Multicenter Case-control Study Research Articles

The Predictors and Risk Factors of 2-Year Rejection in Renal Transplant Patients: A Multicenter Case-Control Study

Introduction: Kidney transplantation is a definitive treatment for end-stage renal disease. It is associated with improved life expectancy and quality of life. One of the most common complications following kidney transplantation is graft rejection. To our knowledge, no previous study has identified rejection risk factors in kidney transplant recipients in Saudi Arabia. Therefore, this study aimed to determine the specific risk factors of graft rejection. Methods: A multicenter case-control study was conducted at four transplant centers in Saudi Arabia. All adult patients who underwent a renal transplant between January 1, 2015 and December 31, 2021 were screened for eligibility. Included patients were categorized into two groups (cases and control) based on the occurrence of biopsy-proven rejection within 2 years. The primary outcome was to determine the risk factors for rejection within the 2 years of transplant. Exact matching was utilized using a 1:4 ratio based on patients’ age, gender, and transplant year. Results: Out of 1,320 screened renal transplant recipients, 816 patients were included. The overall prevalence of 2-year rejection was 13.9%. In bivariate analysis, deceased donor status, the presence of donor-specific antibody (DSA), intraoperative hypotension, Pseudomonas aeruginosa, Candida, and any infection within 2 years were linked with an increased risk of 2-year rejection. However, in the logistic regression analysis, the presence of DSA was identified as a significant risk for 2-year rejection (adjusted OR: 2.68; 95% CI: 1.10, 6.49, p = 0.03). Furthermore, blood infection, infected with Pseudomonas aeruginosa or BK virus within 2 years of transplant, were associated with higher odds of 2-year rejection (adjusted OR: 3.10; 95% CI: 1.48, 6.48, p = 0.003, adjusted OR: 3.23; 95% CI: 0.87, 11.97, p = 0.08 and adjusted OR: 2.76; 95% CI: 0.89, 8.48, p = 0.07, respectively). Conclusion: Our findings emphasize the need for appropriate prevention and management of infections following kidney transplantation to avoid more serious problems, such as rejection, which could significantly raise the likelihood of allograft failure and probably death. Further studies with larger sample sizes are needed to investigate the impact of serum chloride levels prior to transplant and intraoperative hypotension on the risk of graft rejection and failure.

Immunological alterations in patients with current and lifetime suicide ideation and attempts: Examining the relationship with depressive symptoms

BackgroundSuicidal ideation and attempt (SI/SA) have been associated with dysregulation of the immune response and inflammation. However, few studies have explored how innate and acquired cellular immunity impact on the peripheral immune response. Our study addresses this gap by examining the composition of peripheral immune cells and humoral markers among individuals with current SI/SA, individuals with a history of SI/SA, and healthy controls (HC). Additionally, we aim to explore whether depressive symptoms settle the relationship between inflammation and SI/SA. MethodsThis is a multicenter case-control study that included 105 participants. Clinical and demographic characterists together with hemogram parameters, soluble pro and anti-inflamatory factors, and specific innate and adaptive immune cell populations were compared among patients with current SI/SA (n = 21), a history of lifetime SI/SA (n = 42), and HC (n = 42). ResultsPatients with both current and lifetime SI/SA had a significant increase in the absolute count of monocytes and in the monocyte/lymphocyte ratio (MLR). Additionally, patients with current and lifetime SI/SA showed a significant increase in high-sensitivity C- reactive protein (hs-CRP), and patients with lifetime SI/SA also showed higher levels of Erythrocyte Sedimentation Rate (ESR). The cellular inflammatory status of patients with SI/SA was characterized by altered proportions of monocytes with higher levels of nonclassical and intermediate monocytes. No differences were observed in the number of lymphocytes and the proportion of CD4 and CD8 between patients and HC, but we found differences in markers of exhaustion of CD4 lymphocytes, with increased levels of Programmed cell death protein 1 (PD1) in Current SI/SA and Lymphocyte activation gene 3 (LAG3) in Current SI/SA and Lifetime SI/SA compared to HC. The plasmainflammatory status was marked by higher levels of soluble Triggering receptor expressed on myeloid cells 2 (sTREM2) in patients with lifetime SI/SA compared to HC. Finally, the multinomial analysis indicates that inflammation and depressive symptoms are independently associated with SI/SA. ConclusionThis study highlights the association of immunological alterations with SI/SA. Furthremore, SI/SA is independently influenced by depressive symptoms and inflammation. This may have important therapeutic implications, as in these patients, it may be necessary to treat the inflammatory process beyond treating the depressive symptoms.

Risk factors for Nocardia infection among allogeneic hematopoietic cell transplant recipients: A case-control study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence. We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests. Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95% confidence interval [95% CI]: 1.6-62.7), lymphocyte count <500/µL (aOR 8.9, 95% CI: 2.3-34.7), male sex (aOR 8.1, 95% CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95% CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95% CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95% CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58% and 90%, respectively; p<0.0001). We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.

Linezolid-Associated Thrombocytopenia: Assessment of Risk Factors in Patients without Hemato-Oncologic Diseases.

Background: Linezolid is used for Gram-positive bacterial infections. Thrombocytopenia is one of its main adverse effects resulting from myelosuppression. Several studies have assessed risk factors that may increase the risk of this adverse effect. However, most studies included patients with hemato-oncologic diseases, which may confound such assessments. This study aimed to investigate risk factors for linezolid-associated thrombocytopenia in patients without hemato-oncologic diseases. Methods: This was a multicenter retrospective case-control study of adult patients treated with linezolid twice daily for ≥3 days. Patients with hemato-oncologic diseases, active dengue fever, active COVID-19, baseline platelet count <100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, and a recent platelet transfusion within 7 days were excluded. Thrombocytopenia was defined as a drop in platelet count below 100 × 103/mm3. Results: Out of 158 evaluated patients, 33 developed thrombocytopenia, indicating an incidence rate of 20.9%. Of all the risk factors assessed, creatinine clearance of <60 mL/min and bacteremia/infective endocarditis were significantly associated with linezolid-associated thrombocytopenia (adjusted odds ratios, 3.25 and 5.95; 95% CI 1.12-9.45 and 1.23-28.66; p = 0.031 and 0.026, respectively). End of therapy platelet counts were significantly lower in the cases than in the controls (79 vs. 243 × 103/mm3; p < 0.001). Similarly, the percentage of platelet count change was significantly different (-55.1% vs. -10.2%; p < 0.001). Conclusions: In our study, the incidence rate of linezolid-associated thrombocytopenia was 20.9%, and we found that patients with renal impairment and bacteremia may need close monitoring of platelet counts. Prospective studies are warranted to evaluate the potential need for renal dose adjustment.

Towards a tailored approach for patients with acute diverticulitis and abscess formation. The DivAbsc2023 multicentre case–control study

BackgroundThis multicentre case–control study aimed to identify risk factors associated with non-operative treatment failure for patients with CT scan Hinchey Ib-IIb and WSES Ib-IIa diverticular abscesses.MethodsThis study included a cohort of adult patients experiencing their first episode of CT-diagnosed diverticular abscess, all of whom underwent initial non-operative treatment comprising either antibiotics alone or in combination with percutaneous drainage. The cohort was stratified based on the outcome of non-operative treatment, specifically identifying those who required emergency surgical intervention as cases of treatment failure. Multivariable logistic regression analysis to identify independent risk factors associated with the failure of non-operative treatment was employed.ResultsFailure of conservative treatment occurred for 116 patients (27.04%). CT scan Hinchey classification IIb (aOR 2.54, 95%CI 1.61;4.01, P < 0.01), tobacco smoking (aOR 2.01, 95%CI 1.24;3.25, P < 0.01), and presence of air bubbles inside the abscess (aOR 1.59, 95%CI 1.00;2.52, P = 0.04) were independent predictors of failure. In the subgroup of patients with abscesses > 5 cm, percutaneous drainage was not associated with the risk of failure or success of the non-operative treatment (aOR 2.78, 95%CI − 0.66;3.70, P = 0.23).ConclusionsNon-operative treatment is generally effective for diverticular abscesses. Tobacco smoking's role as an independent risk factor for treatment failure underscores the need for targeted behavioural interventions in diverticular disease management. IIb Hinchey diverticulitis patients, particularly young smokers, require vigilant monitoring due to increased risks of treatment failure and septic progression. Further research into the efficacy of image-guided percutaneous drainage should involve randomized, multicentre studies focussing on homogeneous patient groups.Graphical abstract

Risk factors of anastomotic leak in colorectal cancer: a multicentric study in a Latin American country.

The anastomotic leak (AL) is one of the most feared complications of colorectal surgery, since it is associated with a high rate of morbidity, mortality, length of hospital stay and cost of care. Our aim was to determine the risk factors associated with anastomosis leak in colorectal cancer patients who underwent surgical resection with anastomosis. A multicentre observational, analytical, retrospective and case-control study was carried out. For each case, two controls were included from three national hospitals from Lima, Peru during the period 2021-2022. To determine the degree of association, multivariate logistic regression model was carried out. A total of 360 patients were included, 120 from each hospital. The mean age of the population was 68.03 ± 14.21 years old. The majority were 65 years old or older (66.1%), 52.8% were female, and 63.3% had clinical stage III. The 40% of the patients had albumin levels lower than 3.5 g/dL. Regarding the surgery, 96.4% were elective, 68.9% underwent open approach, and 80.8% had an operative time of more than 180 minutes. Most of them had right colon cancer (50.8%). In the multivariate analysis, a significant association was found with the age variable (OR = 2.48; 95%CI:1.24-4.97), clinical tumour level (OR = 2.71; 95%CI:1.34-5.48), American Society of Anesthesiologists (ASA) Score (OR = 3.23; 95%CI:1.10-9.50), preoperative serum albumin (OR = 22.2; 95%CI:11.5-42.9). The most important independent risk factors associated with AL among patients with colorectal cancer were pre-operative such as lower preoperative serum albumin levels, followed by a higher ASA Score, clinical-stage III-IV, and an age ≥65 years old.

Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18–34.5) and severe periodontitis with an OR of 7.48 (1.24–44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87–23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01–6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72–40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Association of glycogen synthase kinase-3β with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3β (GSK-3β), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear. To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment. During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3β activity (rGSK-3β) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3β were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3β and ApoEϵ4 allele predicted for incident MCI was 0.71. Platelet GSK-3β activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.

Tuberculosis Disease in Immunocompromised Children and Adolescents: A Pediatric Tuberculosis Network European Trials Group Multicenter Case-control Study.

In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020. A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004). Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Liquid Biopsy for Detection of Pancreaticobiliary Cancers by Functional Enrichment and Immunofluorescent Profiling of Circulating Tumor Cells and Their Clusters.

Circulating tumor cells (CTCs) have historically been used for prognostication in oncology. We evaluate the performance of liquid biopsy CTC assay as a diagnostic tool in suspected pancreaticobiliary cancers (PBC). The assay utilizes functional enrichment of CTCs followed by immunofluorescent profiling of organ-specific markers. The performance of the assay was first evaluated in a multicentric case-control study of blood samples from 360 participants, including 188 PBC cases (pre-biopsy samples) and 172 healthy individuals. A subsequent prospective observational study included pre-biopsy blood samples from 88 individuals with suspicion of PBC and no prior diagnosis of cancer. CTCs were harvested using a unique functional enrichment method and used for immunofluorescent profiling for CA19.9, Maspin, EpCAM, CK, and CD45, blinded to the tissue histopathological diagnosis. TruBlood® malignant or non-malignant predictions were compared with tissue diagnoses to establish sensitivity and specificity. The test had 95.9% overall sensitivity (95% CI: 86.0-99.5%) and 92.3% specificity (95% CI: 79.13% to 98.38%) to differentiate PBC (n = 49) from benign conditions (n = 39). The high accuracy of the CTC-based TruBlood test demonstrates its potential clinical application as a diagnostic tool to assist the effective detection of PBC when tissue sampling is unviable or inconclusive.

Implications of pregnancy on MCN of the pancreas: A multicentric case-control study

BackgroundMucinous cystic neoplasms (MCN) of the pancreas express estrogen and progesterone receptors. Several case reports describe MCN increasing in size during gestation. The aim of this study is to assess if pregnancy is a risk factor for malignant degeneration of MCN. MethodsAll female patients who underwent pancreatic resection of a MCN between 2011 and 2021 were included. MCN resected or diagnosed within 12 months of gestation were defined perigestational. MCN with high grade dysplasia or an invasive component were classified in the high grade (HG) group. The primary outcome was defined as the correlation between exposure to gestation and peri-gestational MCN to development of HG-MCN. ResultsThe study includes 176 patients, 25 (14 %) forming the HG group, and 151 (86 %) forming the low grade (LG) group. LG and HG groups had a similar distribution of systemic contraceptives use (26 % vs. 16 %, p = 0.262), and perigestational MCN (7 % vs 16 %, p = 0.108). At univariate analysis cyst size ≥10 cm (OR 5.3, p < 0.001) was associated to HG degeneration. Peri gestational MCN positively correlated with cyst size (R = 0.18, p = 0.020). In the subgroup of 14 perigestational MCN patients 29 % had HG-MCN and 71 % experienced cyst growth during gestation with an average growth of 55.1 ± 18 mm. ConclusionsPerigestational MCN are associated to increased cyst diameter, and in the subset of patients affected by MCN during gestation a high rate of growth was observed. Patients with a MCN and pregnancy desire should undergo multidisciplinary counselling.

Diabetes Risk Reduction Diet and Colorectal Cancer Risk.

Diabetes has been associated with colorectal cancer. We evaluated whether adherence to a diabetes risk reduction diet (DRRD) can favorably influence the risk of colorectal cancer. Data came from a multicentric Italian case-control study including 1,953 histologically confirmed colorectal cancer cases and 4,154 hospital controls admitted for acute nonneoplastic diseases. Diet was assessed through a validated and reproducible food frequency questionnaire. The DRRD score was computed assigning higher values for higher consumption of cereal fiber, fruit, coffee, nuts and a higher polyunsaturated/saturated fats ratio and for lower glycemic index and lower consumption of red/processed meat and sweetened beverages and fruit juices. The ORs and the corresponding 95% confidence intervals (CI) of colorectal cancer according to the DRRD score were obtained using logistic regression models adjusting for total energy intake and other major confounders. The DRRD was inversely related to colorectal cancer risk. The ORs of colorectal cancer were 0.77 (95% CI, 0.67-0.89) for the third versus first score tertile (Ptrend < 0.001) and 0.92 (95% CI, 0.87-0.96) for a 3-point increment in the score. Inverse associations were observed for colon and rectal cancers and were consistent in strata of sex, age, and other major covariates. A higher adherence to a DRRD was inversely associated with colorectal cancer risk. Given the high incidence and mortality rates of colorectal cancer, adherence to a DRRD can have relevant prevention and public health implications.

Egyptian urinary stones in the COVID-19 outbreak: a multi-center study

BackgroundUrolithiasis is a unique disease that can cause emergencies and can impair kidney function over time, especially if infections overlap. This work aimed to compare urolithiasis in the pre- and post-pandemic era and to study the impact of the COVID-19 pandemic on patient preferences and decision-making for symptomatic urolithiasis and consequently complications.MethodsThis case–control multi-center study was conducted at the Urology Department of two tertiary centers in XXX. Participants were divided into two groups: group A: patients who had urolithiasis from March 1, 2018, to February 29, 2020 (pre-COVID-19 period), and group B: patients who had urolithiasis from March 1, 2020, to February 28, 2022 (during COVID-19 period).ResultsGroup A had a significantly higher incidence of percutaneous nephrolithotomy (PCNL) without double J stenting (DJ), nephrolithotomy + pyelolithotomy and total PCNL compared to group B which had a lower incidence of URS without DJ and total URS. The operation was delayed among 72 (15.9%) patients during the pandemic. In total, 116 (25.6%) were subjected to previous stone removal surgery. In total, 59 (13%) of patients had COVID-19 infection before stone diagnosis. One hundred thirty-two patients (29.1%) were on vitamin C. The presence of positive family history was statistically significant in patients who underwent ESWL in comparison with patients who underwent endoscopy or surgery (P = 0.03).ConclusionsCOVID-19 significantly impacted endourological services for urinary stones in terms of surgical volume and case complexity.

Integrated 16S rRNA sequencing and metagenomics insights into microbial dysbiosis and distinct virulence factors in inflammatory bowel disease.

The escalation of urbanization correlates with rising rates of inflammatory bowel disease (IBD), necessitating research into new etiological factors. This study aims to elucidate the gut microbiota profiles in IBD patients and compare them with healthy controls in a western city of China. We conducted a multicenter case-control study from the end of 2020, using 16S rRNA gene sequencing (n = 36) and metagenomic sequencing (n = 12) to analyze the gut microbiota of newly diagnosed IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC). Our results demonstrated a significant enrichment of the phylum Proteobacteria, particularly the genus Escherichia-Shigella, in CD patients. Conversely, the genus Enterococcus was markedly increased in UC patients. The core gut microbiota, such as the Christensenellaceae R-7 group, Fusicatenibacter, and Holdemanella, were primarily identified in healthy subjects. Additionally, significant interactions between the microbiome and virulence factors were observed. The findings suggest that oxidative stress may play a pivotal role in the pathology of IBD. This study contributes to the growing dialogue about the impact of gut microbiota on the development of IBD and its variations across different geographies, highlighting potential avenues for further research.

Hearing loss in beta-thalassaemia: An Italian multicentre case-control study.

Despite numerous studies, the true scenario of hearing loss in beta-thalassaemia remains rather nebulous. Pure tone audiometry, chelation therapy, demographics and laboratory data of 376 patients (mean age 38.5 ± 16.6 years, 204 females, 66 non-transfusion-dependent) and 139 healthy controls (mean age 37.6 ± 17.7 years, 81 females) were collected. Patient and control groups did not differ for age (p = 0.59) or sex (p = 0.44). Hypoacusis rate was higher in patients (26.6% vs. 7.2%; p < 0.00001), correlated with male sex (32.6% in males vs. 21.8% in females; p = 0.01) and it was sensorineural in 79/100. Hypoacusis rate correlated with increasing age (p = 0.0006) but not with phenotype (13/66 non-transfusion-dependent vs. 87/310 transfusion-dependent patients; p = 0.16). Sensorineural-notch prevalence rate did not differ between patients (11.4%) and controls (12.2%); it correlated with age (p = 0.01) but not with patients' sex or phenotype. Among adult patients without chelation therapy, the sensorineural hypoacusis rate was non-significantly lower compared to chelation-treated patients while it was significantly higher compared to controls (p = 0.003). Sensorineural hypoacusis rate is high in beta-thalassaemia (about 21%) and it increases with age and in males while disease severity or chelation treatment seems to be less relevant. The meaning of sensorineural-notch in beta-thalassaemia appears questionable.

Prenatal exposure to poly/perfluoroalkyl substances and risk for congenital heart disease in offspring

Congenital heart disease (CHD) is the most prevalent congenital malformation worldwide, and the association between per- and polyfluoroalkyl substances (PFASs) exposure and CHD in population has only received limited study. Therefore, we conducted a multicenter case-control study to explore the associations between prenatal exposure to individual PFASs, and also a PFAS mixture, and CHD risk, including 185 CHDs and 247 controls in China from 2016 to 2021. Thirteen PFASs in maternal plasma were quantified using liquid chromatography-tandem mass spectrometry. Logistic regression and two multipollutant models (Bayesian kernel machine regression [BKMR] and quantile g-computation [qgcomp]) were used to assess the potential associations between any individual PFAS, and also a PFAS mixture, and CHD risk. After adjusting for potential confounders, logistic regression indicated significant associations between elevated levels of perfluorononanoic acid (odds ratio [OR]= 1.30, 95% confidence intervals [CI]: 1.07–1.58), perfluorodecanoic acid (OR=2.07, 95%CI: 1.32–3.26), and perfluoroundecanoic acid (OR=2.86, 95%CI:1.45–5.65) and CHD risk. The BKMR model and qgcomp approach identified that a significant positive association between the PFAS mixture and risk for CHD. These findings provide essential evidence that there is indeed a health crisis associated with PFASs and that it is linked to CHD.

Lower limbs biomechanical deficits associated with stage 1 and 2 posterior tibialis tendon dysfunction during walking

BackgroundPosterior tibialis tendon dysfunction (PTTD) is a chronic degenerative musculoskeletal disorder causing a progressive ankle complex and arch collapse altering lower limb biomechanics. However, biomechanical changes associated with stage 1 and 2 PTTD need to be better characterized during walking to guide clinical recommendations and improve non-operative treatments. Research questionWhat are the lower limb kinematic and kinetic differences between individuals with stage 1 (PTTD1), individuals with stage 2 PTTD (PTTD2) and healthy counterparts during gait? MethodsSixteen PTTD1, 11 PTTD2 and 20 healthy controls were included in this multicentric case-control study to compare their lower limb gait biomechanics. Kinematic and kinetic data were recorded using a three-dimensional motion capture system and a force plate. One-dimensional statistical parametric mapping was used to compare lower limb joint motion and moments between groups during the stance phase. ResultsPTTD1 had minimal biomechanical differences compared with the control group. In contrast, PTTD2 presented significant differences compared with controls and PTTD1. At the ankle, PTTD2 exhibited greater plantarflexion and eversion angles and midfoot dorsiflexion and inversion angles throughout stance compared with controls and PTTD1. PTTD2 presented lower midfoot abduction moments compared with controls. These changes led PTTD2 to exhibit knee and hip adaptative biomechanical mechanisms in the frontal and transverse planes in late stance. PTTD2 had greater knee internal rotation angles and smaller knee external rotation moments compared to controls. PTTD2 had smaller hip internal rotation angles compared with PTTD1 and smaller hip adduction moments compared with controls. SignificancePTTD1 showed minimal biomechanical differences compared to controls and important differences compared to PTTD2. The lower limb biomechanical deficits accentuate as the pathology advances from stage 1 to stage 2. PTTD is a progressive condition needing early clinical management at stage 1 to avoid successive biomechanical changes associated with stage 2.

Acetylcholinesterase enzyme among cancer patients a potential diagnostic and prognostic indicator a multicenter case–control study

Acetylcholinesterase enzyme (AChE) activity is impaired by a variety of inhibitors including organophosphorus pesticides, leading to the accumulation of acetylcholine. In this study, we aimed to determine the association between cancer and the blood level of the (AChE). This is a multicenter hospital-based case–control study conducted in the Radiation and Isotopes Center Khartoum, and Institute of Nuclear Medicine and Molecular Biology and Oncology Gezira. One hundred and fifty participants, half of them cancer patients and half cancer free were recruited. All participants were screened for demographic, environmental, occupational, and clinical characteristics. Blood for the (AChE) activity test was drawn from participants in the two groups. The mean age of the participants was 40.6 ± 14.8 years. Geographical distribution showed the Central Region of Sudan had the highest rate of cancer, followed by North State, Khartoum State, West State, and East State. The most common tumor subtype was breast cancer, followed by leukemia, colon, esophageal, and prostate cancer. Inferential analysis revealed significantly impaired (AChE) activity among cancer patients compared to controls (53.4 ± 20.3% vs. 93.8 ± 8.8, p-value 0.001). There was a significant statistical association between impaired (AChE) activity and cancer. (AChE) activity might be applied in the future as a diagnostic biomarker and therapeutic target. Further large sample and molecular studies are recommended.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study

BackgroundThe majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring.MethodsA multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions.ResultsThere was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed.ConclusionsThe polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

Modeling variation in mixture effects over space with a Bayesian spatially varying mixture model.

Mixture analysis is an emerging statistical tool in epidemiological research that seeks to estimate the health effects associated with mixtures of several exposures. This approach acknowledges that individuals experience many simultaneous exposures and it can estimate the relative importance of components in the mixture. Health effects due to mixtures may vary over space driven by to political, demographic, environmental, or other differences. In such cases, estimating a global mixture effect without accounting for spatial variation would induce bias in effect estimates and potentially lower statistical power. To date, no methods have been developed to estimate spatially varying chemical mixture effects. We developed a Bayesian spatially varying mixture model that estimates spatially varying mixture effects and the importance weights of components in the mixture, while adjusting for covariates. We demonstrate the efficacy of the model through a simulation study that varies the number of mixtures (one and two) and spatial pattern (global, one-dimensional, radial) and magnitude of mixture effects, showing that the model is able to accurately reproduce the spatial pattern of mixture effects across a diverse set of scenarios. Finally, we apply our model to a multi-center case-control study of non-Hodgkin lymphoma (NHL) in Detroit, Iowa, Los Angeles, and Seattle. We identify significant spatially varying positive and inverse associations with NHL for two mixtures of pesticides in Iowa and do not find strong spatial effects at the other three centers. In conclusion, the Bayesian spatially varying mixture model represents a novel method for modeling spatial variation in mixture effects.