusionIn addition to the traditional risk factors for developing type 2 diabetes, a recent COVID-19 infection was associated with the new onset DM in our study. Subsequently screening for diabetes should be strongly recommended for patients post COVID-19 infection.

Impact of youth onset type 2 diabetes during pregnancy on microvascular and cardiac outcomes

AimsTo examine the impact of pregnancy on microvascular and cardiovascular measures in women with youth-onset T2D. MethodsMicrovascular and cardiovascular measures were compared in in a cohort of 116 women who experienced a pregnancy of ≥ 20 weeks gestation and 291 women who did not among women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. ResultsCox regression models adjusted for participant characteristics at baseline including age, race/ethnicity, household income, diabetes duration, HbA1c (>6%), and BMI, demonstrated those who experienced pregnancy had 2.76 (1.38–5.49; p = 0.004) fold increased risk of hyperfiltration (eGFR ≥ 135 ml/min/1.73 m2), compared to those without a pregnancy. No differences were observed in rates of retinopathy (48.9% vs. 41.1%) or neuropathy (23.3% vs. 16.3%) in women who experienced pregnancy vs. women who did not, respectively. In fully adjusted models, pregnancy did not impact changes in echocardiographic or arterial stiffness compared to changes in women who were never pregnant. ConclusionsThese results indicate that pregnancy increases the risk of hyperfiltration in women with youth-onset T2D, but not other micro or macrovascular complications. The rates of vascular complications are very high in youth-onset T2D potentially obscuring micro- and macrovascular changes attributable to pregnancy.Clinical Trial Information: ClinicalTrials.gov numbers,NCT01364350andNCT02310724.

Genotype-phenotype correlation of WT1 mutation-related nephropathy in Chinese children.

This study aimed to analyze the clinical characteristics of nephropathy associated with WT1 gene mutations in Chinese children and explore the relationship between genotype and clinical phenotype. Cases diagnosed at the Guangzhou Women and Children's Medical Center, were combined with those retrieved from PubMed and China National Knowledge Infrastructure (CNKI) databases from January 2015 to June 2022 and integrated into a study cohort; grouped according to gene mutation sites, clinical phenotype, and renal pathological types. The clinical characteristics between groups were compared, and the relationship between genotype and age of onset, clinical phenotype, and pathological type were retrospectively analyzed. The center enrolled 15 confirmed children: seven cases of non-simple nephropathy, including Denys-Drash syndrome (DDS) and Frasier syndrome (FS); eight cases of isolated steroid-resistant nephrotic syndrome (ISRNS); and 13 cases (86.7%) that progressed to end-stage renal disease (ESRD). The initial hemoglobin and bicarbonate levels of patients with clinical non-simple nephropathy were significantly lower than those with simple nephropathy, whereas the serum creatinine levels were higher than those of patients with simple nephropathy. A total of 75 cases of nephropathy associated with WT1 mutations in the study cohort met the inclusion and exclusion criteria. The most common clinical manifestations of WT1 mutations in this cohort were DDS (29/75, 38.7%) and ISRNS (37/75, 49.3%). A renal biopsy was performed in 43 patients, and the common types of renal pathology were focal segmental glomerulosclerosis (23/43, 53.5%) and DMS (13/43, 30.2%). Within the cohort, there were 12 cases (16.0%) in the exon 8 mutation group, 32 (42.6%) in the exon 9 group, 19 (25.3%) in the intron 9 group, and 12 (16.0%) in other gene site mutation groups. Common sites of WT1 mutations in Chinese children were exons 9 and intron 9. Exon 8 mutations were uniquely correlated with the age of onset within three months [5/7; 71.4%; Adjusted standardized residual (AR) = 4.2]. The renal survival time in the exon 8 mutation group was the shortest (P = 0.003). The molecular and biological characteristics of WT1 mutation-related nephropathy determine the clinical type, pathological features, and renal survival time of the disease; and there was a strong correlation between the genotype and clinical phenotype.

Typing myalgic encephalomyelitis by infection at onset: A DecodeME study

Background: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Detailed questionnaire responses from UK-based participants who all reported being diagnosed with ME/CFS by a health professional provided an unparalleled opportunity to investigate, using logistic regression, whether ME/CFS severity or onset type is significantly associated with sex, age, illness duration, comorbid conditions or symptoms. Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females tend to have more comorbidities than males. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia. Conclusions: DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.

Nomogram to Predict Good Neoangiogenesis After Indirect Revascularization Surgery in Patients with Moyamoya Disease: a Case-control Study.

Indirect bypass surgery is an effective treatment for moyamoya disease (MMD), but the success of the surgery depends on the formation of spontaneous collateral vessels, which cannot be accurately predicted before surgery. Developing a prediction nomogram model for neoangiogenesis in patients after indirect revascularization surgery can aid surgeons in identifying suitable candidates for indirect revascularization surgery. This retrospective observational study enrolled patients with MMD who underwent indirect bypass surgery from a multicenter cohort between December 2010 and December 2018. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis identifying potential predictors of good neoangiogenesis. A total of 263 hemispheres of 241 patients (mean ± SD age 24.38 ± 15.78years, range 1-61years) were reviewed, including 168 (63.9%) hemispheres with good postoperative collateral formation and 95 (36.1%) with poor postoperative collateral formation. Based on multivariate analysis, a nomogram was formulated incorporating four predictors, including age at operation, abundance of ICA moyamoya vessels, onset type, and Suzuki stage. The C-index for this nomogram was 0.80. Calibration curve and decision-making analysis validated the fitness and clinical application value of this nomogram. The nomogram developed in this study exhibits high accuracy in predicting good neoangiogenesis after indirect revascularization surgery in MMD patients. This model can be very helpful for clinicians when making decisions about surgical strategies for MMD patients in clinical practice.

Diagnosis and Management of Late-Onset Pompe Disease

Pompe disease is a lysosomal storage disorder, with onset between the first weeks after birth and adulthood, depending on its phenotype. It can affect multiple organ systems and presents itself with a wide variety of symptoms. Thus, recognizing Pompe disease is difficult. Especially since enzyme replacement therapy for Pompe disease was introduced (in Germany in 2006), early diagnosis by means of enzyme activity determination from dried blood spot analysis and genetic verification has become important for outcome and quality of life. When facing an obscure muscular disorder, it is crucial to consider Pompe disease. This article provides an overview about Pompe disease and focuses on the diagnosis of the late onset type. The most important aspects of interdiciplinary care for patients with Pompe disease are presented. Additionally, it contains a section focusing on psychosocial challenges for children with Pompe disease and their families, which may include mental disorders and social retreat, and gives advice on how to support parents of affected children.

The role of diet in multiple sclerosis onset and course: results from a nationwide retrospective birth-year cohort.

To examine (1) the association between childhood diet and developing MS, age of onset and onset type and (2) the association between diet at age 50 and disability and MRI volumes in people with MS (PwMS). The study enrolled 361 PwMS born in 1966 and 125 age- and sex-matched healthy controls (HCs). Information on individual dietary components (fruit, vegetables, red meat, oily fish, whole-grain bread and candy, snacks and fast food) and MS risk factors at the age of 10 and 50 years were collected using questionnaires. Overall diet quality score was calculated for each participant. Multivariable regression analyses were used to evaluate the association between diet at childhood and developing MS, age of onset and onset type and to evaluate diet at age 50, disability and MRI outcomes. Poorer overall diet quality and individual dietary components during childhood (less whole-grain bread, more candy, snacks and fast food and oily fish) were associated with developing MS and onset type (all p < 0.05), but not with the age of onset. Fruit consumption at age 50 was associated with lower disability (Q3 vs. Q1: -0.51; 95% CI: -0.89 to -0.13). Furthermore, several individual dietary components at age 50 were associated with MRI volumetric measures. Higher-diet quality at age 50 was only associated with lower lesion volumes in PwMS (Q2 vs. Q1: -0.3 mL; 95% CI: -0.5 to -0.02). We demonstrate significant associations between dietary factors in childhood and developing MS, age of onset and onset type and between dietary factors at age 50 and disability and MRI-derived volumes.

Increased tissue modulus and hardness in the TallyHO mouse model of early onset type 2 diabetes mellitus.

Individuals with type 2 diabetes mellitus (T2DM) have a higher fracture risk compared to those without T2DM despite having higher bone mineral density (BMD). Thus, T2DM may alter other aspects of resistance to fracture beyond BMD such as bone geometry, microarchitecture, and tissue material properties. We characterized the skeletal phenotype and assessed the effects of hyperglycemia on bone tissue mechanical and compositional properties in the TallyHO mouse model of early-onset T2DM using nanoindentation and Raman spectroscopy. Femurs and tibias were harvested from male TallyHO and C57Bl/6J mice at 26 weeks of age. The minimum moment of inertia assessed by micro-computed tomography was smaller (-26%) and cortical porosity was greater (+490%) in TallyHO femora compared to controls. In three-point bending tests to failure, the femoral ultimate moment and stiffness did not differ but post-yield displacement was lower (-35%) in the TallyHO mice relative to that in C57Bl/6J age-matched controls after adjusting for body mass. The cortical bone in the tibia of TallyHO mice was stiffer and harder, as indicated by greater mean tissue nanoindentation modulus (+22%) and hardness (+22%) compared to controls. Raman spectroscopic mineral:matrix ratio and crystallinity were greater in TallyHO tibiae than in C57Bl/6J tibiae (mineral:matrix +10%, p < 0.05; crystallinity +0.41%, p < 0.10). Our regression model indicated that greater values of crystallinity and collagen maturity were associated with reduced ductility observed in the femora of the TallyHO mice. The maintenance of structural stiffness and strength of TallyHO mouse femora despite reduced geometric resistance to bending could potentially be explained by increased tissue modulus and hardness, as observed at the tibia. Finally, with worsening glycemic control, tissue hardness and crystallinity increased, and bone ductility decreased in TallyHO mice. Our study suggests that these material factors may be sentinels of bone embrittlement in adolescents with T2DM.

The association between weight during early life and multiple sclerosis onset in a nationwide Dutch birth year cohort

ABSTRACT Background The relationship between being overweight during early life and disease course in multiple sclerosis (MS) is unresolved. We investigated the association between being overweight or obese during early life (childhood and adolescence) and MS case status, age of first symptom onset and onset type in people with MS (pwMS) of the same birth year. Methods We enrolled 363 PwMS and 125 healthy controls (HC) from Project Y, a Dutch population-based cross-sectional cohort study including all PwMS born in 1966 and age and sex-matched HC. The associations between weight during childhood and adolescence (non-overweight vs. overweight or obese) and MS, age at symptom onset and onset type (relapsing vs. progressive) were assessed using logistic and linear regressions. In addition, sex-separated associations were explored. Results Being overweight or obese during childhood (OR = 2.82, 95% CI 1.17–6.80) and adolescence (OR = 2.45, 95% CI 1.13–5.34) was associated with developing MS. Furthermore, being overweight or obese during adolescence was associated with a younger age of onset (β = −0.11, p = 0.041). Of all 47 patients with a primary progressive (PP) onset type, only one patient (2.1%) was overweight or obese during childhood, whereas 45 patients with a relapsing remitting (RR) onset (14.3%) were overweight or obese during childhood (PP vs. RR p = 0.017; PP vs. HC p = 0.676; RR vs. HC, p = 0.015). However, using logistic regression analysis we did not find evidence of a significant association. Conclusion In a nationwide population-based birth year cohort, being overweight or obese during childhood or adolescence is associated with MS prevalence and an earlier age of onset, but does not seem to associate with the type of onset.