Ana Berlin

Mid2p stabilizes septin rings during cytokinesis in fission yeast

Septins are filament-forming proteins with a conserved role in cytokinesis. In the fission yeast Schizosaccharomyces pombe, septin rings appear to be involved primarily in cell–cell separation, a late stage in cytokinesis. Here, we identified a protein Mid2p on the basis of its sequence similarity to S. pombe Mid1p, Saccharomyces cerevisiae Bud4p, and Candida albicans Int1p. Like septin mutants, mid2Δ mutants had delays in cell–cell separation. mid2Δ mutants were defective in septin organization but not contractile ring closure or septum formation. In wild-type cells, septins assembled first during mitosis in a single ring and during septation developed into double rings that did not contract. In mid2Δ cells, septins initially assembled in a single ring but during septation appeared in the cleavage furrow, forming a washer or disc structure. FRAP studies showed that septins are stable in wild-type cells but exchange 30-fold more rapidly in mid2Δ cells. Mid2p colocalized with septins and required septins for its localization. A COOH-terminal pleckstrin homology domain of Mid2p was required for its localization and function. No genetic interactions were found between mid2 and the related gene mid1. Thus, these studies identify a new factor responsible for the proper stability and function of septins during cytokinesis.

Role of bud6p and tea1p in the interaction between actin and microtubules for the establishment of cell polarity in fission yeast

BACKGROUND In many cell types, microtubules are thought to direct the spatial distribution of F-actin in cell polarity. Schizosaccharomyces pombe cells exhibit a regulated program of polarized cell growth: after cell division, they grow first in a monopolar manner at the old end, and in G2 phase, initiate growth at the previous cell division site (the new end). The role of microtubule ends in cell polarity is highlighted by the finding that the cell polarity factor, tea1p, is present on microtubule plus ends and cell tips [1]. RESULTS Here, we characterize S. pombe bud6p/fat1p, a homolog of S. cerevisiae Bud6/Aip3. bud6Delta mutant cells have a specific defect in the efficient initiation of growth at the new end and like tea1Delta cells, form T-shaped cells in a cdc11 background. Bud6-GFP localizes to both cell tips and the cytokinesis ring. Maintenance of cell tip localization is dependent upon actin but not microtubules. Bud6-GFP localization is tea1p dependent, and tea1p localization is not bud6p dependent. tea1Delta and bud6Delta cells generally grow in a monopolar manner but exhibit different growth patterns. tea1(Delta)bud6Delta mutants resemble tea1Delta mutants. Tea1p and bud6p coimmunoprecipitate and comigrate in large complexes. CONCLUSIONS Our studies show that tea1p (a microtubule end-associated factor) and bud6p (an actin-associated factor) function in a common pathway, with bud6p downstream of tea1p. To our knowledge, bud6p is the first protein shown to interact physically with tea1p. These studies delineate a pathway for how microtubule plus ends function to polarize the actin cytoskeleton through actin-associated polarity factors.

Palliative Care Interventions for Surgical Patients: A Systematic Review

IMPORTANCE Inpatient palliative care improves symptom management and patient satisfaction with care and reduces hospital costs in seriously ill patients. However, the role of palliative care in the treatment of patients undergoing surgery (surgical patients) remains poorly defined. OBJECTIVE To characterize the content, design, and results of interventions to improve access to palliative care or the quality of palliative care for surgical patients. EVIDENCE REVIEW This systematic review was conducted according to PRIMSA guidelines. Articles were identified through searches of PubMed, PsycINFO, EMBASE, and CINAHL as well as manual review of references. Eligible articles included experimental, quasi-experimental, and observational studies published in English from January 1, 1994, through October 31, 2014, in which patient outcomes of palliative care interventions for adult surgical patients were reported. Data on the study setting, design, intervention, participants, and results were extracted from the final study set and analyzed from December 22, 2014, to February 7, 2015. FINDINGS A total of 3838 abstracts were identified and screened by 2 reviewers, 77 articles were reviewed in full text, and 25 articles (22 unique interventions involving 8575 unique patients) met the study criteria. Interrater agreement was good (κ = 0.78). Nine single-institution retrospective cohort studies, 7 single-institution prospective cohort studies, 7 single-institution randomized clinical studies, and 2 multicenter randomized clinical studies were included. Nineteen of the 23 single-site studies were performed at academic hospitals. Given the heterogeneity of study methods and measures, meta-analysis was not possible. Preoperative decision-making interventions were associated with decreased mortality in 4 studies. Three studies reported improved quality of communication; 4, improved symptom management; and 7, decreased use of health care resources and decreased cost. However, many studies were small, performed in academic settings, and methodologically flawed and did not measure clinically meaningful outcomes. CONCLUSIONS AND RELEVANCE The sparse evidence regarding interventions to introduce or improve palliative care for surgical patients is further limited by methodologic flaws. Rigorous evaluations of standardized palliative care interventions measuring meaningful patient outcomes are needed.

Navigating high-risk surgery: protocol for a multisite, stepped wedge, cluster-randomised trial of a question prompt list intervention to empower older adults to ask questions that inform treatment decisions

Introduction Older patients frequently undergo operations that carry high risk for postoperative complications and death. Poor preoperative communication between patients and surgeons can lead to uninformed decisions and result in unexpected outcomes, conflict between surgeons and patients, and treatment inconsistent with patient preferences. This article describes the protocol for a multisite, cluster-randomised trial that uses a stepped wedge design to test a patient-driven question prompt list (QPL) intervention aimed to improve preoperative decision making and inform postoperative expectations. Methods and analysis This Patient-Centered Outcomes Research Institute-funded trial will be conducted at five academic medical centres in the USA. Study participants include surgeons who routinely perform vascular or oncological surgery, their patients and families. We aim to enrol 40 surgeons and 480 patients over 24 months. Patients age 65 or older who see a study-enrolled surgeon to discuss a vascular or oncological problem that could be treated with high-risk surgery will be enrolled at their clinic visit. Together with stakeholders, we developed a QPL intervention addressing preoperative communication needs of patients considering major surgery. Guided by the theories of self-determination and relational autonomy, this intervention is designed to increase patient activation. Patients will receive the QPL brochure and a letter from their surgeon encouraging its use. Using audio recordings of the outpatient surgical consultation, patient and family member questionnaires administered at three time points and retrospective chart review, we will compare the effectiveness of the QPL intervention to usual care with respect to the following primary outcomes: patient engagement in decision making, psychological well-being and post-treatment regret for patients and families, and interpersonal and intrapersonal conflict relating to treatment decisions and treatments received. Ethics and dissemination Approvals have been granted by the Institutional Review Board at the University of Wisconsin and at each participating site, and a Certificate of Confidentiality has been obtained. Results will be reported in peer-reviewed publications and presented at national meetings. Trial registration number NCT02623335.

Validity and reliability of a novel written examination to assess knowledge and clinical decision making skills of medical students on the surgery clerkship

BACKGROUND The Surgery Clerkship Clinical Skills Examination (CSE) is a novel written examination developed to assess the surgical knowledge, clinical decision making, communication skills, and professionalism of medical students on the surgery clerkship. This study was undertaken to determine its validity. METHODS Data were prospectively collected from July 2011 through February 2013. Multivariate linear and logistic regression analyses were used to assess score trend; convergent validity with National Board of Medical Examiners surgery and medicine subject scores, United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge scores, and evaluation of clinical reasoning and fund of knowledge; and the effect of clerkship order. Exam reliability was assessed using a modified Cronbachs α statistic. RESULTS During the study period, 262 students completed the CSE, with a normal distribution of performance. United States Medical Licensing Examination Step 2 Clinical Knowledge score and end-of-clerkship evaluations of fund of knowledge and clinical reasoning predicted CSE score. Performance on the CSE was independent of clerkship order or prior clerkships. The modified Cronbachs α value for the exam was .67. CONCLUSIONS The CSE is an objective, valid, reliable instrument for assessing students on the surgery clerkship, independent of clerkship order.

Gastrostomy tube placement: An opportunity for establishing patient-centered goals of care

Background. Surgeons and other health care providers are frequently consulted for gastrostomy tube placement in seriously ill patients at risk of outcomes poorly aligned with patient goals. Palliative care assessments have been recommended to guide decision‐making in this setting. We aimed to characterize patient‐centered outcomes and define the extent of unmet palliative care need in patients receiving gastrostomy tubes. Methods. This is a retrospective study of all adult, nontrauma inpatients who underwent gastrostomy tube placement over 16 months at an urban academic medical center. Outcomes included in‐hospital and 1‐year mortality, functional status at discharge, and receipt of palliative care assessment preprocedure. Results. Gastrostomy tubes were placed in 205 patients. In‐hospital and 1‐year mortality rates were 8% and 19%, respectively. Of patients surviving to discharge, 69% were unable to live independently. Among patients with acute brain injury or respiratory failure, 90% died in the hospital or were severely disabled at discharge. Only 12% of patients received a documented palliative care assessment preprocedure. Conclusion. Given high risks of mortality and poor functional outcomes, consideration of gastrostomy tube placement is an appropriate but underutilized trigger for palliative care assessment. This study highlights an untapped opportunity to optimize the goal concordance of treatment in operative intervention.

Intraabdominal Infections in Older Adults

Intraabdominal infections represent a diagnostic and therapeutic challenge in the elderly population. Atypical presentations, diagnostic delays, additional comorbidities, and decreased physiologic reserve contribute to high morbidity and mortality, particularly among frail patients undergoing emergency abdominal surgery. While many infections are the result of age-related inflammatory, mechanical, or obstructive processes, infectious complications of feeding tubes are also common. The pillars of treatment are source control of the infection and judicious use of antibiotics. A patient-centered approach considering the invasiveness, risk, and efficacy of a procedure for achieving the desired outcomes is recommended. Structured communication and time-limited trials help ensure goal-concordant treatment.

Establishing Goals of Care for Patients With Stroke and Feeding Problems: An Interdisciplinary Trigger-Based Continuous Quality Improvement Project

BACKGROUND Few patients with dysphagia because of stroke receive early palliative care (PC) to align treatment goals with their values, as called for by practice guidelines, particularly before enteral access procedures for artificial nutrition. MEASURES To increase documented goals of care (GOC) discussions among acute stroke patients before feeding gastrostomy tube placement. INTERVENTION We undertook a rapid-cycle continuous quality improvement process with interdisciplinary planning, implementation, and performance review to operationalize an upstream trigger for PC referral prompted by the speech and language pathology evaluation. OUTCOMES During a six-month period, 21 patients underwent gastrostomy tube placement; 52% had preprocedure GOC discussions postintervention, with the rate of compliance increasing steadily from 13% (11/87, preintervention) to 100% (2/2) in the final two months. CONCLUSIONS/LESSONS LEARNED We effectively increased documented GOC discussions before feeding gastrostomy tube placement among stroke patients. Systems-based tools and education will enhance this upstream trigger model to ensure early PC for stroke patients.

Outcomes and palliative care utilization in patients with dementia and acute abdominal emergency: opportunities for surgical quality improvement

Background When patients with dementia develop acute surgical abdomen, patients, surrogates, and surgeons need accurate prognostic information to facilitate goal‐concordant decision making. Palliative care can assist with communication, symptom management, and family and caregiver support in this population. We aimed to characterize outcomes and patterns of palliative care utilization among patients with dementia, presenting with abdominal surgical emergency. Method We retrospectively queried the National Inpatient Sample for patients aged >50 years with dementia and acute abdominal emergency who were admitted nonelectively 2009–2013, utilizing ICD‐9‐CM codes for dementia and surgical indication. We characterized outcomes and identified predictors of palliative care utilization. Results Among 15,209 patients, in‐hospital mortality was 10.2%, the nonroutine discharge rate was 67.2%, and 7.5% received palliative care. Patients treated operatively were less likely to receive palliative care than those who did not undergo operation (adjusted OR = 0.50; 95% CI 0.41–0.62). Only 6.4% of patients discharged nonroutinely received palliative care. Conclusion Patients with dementia and acute abdominal emergency have considerable in‐hospital mortality, a high frequency of nonroutine discharge, and low palliative care utilization. In this group, we discovered a large gap in palliative care utilization, particularly among those treated operatively and those who are discharged nonroutinely.

Patient vs. self in surgical practice.

Surgeons share their challenges and dilemmas in making ethical decisions in these twelve personal stories. The three commentary articles draw out the lessons the stories address. The commentators come from diverse backgrounds including sociology, bioethics, nursing, and surgery.