Predicting postoperative systolic dysfunction in mitral regurgitation: CT vs. echocardiography

IntroductionVolume overload from mitral regurgitation can result in left ventricular systolic dysfunction. To prevent this, it is essential to operate before irreversible dysfunction occurs, but the optimal timing of intervention remains unclear. Current echocardiographic guidelines are based on 2D linear measurement thresholds only. We compared volumetric CT-based and 2D echocardiographic indices of LV size and function as predictors of post-operative systolic dysfunction following mitral repair.MethodsWe retrospectively identified patients with primary mitral valve regurgitation who underwent repair between 2005 and 2021. Several indices of LV size and function measured on preoperative cardiac CT were compared with 2D echocardiography in predicting post-operative LV systolic dysfunction (LVEFecho <50%). Area under the curve (AUC) was the primary metric of predictive performance.ResultsA total of 243 patients were included (mean age 57 ± 12 years; 65 females). The most effective CT-based predictors of post-operative LV systolic dysfunction were ejection fraction [LVEFCT; AUC 0.84 (95% CI: 0.77–0.92)] and LV end systolic volume indexed to body surface area [LVESViCT; AUC 0.88 (0.82–0.95)]. The best echocardiographic predictors were LVEFecho [AUC 0.70 (0.58–0.82)] and LVESDecho [AUC 0.79 (0.70–0.89)]. LVEFCT was a significantly better predictor of post-operative LV systolic dysfunction than LVEFecho (p = 0.02) and LVESViCT was a significantly better predictor than LVESDecho (p = 0.03). Ejection fraction measured by CT demonstrated significantly greater reproducibility than echocardiography.DiscussionCT-based volumetric measurements may be superior to established 2D echocardiographic parameters for predicting LV systolic dysfunction following mitral valve repair. Validation with prospective study is warranted

Clinical Assessment of Osteoarthritis Pain: Contemporary Scenario, Challenges, and Future Perspectives

Abstract The multifaceted nature of osteoarthritis (OA) pain presents a challenge in understanding and managing the condition. The diverse pain experiences, progression rates, individual responses to treatments, and complex disease mechanisms contribute to heterogeneity in the clinical studies outcomes. The lack of a standardized methodology for assessing and classifying OA pain challenges healthcare practitioners. This complicates the establishment of universally applicable protocols or standardized guidelines for treatment. This article explores the heterogeneity observed in clinical studies evaluating OA pain treatments, highlighting the necessity for refined methodologies, personalized patient categorization, and consistent outcome measures. It discusses the role of the multidimensional nature of OA pain, underlying pain mechanisms, and other contributing factors to the heterogeneity in outcome measures. Addressing these variations is crucial to establishing a more consistent framework for evidence-based treatments and advancing care of the patient with OA pain

Mannitol versus hypertonic saline for brain relaxation in patients undergoing craniotomy

BACKGROUND: Patients with brain tumour usually suffer from increased pressure in the skull due to swelling of brain tissue. A swollen brain renders surgical removal of the brain tumour difficult. To ease surgical tumour removal, measures are taken to reduce brain swelling, often referred to as brain relaxation. Brain relaxation can be achieved with intravenous fluids such as mannitol or hypertonic saline. This review was conducted to find out which of the two fluids may have a greater impact on brain relaxation. OBJECTIVES: To compare the effects of mannitol versus those of hypertonic saline on intraoperative brain relaxation in patients undergoing craniotomy. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 10), Medline via Ovid SP (1966 to October 2013) and Embase via Ovid SP (1980 to October 2013). We also searched specific websites, such as www.indmed.nic.in, www.cochrane-sadcct.org and www.Clinicaltrials.gov. Selection criteria: We included randomized controlled trials (RCTs) that compared the use of hypertonic saline versus mannitol for brain relaxation. We also included studies in which any other method used for intraoperative brain relaxation was compared with mannitol or hypertonic saline. Primary outcomes were longest follow-up mortality, Glasgow Outcome Scale score at three months and any adverse events related to mannitol or hypertonic saline. Secondary outcomes were intraoperative brain relaxation, intensive care unit (ICU) stay, hospital stay and quality of life. Data collection and analysis: We used standardized methods for conducting a systematic review, as described by the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. All analyses were made on an intention-to-treat basis. We used a fixed-effect model when no evidence was found of significant heterogeneity between studies, and a random-effects model when heterogeneity was likely. MAIN RESULTS: We included six RCTs with 527 participants. Only one RCT was judged to be at low risk of bias. The remaining five RCTs were at unclear or high risk of bias. No trial mentioned the primary outcomes of longest follow-up mortality, Glasgow Outcome Scale score at three months or any adverse events related to mannitol or hypertonic saline. Three trials mentioned the secondary outcomes of intraoperative brain relaxation, hospital stay and ICU stay; quality of life was not reported in any of the trials. Brain relaxation was inadequate in 42 of 197 participants in the hypertonic saline group and in 68 of 190 participants in the mannitol group. The risk ratio for brain bulge or tense brain in the hypertonic saline group was 0.60 (95% confidence interval (CI) 0.44 to 0.83, low-quality evidence). One trial reported ICU and hospital stay. The mean (standard deviation (SD)) duration of ICU stay in the mannitol and hypertonic saline groups was 1.28 (0.5) and 1.25 (0.5) days (P value 0.64), respectively; the mean (SD) duration of hospital stay in the mannitol and hypertonic saline groups was 5.7 (0.7) and 5.7 (0.8) days (P value 1.00), respectively. AUTHORS' CONCLUSIONS: From the limited data available on the use of mannitol and hypertonic saline for brain relaxation during craniotomy, it is suggested that hypertonic saline significantly reduces the risk of tense brain during craniotomy. A single trial suggests that ICU stay and hospital stay are comparable with the use of mannitol or hypertonic saline. However, focus on other related important issues such as long-term mortality, long-term outcome, adverse events and quality of life is needed

Intravenous versus inhalational techniques for rapid emergence from anaesthesia in patients undergoing brain tumour surgery: A Cochrane systematic review

Background: Early and rapid emergence from anaesthesia is desirable for most neurosurgical patients. With the availability of newer intravenous and inhalational anaesthetic agents, all of which have inherent advantages and disadvantages, we remain uncertain as to which technique may result in more rapid early recovery from anaesthesia. The objective of this review was to assess the effects of intravenous versus inhalational techniques for rapid emergence from anaesthesia in patients undergoing brain tumour surgery. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 6) in The Cochrane Library, MEDLINE via Ovid SP (1966 to June 2014) and EMBASE via Ovid SP (1980 to June 2014). We also searched specific websites, such as www.indmed.nic.in, www.cochrane-sadcct. org and www.clinicaltrials.gov (October 2014). We included randomised controlled trials (RCTs) that compared the use of intravenous anaesthetic agents such as propofol and thiopentone with inhalational anaesthetic agents such as isoflurane and sevoflurane for maintenance of general anaesthesia during brain tumour surgery. Primary outcomes were emergence from anaesthesia (assessed by time to follow verbal commands, in minutes) and adverse events during emergence, such as haemodynamic changes, agitation, desaturation, muscle weakness, nausea and vomiting, shivering and pain. Secondary outcomes were time to eye opening, recovery from anaesthesia using the Aldrete or modified Aldrete score (i.e., time to attain score ≥9, in minutes), opioid consumption, brain relaxation (as assessed by the surgeon on a 4- or 5-point scale) and complications of anaesthetic techniques, such as intraoperative haemodynamic instability in terms of hypotension or hypertension (mmHg), increased or decreased heart rate (beats/min) and brain swelling. We used standardised methods in conducting the systematic review, as described by the Cochrane Handbook for Systematic Reviews of Interventions. We used a fixed-effect model when we found no evidence of significant heterogeneity between studies, and a random-effects model when heterogeneity was likely. Results: We included 15 RCTs with 1833 participants. We determined that none of the RCTs were of high methodological quality. For our primary outcomes, pooled results from two trials suggest that time to emergence from anaesthesia, that is, time needed to follow verbal commands, was longer with isoflurane than with propofol (mean difference [MD] –3.29 min, 95% confidence interval [CI] –5.41––1.18, low-quality evidence), and time to emergence from anaesthesia was not different with sevoflurane compared with propofol (MD 0.28 min slower with sevoflurane, 95% CI – 0.56–1.12, four studies, low-quality evidence). Pooled analyses for adverse events suggest lower risk of nausea and vomiting with propofol than with sevoflurane (risk ratio [RR] 0.68, 95% CI 0.51–0.91, low-quality evidence) or isoflurane (RR 0.45, 95% CI 0.26–0.78) and greater risk of haemodynamic changes with propofol than with sevoflurane (RR 1.85, 95% CI 1.07–3.17), but no differences in the risk of shivering or pain. Pooled analyses for brain relaxation suggest lower risk of tense brain with propofol than with isoflurane (RR 0.88, 95% CI 0.67–1.17, low-quality evidence), but no difference when propofol is compared with sevoflurane. Conclusions: The finding of our review is that the intravenous technique is comparable with the inhalational technique of using sevoflurane to provide early emergence from anaesthesia. Adverse events with both techniques are also comparable. However, we derived evidence of low quality from a limited number of studies. The use of isoflurane delays emergence from anaesthesia. These results should be interpreted with caution. RCTs based on uniform and standard methods are needed

Impact of Exercise Training on Cardiac Function Among Patients With Type 2 Diabetes: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PURPOSE: Type 2 diabetes (T2D) is associated with subclinical abnormalities in left ventricular function and an increased downstream risk for heart failure. Exercise training has been associated with significant improvement in cardiorespiratory fitness among these patients. However, its impact on cardiac function is not well established. METHODS: We conducted a meta-analysis including all randomized and nonrandomized trials that evaluated effects of exercise training on cardiac function among patients with T2D. Primary outcomes were measures of left ventricular systolic (global longitudinal strain) and diastolic (early diastolic velocity [e´]) function. The effects of exercise training on peak oxygen uptake; other markers of diastolic dysfunction: mitral peak early-to-late diastolic filling velocity (E/A), mitral inflow to annular ratio (E/e´), and deceleration time (DT); and systolic velocity were also assessed. RESULTS: Our study included 441 patients enrolled in 6 trials. Exercise training significantly improved early diastolic velocity (standardized mean difference [SMD], 0.58; 95% CI, 0.09-1.07), global longitudinal strain (SMD, 0.62; 95% CI, 0.04-1.21), and peak oxygen uptake (SMD, 1.43; 95% CI, 0.51-2.35) as compared with control group. However, no significant changes were observed in other markers of diastolic function (E/A, E/e´ and DT) and systolic velocity. CONCLUSION: Exercise training in patients with T2D is associated with a significant improvement in some echocardiographic indicators of systolic and diastolic function and cardiorespiratory fitness. These findings suggest that exercise training may improve subclinical systolic and diastolic dysfunction in patients at risk for clinical heart failure

Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis

Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (−) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (−) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (−) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers

An infectious murine model for studying the systemic effects of opioids on early HIV pathogenesis in the gut

Opioids are known to exacerbate HIV pathogenesis, however current studies have been limited by models of HIV infection. Given that HIV causes many systemic effects via direct infection of host cells as well as indirect bystander effects, it is important to establish a systemic infection model in a small animal so that genetic tools can be utilized to elucidate the mechanisms of action. In this study, we describe the systemic effects of EcoHIV infection, a modified HIV which can infect mouse cells, in conjunction with morphine. We observed that EcoHIV infection with opioid treatment induces bacterial translocation from the lumen of the gut into systemic compartments such as liver, which is similar to observations in human patients with LPS. Bacterial translocation corresponds with alterations in gut morphology, disorganization of the tight junction protein occludin, and a concurrent increase in systemic inflammation in both IL-6 and TNFα. Long term infection also had increased expression of inflammatory cytokines in the CNS when co-treated with morphine. Overall, we conclude that EcoHIV is an appropriate model to study the effects of opioids on HIV pathogenesis, including the HIV-induced pathology at early stages of pathogenesis in the gut

Machine learning facilitates the prediction of long-term mortality in patients with tricuspid regurgitation

Objective Tricuspid regurgitation (TR) is a prevalent valve disease associated with significant morbidity and mortality. We aimed to apply machine learning (ML) to assess risk stratification in patients with ≥moderate TR.Methods Patients with ≥moderate TR on echocardiogram between January 2005 and December 2016 were retrospectively included. We used 70% of data to train ML-based survival models including 27 clinical and echocardiographic features to predict mortality over a 3-year period on an independent test set (30%). To account for differences in baseline comorbidities, prediction was performed in groups stratified by increasing Charlson Comorbidity Index (CCI). Permutation feature importance was calculated using the best-performing model separately in these groups.Results Of 13 312 patients, mean age 72 ± 13 years and 7406 (55%) women, 7409 (56%) had moderate, 2646 (20%) had moderate–severe and 3257 (24%) had severe TR. The overall performance for 1-year mortality by 3 ML models was good, c-statistic 0.74–0.75. Interestingly, performance varied between CCI groups, (c-statistic = 0.774 in lowest CCI group and 0.661 in highest CCI group). The performance decreased over 3-year follow-up (average c-index 0.78). Furthermore, the top 10 features contributing to these predictions varied slightly with the CCI group, the top features included heart rate, right ventricular systolic pressure, blood pressure, diuretic use and age.Conclusions Machine learning of common clinical and echocardiographic features can evaluate mortality risk in patients with TR. Further refinement of models and validation in prospective studies are needed before incorporation into the clinical practice