Stefanos G. Millas

Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex

Sentrin‐1/SUMO‐1 is a novel ubiquitin‐like protein, which can covalently modify a limited number of cellular proteins. Here we report the identification of the sentrin‐activating enzyme complex, which consists of two proteins AOS1 and UBA2. Human AOS1 is homologous to the N‐terminal half of E1, whereas human UBA2 is homologous to the C‐terminal half of E1. The human UBA2 gene is located on chromosome 19q12. Human UBA2 could form a β‐mercaptoethanol‐sensitive conjugate with members of the sentrin family, but not with ubiquitin of NEDD8, in the presence of AOS1. Identification of human UBA2 and AOS1 should allow a more detailed analysis of the enzymology of the activation of ubiquitin‐like proteins.

Acute Appendicitis: Controversies in Diagnosis and Management

Appendicitis is a common problem; there are more than 300,000 hospital discharges for appendicitis in the United States per year. Although the clinical scenario of periumbilical pain migrating to the right lower quadrant is classically associated with acute appendicitis, the presentation is rarely typical and the diagnosis cannot always be based on history and physical examination alone. Diagnostic errors are common, with over-diagnosis leading to negative appendectomies and with delays in diagnosis leading to perforations. The misdiagnosis of appendicitis has significant economic ramifications; in a nationwide study of administrative data over a 1-year period in the late 1990s, a negative appendectomy rate of 15% resulted in more than

Should perioperative supplemental oxygen be routinely recommended for surgery patients? A Bayesian meta-analysis.

740 million in hospital charges. Diagnostic strategies for evaluating patients with abdominal pain and for identifying patients with suspected appendicitis should all start with a thorough history and physical examination. The Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) published guidelines that recommend the establishment of local pathways for the diagnosis and management of acute appendicitis. The guidelines note that the combination of clinical and laboratory findings of characteristic abdominal pain, localized tenderness, and laboratory evidence of inflammation will identify most patients with suspected appendicitis. Other diagnostic strategies may include radiologic imaging or the use of scoring systems with or without computer support. Ultimately, the ‘‘gold standard’’ for a positive diagnosis is the histopathologic confirmation of appendicitis, although standard criteria are lacking. A negative diagnosis may be confirmed by intra-operative findings or clinical follow-up or both. There are different measures for evaluating a diagnostic test or strategy (Table 1). Sensitivity refers to the proportion of true positive tests among all patients who have the disease (A/[AþC]). Specificity refers to the proportion of true negatives among all patients who do not have the disease (D/[BþD]). Highly sensitive tests rule disease out, whereas highly specific tests rule disease in. Accuracy refers to the proportion of true positives and negatives among all patients tested ([AþD]/ [AþBþCþD]). The positive predictive value of a test refers to the proportion of true positives among all patients who test positive (A/[AþB]), whereas the negative predictive value refers to the proportion of true negatives among all patients who test negative (D/[CþD]). The predictive values of a test should be applied with caution to local patients as they depend upon the incidence

Facilitators and barriers of implementing enhanced recovery in colorectal surgery at a safety net hospital: A provider and patient perspective.

Objective:The purpose of this study is to use updated data and Bayesian methods to evaluate the effectiveness of hyperoxia to reduce surgical site infections (SSIs) and/or mortality in both colorectal and all surgery patients. Because few trials assessed potential harms of hyperoxia, hazards were not included. Background:Use of hyperoxia to reduce SSIs is controversial. Three recent meta-analyses have had conflicting conclusions. Methods:A systematic literature search and review were performed. Traditional fixed-effect and random-effect meta-analyses and Bayesian meta-analysis were performed to evaluate SSIs and mortality. Results:Traditional meta-analysis yielded a relative risk of an SSI with hyperoxia among all surgery patients of 0.84 [95% confidence interval (CI): 0.73–0.97] and 0.84 (95% CI: 0.61–1.16) for the fixed-effect and random-effect models, respectively. The probabilities of any risk reduction in SSIs among all surgery patients were 77%, 81%, and 83% for skeptical, neutral, and enthusiastic priors. The subset analysis of colorectal surgery patients increased the probabilities to 86%, 89%, and 92%. The probabilities of at least a 10% reduction were 57%, 62%, and 68% for all surgery patients and 71%, 75%, and 80% among the colorectal surgery subset. Conclusions:There is a moderately high probability of a benefit to hyperoxia in reducing SSIs in colorectal surgery patients; however, the magnitude of benefit is relatively small and might not exceed treatment hazards. Further studies should focus on generalizability to other patient populations or on treatment hazards and other outcomes.

What is the quality of reporting of studies of interventions to increase compliance with antibiotic prophylaxis

BACKGROUND Enhanced Recovery After Surgery (ERAS) pathways are known to decrease complications and duration of stay in colorectal surgery patients. However, it is unclear whether an ERAS pathway would be feasible and effective at a safety-net hospital. The aim of this study was to identify local barriers and facilitators before the adoption of an ERAS pathway for patients undergoing colorectal operations at a safety-net hospital. METHODS Semistructured interviews were conducted to assess the perceived barriers and facilitators before ERAS adoption. Stratified purposive sampling was used. Interviews were audiotaped, transcribed verbatim, and analyzed using content analysis. Analytic and investigator triangulation were used to establish credibility. RESULTS Interviewees included 8 anesthesiologists, 5 surgeons, 6 nurses, and 18 patients. Facilitators identified across the different medical professions were (1) feasibility and alignment with current practice, (2) standardization of care, (3) smallness of community, (4) good teamwork and communication, and (5) caring for patients. The barriers were (1) difficulty in adapting to change, (2) lack of coordination between different departments, (3) special needs of a highly comorbid and socioeconomically disadvantaged patient population, (4) limited resources, and (5) rotating residents. Facilitators identified by the patients were (1) welcoming a speedy recovery, (2) being well-cared for and satisfied with treatment, (3) adequate social support, (4) welcoming early mobilization, and (5) effective pain management. The barriers were (1) lack of quiet and private space, (2) need for more patient education and counseling, and (3) unforeseen complications. CONCLUSION Although limited hospital resources are perceived as a barrier to ERAS implementation at a safety-net hospital, there is strong support for such pathways and multiple factors were identified that may facilitate change. Inclusion of patient perspectives is critical to identifying challenges and facilitators to implementing ERAS changes focused on optimizing patient perioperative health and outcomes.

Cytomegalovirus Enteritis Manifesting as Recurrent Bowel Obstruction and Jejunal Perforation in Patient with Acquired Immunodeficiency Syndrome: Rare Report of Survival and Review of the Literature

BACKGROUND Despite studies reporting successful interventions to increase antibiotic prophylaxis compliance, surgical site infections remain a significant problem. The reasons for this lack of improvement are unknown. This review evaluates the internal and external validity of quality improvement studies of interventions to increase surgical antibiotic prophylaxis compliance. STUDY DESIGN Three investigators independently performed systematic literature searches and selected eligible studies that evaluated interventions to improve perioperative antibiotic prophylaxis timing, type, and/or discontinuation. Studies published before the Surgical Infection Prevention project inception in 2002 were excluded. Each study was assessed based on modified criteria for evaluating quality improvement studies (Standards for Quality Improvement Reporting Excellence) and for facilitating implementation of evidence into practice (Reach-Efficacy-Adoption-Implementation-Maintenance). RESULTS Forty-six articles met inclusion criteria; 93% reported improvement in antibiotic prophylaxis compliance. Surgical site infections were evaluated in 50% of studies and 65% reported an improvement. Less than 5% of studies used randomization, allocation concealment, or blinding. Nine percent of studies described efforts to minimize bias in the design results and analysis and 13% described a sample size calculation. Approximately one-third of studies described participant adoption of the intervention (26%), factors affecting generalizability (33%), or implementation barriers (37%). Most studies (80%) used multiple interventions; no single intervention was associated with change in compliance. Studies with the lowest baseline compliance showed the greatest improvement, regardless of the intervention(s). CONCLUSIONS The methodology and reporting of quality improvement studies on perioperative antibiotic prophylaxis is suboptimal, and factors that would improve generalizability of successful intervention implementation are infrequently reported. Clinicians should use caution in applying the results of these studies to their general practice.

A phase II clinical study to assess the feasibility of self and partner anal examinations to detect anal canal abnormalities including anal cancer

BACKGROUND Cytomegalovirus (CMV) enteritis presenting with perforation in the setting of acquired immunodeficiency syndrome (AIDS) represents a particularly deadly combination. METHODS Case report and review of the pertinent literature. CASE REPORT The authors report a patient with AIDS and CMV enteritis presenting as recurrent small-bowel obstruction and leading to perforation of the jejunum with subsequent survival. CONCLUSION This is believed to represent the second case in the English-language literature of survival after CMV-induced small intestinal perforation in a patient with AIDS.

Shared decision-making during surgical consultation for gallstones at a safety-net hospital

Objective Anal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men. Methods A clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27–78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples. The clinician then performed a DARE without immediately disclosing results, after which the man or couple performed an SAE or PAE, respectively. Percentage agreement with the clinician DARE in addition to sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the SAE, PAE and overall. Results Men had a median age of 52 years, 42.5% were African American and 60.5% were HIV positive. DARE detected abnormalities in 12 men while the men’s SAE/PAEs detected 9 of these. A total of 93.0% of men classified the health of their anal canal correctly (95% CI 89.5 to 96.5). Overall percentage agreement, sensitivity and specificity were 93.0%, 75.0% and 94.2%, respectively, while PPV and NPV were 45.0% and 98.3%, respectively. The six men who detected the abnormality had nodules/masses ≥3 mm in size. More than half of men (60.5%) reported never checking their anus for an abnormality; however, after performing an SAE/PAE, 93.0% said they would repeat it in the future. Conclusion These results suggest that tumours of ≥3 mm may be detectable by self or partner palpation among MSM and encourage further investigation given literature suggesting a high cure rate for anal cancer tumours ≤10 mm.

624 Implementation of Best Practices in Colorectal Surgery at a Safety Net Hospital: Facilitators and Barriers

Background. Understanding patient perspectives regarding shared decision‐making is crucial to providing informed, patient‐centered care. Little is known about perceptions of vulnerable patients regarding shared decision‐making during surgical consultation. The purpose of this study was to evaluate whether a validated tool reflects perceptions of shared decision‐making accurately among patients seeking surgical consultation for gallstones at a safety‐net hospital. Methods. A mixed methods study was conducted in a sample of adult patients with gallstones evaluated at a safety‐net surgery clinic between May to July 2016. Semi‐structured interviews were conducted after their initial surgical consultation and analyzed for emerging themes. Patients were administered the Shared Decision‐Making Questionnaire and Autonomy Preference Scale. Univariate analyses were performed to identify factors associated with shared decision‐making and to compare the results of the surveys to those of the interviews. Results. The majority of patients (N = 30) were female (90%), Hispanic (80%), Spanish‐speaking (70%), and middle‐aged (45.7 ± 16 years). The proportion of patients who perceived shared decision‐making was greater in the Shared Decision‐Making Questionnaire versus the interviews (83% vs 27%, P < .01). Age, sex, race/ethnicity, primary language, diagnosis, Autonomy Preference Scale score, and decision for operation was not associated with shared decision‐making. Contributory factors to this discordance include patient unfamiliarity with shared decision‐making, deference to surgeon authority, lack of discussion about different treatments, and confusion between aligned versus shared decisions. Conclusion. Available questionnaires may overestimate shared decision‐making in vulnerable patients suggesting the need for alternative or modifications to existing methods. Furthermore, such metrics should be assessed for correlation with patient‐reported outcomes, such as satisfaction with decisions and health status.

Differential regulation of sentrinized proteins by a novel sentrin- specific protease

S A T A b st ra ct s females (age 62.0±10.8 years). Median follow up period was 67.3+/-17.8months (range:12.3102.2months). CT scans were available in 651 patients (CT follow up duration : median 44.6months, range 12.3-82.8months). Preoperative VAT obesity was observed in 323 patients (49.4%) and SAT obesity in 266 (47%). Preoperative VAT obesity was associated with earlier TNM stage (p=0.042) and negative venous invasion (p=0.02). After surgery, 266 patients (53%) showed increase in VAT, and 358 patients (63.3%) in SAT after surgery. Chemotherapy did not influence in VAT or SAT changes (p=0.086). Increase in VAT amount after surgery was associated with pathologic differentiation and increase in SAT with T stage and TNM stage. By Kaplan Meier analysis, increased VAT and SAT after surgery showed higher OS (p=0.001, 0.03) and DFS (p=0.004, 0.02) in stage 3. On univariate analysis, TNM stage, pathologic differentiation, perineural invasion, preoperative CEA level, postoperative VAT and SAT change were significant predictors of OS and DFS. Preoperative VAT obesity was not associated with OS (p=0.148) and DFS (p=0.615). By multivariate Cox regression analysis, TNM stage (p=0.049), differentiation (p=0.006), perineural invasion (p=0.000) and postoperative VAT change (HR, decrease : increase = 1 : 0.493, p=0.012) were significant predictors for OS and DFS. Conclusions> In contrary to other studies, preoperative visceral obesity was not a predictor for poor prognosis in our cohort of patients. Instead, the increase in visceral fat amount after surgery was a significant positive predictor of overall and disease free survival in CRC patients undergoing curative resection.