Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Clinical characteristics and long-term management for patients with vitamin D-dependent rickets type II: a retrospective study at a single center in Saudi Arabia.

Introduction: Hereditary Vitamin D-dependent rickets type II (HVDDR-type II) is a rare autosomal recessive disorder caused by molecular variation in the gene encoding the vitamin D receptor (VDR). This study aims to evaluate phenotype and genotype characteristics and long-term follow-up of the largest group of patients with (HVDDR-type II) in Saudi Arabia. Methodology: We conducted a retrospective chart review to collect the clinical, biochemical, and genetic data for all HVDDR-type II patients currently receiving treatment at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. Results: A total of 42 patients, 57.1% female, and 42.9% male were included in the study. Seven patients were treated with high doses of oral calcium, while 35 patients were treated with IV calcium infusion. The median age at presentation was 15.5 months. Alopecia was found in 97.6%, 21.4% presented with bowing legs, 14.3% with delayed walking, 9.5% with seizure, and 2.4% presented with respiratory failure, while a family history of the disease was positive in 71.4% of total patients. Molecular genetic testing of the VDR gene in our cohort identified six different gene variants c.885 C>A (p.Tyr295Ter), c.88 C>T (p.Arg30Ter), c.1036G>A (p.Val346Met), c.820C>T (p.Arg274Cys), c.803 T>C (p.Ile268Thr), and c.2T>G (p.Met1?). Conclusion: We are describing the largest cohort of patients with HVDDR-type II, their clinical biochemical findings, and the most prevalent genetic variants in our population.

The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents.

INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Would the one-stage combined approach lead to better long-term neurological outcomes than the posterior approach alone in multilevel degenerative cervical myelopathy patients with T2-Weighted increased signal intensity? An 8-year follow-up results and propensity score matching analysis.

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.

The predictors of short and long term urinary continence recovery after laparoscopic radical prostatectomy: a single cancer center report in China.

PURPOSE: To evaluate the predictors for short and long term urinary continence (UC) recovery after laparoscopic radical prostatectomy (LRP) from clinical and oncological variables. METHODS: We retrospectively collected data from 142 prostate cancer patients who underwent LRP between September 2014 and June 2021 at a tumor specialist diagnosis and treatment center in China. The rate of post-prostatectomy incontinence (PPI) was evaluated from immediate and at 3, 6 and 12 mo after LRP, and UC was defined as the use of no or one safety pad. Sixteen clinical and oncological variables were analyzed by univariate and multivariate regression analysis to determine whether they were associated with short (3 mo) or long term (12 mo) UC recovery after LRP. RESULTS: After eliminating patients who were lost to follow-up, 129 patients were eventually included. The mean ± SD age was 68 ± 6.3 years. The UC rates of immediate, 3, 6 and 12 mo after the operation were 27.9%, 54.3%, 75.2% and 88.4%, respectively. Multivariate analyses revealed that membranous urethral length (MUL) was a protective predictor of UC after catheter extraction(P < 0.001), and at 3 mo (P < 0.001), 6 mo (P < 0.001) and 12 mo (P = 0.009) after surgery. CONCLUSION: MUL is a significant independent factor that can contribute to short and long term UC recovery post-LRP, which may assist clinicians and their patients in counseling of treatment.

Oligo-residual disease in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer: incidence, pattern of failure, and clinical value of local consolidative therapy.

OBJECTIVES: To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients with measurable disease in three academic centers were screened and those with adequate follow-up were included. Oligo-residual disease (ORD) was defined as residual tumors limited to three organs and five lesions evaluated at the best response among patients with partial response or stable disease after PD-1/PD-L1 inhibitors. Oligometastatic and multiple-metastatic disease (OMD/MMD) were similarly classified at baseline. Locoregional interventions, administered after effective treatment of PD-1/PD-L1 inhibitors and before initial disease progression, were defined as LCT. Patterns of initial progressive disease (PD) were classified as involving only residual sites (RP), only new sites (NP), or a combination of both (BP). RESULTS: Among the 698 patients included, ORD was documented in 73 (47.1%) of 155 patients with baseline OMD and 60 (11.0%) of 543 patients with baseline MMD. With a median follow-up of 31.0 (range, 6.0-53.0) months, 108 patients with ORD developed initial PD, with RP, NP, and BP occurring in 51 (47%), 23 (21.3%), and 34 (31.5%), respectively. Among the 133 patients with ORD, those receiving LCT (n = 43) had longer progression-free survival (HR = 0.58, 95% CI 0.40-0.85, p = 0.01) and overall survival (HR = 0.49, 95% CI 0.30-0.79, p < 0.0001). CONCLUSION: ORD occurs with a clinically relevant frequency among PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients and LCT may provide extra survival benefits in those with ORD.

Time In Tight Range in children and adolescents with type 1 diabetes: A cross-sectional observational single centre study evaluating efficacy of new advanced technologies.

INTRODUCTION: Early and tight glycaemic control is crucial to prevent long-term complications of Type 1 Diabetes (T1D). The aim of our study was to compare glucose metrics, including Time In Tight Range (TITR), in a real-world setting. METHODS: We performed a single-centre cross-sectional study in 534 children and adolescents with T1D. Participants were divided into four groups (multiple daily injections + real-time Continuous glucose monitoring (CGM), multiple daily injections + intermittently scanned CGM, sensor augmented pump (SAP), and Advanced Hybrid Closed-Loop (AHCL). Demographical and clinical data were collected and analysed. RESULTS: The group with AHCL showed significantly higher Time In Range (TIR) (71.31% ± 10.88) than SAP (57.82% ± 14.98; p < 0.001), MDI + rtCGM (54.56% ± 17.04; p < 0.001) and MDI + isCGM (52.17% ± 19.36; p < 0.001) groups with a lower Time Above Range (p < 0.001). The group with AHCL also showed lower Time Below Range than MDI + isCGM and SAP groups (p < 0.01). The overall TITR was 37% ± 14 with 19% of participants who reached a TITR ≥50% with a mean TIR of 81%. AHCL had significantly higher TITR (45.46% ± 11.77) than SAP (36.25% ± 13.53; p < 0.001), MDI + rtCGM (34.03% ± 13.89; p < 0.001) and MDI + isCGM (33.37% ± 15.84; p < 0.001) groups with a lower Coefficient of Variation (p < 0.001). CONCLUSIONS: Our study indicates that AHCL ensures a better glycaemic control with an improvement in both TIR and TITR, along with a reduction in CV. Implementation of automated insulin delivery systems should be considered in the treatment of children and adolescents with T1D.

Predicting successful ageing among older adults seems possible even as far as two decades ahead.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants' physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing. RESULTS: All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models. CONCLUSIONS: Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully.

Application of modified Yamane technique in intrascleral intraocular lens fixation combined with or without iris reconstruction.

AIMS: To explore the application and long-term clinical effects of modified Yamane technique in intrascleral intraocular lens (IOL) fixation combined with or without iris reconstruction. SETTINGS AND DESIGN: The data of patients receiving IOL fixation with modified Yamane technique in an ophthalmology department between December 2021 and August 2023 were analyzed retrospectively. The longest follow-up duration was > 12 months. METHODS AND MATERIAL: The trailing haptic was fixed with the needle before the leading haptic. The silicone haptic stoppers were used to stabilize the IOL when iris reconstruction was combined. Preoperative and postoperative best-corrected visual acuity (BCVA), corneal endothelial cells (CECs), postoperative intraocular pressure (IOP), surgical indications and methods, and postoperative complications were recorded. Anterior segment optical coherence tomography (OCT) was used to evaluate IOL decentration and tilt. The paired sample t-test or Wilcoxon rank sum test were used to compare the results of the same index before and after the operation. RESULTS: Twelve patients (12 eyes) were included in this cohort. There were 1 case of IOL dislocation, eight cases of lens dislocation or subluxation, and three cases of aphakia. Traumatic lens dislocation was the main cause of aphakia. Primary lens extraction was performed in previous surgeries, and all three were combined with pars plana vitrectomy (PPV). Four of 12 patients underwent IOL fixation and iris reconstruction. The mean age of participants was 63 ± 10.61 years. The mean BCVA increased from 0.89 ± 0.72 logMAR to 0.39 ± 0.56 logMAR at the last visit (p < 0.05). The postoperative relative refractive error was - 0.13 ± 0.42 D (-0.60 D to + 0.57 D). The OCT showed that the IOLs were well centered, with a mean decentration of 0.20 ± 0.13 mm and a mean tilt of 2.31°±0.93°. Ten patients did not experience any complications. CONCLUSIONS: The modified Yamane technique in IOL fixation surgery, especially combined with iris reconstruction, reduces operation difficulty, increases operational stability and safety, and improves postoperative visual acuity without serious intra- or postoperative complications. The long-term improvement effect was remarkable.

Improvement of absorbability, osteoconductivity, and strength of a ß-tricalcium phosphate spacer for opening wedge high tibial osteotomy: clinical evaluations with 106 patients.

BACKGROUND: An ideal synthetic spacer for medial opening wedge high tibial osteotomy (MOWHTO) has not yet been developed. The authors have developed a new ß-tricalcium phosphate (ß-TCP) spacer with 60% porosity (N-CP60) by modifying the micro- and macro-pore structures of a conventional ß-TCP spacer (CP60) that is widely used in clinical practice. The purpose of this study was to compare the absorbability, osteoconductivity, and in vivo strength of the N-CP60 spacer with those of the CP60 spacer, when used in MOWHTO. METHODS: First, the porosity, diameter distribution of macro- and micropores, and compressive strength of each ß-TCP block were examined using methodology of biomaterial science. Secondly, a clinical study was performed using a total of 106 patients (106 knees) with MOWHTO, who were followed up for 18 months after surgery. In these knees, the N-CP60 and CP-60 spacers were implanted into 49 tibias and 57 tibias, respectively. The absorbability and osteoconductivity were radiologically evaluated by measuring the area of the implanted spacer remaining unabsorbed and assessing with the Hemert's score, respectively. The incidence of cracking in the implanted spacers was determined using computed radiography. Statistical comparisons were made with non-parametric tests. The significance level was set at p = 0.05. RESULTS: The N-CP60 and CP60 blocks had almost the same porosity (mean, 61.0% and 58.7%, respectively). The diameter of macropores was significantly larger (p < 0.0001) in the N-CP60 block than in the CP60 block, while the diameter of micropores was significantly smaller (p = 0.019) in the N-CP60 block. The ultimate strength of the N-CP60 block (median, 36.8 MPa) was significantly greater (p < 0.01) than that of the CP60 block (31.6 MPa). As for the clinical evaluations, the absorption rate of the N-CP60 spacer at 18 months after implantation (mean, 48.0%) was significantly greater (p < 0.001) than that of the CP60 spacer (29.0%). The osteoconductivity of the N-CP60 spacer was slightly but significantly higher (p = 0.0408) than that of the CP60 spacer only in zone 1. The incidence of in vivo cracking of the posteriorly located N-CP60 spacer at one month (mean, 75.5%) was significantly lower (p = 0.0035) than that of the CP60 spacer (91.2%). CONCLUSIONS: The absorbability, osteoconductivity, and compressive strength of the new N-CP60 spacer were significantly improved by modifying the macro- and micro-pore structures, compared with the conventional CP60 spacer. The N-CP60 spacer is more clinically useful than the CP60 spacer. TRIAL REGISTRATION NUMBER: H29-0002.

Comparison of gasless transaxillary endoscopic thyroidectomy, endoscopic thyroidectomy via areola approach and conventional open thyroidectomy in patients with unilateral papillary thyroid carcinoma.

BACKGROUND: Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. METHODS: Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. RESULTS: Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. CONCLUSIONS: The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

Long-term cardiac computed tomography follow-up after left atrial appendage occlusion.

BACKGROUND: Left atrial appendage occlusion (LAAO) is performed increasingly, but long-term follow-up imaging data are lacking. AIMS: The aim of this study was to evaluate the safety and durability of the Amplatzer Amulet device >4 years after LAAO. METHODS: This was a prospective observational cohort study including 52 patients implanted with the Amplatzer Amulet device at Aarhus University Hospital, Denmark. A >4-year follow-up cardiac computed tomography (CT) scan after LAAO was performed and compared with the results from the 2-month and 12-month scans. The primary outcome was left atrial appendage (LAA) sealing based on distal LAA contrast patency and peridevice leakage (PDL), stratified into complete occlusion (grade 0 [G0]) and grade 1-3 leakage (G1-3), respectively. Secondary outcomes were low- and high-grade hypoattenuated thickening (HAT), device-related thrombosis (DRT) and device durability. RESULTS: The median (interquartile range [IQR]) follow-up time from LAAO to the latest CT scan was 5.8 years (4.5; 6.3). At 2-month (n=52), 12-month (n=27) and >4-year CT follow-ups (n=52), rates of both complete occlusion (33%, 37%, 35%) and G2 leaks (52%, 52%, 48%) remained stable. Rates of G1 leaks varied (14%, 4%, 6%) and G3 leaks rose (2%, 7%, 12%) from earliest to latest follow-up. The median left atrial (LA) volume increased from 127 mL (96; 176) to 144 mL (108; 182) and 147 mL (107; 193). No DRT was found. The structural device integrity was preserved. CONCLUSIONS: This study indicates a stable LAA sealing status throughout the follow-up period, emphasising the importance of the procedural result in avoiding PDL. Few patients displayed PDL progression, which might partly be related to LA remodelling with increasing volume. The long-term device durability appears excellent. Larger studies are warranted to confirm these findings.

Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up.

BACKGROUND: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life. METHODS: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1-3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year. RESULTS: Objectively assessed olfactory dysfunction at 1-3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+. CONCLUSION: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.

Significance of metastatic lymph nodes ratio in overall survival for patients with resected nonsmall cell lung cancer: a retrospective cohort study.

OBJECTIVE: The tumor, node and metastasis stage is widely applied to classify lung cancer and is the foundation of clinical decisions. However, increasing studies have pointed out that this staging system is not precise enough for the N status. In this study, we aim to build a convenient survival prediction model that incorporates the current items of lymph node status. METHODS: We performed a retrospective cohort study and collected the data from resectable nonsmall cell lung cancer (NSCLC) (IA-IIIB) patients from the Surveillance, Epidemiology, and End Results database (2006-2015). The x-tile program was applied to calculate the optimal threshold of metastatic lymph node ratio (MLNR). Then, independent prognostic factors were determined by multivariable Cox regression analysis and enrolled to build a nomogram model. The calibration curve as well as the Concordance Index (C-index) were selected to evaluate the nomogram. Finally, patients were grouped based on their specified risk points and divided into three risk levels. The prognostic value of MLNR and examined lymph node numbers (ELNs) were presented in subgroups. RESULTS TOTALLY,: 40853 NSCLC patients after surgery were finally enrolled and analyzed. Age, metastatic lymph node ratio, histology type, adjuvant treatment and American Joint Committee on Cancer 8th T stage were deemed as independent prognostic parameters after multivariable Cox regression analysis. A nomogram was built using those variables, and its efficiency in predicting patients' survival was better than the conventional American Joint Committee on Cancer stage system after evaluation. Our new model has a significantly higher concordance Index (C-index) (training set, 0.683 v 0.641, respectively; P < 0.01; testing set, 0.676 v 0.638, respectively; P < 0.05). Similarly, the calibration curve shows the nomogram was in better accordance with the actual observations in both cohorts. Then, after risk stratification, we found that MLNR is more reliable than ELNs in predicting overall survival. CONCLUSION: We developed a nomogram model for NSCLC patients after surgery. This novel and useful tool outperforms the widely used tumor, node and metastasis staging system and could benefit clinicians in treatment options and cancer control.

Long-term clinical outcomes of bariatric surgery in adults with severe obesity: A population-based retrospective cohort study.

BACKGROUND: Bariatric surgery leads to sustained weight loss in a majority of recipients, and also reduces fasting insulin levels and markers of inflammation. We described the long-term associations between bariatric surgery and clinical outcomes including 30 morbidities. METHODS: We did a retrospective population-based cohort study of 304,157 adults with severe obesity, living in Alberta, Canada; 6,212 of whom had bariatric surgery. We modelled adjusted time to mortality, hospitalization, surgery and the adjusted incidence/prevalence of 30 new or ongoing morbidities after 5 years of follow-up. RESULTS: Over a median follow-up of 4.4 years (range 1 day-22.0 years), bariatric surgery was associated with increased risk of hospitalization (HR 1.46, 95% CI 1.41,1.51) and additional surgery (HR 1.42, 95% CI 1.32,1.52) but with a decreased risk of mortality (HR 0.76, 95% CI 0.64,0.91). After 5 years (median of 9.9 years), bariatric surgery was associated with a lower risk of severe chronic kidney disease (HR 0.45, 95% CI 0.27,0.75), coronary disease (HR 0.49, 95% CI 0.33,0.72), diabetes (HR 0.51, 95% CI 0.47,0.56), inflammatory bowel disease (HR 0.55, 95% CI 0.37,0.83), hypertension (HR 0.70, 95% CI 0.66,0.75), chronic pulmonary disease (HR 0.75, 95% CI 0.66,0.86), asthma (HR 0.79, 95% 0.65,0.96), cancer (HR 0.79, 95% CI 0.65,0.96), and chronic heart failure (HR 0.79, 95% CI 0.64,0.96). In contrast, after 5 years, bariatric surgery was associated with an increased risk of peptic ulcer (HR 1.99, 95% CI 1.32,3.01), alcohol misuse (HR 1.55, 95% CI 1.25,1.94), frailty (HR 1.28, 95% 1.11,1.46), severe constipation (HR 1.26, 95% CI 1.07,1.49), sleep disturbance (HR 1.21, 95% CI 1.08,1.35), depression (HR 1.18, 95% CI 1.10,1.27), and chronic pain (HR 1.12, 95% CI 1.04,1.20). INTERPRETATION: Bariatric surgery was associated with lower risks of death and certain morbidities. However, bariatric surgery was also associated with increased risk of hospitalization and additional surgery, as well as certain other morbidities. Since values and preferences for these various benefits and harms may differ between individuals, this suggests that comprehensive counselling should be offered to patients considering bariatric surgery.

Correlation between the triglyceride-glucose index and chronic kidney disease among adults with metabolic-associated fatty liver disease: fourteen-year follow-up.

Background and aims: According to previous studies, triglyceride-glucose (TyG) is related to chronic kidney disease (CKD), but no studies have explored the correlation between TyG and CKD among adults with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to explore the associations of the TyG index with CKD among adults with MAFLD. Methods: In this retrospective observational cohort study, data from 11,860 participants who underwent a minimum of three health assessments between 2008 and 2015 were retrospectively collected. Participants were followed up until the final medical visit or health examination. CKD refers to an eGFR < 60 mL/min per 1·73 m2 or the occurrence of two or more incidents of proteinuria. Results: Within a median 10·02-year follow-up period, 2005 (16·9%) participants reported developing CKD. Multivariate Cox regression models indicated a noticeable correlation between the TyG index and CKD incidence (HR per unit increase, 1.19; 95% CI: 1.09-1.29) and between the TyG index and CKD incidence (HR per SD increase, 1.12; 95% CI: 1.06-1.18). The CKD incidence increased by 1.8 times in participants in the highest TyG index quartile relative to patients in the lowest quartile of the TyG index quartile (HR 1·18, 95% CI: 1.01-1.38, P = 0.007). According to subgroup analysis, an elevated TyG index is likely to become more harmful to participants younger than 60 years (P for interaction = 0.035). Conclusion: An elevated TyG index may increase CKD incidence among MAFLD adults, particularly among younger people. Early intervention may help reduce the incidence of CKD.

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

Applicability of Oculomics for Individual Risk Prediction: Repeatability and Robustness of Retinal Fractal Dimension Using DART and AutoMorph.

Purpose: To investigate whether fractal dimension (FD)-based oculomics could be used for individual risk prediction by evaluating repeatability and robustness. Methods: We used two datasets: "Caledonia," healthy adults imaged multiple times in quick succession for research (26 subjects, 39 eyes, 377 color fundus images), and GRAPE, glaucoma patients with baseline and follow-up visits (106 subjects, 196 eyes, 392 images). Mean follow-up time was 18.3 months in GRAPE; thus it provides a pessimistic lower bound because vasculature could change. FD was computed with DART and AutoMorph. Image quality was assessed with QuickQual, but no images were initially excluded. Pearson, Spearman, and intraclass correlation (ICC) were used for population-level repeatability. For individual-level repeatability, we introduce measurement noise parameter λ, which is within-eye standard deviation (SD) of FD measurements in units of between-eyes SD. Results: In Caledonia, ICC was 0.8153 for DART and 0.5779 for AutoMorph, Pearson/Spearman correlation (first and last image) 0.7857/0.7824 for DART, and 0.3933/0.6253 for AutoMorph. In GRAPE, Pearson/Spearman correlation (first and next visit) was 0.7479/0.7474 for DART, and 0.7109/0.7208 for AutoMorph (all P < 0.0001). Median λ in Caledonia without exclusions was 3.55% for DART and 12.65% for AutoMorph and improved to up to 1.67% and 6.64% with quality-based exclusions, respectively. Quality exclusions primarily mitigated large outliers. Worst quality in an eye correlated strongly with λ (Pearson 0.5350-0.7550, depending on dataset and method, all P < 0.0001). Conclusions: Repeatability was sufficient for individual-level predictions in heterogeneous populations. DART performed better on all metrics and might be able to detect small, longitudinal changes, highlighting the potential of robust methods.

Long-term endoscopic gastric mucosal changes up to 20 years after Helicobacter pylori eradication therapy.

Helicobacter pylori eradication therapy reduces the risk of gastric cancer. However, it is unclear whether the severity of risk factors for gastric cancer such as atrophy and intestinal metaplasia are reduced after eradication in the long term. We aimed to study long-term changes in endoscopic risk factors for gastric cancer up to 20 years post-eradication. The endoscopic severity of gastritis according to the Kyoto Classification of Gastritis in 167 patients was retrospectively evaluated over an average follow-up 15.7 years. A significant improvement in mean total gastric cancer risk score (4.36 ± 1.66 to 2.69 ± 1.07, p < 0.001), atrophy (1.73 ± 0.44 to 1.61 ± 0.49, p = 0.004), and diffuse redness (1.22 ± 0.79 to 0.02 ± 0.13, p < 0.001) was observed compared to baseline in the Eradication group. However, there was no change in the never infection and current infection groups. The frequency of map-like redness increased over time until 15 years (3.6% to 18.7%, p = 0.03). The Cancer group had significantly higher risk scores at all time points. Endoscopic atrophy significantly improved in eradicated patients over long-term, suggested that eradication is one of the key elements in gastric cancer prevention. Individualized surveillance strategies based on endoscopic gastritis severity before eradication may be important for those at risk of gastric cancer.

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study.

Aims: We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. Material and methods: We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. Results: The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. Conclusions: In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.