SWAN pathway-network identification of common aneuploidy-based oncogenic drivers.

Haploinsufficiency drives Darwinian evolution. Siblings, while alike in many aspects, differ due to monoallelic differences inherited from each parent. In cancer, solid tumors exhibit aneuploid genetics resulting in hundreds to thousands of monoallelic gene-level copy-number alterations (CNAs) in each tumor. Aneuploidy patterns are heterogeneous, posing a challenge to identify drivers in this high-noise genetic environment. Here, we developed Shifted Weighted Annotation Network (SWAN) analysis to assess biology impacted by cumulative monoallelic changes. SWAN enables an integrated pathway-network analysis of CNAs, RNA expression, and mutations via a simple web platform. SWAN is optimized to best prioritize known and novel tumor suppressors and oncogenes, thereby identifying drivers and potential druggable vulnerabilities within cancer CNAs. Protein homeostasis, phospholipid dephosphorylation, and ion transport pathways are commonly suppressed. An atlas of CNA pathways altered in each cancer type is released. These CNA network shifts highlight new, attractive targets to exploit in solid tumors.

Successful treatment of 3 naturally acquired cases of canine cheyletiellosis with fluralaner.

Three dogs were diagnosed with naturally occurring cheyletiellosis based on clinical signs and visualization of parasites and ova. Treatment with fluralaner (orally) resulted in a rapid resolution of clinical signs with no evidence of mites or ova at 1 or 2 mo post-treatment. This is apparently the first published report of an isoxazoline being used to successfully treat cheyletiellosis in veterinary medicine. Therefore, fluralaner may be an effective option for treatment or prevention of canine cheyletiellosis, although research is needed to confirm its effectiveness for treatment of cheyletiellosis in dogs and other species. Key clinical message: This is apparently the first published report of an isoxazoline being used to successfully treat cheyletiellosis in companion animal practice. These parasites are both contagious and zoonotic and there are currently no approved products for treatment or prevention of cheyletiellosis.

Traitement réussi de 3 cas de cheylétiellose canine acquis naturellement avec du fluralaner. Trois chiens ont été diagnostiqués avec une cheylétiellose acquise naturellement sur la base des signes cliniques et la visualisation des parasites et des œufs. Un traitement avec du fluralaner (oralement) a résulté en une résolution rapide des signes cliniques sans aucune évidence de mites ou d'œufs à 1 ou 2-mois post-traitement. Ceci semble être le premier rapport publié d'un isoxazoline utilisé pour traiter avec succès la cheylétiellose en médecine vétérinaire. Ainsi, le fluralaner serait une option efficace pour le traitement ou la prévention de la cheylétiellose canine, bien que de la recherche soit nécessaire pour confirmer son efficacité pour le traitement de la cheylétiellose chez les chiens et les autres espèces.Message clinique clé :Ceci semble être le premier rapport publié de l'utilisation d'un isoxazoline pour traiter avec succès la cheylétiellose en pratique des animaux de compagnie. Ces parasites sont contagieux et zoonotiques et il n'y a à l'heure actuelle aucun produit approuvé pour le traitement ou la prévention de la cheylétiellose.(Traduit par Dr Serge Messier).

Factors impacting resident outcomes from COVID-19 outbreaks in Residential Aged Care Facilities in Sydney Local Health District: testing an infection prevention and control scoring system.

BACKGROUND: COVID-19 outbreaks have disproportionately affected Residential Aged Care Facilities (RACFs) around the world, with devastating impacts for residents and their families. Many factors such as community prevalence, facility layout, and infection control practices have been linked to resident outcomes. At present, there are no scoring systems designed to quantify these factors and assess their level of association with resident attack rates and mortality rates. METHODS: We constructed a novel Infection Prevention and Control (IPC) scoring system to quantify facility layout, ability to cohort residents, and IPC practices in RACFs. We conducted a retrospective observational cohort study of COVID-19 outbreaks, applying our IPC scoring system to all COVID-19 outbreaks occurring in RACFs in Sydney Local Health District during the Delta and Omicron waves of the COVID-19 pandemic in New South Wales, Australia. RESULTS: Twenty-six COVID-19 outbreaks in 23 facilities in the Delta wave, and 84 outbreaks in 53 facilities in the Omicron wave were included in the study. A linear Generalised Estimating Equation model was fitted to the Omicron data. Higher IPC scores were associated with higher attack rates and mortality rates. Facilities with IPC scores greater than 75.0% had attack rates 19.6% higher [95% CI: 6.4%-32.8%] and mortality rates 1.7% higher [95% CI: 0.6%-2.7%] than facilities with an IPC score of less than 60.0%. CONCLUSIONS: The results of this study suggest the utility of the IPC scoring system for identifying facilities at greater risk of adverse outcomes from COVID-19 outbreaks. While further validation and replication of accuracy is required, the IPC scoring system could be used and adapted to improve planning, policy, and resource allocation for future outbreaks.

Hyperpigmented Mycosis Fungoides Masquerading as Longstanding Lichen Planus Pigmentosus: A Diagnostic Pitfall.

BACKGROUND: Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. CASE PRESENTATION: We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. ASSESSMENT: Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. DIAGNOSIS: A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. CONCLUSION: This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.

Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors.

Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer.

Feline urinary tract pathogens in western Canada: Prevalence of bacterial species and antimicrobial resistance from 2012 to 2018.

Objective: The aim of this study was to investigate the bacterial population and antimicrobial resistance of bacteria isolated from feline urine from 2012 to 2018 in the Canadian provinces of Alberta and British Columbia. Animals and procedure: IDEXX Reference Laboratories provided data from urine samples submitted from Alberta and British Columbia for aerobic culture and susceptibility testing from January 1, 2012 to December 31, 2018. The analysis included 8084 bacterial isolates from 7522 cystocentesis samples, with at least 1000 colony-forming units per mL. Results: Escherichia coli, Enterococcus species, and Staphylococcus species were the most commonly isolated bacteria, at 60.0%, 22.7%, and 11.8%, respectively. The proportions did not vary significantly throughout the study period or between British Columbia and Alberta. Apart from an increase in the resistance of Staphylococcus species to clindamycin, there was minimal change in the antimicrobial susceptibility of the 3 most commonly isolated bacteria over the study period. More than 85% of Gram-positive organisms were susceptible to amoxicillin with or without clavulanic acid, and > 85% of Gram-negative organisms were susceptible to amoxicillin with clavulanic acid and trimethoprim with sulfamethoxazole. Conclusion and clinical relevance: Treatment with amoxicillin, with or without clavulanic acid, may be considered for bacterial feline lower urinary tract disease in Alberta and British Columbia while awaiting culture results.

Agents pathogènes des voies urinaires félines dans l'Ouest canadien: prévalence des espèces bactériennes et résistance aux antimicrobiens de 2012 à 2018. Objectif: Le but de cette étude était d'étudier la population bactérienne et la résistance antimicrobienne des bactéries isolées de l'urine féline de 2012 à 2018 dans les provinces canadiennes de l'Alberta et de la Colombie-Britannique. Animaux et procédure: Les Laboratoires de référence IDEXX ont fourni des données à partir d'échantillons d'urine soumis par l'Alberta et la Colombie-Britannique pour une culture aérobie et des tests de sensibilité du 1er janvier 2012 au 31 décembre 2018. L'analyse comprenait 8084 isolats bactériens provenant de 7522 échantillons d'urine obtenus par cystocentèse, avec au moins 1000 unités formant des colonies/mL. Résultats: Escherichia coli, les espèces appartenant aux genres Enterococcus et Staphylococcus étaient les bactéries les plus couramment isolées, à 60,0 %, 22,7 % et 11,8 %, respectivement. Les proportions n'ont pas varié de manière significative tout au long de la période d'étude ni entre la Colombie-Britannique et l'Alberta. Hormis une augmentation de la résistance des espèces de Staphylococcus à la clindamycine, il y a eu un changement minime de la sensibilité aux antimicrobiens des 3 bactéries les plus couramment isolées au cours de la période d'étude. Plus de 85 % des organismes à Gram positif étaient sensibles à l'amoxicilline avec ou sans acide clavulanique, et > 85 % des organismes à Gram négatif étaient sensibles à l'amoxicilline avec acide clavulanique et à la combinaison triméthoprime-sulfaméthoxazole. Conclusion et pertinence clinique: Un traitement à l'amoxicilline, avec ou sans acide clavulanique, peut être envisagé pour les infections bactérienne urinaires félines en Alberta et en Colombie-Britannique en attendant les résultats de la culture.(Traduit par Dr Serge Messier).

Autophagy modulating therapeutics inhibit ovarian cancer colony generation by polyploid giant cancer cells (PGCCs).

BACKGROUND: Genomic instability and chemoresistance can arise in cancer due to a unique form of plasticity: that of polyploid giant cancer cells (PGCCs). These cells form under the stress of chemotherapy and have higher than diploid chromosome content. PGCCs are able to then repopulate tumors through an asymmetric daughter cell budding process. PGCCs have been observed in ovarian cancer histology, including the deadly and common form high-grade serous ovarian carcinoma (HGSC). We previously discovered that drugs which disrupt the cellular recycling process of autophagy are uniquely efficacious in pre-clinical HGSC models. While autophagy induction has been associated with PGCCs, it has never been previously investigated if autophagy modulation interacts with the PGCC life cycle and this form of tumor cell plasticity. METHODS: CAOV3 and OVCAR3 ovarian cancer cell lines were treated with carboplatin or docetaxel to induce PGCC formation. Microscopy was used to characterize and quantify PGCCs formed by chemotherapy. Two clinically available drugs that inhibit autophagy, hydroxychloroquine and nelfinavir, and a clinically available activator of autophagy, rapamycin, were employed to test the effect of these autophagy modulators on PGCC induction and subsequent colony formation from PGCCs. Crystal violet-stained colony formation assays were used to quantify the tumor-repopulating stage of the PGCC life cycle. RESULTS: Autophagy inhibitors did not prevent PGCC formation in OVCAR3 or CAOV3 cells. Rapamycin did not induce PGCC formation on its own nor did it exacerbate PGCC formation by chemotherapy. However, hydroxychloroquine prevented efficient colony formation in CAOV3 PGCCs induced by carboplatin (27% inhibition) or docetaxel (41% inhibition), as well as in OVCAR3 cells (95% and 77%, respectively). Nelfinavir similarly prevented colony formation in CAOV3 PGCCs induced by carboplatin (64% inhibition) or docetaxel (94% inhibition) as well as in OVCAR3 cells (89% and 80%, respectively). Rapamycin surprisingly also prevented PGCC colony outgrowth (52-84% inhibition). CONCLUSIONS: While the autophagy previously observed to correlate with PGCC formation is unlikely necessary for PGCCs to form, autophagy modulating drugs severely impair the ability of HGSC PGCCs to form colonies. Clinical trials which utilize hydroxychloroquine, nelfinavir, and/or rapamycin after chemotherapy may be of future interest.

Targeting circulating monocytes with CCL2-loaded liposomes armed with an oncolytic adenovirus.

Oncolytic viruses (OVs) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provide an opportunity to target OVs via circulation to inaccessible tumors using liposome-assisted drug delivery.

Examining the potential of VR program Tilt Brush in reducing anxiety.

Recent advancement in technology has made virtual reality (VR) more accessible and immersive than ever before, resulting in its increasing utility in various industries. Despite this, VR has remained an underutilised tool within clinical psychology. This study aimed to explore the potential of using VR for therapeutic benefits through examining the level of flow and anxiety-reducing effects of freeform drawing in real life (on paper) versus drawing in VR (using Tilt Brush) via a randomised-controlled trial with 40 participants. State and trait anxiety was measured using the State-Trait Anxiety Inventory, level of flow was measured using the Long Flow State Scale, and level of presence was measured using the iGroup Presence Questionnaire. Overall level of flow was not significantly different between both groups, implying drawing in VR induces as much flow as drawing in real life. Level of flow was positively correlated to level of presence experienced in the VR group (p < .01). Although there was no significant interaction effect, both groups experienced an overall decrease in state anxiety, with the VR group experiencing a significant reduction of state anxiety from pre- to post-test (p < .01).

Genetic evidence supports a range extension for the Brazilian cownose ray Rhinoptera brasiliensis in the western North Atlantic.

We report 24 new records of the Brazilian cownose ray Rhinoptera brasiliensis outside its accepted geographic range. Sequencing of a 442-base pair portion of the mitochondrial NADH dehydrogenase subunit 2 gene for 282 Rhinoptera samples revealed eight records off the east coast of the USA and 16 from the eastern Gulf of Mexico. Both sexes of all life stages were documented in all seasons over multiple years in the Indian River and Lake Worth lagoons, Florida, indicating that their range extends further in the western North Atlantic than previously described.

Delay in emergency hernia surgery is associated with worse outcomes.

BACKGROUND: Patients requiring emergent surgery for hernia vary widely in presentation and management. The purpose of this study was to determine if the variation in timing of urgent surgery impacts surgical outcomes. METHODS: The national NSQIP database for years 2011-2016 was queried for emergent surgeries for abdominal hernia resulting in obstruction or gangrene by primary post-op diagnosis. Diaphragmatic hernias were excluded. Patients were grouped by surgical timing from admission to day of surgery: same day, next day, and longer delay. Multinomial propensity score weighting was used to address potential differences in underlying covariates' clustering across the timing groups followed by multivariable logistic regression of morbidity and mortality. RESULTS: Weighted analysis yielded an effective sample size of 76,364. Hernia types included inguinal (20.9%); femoral (6.7%); umbilical (20.2%); ventral (41.0%); and other (10.4%). Delayed surgery was associated with increased rates of major complications (26.4% vs. 20.9%, p < 0.001), longer operative times (+ 12.5 min, p < 0.001), longer postoperative lengths of stay (+ 1.6 days, p < 0.001), increased re-operations (5.9% vs. 4.7%, p = 0.019), increased readmissions (7.0% vs. 5.7%, p = 0.004), and increased 30-day mortality (2.4% vs. 1.7%, p = 0.002). When controlling for other factors, next-day surgery (OR 1.23, 95% CI 1.05-1.45, p = 0.009) and surgery delayed more than one day (OR 1.40, 95% CI 1.13-1.73, p < 0.002) were associated with an increased odds of a major complication. Mortality and readmission by timing of surgery were not independently significant. CONCLUSIONS: Delay in surgery for emergent hernias increased the odds of major morbidity but not mortality. Patients presenting with hernia and an indication for urgent surgical intervention may benefit from an operation as soon as feasible rather than warrant waiting for further physiologic optimization, medical clearance, or specialized surgical personnel.

Compliance with preoperative care measures reduces surgical site infection after colorectal operation.

BACKGROUND: Surgical site infections (SSIs) are a major cause of morbidity complicating colorectal operations. Several evidence-based preoperative strategies are associated with decreased SSI rates. We hypothesize that compliance with multiple strategies is associated with lower incidence of SSI after the elective colorectal operation. METHODS: Preoperative care measure compliance before colorectal operations were assessed. Measures included antiseptic wash the night before and day of operation, oral antibiotic, and mechanical bowel preparation, antibiotic prophylaxis, Chloraprep skin preparation, and hair clipping. Rates of SSI after colectomy and other pertinent outcomes were stratified by full and partial compliance with preoperative measures. Exclusion criteria included bowel perforation, ischemia, complete obstruction, intra-abdominal abscess, and no intraoperative skin closure. RESULTS: Eight hundred twenty-six subjects underwent colectomy between 2010 and 2016; 469 met inclusion criteria. Compliance with all measures occurred in 214 (46%) and was independently associated with lower postoperative infection rates (odds ratio [OR], 0.37; confidence interval [CI], 0.16-0.85; P = 0.02). SSI occurred in 51 (11%): was superficial in 35 (7%); deep in 5 (1%); and organ space in 11 (2%). SSI rates were reduced from 16% (partial or no compliance group) to 5% (full compliance group). No stand-alone intervention was independently associated with decreased SSI rate. Multivariate analysis found the following factors associated with a lower risk of SSI: full compliance with all five process measures, lower BMI, nonsmoker, and minimally invasive operation. DISCUSSION AND CONCLUSION: Compliance with preoperative care strategies reduces rates of SSI after colectomy with a cumulative effect more pronounced than any single intervention reinforcing the need for protocol-driven and evidence-based care for patients undergoing colorectal operations.

The academic tweet: Twitter as a tool to advance academic surgery.

Social media, Twitter in particular, has emerged as an essential tool for surgeons. In the realm of academic surgery, it enables surgeons to advance the core values of academic surgery, as outlined by the Association for Academic Surgery: inclusion, leadership, innovation, scholarship, and mentorship. This article details the ways in which surgeons are using Twitter to embody these values and how the Twitter account for the Association of Academic Surgeons accomplishes its goal of inspiring and developing young academic surgeons.

Organizational conditions for engagement in quality and safety improvement: a longitudinal qualitative study of community pharmacies.

BACKGROUND: While efforts have been made to bring about quality and safety improvement in healthcare, it remains by no means certain that an improvement project will succeed. This suggests a need to better understand the process and conditions of improvement. The current study addresses this question by examining English community pharmacies attempting to undertake improvement activities. METHOD: The study used a longitudinal qualitative design, involving a sample of ten community pharmacies. Each pharmacy took part in a series of improvement workshops, involving use of the Manchester Patient Safety Framework (MaPSaF), over a twelve-month period. Qualitative data were collected from the workshops, from follow-up focus groups and from field notes. Template analysis was used to identify themes in the data. RESULTS: The progress made by pharmacies in improving their practice can be described in terms of a behavioural change framework, consisting of contemplation (resolving to make changes if they are required), planning (deciding how to carry out change) and execution (carrying out and reflecting on change). Organizational conditions supporting change were identified; these included the prioritisation of improvement, a commitment to change, a trusting and collaborative relationship between staff and managers, and knowledge about quality and safety issues to work on. CONCLUSIONS: Our study suggests a process by which healthcare work units might undergo improvement. In addition to recognising and providing support for this process, it is important to establish an environment that fosters improvement, and for work units to ensure that they are prepared for undergoing improvement activities.

Diverted by dazzle: perceived movement direction is biased by target pattern orientation.

'Motion dazzle' is the hypothesis that predators may misjudge the speed or direction of moving prey which have high-contrast patterning, such as stripes. However, there is currently little experimental evidence that such patterns cause visual illusions. Here, observers binocularly tracked a Gabor target, moving with a linear trajectory randomly chosen within 18° of the horizontal. This target then became occluded, and observers were asked to judge where they thought it would later cross a vertical line to the side. We found that internal motion of the stripes within the Gabor biased judgements as expected: Gabors with upwards internal stripe motion relative to the overall direction of motion were perceived to be crossing above Gabors with downwards internal stripe movement. However, surprisingly, we found a much stronger effect of the rigid pattern orientation. Patches with oblique stripes pointing upwards relative to the direction of motion were perceived to cross above patches with downward-pointing stripes. This effect occurred only at high speeds, suggesting that it may reflect an orientation-dependent effect in which spatial signals are used in direction judgements. These findings have implications for our understanding of motion dazzle mechanisms and how human motion and form processing interact.

Discharge destination and readmission rates in older trauma patients.

BACKGROUND: In older trauma patients, the impact of discharge destination on readmission rates is not known. The objective of this study was to evaluate the association between the discharge destination and the 30-day readmission rate in older trauma patients. MATERIALS AND METHODS: A previously validated database of all patients aged 45 years or older undergoing trauma evaluation at our level 1 trauma center between January 1, 2008 and December 31, 2008 was analyzed to retrospectively compare the incidences of 30-day readmission between patients discharged to home, to inpatient rehabilitation facilities, and to other extended care facilities (ECFs). Demographic information including age and gender and potentially confounding factors including injury severity, trauma activation level, comorbidities, medications, and preinjury functional status were included. Univariate analysis was undertaken using chi-square testing. Multiple logistic regression was performed with potential confounding variables to evaluate for independent contribution to readmission risk. RESULTS: A total of 960 patients were evaluated; 81 patients (8.4%) were excluded, leaving 879 patients included in the analysis. Seventy-six patients (8.6%) were readmitted within 30 d of discharge. Overall, 6% of those discharged to home, 13% of those discharged to ECF, and 16% of those discharged to rehabilitation were readmitted (P < 0.01 on univariate analysis). Overall, 866 (98.5%) patients had data recorded for all variables analyzed using multiple logistic regression; among these, only discharge destination was independently associated with the rate of readmission (P < 0.01). CONCLUSIONS: Discharge to ECFs and inpatient rehabilitation facilities appear to be an independent risk factor for hospital readmissions in this population despite controlling for injury severity and comorbidities. Recognition of this risk factor may aid in the disposition planning of these patients and suggests the need for further evaluation of this correlation at other US medical centers.

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

INTRODUCTION: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. METHODS: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. RESULTS: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. CONCLUSION: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

History of Social Media in Surgery.

In many ways, the history of surgeons on Twitter echoes the initial resistance and ultimate mass adoption of laparoscopic surgery that led to the field of minimally invasive surgery. At its inception, social media was similarly met with skepticism and concerns of threats to professionalism. Despite these concerns, numerous surgeons and other physicians pioneered the use of social media to establish a virtual medical community and share scientific knowledge regarding a variety of topics including medical conferences, journal publications, and more. After these initial successes, surgeons' views have evolved, leading to mass adoption of social media and participation on Twitter as a means of professional networking and dissemination of science. This article chronicles that history.