Following autophagy step by step

Autophagy is an evolutionarily conserved lysosomal degradation route for soluble components of the cytosol and organelles. There is great interest in identifying compounds that modulate autophagy because they may have applications in the treatment of major diseases including cancer and neurodegenerative disease. Hundeshagen and colleagues describe this month in BMC Biology a screening assay based on flow cytometry that makes it possible to track distinct steps in the autophagic process and thereby identify novel modulators of autophagy

The surgical patient of yesterday, today, and tomorrow — a time-trend analysis based on a cohort of 8.7 million surgical patients

Background: Global healthcare delivery is challenged by the aging population and the increase in obesity and type 2 diabetes. The extent to which such trends affect the cohort of patients the authors surgically operate on remains to be elucidated. Comprising of 8.7 million surgical patients, the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database can be analyzed to investigate the echo of general population dynamics and forecast future trends. Material and methods: The authors reviewed the ACS-NSQIP database (2008–2020) in its entirety, extracting patient age, BMI, and diabetes prevalence. Based on these data, the authors forecasted future trends up to 2030 using a drift model. Results: During the review period, median age increased by 3 years, and median BMI by 0.9 kg/m2. The proportion of patients with overweight, obesity class I, and class II rates increased. The prevalence of diabetes rose between 2008 (14.9%) and 2020 (15.3%). The authors forecast the median age in 2030 to reach 61.5 years and median BMI to climb to 29.8 kg/m2. Concerningly, in 2030, eight of ten surgical patients are projected to have a BMI above normal. Diabetes prevalence is projected to rise to 15.6% over the next decade. Conclusion: General population trends echo in the field of surgery, with the surgical cohort aging at an alarmingly rapid rate and increasingly suffering from obesity and diabetes. These trends show no sign of abating without dedicated efforts and call for urgent measures and fundamental re-structuring for improved future surgical care

Association of age with perioperative morbidity among patients undergoing surgical management of minor burns

INTRODUCTION: Burn injuries are associated with significant morbidity, often necessitating surgical management. Older patients are more prone to burns and more vulnerable to complications following major burns. While the relationship between senescence and major burns has already been thoroughly investigated, the role of age in minor burns remains unclear. To better understand differences between elderly and younger patients with predominantly minor burns, we analyzed a multi-institutional database. METHODS: We reviewed the 2008-2020 ACS-NSQIP database to identify patients who had suffered burns according to ICD coding and underwent initial burn surgery. RESULTS: We found 460 patients, of which 283 (62%) were male and 177 (38%) were female. The mean age of the study cohort was 46 ± 17 years, with nearly one-fourth (n = 108; 23%) of all patients being aged ≥60 years. While the majority (n = 293; 64%) suffered from third-degree burns, 22% (n = 99) and 15% (n = 68) were diagnosed with second-degree burns and unspecified burns, respectively. An average operation time of 46 min, a low mortality rate of 0.2% (n = 1), a short mean length of hospital stay (1 day), and an equal distribution of in- and outpatient care (51%, n = 234 and 49%, n = 226, respectively) indicated that the vast majority of patients suffered from minor burns. Patients aged ≥60 years showed a significantly prolonged length of hospital stay (p0.0001), creatinine (p>0.0001), white blood cell count (p=0.02), partial thromboplastin time (p = 0.004), and lower levels of albumin (p = 0.0009) and hematocrit (p>0.0001) were identified as risk factors for the occurrence of any complication. Further, complications were more frequent among patients with lower body burns. DISCUSSION: In conclusion, patients ≥60 years undergoing surgery for predominantly minor burns experienced significantly more complications. Minor lower body burns correlated with worse outcomes and a higher incidence of adverse events. Decreased levels of serum albumin and hematocrit and elevated values of blood urea nitrogen, creatinine, white blood count, and partial thromboplastin time were identified as predictive risk factors for complications

Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients

Background: Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction. Methods: All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase. Results: Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction. Conclusion: Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation

Simulating Surgical Skills in Animals: Systematic Review, Costs & Acceptance Analyses

Background:Modern surgery demands high-quality and reproducibility. Due to new working directives, resident duty hours have been restricted and evidence exists that pure on-the-job training provides insufficient exposure. We hypothesize that supplemental simulations in animal models provide a realistic training to augment clinical experiences. This study reviews surgical training models, their costs and survey results illustrating academic acceptance. Methods:Animal models were identified by literature research. Costs were analyzed from multiple German and Austrian training programs. A survey on their acceptance was conducted among faculty and medical students. Results:915 articles were analyzed, thereof 91 studies describedin-vivoanimal training models, predominantly for laparoscopy (30%) and microsurgery (24%). Cost-analysis revealed single-training costs between 307euro and 5,861euro depending on model and discipline. Survey results illustrated that 69% of the participants had no experience, but 66% would attend training under experienced supervision. Perceived public acceptance was rated intermediate by medical staff and students (4.26;1-low, 10 high). Conclusion:Training in animals is well-established and was rated worth attending in a majority of a representative cohort to acquire key surgical skills, in light of reduced clinical exposure. Animal models may therefore supplement the training of tomorrow's surgeons to overcome limited hands-on experience until virtual simulations can provide such educational tools

Association of age with perioperative morbidity among patients undergoing surgical management of minor burns

Introduction: Burn injuries are associated with significant morbidity, often necessitating surgical management. Older patients are more prone to burns and more vulnerable to complications following major burns. While the relationship between senescence and major burns has already been thoroughly investigated, the role of age in minor burns remains unclear. To better understand differences between elderly and younger patients with predominantly minor burns, we analyzed a multi-institutional database. Methods: We reviewed the 2008-2020 ACS-NSQIP database to identify patients who had suffered burns according to ICD coding and underwent initial burn surgery. Results: We found 460 patients, of which 283 (62%) were male and 177 (38%) were female. The mean age of the study cohort was 46 ± 17 years, with nearly one-fourth (n = 108; 23%) of all patients being aged ≥60 years. While the majority (n = 293; 64%) suffered from third-degree burns, 22% (n = 99) and 15% (n = 68) were diagnosed with second-degree burns and unspecified burns, respectively. An average operation time of 46 min, a low mortality rate of 0.2% (n = 1), a short mean length of hospital stay (1 day), and an equal distribution of in- and outpatient care (51%, n = 234 and 49%, n = 226, respectively) indicated that the vast majority of patients suffered from minor burns. Patients aged ≥60 years showed a significantly prolonged length of hospital stay (p0.0001), creatinine (p>0.0001), white blood cell count (p=0.02), partial thromboplastin time (p = 0.004), and lower levels of albumin (p = 0.0009) and hematocrit (p>0.0001) were identified as risk factors for the occurrence of any complication. Further, complications were more frequent among patients with lower body burns. Discussion: In conclusion, patients ≥60 years undergoing surgery for predominantly minor burns experienced significantly more complications. Minor lower body burns correlated with worse outcomes and a higher incidence of adverse events. Decreased levels of serum albumin and hematocrit and elevated values of blood urea nitrogen, creatinine, white blood count, and partial thromboplastin time were identified as predictive risk factors for complications