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Background: Frailty is a recent multidimensional concept of a contemporary growing interest for understanding the complex health status of elderly population. We aimed to assess the impact of frailty scores on the outcome and complication rate of holmium laser enucleation of prostate (HoLEP). Methods: A 7-year data of HoLEP patients in a single tertiary referral center were reviewed. The preoperative, operative, early, and late postoperative outcome data were collected and compared according to the preoperative frailty scores. Frailty was assessed preoperatively using the Modified Hopkins frailty score. Results: The study included 837 patients categorized into two groups: group I included 533 nonfrail patients (frailty score = 0), whereas group II included 304 frail patients (frailty score ≥1). The median (interquartile range) age was 70 (11) and 75 (11) years for groups I and II, respectively (<0.001). The 30-day perioperative complication rate (p = 0.005), blood transfusion (p = 0.013), failed voiding trial (p = 0.0015), and 30-day postoperative readmission (p = 0.0363) rates were significantly higher in frail patients of group II. The two groups were statistically comparable regarding postoperative international prostate symptom score (p = 0.6886, 0.6308, 0.9781), incontinence rate (p = 0.475, 0.592, 0.1546), postvoid residual (p = 0.5801, 0.1819, 0.593) at 6 weeks and 3 months, and 1-year follow-up intervals, respectively. Conclusion: In elderly patients undergoing HoLEP, the preoperative frailty scores strongly correlate with the risk of perioperative complications. Frail patients should be counseled regarding their relative higher risk of early perioperative complications although they gain the same functional profit of HoLEP as nonfrail patients. [ABSTRACT FROM AUTHOR]

Introduction: One of the main adverse outcomes following Holmium laser enucleation of the prostate (HoLEP) is the development of transient de novo urinary incontinence (UI). We aimed to evaluate the correlation of multiple risk factors to UI rates post‐HoLEP. Methods: A review of prospectively maintained 7 year database for HoLEP patients in a single center was performed. UI data at 6 week, 3 month, and 1 year follow‐up intervals were assessed with bivariate and multivariate analysis of multiple potential risk factors. Results: The study included 666 patients with median (IQR) age of 72 (66–78) years old and median (IQR) preoperative prostate volume of 89 (68–126) gm. UI was seen in 287 (43%), 100 (15%) and 26 (5.8%) at 6 week, 3 month, and 1 year follow up occasions respectively. At 6 weeks follow up, UI type was stress, urge and mixed in 121 (18.16%), 118 (17.72) and 48 (7.21%) patients respectively. Using a multivariate regression analysis, obesity and pre‐operative UI were associated with postoperative UI rate at both 6 week (p =.0065,.031) and 3 month (p =.0261,.044) follow up encounters respectively. Also, larger specimen weight was another predictor for 6 week UI (p =.0399) while higher frailty score was a predictor for UI at 3 month occasion (p =.041). Conclusion: Patients with preoperative UI, obesity, frailty, and large prostate volume are at higher risk of short‐term UI post‐HoLEP up to 3 months. Patients with one or more of these risk factors should be counseled regarding the higher risk of UI. [ABSTRACT FROM AUTHOR]

Background: Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. Key to its pathogenesis is the degree of intraoperative bacterial contamination at the surgical site. The purpose of this study was to evaluate a novel wound retractor at reducing bacterial contamination.Methods: A prospective multicenter pilot study utilizing a novel wound retractor combining continuous irrigation and barrier protection was conducted in patients undergoing elective colorectal resections. Culture swabs were collected from the incision edge prior to device placement and from the exposed and protected incision edge prior to device removal. The primary and secondary endpoints were the rate of enteric and overall bacterial contamination on the exposed incision edge as compared to the protected incision edge, respectively. The safety endpoint was the absence of serious device-related adverse events.Results: A total of 86 patients were eligible for analysis. The novel wound retractor was associated with a 66% reduction in overall bacterial contamination at the protected incision edge compared to the exposed incision edge (11.9 vs. 34.5%, P < 0.001), and 71% reduction in enteric bacterial contamination (9.5% vs. 33.3%, P < 0.001). The incisional SSI rate was 2.3% in the primary analysis and 1.2% in those that completed the protocol. There were no adverse events attributed to device use.Conclusions: A novel wound retractor combining continuous irrigation and barrier protection was associated with a significant reduction in bacterial contamination. Improved methods to counteract wound contamination represent a promising strategy for SSI prevention (NCT 02413879). [ABSTRACT FROM AUTHOR]

Lower limb ischemia in diabetic patients is a result of macro- and microcirculation dysfunction. Diabetic patients undergoing limb amputation carry high mortality and morbidity rates, and decision making concerning the level of amputation is critical. Aim of this study is to evaluate a novel microdialysis technique to monitor tissue microcirculation preoperatively and predict the success of limb amputation in such patients. Overall, 165 patients with type 2 diabetes mellitus undergoing lower limb amputation were enrolled. A microdialysis catheter was placed preoperatively at the level of the intended flap for the stump reconstruction, and the levels of glucose, glycerol, lactate and pyruvate were measured for 24 consecutive hours. Patients were then amputated and monitored for 30 days regarding the outcome of amputation. Failure of amputation was defined as delayed healing or stump ischemia. Patients were divided into two groups based on the success of amputation. There was no difference between the two groups regarding gender, ASA score, body mass index, comorbidities, diagnostic modality used, level of amputation, as well as glucose, glycerol, and pyruvate levels. However, local concentrations of lactate were significantly different between the two groups and lactate/pyruvate (L/P) ratio was independently associated with failed amputation (threshold defined at 25.35). Elevated preoperative tissue L/P ratio is independently associated with worse outcomes in diabetic patients undergoing limb amputation. Therefore, preoperative tissue L/P ratio could be used as a predicting tool for limb amputation's outcome, although more clinical data are needed to provide safer conclusions. [ABSTRACT FROM AUTHOR]

Background: Increased focus on reducing patient harm has led to surgical safety initiatives, including time-out, surgical safety checklists, and debriefings. The perception of the lay public of the surgical safety process is largely unknown. Methods: A 20-question survey focused on perceptions of surgical safety practice was distributed to a random sample of patients following elective operations requiring hospitalization. Responses were measured by a 7-point Likert scale. Qualitative feedback was obtained through nonphysician-moderated sessions. Participation was voluntary and anonymous. Results: Surveys were distributed to 345 patients of whom 102 (29.5%) responded. Overall, patients felt safe as evidenced by scores for the questions ''I felt safe the day of my surgery" (6.53 ± 0.72) and "Mistakes rarely happen during surgery" (5.39 ± 1.51). Patients undergoing their first surgery and patients with higher income levels were associated with a significant decrease in specific safety perceptions. Qualitative feedback sessions identified the physician-patient relationship as the most important factor positively influencing patient safety perceptions. Conclusion: Current surgical safety practice is perceived positively by our patients; however, patients still identify physicianpatient interactions, relationships, and trust as the most positive factors influencing their perception of the safety environment. [ABSTRACT FROM AUTHOR]

Introduction: In contrast with victims of major trauma, patients who suffer minor injuries receive little specialist input. In most cases, this causes no difficulty, but there are situations where minor trauma results in persistent disability affecting the quality of life. Case Presentation: A young man sustained a perineal puncture wound resulting from a fall onto a bush. Following an initial delay, he sought medical advice for a continual pain in his right leg, and a discharging perineal wound. A computed tomography (CT) scan and flexible sigmoidoscopy failed to identify the cause, and he was subsequently discharged from hospital. One year after his initial presentation, a magnetic resonance imaging (MRI) scan identified a retained foreign body consistent with a fragment of wood. Conclusions: Penetrating trauma from wooden fragments provides a diagnostic challenge. A stubborn discharge from a wound must always raise the suspicion of retained fragment. Early and appropriate surgical exploration is imperative. [ABSTRACT FROM AUTHOR]

Background: Residents and fellows perform a large portion of the hands-on patient care in tertiary referral centers. As frontline providers, they are well suited to identify quality and patient safety issues. As payment reform shifts hospitals to a fee-for-value-type system with reimbursement contingent on quality outcomes, preventive health, and patient satisfaction, house staff must be intimately involved in identifying and solving care delivery problems related to quality, outcomes, and patient safety. Many challenges exist in integrating house staff into the quality improvement infrastructure; these challenges may ideally be managed by the development of a house staff quality council (HSQC). Methods: Residents and fellows at Scott & White Memorial Hospital interested in participating in a quality council submitted an application, curriculum vitae, and letter of support from their program director. Twelve residents and fellows were selected based on their prior quality improvement experience and/or their interest in quality and safety initiatives. Results: In only 1 year, our HSQC, an Alliance of Independent Academic Medical Centers National Initiative III project, initiated 3 quality projects and began development of a fourth project. Conclusion: Academic medical centers should consider establishing HSQCs to align institutional quality goals with residency training and medical education. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) surgical safety checklist has been shown to decrease mortality and complications and has been adopted worldwide. However, system flaws and human errors persist. Identifying provider perspectives of patient safety initiatives may identify strategies for improvement. The purpose of this study was to determine provider perspectives of surgical safety checklist implementation in an effort to improve initiatives that enhance surgical patients' safety. Methods: In September 2010, a WHO-adapted surgical safety checklist was implemented at our institution. Surgical teams were invited to complete a checklist-focused questionnaire 1 month before and 1 year after implementation. Baseline and follow-up results were compared. Results: A total of 437 surgical care providers responded to the survey: 45% of providers responded at baseline and 64% of providers responded at follow-up. Of the total respondents, 153 (35%) were nurses, 104 (24%) were anesthesia providers, and 180 (41%) were surgeons. Overall, we found an improvement in the awareness of patient safety and quality of care, with significant improvements in the perception of the value of and participation in the time-out process, in surgical team communication, and in the establishment and clarity of patient care needs. Some discordance was noted between surgeons and other surgical team members, indicating that barriers in communication still exist. Overall, approximately 65% of respondents perceived that the checklist improved patient safety and patient care; however, we found a strong negative perception of operating room efficiency. Conclusion: Implementation of a surgical safety checklist improves perceptions of surgical safety. Barriers to implementation exist, but staff feedback may be used to enhance the sustainability and success of patient safety initiatives. [ABSTRACT FROM AUTHOR]

Background: It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-2/Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. We designed the BH3 α-helix mimetic JY-1-106 to engage the hydrophobic BH3-binding grooves on the surfaces of both Bcl-xL and Mcl-1. Methods: JY-1-106-protein complexes were studied using molecular dynamics (MD) simulations and the SILCS methodology. We have evaluated the in vitro effects of JY-1-106 by using a fluorescence polarization (FP) assay, an XTT assay, apoptosis assays, and immunoprecipitation and western-blot assays. A preclinical human cancer xenograft model was used to test the efficacy of JY-1-106 in vivo. Results: MD and SILCS simulations of the JY-1-106-protein complexes indicated the importance of the aliphatic side chains of JY-1-106 to binding and successfully predicted the improved affinity of the ligand for Bcl-xL over Mcl-1. Ligand binding affinities were measured via an FP assay using a fluorescently labeled Bak-BH3 peptide in vitro. Apoptosis induction via JY-1-106 was evidenced by TUNEL assay and PARP cleavage as well as by Bax-Bax dimerization. Release of multi-domain Bak from its inhibitory binding to Bcl-2/Bcl-xL and Mcl-1 using JY-1-106 was detected via immunoprecipitation (IP) western blotting. At the cellular level, we compared the growth proliferation IC50s of JY-1-106 and ABT-737 in multiple cancer cell lines with various Bcl-xL and Mcl-1 expression levels. JY-1-106 effectively induced cell death regardless of the Mcl-1 expression level in ABT-737 resistant solid tumor cells, whilst toxicity toward normal human endothelial cells was limited. Furthermore, synergistic effects were observed in A549 cells using a combination of JY-1-106 and multiple chemotherapeutic agents. We also observed that JY-1-106 was a very effective agent in inducing apoptosis in metabolically stressed tumors. Finally, JY-1-106 was evaluated in a tumor-bearing nude mouse model, and was found to effectively repress tumor growth. Strong TUNEL signals in the tumor cells demonstrated the effectiveness of JY-1-106 in this animal model. No significant side effects were observed in mouse organs after multiple injections. Conclusions: Taken together, these observations demonstrate that JY-1-106 is an effective pan-Bcl-2 inhibitor with very promising clinical potential. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine whether methicillin-resistant Staphylococcus aureus (MRSA) colonization affects surgical site infections (SSI) after major gastrointestinal (GI) operations. Methods: We retrospectively reviewed the charts of all patients undergoing major GI surgery from December 2007 to August 2009. All patients were tested for MRSA colonization and grouped according to results (MRSA+, methicillin-sensitive S. aureus [MSSA]+, and negative). Data analyzed included demographics, incidence of SSI, and wound culture results. Results: A total of 1,137 patients were identified; 78.9 % negative, 14.7 % MSSA+, and 6.4 % MRSA+. The mean age was 59.5 years, 44.5 % of the patients were men, and 47.9 % of the patients underwent colorectal operation. SSI was identified in 101 (8.9 %) patients and was higher in the MRSA+ group than the negative and MSSA+ groups (13.7 vs. 9.4 vs. 4.2 %; p < 0.05). Although MRSA colonization had an odds ratio of 1.43 for developing an SSI, it was not a significant independent risk factor. However, the MRSA+ group was strongly associated with MRSA cultured from the wound when SSI was present (70 vs. 8.5 %; p < 0.0001). Conclusions: MRSA colonization is not an independent risk factor for SSI following major GI operations; however, it is strongly predictive of MRSA-associated SSI in these patients. Preoperative MRSA nasal swab test with decolonization may reduce the incidence of MRSA-associated SSI after major GI surgery. [ABSTRACT FROM AUTHOR]

AbstractBackground and Purpose:Minimally invasive adrenalectomy is the preferred surgical approach for small, benign adrenal neoplasms. Posterior retroperitoneoscopic adrenalectomy is associated with potential surgical advantages. We sought to investigate the feasibility and early outcomes for robot-assisted posterior adrenalectomy, which has not been previously reported.Patients and Methods:Patients were selected for adrenalectomy based on standard clinical indications. The study was conducted under a protocol approved by the Institutional Review Board. Patients with adrenal masses larger than 7.0 cm, or with a body mass index (BMI) greater than 40, were excluded. Patient demographics, clinical and pathologic data, operative times, and patient outcomes were collected prospectively.Results:Six consecutive patients underwent robot-assisted posterior retroperitoneoscopic adrenalectomy (RAPRA) between June 23, 2009 and January 21, 2010. Five women and one man, ages 45 to 75 years (mean 55.5 years), with a mean BMI of 30, were included. There were three right adrenal tumors and three left adrenal tumors. Mean operative time was 121 minutes with a mean robot time of 57 minutes for the five patients in whom the entire adrenal dissection was performed robotically. There was essentially no morbidity and no mortality.Conclusion:This study represents the first report of RAPRA, and demonstrates the feasibility of performing this procedure with good patient outcomes. [ABSTRACT FROM AUTHOR]

Midgut malrotation most commonly presents in young children. This diagnosis is not often entertained in the adolescent or adult with abdominal complaints. We reviewed our experience with this subset of malrotation patients. A retrospective review of medical records from adolescent or adult patients identified with a diagnosis of anomaly of intestinal fixation or malrotation, who were treated within our health system between 1993 and 2004. A total of 33 patients were diagnosed with malrotation and treated with Ladd’s procedure. Acute abdominal pain was present in 50%, and chronic complaints were present in the other patients. Initial work-up included computed tomography (CT) scan (28%), upper gastrointestinal (UGI) study (38%), and plain films (47%) Postoperative complications occurred more frequently in patients that were operated on emergently (60%) than in those that underwent elective surgery (22%; p = 0.04). This large case series of intestinal malrotation in the nonpediatric age group suggests that Ladd’s procedure can be performed very safely. Moreover, the results suggest that patients with known malrotation should have Ladd’s procedure performed electively rather than urgently. [ABSTRACT FROM AUTHOR]

Transforming growth factor (TGF)-β-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-β inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-β-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-β-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-β/Smad3. Total RNA samples were analyzed using Affymetrix oligo- nucleotide microarrays. We found that TGF-β regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Further- more, TGF-β activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-β induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-β-induced apoptosis in RIE-1/Smad3 cells. [ABSTRACT FROM AUTHOR]

PURPOSE: Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. The purpose of this study was to define the characteristics and survival patterns of transplant patients developing tie novo colorectal cancer. METHODS: The Israel Penn International Transplant Tumor Registry was queried for patients with cob rectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based cob rectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database. RESULTS: A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and coborectab cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantation patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P < 0.001), and a worse five-year survival (overall, 44 vs. 62 percent, P < 0.001; Dukes A&B, 74 vs. 90 percent, P < 0.001; Dukes C, 20 vs. 66 percent, P < 0.001; and Dukes D, 0 vs. 9 percent, P = 0.08). CONCLUSIONS: Transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. These data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted. [ABSTRACT FROM AUTHOR]

Glutamine starvation induces apoptosis in enterocytes; therefore glutamine is important in the maintenance of gut mucosal homeostasis. However, the molecular mechanisms are unknown. The caspase family of proteases constitutes the molecular machinery that drives apoptosis. Caspases are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were to (1) identify specific caspases activated by glutamine starvation and (2) determine whether a general caspase inhibitor blocks glutamine starvation-induced apoptosis in intestinal epithelial cells. Rat intestinal epithelial (RIE-I) cells were deprived of glutamine. Specific caspase activation was measured using fluorogenic substrate assay. Apoptosis was quantified by DNA fragmentation and Hoechst nuclear staining. Glutamine starvation of RIE-1 cells resulted in the time-dependent activation of caspases 3 (10 hours) and 2 (18 hours), and the induction of DNA fragmentation (12 hours). Caspases 1 and 8 remained inactive. ZVAD-fluoromethyl ketone, a general caspase inhibitor, completely blocked glutamine starvation-induced caspase activation, DNA fragmentation, and nuclear condensation. These results indicate that glutamine starvation selectively activates specific caspases, which leads to the induction of apoptosis in PIE-1 cells. Furthermore, inhibition of caspase activity blocked the induction of apoptosis, suggesting that caspases are potential molecular targets to attenuate apoptotic responses in the gut. [ABSTRACT FROM AUTHOR]

Novel chemotherapeutic agents are needed to treat gastric cancer for which the prognosis remains dismal. The antitumor alkaloid camptothecin (CPT) may be useful in the treatment of certain solid tumors; however, its effects on gastric cancer are largely undefined. The purpose of our study was to characterze the effects of CPT on human gastric tumors in vivo and to determine the cellular mechanisms involved in CPT-mediated inhibition. Two human gastric cancers, WIL and TOR, were transplanted sub-cutaneously into athymic nude mice. After tumors reached 50 to 100 mm2, mice were randomized into three groups to receive injections of either low-dose CPT (5 mg/kg), high-dose CPT (10 mg/kg), or vehicle (control) intraperitoneally 3 days a week for 3 weeks. Tumors were measured and weighed, and protein levels of the cell cycle inhibitor, p21Wafl/Cipl, and the antiapopton’c protein, Bcl-2, were assessed. Both dosages of CPT significantly inhibited growth of WIL and TOR gastric tumors. CPT (10 mg/kg) reduced tumor size compared to baseline, establishing this as a tumoricidal dosage. Treatment with CPT was associated with increased levels of p21Wafl/Cipl and decreased levels of Bcl-2. CPT effectively kills human gastric cancers associated with increased levels of p2 lW’Cipi and decreased levels of Bcl-2. By activating cell cycle withdrawal and cell death through induction of p2 lWafl/Cipl and downregulation of Bcl-2, CPT may be an effective agent for gastric cancer. [ABSTRACT FROM AUTHOR]