Harvesting and amplifying gene cassettes confers cross-resistance to critically important antibiotics.

Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales. Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In37 have been "harvested" by insertion sequence IS26 as a transposon that is widely disseminated among the Enterobacterales. This transposon encodes the enzymes AAC(6')-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS26/In37-derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.

A framework for role allocation in education, research and leadership services in Canadian academic divisions of general surgery: a modified Delphi consensus.

BACKGROUND: Moving toward a funding standard similar to that for clinical services for roles essential to the functioning of education, research and leadership services within divisions of general surgery is necessary to strengthen divisional resilience. We aimed to identify roles and underlying tasks in these services central to sustainable functioning of Canadian academic divisions of general surgery. METHODS: Between June 2018 and October 2020, we used a 4-step modified Delphi method (online survey, face-to-face nominal group technique [n = 12], semistructured telephone interview [n = 8] and nominal group technique [n = 12]) to achieve national consensus from an expert panel of all 17 heads of academic divisions of general surgery in Canada on the roles and accompanying tasks essential to education, research and leadership services within an academic division of general surgery. We used 70% agreement to determine consensus. RESULTS: The expert panel agreed that a framework for role allocation in education, research and leadership services was relevant and necessary. Consensus was reached for 7 roles within the educational service, 3 roles within the research service and 5 roles within the leadership service. CONCLUSION: Our framework represents a national consensus that defines role standards for education, research and leadership services in Canadian academic divisions of general surgery. The framework can help divisions build resiliency, and enable sustained and deliberate advances in these services.

Propelling microdroplets generated and sustained by liquid-liquid phase separation in confined spaces.

Flow transport in confined spaces is ubiquitous in technological processes, ranging from separation and purification of pharmaceutical ingredients by microporous membranes and drug delivery in biomedical treatment to chemical and biomass conversion in catalyst-packed reactors and carbon dioxide sequestration. In this work, we suggest a distinct pathway for enhanced liquid transport in a confined space via propelling microdroplets. These microdroplets can form spontaneously from localized liquid-liquid phase separation as a ternary mixture is diluted by a diffusing poor solvent. High speed images reveal how the microdroplets grow, break up and propel rapidly along the solid surface, with a maximal velocity up to ∼160 µm s-1, in response to a sharp concentration gradient resulting from phase separation. The microdroplet propulsion induces a replenishing flow between the walls of the confined space towards the location of phase separation, which in turn drives the mixture out of equilibrium and leads to a repeating cascade of events. Our findings on the complex and rich phenomena of propelling droplets suggest an effective approach to enhanced flow motion of multicomponent liquid mixtures within confined spaces for time effective separation and smart transport processes.

Reference Materials for Phase Equilibrium Studies. 1. Liquid-Liquid Equilibria (IUPAC Technical Report).

This article is the first of three projected IUPAC Technical Reports resulting from IUPAC Project 2011-037-2-100 (Reference Materials for Phase Equilibrium Studies). The goal of that project was to select reference systems with critically evaluated property values for the validation of instruments and techniques used in phase equilibrium studies for mixtures. This Report proposes seven systems for liquid-liquid equilibrium studies, covering the four most common categories of binary mixtures: aqueous systems of moderate solubility, non-aqueous systems, systems with low solubility, and systems with ionic liquids. For each system, the available literature sources, accepted data, smoothing equations, and estimated uncertainties are given.

Probing Contaminant Transport to and from Clay Surfaces in Organic Solvents and Water Using Solution Calorimetry.

Clays, in tailings, are a significant ongoing environmental concern in the mining and oilsands production industries, and clay rehabilitation following contamination poses challenges episodically. Understanding the fundamentals of clay behavior can lead to better environmental impact mitigation strategies. Systematic calorimetric measurements are shown to provide a framework for parsing the synergistic and antagonistic impacts of trace (i.e., parts per million level) components on the surface compositions of clays. The enthalpy of solution of as-received and "contaminated" clays, in as-received and "contaminated" organic solvents and water, at 60 °C and atmospheric pressure, provides important illustrative examples. Clay contamination included pre-saturation of clays with water and organic liquids. Solvent contamination included the addition of trace water to organic solvents and trace organic liquids to water. Enthalpy of solution outcomes are interpreted using a quantitative mass and energy balance modeling framework that isolates terms for solvent and trace contaminant sorption/desorption and surface energy effects. Underlying surface energies are shown to dominate the energetics of the solvent-clay interaction, and organic liquids as solvents or as trace contaminants are shown to displace water from as-received clay surfaces. This approach can be readily extended to include pH, salts, or other effects and is expected to provide mechanistic and quantitative insights underlying the stability of clays in tailings ponds and the behaviors of clays in diverse industrial and natural environments.

Patients aged 80 years and older accrue similar benefits from total parenteral nutrition compared to middle-aged patients.

Age is becoming less of a consideration to aggressive medical and surgical interventions. The aim of this study was to evaluate whether patients older than 80 years showed similar gains from total parenteral nutrition (TPN) in terms of nutritional and inflammatory markers compared to patients 35 to 50 years old. A database of patients aged ≥80 years old (group 1) and patients between 35 and 50 (group 2), on TPN for greater than 1 week, was compiled from the Nutrition Support Service (NSS) database. Patients had C-reactive protein (CRP), prealbumin, and albumin drawn twice weekly. Patients were matched 1:1 based on gender, diabetes, smoking, Subjective Global Assessment score, and diagnosis. Both groups showed comparable improvements in nutritional and inflammatory markers. There were no statistically significant differences in weekly changes to prealbumin, albumin, CRP, and CRP:prealbumin (C:P) ratio between group 1 and group 2 patients. Both groups had similar complication rates (line-related thrombosis, catheter-related bloodstream infections, intra-abdominal sepsis), days on TPN, length of hospitalization, and mortality rate. Patients older than 80 years benefit from aggressive nutritional support by administration of TPN. Age should not be used as an exclusion criterion for patients requiring TPN.

Observation of liquid-crystal formation during melting of D-(+)-glucose.

Liquid crystals, observed as maltese crosses under cross-polarized light, form in D-(+)-glucose immediately upon melting, at ∼416 K, and become an isotropic liquid at ∼500 K. Differential scanning calorimetry (DSC) results show two overlapping endothermic peaks corresponding to the formation and disappearance of the liquid crystals. Thermogravimetric analysis (TGA) confirmed that D-(+)-glucose undergoes thermal decomposition upon melting. Cooling and reheating isotropic samples previously heated to 500 K do not lead to the reappearance of the liquid crystals. The formation of liquid crystals is irreversible. Further study is required to determine which components among the decomposition intermediates or products of D-(+)-glucose are responsible for the formation of liquid crystals and whether they have process or product applications.

Long-term outcome of laparoscopic Nissen and laparoscopic Toupet fundoplication for gastroesophageal reflux disease: a prospective, randomized trial.

BACKGROUND: A prospective, randomized trial was performed to evaluate the long-term outcome and patient satisfaction of laparoscopic complete 360 degrees fundoplication compared with partial posterior 270 degrees fundoplication. Partial fundoplication is purported to have fewer side effects with a higher failure rate in controlling gastroesophageal reflux disease (GERD), while complete fundoplication is thought to result in more dysphagia and gas-related symptoms. METHODS: Patients were randomized to either laparoscopic Nissen (LN) or laparoscopic Toupet (LT) fundoplication. Esophageal manometry, 24-h pH studies, a detailed questionnaire, and a visual analog symptom (VAS) score were completed before and after surgery. A final global outcome questionnaire was performed. Failure was defined as recurrent GERD requiring revision surgery, maintenance proton pump inhibitor (PPI) therapy, or surgery for postoperative dysphagia. RESULTS: One hundred patients were randomized to LN (50) or LT (50). There were no differences between LN and LT with respect to postoperative symptoms and physiological variables except a higher wrap pressure in the LN group (15.2 vs. 12.0 mmHg). Dysmotility improved in 8/14 (57%) and 6/11 (54%) patients in the LN group and the LT group, respectively, after surgery. There was no correlation between dysmotility and dysphagia both pre- and post surgery in the two groups. Recurrent symptoms of GERD occurred in 8/47 (17.0%) and 8/48 (16.6%) in the LN group and the LT group, respectively. Outcome of patients with dysmotility was similar to those with normal motility in both groups. At final follow-up (59.76 + or - 24.23 months), in the LN group, 33/37 (89.1%) would recommend surgery to others, 32/37 (86.4%) would have repeat surgery, and 34/37 (91.8%) felt they were better off than before surgery. The corresponding numbers for the LT group (follow-up = 55.18 + or - 25.97 months) were 35/36 (97.2%), 30/36 (83.3%), and 33/36 (91.6%). CONCLUSION: LN and LT are equally effective in restoring the lower esophageal sphincter function and provide similar long-term control of GERD with no difference in dysphagia. Esophageal dysmotility had no influence on the outcome of either operation.

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

BACKGROUND: Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. METHODS: Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. RESULTS: Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. CONCLUSIONS: Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival.

PURPOSE: To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 ((90)Y) glass microspheres. MATERIALS AND METHODS: Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of (90)Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients. RESULTS: There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors. CONCLUSION: (90)Y hepatic treatments are well tolerated with acceptable toxicities; tumor response and median survival are promising.

Variceal recurrence, rebleeding, and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices.

OBJECTIVE: This study tested the validity of the hypothesis that eradication of esophageal varices by repeated injection sclerotherapy would reduce recurrent variceal bleeding and death from bleeding varices in a high-risk cohort of alcoholic patients with cirrhosis. SUMMARY BACKGROUND DATA: Although banding of esophageal varices is now regarded as the most effective method of endoscopic intervention, injection sclerotherapy is still widely used to control acute esophageal variceal bleeding as well as to eradicate varices to prevent recurrent bleeding. This large single-center prospective study provides data on the natural history of alcoholic cirrhotic patients with bleeding varices who underwent injection sclerotherapy. METHODS: Between 1984 and 2001, 287 alcoholic cirrhotic patients (225 men, 62 women; mean age, 51.9 years; range, 24-87 years; Child-Pugh grades A, 39; B, 116; C, 132) underwent a total of 2565 upper gastrointestinal endoscopic sessions, which included 353 emergency and 1015 elective variceal injection treatments. Variceal rebleeding, eradication, recurrence, and survival were recorded. RESULTS: Before eradication of varices was achieved, 104 (36.2%) of the 287 patients had a total of 170 further bleeding episodes after the first endoscopic intervention during the index hospital admission. Rebleeding was markedly reduced after eradication of varices. In 147 (80.7%) of 182 patients who survived more than 3 months, varices were eradicated after a mean of 5 injection sessions and remained eradicated in 69 patients (mean follow-up, 34.6 months; range, 1-174 months). Varices recurred in 78 patients and rebled in 45 of these patients. Median follow-up was 32.3 months (mean, 42.1 months; range, 3-198.9 months). Cumulative overall survival by life-table analysis was 67%, 42%, and 26% at 1, 3, and 5 years, respectively. A total of 201 (70%) patients died during follow-up. Liver failure was the most common cause of death. CONCLUSION: Repeated sclerotherapy eradicates esophageal varices in most alcoholic cirrhotic patients with a reduction in rebleeding. Despite control of variceal bleeding, survival at 5 years was only 26% because of death due to liver failure in most patients.

Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26.

OBJECTIVE: To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. DESIGN: Prospective, longitudinal follow-up of patients diagnosed with choroidal melanoma who were enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study Group. METHODS: Systemic and laboratory evaluations were performed during follow-up according to a standard protocol for 2320 patients enrolled in the Collaborative Ocular Melanoma Study trials without evidence of melanoma metastasis or other primary cancer at baseline. RESULTS: Seven hundred thirty-nine patients were diagnosed with at least 1 site of metastasis during follow-up after treatment for choroidal melanoma. Five- and 10-year cumulative metastasis rates were 25% (95% confidence interval, 23%-27%) and 34% (95% confidence interval, 32%-37%), respectively. Liver was the most common site (89%). The death rate following the report of melanoma metastasis was 80% at 1 year (95% confidence interval, 77%-83%) and 92% at 2 years (95% confidence interval, 89%-94%). Overall survival after metastasis did not vary by baseline size of primary tumor nor treatment for metastasis (when known). Long-term survival after diagnosis of metastasis was uncommon; only 8 patients survived 5 or more years. CONCLUSION: Metastasis rate increased significantly with increasing primary tumor dimensions at time of patient enrollment. Prognosis after metastatic disease remains poor. Effective methods are needed to prevent, diagnose, and treat metastasis from choroidal melanoma.

Second primary cancers after enrollment in the COMS trials for treatment of choroidal melanoma: COMS Report No. 25.

OBJECTIVE: To report sites of second primary cancer and the time to first diagnosis during routine follow-up after treatment for choroidal melanoma. DESIGN: Prospective longitudinal follow-up of patients enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study (COMS) Group. METHODS: Baseline and annual or semiannual systemic and laboratory evaluations were performed according to a standard protocol for 2320 patients enrolled in the COMS without evidence of melanoma metastasis or other primary cancer at baseline. Deaths were coded by a mortality coding committee. RESULTS: Subsequent to treatment for choroidal melanoma, a total of 222 patients were diagnosed with a second primary cancer other than basal or squamous cell skin cancer (5-year rate of 7.7% [95% confidence interval, 6.6%-9.0%]). The most common sites were prostate (23% of reported cases) and breast (17%); 12 of these 222 patients were diagnosed simultaneously with second primary cancers in 2 or more sites. Of these 222 patients, 113 died; 37 (33%) were coded as dead with melanoma metastasis, 33 (29%) as dead with a malignant tumor other than metastatic melanoma, and 13 (11%) as dead with a malignancy of uncertain origin. Radiotherapy did not significantly increase the development of second primary cancers. The rate of diagnosis of second primary cancer did not differ significantly by smoking status, although the rate in former smokers was increased vs that observed in either current smokers or those who never smoked. CONCLUSION: Routine medical surveillance for development of second primary cancers among patients treated for choroidal melanoma is important, especially for those with a history of smoking, regardless of the size of choroidal melanoma at the time of treatment.

Screening for metastasis from choroidal melanoma: the Collaborative Ocular Melanoma Study Group Report 23.

PURPOSE: To describe the predictive value of liver function tests (LFTs), chest x-ray, and diagnostic imaging for detecting melanoma metastasis during routine follow-up after treatment for choroidal melanoma. MATERIALS AND METHODS: Prospective longitudinal follow-up of patients enrolled onto two randomized trials was conducted by the Collaborative Ocular Melanoma Study (COMS) Group. Baseline and annual or semiannual systemic and laboratory evaluations were performed according to a standard protocol for 2320 patients enrolled on the COMS. RESULTS: COMS patients were screened annually for metastasis and new cancers using LFTs (alkaline phosphatase, AST, ALT, or bilirubin). Elevated findings (1.5 to 2 times upper limit of normal) on LFT prompted a diagnostic or imaging test to confirm or rule out cancer recurrence. Of 714 patients with clinical reports of metastasis, 675 patients died. Of these 675 patients, all but four had either histopathologically confirmed or clinically suspected metastatic melanoma present at the time of death. Among all patients, the 5-year cumulative diagnosis rate of metastatic melanoma was 24% (95% CI, 22% to 27%). Based on all patients with reported metastasis, the sensitivity, specificity, positive predictive value and negative predictive value associated with at least one abnormal LFT before first diagnosis of metastasis at any site was 14.7%, 92.3%, 45.7% and 71.0%, respectively. CONCLUSION: Use of LFTs results followed by diagnostic tests has high specificity and predictive values but low sensitivity. Better tests are needed to identify earlier metastatic disease associated with choroidal melanoma.

Laparoscopy-assisted repair of diaphragm injuries.

In this study we review our experience with an alternative laparoscopy-assisted technique for repair of diaphragm injuries. All patients admitted with an isolated diaphragm injury who underwent laparoscopy-assisted repair between January 1996 and February 2000 were included in the study. The diagnosis of the diaphragm injury was either obvious, with omentum herniating through the chest wall, or occult with confirmation of the injury at laparoscopy. Repair of the diaphragm was performed using standard surgical instruments via a 4-cm subcostal incision with use of abdominal wall traction and the laparoscope for visualization of the defect. A total of 24 patients underwent successful laparoscopy-assisted repair; There were twenty men and four women with an average age of 28.8 years (range 23-49 years). The average Revised Trauma score was 12. There were 23 grade II and 2 grade III diaphragm injuries. The mean operative time was 61 minutes (range 25-120 minutes) and the average hospital stay from the time of surgery to the time of discharge was 2.29 days (range 1-4 days). The procedure failed in one patient as a result of gaseous distension of the bowel. One patient developed a tension pneumothorax, and two others developed atelectasis. Laparoscopic-assisted repair of isolated diaphragm injuries using abdominal wall traction and standard surgical instruments is a feasible option with minimal morbidity and no mortality.