Clinical Disease Research Articles

Severe clinical phenotypes of heterozygous females with X-linked chronic granulomatous disease

Female X-linked chronic granulomatous disease (XL-CGD) carriers may develop severe clinical disease including infections with CGD-defining pathogens and inflammatory disorders. Similar to males with XL-CGD, female carriers warrant ongoing evaluation and prophylaxis where indicated.

A Rapid, Sensitive, and High-throughput Method for the Simultaneous Determination of Antihypertensive Drug Combinations in Dog Plasma by UHPLC-MS/MS: The Assessment of Predicable Bioequivalence of In-vitro Dissolution Condition.

Essential hypertension is a common clinical disease and a risk factor for cardiovascular and cerebrovascular diseases. Olmesartan medoxomil, amlodipine, and hydrochlorothiazide are commonly used antihypertensive drugs. The aim of this study was to establish a robust UPLC-MS/MS method for the simultaneous determination of olmesartan medoxomil, amlodipine, and hydrochlorothiazide in dog plasma. At the same time, the in vivo and in vitro release studies were conducted, and a preliminary in vitro-in vivo correlation (IVIVC) evaluation was performed. The bioequivalence experiment was conducted with a double-crossed design. Three major components were extracted and analyzed by UHPLC-MS/MS. With the MRM scan, olmesartan and amlodipine were quantified by fragment conversion (m/z 447.10→190.10) and (m/z 408.95→294.00) under positive ESI mode, while hydrochlorothiazide was quantified with fragment conversion (m/z 295.90→268.90) under negative ESI mode. The in vitro release studies were performed using a USP paddle, and the dissolution medium was chosen from pH 6.0 to pH 6.8 according to the BCS classification of compounds. The IVIVC was calculated using the Wagner-Nelson equation. The linear ranges of olmesartan, amlodipine, and hydrochlorothiazide in the plasma were 5.0-2500, 0.1-50, and 3.0-1500 ng/mL, respectively. All accuracies were within 3.8% of the target values, and the findings revealed that intra-day and inter-day accuracies were less than 12.1%. Moreover, the recoveries exceeded 88.3%, the matrix effect tests were positive, and the stability tests were positive. With the establishment of correlation, the distinguishable dissolution condition (pH 6.8) was selected as the predictable condition. The established method was suitable for the preclinical pharmacokinetic study of tripartite drugs with strong specificity and high sensitivity. Through the evaluation of IVIVC, the connection between in vivo and in vitro drug testing was initially established.

The Association between the Response to Rituximab with Sociodemographic Data and Disease Characteristics Among a Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Rituximab (RTX), a monoclonal antibody with anti-CD20 action, is now used as a treatment. Even with proper RTX use, some patients showed variations in response. Objective: To assess the association of different sociodemographic data and disease characteristics with RTX responsiveness in RA patients. Methods: A cross-sectional study was conducted in the Specialized Center of Rheumatology at Baghdad Teaching Hospital in Baghdad, Iraq. The study included 90 RA patients who received a 1000mg RTX intravenous infusion for at least six months. The collected sociodemographic data included age, gender, smoking status, body mass index (BMI), disease characteristics such as co-morbidities, and the use of previous biological agents. The activity of RA was assessed by the 28-joint Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI). Results: Upon measuring the DAS28, the enrolled patients were divided into RTX responders (50 patients) and RTX non-responders (40 patients). Patients with a family history of RA were significantly higher in the RTX responders (21% versus 2% in the non-responders group). The responders had a significantly longer RA duration (p=0.030).The mean of CDAI and DAS28 were significantly higher in patients with no family history of RA than in those with a family history of RA. Conclusions: Disease duration, family history, and the use of previous biological agents could be considered as possible predictors of response to RTX, thereby saving time and treatment costs.

Janus kinase inhibitors versus tumor necrosis factor inhibitors in rheumatoid arthritis: meta-analytical comparison of efficacy and safety.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by persistent inflammation leading to progressively worse disability. Janus kinase (JAK) inhibitors and tumor necrosis factor (TNF) inhibitors are pivotal in RA treatment, yet their comparative efficacy remains underexplored. This study aimed to compare the efficacy and safety of JAK inhibitors and TNF inhibitors in treating RA using data from randomized controlled trials (RCTs). A meta-analysis and outcomes analysis were based on results of the Health Assessment Questionnaire Disability Index (HAQ-DI), Clinical Disease Activity Index (CDAI), Visual Analogue Scale (VAS), and Patient Global Assessment Scale (PtGA) and other indices as incidences of venous thromboembolism (VTE) and malignancy. The JAK inhibitors caused a statistically significant improvement in the HAQ-DI score [MD = 0.08, 95% CI (0.03, 0.12), p = 0.0008] compared with the TNF inhibitors. However, no significant difference was observed between the two drug classes in the CDAI score [MD = -2.03, 95% CI (-9.27, 5.22), p = 0.58]. JAK inhibitors were associated with an increase in the VAS score [MD = 3.62, 95% CI (0.86, 6.38), p = 0.01], but there was no significant difference in the PtGA score [MD = 1.91, 95% CI (-3.25, 7.08), p = 0.47]. JAK inhibitors demonstrated superior efficacy in improving the functional status and reducing the disease activity in RA patients compared with TNF inhibitors. Both drug classes exhibited comparable safety profiles for VTE and malignancies, though JAK inhibitors had a higher risk for thromboembolism.

The change over time in the prescription pattern of the first targeted drug after failure of conventional therapy in patients with rheumatoid arthritis: a 20-year real-world experience.

To evaluate the change over time in the pattern of the first biologic/targeted synthetic drug (b/tsDMARD) prescription and baseline characteristics in patients with rheumatoid arthritis (RA) from 1999 to the present. A retrospective data analysis from RA patients enrolled in an Italian single-center registry was conducted. The analysis was limited to all the patients who received the first b/tsDMARD between October 1999 and December 2022. Patients were stratified according to the date of b/tsDMARD initiation into 4 groups (1999-2004, 2005-2010, 2011-2016, and 2017-2022) and a comparative analysis of prescription patterns and patients' baseline characteristics was performed. The study population included 1206 patients. The characteristics of patients at baseline in the 4 groups were similar overall, with the exception of disease duration (12.26, 10.5, 9.7, 8.1 years, respectively; p<0.0001), mean number of conventional DMARDs used before the first b/tsDMARD (3, 2.5, 2.1, 1.4, respectively; p<0.0001), and mean clinical disease activity index (CDAI) score (30.1, 24.3, 21.8, 20.4, respectively; p<0.0001). A progressive reduction (from 95 to 43% of patients) in the prescription of first-line TNF-α inhibitors toward other mechanisms of action has been observed. The rate of patients treated with b/tsDMARDs as monotherapy progressively increased (from 18 to 26%) especially among those not receiving a TNFα inhibitor. The expansion of the therapeutic armamentarium has changed the management strategy of RA over time towards an earlier introduction of targeted drugs (increasingly often as monotherapy) in patients with progressive lower disease activity and a history of failure with fewer previous conventional drugs.

Donor-derived bartonellosis in solid organ transplant recipients from unhoused donors in Alberta

Bartonella quintana infection is rarely described to be transmitted through solid organ transplant (SOT). We report a cluster of using donor-derived B quintana infection and the attack rate from Bartonella seropositive donors. In this retrospective study of SOT recipients that received an organ from an unhoused deceased donor (UDD) in Alberta in 2022-2023, serology testing for Bartonella was performed indirect immunofluorescent assay on UDDs and recipients of UDDs with positive serology. Titers ≥1:64 were considered positive. During the study period, 31/32 UDDs were tested for immunoglobulin G to Bartonella (20 negative, 11 positive for B quintana and/or B henselae). Thirty-two organs were transplanted from the 11 seropositive donors. Six SOT recipients developed bartonellosis secondary to B quintana (4 SOT recipients received organs from 3 seropositive donors, and 2 SOT recipients from 1 UDD with no stored sample for testing). The attack rate for clinical disease from positive donors was 12.5% (4/32). The main presentation was skin nodules/papules (median 5.5 months) with bacillary angiomatosis in 4/6. Bartonella serology was positive in 5/6 SOT recipients (initially negative in 2) and blood B quintana quantitative polymerase chain reaction in 1. None had visceral involvement. All donors had history of substance use. This outbreak of bartonellosis reinforces the potential for unexpected donor-transmitted infections. Clinicians should be aware of high transmission of B quintana through transplant from infected UDDs.

Pediatric parkinsonism: In-depth clinical definition and semeiology

Pediatric parkinsonism: In-depth clinical definition and semeiology

Ultra-Processed Foods Consumption Is Positively Associated with the Clinical Activity of Inflammatory Bowel Diseases: A Cross-Sectional Single-Center Study

Introduction: Western diet pattern and its food components have been suggested to impact inflammatory bowel diseases (IBDs) clinical course. However, the importance of food processing level is uncertain. We aimed to evaluate whether the intake of foods with varying processing levels is associated with disease activity in IBD patients. Methods: This cross-sectional study was performed at a tertiary center between August 2019 and June 2022. Consecutive adult IBD patients were recruited. Clinical disease activity was defined using HBI (Crohn’s disease) and SCCAI (ulcerative colitis). Dietary intake was assessed using a food frequency questionnaire (FFQ) and a dedicated validated processed food questionnaire (PFQ) that categorizes dietary intake into three groups of processed food levels: unprocessed/minimally processed, processed, and ultra-processed. Adjusted odds ratios for active disease were determined using a multivariable logistic regression. Results: A total of 242 IBD patients (62.8% Crohn’s disease patients) were enrolled, of whom 73.1% were in clinical remission. A higher (upper tertile vs. lowest tertile) unprocessed/minimally processed foods consumption was negatively associated with active disease (OR = 0.38, 95% CI: 0.14–0.99), while high consumption of ultra-processed foods (UPFs) was positively associated with clinically active disease (OR = 3.82, 95% CI: 1.49–9.8). Consumption of UPF groups, almost invariably, was positively associated with clinically active disease, while consumption of the ultra-processed meats group had the strongest association (OR = 4.45, 95% CI: 2.07–9.79). Conclusion: Higher consumption of UPFs is positively associated with clinically active IBD, while higher consumption of unprocessed/minimally processed foods may be protective. Prospective studies are needed to confirm these associations.

Accuracy of GynTect® Methylation Markers to Detect Recurrent Disease in Patients Treated for CIN3: A Proof-of-Concept Case-Control Study.

Post-treatment follow-up in women with CIN3 is mandatory due to relapse in up to 15% of patients within 2 years. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our proof-of-concept case-control study was to evaluate the performance of the methylation test GynTect® for the detection of recurrent CIN2/3 during follow-up. Residual clinical material from a recent, prospective, multicenter, observational study was available for further analysis. We studied a sample of 17 cases with recurrent CIN2/3 diagnosed within 24 months of follow-up and 31 controls without recurrence. DNA from cervical scrapes at baseline (immediately before CIN3 surgery) and up to three follow-up visits were analyzed for hrHPV and GynTect® methylation status. Cytology data were available from the previous study. Overall, 12 cases and 21 controls were GynTect-positive at baseline. In these subgroups, single test sensitivity at first follow-up was 67% (95% CI 39-87%) for GynTect® compared to 83% (95% CI 55-96%) for hrHPV (p = 0.50). Single test specificity was significantly higher for GynTect® (90%, 95% CI 71-98% vs. 62%, 95% CI 40-80%) (p = 0.03). In a co-testing setting, both hrHPV/cytology and GynTect®/cytology detected all recurrences. Specificity for GynTect®/cytology was higher than for hrHPV/cytology, but this difference was not statistically significant. In conclusion, for initially GynTect-positive patients, both hrHPV and GynTect® tests detected recurrent disease with similar sensitivity, but the GynTect® assay has a higher specificity. Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect®/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance.

Enhancing Liver Disease Detection and Management with Advanced Machine Learning Models

The prevalence of hearing loss has risen making it a significant public health issue. Hearing loss is caused by complicated pathophysiological pathways, with various risk factors identified, such as hereditary factors, inflammatory processes, systemic disorders, noise exposure, medicines, oxidative stress, and age. Metabolic syndrome is a medical condition characterized by the presence of hypertension, central obesity, hyperlipidemia, and diabetes. Metabolic syndrome has been linked to several clinical diseases, such as stroke, heart attack, cardiovascular disease-related death, and diabetes. A cross-sectional study was done on 100 patients with metabolic syndrome which used specific cut-off points of waist circumference, fasting glucose levels, blood pressure, triglyceride, and high-density lipoprotein cholesterol levels to diagnose the condition. Among these five criteria, at least three had to be met, and the presence of additional criteria indicated greater severity. Audiological evaluation with pure tone audiometry was done and recorded. Statistical analysis was performed to determine the significance of the results. The majority of the patients (62%) had unilateral hearing loss, amongst which sensory-neural type and moderately severe hearing loss were the most common type (67%) and severity (61%) of hearing loss respectively. Chi-square tests were done for the comparison of type, severity, and laterality of hearing loss with age, gender of the patients, and criteria fulfilled for metabolic syndrome. The severity of hearing loss had a statistically significant association with the age of the patients and the number of criteria fulfilled for metabolic syndrome with a p-value of 0.003. There was a statistically significant association between the severity of hearing loss and the age of the patients and the number of criteria fulfilled for metabolic syndrome with a p-value of 0.004. Metabolic syndrome affects the auditory system in several ways. It damages hearing and exacerbates presbycusis. Hearing loss worsens as components of the metabolic syndrome increase.

Directed differentiation of human embryonic stem cells into conjunctival epithelial cells

Severe conjunctival damage can lead to extensive ocular cicatrisation, fornix shortening, and even ocular surface failure, resulting in significant vision impairment. Conjunctival reconstruction is the primary therapeutic strategy for these clinical conjunctival diseases. However, there have been limited studies on induced differentiation of conjunctival epithelial cells derived from stem cells. In this study, we established a chemical defined differentiation protocol from human embryonic stem cells (hESCs) into conjunctival epithelial cells. hES cell line H1 was used for differentiation, and RT-qPCR, immunofluorescence staining, Periodic-acid-Schiff staining (PAS), and transcriptome analysis were employed to identify the differentiated cells. Here, to imitate the development of the vertebrate conjunctiva, hESCs were induced using a three-step process involving first chetomin was used to induce ocular surface ectoderm, then nicotinamide was used to induce ocular surface epithelial progenitor cells, and finally epidermal growth factor, keratinocyte growth factor and other factors were used to differentiate mature conjunctival epithelial cells. hESC-derived conjunctival epithelial cells expressed mature conjunctival epithelial lineage markers (including PAX6, P63, K13). The presence of goblet cells was confirmed by positive PAS. Transcriptome analysis revealed that hESC-derived conjunctival epithelial cells possessed a more naïve phenotype, and exhibited greater proliferation capacity compared to mature human conjunctival epithelial cells, suggesting their potential as alternative seed cells for conjunctival reconstruction.

Disease Damage in Juvenile Idiopathic Arthritis.

To estimate the prevalence and predictors of disease-related damage in children with juvenile idiopathic arthritis (JIA) in a resource-limited setting. A single-centre study was conducted from January 2021 - December 2022. Children (≤ 18 y) diagnosed with JIA as per International League of Associations for Rheumatology (ILAR) criteria, with a disease duration of more than one year, were enrolled for this study. The articular and extra-articular damage was assessed using the juvenile arthritis damage index (JADI) and modified JADI scores. Disease activity and disabilities were evaluated using the clinical juvenile arthritis disease activity score (cJADAS) and Childhood Health Assessment Questionnaire (CHAQ). One hundred and five children [44% (n = 42) boys] with JIA were enrolled in the study. The mean (SD) age of children at enrolment was 158 (46.2) mo. The median (IQR) disease duration was 48 (36-72) mo. Articular damage (JADI score ≥ 1) was present in 48.6%, and extra-articular damage (JADI-E ≥ 1) was observed in 21.9% of children. Half of the children (n = 22) with enthesitis-related arthritis (ERA) had joint damage (modified JADI score ≥ 1). Four children had ocular damage due to uveitis. Among the factors associated with articular damage, the odds of articular damage were high in those with positive rheumatoid factor (RF) and/ or anti-cyclic citrullinated peptides (CCPs) [OR: 4.4, 95% CI (1.00-19.60)]. 48.6% of children with JIA had articular damage, while 21.9% of the children had extra-articular damage. Children with RF and/ or anti-CCP positivity are associated with higher odds of joint damage.

Relationships of mitochondrial DNA mutations and select clinical diagnoses in perinatally HIV- and ART-exposed uninfected children

The prevalence of pathogenic mutations within mitochondrial (mt) DNA of youth who were perinatally exposed to HIV and ART but remained uninfected (YHEU) were assessed relative to phenotypic clinical indicators of mitochondrial dysfunction (MtD). This was a cross-sectional, nested case-control study. A total of 144 cases met at least one clinical MtD definition and were matched with up to two controls each (n = 287). At least one risk mutation was present in nearly all YHEU (97 %). No differences in mutation frequencies were observed between metabolic or neurodevelopmental cases and respective controls; however, higher frequencies were found in controls versus respective neurologic or growth cases.

Post COVID-19 conditions in an Australian pediatric cohort, 3 months following a Delta outbreak.

Pediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents. The parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment. 1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID. During an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention. Our study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity.

Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study

Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics. For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (Ro) estimates. Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall Ro was 1·25. Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low Ro. Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control. None.

DUSP5 deficiency suppresses the progression of acute kidney injury by enhancing autophagy through AMPK/ULK1 pathway

Acute kidney injury (AKI) represents a critical clinical disease characterized by the rapid decline in renal function, carrying a substantial burden of morbidity and mortality. The treatment of AKI is frequently limited by its variable clinical presentations and intricate pathophysiology, highlighting the urgent need for a deeper understanding of its pathogenesis and potential therapeutic targets. Dual-specific protein phosphatase 5 (DUSP5), a member of the serine-threonine phosphatase family, possesses the capability to dephosphorylate extracellular regulated protein kinases (ERK). DUSP5 has emerged as a pivotal player in modulating metabolic signals, inflammatory responses, and cancer progression, while also being closely associated with various kidney diseases. This study systematically scrutinized the function and mechanism of DUSP5 in AKI for the first time, unveiling a substantial increase in DUSP5 expression during AKI. Moreover, DUSP5 knockdown was observed to attenuate the production of inflammatory factors and apoptotic cells in renal tubular epithelial cells by enhancing AMPK/ULK1-mediated autophagy, thus improving renal function. In a word, DUSP5 knockdown in AKI effectively impede disease progression by activating autophagy. This finding holds promise for introducing fresh perspectives and targets for AKI treatment.

The long-term efficacy and safety of balloon dilation eustachian tuboplasty combined with tympanostomy tube insertion for patients with otitis media with effusion: study protocol for a prospective randomized controlled trial

BackgroundOtitis media with effusion (OME) is a common disease in ear, nose, and throat clinics characterized by aural fullness and hearing loss and mainly caused by eustachian tube dysfunction (ETD). Tympanostomy tube insertion (TTI) is a conventional surgical treatment option that can alleviate symptoms but does not provide a definitive cure, and it is prone to recurrence. Balloon dilation eustachian tuboplasty (BDET) has become a novel procedure for the treatment of ETD, demonstrating significant potential in addressing the aforementioned limitations. However, it is not widely available in the clinic and few high-quality randomized clinical trials was conducted to investigate its long-term efficacy and security in OME. Therefore, the purpose of this study is to verify the efficacy of BDET combined with TTI for patients with OME and its prospects for providing a definitive cure.Methods and analysisThis is a prospective, parallel-group, single-blind, randomized controlled prospective trial. Totally 124 patients with OME will be randomized into either group A or B. Group A will receive conventional therapy (TTI) while group B will use BDET therapy in addition to TTI. Outcome assessments will take place at baseline and at the 3rd, 6th, 12th, and 24th months after surgery. The primary outcome is eustachian tube function, which will be measured by the eustachian tube dysfunction questionnaire (ETDQ-7) and eustachian tube score (ETS). The secondary outcomes include middle ear function, hearing situation, and quality of life, which will be measured by acoustic impedance measurement, pure-tone audiometry, and Chinese-version Chronic Ear Survey (CCES). The main analysis of change in the outcomes will use mixed-model with repeated measures (MMRM) analyses of variance (ANOVAs).DiscussionThis is the first prospective trial in Chinese populations that aims to validate the long-term efficacy and safety of BDET-combined TTI therapy in patients with OME. This parallel-group, single-blind, randomized controlled trial may provide an opportunity to decrease the recurrence rate of OME and explore a definitive cure for patients with OME. This trial’s rigorous design enhances the reliability of the findings, ensuring a robust answer to the research question. In the future, the research team will further expand upon the clinical evidence and applications of the BDET combined therapy.Trial registrationChinese Clinical Trial Registry ChiCTR2400079632. Registered on 8 January 2024, https://www.chictr.org.cn/bin/project/edit?pid=214452.

Multiple sclerosis in Somali Americans: Nature or nurture?

BackgroundDifferences in the MS course between White and Black populations is well accepted. The existence of a large Somali immigrant population in Minnesota facilitates a study of MS characteristics in this immigrant native African population. The objective of this study was to compare Somali American (SA), African American (AA), and White American (WA) persons with MS (pwMS) regarding clinical features and disease modifying therapy (DMT) use. MethodsThis single center (Mayo Clinic) geographically-restricted retrospective cohort study (residing within 250 miles of Rochester, MN, USA) included participants seen before May 2023. Age at immigration to the USA; age at MS onset; DMT use/type; MS phase/phenotype; age at progressive MS (PMS) onset; and proportion with severe MS (expanded disability status scale-EDSS ≥6) were examined. Results18 SApwMS, 92 AApwMS, and 94 WApwMS were included. Of the 15 SApwMS not born in USA, 3/15 immigrated pre-puberty, 3/15 peri‑puberty, 8/15 post-puberty, and 1/15 at an unknown date. SApwMS were younger at MS onset (median years, interquartile range (IQR)=25, 22–33 vs. AApwMS: 31, 25–38; p = 0.049 vs. WApwMS: 35, 27–41; p = 0.022). DMT use frequencies were 13/19 SApwMS, 69/92 AApwMS, 80/94 WApwMS (p > 0.05). SApwMS were treated with DMT earlier than AApwMS (HR 2.16, p = 0.012) and WApwMS (HR 1.86, p = 0.041). SApwMS were less commonly treated with natalizumab (SApwMS 0 %, AApwMS 13 %, WApwMS 25 %; p = 0.035) and anti-CD20 therapies (SApwMS 23 %, AApwMS 23 %, WApwMS 48 %; p = 0.005). PMS occurred in 3/19 SApwMS, 28/92 AApwMS and 29/94 WApwMS (p > 0.05). Age of PMS onset in SApwMS (47 years, 34–57) was similar to WApwMS (47 years, 31–71; p > 0.05) but older than AApwMS (41 years, 18–7; p = 0.008). ConclusionsSApwMS that recently immigrated to the USA have similar disease course to WApwMS, and better than AApwMS from the same geographical region.

Clinical characteristics and long-term disease course in patients with Crohn's disease as diagnosed by video capsule endoscopy: a multicenter retrospective matched case-control study.

Video capsule endoscopy is rarely used to diagnose Crohn's disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases. This multicenter study included patients with Crohn's disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn's disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393-1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn's disease-related hospitalization, and surgeries (log-rank test P< 0.05). Patients with Crohn's disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.

Tracking the burden, distribution, and impact of Post-COVID conditions in diverse populations for children, adolescents, and adults (Track PCC): passive and active surveillance protocols

BackgroundTrack PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection).MethodsThe study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection.DiscussionThese data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients.