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.

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.

Acute sleep deprivation induces synaptic remodeling at the soleus muscle neuromuscular junction in rats.

Sleep is important for cognitive and physical performance. Sleep deprivation not only affects neural functions but also results in muscular fatigue. A good night's sleep reverses these functional derangements caused by sleep deprivation. The role of sleep in brain function has been extensively studied. However, its role in neuromuscular junction (NMJ) or skeletal muscle morphology is sparsely addressed although skeletal muscle atonia and suspended thermoregulation during rapid eye movement sleep possibly provide a conducive environment for the muscle to rest and repair; somewhat similar to slow-wave sleep for synaptic downscaling. In the present study, we have investigated the effect of 24 h sleep deprivation on the NMJ morphology and neurochemistry using electron microscopy and immunohistochemistry in the rat soleus muscle. Acute sleep deprivation altered synaptic ultra-structure viz. mitochondria, synaptic vesicle, synaptic proteins, basal lamina, and junctional folds needed for neuromuscular transmission. Further acute sleep deprivation showed the depletion of the neurotransmitter acetylcholine and the overactivity of its degrading enzyme acetylcholine esterase at the NMJ. The impact of sleep deprivation on synaptic homeostasis in the brain has been extensively reported recently. The present evidence from our studies shows new information on the role of sleep on the NMJ homeostasis and its functioning.

Effect of Tratak (Yogic Ocular Exercises) on Intraocular Pressure in Glaucoma: An RCT.

Introduction: In healthy subjects, the intraocular pressure (IOP) is maintained by a dynamic equilibrium between continuous production of aqueous humor by ciliary bodies and continuous outflow through the two drainage pathways: trabecular meshwork and uveoscleral outflow. Here, we hypothesized that yogic ocular exercises, including extraocular muscles exercise, and modified Tratak Kriya (mTK), might reduce the IOP as well as stress and improve quality of life (QoL) in patients with glaucoma. Methodology: A parallel two-arm randomized controlled trial (RCT) was conducted in glaucoma patients (Control group and Intervention group). Control group patients were on standard medical treatment and intervention group patients practiced a Yoga-based lifestyle intervention (YBLI) for 4 weeks as add-on therapy with their standard medical treatment. All Participants were assessed at baseline day 1, day 14 (D14), and day 28 (D28). A minimum of 30 patients were recruited in each group. Results: We did not observe any statistically significant different mean IOP of right (IOP-r) or, left eyes at any time point as well as cortisol level and QoL between the two groups. However, with in intervention group, there was a reduction in IOP-r at D14 (15.54 ± 2.81 mmHg) and D28 (15.24 ± 3.1 mmHg), P = 0.006 and 0.001, respectively, compared to their baseline IOP (16.26 ± 2.98). Conclusion: Based on the present RCT, yoga-based ocular exercises practiced here cannot be recommended for management of raised IOP in glaucoma patients. Further larger studies are warranted with yoga-based interventions in patients with glaucoma. Clinical Trial Registration Number: CTRI/2016/03/006703.

Predictive value of intraoperative D-wave and m-MEP neurophysiological monitoring in patients with preoperative motor deficits in immediate and late postoperative period.

BACKGROUND: Presence of preoperative motor deficits in patients poses a distinct challenge in monitoring the integrity of corticospinal tracts during spinal surgeries. The inconsistency of the motor-evoked potentials is such patients, limits its clinical utility. D-wave is a robust but less utilized technique for corticospinal tract monitoring. The comparative clinical value of these two techniques has not been evaluated in the patients with preoperative deficits. OBJECTIVES: The objective of the study was to compare the predictive utility of myogenic Motor Evoked Potentials (m-MEP) and D-wave in terms of recordability and their sensitivity and specificity in predicting transient and permanent new motor deficits. MATERIALS AND METHODS: Thirty-one patients with preoperative motor deficit scheduled to undergo spinal surgery were included in the study. Intraoperative m-MEP and D-wave changes were identified and correlated with postoperative neurology in the immediate postoperative period and at the time of discharge. RESULTS: The mean preoperative motor power of the patient pool in left and right lower limb was 2.97 ± 1.56 and 3.32 ± 1.49, respectively. The recordability of m-MEPs and D-wave was observed to be 79.4% and 100%, respectively. The m-MEP predicted the motor deterioration in immediate postoperative period with 100% sensitivity and 80% specificity, while D-wave had 14% sensitivity and 100% specificity. At the time of discharge, m-MEPs' specificity reduced to 61%, while D-wave demonstrated 100% specificity. CONCLUSIONS: D-wave has a better recordability than m-MEPs in neurologically compromised patients. D-wave predicts development of long-term deficits with 100% specificity, while m-MEPs have a high sensitivity for transient neurological deficit. A combination of D-wave and m-MEP is recommended for monitoring the integrity of the corticospinal tract in patients with preoperative motor deficits.

Cytokine and growth factor profile in endometriosis: a multiplex analysis of peritoneal fluid to assess diagnostic utility.

We aimed to assay cytokines and growth factors in peritoneal fluid samples from women with and without endometriosis to understand the inflammatory milieu, and assess their potential diagnostic utility. This cross-sectional study conducted at a tertiary care hospital included 54 women, aged 20-45 years, with regular menstrual history and undergoing diagnostic/therapeutic laparoscopy for infertility and/or pain. Peritoneal fluid samples were collected after insertion of trocar & laparoscope but prior to other surgical intervention. A multiplex immunoassay of 27 cytokines and growth factors was performed. The concentration of FGF2 and CSF3 were significantly lower in women with endometriosis than without endometriosis (p = .043 and .003, respectively). The levels of CCL2 and IL1RN were significantly higher in moderate-severe than in minimal-mild endometriosis (p = .038 and .043, respectively). Phase-specific comparison revealed that in proliferative phase, the levels of CSF2 and CSF3 were lower in women with endometriosis than without the disease (p = .047 and .013, respectively). The ROC curve analysis provided a cutoff value 0.78 and 0.76 for FGF2 and CSF3, respectively. Cytokines and growth factors such as FGF2, CSF3, CSF2, CCL2 and IL1RN seem to contribute to the pathogenesis of endometriosis and may have a potential utility for the diagnosis of endometriosis.

Framingham Risk Score and Estimated 10-Year Cardiovascular Disease Risk Reduction by a Short-Term Yoga-Based LifeStyle Intervention.

OBJECTIVE: The aim of this study was to evaluate the efficacy of a short-term yoga-based lifestyle intervention program in lowering Framingham Risk Score (FRS) and estimated 10-year cardiovascular risk. METHODS: This was a single-arm, pre-post interventional study including data from a historical cohort with low to moderate risk for cardiovascular disease (CVD). It was conducted in a tertiary-care hospital. Participants with low (0 or 1 CVD risk factors) to moderately high risk (10-year risk between 10% and 20% and two or more CVD risk factors) were included. Participants with previously diagnosed CVD, defined as a history of myocardial infarction, congestive heart failure, or cerebrovascular accident, were excluded from the analysis. However, those with controlled hypertension were included. Intervention included a pretested short-term yoga-based lifestyle intervention, which included asanas (physical postures), pranayama (breathing exercises), meditation, relaxation techniques, stress management, group support, nutrition awareness program, and individualized advice. The intervention was for 10 days, spread over 2 weeks. However, participants were encouraged to include it in their day-to-day life. Outcomes included changes in FRS, and estimated 10-year CVD risk from baseline to week 2. A gender-based subgroup analysis was also done, and correlation between changes in FRS and cardiovascular risk factors was evaluated. RESULTS: Data for 554 subjects were screened, and 386 subjects (252 females) were included in the analysis. There was a significant reduction in FRS (p < 0.001) and estimated 10-year cardiovascular risk (p < 0.001) following the short-term yoga-based intervention. There was a strong positive correlation between reduction in FRS and serum total cholesterol (r = 0.60; p < 0.001). There was a moderate positive correlation between reduction in FRS and low-density lipoprotein cholesterol (r = 0.58; p < 0.001), and a weak but positive correlation between reduction in FRS and triglycerides (r = 0.26; p ≤ 0.001), serum very-low-density lipoprotein cholesterol (r = 0.29; p < 0.001), and systolic blood pressure (r = 0.20; p ≤ 0.001). CONCLUSIONS: This yoga-based lifestyle intervention program significantly reduced the CVD risk, as shown by lowered FRS and estimated 10-year CVD risk. Further testing of this promising intervention is warranted in the long term.

Interleukin-6, vitamin D & diabetes risk-factors modified by a short-term yoga-based lifestyle intervention in overweight/obese individuals.

BACKGROUND & OBJECTIVES: Several diabetes prevention programmes have demonstrated a reduction in incidence of diabetes in individuals with prediabetes through weight loss. Short-term yoga-based lifestyle intervention programmes have also been shown to be efficacious in weight loss. This study was undertaken to investigate if interleukin (IL)-6, vitamin D, neopterin, vaspin, and diabetes risk factors can be modified by a short-term yoga-based lifestyle intervention in overweight/obese subjects. METHODS: In this pilot study, 34 overweight/obese [body mass index (BMI) ≥ 23 to <35 kg/m [2] per Asian cut-off values] individuals were enrolled, and received directly supervised intervention for 10 days. Thereafter, they were advised to follow this yoga-based lifestyle at home for one month, and were reassessed for study variables at day 30. RESULTS: There was a reduction from baseline to day 10 in weight ( p <0.001), BMI ( P <0.001), waist/hip-ratio ( P <0.05), blood glucose ( P <0.01), and a significant improvement in lipid profile. There was a decrease in median fasting insulin ( P <0.05), homeostatic model assessment-insulin resistance ( P <0.01), and IL-6 ( Pp <0.05). A non-significant increase in 25-OH-vitamin D, and a decrease in neopterin and vaspin were observed. Twenty subjects returned for follow up assessments. At day 30, weight loss was sustained while systolic blood pressure also showed reduction ( P <0.05). Changes in vitamin D levels were significantly and negatively correlated with changes in weight, BMI and fasting blood glucose, and positively with change in high density lipoprotein. Changes in body weight and BMI significantly and positively correlated with insulin. Changes in IL-6 levels positively and significantly correlated with change in neopterin levels. INTERPRETATION & CONCLUSIONS: The findings showed that IL-6, vitamin D, and diabetes risk factors were favourably modified by a short-term yoga-based lifestyle intervention in obesity. This study also highlighted the challenges in compliance associated with the follow up of subjects following an aggressive supervised intervention of 10 days.

Distinct peritoneal fluid ghrelin and leptin in infertile women with endometriosis and their correlation with interleukin-6 and vascular endothelial growth factor.

OBJECTIVE: The objective of the present study was to evaluate the levels of leptin, ghrelin, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in peritoneal fluid in patients with endometriosis and infertility, and study their correlation. DESIGN AND SETTING: This cross-sectional study included women undergoing diagnostic and/or therapeutic laparoscopy for endometriosis with chief complaint of infertility and/or pain at a tertiary care hospital. Based upon laparoscopic and histopathological findings, patients were categorized as with endometriosis and no endometriosis. Of the 50 patients with infertility (age 23-41 years), 19 had endometriosis while 31 had no endometriosis. The markers were assessed using ELISA kits. RESULTS: The median levels of leptin in patients with endometriosis (10.20 ng/mL) were higher (p = 0.04) and median levels of ghrelin in patients with endometriosis (150.4 pg/mL) were lower (p = 0.037) versus patients with no endometriosis (5.07 ng/mL and 229.6 pg/mL, respectively). The median levels of IL-6 and VEGF in patients with endometriosis were not different between the groups. The correlation analyses showed that leptin levels and IL-6 were positively correlated (p = 0.0001). CONCLUSIONS: The results suggest that ghrelin and leptin might play a key role in pathophysiology of endometriosis, and leptin is associated with inflammation in endometriosis.

High-density lipoprotein cholesterol increases following a short-term yoga-based lifestyle intervention: a non-pharmacological modulation.

OBJECTIVES: The objective of the study was to assess the effect of a brief but comprehensive yoga-based lifestyle intervention on high-density lipoprotein cholesterol (HDL-c). METHODS: This prospective interventional study was performed at the Integral Health Clinic (IHC), an outpatient facility at All India Institute of Medical Sciences, New Delhi, a tertiary health care centre, conducting yoga-based lifestyle intervention programmes for prevention and management of chronic diseases. The study included apparently healthy normal weight, overweight and obese subjects who underwent a pretested 10-day yoga-based programme including asanas (postures), pranayama (breathing exercises), meditation, group discussions, lectures and individualized advice on stress management and healthy diet. The primary outcome measure was change in serum HDL-c at day 10 versus day 0. RESULTS: 238 participants (147 women, 91 men, 38.81±11.40 years) were included in the study. There was a significant increase in HDL-c levels from baseline to day 10 (42.93±5.00 vs 43.52±5.07 mg/dL, P = 0.043). Notably, HDL-c was significantly improved in those for whom the baseline HDL-c levels were lower than the recommended values. Also, there was a reduction in blood pressure, fasting blood glucose, and improvement in other lipid profile variables. CONCLUSION: This yoga-based lifestyle intervention significantly increased HDL-c levels in a short duration of 10 days. This has additional clinical relevance as HDL-c is suggested to be one of the strongest statistically independent predictors of major cardiovascular events.