Large Cohort Of Patients Research Articles

Prevalence of omalizumab resistant chronic urticaria and real world effectiveness of dupilumab in omalizumab refractory chronic urticaria patients: a single center experience.

Chronic urticaria (CU) is characterized by wheals, angioedema, or both lasting for ≥ 6 weeks with chronic spontaneous urticaria (CSU) being the most common subtype. Omalizumab-resistant CSU cases represent an unmet clinical need. In this study, we aimed to assess the prevalence and predictors of omalizumab failure in a large cohort of CU patients and assess the effectiveness of dupilumab for omalizumab-recalcitrant CU. Of 338 CU patients, 33 received omalizumab. 69.7% (23 patients) were responders and 30.3% (10 patients) non-responders. Bivariate regression demonstrated that female sex (adjusted OR [aOR] = 1.53; 95%CI = 1.14-2.06), higher baseline UAS7 (aOR = 1.05; 95%CI = 1.01-1.09) and older age (controlling for sex) (aOR = 1.00; 95%CI = 1.00, 1.01) were associated with omalizumab failure. Of 10 omalizumab-refractory patients, three were well controlled with cyclosporine (all children), whereas the seven adults failed on average 5.6 ± 2.6 therapies including cyclosporine. All 7 achieved a complete response with dupilumab with time to response varying between 1 to 6 months. While our results suggest a favourable efficacy of dupilumab omalizumab-resistant cases, future confirmatory studies are required.

Exploring biomarkers as predictors of left ventricular recovery in a national registry of takotsubo syndrome patients (RETAKO)

Abstract Funding Acknowledgements None. Introduction Tako-Tsubo Syndrome (TTS) is characterized by transient dysfunction of the left ventricle (LV) of uncertain etiology, although considered a benign entity, TTS has a mortality rate and complications similar to STEMI patients (1). Late LV recovery (>10 days) has been associated with a worse prognosis. Currently, there is no data on biomarkers that can predict the disease's progression. Purpose We aim to correlate different biomarkers with LV recovery in TTS patients. Method We used data from the National Multicenter Registry on Tako-Tsubo Syndrome (RETAKO). Information on biomarkers, including NT-proBNP, C-reactive protein (CRP), leukocytes, and platelets, was collected both upon admission and at peak values. Early recovery was considered when it occurred within the first 10 days after the index event. A non-parametric correlation analysis was conducted to assess the predictive capacity of different biomarkers on LV recovery. Results Out of a total of 1,463 patients, 373 (25.5%) experienced late LV recovery. The average age was around 73 years, with the majority of the sample being women (86%). Significant differences were observed between the groups in NT-proBNP, CRP, and peak values of leukocytes and platelets, with higher levels in the late recovery group. In the linear correlation analysis, a significant association was found between late recovery and higher levels of NT-proBNP, peak leukocytes and platelets, however it was not statistically significant for the levels of CRP. Conclusions In a large national cohort of TTS patients, higher levels of NT-proBNP, peak of leukocytes and platelets during the hospital stay were significantly associated with late LV recovery. This recovery appears to depend on the degree of LV dysfunction and the inflammatory response.Biomarkers table 1

Mortality risk score for patients with Chagas cardiomyopathy and pacemaker.

Prognosis of Chronic Chagasic Cardiomyopathy (CCC) patients depends on functional and clinical factors. Bradyarrhythmia requiring pacemaker is a common complication. Prognosis of these patients is poorly studied, and mortality risk factors are unknown. We aimed to identify predictors of death and to define a risk score for mortality in a large cohort of CCC patients with pacemaker. It was an observational, unicentric and prospective study. The endpoint was all-cause mortality. Cox regression was used to identify predictors of death and to define a risk score. Bootstrapping method was used to internal score validation. We included 555 patients and after a mean follow-up of 3.7±1.5 years, 100 (18%) deaths occurred. Predictors of death were: right ventricular dysfunction (HR [hazard ratio] 2.24; 95%CI 1.41-3.53; P = 0.001); heart failure class III or IV (HR 2.16; 95% confidence interval [95%CI] 1.16-4.00; P = 0.014); renal disease (HR 2.14; 95%CI 1.24-3.68; P = 0.006); left ventricular end-systolic diameter > 44mm (HR 1.97; 95%CI 1.26-3.05; P = 0.003); atrial fibrillation (HR 1.94; 95%CI 1.25-2.99; P = 0.003) and cardiomegaly on X-ray (HR 1.87; 95%CI 1.10-3.17; P = 0.020). The score identified patients with: low (0-20 points), intermediate (21-30 points) and high risk (>31points). The optimism-corrected C-statistic of the predictive model was 0.751 (95% CI 0.696-0.806). Internal validation with bootstrapping revealed a calibration slope of 0.946 (95% CI 0.920-0.961), reflecting a small degree of over-optimism and C-statistic of 0.746 (95% CI 0.692-0.785). This study identified predictors of mortality in CCC patients with pacemaker defining a simple, validated and specific risk score.

Ultra-low-dose vs. standard-of-care-dose CT of the chest in patients with post-COVID-19 conditions—a prospective intra-patient multi-reader study

Abstract Objectives To conduct an intrapatient comparison of ultra-low-dose computed tomography (ULDCT) and standard-of-care-dose CT (SDCT) of the chest in terms of the diagnostic accuracy of ULDCT and intrareader agreement in patients with post-COVID conditions. Methods We prospectively included 153 consecutive patients with post-COVID-19 conditions. All participants received an SDCT and an additional ULDCT scan of the chest. SDCTs were performed with standard imaging parameters and ULDCTs at a fixed tube voltage of 100 kVp (with tin filtration), 50 ref. mAs (dose modulation active), and iterative reconstruction algorithm level 5 of 5. All CT scans were separately evaluated by four radiologists for the presence of lung changes and their consistency with post-COVID lung abnormalities. Radiation dose parameters and the sensitivity, specificity, and accuracy of ULDCT were calculated. Results Of the 153 included patients (mean age 47.4 ± 15.3 years; 48.4% women), 45 (29.4%) showed post-COVID lung abnormalities. In those 45 patients, the most frequently detected CT patterns were ground-glass opacities (100.0%), reticulations (43.5%), and parenchymal bands (37.0%). The accuracy, sensitivity, and specificity of ULDCT compared to SDCT for the detection of post-COVID lung abnormalities were 92.6, 87.2, and 94.9%, respectively. The median total dose length product (DLP) of ULDCTs was less than one-tenth of the radiation dose of our SDCTs (12.6 mGy*cm [9.9; 15.5] vs. 132.1 mGy*cm [103.9; 160.2]; p < 0.001). Conclusion ULDCT of the chest offers high accuracy in the detection of post-COVID lung abnormalities compared to an SDCT scan at less than one-tenth the radiation dose, corresponding to only twice the dose of a standard chest radiograph in two views. Clinical relevance statement Ultra-low-dose CT of the chest may provide a favorable, radiation-saving alternative to standard-dose CT in the long-term follow-up of the large patient cohort of post-COVID-19 patients.

Exome Sequencing has a high diagnostic rate in sporadic congenital hypopituitarism and reveals novel candidate genes.

The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.

Real-World Safety and Outcome of First-Line Pembrolizumab Monotherapy for Metastatic NSCLC with PDL-1 Expression ≥ 50%: A National Italian Multicentric Cohort (“PEMBROREAL” Study)

Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan–Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6–10.0) and 25.5 months (95% CI: 21.8–31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Association of the C3953T (rs1143634) variant of the interleukin 1 beta gene with the features of a complicated course of COVID-19-associated pneumonia.

The pro-inflammatory cytokine IL-1 plays an important role in severe COVID-19. A change in IL-1 production may be associated with a mutation in the IL1Β gene. Our study analyzed the impact of the IL1Β gene variants (rs1143634) on disease progression in patients with severe COVID-19 pneumonia, taking into account treatment strategies. The study enrolled 117 patients with severe COVID-19 pneumonia. The IL1Β gene variants were identified using the polymerase chain reaction-restriction fragment length polymorphism method. In the group of patients, the following genotype frequencies were found based on the investigated rs1143634 variant of the IL1Β gene: CC-65.8%, CT-28.2%, and TT-6.0%. Our results showed that the group of patients with the T allele of the IL1Β gene had higher leukocyte counts (p = 0.040) and more pronounced lymphopenia (p = 0.007). It was determined that patients carrying the T allele stayed on ventilators significantly longer (p = 0.049) and required longer treatment with corticosteroids (p = 0.045). Identifying variants of the IL1Β gene can be used as a predictive tool for assessing the severity of COVID-19 pneumonia and tailoring personalized treatment strategies. Further research with a larger patient cohort is required to validate these findings.

Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study

BackgroundOral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies.MethodsA total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL.ResultsThe study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL.ConclusionThe clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Periprosthetic Joint Infection in Patients With Arthroplasty Undergoing Perioperative Colonoscopy

Periprosthetic joint infection (PJI) is a rare but devastating complication. Most patients undergoing total joint arthroplasty (TJA) also need routine screening colonoscopy, in which transient bacteremia may be a potential source for hematogenous PJI. Patients and surgeons must decide on an optimal time span or sequence for these 2 generally elective procedures, but no such guidelines currently exist. To evaluate associations of colonoscopy with the risk of post-TJA PJI for the development of clinical practice recommendations for colonoscopy screening in patients undergoing TJA. This retrospective cohort study of Military Health System (MHS) beneficiaries older than 45 years who underwent TJA from January 1, 2010, to December 31, 2016, used propensity score matching and logistic regression to evaluate associations of colonoscopy with PJI risk. Statistical analyses were conducted between January and October 2023. Colonoscopy status was defined by Current Procedural Terminology code for diagnostic colonoscopy within 6 months before or 6 months after TJA. Periprosthetic joint infection status was defined by a PJI International Classification of Diseases code within 1 year after TJA and within 1 year from the post-TJA index colonoscopy date. Analyses included 243 671 patients (mean [SD] age, 70.4 [10.0] years; 144 083 [59.1%] female) who underwent TJA in the MHS from 2010 to 2016. In the preoperative colonoscopy cohort, 325 patients (2.8%) had PJI within 1 year postoperatively. In the postoperative colonoscopy cohort, 138 patients (1.8%) had PJI within 1 year from the index colonoscopy date. In separate analyses of colonoscopy status within 6 months before and 6 months after TJA, younger age, male sex, and several chronic health conditions (diabetes, kidney disease, and pulmonary disease) were each associated with higher PJI risk. However, no association was found with PJI risk for perioperative colonoscopy preoperatively (adjusted odds ratio, 1.10; 95% CI, 0.98-1.23) or postoperatively (adjusted odds ratio, 0.90; 95% CI, 0.74-1.08). In this large retrospective cohort of patients undergoing TJA, perioperative screening colonoscopy was not associated with PJI and should not be delayed for periprocedural risk. However, health conditions were independently associated with PJI and should be medically optimized.

Germline DNA methylation analysis reveals distinct alterations in a large cohort of patients with germline SDHB pathogenic variant

Germline DNA methylation analysis reveals distinct alterations in a large cohort of patients with germline SDHB pathogenic variant

Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?

BackgroundCurrent treatments for chronic hepatitis B management include orally administered nucleos(t)ide analogues, such as tenofovir (TDF), which is an acyclic adenine nucleotide analogue used both in HBV and human immune deficiency virus (HIV). The course of HBV infection is mainly dependent on viral factors, such as HBV genotypes, immunological features and host genetic variables, but a few data are available in the context of HBV, in particular for polymorphisms of genes encoding proteins involved in drug metabolism and elimination.Consequently, the aim of this study was to evaluate the potential impact of genetic variants on TDF plasma and urine concentrations in patients with HBV, considering the role of HBV genotypes. MethodsA retrospective cohort study at the Infectious Disease Unit of Amedeo di Savoia Hospital, Torino, Italy, was performed. Pharmacokinetic analyses were performed through liquidi chromatography, whereas pharmacogenetic analyses through real-time PCR. FindingsSixty - eight patients were analyzed: ABCC4 4976 C>T genetic variant showed an impact on urine TDF drug concentrations (p = 0.014). In addition, SLC22A6 453 AA was retained in the final regression multivariate model considering factors predicting plasma concentrations, while ABCC4 4976 TC/CC was the only predictor of urine concentrations in the univariate model. InterpretationIn conclusion, this is the first study showing a potential impact of genetic variants on TDF plasma and urine concentrations in the HBV context, but further studies in different and larger cohorts of patients are required.

Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity.Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety.Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation.In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively.Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method.Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers.For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.

Persistent intracranial steno-occlusion from calcified embolism: a treatment challenge.

Calcified arterial cerebral embolism is a rare occurrence among large and medium vessel occlusions causing ischemic stroke and its diagnosis and treatment is a challenge. The sources of calcified embolism might be a calcific atheroma from the aortic arch and carotid artery, but also heart valve disease has been reported in the literature. Calcified embolism is frequently simultaneous on multiple vascular territories. The prognosis of patients is usually poor, including patients treated by using endovascular thrombectomy (EVT) and this diagnosis could be easily missed in the acute phase. In addition, the optimal secondary prevention has not been yet fully stated. We are presenting two cases of acute stroke due to calcified embolism in the middle cerebral artery (MCA) coming from a complicated carotid atheroma, non-stenosing in the first case (a 49years old man) and stenosing in the second case (a 71years old man) without clinical indications to intravenous thrombolysis and/or EVT, extensively investigated in the acute phase and followed-up for over 12months with a favorable clinical course and the persisting steno-occlusion in the involved MCA. In both cases, antiplatelet treatment and targeting of vascular risk factors were done without recurrences in the follow-up period. Cerebral calcified embolism has been reported in 5.9% of cases of acute ischemic stroke in a single center series and only in 1.2% of a large retrospective cohort of EVT-treated patients. In both series the prognosis was poor and only one third of EVT-treated patients had functional independence at 3-months follow-up. The natural history of these subtype of ischemic stroke is relatively poorly understood and both etiological diagnosis and treatment have not yet defined. It is possible that some cases might be underdiagnosed and underreported. Calcified cerebral embolism is a rare cause of stroke, but it is largely underreported and both acute phase and secondary preventive treatment have to be defined.

Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Developmental uterovaginal anomalies and histologic findings in transgender patients receiving gender-affirming hysterectomies: A large case series.

To describe the incidence of uterovaginal anomalies and histologic findings in transgender and nonbinary (TGNB) patients seeking hysterectomies. All patients receiving gender-affirming hysterectomies between 2013 and 2023 were retrospectively reviewed. Primary outcomes included uterovaginal anomalies and histological findings. Multivariable logistic regressions were performed to evaluate relationships between variables of interest and whether they predict findings of uterovaginal anomalies, inactive endometrium, adenomyosis, leiomyoma, endometriosis, and cervical atrophy. 278 patients received hysterectomies at an average age of 29.2 ± 8.3 years. Seven patients (2.5%) were found to have a developmental anomaly, including two bicornuate uterus (0.7%), two unicornuate uterus (0.7%), one septate uterus (0.4%), and two vaginal septum (0.7%). 60 patients (21.6%) were found to have inactive endometrium and 26 patients (9.4%) had cervical atrophy. Although 262 patients (94.2%) were on testosterone therapy, hormone duration was not a significant predictor of any uterine findings. This study describes uterovaginal anomalies in a large cohort of patients receiving gender-affirming hysterectomies. Although long-term testosterone use is commonly believed to be associated with endometrial and cervical atrophy, this study shows no such association.

Clinical and genetic characterization of a large cohort of patients with premature ovarian failure

Clinical and genetic characterization of a large cohort of patients with premature ovarian failure

Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study

Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study

Mesenteric Ischemia after Cardiac Surgery.

Mesenteric ischemia (Me-Is) after cardiac surgery is underreported in present literature but has still earned the bad reputation of a dismal prognosis. This study adds clinical outcomes in a large patient cohort. Between 2009 and 2019 of the 22,590 patients undergoing cardiac surgery at our facility 106 (0.47%) developed Me-Is postoperatively. Retrospective patient data was analyzed. Additionally, patients were stratified by outcome-survivors and nonsurvivors. Patients were predominantly male (n = 68, 64.2%), mean age was 71.2 ± 9.3 years. Most procedures were elective (n = 85, 80.2%) and comprised of more complex combined procedures (50.9%) and redos (17.9%). Mean EuroSCORE II averaged 10.9 ± 12.2%. Survival at 30 days was 49.1% (n = 52). Clinical baseline and procedural characteristics did not differ significantly between survivors and nonsurvivors. The median postoperative interval until symptom onset was 5 days in both groups. Survivors were more frequently diagnosed by computed tomography and nonsurvivors based on clinical symptoms. Me-Is was predominantly nonocclusive (n = 84, 79.2%). Laparotomy was the main treatment in both groups (n = 45, 78.8% vs. n = 48, 88.9%, p = 0.94). Predictors of mortality were maximum norepinephrine doses (hazard ratio [HR] 8.29, confidence interval [CI] 3.39-20.26, p < 0.0001), lactate levels (HR 1.06, CI 1.03-1.09), and usage of inotropes (HR 2.46, CI 1.41-4.30). The prognosis of Me-Is following cardiac surgery is poor-independently from diagnostic or treatment patterns. There exists a significant asymptomatic time period postoperatively, in which pathophysiologic processes seem to cross the Rubicon. After clinical demarcation, the further course can almost no longer be influenced.

Electrocardiographic abnormalities in patients with microtia

The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.

A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases

Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients’ blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies.