Transverse versus longitudinal mucosal incision during POEM for esophageal motility disorders: a randomized trial.

BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.

Gastroesophageal reflux following per-oral endoscopic myotomy: Can we improve outcomes?

This editorial is an analysis the review article by Nabi et al recently published in this journal. Achalasia Cardia is a disease whose pathophysiology is still unclear. It is known that there is inflammation of unknown aetiology leading to loss of ganglion cells in the muscularis propria. The end result is lower oesophageal sphincter spasm, loss of receptive relaxation, decreased oesophageal peristalsis, all leading on to varying degrees of dysphagia. The treatment of this condition is palliative in nature, performed by myotomy of the lower oesophagus either surgically or endoscopically. Gastroesophageal reflux disease (GERD) has been associated with the myotomy performed, particularly with the Peroral Endoscopic Myotomy (POEM) procedure. Nabi et al have provided an excellent overview of the latest developments in predicting, preventing, evaluating, and managing GERD subsequent to POEM. Based on this theme, this review article explores the concept of using histology of the oesophageal muscle layer, to grade the disease and thereby help tailoring the length/type of myotomy performed during the POEM procedure. In the future, will a histology based algorithm available preoperatively, help modify the POEM procedure, thereby decreasing the incidence of GERD associated with POEM?

Right ventricle pierced by a traditional sharp hair straightener: a case report.

The case presents a traumatic ventricular perforation of a girl, accidentally felt on a sharp instrument. The uniqueness of the case presented is due to the very high infrequency of injuries with this type of sharp object. The 7-year-old girl was transported to the hospital after accidentally falling on a sharp instrument. The child had no signs of heart failure. On opening the chest, it was found that the metal object was lodged in the right ventricle. Quickly proceeded to remove the object and suture the entry hole. After a short hospitalization, the child was discharged completely cured.

Cardiovascular Autonomic Deficits in Different Types of Achalasia.

Background and objective Achalasia cardia is a primary esophageal motility disorder, and the etiopathology of this disease's progression is not known. Moreover, autonomic dysfunction has not been studied in different types of achalasia. In light of this, we aimed to address this lack of data in this study. Methods The diagnosis of achalasia was done using high-resolution esophageal manometry (HRM)-based Chicago classification v4.0. Autonomic function tests (AFT) such as the head-up tilt test, deep breathing test (DBT), Valsalva maneuver (VM), handgrip test (HGT), and cold pressor test (CPT), as well as the heart rate variability (HRV) test, were performed among the cohort and the results were compared with those of 39 age- and sex-matched healthy controls. Results AFT and HRV tests were done on 62 patients (30 achalasia type I, 28 type II, and 4 type III) and compared with 39 age- and sex-matched healthy controls. The mean duration of symptoms, high Eckardt score, and dysphagia were most common in type I achalasia, followed by type II and III. The results of AFT showed a generalized loss of parasympathetic and baroreflex-independent sympathetic reactivity in all types of achalasia. However, baroreflex-dependent cardiovascular adrenergic reactivity was normal. Regarding cardiac autonomic tone, there was a loss of parasympathetic and sympathetic influence, but sympathovagal balance was maintained. The severity of the loss of autonomic functions was higher in type I, followed by type II. Conclusions In all types of achalasia, parasympathetic reactivity, baroreflex-independent sympathetic reactivity, and cardiac autonomic tone were lower compared to healthy controls, and the severity of dysfunction increased during the progression of the disease from type II to type I.

Case Report: The molecular fingerprint and the clinical implication of an exceptional response to neoadjuvant therapy in a metastatic cardia adenocarcinoma.

Background: Globally, gastric cancer holds the fifth position in terms of prevalence among malignant tumors and is the fourth leading cause of cancer-related mortality. Particular attention should be paid to cardia adenocarcinoma (CA) due to its increasing incidence and poor prognosis. Diagnosis of CA frequently occurs in advanced stages because of its late symptoms. In such cases, neoadjuvant chemotherapy is the primary treatment option. The response to chemotherapy depends on multiple variables including the tumor's molecular profile, the patient's performance status, and the feasibility of using targeted therapy. Patients exhibiting an exceptional response, defined as a complete response to medical therapy lasting more than 1 year, or a partial response or stable disease lasting more than 2 years, are rarely described. This case report presents one of the longest-lasting exceptional responses to chemotherapy in metastatic cardia adenocarcinoma and discusses its clinical implications. Case presentation: A 49-year-old male patient presented with cardia adenocarcinoma (human epidermal growth factor receptor 2 negative, mismatch repair proficient) and liver metastases. Molecular profiling identified a pathogenic mutation in the TP53 gene (R123W; Arg123Trp) as the sole alteration found. Five months after initiating the neoadjuvant chemotherapy with fluorouracil-leucovorin-oxaliplatin-docetaxel, the patient achieved a complete clinical response. The molecular profile was compared with others previously documented in an international data portal, revealing a similar pattern. At 4 years and 3 months from diagnosis, the exceptional response was still confirmed. The patient underwent a cumulative number of 33 cycles of chemotherapy, leading to chemotherapy-induced liver damage. Conclusions: Exceptional responses to neoadjuvant chemotherapy in cardia adenocarcinomas are rarely reported. The documentation of exceptional responses to cancer therapies should be included in large data repositories to explore the molecular fingerprint of these tumors. In such cases, the clinical implications of long-term chemotherapy should always be taken into account.

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Association of Cardiovascular Health in Young Adulthood with Long-Term Blood Pressure Trajectories.

BACKGROUND: Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life BP trajectories. METHODS: Baseline CVH (defined by 7 of AHA's Life's Essential 8 [LE8] metrics, excluding BP) was measured in YA with individual metrics scored and averaged as a composite LE8 score. Categorical CVH status was defined as high, moderate, and low. Latent class analysis was used to identify trajectories of mid-BP (mean of SBP and DBP) from average ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status (continuously and categorically) with mid-life BP trajectory group membership. RESULTS: There were 3,688 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study in YA with follow-up data for mid-life BP trajectories. We observed 3 BP trajectory groups, labeled as Persistently-Low, Middle, and High-Increasing. On average, each 10-points higher baseline LE8 score (mean [SD] of 73.5 [13.1]) in YA was associated with adjusted odds ratios of 0.78 (95% CI, 0.72-0.84) for membership in the Middle and 0.65 (0.57-0.73) for membership in the High-Increasing trajectory groups. Compared with categorical low CVH status at baseline, those with high CVH were significantly less likely to be in the Middle and High-Increasing BP trajectory groups. CONCLUSIONS: Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that young adult CVH promotion may be important for primordial prevention of hypertension.

End-Stage Achalasia With Megaesophagus Refractory to Two Heller Myotomies.

Achalasia is a motility disorder of the esophagus in which the lower esophageal sphincter fails to relax. Megaesophagus is a rare complication of achalasia characterized by severe dilatation of the esophagus, often indicative of end-stage achalasia. Typical presenting symptoms include dysphagia, nausea, vomiting, weight loss, and chest pain. The majority of patients with achalasia typically have excellent outcomes after surgical intervention with Heller myotomy. We discuss an interesting case of unsuccessful surgical intervention and hypothesize the reason for its failure in our patient.

Efficacy and safety of laparoscopic Heller's myotomy versus pneumatic dilatation for achalasia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Achalasia has several treatment modalities. We aim to compare the efficacy and safety of laparoscopic Heller myotomy (LHM) with those of pneumatic dilatation (PD) in adult patients suffering from achalasia. METHODS: We searched Cochrane CENTRAL, PubMed, Web of Science, SCOPUS and Embase for related clinical trials about patients suffering from achalasia. The quality appraisal and assessment of risk of bias were conducted with GRADE and Cochrane's risk of bias tool, respectively. Homogeneous and heterogeneous data was analyzed under fixed and random-effects models, respectively. RESULTS: The pooled analysis of 10 studies showed that PD was associated with a higher rate of remission at three months, one year, three years and five years (RR = 1.25 [1.09, 1.42] (p = 0.001); RR = 1.13 [1.05, 1.20] (p = 0.0004); RR = 1.48 [1.19, 1.82] (p = 0.0003); RR = 1.49 [1.18, 1.89] (p = 0.001)), respectively. LHM was associated with lower number of cases suffering from adverse events, dysphagia and relapses (RR = 0.50 [0.25, 0.98] (p = 0.04); RR = 0.33 [0.16, 0.71] (p = 0.004); RR = 0.38 [0.15, 0.97] (p = 0.04)), respectively. There is no significant difference between both groups regarding the lower esophageal pressure, perforations, remission rate at two years, Eckardt score after one year and reflux. CONCLUSION: PD had higher remission rates than LHM at three months, one year and three years, but not at two years or five years. More research is needed to determine whether PD has a significant advantage over LHM in terms of long-term remission rates.

Prediction, prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy: An update.

Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Utility of multimodal longitudinal imaging data for dynamic prediction of cardiovascular and renal disease: the CARDIA study.

Background: Medical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD). Methods: In a multi-centered cohort of 5,114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy x-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985-2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors. Results: Longitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors; best model's C-index = 0.80-0.83 up to 20 years from baseline) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10-15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction. Conclusions: Longitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.

Delayed Presentation of Malignancy-Associated Pseudoachalasia of the Gastric Cardia.

Pseudoachalasia is a condition in which symptoms, manometry, and imaging findings highly resemble primary achalasia but has a secondary etiology. The majority of patients with pseudoachalasia have the condition as the result of a malignancy, most often at the gastroesophageal junction. There may be issues with timely identification of this malignancy as symptoms are often obscure with diagnostic testing yielding nonspecific results. We describe a case of a 65-year-old diabetic female smoker with a four-month history of intractable vomiting, abdominal pain, and weight loss who was belatedly found to have an adenocarcinoma at the gastric cardia necessitating a total gastrectomy and chemotherapy administration. The case educates clinicians on the clinical alarm symptoms related to malignant pseudoachalasia and stresses the paramount importance of performing a timely esophagogastroduodenoscopy in all cases of achalasia, even with seemingly normal imaging, to rule out pseudoachalasia related to malignancy.

Trends of gastric cancer burdens attributable to risk factors in China from 2000 to 2050.

Background: The incidence of gastric cancer (GC) decreased in past decades, which was thought largely attributable to risk factors control, yet China still accounts for 44% of global GC burdens. We aimed to estimate changing trajectories of proportions of GC burdens attributable to modifiable risk factors from 2000 to 2050 in China, to inform future targeted preventive strategies. Methods: The incidence and new cases of GC were predicted to 2050 using Bayesian age-period-cohort model based on incidence data by anatomical subsites drawn from 682 cancer registries from National Central Cancer Registry. Population attributable fractions (PAFs) were calculated based on prevalence of risk factors and relative risks with GC. Temporal trends of PAFs were described by sex and categories of risk factors using joinpoint analysis. Findings: We observed declining trends of PAFs of Helicobacter pylori (H. pylori) infection, smoking, pickled vegetable and alcohol consumption, but increasing trends of PAFs of unhealthy body mass index and diabetes for GC in China. The combined PAFs of these risk factors were estimated to decrease by 10.57% from 2000 to 2050 for GC. We estimated there will be 279,707 GC (122,796 cardia gastric cancer [CGC] and 156,911 non-cardia gastric cancer [NCGC]) cases in 2050. Out of these cases, 70.18% of GC cases could be attributable to modifiable risk factors, while H. pylori infection was predicted to be responsible for 40.7% of CGC and 62.1% of NCGC cases in 2050. Interpretation: More than half of GC remained attributable to modifiable risk factors in China. Continued effective strategies on risk factors control are needed to reduce the burden of this highly life-threatening cancer in future. Funding: Beijing Nova Program (No. Z201100006820069), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-023), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-010), Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).

A retrospective study of 3D measurement and analysis applied in the morphological evaluation of achalasia cardia.

Background: Achalasia cardia (AC) is defined as a disorder of esophageal motility whose diagnostic gold standard depends on high-resolution manometry (HRM). The invasiveness of HRM can cause difficulties in diagnosis, treatment, and follow-up for patients with AC. Thus, we aimed to investigate the function of 3D reconstruction and measurement to prove the wide application of this alternative non-invasive approach for AC. Methods: A total of 126 patients with AC and 40 healthy subjects in Tianjin Medical University General Hospital from January 2018 to October 2022 were enrolled in this retrospective study. Chest CT images of these subjects were used to reconstruct the 3D models of the esophagus, stomach, spine, left crus, and right crus. Measurements of esophagus length, volume of esophagus, gastroesophageal insertion angle (His angle), max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, esophagus-spine angle, and spine-lower esophageal sphincter (LES) angle were applied based on the models. Results: Retrocardiac esophagus length, volume of esophagus, max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, thoracic esophagus-spine angle, and spine-LES angle in the AC group were higher than those in the control group (all P values <0.05). Among the three subtypes of AC, thoracic esophagus length, intra-abdominal LES length, volume of esophagus, His angle, esophagus maximum transverse and longitudinal diameter, and thoracic esophagus-spine angle all presented statistical differences (all P values <0.05). Correlation analysis revealed that manometric types were positively associated with His angle [r=0.196; 95% confidence interval (CI): 0.009, 0.372; P=0.028] but negatively associated with volume of esophagus (r=-0.480; 95% CI: -0.639, -0.310; P<0.001), esophagus maximum transverse diameter (r=-0.551; 95% CI: -0.679, -0.400; P<0.001), esophagus maximum longitudinal diameter (r=-0.518; 95% CI: -0.649, -0.366; P<0.001), and thoracic esophagus-spine angle (r=-0.324; 95% CI: -0.479, -0.157; P<0.001). Conclusions: This study successfully presented the differences in esophageal length, volume, thickness, and angles between healthy subjects and different AC subtypes on the basis of 3D reconstruction and measurement. Thus, 3D model and measurement can be regarded as a good support for further research and make a valuable contribution to developing non-invasive approaches for AC management.

An elevated urinary albumin-to-creatinine ratio increases the risk of incident cardia-cerebrovascular disease in individuals with type 2 diabetes.

AIMS: We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). METHODS: We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). Cox regression models and restricted cubic spline were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. RESULTS: During a median follow-up of 4.05 years, 560 participants developed first CVD event (6.24%). After adjustment for potential confounders, participants with microalbuminuria had higher risks of CVD compared with normal uACR, with HRs of 1.57(95% CI 1.04-2.37) for myocardial infarction, 1.24(95% CI 1.00-1.54) for ischemic stroke,1.62(95% CI 0.73-3.61) for hemorrhagic stroke, and 1.30(95% CI 1.07-1.57) for total CVD. The risks gradually attenuated with uACR increase, with HRs of 2.86(95% CI 1.63-5.00) for myocardial infarction, 2.46(95% CI 1.83-3.30) for ischemic stroke, 4.69(95% CI 1.72-12.78) for hemorrhagic stroke, and 2.42(95% CI 1.85-3.15) for total CVD in macroalbuminuria. The addition of uACR to established CVD risk models improved the CVD risk prediction efficacy. CONCLUSIONS: Increasing uACR, even below the normal range, is an independent risk factor for new-onset CVD in T2D population. Furthermore, uACR could improve the risk prediction for CVD among community based T2D patients.

Evidence for the Association Between Adverse Childhood Family Environment, Child Abuse, and Caregiver Warmth and Cardiovascular Health Across the Lifespan: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: This study aimed to quantify the association between childhood family environment and longitudinal cardiovascular health (CVH) in adult CARDIA (Coronary Artery Risk Development in Young Adults) Study participants. We further investigated whether the association differs by adult income. METHODS: We applied the CVH framework from the American Heart Association including metrics for smoking, cholesterol, blood pressure, glucose, body mass index, physical activity, and diet. CVH scores (range, 0-14) were calculated at years 0, 7, and 20 of the study. Risky Family environment (range, 7-28) was assessed at year 15 retrospectively, for childhood experiences of abuse, caregiver warmth, and family or household challenges. Complete case ordinal logistic regression and mixed models associated risky family (exposure) with CVH (outcome), adjusting for age, sex, race, and alcohol use. RESULTS: The sample (n=2074) had a mean age of 25.3 (±3.5) years and 56% females at baseline. The median risky family was 10 with ideal CVH (≥12) met by 288 individuals at baseline (28.4%) and 165 (16.3%) at year 20. Longitudinally, for every 1-unit greater risky family, the odds of attaining high CVH (≥10) decreased by 3.6% (OR, 0.9645 [95% CI, 0.94-0.98]). Each unit greater child abuse and caregiver warmth score corresponded to 12.8% lower and 11.7% higher odds of ideal CVH (≥10), respectively (OR, 0.872 [95% CI, 0.77-0.99]; OR, 1.1165 [95% CI, 1.01-1.24]), across all 20 years of follow-up. Stratified analyses by income in adulthood demonstrated associations between risky family environment and CVH remained significant for those of the highest adult income (>$74k), but not the lowest (<$35k). CONCLUSIONS: Although risky family environmental factors in childhood increase the odds of poor longitudinal adult CVH, caregiver warmth may increase the odds of CVH, and socioeconomic attainment in adulthood may contextualize the level of risk. Toward a paradigm of primordial prevention of cardiovascular disease, childhood exposures and economic opportunity may play a crucial role in CVH across the life course.

Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

Long-term outcomes of laparoscopic Heller's myotomy with angle of His accentuation in patients of achalasia cardia.

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.