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The health-beneficial effects of nutraceuticals in various diseases have received enhanced attention in recent years. Aging is a continuous process wherein physiological activity of an individual declines over time and is characterized by various indefinite hallmarks which contribute toward aging-related comorbidities in an individual which include many neurodegenerative diseases, cardiac problems, diabetes, bone-degeneration, and cancer. Cellular senescence is a homeostatic biological process that has an important function in driving aging. Currently, a growing body of evidence substantiates the connection between epigenetic modifications and the aging process, along with aging-related diseases. These modifications are now being recognized as promising targets for emerging therapeutic interventions. Considering that almost all the biological processes are modulated by RNAs, numerous RNA-binding proteins have been found to be linked to aging and age-related complexities. Currently, studies have shed light on the ability of the nutraceutical Withania somnifera (Ashwagandha) to influence RNA expression, stability, and processing, offering insights into its mechanisms of action. By targeting RNA-related pathways, Withania somnifera may exhibit promising effects in ameliorating age-associated molecular changes, which include modifications in gene expression and signaling networks. This review summarizes the potential role of Withania somnifera as a nutraceutical in modulating RNA-level changes associated with aging, encompassing both in vitro and in vivo studies. Taken together, the putative role(s) of Withania in modulation of key RNAs will provide insights into understanding the aging process and facilitate the development of various preventive and therapeutic strategies employing nutraceuticals for healthy aging.

Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. Withania somnifera has been used for thousands of years in traditional medicine as a nutraceutical for its numerous health benefits including regenerative and adaptogenic effects. Recent preclinical and clinical studies on the role of Withania somnifera and its active compounds in treating aging, inflammation, and oxidative stress have shown promise for its use in healthy aging. We discuss the chemistry of Withania somnifera, the etiology of inflammaging and the protective role(s) of Withania somnifera in inflammaging in key organ systems including brain, lung, kidney, and liver as well as the mechanistic underpinning of these effects. Furthermore, we elucidate the beneficial effects of Withania somnifera in oxidative stress/DNA damage, immunomodulation, COVID-19, and the microbiome. We also delineate a putative protein–protein interaction network of key biomarkers modulated by Withania somnifera in inflammaging. In addition, we review the safety/potential toxicity of Withania somnifera as well as global clinical trials on Withania somnifera. Taken together, this is a synthetic review on the beneficial effects of Withania somnifera in inflammaging and highlights the potential of Withania somnifera in improving the health-related quality of life (HRQoL) in the aging population worldwide.

Background The safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion presenting beyond 24 hours from last known well (LKW) remains undetermined. Methods In this single center study, we identified patients with large vessel occlusion who were eligible for EVT based on noncontrast computed tomography (CT)/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥5, National Institutes of Health Stroke Scale of ≥6, and presenting beyond 24 hours from LKW, between January 2018 and March 2022. During the study period, EVT service limitations meant patients eligible for EVT presenting outside service hours, routinely received best medical management (BMM). Functional and safety outcomes were compared between patients receiving EVT or BMM following multivariable adjustment for age, baseline stroke severity, Alberta Stroke Program Early CT Score, time from LKW, IV thrombolysis, and clot location. Results Among 35 patients presenting beyond 24 hours from LKW and eligible for EVT, 19 (54%) were treated with EVT and 16 (46%) with BMM. Alberta Stroke Program Early CT Score were similar across both groups (EVT: 7 [6.75–8] versus BMM: 7 [6–8]), but not the baseline National Institutes of Health Stroke Scale (EVT: 17 [11–19.5] versus BMM: 20 [9.75–26]). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.3% versus 0%; P=0.28) or mortality (26.3% versus 37.5%; P=0.42) rates, respectively. The modified Rankin scale at 90 days (adjusted common odds ratio [OR], 1.94; [95% CI 0.42–8.87]; P=0.39) and functional independence rate, although numerically higher in the EVT group compared with the BMM group (modified Rankin scale≤2; 36.9% versus 18.8%; adjusted OR, 4.34; [95% CI 0.34–54.83]; P=0.25), were not significantly different. 94.7% of patients treated with EVT achieved successful reperfusion (modified thrombolysis in cerebral infarction 2b–3). Conclusion In routine clinical practice, EVT beyond 24 hours from LKW appears safe and feasible, when performed in patients with acute ischemic stroke who were deemed eligible for EVT by noncontrast CT /CT angiography alone. A large collaborative randomized trial assessing the efficacy of EVT beyond 24 hours is warranted. Our findings provide a basis for the sample size estimate for an adequately powered trial.

Background Patients with acute ischemic stroke onset during hospital admission often have concurrent illnesses, increased underlying comorbidities and are often associated with a delayed recognition of stroke onset, compared with patients with stroke onset in the community (community‐onset stroke [COS]). Endovascular thrombectomy (EVT) for large‐vessel occlusion in acute ischemic stroke has been proven to be effective, though the safety and feasibility of EVT among patients with in‐hospital stroke (IHS) onset remains undetermined. We aim to compare the workflow and clinical outcomes for patients undergoing EVT following IHS onset and COS. Methods Using data from a national stroke registry, we used propensity score‐matched individual‐level data of patients who underwent EVT, following IHS and COS, between October 2015 and March 2020. Univariate analysis was performed to assess the procedural, functional, and safety outcomes. Results We included 4353 patients (COS, 4104 [249 after propensity score matching]; IHS, 249 [249 after propensity score matching]). Compared with COS, patients with IHS had similar modified Rankin Scale on discharge (odds ratio [OR], 0.98 [95% CI, 0.72–1.34]; P=0.96) and at 6 months (OR, 1.25 [95% CI, 0.71–2.24]; P=0.48). No significant difference in achieving good functional outcome (modified Rankin Scale ≤ 2 at discharge; 31.3% [IHS] versus 29.3% [COS]; OR,=1.10 [95% CI 0.74–1.60]; P=0.61), successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b–3), P=0.82; or safety outcomes of symptomatic intracranial hemorrhage (P=0.64) and in‐hospital mortality (P=0.26) were demonstrated. Shorter time interval from stroke onset to imaging in the IHS group (IHS, 80±88 versus COS, 216±292 minutes) was observed. The imaging‐to‐arterial‐puncture time was not significantly different between the groups (IHS, 160±140 versus COS, 162±184 minutes; P=0.85). Conclusions EVT in patients with IHS is safe and feasible, with comparable functional and safety outcomes to patients with COS, in this national stroke registry. Continued efforts are required to improve the inpatient stroke workflow in recognizing stroke symptoms and initiating reperfusion treatment for eligible patients with IHS.

Introduction The efficacy and safety of endovascular thrombectomy (EVT) beyond 6 hours from acute ischaemic stroke (AIS) onset for patients with proximal large vessel occlusion (LVO) selected without CT perfusion or MR imaging is undetermined in routine clinical practice. Methods In this single centre study, we identified consecutive AIS patients with an ICA or M1 MCA segment occlusion who were eligible for EVT based on non‐contrast CT/CT angiography (without CT perfusion or MR imaging) using an Alberta Stroke Program Early CT Score (ASPECTS) of ≥ 6, and an NIHSS score of≥ 6, presenting beyond 6 hours from stroke onset, between January 2018 and March 2022. During the study period, EVT capacity limitations meant EVT‐eligible patients presenting out of regular working hours (between 18.00 and 08.00 on weekdays) or on weekends, consistently received best medical management (BMM). This systemic unavailability of EVT, allows a comparison of EVT and BMM in patients who meet the same inclusion criteria, in which selection based on physician‐related bias is significantly reduced. Functional outcomes (modified Rankin Scale (mRS) at 90 days), symptomatic intracranial haemorrhage (sICH) and mortality at 90 days were compared between patients receiving EVT or BMM following multivariable adjustment for age, sex, baseline stroke severity, ASPECTS, onset‐to‐neuroimaging time, IV thrombolysis, and clot location.Pre‐specified subgroup analyses were performed. Results Among 4802 AIS patients, 150 patients (3.1%) presenting beyond 6‐hours of onset were eligible for EVT: 74 (49%) treated with EVT and 76 (51%) with BMM. Compared to the BMM group, patients treated with EVT had significantly improved functional outcome (mRS) (adjusted common OR = 2.23, 95%CI 1.18‐4.22, p = 0.013), and higher rates of functional independence (mRS≤2; 39.2.% vs 9.2%; aOR = 4.73, 95%CI 1.64‐13.63, p = 0.004). No significant difference was observed between the EVT and BMM groups in the sICH (5.4% vs 2.6%, p = 0.94) or mortality (20.2% vs 47.3%, p = 0.16) rates, respectively. EVT remained effective within the 6–12 hour and >12 hour time window subgroups. No significant treatment interaction was observed in all subgroups. Conclusions In routine clinical practice, of the 3.1% of patients in our AIS population presenting after 6 hours from stroke onset who were deemed eligible for EVT by NCCT/CTA alone, those treated with EVT achieved significantly improved functional outcome, compared to patients treated with BMM only. No significant differences were noted between the two groups with respect to sICH and mortality. While confirmatory randomised trials are awaited, these findings suggest that EVT is effective and safe when performed in AIS patients selected without CTP or MRI beyond 6 hours from stroke onset.

Background The efficacy and safety of endovascular thrombectomy (EVT) >6 hours from acute ischemic stroke (AIS) onset for patients selected without computed tomography (CT) perfusion or magnetic resonance imaging is undetermined in routine clinical practice. Methods In this single‐center study, we identified consecutive late‐presenting patients with AIS who were eligible for EVT on the basis of noncontrast CT/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥6, >6 hours from stroke onset, between January 2018 and March 2022. During the study period, EVT capacity limitations meant EVT‐eligible patients presenting out of regular working hours, consistently received best medical management (BMM). Functional outcomes (modified Rankin Scale at 90 days), symptomatic intracranial hemorrhage, and mortality at 90 days were compared between patients receiving EVT or BMM following multivariable adjustment for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score, onset‐to‐neuroimaging time, intravenous thrombolysis, and clot location. Results Among 4802 patients with AIS, 150 patients (3.1%) presenting beyond 6 hours of onset were eligible for EVT: 74 (49%) treated with EVT and 76 (51%) with BMM. Compared with the BMM group, patients treated with EVT had significantly improved functional outcome (modified Rankin Scale) (adjusted common odds ratio, 2.23 [95% CI, 1.18–4.22]; P=0.013), and higher rates of functional independence (modified Rankin Scale ≤2; 39.2.% versus 9.2%; adjusted odds ratio, =4.73 [95% CI, 1.64–13.63]; P=0.004). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.4% versus 2.6%; P=0.94) or mortality (20.2% versus 47.3%; P=0.16) rates, respectively. Conclusion In routine clinical practice, of the 3.1% of patients in our AIS population presenting after 6 hours from stroke onset who were deemed eligible for EVT by noncontrast CT/CT angiography alone, those treated with EVT achieved significantly improved functional outcome, compared with patients treated with BMM only. No significant differences were noted between the 2 groups with respect to symptomatic intracranial hemorrhage and mortality. While confirmatory randomized trials are awaited, these findings suggest that EVT is effective and safe when performed in patients with AIS selected without CT perfusion or magnetic resonance imaging >6 hours from stroke onset.

Multiple myeloma (MM) is an aggressive cancer characterised by malignancy of the plasma cells and a rising global incidence. The gold standard for optimum response is aggressive chemotherapy followed by autologous stem cell transplantation (ASCT). However, majority of the patients are above 60 years and this presents the clinician with complications such as ineligibility for ASCT, frailty, drug-induced toxicity and differential/partial response to treatment. The latter is partly driven by heterogenous genotypes of the disease in different subpopulations. In this review, we discuss emerging single cell technologies and applications in MM, population pharmacogenetics of MM, resistance to chemotherapy, genetic determinants of drug-induced toxicity, molecular signal transduction, as well as the role(s) played by epigenetics and noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that influence the risk and severity of the disease. Taken together, our discussions further our understanding of genetic variability in ‘myelomagenesis’ and drug-induced toxicity, augment our understanding of the myeloma microenvironment at the molecular and cellular level and provide a basis for developing precision medicine strategies to combat this malignancy.

Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer’s disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer’s disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1β and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.

Background Pancreaticopleural fistulas are among the rarest complications of chronic pancreatitis. The main objective of the research, conducted on a total of seven patients, was to evaluate the effectiveness of early endoscopic management of pancreaticopleural fistula. Methods The diagnosis of fistula was reached when fistulous tract was demonstrated on imaging studies and/or pleural fluid amylase level was greater than 2,000 U/L. The data were retrospectively analyzed from the records. Results The prototype patient in our series was a chronic alcoholic male with median age of 45 years. Computed tomography scan was performed in all the seven patients but could diagnose leak only in four patients. Magnetic resonance cholangiopancreatography was better in the remaining three patients for diagnosing fistula. Endoscopic retrograde cholangiopancreatography was the most sensitive test that diagnosed fistula in all the seven patients. Pancreatic duct (PD) cannulation was successful and pancreatic sphincterotomy with PD stenting was performed in all the seven patients. We could avoid surgical intervention in our patients. Conclusions We advise early endoscopic treatment within 7 days of symptom onset as opposed to 3 weeks, which was proposed previously. Medical therapies should be complimentary to PD stenting.

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of

Esophageal mucosal bridge is an elastic stretchable structure, connecting across the lumen, extending either obliquely or horizontally, more commonly seen in the mid or lower esophagus. It can be either congenital or secondary (acquired). Acquired ones are secondary to reflux esophagitis, corrosive esophageal injury, drug-induced esophagitis, radiation esophagitis, Crohn’s disease, Mallory-Weiss syndrome, malignant tumors, and infections like candidiasis, HSV, CMV, or tuberculosis. We present a case of an elderly female, who presented with progressive dysphagia for 3 months, more commonly to solids without any history of anorexia or weight loss. No history of corrosive ingestion, radiation exposure, or prior history of any surgical or endoscopic intervention was present. Upper gastrointestinal endoscopy revealed esophageal mucosal bridge at 20 and 25 cm from incisors and mucosal tag. Endoscopic resection was carried out successfully with hot biopsy forceps and needle knife after prophylactic application of hemoclips at two ends of each bridge, without any adverse event. Esophageal mucosal bridge, though rarely reported, should be kept in the differential diagnosis of patients presenting with dysphagia. Endoscopic resection with hot biopsy forceps or needle knife seems to be effective.

Neuropathic pain is a chronic pain condition seen in patients with diabetic neuropathy, cancer chemotherapy-induced neuropathy, idiopathic neuropathy as well as other diseases affecting the nervous system. Only a small percentage of people with neuropathic pain benefit from current medications. The complexity of the disease, poor identification/lack of diagnostic and prognostic markers limit current strategies for the management of neuropathic pain. Multiple genes and pathways involved in human diseases can be regulated by microRNA (miRNA) which are small non-coding RNA. Several miRNAs are found to be dysregulated in neuropathic pain. These miRNAs regulate expression of various genes associated with neuroinflammation and pain, thus, regulating neuropathic pain. Some of these key players include adenylate cyclase (Ac9), toll-like receptor 8 (Tlr8), suppressor of cytokine signaling 3 (Socs3), signal transducer and activator of transcription 3 (Stat3) and RAS p21 protein activator 1 (Rasa1). With advancements in high-throughput technology and better computational power available for research in present-day pharmacology, biomarker discovery has entered a very exciting phase. We dissect the architecture of miRNA biological networks encompassing both human and rodent microRNAs involved in the development of neuropathic pain. We delineate various microRNAs, and their targets, that may likely serve as potential biomarkers for diagnosis, prognosis, and therapeutic intervention in neuropathic pain. miRNAs mediate their effects in neuropathic pain by signal transduction through IRAK/TRAF6, TLR4/NF-κB, TXIP/NLRP3 inflammasome, MAP Kinase, TGFβ and TLR5 signaling pathways. Taken together, the elucidation of the landscape of signature miRNA regulatory networks in neuropathic pain will facilitate the discovery of novel miRNA/target biomarkers for more effective management of neuropathic pain.

Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Despite advances in antihyperglycemic therapeutics, the management of diabetes is limited due to its complexity and associated comorbidities, including diabetic neuropathy, diabetic nephropathy and diabetic retinopathy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the ‘symptom complex’ in diabetes. We review various miRNAs and lncRNAs implicated in diabetes and delineate ncRNA biological networks as well as key ncRNA targets in diabetes. Further, we discuss the spatial regulation of ncRNAs and their role(s) as prognostic markers in diabetes. We also shed light on the molecular mechanisms of signal transduction with diabetes-associated ncRNAs and ncRNA-mediated epigenetic events. Lastly, we summarize clinical trials on diabetes-associated ncRNAs and discuss the functional relevance of the dysregulated ncRNA interactome in diabetes. This knowledge will facilitate the identification of putative biomarkers for the therapeutic management of diabetes and its comorbidities. Taken together, the elucidation of the architecture of signature ncRNA regulatory networks in diabetes may enable the identification of novel biomarkers in the discovery pipeline for diabetes, which may lead to better management of this metabolic disorder.

Esophageal perforation is a life-threatening condition with a high mortality rate. First described around 300 years ago, management of this fatal condition has emerged from surgical to endoscopic modalities with much less morbidity and mortality when instituted early. We present this case of 55-year-old male, with double esophageal perforation by meat bone, perforating lower esophageal wall, leading to localized hydropneumothorax on right side with mild bilateral pleural effusion managed endoscopically with Over-the-Scope-Clip. Endoscopic management of esophageal perforation has been well mentioned in literature, without any mention of such management in case of double esophageal perforation. Surgery with or without endoscopy remains the main stay of management of such cases.

Background: Detecting and isolating cases of COVID-19 are amongst the key elements listed by the WHO to reduce transmission. This approach has been reported to reduce those symptomatic with COVID-19 in the population by over 90%. Testing is part of a strategy that will save lives. Testing everyone maybe ideal, but it is not practical. A risk tool based on patient demographics and clinical parameters has the potential to help identify patients most likely to test negative for SARS-CoV-2. If effective it could be used to aide clinical decision making and reduce the testing burden.Methods: At the time of this analysis, a total of 9,516 patients with symptoms suggestive of Covid-19, were assessed and tested at Mount Sinai Institutions in New York. Patient demographics, clinical parameters and test results were collected. A robust prediction pipeline was used to develop a risk tool to predict the likelihood of a positive test for Covid-19. The risk tool was analyzed in a holdout dataset from the cohort and its discriminative ability, calibration and net benefit assessed.Results: Over 48% of those tested in this cohort, had a positive result. The derived model had an AUC of 0.77, provided reliable risk prediction, and demonstrated a superior net benefit than a strategy of testing everybody. When a risk cut-off of 70% was applied, the model had a negative predictive value of 96%.Conclusion: Such a tool could be used to help aide but not replace clinical decision making and conserve vital resources needed to effectively tackle this pandemic.

In recent times, the role(s) of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in the pathogenesis of various cancers has received great attention. Indeed, there is also a growing recognition of regulatory RNA cross-talk, i.e., lncRNA-miRNA interactions, that may modulate various events in carcinogenesis and progression to metastasis. This review summarizes current evidence in the literature of lncRNA-miRNA interactions in various cancers such as breast, liver, stomach, lung, prostate, bladder, colorectal, blood, brain, skin, kidney, cervical, laryngeal, gall bladder, and bone. Further, the potential prognostic and theragnostic clinical applications of lncRNA-miRNA interactions in cancer are discussed along with an overview of noncoding RNA (ncRNA)-based studies that were presented at the American Society of Clinical Oncology (ASCO) 2015. Interestingly, the last decade has seen tremendous innovation, as well as increase in complexity, of the cancer biological network(s) from mRNA- to miRNA- and lncRNA-based networks. Thus, biological networks devoted to understanding regulatory interactions between these ncRNAs would be the next frontier in better elucidating the contributions of lncRNA-miRNA interactions in cancer. Herein, a cancer biological network of lncRNA-miRNA interactions is presented wherein “edges” connect interacting lncRNA-miRNA pairs, with each ncRNA serving as a discrete “node” of the network. In conclusion, the untapped potential of lncRNA-miRNA interactions in terms of its diagnostic, prognostic and therapeutic potential as targets for clinically actionable intervention as well as biomarker validation in discovery pipelines remains to be explored. Future research will likely harness this potential so as to take us closer to the goal of “precision” and “personalized medicine” which is tailor-made to the unique needs of each cancer patient, and is clearly the way forward going into the future.

A 12-year-old ASA I female patient underwent correction of posterior scoliosis of dorsolumbar spine under total intravenous anesthesia using a combination of remifentanil and propofol. Induced hypotension was maintained between 55 and 65 mmHg. Intraoperatively, patient received a single injection of 1.0 g paracetamol. Surgery lasted 6 h and 40 min and was essentially uneventful. A follow-up investigation in the intensive care unit 6 h after the surgery revealed alanine transaminase levels of 547 I/U. This increased to 924 I/U on the 2 nd postoperative day after the patient received 500 mg per-rectal paracetamol. Stopping administration of paracetamol restored alanine transaminase level to normal without needing N-acetylcysteine.