Statistical Coupling Analysis Predicts Correlated Motions in Dihydrofolate Reductase.

The role of dynamics in enzymatic function is a highly debated topic. Dihydrofolate reductase (DHFR), due to its universality and the depth with which it has been studied, is a model system in this debate. Myriad previous works have identified networks of residues in positions near to and remote from the active site that are involved in dynamics and others that are important for catalysis. For example, specific mutations on the Met20 loop in E. coli DHFR (N23PP/S148A) are known to disrupt millisecond-timescale motions and reduce catalytic activity. However, how and if networks of dynamically coupled residues influence the evolution of DHFR is still an unanswered question. In this study, we first identify, by statistical coupling analysis and molecular dynamic simulations, a network of coevolving residues, which possess increased correlated motions. We then go on to show that allosteric communication in this network is selectively knocked down in N23PP/S148A mutant E. coli DHFR. Finally, we identify two sites in the human DHFR sector which may accommodate the Met20 loop double proline mutation while preserving dynamics. These findings strongly implicate protein dynamics as a driving force for evolution.

Feasibility and Accuracy of Wrist-Worn Sensors for Perioperative Monitoring During and After Major Abdominal Surgery: An Observational Study.

INTRODUCTION: Continuous, ambulatory perioperative monitoring using wearable devices has shown promise for earlier detection of physiological deterioration and postoperative complications, preventing 'failure-to-rescue'. This study aimed to compare the accuracy of vital signs measured by wrist-based wearables with gold standard measurements from vital signs monitors or nurse assessments in major abdominal surgery. METHODS: Adult patients were eligible for inclusion in this prospective observational study validating the Empatica E4 wrist sensor intraoperatively and postoperatively. The primary outcomes were the 95% limits of agreement (LoA) between manual and device recordings of heart rate (HR) and temperature evaluated via Bland-Altman analysis. Secondary analysis was conducted using Clarke-Error grid analysis. RESULTS: Overall, 31 patients were recruited, and 27 patients completed the study. The median duration of recording per patient was 70.3 h, and a total of 2112 h of data recording were completed. Wrist-based HR measurement was accurate and moderately precise (bias: 0.3 bpm; 95% LoA -15.5 to 17.1), but temperature measurement was neither accurate nor precise (bias -2.2°C; 95% LoA -6.0 to 1.6). On Clarke-Error grid analysis, 74.5% and 29.6% of HR and temperature measurements, respectively, fell within the acceptable range of reference standards. CONCLUSIONS: Continuous perioperative monitoring of HR and temperature after major abdominal surgery using wrist-based sensors is feasible but was limited in this study by low precision. While wrist-based devices offer promise for the continuous monitoring of high-risk surgical patients, current technology is inadequate. Ongoing device hardware and software innovation with robust validation is required before such technologies can be routinely adopted in clinical practice.

Risk prediction algorithms for prolonged postoperative ileus: A systematic review.

AIM: Prolonged postoperative ileus (PPOI) is common and is associated with a significant healthcare burden. Previous studies have attempted to predict PPOI clinically using risk prediction algorithms. The aim of this work was to systematically review and compare risk prediction algorithms for PPOI following colorectal surgery. METHOD: A systematic literature search was conducted using MEDLINE, Embase, Web of Science and CINAHL Plus. Studies that developed and/or validated a risk prediction algorithm for PPOI in adults following colorectal surgery were included. Data were collected on study design, population and operative characteristics, the definition of PPOI used and risk prediction algorithm design and performance. Quality appraisal was assessed using the PROBAST tool. RESULTS: Eleven studies with 87 549 participants were included in our review. Most were retrospective, single-centre analyses (6/11, 55%) and rates of PPOI varied from 10% to 28%. The most commonly used variables were sex (8/11, 73%), age (6/11, 55%) and surgical approach (5/11, 45%). Area under the curve ranged from 0.68-0.78, and only three models were validated. However, there was significant variation in the definition of PPOI used. No study reported sensitivity, specificity or positive/negative predictive values. CONCLUSION: Currently available risk prediction algorithms for PPOI appear to discriminate moderately well, although there is a lack of validation data. Future studies should aim to use a standardized definition of PPOI, comprehensively report model performance and validate their findings using internal and external methodologies.

Validation of body surface colonic mapping (BSCM) against high resolution colonic manometry for evaluation of colonic motility.

Abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaires evaluated participants' preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range 38-63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range 0.47-0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility.

Tepsin binds LC3B to promote ATG9A trafficking and delivery.

Tepsin is an established accessory protein found in Adaptor Protein 4 (AP-4) coated vesicles, but the biological role of tepsin remains unknown. AP-4 vesicles originate at the trans-Golgi network (TGN) and target the delivery of ATG9A, a scramblase required for autophagosome biogenesis, to the cell periphery. Using in silico methods, we identified a putative LC3-Interacting Region (LIR) motif in tepsin. Biochemical experiments using purified recombinant proteins indicate tepsin directly binds LC3B preferentially over other members of the mammalian ATG8 family. Calorimetry and structural modeling data indicate this interaction occurs with micromolar affinity using the established LC3B LIR docking site. Loss of tepsin in cultured cells dysregulates ATG9A export from the TGN as well as ATG9A distribution at the cell periphery. Tepsin depletion in a mRFP-GFP-LC3B HeLa reporter cell line using siRNA knockdown increases autophagosome volume and number, but does not appear to affect flux through the autophagic pathway. Reintroduction of wild-type tepsin partially rescues ATG9A cargo trafficking defects. In contrast, reintroducing tepsin with a mutated LIR motif or missing N-terminus drives diffuse ATG9A subcellular distribution. Together, these data suggest roles for tepsin in cargo export from the TGN; ensuring delivery of ATG9A-positive vesicles; and in overall maintenance of autophagosome structure.

An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm.

BACKGROUND: Blepharospasm is treated with botulinum toxin, but obtaining satisfactory results is sometimes challenging. OBJECTIVE: The aim is to conduct an exploratory trial of oral dipraglurant for blepharospasm. METHODS: This study was an exploratory, phase 2a, randomized, double-blind, placebo-controlled trial of 15 participants who were assigned to receive a placebo or dipraglurant (50 or 100 mg) and assessed over 2 days, 1 and 2 hours following dosing. Outcome measures included multiple scales rated by clinicians or participants, digital video, and a wearable sensor. RESULTS: Dipraglurant was well tolerated, with no obvious impact on any of the measurement outcomes. Power analyses suggested fewer subjects would be required for studies using a within-subject versus independent group design, especially for certain measures. Some outcome measures appeared more suitable than others. CONCLUSION: Although dipraglurant appeared well tolerated, it did not produce a trend for clinical benefit. The results provide valuable information for planning further trials in blepharospasm. © 2024 International Parkinson and Movement Disorder Society.

Problems in management of medication overuse headache in transgender and gender non-conforming populations.

Primary headache disorders, such as migraine, account for a significant portion of disability rates worldwide, yet patients still struggle to receive the adequate medical and emotional support necessary to improve health outcomes. Insufficient pain management through either impractical pharmaceutical treatments or absent emotional support networks can worsen physical and mental health outcomes since comorbidities commonly associated with headache include hypertension, diabetes, depression, and anxiety. A lack of awareness on headache pathology and its observable severity can lead to pain-related prejudice that destroys beneficial aspects of patient self-advocacy and self-efficacy, thus potentially discouraging the use of healthcare services in favor of maladaptive coping skills. Acute treatments for primary headache disorders include non-steroidal anti-inflammatory drugs (i.e., aspirin, ibuprofen), triptans (i.e., sumatriptan), and opioids; however, continuous use of these pain-relieving agents can generate a secondary headache known as medication overuse headache (MOH). Recent work highlighting the overlap of morphological and functional brain changes in MOH and substance use disorder (SUD) suggests that insufficient pain management encourages analgesic misuse. The LGBTQ+ community-specifically transgender and gender non-conforming persons-struggles with high rates of mental illness and substance abuse. Since gender-affirming sex hormone therapy influences migraine progression, transgender and gender non-conforming (trans*) patients on hormone therapy have a higher risk for worsening migraine symptoms. However, trans* patients are less likely to have access to appropriate pain management techniques, thus preventing positive health outcomes for this vulnerable population.

Variation in the definition of 'failure to rescue' from postoperative complications: a systematic review and recommendations for outcome reporting.

BACKGROUND: Failure to rescue is the rate of death amongst patients with postoperative complications and has been proposed as a perioperative quality indicator. However, variation in its definition has limited comparisons between studies. We systematically reviewed all surgical literature reporting failure to rescue rates and examined variations in the definition of the 'numerator,' 'denominator,' and timing of failure to rescue measurement. METHODS: Databases were searched from inception to 31 December 2022. All studies reporting postoperative failure to rescue rates as a primary or secondary outcome were included. We examined the complications included in the failure to rescue denominator, the percentage of deaths captured by the failure to rescue numerator, and the timing of measurement for complications and mortality. RESULTS: A total of 359 studies, including 212,048,069 patients, were analyzed. The complications included in the failure to rescue denominator were reported in 295 studies (82%), with 131 different complications used. The median number of included complications per study was 10 (interquartile range 8-15). Studies that included a higher number of complications in the failure-to-rescue denominator reported lower failure-to-rescue rates. Death was included as a complication in the failure to rescue the denominator in 65 studies (18%). The median percentage of deaths captured by the failure to rescue calculation when deaths were not included in the denominator was 79%. Complications (52%) and mortality (40%) were mostly measured in-hospital, followed by 30-days after surgery. CONCLUSION: Failure to rescue is an important concept in the study of postoperative outcomes, although its definition is highly variable and poorly reported. Researchers should be aware of the advantages and disadvantages of different approaches to defining failure to rescue.

Molecular mechanisms of hormones implicated in migraine and the translational implication for transgender patients.

Migraine is a primary headache disorder recognized by the World Health Organization as one of the most poorly understood and debilitating neurological conditions impacting global disability. Chronic pain disorders are more frequently diagnosed among cisgender women than men, suggesting that female sex hormones could be responsible for mediating chronic pain, including migraine and/or that androgens can be protective. This review discusses the major gonadal hormones, estrogens, progesterone, and testosterone in the context of molecular mechanisms by which they play a role in migraine pathophysiology. In addition, the literature to date describing roles of minor sex hormones including prolactin, luteinizing hormone, follicular stimulating hormone, and gonadotropin releasing hormone in migraine are presented. Because transgender and gender non-conforming (trans*) individuals are an underserved patient population in which gender-affirming sex hormone replacement therapy (HRT) is often medically necessary to align biological sex with gender identity, results from cisgender patient populations are discussed in the context of these major and minor sex hormones on migraine incidence and management in trans* patients.

Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies.

Muscular dystrophies are a heterogeneous group of genetic muscle-wasting disorders that are subdivided based on the region of the body impacted by muscle weakness as well as the functional activity of the underlying genetic mutations. A common feature of the pathophysiology of muscular dystrophies is chronic inflammation associated with the replacement of muscle mass with fibrotic scarring. With the progression of these disorders, many patients suffer cardiomyopathies with fibrosis of the cardiac tissue. Anti-inflammatory glucocorticoids represent the standard of care for Duchenne muscular dystrophy, the most common muscular dystrophy worldwide; however, long-term exposure to glucocorticoids results in highly adverse side effects, limiting their use. Thus, it is important to develop new pharmacotherapeutic approaches to limit inflammation and fibrosis to reduce muscle damage and promote repair. Here, we examine the pathophysiology, genetic background, and emerging therapeutic strategies for muscular dystrophies.

Interventions to Improve Patient Care on Surgical Ward Rounds: A Systematic Review.

BACKGROUND: Ward rounds are an essential component of surgical and perioperative care. However, the relative effectiveness of different interventions to improve the quality of surgical ward rounds remains uncertain. The aim of this systematic review was to evaluate the efficacy of various ward round interventions among surgical patients. METHODS: A systematic literature search of the MEDLINE (OVID), EMBASE (OVID), Scopus, Cumulative Index of Nursing and Allied Health (CINAHL), and PsycInfo databases was performed on 7 October 2022 in accordance with PRISMA guidelines. All studies investigating surgical ward round quality improvement strategies with measurable outcomes were included. Data were analysed via narrative synthesis based on commonly reported themes. RESULTS: A total of 28 studies were included. Most were cohort studies (n = 25), followed by randomised controlled trials (n = 3). Checklists/proformas were utilised most commonly (n = 22), followed by technological (n = 3), personnel (n = 2), and well-being (n = 1) quality improvement strategies. The majority of checklist interventions (n = 21, 95%) showed significant improvements in documentation compliance, staff understanding, or patient satisfaction. Other less frequently reported ward round interventions demonstrated improvements in communication, patient safety, and reductions in patient stress levels. CONCLUSIONS: Use of checklists, technology, personnel, and well-being improvement strategies have been associated with improvements in ward round documentation, communication, as well as staff and patient satisfaction. Future studies should investigate the ease of implementation and long-term durability of these interventions, in addition to their impact on clinically relevant outcomes such as patient morbidity and mortality.

Tepsin binds LC3B to promote ATG9A export and delivery at the cell periphery.

Tepsin is an established accessory protein found in Adaptor Protein 4 (AP-4) coated vesicles, but the biological role of tepsin remains unknown. AP-4 vesicles originate at the trans -Golgi network (TGN) and target the delivery of ATG9A, a scramblase required for autophagosome biogenesis, to the cell periphery. Using in silico methods, we identified a putative L C3-Interacting R egion (LIR) motif in tepsin. Biochemical experiments using purified recombinant proteins indicate tepsin directly binds LC3B, but not other members, of the mammalian ATG8 family. Calorimetry and structural modeling data indicate this interaction occurs with micromolar affinity using the established LC3B LIR docking site. Loss of tepsin in cultured cells dysregulates ATG9A export from the TGN as well as ATG9A distribution at the cell periphery. Tepsin depletion in a mRFP-GFP-LC3B HeLa reporter cell line using siRNA knockdown increases autophagosome volume and number, but does not appear to affect flux through the autophagic pathway. Re-introduction of wild-type tepsin partially rescues ATG9A cargo trafficking defects. In contrast, re-introducing tepsin with a mutated LIR motif or missing N-terminus does not fully rescue altered ATG9A subcellular distribution. Together, these data suggest roles for tepsin in cargo export from the TGN; delivery of ATG9A-positive vesicles at the cell periphery; and in overall maintenance of autophagosome structure.

Spinal gout diagnosis in chiropractic practice: narrative review.

Objective: To review and summarize the recent literature, increase awareness and provide guidance for chiropractic physicians regarding the diagnosis of spinal gout. Methods: A search of PubMed was undertaken for recent case reports, reviews and trials relating to spinal gout. Results: Our analysis of 38 cases of spinal gout revealed that 94% of spinal gout patients presented with back or neck pain, 86% displayed neurological symptoms, 72% had a history of gout, and 80% had raised serum uric acid levels. Seventy-six percent of cases proceeded to surgery. A combination of clinical findings, laboratory tests and appropriate utilization of Dual Energy Computed Tomography (DECT) has the potential to improve early diagnosis. Conclusion: Gout is an uncommon cause of spine pain; however, it must be considered in the differential diagnosis as outlined in this paper. Increased awareness of the signs of spinal gout and earlier detection and treatment has the potential to improve the quality of life of patients and reduce the need for surgery.

Objectif: Examiner et résumer la littérature récente, sensibiliser les médecins chiropraticiens et les guider dans le diagnostic de la goutte spinale. Méthodes: Une recherche a été entreprise dans PubMed pour trouver des rapports de cas, des études et des essais récents concernant la goutte spinale. Résultats: Notre analyse de 38 cas de goutte spinale a révélé que 94 % des patients souffrant de goutte spinale présentaient des douleurs dorsales ou cervicales, 86 % des symptômes neurologiques, 72 % des antécédents de goutte et 80 % une élévation du taux d'acide urique sérique. Soixante-seize pour cent des cas ont donné lieu à une intervention chirurgicale. La combinaison des résultats cliniques, des tests de laboratoire et de l'utilisation appropriée de la tomographie informatisée à double énergie (DECT) peut améliorer les chances d'un diagnostic précoce. Conclusion: La goutte est une cause peu fréquente de douleur vertébrale, mais elle doit être prise en compte dans le diagnostic différentiel, comme indiqué dans le présent document. Une meilleure connaissance des signes de la goutte spinale et une détection et un traitement plus précoces pourraient améliorer la qualité de vie des patients et réduire la nécessité d'une intervention chirurgicale.

An interaction between ß'-COP and the ArfGAP, Glo3, maintains post-Golgi cargo recycling.

The essential COPI coat mediates retrieval of transmembrane proteins at the Golgi and endosomes following recruitment by the small GTPase, Arf1. ArfGAP proteins regulate COPI coats, but molecular details for COPI recognition by ArfGAPs remain elusive. Biochemical and biophysical data reveal how ß'-COP propeller domains directly engage the yeast ArfGAP, Glo3, with a low micromolar binding affinity. Calorimetry data demonstrate that both ß'-COP propeller domains are required to bind Glo3. An acidic patch on ß'-COP (D437/D450) interacts with Glo3 lysine residues located within the BoCCS (binding of coatomer, cargo, and SNAREs) region. Targeted point mutations in either Glo3 BoCCS or ß'-COP abrogate the interaction in vitro, and loss of the ß'-COP/Glo3 interaction drives Ste2 missorting to the vacuole and aberrant Golgi morphology in budding yeast. These data suggest that cells require the ß'-COP/Glo3 interaction for cargo recycling via endosomes and the TGN, where ß'-COP serves as a molecular platform to coordinate binding to multiple proteins, including Glo3, Arf1, and the COPI F-subcomplex.

Characterising nationwide reasons for unplanned hospital readmission after colorectal cancer surgery.

BACKGROUND: Readmissions after colorectal cancer surgery are common, despite advancements in surgical care, and have a significant impact on both individual patients and overall healthcare costs. The aim of this study was to determine the 30-and 90 days readmission rate after colorectal cancer surgery, and to investigate the risk factors and clinical reasons for unplanned readmissions. METHOD: A multicenter, population-based study including all patients discharged after index colorectal cancer resection from 2010 to 2020 in Aotearoa New Zealand (AoNZ) was completed. The Ministry of Health National Minimum Dataset was used. Rates of readmission at 30 days and 90 days were calculated. Mixed-effect logistic regression models were built to investigate factors associated with unplanned readmission. Reasons for readmission were described. RESULTS: Data were obtained on 16,885 patients. Unplanned 30-day and 90-day hospital readmission rates were 15.1% and 23.7% respectively. The main readmission risk factors were comorbidities, advanced disease, and postoperative complications. Hospital level variation was not present. Despite risk adjustment, R2 value of models was low (30 days: 4.3%, 90 days: 5.2%). The most common reasons for readmission were gastrointestinal causes (32.1%) and wound complications (14.4%). Rates of readmission did not improve over the 11 years study period (p = 0.876). CONCLUSION: Readmissions following colorectal resections in AoNZ are higher than other comparable healthcare systems and rates have remained constant over time. While patient comorbidities and postoperative complications are associated with readmission, the explanatory value of these variables is poor. To reduce unplanned readmissions, efforts should be focused on prevention and early detection of post-discharge complications.

Hyperactive Distal Colonic Motility and Recovery Patterns Following Right Colectomy: A High-Resolution Manometry Study.

BACKGROUND: Postoperative ileus results in morbidity, prolonged hospitalization, and increased health care expenditure. However, the underlying abnormalities in motility remain poorly understood. Recent high-resolution manometry studies demonstrated that the distal colon becomes hyperactive with a cyclic motor pattern postoperatively, but they did not track this activity beyond 16 hours after surgery. OBJECTIVE: This study used high-resolution manometry to evaluate distal colonic motility during the first 4 days after right-sided colectomy. DESIGN: An observational study of perioperative high-resolution colonic manometry using a 36-sensor catheter with 1-cm resolution. SETTING: A single tertiary hospital. PATIENTS: Adult patients undergoing elective laparoscopic or open right-sided colonic resection. MAIN OUTCOME MEASURES: Occurrence of distal colonic motor patterns during the perioperative period, defined according to a published classification system. Clinical markers of gut recovery included time to first stool, oral diet, and prolonged postoperative ileus. RESULTS: Seven patients underwent perioperative manometry recordings. Hyperactive cyclic motor patterns emerged intraoperatively and peaked in the first 12 hours postoperatively, occupying 81.8% ± 3.9% of the recording. This gradually returned to normal during the first 4 days, reaching 19.0% ± 4.4% ( p = 0.002). No patient had a bowel movement before this hyperactivity resolved. High-amplitude propagating sequences were absent in early postoperative recordings, and their return temporally correlated with the passage of stool. Abnormal high-amplitude repetitive 0.5 to 1 cycle per minute activity was observed in the left colon of 1 patient with prolonged ileus. LIMITATIONS: The invasive nature of recordings limited this study to a small sample size. CONCLUSIONS: Cyclic motor patterns are markedly hyperactive in the distal colon after right-sided colectomy and resolve during the first 4 postoperative days. High-amplitude propagating sequences are inhibited by surgery and gradually recover. Bowel function may not return until these changes resolve. Other abnormal repetitive hyperactive patterns could contribute to the development of prolonged ileus. See Video Abstract at http://links.lww.com/DCR/B967 . MOTILIDAD HIPERACTIVA DEL COLON DISTAL Y PATRONES DE RECUPERACIN DESPUS DE COLECTOMA DERECHA UN ESTUDIO DE MANOMETRA DE ALTA RESOLUCIN: ANTECEDENTES:El íleo post-operatorio produce una morbilidad significativa, una hospitalización prolongada y un aumento del gasto sanitario. Sin embargo, las anomalías subyacentes en la motilidad siguen siendo poco conocidas. Estudios recientes de manometría de alta resolución demostraron que el colon distal se vuelve hiperactivo con un patrón motor cíclico en el post-operatorio, pero no registraron esta actividad más allá de las 16 horas posteriores a la cirugía.OBJETIVO:Utilizar la manometría de alta resolución para evaluar la motilidad del colon distal durante los primeros cuatro días después de la colectomía del lado derecho.DISEÑO:Estudio observacional de pacientes sometidos a manometría colónica perioperatoria de alta resolución mediante catéter de 36 sensores con 1 cm de resolución.AJUSTE:Un solo hospital terciario.PACIENTES:Pacientes adultos sometidos a resección laparoscópica o abierta de colon del lado derecho de forma electiva.PRINCIPALES MEDIDAS DE RESULTADO:AAparición de patrones motores del colon distal durante el período perioperatorio, definidos según un sistema de clasificación publicado. Los marcadores clínicos de recuperación intestinal incluyeron, tiempo hasta la primera evacuación, dieta oral e íleo posoperatorio prolongado.RESULTADOS:Siete pacientes fueron sometidos a registros de manometría perioperatoria. Los patrones motores cíclicos hiperactivos emergieron intraoperatoriamente y alcanzaron su punto máximo en las primeras 12 horas post-operatorias, ocupando 81,8 ± 3,9% del registro. Esto volvió gradualmente a la normalidad durante los primeros cuatro días, alcanzando el 19,0 ± 4,4% (p = 0,002). Ningún paciente tuvo una evacuación intestinal antes de que se resolviera esta hiperactividad. Las secuencias de propagación de alta amplitud estaban ausentes en las grabaciones post-operatorias tempranas y su retorno se correlacionó temporalmente con el paso de las heces. Se observó actividad anormal de alta amplitud repetitiva de 0,5-1 ciclo / minuto en el colon izquierdo de un paciente con íleo prolongado.LIMITACIONES:La naturaleza invasiva de las grabaciones limitó este estudio a un tamaño de muestra pequeño.CONCLUSIONES:Los patrones motores cíclicos son marcadamente hiperactivos en el colon distal después de la colectomía del lado derecho y se resuelven gradualmente durante los primeros cuatro días posoperatorios. Las secuencias de propagación de gran amplitud se inhiben mediante cirugía y se recuperan gradualmente. Es posible que la función intestinal no regrese hasta que estos cambios se resuelvan. Otros patrones hiperactivos repetitivos anormales podrían contribuir al desarrollo de íleo prolongado. Consulte Video Resumen en http://links.lww.com/DCR/B967 . (Traducción-Dr. Mauricio Santamaria ).

"Failure to Rescue" following Colorectal Cancer Resection: Variation and Improvements in a National Study of Postoperative Mortality.

OBJECTIVE: To examine variation in "failure to rescue" (FTR) as a driver of differences in mortality between centres and over time for patients undergoing colorectal cancer surgery. BACKGROUND: Wide variation exists in postoperative mortality following colorectal cancer surgery. FTR has been identified as an important determinant of variation in postoperative outcomes. We hypothesized that differences in mortality both between hospitals and over time are driven by variation in FTR. METHODS: A national population-based study of patients undergoing colorectal cancer resection from 2010 to 2019 in Aotearoa New Zealand was conducted. Rates of 90-day FTR, mortality, and complications were calculated overall, and for surgical and nonoperative complications. Twenty District Health Boards (DHBs) were ranked into quartiles using risk- and reliability-adjusted 90-day mortality rates. Variation between DHBs and trends over the 10-year period were examined. RESULTS: Overall, 15,686 patients undergoing resection for colorectal adenocarcinoma were included. Increased postoperative mortality at high-mortality centers (OR 2.4, 95% CI 1.8-3.3) was driven by higher rates of FTR (OR 2.0, 95% CI 1.5-2.8), and postoperative complications (OR 1.4, 95% CI 1.3-1.6). These trends were consistent across operative and nonoperative complications. Over the 2010 to 2019 period, postoperative mortality halved (OR 0.5, 95% CI 0.4-0.6), associated with a greater improvement in FTR (OR 0.5, 95% CI 0.4-0.7) than complications (OR 0.8, 95% CI 0.8-0.9). Differences between centers and over time remained when only analyzing patients undergoing elective surgery. CONCLUSION: Mortality following colorectal cancer resection has halved over the past decade, predominantly driven by improvements in "rescue" from complications. Differences in FTR also drive hospital-level variation in mortality, highlighting the central importance of "rescue" as a target for surgical quality improvement.

Experimental and Computational Studies of Ruthenium Complexes Bearing Z-Acceptor Aluminum-Based Phosphine Pincer Ligands.

Reaction of [Ru(C6H4PPh2)2(Ph2PC6H4AlMe(THF))H] with CO results in clean conversion to the Ru-Al heterobimetallic complex [Ru(AlMePhos)(CO)3] (1), where AlMePhos is the novel P-Al(Me)-P pincer ligand (o-Ph2PC6H4)2AlMe. Under photolytic conditions, 1 reacts with H2 to give [Ru(AlMePhos)(CO)2(µ-H)H] (2) that is characterized by multinuclear NMR and IR spectroscopies. DFT calculations indicate that 2 features one terminal and one bridging hydride that are respectively anti and syn to the AlMe group. Calculations also define a mechanism for H2 addition to 1 and predict facile hydride exchange in 2 that is also observed experimentally. Reaction of 1 with B(C6F5)3 results in Me abstraction to form the ion pair [Ru(AlPhos)(CO)3][MeB(C6F5)3] (4) featuring a cationic [(o-Ph2PC6H4)2Al]+ ligand, [AlPhos]+. The Ru-Al distance in 4 (2.5334(16) Å) is significantly shorter than that in 1 (2.6578(6) Å), consistent with an enhanced Lewis acidity of the [AlPhos]+ ligand. This is corroborated by a blue shift in both the observed and computed νCO stretching frequencies upon Me abstraction. Electronic structure analyses (QTAIM and EDA-ETS) comparing 1, 4, and the previously reported [Ru(ZnPhos)(CO)3] analogue (ZnPhos = (o-Ph2PC6H4)2Zn) indicate that the Lewis acidity of these pincer ligands increases along the series ZnPhos < AlMePhos < [AlPhos]+.