Predicting major complications in patients undergoing laparoscopic and open hysterectomy for benign indications

Background:Hysterectomy, the most common gynecological operation, requires surgeons to counsel women about their operative risks. We aimed to develop and validate multivariable logistic regression models to predict major complications of laparoscopic or abdominal hysterectomy for benign conditions.Methods:We obtained routinely collected health administrative data from the English National Health Service (NHS) from 2011 to 2018. We defined major complications based on core outcomes for postoperative complications including ureteric, gastrointestinal and vascular injury, and wound complications. We specified 11 predictors a priori. We used internal–external cross-validation to evaluate discrimination and calibration across 7 NHS regions in the development cohort. We validated the final models using data from an additional NHS region.Results:We found that major complications occurred in 4.4% (3037/68 599) of laparoscopic and 4.9% (6201/125 971) of abdominal hysterectomies. Our models showed consistent discrimination in the development cohort (laparoscopic, C-statistic 0.61, 95% confidence interval [CI] 0.60 to 0.62; abdominal, C-statistic 0.67, 95% CI 0.64 to 0.70) and similar or better discrimination in the validation cohort (laparoscopic, C-statistic 0.67, 95% CI 0.65 to 0.69; abdominal, C-statistic 0.67, 95% CI 0.65 to 0.69). Adhesions were most predictive of complications in both models (laparoscopic, odds ratio [OR] 1.92, 95% CI 1.73 to 2.13; abdominal, OR 2.46, 95% CI 2.27 to 2.66). Other factors predictive of complications included adenomyosis in the laparoscopic model, and Asian ethnicity and diabetes in the abdominal model. Protective factors included age and diagnoses of menstrual disorders or benign adnexal mass in both models and diagnosis of fibroids in the abdominal model.Interpretation:Personalized risk estimates from these models, which showed moderate discrimination, can inform clinical decision-making for people with benign conditions who may require hysterectomy.

Hysterectomy is one of the most frequently performed surgical procedures. Canada has one of the highest rates of hysterectomy globally, with one-third of women undergoing this procedure before 60 years of age.¹ Minimal access approaches are favoured by both clinicians and patients,² and the proportion of hysterectomies being undertaken by a laparoscopic approach has increased substantially in many countries over the last 10 years.^3–7 The evidence-based medicine paradigm for surgical approaches to hysterectomy for benign disease advocates that the chosen surgical approach should be discussed with the patient by their surgeon and decided in light of the relative benefits and risks.² This advice is echoed by national guidelines.^8,9Most clinicians undertaking hysterectomy will intuitively identify patient characteristics that have the potential to increase the complexity and complications of surgery. A 2016 systematic review of studies that reported significant associations between patient characteristics and surgical outcomes for laparoscopic hysterectomy and a 2020 population-based prospective cohort study using data from the Danish hysterectomy database have suggested that older age, race, raised body mass index (BMI), diabetes mellitus, increased uterine weight, fibroids, endometriosis and adhesions are predictors of complications in patients undergoing hysterectomy for benign indications.^10,11 However, assimilating this information to individualize and anticipate the precise risk for each patient if there are multiple factors present can be challenging. A 2020 systematic review reported that surgeons in other specialties were outperformed by risk prediction models in estimating postoperative risk and outcomes; their discriminatory ability showed greater variation (C-statistic 0.51–0.75) than other risk prediction tools.¹²Patients should be given information about potential risks before surgery to manage expectations.¹³ This is especially important when surgery is considered for benign disease because nonsurgical options are often available.Our aim was to generate prediction models that can be used in conjunction with a surgeon’s intuition to enhance preoperative patient counselling and match the advances made in the technical aspects of surgery. We sought to quantify the proportion of patients who underwent hysterectomy for benign disease and will have a major complication, and to develop and validate prognostic models to individualize this risk, using a national data set.     

Observations on the exoerythrocytic stages of different isolates of Plasmodium cynomolgi in hepatocytes of New World aotus and Saimiri monkeys

Sporozoites of 3 isolates of Plasmodium cynomolgi dissected from the salivary glands of Anopheles dirus and Anopheles quadrimaculatus were injected intravenously into 9 New World monkeys. Liver stage parasites were demonstrated in all 9 animals; 7 of these animals also produced blood stages after prepatent periods of 9 to 23 days.     

Pseudomonas aeruginosa Population Structure Revisited

At present there are strong indications that Pseudomonas aeruginosa exhibits an epidemic population structure; clinical isolates are indistinguishable from environmental isolates, and they do not exhibit a specific (disease) habitat selection. However, some important issues, such as the worldwide emergence of highly transmissible P. aeruginosa clones among cystic fibrosis (CF) patients and the spread and persistence of multidrug resistant (MDR) strains in hospital wards with high antibiotic pressure, remain contentious. To further investigate the population structure of P. aeruginosa, eight parameters were analyzed and combined for 328 unrelated isolates, collected over the last 125 years from 69 localities in 30 countries on five continents, from diverse clinical (human and animal) and environmental habitats. The analysed parameters were: i) O serotype, ii) Fluorescent Amplified-Fragment Length Polymorphism (FALFP) pattern, nucleotide sequences of outer membrane protein genes, iii) oprI, iv) oprL, v) oprD, vi) pyoverdine receptor gene profile (fpvA type and fpvB prevalence), and prevalence of vii) exoenzyme genes exoS and exoU and viii) group I pilin glycosyltransferase gene tfpO. These traits were combined and analysed using biological data analysis software and visualized in the form of a minimum spanning tree (MST). We revealed a network of relationships between all analyzed parameters and non-congruence between experiments. At the same time we observed several conserved clones, characterized by an almost identical data set. These observations confirm the nonclonal epidemic population structure of P. aeruginosa, a superficially clonal structure with frequent recombinations, in which occasionally highly successful epidemic clones arise. One of these clones is the renown and widespread MDR serotype O12 clone. On the other hand, we found no evidence for a widespread CF transmissible clone. All but one of the 43 analysed CF strains belonged to a ubiquitous P. aeruginosa “core lineage” and typically exhibited the exoS ⁺/exoU ⁻ genotype and group B oprL and oprD alleles. This is to our knowledge the first report of an MST analysis conducted on a polyphasic data set.     

Additional observations on the sporozoite transmission of Plasmodium knowlesi to monkeys

Saimiri boliviensis monkeys were infected by the intravenous injection of 50 sporozoites of the H strain of Plasmodium knowlesi dissected from the salivary glands of Anopheles dirus mosquitoes; prepatent periods were 11, 12, 13, 13, 13, and 16 days. Sporozoites of P. knowlesi stored frozen for 7 days, 53 days, 20 mo, 7 yr and 7 mo, and 11 yr and 5 mo induced infections in Macaca mulatta monkeys with prepatent periods of 7, 6, 8, 10, and 7 days, respectively. After frozen storage for 11 yr and 5 mo, infections were induced in S. boliviensis with prepatent periods of 10-13 days.     

Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome

AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a key role in the regulation of energy metabolism. In humans, mutations in the gamma2-subunit of AMPK cause cardiac hypertrophy associated with Wolff-Parkinson-White syndrome, characterized by ventricular preexcitation. The effect of these mutations on AMPK activity and in development of the disease is enigmatic. Here we report that transgenic mice with cardiac-specific expression of gamma2 harboring a mutation of arginine residue 531 to glycine (RG-TG) develop a striking cardiac phenotype by 4 wk of age, including hypertrophy, impaired contractile function, electrical conduction abnormalities, and marked glycogen accumulation. At this stage, AMPK activity isolated from hearts of RG-TG mice was almost completely abolished but could be restored after phosphorylation by an upstream AMPK kinase. At 1 wk of age, there was no detectable evidence of a cardiac phenotype, and AMPK activity in RG-TG hearts was similar to that in nontransgenic, control mice. We propose that mutations in gamma2 lead to suppression of total cardiac AMPK activity secondary to increased glycogen accumulation. The subsequent decrease in AMPK activity provides a mechanism that may explain the development of cardiac hypertrophy in this model.     

Diversifying the biological sciences: past efforts and future challenges

I am honored to receive the E. E. Just Award for 2010. In my invited essay, I have opted to discuss the state of diversity in the biological sciences with some recommendations for moving forward toward a more positive and inclusive academy. The need to develop cohorts of minority scientists as support groups and to serve as role models within our institutions is stressed, along with the need to ensure that minority scientists are truly included in all aspects of the academy. It is imperative that we increase our efforts to prepare for the unique challenges that we will face as the United States approaches a "majority minority" population in the next 50 years.     

Allozyme electrophoresis still represents a powerful technique in the management of coral reefs

Understanding genetic variability and gene flow between populations of scleractinian corals separated by one to several hundred kilometers is crucially important as we head into a century of climate change in which an understanding of the connectivity of populations is a critically important question in management. Genetic methods that directly use molecular variance in the DNA should offer greater precision in detecting differences among individuals and populations than the more traditional allozyme electrophoresis. However, this paper highlights the point that the limited number of DNA markers that have been identified for scleractinian coral genetic studies do not necessarily offer greater precision than that offered by allozymes. In fact, at present allozyme electrophoresis yields greater information than the eight different DNA markers used in this study. Given the relative ease of use of allozymes and the wealth of comparable data sets from numerous previously published studies, allozyme electrophoresis should not be dismissed for population structure and connectivity studies on coral reefs. While continued effort should be placed into searching for new DNA markers, until a more sensitive DNA marker becomes available for scleractinian corals, allozyme electrophoresis remains a powerful and relevant technique for understanding the connectivity of coral population studies.     

Shoal sex composition affects exploration in the Mediterranean killifish

As a consequence of sexual selection, males and females may exhibit wide behavioural differences, for example, spatial behaviour. In fish, the two sexes often show different exploratory tendencies. This sex difference has been usually studied by testing individual fish. As many fish species live in social groups with different sex composition, the aforementioned approach might not picture the natural variation of the exploratory behaviour expressed by males and females. Here, we observed shoals of four Mediterranean killifish, Aphanius fasciatus, with three different sex compositions (4 females, 4 males, or 2 females and 2 males) during the exploration of a novel environment. Sex composition of the shoals did not predict the latency to emerge from a shelter into the novel environment. However, once emerged, shoals composed by four males displayed reduced exploratory behaviour compared to 4‐female and mixed‐sex shoals. These results indicated that sex differences in exploration subsist also at group level and highlighted the importance of sex composition in determining the behaviour of the entire shoal.