Curative role of lactulose, L-carnitine, alpha-lipoic acid and combination of L-carnitine and alpha-lipoic acid in a rat model of acute hepatic encephalopathy: Biochemical observations

Purpose: To determine whether a combination L-carnitine and α-lipoic acid (ALA) can alleviate the toxic effects of thioacetamide (TAA) via their potent antioxidant and free radical-scavenging activities.Methods: Rats were injected with TAA for 3 days to induce acute hepatic failure. TAA induced rats were treated with each of lactulose, L-carnitine and ALA alone and a combination of L-carnitine and ALA for 3 months. Thereafter, biochemical indices, ammonia levels, oxidative stress markers, and the levels of inflammatory markers were assessed in serum, liver and brain.Results: A significant improvement was observed after 3 months of antioxidants treatment. Lactulose, L-carnitine and ALA significantly decreased serum concentrations of alanine transaminase (ALT), aspartate aminotransaminase (AST) and level of total bilirubin while both levels of total protein (TP) and albumin (ALB) were significantly increased (p < 0.05 ) compared to TAA group. In addition, each of antioxidants alone significantly decreased ammonia (NH3) concentrations of serum, liver and brain in TAA-induced rats. Treatment with antioxidants for 3 months significantly (p < 0.05) decreased Malondialdehyde (MDA) and nitric oxide (NO) while antioxidant enzyme activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly increased (p < 0.05) in liver and brain tissues. The expressions of serum tumor necrosis factor-α (TNF-α) and soluble protein (S100-β) were significantly (p < 0.05) down-regulated in TAA-induced rats.Conclusion: L-carnitine in combination with ALA can mitigate HE induced experimentally in rats. The protective efficacy of L-carnitine in combination with ALA in HE can be attributed to suppression of oxidative stress, ammonia concentration and the levels of inflammatory markers. Thus, it may have the potential to be used to treat liver cirrhosis in clinical settings.Keywords: Lactulose, L-carnitine, α-Lipoic acid, Hepatic encephalopathy, Thioacetamide, Oxidative stress, Cirrhosis, Acute liver injur

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Molecular mechanisms of the anti-obesity potential effect of Moringa oleifera in the experimental model

Objective: To elucidate the molecular mechanisms of the potent anti-obesity effect of Moringa oleifera Lam. (M. oleifera) ethanolic extract and to clarify the link between these mechanisms and the associated metabolic and vascular risks in the experimental model of visceral obesity. Methods: M. oleifera ethanolic extract was orally administered at 600 mg/kg body weight in obese female rats daily for 12 weeks. At the end of treatment, body weight was determined, and the atherogenic index, coronary artery index, glucose level, insulin resistance status, liver and kidney functions were assessed. Also, the mRNA of leptin, adiponectin and resistin in visceral adipose tissue was determined by quantitative real time-PCR. Results: The results showed that M. oleifera extract down-regulated mRNA expression of leptin and resistin, while it up-regulated adiponectin gene expression in obese rats relative to untreated obese control counterparts. This amelioration of genes expression was paralleled by a reduction in body weight and improvement of the atherogenic index and coronary artery index, as well as glucose level and insulin resistance value without adverse effects on liver or kidney functions, versus the untreated obese control ones. Conclusions: It is reasonable to assume that the anti-obesity, anti-atherogenic and anti-diabetic properties of M. oleifera are mechanistically achieved via working directly on the adipokines of the visceral adipose tissue. Therefore, M. oleifera may be a good therapeutic candidate for the symptoms of metabolic syndrome

Clinical diagnosis of distal diabetic polyneuropathy using neurological examination scores: correlation with nerve conduction studies

Aim The aim of this study was to diagnose diabetic sensorimotor polyneuropathy using neurological examination scores and to correlate the findings with nerve conduction studies (NCS). Patients and methods Thirty patients with type 2 diabetes were included in the study. Detection and grading of neuropathy were carried out based on the Diabetic Neuropathy Symptom (DNS) Score, modified Neuropathy Symptom Score (NSS), Diabetic Neuropathy Examination (DNE), and modified Neuropathy Disability Score (NDS). For the NCS, amplitudes, velocities, and latencies of seven nerves - that is, four motor (median, ulnar, tibial, and common peroneal) and three sensory (median, ulnar, and sural) nerves - were recorded. If the patient had two or more abnormal findings in any of these nerves, the patient was diagnosed as having peripheral sensorimotor neuropathy. Thereafter, the sensitivity, specificity, and diagnostic efficacy of each neurological score were recorded taking NCS as the gold standard. Results Diabetic sensorimotor polyneuropathy was diagnosed clinically and electrophysiologically in 17 patients (56.7%). However, there were nine cases (30%) of subclinical neuropathy. Neurological examination scores were significantly correlated with each other and with individual variables of NCS and the nerve conduction sum score. Taking the NCS as gold standard, DNS, modified NSS, DNE, and modified NDS had 65.4, 61.5, 30.8, and 61.5% sensitivity and 100, 75, 100, and 100% specificity, respectively. Their diagnostic efficacies were 70, 63.3, 40, and 66.7%, respectively. Conclusion Neurological examination scores can detect and grade neuropathy in the majority of cases. However, NCS was accurate for detection of diabetic sensorimotor polyneuropathy, especially for the subclinical neuropathies

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research