Pre-Operative Group and Save in Elective and Emergency Laparoscopic Cholecystectomy: Necessity, Cost-Effectiveness, and Own Experience.

Background: Laparoscopic cholecystectomy is associated with a high safety profile. This study seeks to quantify the incidence of blood transfusion in both the elective and emergency settings, examine related patient outcomes, and investigate selection criteria for pre-operative Group and Save (G&S) sampling. Methods: A prospective multi-centre observational study was conducted to investigate patients undergoing either elective or emergency laparoscopic cholecystectomy in the UK between January 2020 and May 2021. Multivariate logistical regression models were used to identify patient factors associated with the risk of transfusion and explore outcomes linked to pre-operative G&S sampling. Results: This study comprised 959 patients, with 631 (65.8%) undergoing elective cholecystectomy and 328 (34.2%) undergoing emergency surgery. The median age was 48 years (range: 35-59), with 724 (75.5%) of the patients being female. Only five patients (0.5%) required blood transfusions, receiving an average of three units, with the first unit administered approximately six hours post-operatively. Among these cases, three patients (60%) had underlying haematological conditions. In adjusted models, male gender was significantly associated with the need for a blood transfusion (OR 11.31, p = 0.013), while the presence of a pre-operative Group and Save sample did not demonstrate any positive impact on patient outcomes. Conclusions: The incidence of blood transfusion following laparoscopic cholecystectomy is very low. Male gender and haematological conditions may present as independent risk factors. Pre-operative G&S sampling did not yield any positive impact on patient outcomes and could be safely excluded in both elective and emergency cases, although certain population subsets will warrant further consideration.

2-Methoxyestradiol ameliorates doxorubicin-induced cardiotoxicity by regulating the expression of GLUT4 and CPT-1B in female rats.

The clinical usage of doxorubicin (DOX) is hampered due to cardiomyopathy. Studies reveal that estrogen (E2) modulates DOX-induced cardiotoxicity. Yet, the exact mechanism is unclear. The objective of the current study is to evaluate the influence of E2 and more specifically its metabolite 2-methoxyestradiol (2ME) on cardiac remodeling and the reprogramming of cardiac metabolism in rats subjected to DOX cardiotoxicity. Seventy-two female rats were divided into groups. Cardiotoxicity was induced by administering DOX (2.5 mg/kg three times weekly for 2 weeks). In some groups, the effect of endogenous E2 was abolished by ovariectomy (OVX) or by using the estrogen receptor (ER) blocker Fulvestrant (FULV). The effect of administering exogenous E2 or 2ME in the OVX group was studied. Furthermore, the influence of entacapone (COMT inhibitor) on induced cardiotoxicity was investigated. The evaluated cardiac parameters included ECG, histopathology, cardiac-related enzymes (creatine kinase isoenzyme-MB (CK-MB) and lactate dehydrogenase (LDH)), and lipid profile markers (total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL)). The expression levels of key metabolic enzymes (glucose transporter-4 (GLUT4) and carnitine palmitoyltransferase-1B (CPT-1B)) were assessed. Our results displayed that co-treatment of E2 and/or 2ME with DOX significantly reduced DOX-induced cardiomyopathy and enhanced the metabolism of the heart through the maintenance of GLUT4 and CPT-1B enzymes. On the other hand, co-treatment of DOX with OVX, entacapone, or FULV increased the toxic effect of DOX by further reducing these important metabolic enzymes. E2 and 2ME abrogate DOX-induced cardiomyopathy partly through modulation of GLUT 4 and CPT-1B enzymes.

Does Omentopexy Make a Difference in Laparoscopic Sleeve Gastrectomy for Obesity Treatment? A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the comparative outcomes of laparoscopic sleeve gastrectomy with omentopexy (LSGO) versus conventional laparoscopic sleeve gastrectomy (LSG) for obesity treatment. A systematic online search was conducted using the available online databases, and Revman software was used for data analysis. Twenty-two eligible comparative studies were included (n = 9,321). LSGO showed a significantly lower rate of gastric leak (P = 0.0001), staple line bleeding (P = 0.00001), and gastric torsion (P = 0.002) in comparison to the LSG group. Operative time was significantly shorter in the LSG group (P = 0.00001); however, the length of hospital stay was in favour of the LSGO (P = 0.00001). Compared to LSG without omentopexy, LSG with omentopexy provides a significantly lower rate of postoperative complications and shorter LOS at the expense of operative time.

Estrogen Attenuates Diethylnitrosamine-Induced Hepatocellular Carcinoma in Female Rats via Modulation of Estrogen Receptor/FASN/CD36/IL-6 Axis.

This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.

Tackling a Post-COVID-19 Cholecystectomy Waiting List: Are We Meeting the Challenge?

Background and Objectives: The COVID-19 pandemic has led to a tremendous backlog in elective surgical activity. Our hospital trust adopted an innovative approach to dealing with elective waiting times for cholecystectomy during the recovery phase from COVID-19. This study aimed to evaluate trends in overall cholecystectomy activity and the effect on waiting times. Materials and Methods: A prospective observational study was undertaken, investigating patients who received a cholecystectomy at a large United Kingdom hospital trust between February 2021 and February 2022. There were multiple phased strategies to tackle a 533-patient waiting list: private sector, multiple sites including emergency operating, mobile theatre, and seven-day working. The correlation of determination (R2) and Kruskal-Wallis analysis were used to evaluate trends in waiting times across the study period. Results: A total of 657 patients underwent a cholecystectomy. The median age was 49 years, 602 (91.6%) patients had an ASA of 1-2, and 494 (75.2%) were female. A total of 30 (4.6%) patients were listed due to gallstone pancreatitis, 380 (57.8%) for symptomatic cholelithiasis, and 228 (34.7%) for calculous cholecystitis. Median waiting times were reduced from 428 days (IQR 373-508) to 49 days (IQR 34-96), R2 = 0.654, p < 0.001. For pancreatitis specifically, waiting times had decreased from a median of 218 days (IQR 139-239) to 28 (IQR 24-40), R2 = 0.613, p < 0.001. Conclusions: This study demonstrates the methodology utilised to safely and effectively tackle the cholecystectomy waiting list locally. The approach utilised here has potential to be adapted to other units or similar operation types in order to reduce elective waiting times.

Optimizing heterotrophic nitrification process: The significance of demand-driven aeration and organic matter concentration.

Heterotrophic nitrification and aerobic denitrification (HNAD) sludge were successfully acclimated. The effects of organics and dissolved oxygen (DO) on nitrogen and phosphorus removal by the HNAD sludge were investigated. The nitrogen can be heterotrophically nitrified and denitrified in the sludge at a DO of 6 mg/L. The TOC/N (total organic carbon to nitrogen) ratio of 3 was found to result in removal efficiencies of over 88% for nitrogen and 99% for phosphorus. The use of demand-driven aeration with a TOC/N ratio of 1.7 improved nitrogen and phosphorus removal from 35.68% and 48.17% to 68% and 93%, respectively. The kinetics analysis generated an empirical formula, Ammonia oxidation rate = 0.08917·(TOC·Ammonia)0.329·Biomass0.342. The nitrogen, carbon, glycogen, and poly-ß-hydroxybutyric acid (PHB) metabolism pathways of HNAD sludge were constructed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). The findings suggest that heterotrophic nitrification precedes aerobic denitrification, glycogen synthesis, and PHB synthesis.

Head and neck cancer: A 6-year retrospective analysis and review of three common triaging systems.

OBJECTIVES: In the United Kingdom, head and neck cancer (HNC) cases continue to rise and are the fourth commonest cancers in men. Additionally, in the last decade, the incidence rise in women is twice their male counterpart, signifying the need for robust and dynamic triaging systems to maintain high pick-up rates across both genders. This study investigates local risk factors associated with HNC and reviews the most commonly used guidelines and risk calculator tool for two-week-wait (2ww) HNC clinics. DESIGN: Six-year retrospective case-control analysis of 2ww HNC clinics within a district general hospital in Kent studying symptoms and risk factors. RESULTS: Two hundred cancer patients (128M:72F) were identified and compared against 200 randomised non-cancer patients (78M:122F). Increasing age, male gender, smoking, previous cancer and neck lumps were statistically relevant risk factors for HNC (p < .001). HNC mortality at 1 and 5 years was 21% and 26%, respectively. Adjusting guidelines to improve local services obtained the following area under curve (AUC) scores: NICE guidelines 67.3, Pan-London 58.0 and HNC risk calculator version 2 (HaNC-RC V.2) 76.5. Our adjusted HaNC-RC V.2 improved sensitivity by 10% to 92%, and theoretically reduces local general practice referrals by 61% when utilising triaging staff. CONCLUSION: Our data portray the primary risk factors as increasing age, male gender and smoking for this demographic. The presence of a neck lump was the most significant symptom within our cohort. This study demonstrates a critical balance when adjusting sensitivity and specificity of guidelines and proposes that departments adjust diagnostic tools for their local demographic to improve referral numbers and patient outcomes.

Does percutaneous cholecystostomy timing in high anaesthetic-risk patients impact on outcome?

The optimal timing for percutaneous cholecystostomy (PCT) in patients with acute biliary sepsis, who are high-risk for cholecystectomy, requires further investigation. We aimed to study local factors influencing the timing to PCT placement, and investigate patient outcomes in early (≤ 48 h) vs. delayed PCT over a six-year period. A retrospective observational study investigating patients who required a PCT at a single hospital in the UK between January 2014 and December 2019. Placement of a PCT was at the discretion of the on-call surgical consultant according to their own personal experience and not based on a standard local protocol. Clinical outcomes, hospital statistics and details of any subsequent bridging surgery were analysed using multivariate logistic regression models adjusting for age, sex, Charlson Comorbidity Index (CCI) and American Society of Anaesthesiologists (ASA) grade. There were 72 patients with 35/72 (48.6%) classed as TG18 AC grade 3; 26/72 (36.1%) had an early PCT placed and 46/72 (63.9%) delayed. Median age was 76 (65-83) years, 52.8% were female, and 51.4% were classed ASA ≥ 3 with 94.0% scoring CCI > 2. Trial on antibiotic therapy was the primary reason for delayed PCT. In adjusted models, early PCT was associated with a shorter length in hospital stay (OR 3.02, p = 0.044), successful definitive treatment (OR 6.26, p = 0.009); and reduced likelihood for catheter dislodgment (OR 0.12, p = 0.004) with fewer patients bridging to later emergency open surgery (OR 0.19, p = 0.024). Clinical outcomes may be superior in urgent or early PCT for high anaesthetic-risk patients following acute biliary sepsis.

Association between Periodontitis and Chronic Rhinosinusitis Involving Maxillary Sinus Measured by Lund Mackay Staging System.

This study aimed to evaluate the association between periodontitis and chronic rhinosinusitis (CRS) via cone-beam-computed tomography (CBCT) using the Lund-Mackay staging system. CBCT images from different departments of the school of dentistry, at Prince Sattam University were evaluated for the presence of rhinosinusitis. All the CBCT scans were exposed for multiple indications, and no patients had a scan exposed solely for this study. The Lund-Mackay staging system was used to measure the CRS in the CBCT. Descriptive statistics for the frequencies and percentages were used to summarize the data. Logistic regression was used to examine the associations between periodontitis and CRS. Each variable was assessed individually by using multivariable analysis. Collinearity issues among the variables were solved to select a limited set of factors using a stepwise variable selection procedure. A total of 399 CBCT images were included in the current research. Logistic regression showed that only gender was significantly associated (p = 0.0001) with the presence of CRS. However, a stepwise variable selection procedure included gender and bone loss as significantly associated with CRS. No significant difference was observed between unilateral vs. bilateral CRS in gender, bone loss, medical status, and periodontitis. However, only gender showed a significant difference in both bilateral vs. no CRS and unilateral vs. no CRS. Periodontitis is not associated with CRS. However, gender has a significant influence on CRS.

Performances and enhanced mechanisms of nitrogen removal in a submerged membrane bioreactor coupled sponge iron system.

Sponge iron is a potential material for nitrogen removal, but lack of a study about nitrogen removal in a membrane bioreactor (MBR) coupled with sponge iron. The performances and mechanisms of nitrogen removal of SI-MBR were investigated and compared it with that in GAC-MBR. The results showed that the average rate of organic matter removal in the SI-MBR was 92.74%, which was higher than that in the GAC-MBR (87.48%). And the average effluent NO2--N and NO3--N concentration in the SI-MBR (0.02 mg/L and 3.73 mg/L) was lower than that in the GAC-MBR (0.05 mg/L and 7.51 mg/L). Meanwhile, the highest nitrification rate and denitrification rate was respectively 3.544 ± 0.25 mg/(g VSS·h) and 6.643 ± 0.2 mg/(g VSS·h) in the SI-MBR, which was higher than that (3.094 ± 0.25 mg/(g VSS·h) and (6.376 ± 0.2 mg/(g VSS·h)) in the GAC-MBR. Additionally, the bacterial activities (e.g., DHA activity and respiratory activity) were obviously enhanced through the iron ion from sponge iron. The bacterial community in the SI-MBR system was more richness and diverse than that in the GAC-MBR. Ultimately, the mechanisms of enhanced biological nitrogen removal with sponge iron in MBR were analyzed. On the surface of sponge iron, the DIRB and FOB could use the iron ion from sponge iron as the electron transfer to improve the nitrogen and organic removal. With sponge iron, there is not only the nitrification bacteria and heterotrophic denitrifying microorganism enriched, but also the autotrophic denitrifying bacteria abounded obviously. The autotrophic denitrifying bacteria could use Fe(II) as an electron donor to achieve denitrification and enhance the nitrogen removal.

Growth Optimization and Secondary Metabolites Evaluation of Anabaena variabilis for Acetylcholinesterase Inhibition Activity.

Cyanobacteria comprise a good natural resource of a potential variety of neuro-chemicals, including acetylcholinesterase inhibitors essential for Alzheimer's disease treatment. Accordingly, eight different cyanobacterial species were isolated, identified, and evaluated on their growth on different standard nutrient media. It was found that the modified Navicula medium supported the highest growth of the test cyanobacteria. The effects of methylene chloride/methanol crude extracts of the test cyanobacteria on acetylcholinesterase activity were examined and compared. Anabaena variabilis (KU696637.1) crude extract recorded the highest acetylcholinesterase inhibition (62 ± 1.3%). Navicula medium chemical components were optimized through a Plackett-Burman factorial design. The biomass of Anabaena variabilis increased significantly when grown on the optimized medium compared to that of control. The chemical analysis of the fractions derived from Anabaena variabilis showed the presence of two compounds in significant amounts: the flavonoid 5,7-dihydroxy-2-phenyl-4H-chrome-4-one and the alkaloid 4-phenyl-2-(pyridin-3-yl) quinazoline. Molecular docking studies revealed that both compounds interact with the allosteric binding site of acetylcholinesterase at the periphery with π-π stackings with Tyr341 and Trp286 with good, predicted partition coefficient. The compounds obtained from this study open the door for promising drug candidates to treat Alzheimer's disease for their better pharmacodynamics and pharmacokinetic properties.

Rectus sheath catheter analgesia versus standard care following major abdominal surgery: An observational study of 911 patients.

BACKGROUND: It is unknown whether rectus sheath catheter (RSC) continuous infusion of local anaesthetic is superior to standard post-operative opiate analgesia following major abdominal surgery. Previous audit in our Trust had suggested RSC was very effective and reduced opiate analgesia use. We aimed to see if this was maintained as the technique became more widespread comparing clinical outcomes and post-operative opiate analgesia requirements between patients who had RSCs and those that did not following major abdominal surgery over a 32-month period. METHODS: A retrospective observational study investigated patients who had major abdominal surgery at a single centre in the UK between January 2018 and August 2020. Placement of RSCs was at the discretion of the surgical team according to their own personal choice. All patients having the procedure in both an elective and non-elective setting have been included in this study, including patients requiring higher level care after emergency surgery. Clinical outcomes and post-operative opiate analgesia requirements (oral and intravenous) were analysed using multivariate logistic regression models adjusting for American Association of Anesthesiologists (ASA) grade and type of surgery (emergency vs elective and open vs laparoscopic). RESULTS: There were 911 patients; 276/911 (30.3%) RSC and 635/911 (69.7%) non-RSC. Median age was 64 (52-74) years; 51.6% were male. In the adjusted models, RSC was associated with a reduced likelihood of serious complications (OR 0.49 (95% CI 0.33, 0.72); p < 0.001) and lower length of stay in ICU (OR 0.95 (95% CI 0.91, 0.99); p = 0.029). RSC was not associated with reduced post-operative opiate analgesia use. There were 3/276 (1.1%) adverse events following RSC placement during the period of data collection. CONCLUSIONS: Clinical outcomes may be superior for patients following major abdominal surgery when RSCs are placed for post-operative analgesia but uncertainty remains. This paper highlights the difficulty with retrospective non-selected data in answering this question. High quality prospective randomised data are required to determine the effects on clinical outcomes and post-operative opiate analgesia requirements.

Recovery of Surgical Training Through Extended Laparoscopic Simulation Training.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has adversely affected surgical training internationally. Laparoscopic surgery has a steep learning curve necessitating repetitive procedural practice. We evaluate the efficacy of short- and long-duration simulation training on participant skill acquisition to support the recovery of surgical training.  Methods A prospective, observational study involving 18 novice medical students enrolled in a five-week course. Nodal timed assessments involved three tasks: hoop placement, stacking of sugar cubes and surgical cutting. One month post-completion, we compared the ability of six novice course participants to that of six surgical trainees who completed a smaller portion of the course curriculum. Results Course participants (n=18) completed tasks 111% faster on their third and last course attempt. The surgical trainee group (n=6) took 46% longer to complete tasks compared to the six re-invited course participants, whose ability continued to advance on their fourth effort with a combined 154% earlier completion time compared to try one. Conclusions This study supports the adoption of a structured, extended, regular and spaced-out simulation course or curriculum to cultivate greater skill acquisition and retention amongst surgical trainees, and improve patient care.

Improving Secondary Bone Protection Prescription in Patients Admitted With a Femoral Neck Fracture.

Background The socioeconomic burden caused by fragility fractures is well recognised in today's ageing society, with hip fractures making a notable contribution. There is a significant national drive for secondary-prevention bone-protection prescription given the high morbidity and mortality rates of femoral neck fractures. A Specific, Measurable, Achievable, Relevant, Time-bound (SMART) aim was constructed to reach the gold standard in a level 2 trauma centre, utilising the Model for Improvement methodology. Methodology Baseline data were collected for 79 consecutive patients admitted with a neck of femur fracture. A total of 14% were managed with bone-protection plans. The root cause analysis identified three elements having a major impact on the prescription of secondary bone-protection medication: the lack of awareness, education, and a structured multidisciplinary team (MDT) approach. Appropriate plan-do-study-act cycles were implemented and change audited. Results Following cycles one and two, the mean percentage of patients managed with bone-protection plans increased from 14% to 44% and 76%, respectively. A statistical process control chart demonstrated positive change for each cycle, with p-values of <0.01 and <0.001, respectively. After our final cycle, 100% of patients suffering from a femoral neck fracture were being managed with appropriate bone-protection plans according to the Royal College of Physicians' national hip fracture database. We observed 100% sustainability two years later, despite the coronavirus disease 2019 pandemic service disruptions and redeployment of staff. Conclusions Departmental awareness and education played an important role in this quality improvement project. The ultimatum and sustainability intervention was 'responsibility charting' among the MDT: setting clear roles within the team to deliver better patient care.

The Prevalence of Anaemia in a District General Hospital in the United Kingdom.

Aim Investigating the prevalence of hospital-acquired anaemia in a United Kingdom (UK) secondary care setting to describe the level of appropriate management prior to discharge back to primary care. Design and settings An observational study of 13 medical and surgical wards in a UK district general hospital. Method Single-day examination of notes, blood results and drug charts, with a 30-day follow up, using pre-set definitions of anaemia and exclusion criteria. Results Two hundred and sixty-seven patients were included. Of them, 52% were anaemic on admission, 62.2% were anaemic on the study day, 16% had hospital-acquired anaemia and 49%-82% had no biochemical indices checked during the admission or in the last 12 months. Also, 53% of anaemic patients are being discharged without appropriate treatment, with over a third being under-investigated. Conclusion The prevalence of anaemia in a UK district general hospital is high. Causes of anaemia are complex, posing a potentially modifiable risk factor for falls, readmission and mortality.

Text Parsing-Based Identification of Patients with Poor Glaucoma Medication Adherence in the Electronic Health Record.

PURPOSE: To assess the feasibility of automated text parsing screening of physician notes in the electronic health record (EHR) to identify glaucoma patients with poor medication compliance. DESIGN: Cross-sectional study. METHODS: An automated EHR extraction identified a cohort of patients at the University of Michigan with a diagnosis of glaucoma, ≥40 years old, taking ≥1 glaucoma medication, and having no cognitive impairment. Self-reported medication adherence was assessed with 2 validated instruments: the Chang scale and the Morisky medication adherence scale. In tandem, a text parsing tool that abstracted data from the EHR was used to search for combinations of the following words in patient visit notes: "not," "non," "n't," "no," or "poor" accompanied by "adherence," "adherent, "adhering," "compliance," "compliant," or "complying." The proportion of patients with self-reported poor adherence was compared between the EHR extraction and text parsing identification using a Fisher exact test. RESULTS: Among 736 participants, 20.0% (n = 147) self-reported poor adherence and 6.1% (n = 45) had EHR documentation of poor adherence (P < .0001). Using text parsing as a pre-screening tool, 22 of the 45 patients (48.9%) with non-adherence identified by text parsing also self-reported poor medication adherence compared to the 20.0% by self-report overall (P < .0001). CONCLUSIONS: Text parsing physician notes to identify patients' noncompliance to their medications identified a larger proportion of patients who then self-reported poor medication adherence than an automated EHR pull alone but was limited by the small number of patients identified. Optimizing the documentation of medication adherence would maximize the utility of this automated approach to identify medication noncompliance.

Perceptions On Reciprocal Peer Teaching Among Medical Students As Learners And As Tutors.

OBJECTIVES: The College of Medicine at Imam University has incorporated reciprocal peer-teaching into the curriculum in the form of peer-led seminars. The aim was to evaluate this program and ascertain student perceptions. METHODS: A cross-sectional survey of medical students attached to the Internal Medicine I and II courses was conducted in 2018. The questionnaire evaluated perceptions about the peer-teaching program, tutors' knowledge, skills and attitudes, both from a student and a tutor perspective. RESULTS: Based on a 63% response rate from a total of 410 students, 34.5% of learners agreed that peer-tutoring was the most effective method of clinical teaching and 30.3% disagreed. More students reported that peer-led seminars did not prepare them for their exams (38.4%) compared to those who reported it did (27.9%). More than 40% of participants reported the tutors were approachable, created a welcoming learning environment and provided targeted information. From a tutor perspective, more than 70% of participants reported that they developed personally and professionally, improved their collaborative, communication, tutoring and presentation skills and confidence. Female students reported they benefited more as tutors compared to male students. CONCLUSION: Students regard obligatory reciprocal peer-teaching in the form of peer-led seminars as similar to faculty teaching and an overwhelming majority report that they benefit both personally and professionally from leading seminars. As doctors are expected to teach and train younger generations, medical schools should prepare all students for such roles. A system that provides an opportunity for every student to become a peer-teacher can fulfil this need.

Treatment of prolonged tacrolimus toxicity using phenytoin in a haemodialysis patient.

WHAT IS KNOWN AND OBJECTIVE: Treatment of tacrolimus toxicity includes holding tacrolimus and supportive care. The objective is to describe considerations for pharmacologic induction of tacrolimus metabolism. CASE DESCRIPTION: A 52-year-old male with a failed renal transplant on chronic haemodialysis developed tacrolimus toxicity due to a drug-drug interaction with darunavir/ritonavir. Tacrolimus concentrations were >60 ng/mL for 10 days despite holding tacrolimus and darunavir/ritonavir. Development of encephalopathy prompted initiation of phenytoin to induce tacrolimus metabolism. Tacrolimus concentration was <2 ng/mL within 4 days and mental status normalized. WHAT IS NEW AND CONCLUSION: Phenytoin metabolic induction is a therapeutic option for prolonged tacrolimus toxicity.

Ochratoxin A induces cytoprotective autophagy via blocking AKT/mTOR signaling pathway in PK-15 cells.

Ochratoxin A (OTA) could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic process that plays an important role in the maintenance of cellular homeostasis under stress. However, the role of autophagy in OTA-induced nephrotoxicity is unknown. In the present study, we demonstrated that OTA treatment at 2.0-8.0 µM could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and increased apoptotic nuclei. Meantime, autophagy was triggered when OTA was administrated, as indicated by markedly increased expressions of LC3-II, ATG5 and Beclin-1, accumulation of GFP-LC3 dots and increased double- or single-membrane vesicles. OTA treatment decreased p-AKT and p-mTOR activities, and OTA-induced autophagy was inhibited when insulin was applied. Furthermore, OTA treatments with autophagy inhibitors (3-methyladenine or chloroquine) or knockdown of autophagy-related genes (ATG5 or Beclin-1) resulted in significantly reduced autophagy level and enhanced cytotoxicity. In conclusion, OTA induces cytoprotective autophagy against its cytotoxicity and inactivation of AKT/mTOR axis plays a critical role in autophagy induction.