Large Population Studies Research Articles

Association between wet-bulb globe temperature and kidney function in different geographic regions in a large Taiwanese population study.

The worldwide prevalence and incidence rates of end-stage renal disease have been increasing, and the trend is pronounced in Taiwan. This is especially evident in southern Taiwan, where the wet-bulb globe temperature (WBGT) is consistently higher than in other regions. The association between kidney function and WBGT has not been fully investigated. Therefore, the aim of this study was to evaluate the association between estimated glomerular filtration rate (eGFR) and WBGT and variations in this association across different geographic regions in Taiwan. We used the Taiwan Biobank (TWB) to obtain data on community-dwelling individuals, linked these data with WBGT data obtained from the Central Weather Bureau and then processed the data using a machine learning model. WBGT data were recorded during the working period of the day from 8:00 a.m. to 5:00 p.m. These data were then compiled as 1-year, 3-year and 5-year averages, recorded prior to the survey year of the TWB of each participant. We identified 114483 participants who had WBGT data during 2012-2020. Multivariable analysis showed that, in northern Taiwan, increases in 1- and 3-year averages of WBGT during the working period (β=-0.092, P=.043 and β=-0.193, P<.001, respectively) were significantly associated with low eGFR. In southern Taiwan, increases in 1-, 3- and 5-year averages of WBGT during the working period (β=-0.518, P<.001; β=-0.690, P<.001; and β=-0.386, P=.001, respectively) were gnificantly associated with low eGFR. These findings highlight the importance of heat protection for people working outdoors or in high-temperature environments as a measure to prevent negative impacts on kidney function. Moreover, we observed that in southern Taiwan, every 1°C increase in WBGT had a greater impact on the decrease in eGFR compared with other regions in Taiwan.

Pilot Feasibility Study: 18 F-DPA-714 PET/CT Macrophage Imaging in Triple-Negative Breast Cancers (EITHICS).

Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted. The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as "above muscular," "equal to muscular," and "below muscular" with reference to the muscular background. For the "above muscular" group (2 HAB and 2 MAB), "equal muscular" group (3 HAB, 3 MAB, and 1 LAB), and "below muscular" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02). This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.

Trans rectus sheath extra-peritoneal procedure (TREPP) for inguinal hernia repair under local anesthesia with sedation in the outpatient clinic: a feasibility study.

The Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) is an open procedure in which the mesh is placed in the preperitoneal space and is therefore associated with less chronic post-operative inguinal pain. TREPP is primarily performed under general or spinal anesthesia, however, it is also possible to perform under sedation and local anesthesia with potentially advantages. This retrospective feasibility pilot study investigates the safety and efficiency of TREPP under local anesthesia in the outpatient clinic in comparison with Lichtenstein. Between 2019 and 2022, all patients who underwent an elective inguinal hernia repair under local anesthesia in the outpatient clinic operation theatre were assessed. 34 patients in the TREPP group and 213 patients in the Lichtenstein group were included. Outcomes were complications, operating time, theatre time, and early inguinal hernia recurrence within 8 weeks and 6 months post-operatively. No significant differences in complications such as wound infection, hematoma, seroma, urine retention and early recurrence between TREPP and Lichtenstein were found. Post-operative pain at 8 weeks was not significantly higher after Lichtenstein (8.8% vs. 18.8%, P = 0.22). Operating time (21.0 (IQR: 16.0-27.3) minutes vs. 39.0 (IQR: 31.5-45.0) minutes, P < 0.001) and theatre time (37.5 (IQR: 30.8-42.5) minutes vs. 54.0 (IQR: 46.0-62.0) minutes, P < 0.001) was significantly shorter for TREPP. This pilot study showed that TREPP appears to be feasible to perform safely under local anesthesia with comparable complication rates and substantially shorter operation time than Lichtenstein. These results justify further research with a larger study population and a longer period of follow up in order to provide firm conclusions.

Epidemiology of Pediatric Cardiomyopathy in a Mediterranean Population.

Our knowledge regarding the epidemiology of pediatric cardiomyopathy is based on large national population studies reporting an annual incidence of 1 case per 100,000 children, with a higher incidence observed in infancy and among selected populations. The aim here is to document the epidemiology of pediatric cardiomyopathy in a Mediterranean population. Children younger than 18 years of age living on the Mediterranean island of Crete, Greece, who have been evaluated since the establishment of tertiary pediatric cardiology services (2002-2022) were included in this retrospective study. A total of 40 children were included, corresponding to an average annual incidence of pediatric cardiomyopathy of 1.59 cases (95% CI: 1.4-2.3) and a prevalence of 26 cases per 100,000 children. In decreasing order of frequency, most cases corresponded to dilated (50%), followed by hypertrophic (42.5%), arrhythmogenic (5%), and restrictive (2.5%) cardiomyopathy. An etiology was identified in 40%, including a genetic diagnosis in 22.5%. The incidence of pediatric cardiomyopathy in the Mediterranean island of Crete is higher compared with that reported previously for other Caucasian populations. Further study is needed to investigate the exact prevalence and specific genetic factors associated with the epidemiology of pediatric cardiomyopathy in Mediterranean populations.

Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma.

This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.

Sex difference in the associations among hyperuricemia with self-reported peptic ulcer disease in a large Taiwanese population study.

Hyperuricemia may play a role in various systemic diseases. However, few studies have investigated the relationship between hyperuricemia and the risk of peptic ulcer disease (PUD). Therefore, in this population-based study, we enrolled over 120,000 participants from the Taiwan Biobank (TWB) and examined the risk factors for self-reported PUD. In addition, we investigated sex differences in the association between hyperuricemia and self-reported PUD. Data of 121,583 participants were obtained from the TWB. Male participants with a serum uric acid level >7 mg/dl and female participants with a serum uric acid level >6 mg/dl were classified as having hyperuricemia. Details of self-reported PUD were obtained by questionnaire. The association between hyperuricemia and self-reported PUD in the male and female participants was examined using multivariable logistic regression analysis. The overall prevalence of self-reported PUD was 14.6%, with a higher incidence in males (16.5%) compared to females (13.5%). After multivariable adjustment, male sex [vs. female sex; odds ratio (OR) = 1.139; 95% confidence interval (CI) = 1.084-1.198; p < 0.001], and hyperuricemia (OR = 0.919; 95% CI = 0.879-0.961; p < 0.001) were significantly associated with self-reported PUD. Further, a significant interaction was found between sex and hyperuricemia on self-reported PUD (p = 0.004). Hyperuricemia was associated with a low risk of self-reported PUD in males (OR = 0.890; 95% CI = 0.837-0.947; p < 0.001) but not in females (p = 0.139). The prevalence of self-reported PUD was higher in the male participants than in the female participants. Hyperuricemia was associated with low prevalence of self-reported PUD in males, but not in females. Further studies are needed to clarify the mechanisms behind these observations and verify the potential protective role of hyperuricemia on the development of self-reported PUD.

Comments on "Association between ambient air pollutant interaction with kidney function in a large Taiwanese population study" by Su et al. (https://doi.org/10.1007/s11356-023-28042-6).

Comments on "Association between ambient air pollutant interaction with kidney function in a large Taiwanese population study" by Su et al. (https://doi.org/10.1007/s11356-023-28042-6).

Intestinal Microbiota Increases Cell Proliferation of Colonic Mucosa in Human-Flora-Associated (HFA) Mice.

Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16). One hour before sacrifice, all mice were intraperitoneally inoculated with 5-bromodeoxyuridine (BrdU), and the number of BrdU-positive cells/total cells (labelling index, LI), both in the jejunum and the colon, was evaluated by immunohistochemistry. Samples were also observed by scanning electron microscopy (SEM). Moreover, the microbiota composition in the large bowel of the HFA mice was compared to that of of human donor's fecal sample. No differences in LI were found in the small bowels of the HFA, holoxenic, and germ-free mice. Conversely, the LI in the large bowel of the HFA mice was significantly higher than that in the germ-free and holoxenic counterparts (p = 0.017 and p = 0.048, respectively). In the holoxenic and HFA mice, the SEM analysis disclosed different types of bacteria in close contact with the intestinal epithelium. Finally, the colonic microbiota composition of the HFA mice widely overlapped with that of the human donor in terms of dominant populations, although Bifidobacteria and Lactobacilli disappeared. Despite the small sample size analyzed in this study, these preliminary findings suggest that human intestinal microbiota may promote a high proliferation rate of colonic mucosa. In light of the well-known role of uncontrolled proliferation in colorectal carcinogenesis, these results may deserve further investigation in a larger population study.

The aging gastrointestinal tract: Epidemiology and clinical significance of disorders of gut-brain interaction in the older general population.

Most previous reports on the prevalence of disorders of gut-brain interaction (DGBI) show higher rates in younger individuals. Exceptions are faecal incontinence and functional constipation. To compare prevalence rates for 22 DGBI and 24 primary symptoms, by age, using the Rome Foundation Global Epidemiology (RFGES) study dataset. The RFGES dataset enables diagnosis of 22 DGBI among 54,127 participants (≥18 years) in 26 countries. Older age was defined as ≥65 years. We assessed differences between age groups by sex, geographic region, somatisation, abnormal anxiety and depression scores, quality of life (QoL), individual gastrointestinal symptoms and disease severity for irritable bowel syndrome (IBS). Rates for any DGBI were 41.9% and 31.9% in the <65 and ≥65 age groups, respectively. For all Rome IV diagnoses except faecal incontinence, rates were higher in the younger group. The older group had lower scores for any DGBI by geographic region, non-gastrointestinal somatic symptoms, abnormal anxiety and depression scores, and IBS severity, and better scores for QoL. The mean number of endorsed symptoms and their frequency were higher in the younger group. In this large general population study, the prevalence and impact of DGBI, apart from faecal incontinence, were higher in the younger group. Despite this, DGBI rates are still high in absolute terms in the ≥65 age group and necessitate clinical awareness and, perhaps, an age-specific treatment approach.

Short-Term Morbidity and Mortality after Distal Femur Open Reduction Internal Fixation in the Geriatric Population.

Distal femur fractures remain a significant cause of morbidity and mortality for elderly patients. There is a lack of large population studies investigating short-term outcomes after distal femur c in elderly patients. The purpose of this study is to assess the incidence of and risk factors for various short-term outcomes after distal femur open reduction internal fixation (ORIF) in the geriatric population. The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database was used to identify all primary distal femur ORIF cases in patients 60+ years old between January 1, 2015 and December 31, 2020 using Current Procedural Terminology (CPT) codes 27511, 27513, and 27514. Demographic, medical, and surgical variables were extracted for all patients. Propensity score matching was used to match cases in the two age groups based on various demographic and medical comorbidity variables. Several 30-day outcome measures were compared between the 60-79-year-old and 80+-year-old groups both before and after matching. Subsequent multivariate logistic regression was used to identify independent risk factors for 30-day outcome measures in the matched cohort. A total of 2913 patients were included in the final cohort: 1711 patients in the 60-79-year-old group and 1202 patients in the 80+-year-old group. Most patients were female (n = 2385; 81.9%). Prior to matching, the older group had a higher incidence of 30-day mortality (1.9% vs. 6.2%), readmission (3.7% vs. 9.7%, p = 0.024), and non-home discharge (74.3% vs. 89.5%, p < 0.001). Additionally, the older group had a higher rate of blood loss requiring transfusion (30.9% vs. 42.3%, p < 0.001) and medical complications (10.4% vs. 16.4%, p < 0.001), including myocardial infarction (0.7% vs. 2.7%, p < 0.001), pneumonia (2.7% vs. 4.6%, p = 0.008), and urinary tract infection (4.1% vs. 6.1%, p = 0.0188). After matching, the older group consistently had a higher incidence of mortality, non-home-discharge, blood loss requiring transfusion, and myocardial infarction. Various independent risk factors were identified for 30-day morbidity and mortality, including American Society of Anesthesiologists (ASA) classification, body mass index (BMI) status, operative duration, and certain medical comorbidities. Geriatric patients undergoing distal femur ORIF are at significant risk for 30-day morbidity and mortality. After matching, octogenarians and older patients specifically are at increased risk for mortality, non-home discharge, and surgical complications compared to patients aged 60-79 years old. Multiple factors, such as BMI status, ASA classification, operative time, and certain medical comorbidities, are independently associated with poor 30-day outcomes.

Impact of cancer treatment in patients with inflammatory bowel disease: A systematic review and meta analysis.

e23084 Background: The association between cancer treatments and impact of inflammatory bowel diseases (IBD) remains uncertain. Given the growing prevalence of IBD globally, it is crucial to understand the impact of various cancer treatments in this patient population to make informed decisions and optimize outcomes. Thus, the objective of our systematic review is to assess how cancer treatments impact the activity of underlying IBD. Methods: We performed a systematic review of the literature on cancer therapy in patients with pre-existing IBD. Various databases like PubMed, Cochrane, Embase and Google Scholar were searched for studies reporting effects of cancer treatment in patients with IBD, till February 1, 2024. Studies without relevant data were excluded. The outcomes studied were the flares of IBD following cancer treatment and initiation of systemic steroids or biologics for management of IBD flares. Results: In total, 36 studies were included which comprised 1,443 patients with IBD who received cancer treatment. The overall occurrence of IBD flares in patients with IBD receiving cancer treatment was 28% (CI 22.9%-33.8%, I2= 68%) out of which 35.9% (CI 27.5% - 45.3%, I2= 40) had received immune checkpoint inhibitor therapy. The flares resulted in the utilization of systemic steroids and biologics in 27% and 10% respectively. Conclusions: While the data suggests a high proportion of patients with IBD experience flares during cancer treatment, all of the reported episodes were manageable with steroids and/or biologics. However, the population studied only included 1443 patients, and larger population studies are required to optimize individual outcomes, and to explore methods to minimize severity and frequency of flares, when possible.

Simultaneous isolation of intact brain cells and cell-specific extracellular vesicles from cryopreserved Alzheimer’s disease cortex

BackgroundThe neuronal and gliaI populations within the brain are tightly interwoven, making isolation and study of large populations of a single cell type from brain tissue a major technical challenge. Concurrently, cell-type specific extracellular vesicles (EVs) hold enormous diagnostic and therapeutic potential in neurodegenerative disorders including Alzheimer’s disease (AD). New MethodPostmortem AD cortical samples were thawed and gently dissociated. Following filtration, myelin and red blood cell removal, cell pellets were immunolabeled with fluorescent antibodies and analyzed by flow cytometry. The cell pellet supernatant was applied to a triple sucrose cushion for brain EV isolation. ResultsNeuronal, astrocyte and microglial cell populations were identified. Cell integrity was demonstrated using calcein AM, which is retained by cells with esterase activity and an intact membrane. For some experiments cell pellets were fixed, permeabilized, and immunolabeled for cell-specific markers. Characterization of brain small EV fractions showed the expected size, depletion of EV negative markers, and enrichment in positive and cell-type specific markers. Comparison with existing methods and conclusionsWe optimized and integrated established protocols, aiming to maximize information obtained from each human autopsy brain sample. The uniqueness of our method lies in its capability to isolate cells and EVs from a single cryopreserved brain sample. Our results not only demonstrate the feasibility of isolating specific brain cell subpopulations for RNA-seq but also validate these subpopulations at the protein level. The accelerated study of EVs from human samples is crucial for a better understanding of their contribution to neuron/glial crosstalk and disease progression.

Photoplethysmography recordings preceding onset atrial fibrillation show a higher heart rate variability - a TeleCheck-AF subanalysis

Abstract Background An increased heart rate variability (HRV), mostly assessed by 12-lead electrocardiogram (ECG) or long-term Holter monitoring, can be associated with the onset of atrial fibrillation (AF). Data evaluating HRV measurements using digital devices, especially those using photoplethysmography (PPG), in patients at risk for AF are sparse. In this analysis, we aimed to assess if hand-held-based non-continuous PPG measurements can provide short-term HRV to predict AF. Methods Patients from the TeleCheck-AF project with at least one PPG measurement in AF and one measurement in sinus rhythm (SR) were analyzed. Briefly, patients were provided with a PPG-based heart rate/rhythm monitoring smartphone app. They were instructed to record a PPG measurements three times daily and in case of symptoms for seven consecutive days. Short-term HRV using root mean square of successive normal-to-normal interval differences (RMSSD) was calculated in recordings in SR and compared between those not preceding and preceding an episode of AF (figure 1). Results Overall, 136 patients [56.3% men, median age 66 (59; 72) years] were included in the analysis. Median total number of recordings per patient was 24 (19; 30) including 4 (2;7) AF episodes per 1 week recording period. RMSSD was significantly higher in PPG measurements preceding an AF episode than in PPG measurements not preceding an AF episode [42.5 (33.2;70.7)ms vs. 41.1 (32.4;54.7)ms; p&amp;lt;0.001]. Between-group comparison revealed no significant difference for gender, age, previous ablation or betablocker therapy (p=0.824; p=0.484; p=0.519 and p=0.624, respectively). Conclusion Short-term HRV based on RMSSD, assessed by digital hand-held devices is significantly higher in PPG recordings preceding an AF episode than in measurements not preceding a consecutive AF episode. Whether PPG-recording derived short-term HRV can help to predict onset-AF warrants further study in larger populations. Figure 1: Patient example and exemplary analysis scheme, depicting the total number of recordings (n=14). HRV of recordings in sinus rhythm (SR) not preceding an episode of atrial fibrillation (AF) (A; grey circles) were compared to recordings preceding a consecutive AF episode (B; blue circles).Figure 1

#2224 Higher serum level of indoxyl sulfate is not associated with increased abdominal aorta calcification in patients on maintenance hemodialysis

Abstract Background and Aims Vascular calcification is strongly associated with an increase in all-cause and cardiovascular mortality, especially in patients with and stage renal disease. Results of numerous experimental studies have shown direct toxic effect of microbial-derived uremic toxins on vascular endothelial and smooth muscle cells which may contribute vascular calcification. Meanwhile, the effects of these metabolites on vascular remodeling in patients receiving dialysis treatment remains largely unclear. Here we aimed to investigate the relationship between serum level of the uremic toxin indoxyl sulfate and severity of abdominal aorta calcification (AAC) in patients on maintenance hemodialysis. Method This single-center, cross-sectional study included eighty (40 men, average age – 59,7±11,8 years) clinically stable patients receiving hemodialysis treatment for 52(21,3-120) months. 13(16,3%) participants had history of smoking, 27(33,8%) were diabetic, 63(78,8%) had high blood pressure, 17(21,3%) – previous history of ischemic heart disease, including 5(6,3%) suffered a myocardial infarction. Severity of AAC was determined by lateral lumbar radiography with Kauppila scoring. The total AAC score ranged from 0 to 24 points, and a higher AAC score indicated a more pronounced degree of calcification. Routine laboratory data were collected before hemodialysis session after fasting for 12 hours. Serum concentration of indoxyl sulfate was assessed by ELISA using commercially available kit (Cloud-Clone Corp., USA). Statistical analysis was performed with IBM SPSS Statistics 26 program. Non-parametric Spearman's rank correlation method was used to evaluate the associations between the studied parameters. Value of p &amp;lt;0.05 was considered statistically significant in all tests. Results Median serum indoxyl sulfate was 2,1(1,4-3,0) μmol/l (the same parameter in relatively healthy individuals without impaired renal function is 0,1(0-0,3) μmol/l, р˂0,001). Serum levels of calcium (Ca) was 2,27(2,1-2,5) mmol/l, ionized calcium (Ca++) – 1,15(1,1-1,3) mmol/l, phosphate (P) – 1,6(1,3-2,0) mmol/l, intact parathyroid hormone (iPTH) – 303(162,2-492,8) pg/ml, total cholesterol (TH) – 4,5(3,5-5,4) mmol/l, low-density lipoprotein (LDL) – 2,6(2,0-3,3) mmol/l. AAC score in hemodialysis participants was 4,5(0,0-9,0) and significantly correlated with age (r=0,693; р˂0,001), Ca (r=0,208; р=0,04) and iPTH (r=0,418; р=0,021) but not with other indicators, including indoxyl sulfate concentration (r=0,164; р=0,147). Conclusion Our preliminary results do not allow to consider the elevated level of indoxyl sulfate as a factor contributing to increased AAC in patients on maintenance hemodialysis. Further prospective studies in larger populations should clarify the true role of indoxyl sulfate in vascular remodeling in individuals with chronic kidney disease.

#901 Natural history of idiopathic nephrotic syndrome: the UK National RaDaR Idiopathic Nephrotic Syndrome Cohort

Abstract Background and Aims Idiopathic nephrotic syndrome (INS) is an important class of proteinuric renal disease leading to kidney failure (KF). Here we describe the natural history of INS and congenital nephrotic syndrome (NS) using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4610 patients with NS not attributable to glomerulonephritis or systemic disorders recruited from 107 adult and paediatric kidney units across the UK since 2010. Method Participant eligibility of RaDaR-INS Cohort patients included ≥12 months observation from disease onset and no KF (CKD stage 5 or on renal replacement therapy) at or prior to disease onset. Disease onset date was defined as first database occurrence of kidney biopsy, primary diagnosis or protein-creatinine ratio (PCR) ≥1.5 g/g. Participants were sub-categorized into those with a genetic diagnosis (INS-genetic), biopsy-proven FSGS (FSGS-biopsy), biopsy–proven minimal change disease (MCD-biopsy) and those with no genetic or biopsy-proven diagnosis (INS-no genetic or biopsy diagnosis). Participants with a biopsy-proven MCD diagnosis and a subsequent biopsy proven FSGS diagnosis were included in both MCD-biopsy and FSGS-biopsy categories and formed a category of their own (MCD progressing to FSGS). Longitudinal proteinuria, assessed as time-average protein-to-creatinine ratio (TA-PCR), and eGFR slope were calculated over the full duration of follow-up or until KF. Kidney survival was calculated from disease onset to event (KF or death) and censored at last follow-up. Results Of the 4066 patients meeting eligibility, median age at disease onset was 28 years (IQR 6-51), with children (&amp;lt;18 yrs) representing 39% of the study population. Median proteinuria was 6.4 g/g (IQR 3.1-10.8; n = 923), while mean eGFR was 118 mL/min/1.73 m2 (SD 49; n = 240) and 69 mL/min/1.73 m2 (SD 34; n = 906) for children and adults, respectively. Median follow-up duration was 8.2 yrs (IQR 4.3-13.1) with KF/death events occurring in 30% of patients. Mean TA-PCR was greater in children than adults (5.0 g/g (SD 13.9) vs. 1.9 g/g (SD 2.5), as was annual rate of loss of eGFR (−7.4 mL/min/1.73 m2 (SD 21.8) vs. −3.1 mL/min/1.73 m2 (SD 10.2)). Characteristics at disease onset and clinical outcomes of the INS cohort sub-categories are presented in Fig. 1. Kaplan Meier survival plots of each sub-category, and further divided into children and adults, illustrate the poor survival probability for patients with FSGS, particularly INS-genetic patients who are predominantly diagnosed in childhood (Fig. 2). While INS with no genetic or biopsy diagnosis presenting in childhood exhibits disease course and outcomes similar to MCD-biopsy patients, those diagnosed in adulthood have a more rapid disease course similar to FSGS-biopsy patients. Conclusion The RaDaR-INS cohort represents a large study population with lengthy follow-up data. These analyses illustrate the difference in disease progression and survival rates for INS patients with different causes or histological descriptions, highlighting in particular an unmet need for effective treatments for patients with nephrotic syndrome and FSGS.

Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study.

Keratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases. A genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90. Our present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3: rs2300163, EYA1: rs1077435, ASS1: rs141365191, and CHTF8: rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1: rs12622211, RXRA-COL5A1: rs3118515, rs3132306, rs1536482, rs3118520, KAT6B: rs192187772, RAP2A-IPO5: rs41361245) were observed to be associated with CCT, and one SNP (USP13: rs6767552) was found to be associated with Km. In the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.

Combined topography-guided photorefractive keratectomy and corneal collagen crosslinking.

This study aimed to report the long-term results of combined topography-guided photorefractive keratectomy (PRK) and accelerated corneal collagen cross-linking (CXL) for keratoconus using the Zeiss refractive coordinated system. A prospective interventional study was conducted in a tertiary eye care hospital in South India. Patients with mild-to-moderate progressive keratoconus and corneal pachymetry greater than 450 µm were included. They underwent customized topography-guided PRK followed by CXL. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings and complications were evaluated at 1, 3, 6, 12, and 24 months postoperatively. Thirty patients (30 eyes) were included in the study. All study parameters showed a statistically significant improvement postoperatively over baseline values. At 24 months, the mean UDVA improved from 0.8 ± 0.180 logarithm of the minimum angle of resolution (logMAR) to 0.38 ± 0.118 logMAR ( P -value <0.001) and CDVA improved from 0.467 ± 0.142 logMAR to 0.227 ± 0.078 logMAR ( P -value <0.001). The mean flat, steep, and maximum keratometry values were significantly reduced by 2.133, 3, and 4.54 diopters, respectively, at the last follow-up examination ( P -value <0.001). The combined topography-guided PRK and accelerated CXL procedure seem to be a promising treatment alternative for early keratoconus. This is the first such study on the Zeiss refractive coordinated system. However, further studies with a larger study population and longer follow-up periods are required to draw final conclusions about the benefits of this procedure in keratoconus.

A novel radiomics-based technique for identifying vulnerable coronary plaques: a follow-up study.

Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

Assessment of quantitative microflow Vascular Index in testicular cancer

PurposeUltrasound (US) is the primary imaging modality when a testicular tumor is suspected. Superb microvascular imaging (SMI) is a novel, highly sensitive Doppler technique that allows quantification of flow signals by determination of the Vascular Index (VI).The aim of the present study is to investigate the diagnostic significance of the SMI-derived VI in normal testicular tissue and testicular cancer. MethodsThis retrospective analysis included patients who underwent testicular US in our department from 2018 to 2022. Inclusion criteria were: i) sufficient image quality of the stored images, ii) US with standardized SMI-default setting (colour gain of 44 ± 5), iii) patient age ≥ 18 years, and iv) normal testicular findings or testicular tumor with histopathological workup. US examinations were performed as part of clinical routine using a high-end ultrasound system (Aplio i800/i900, Canon Medical Systems Corporation, Tochigi, Japan). Statistical analysis included Chi-square test and Mann-Whitney U tests and receiver operating characteristic (ROC) curve analysis. ResultsA total of 62 patients (31 each with normal findings and testicular tumors) were included. The VI differed statistically significantly (p < 0.001) between normal testis (median 2.5 %) and testicular tumors (median 17.4 %). Like vascular patterns (p < 0.001), the VI (p = 0.030) was shown to distinguish seminomas (median 14.8 %), non-seminomas (median 17.6 %) and lymphomas (median 34.5 %). ConclusionsIn conclusion, our study has shown the VI to be a quantitative tool that can add information for differentiating testicular tumor entities. While further confirmation in larger study populations is desirable, our results suggest that the VI may be a useful quantitative parameter.

Preoperative Tyrosine Kinase Inhibitors Before Percutaneous Cryoablation for Clinical T1b Renal Tumors.

Purpose To treat renal cell carcinoma, local ablative therapy is a viable alternative treatment option. Traditionally, cryoablation has been used for the treatment of T1a renal tumors. However, recent technological developments have expanded its application to encompass select T1b renal tumors. Here, we present a retrospective study of the utilization of preoperative tyrosine kinase inhibitors(TKIs) to induce tumor shrinkage and achieve favorable outcomes in percutaneous cryoablation (PCA). Methods We retrospectively evaluated the data from nine patients with clinical T1b renal tumors who underwent PCA. Six patients with TKI pretreatment at our institution between 2016 and 2018 were included in the study. We evaluated the safety and efficacy of preoperative TKIs prior to PCA. Results All patients received axitinib with a median treatment duration of 80.5 days (IQR: 49-85). All patients experienced tumor shrinkage (median: 13.5 mm; IQR: 7-16); five experienced downstaging to T1a following tumor shrinkage. There were no severe adverse events (common terminology criteria for adverse events (CTCAE) grade ≥ 3) in TKIs. After the discontinuation of TKIs for two weeks, all PCA procedures were performed successfully without any severe complications. During a median follow-up of 46 months, no local recurrence was observed in any of these cases. Conclusion In cases with large renal tumors, TKI pretreatment prior to PCA had potential benefits in terms of tumor shrinkage and long-term local control rate. Further well-designed studies in larger populations are needed to validate our findings.