Predictors of 30-Day Mortality Among Dutch Patients Undergoing Colorectal Cancer Surgery, 2011-2016.

Importance: Quality improvement programs for colorectal cancer surgery have been introduced with benchmarking based on quality indicators, such as mortality. Detailed (pre)operative characteristics may offer relevant information for proper case-mix correction. Objective: To investigate the added value of machine learning to predict quality indicators for colorectal cancer surgery and identify previously unrecognized predictors of 30-day mortality based on a large, nationwide colorectal cancer registry that collected extensive data on comorbidities. Design, Setting, and Participants: All patients who underwent resection for primary colorectal cancer registered in the Dutch ColoRectal Audit between January 1, 2011, and December 31, 2016, were included. Multiple machine learning models (multivariable logistic regression, elastic net regression, support vector machine, random forest, and gradient boosting) were made to predict quality indicators. Model performance was compared with conventionally used scores. Risk factors were identified by logistic regression analyses and Shapley additive explanations (ie, SHAP values). Statistical analysis was performed between March 1 and September 30, 2020. Main Outcomes and Measures: The primary outcome of this cohort study was 30-day mortality. Prediction models were trained on a training set by performing 5-fold cross-validation, and outcomes were measured by the area under the receiver operating characteristic curve on the test set. Machine learning was further used to identify risk factors, measured by odds ratios and SHAP values. Results: This cohort study included 62 501 records, most patients were male (35 116 [56.2%]), were aged 61 to 80 years (41 560 [66.5%]), and had an American Society of Anesthesiology score of II (35 679 [57.1%]). A 30-day mortality rate of 2.7% (n = 1693) was found. The area under the curve of the best machine learning model for 30-day mortality (0.82; 95% CI, 0.79-0.85) was significantly higher than the American Society of Anesthesiology score (0.74; 95% CI, 0.71-0.77; P < .001), Charlson Comorbidity Index (0.66; 95% CI, 0.63-0.70; P < .001), and preoperative score to predict postoperative mortality (0.73; 95% CI, 0.70-0.77; P < .001). Hypertension, myocardial infarction, chronic obstructive pulmonary disease, and asthma were comorbidities with a high risk for increased mortality. Machine learning identified specific risk factors for a complicated course, intensive care unit admission, prolonged hospital stay, and readmission. Laparoscopic surgery was associated with a decreased risk for all adverse outcomes. Conclusions and Relevance: This study found that machine learning methods outperformed conventional scores to predict 30-day mortality after colorectal cancer surgery, identified specific patient groups at risk for adverse outcomes, and provided directions to optimize benchmarking in clinical audits.

Synthesis and Structure-Activity Relationship of Xenocoumacin 1 and Analogues as Inhibitors of Ribosomal Protein Synthesis.

Ribosomal protein synthesis is an important target in antibacterial drug discovery. Numerous natural products have served as starting points for the development of antibiotics. We report here the total synthesis of xenocoumacin 1, a natural product that binds to 16S ribosomal RNA at a highly conserved region, as well as analogues thereof. Preliminary structure-activity relationship studies were aimed at understanding and modulating the selectivity between eukaryotic and prokaryotic ribosomes. Modifications were mainly tolerated in the aromatic region. Whole-cell activity against Gram-negative bacteria is limited by efflux and penetration, as demonstrated in genetically modified strains of E. coli. Analogues with high selectivity for eukaryotic ribosomes were identified, but it was not possible to obtain inhibitors selective for bacterial protein synthesis. Achieving high selectivity (albeit not the desired one) was thus possible despite the high homology between eukaryotic and prokaryotic ribosomes in the binding region.

Harbouring group B streptococci in a neonatal intensive care unit led to an outbreak among preterm infants.

We report a nosocomial outbreak with group B streptococci (GBS) in a level two neonatal intensive care unit (NICU) at Sachs' Children and Youth Hospital, Stockholm, Sweden, in 2014. There were five very preterm infants with severe late-onset septicaemia, and 10 further infants were colonised. Pulsed-field gel electrophoresis and multilocus sequence typing genetic characterisation showed that one GBS strain was the cause: serotype Ia, sequence type 23, clonal complex 23. The NICU environment cultures revealed GBS reservoirs on surfaces near sick and colonised patients. We identified workflows and guidelines that could increase the risks of nosocomial infections. Conclusion: This nosocomial GBS outbreak among preterm infants demonstrates that GBS can be harboured in the NICU environment.

Experiences and consequences of living with extended-spectrum ß-lactamase-producing bacteria: A qualitative study.

BACKGROUND: The number of people who become carriers of antibiotic-resistant extended-spectrum ß-lactamase (ESBL)-producing bacteria is steadily increasing. A carrier of ESBL can potentially be stressful for individuals, affecting their daily lives. METHODS: The purpose of this study was to increase the understanding of experiences and consequences of being an ESBL carrier. A modified version of the grounded theory was used to analyze 16 open interviews. RESULTS: The analysis resulted in the core category "to handle the new life situation." The results showed a lack of information being passed by attending doctors to study participants about ESBL and the consequences for their daily lives. This insufficient information initially caused fear and anxiety, leading to participants instead searching for information themselves using the Internet. Armed with this information, they developed strategies to continue with their lives as before. As patients they experienced staff that were respectful, showed no stigmatization toward ESBL carriership, and used correct hygiene routines. CONCLUSIONS: When the information from the attending doctor about ESBL carriers is insufficient, patients often use the Internet to obtain additional information. With the use of this information, patients develop strategies to cope with their lives.

Changing trends in end-stage renal disease patients with diabetes.

BACKGROUND: Worldwide, diabetes has become the most common cause of end-stage renal disease (ESRD), yet Swiss data are largely lacking. METHODS: This observational study examined ESRD patients with diabetes mellitus (ESRD-DM) at end of 2009 and 2014. The prevalence and characteristics of ESRD-DM patients were collected in all dialysis facilities in the Canton of Vaud of Switzerland in 2009 and in 2014, and the 5-year mortality rate was assessed. RESULTS: A total of 107 and 140 ESRD-DM patients underwent dialysis at end of 2009 and 2014, respectively. Within the 5-year period a total of 167 incidental ESRD-DM patients required dialysis, corresponding to an estimated incidental rate of 0.84/1000 person-years in the diabetic population. In 2009, all patients with ESRD-DM underwent haemodialysis, decreasing to 96.2% in 2014, with 3.8% on peritoneal dialysis. Age, sex, body mass index, type of diabetes, duration of diabetes, cause of ESRD, dialysis duration, dialysis frequency, vascular access, and glycosylated haemoglobin levels did not differ between 2009 and 2014. In 2014, macrovascular comorbidity was reported more often than in 2009, but not amputations. Haemoglobin level decreased significantly from 117.9 g/l to 112.3 g/l. Calcium-containing phosphate binder and angiotensin-converting enzyme inhibitor use significantly decreased, whereas iron therapy significantly increased with time. The 5-year mortality rate was 61.7%. Five-year survivors were significantly younger and had a higher body mass index. CONCLUSIONS: The growing prevalence of ESRD-DM emphasises that prevention of chronic kidney disease and its progression should be a public health priority in Switzerland.