Structured Textbook Review and Individualized Learning Plans Successfully Remediate Underperforming Residents and Improve General Surgery Program Performance on the ABSITE.

Background: We endeavored to create an evidence-based curriculum to improve general surgery resident fund of knowledge. Global and resident-specific interventions were employed to this end. These interventions were monitored via multiple choice question results on a weekly basis and American Board of Surgery In-Training Examination (ABSITE) performance. Methods: This study was performed in a prospective manner over a 2-year period. A structured textbook review with testing was implemented for all residents. A focused textbook question-writing assignment and a Surgical Council on Resident Education (SCORE)-based individualized learning plan (ILP) were implemented for residents scoring below the 35th percentile on the ABSITE. Results: Curriculum implementation resulted in a statistically significant reduction in the number of residents scoring below the 35th percentile, from 50% to 30.8% (P = .023). One hundred percent of residents initially scoring below the 35th percentile were successfully remediated over the study period. Average overall program ABSITE percentile scores increased from 38.5% to 51.4% over a 2-year period. Conclusion: Structured textbook review and testing combined with a question-writing assignment and a SCORE-focused ILP successfully remediated residents scoring below the 35th percentile and improved general surgery residency ABSITE performance.

Comparison between transpapillary versus transmural endoscopic ultrasound-guided decompression for biliary obstruction: a meta-analysis.

BACKGROUND: Recent advances have led to the development of transmural endoscopic ultrasound guided biliary drainage (EUS-BD) for cases where the duodenal papilla cannot be accessed. OBJECTIVES: We performed a meta-analysis comparing efficacy and complications of both approaches for biliary drainage. REVIEW METHODS: English articles were searched in PubMed. Primary outcomes included technical success and complications. Secondary outcomes were clinical success and subsequent stent malfunction. Patient demographics and etiology of obstruction were collected and relative risk ratios and 95% CIs were calculated. P-value <0.05 was considered as statistically significant. RESULTS: Initial database search yielded 245 studies from which 7 were chosen based upon inclusion criteria for final analysis. There was no statistically different relative risk for technical success when comparing primary EUS-BD to endoscopic retrograde cholangiopancreatography (ERCP) (RR: 1.04) or overall procedural complication rate (RR 1.39). EUS-BD did have increased specific risk of cholangitis (RR: 3.01). Likewise, primary EUS-BD and ERCP had similar RR for clinical success (RR: 1.02) and overall stent malfunction (RR: 1.55), but stent migration was higher in the primary EUS-BD group (RR: 5.06). CONCLUSIONS: Primary EUS-BD may be considered when the ampulla cannot be accessed, when there is gastric outlet obstruction, or presence of a duodenal stent.

Perforated Sigmoid Diverticulitis Within a Strangulated Inguinal Hernia.

We present a rare case of perforated diverticulitis within an inguinal hernia sac adjacent to a synthetic mesh from a prior incisional hernia. An 80-year-old-female presented to the ED with abdominal pain. Cross-sectional imaging was significant for a small bowel obstruction with a transition point in the right lower quadrant (RLQ). On physical exam, the patient had palpable bilateral inguinal hernias that were reducible; however, after 48 hours of nonoperative management she failed to progress. Repeat imaging was concerning for incarcerated bowel within the inguinal hernia sac. She was taken to the operating room for exploratory laparotomy where the right inguinal hernia sac was found to contain sigmoid colon with diverticular perforation. A small bowel resection, right hemicolectomy and Hartmann's procedure were performed. The previously placed synthetic mesh was not contaminated during this operation and was not removed. Her hospital course was otherwise unremarkable but prolonged by the patient's deconditioned state.

T-tube Duodenostomy for the Difficult Duodenum.

Tube duodenostomy has been described as a useful technique in the management of difficult duodenum arising from a variety of pathologies. In addition, the use of a t-tube for the duodenostomy presents a resourceful option in the event of Malecot or other such catheter unavailability. The aim of our study is to describe the technique and outcomes associated with this approach. During a six-month period in 2020, t-tube duodenostomies were performed in three patients for duodenal stump perforation: the first case involved a patient with Roux-en-Y esophagojejunostomy anatomy; the second involved duodenal stump closure security following Billroth II gastrectomy for peptic ulcer disease; and the third involved decompression following primary closure of duodenal perforation. All duodenostomies were performed with a t-tube that was trimmed with the back wall divided and then secured via the Witzel approach. The t-tube duodenostomies were performed during the index operations of all patients. No patient required additional operations. There was no mortality. All patients were closely monitored postoperatively with duodenostomies kept in place for six weeks. One patient developed a small leak after a trial of tube clamping, which was managed with continued tube drainage and antibiotics prior to definitive removal. The mean length of stay was 20.3 days with two patients being discharged to rehab. T-tube duodenostomy is a simple technique that helps avoid the blowout of the vulnerable duodenal stump in situations of biliopancreatic limb pathology, ulcerative disease, or injury.

Impact of Laparoscopy on Training: Are Open Appendectomy and Cholecystectomy on the Brink of Extinction?

The operative experience of present-day surgical residency training has evolved as a result of the contributions of laparoscopic surgery. Some traditional open procedures are now more descriptive and less of a familiarity to many general surgery residents (GSRs). The aim of this study was to investigate how open operative experience compares with laparoscopy for GSRs. A retrospective, multicenter, consecutive cohort study of all patients undergoing surgical intervention involving the appendix and gallbladder identified from the ACS-NSQIP database over a 2.5-year period. All GSR postgraduate year-level operative experience was recorded. Of 777 procedures, 13 laparoscopic appendectomy conversions to open (4.3%) by Rocky-Davis (15%) or lower midline (84.6%) incisions were performed versus 285 that remained laparoscopic (95.6%). Fifty (10.4%) open cholecystectomies (38 open + 10 conversions + 2 common bile duct (CBD) exploration), 27 (5.6%) laparoscopic cholecystectomies with cholangiogram, and 402 (83.9%) laparoscopic cholecystectomies were performed. Twenty-nine different GSRs participated in procedures. Eighty-five (10.9%) operations were performed with multi-postgraduate year levels. Surgical residents have an unequal operative experience for case-specific open procedures. A competency-based system to demonstrate a resident's hands-on surgical skills is fundamental to residency training and should be considered for specific types of low-volume open surgical cases.

Can Planned Traffic Patterns Improve Survival Among the Injured During Mass Casualty Motorcycle Rallies?

BACKGROUND: Mass casualty events are infrequent and create an abrupt surge of patients requiring emergency medical services within a brief period. We hypothesize that implementation of a controlled "traffic loop" pattern during a planned high-volume motorcycle rally could improve overall mortality and impact patient outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of all motorcycle-related injuries during the city's annual motorcycle rally over a 4-y period. Comparative analysis was completed between those injured during "nontraffic loop" hours versus the city's scheduled 23-mile, 3-d "traffic loop" pattern. The two groups were compared for age, gender, injuries, Injury Severity Score, Glasgow Coma Scale, length of stay, ventilator-free days, and mortality. The primary outcome was mortality. RESULTS: A total of 139 patients were included (120 nonloop and 19 loop). Mean (standard deviation) age was 36.1 (11.2) y and 72.1% were male. Both groups were equivalent in age, gender, Injury Severity Score, and Glasgow Coma Scale. Traffic loop patients required longer intensive care unit length of stay, (median = 9.0, range: 1-49 d), ventilator days (median = 29.5), (range: 1-49 d) and experienced abdominal trauma (P = 0.002). Emergency medical services transport times during loop hours had shorter response times than the nonloop injury group (7.79 ± 5.2 min and 13.22 ± 14.01 min (P = 0.049). No deaths occurred during the city's scheduled traffic loop (0 versus 22, P = 0.0447). CONCLUSIONS: Controlled traffic patterns during high-volume city gatherings can improve overall mortality and morbidity. Regional trauma system preparedness with field triage guidelines and coordinated trauma care is warranted to effectively care for the injured.

Bacteriology and Comorbidities in Patients Requiring Surgical Management of Empyema.

Concern over the changing bacteriology of empyema has led to numerous attempts to characterize the most common locoregional bacterial isolates. The purpose of this study is to better characterize the bacteriology and demographics in patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia requiring surgery for empyema. All patients diagnosed with empyema preoperatively and had either a video-assisted thoracoscopic or open decortication surgery from January 2010 to September 2015 were reviewed. Forty-seven patients were identified with a mean age of 54.7 ± 16.8 years (X ± SD). Sixty per cent of patients had CAP. Anaerobes were the most common isolate at 21 per cent, followed by Streptococcus species and Staphylococcus aureus (50% Methicillin Resistant). Coagulase-negative Staphylococcus species were the next most frequent at 13 per cent. Hospital-acquired pneumonia patients had a higher incidence of S. aureus infections (P = 0.047). Cancer history had higher rates of both fungal (P = 0.004) and gram-negative infections (P = 0.03). Older patients had increased incidence of gram-negative infections (P = 0.05). The median length of stay for CAP patient who were intravenous drug abusers (n = 3) were 31 days (95% confidence interval (CI) [15, NA]), which was significantly longer than the others (median 12 days, 95% CI: [9, 18], P = 0.014). Streptococcus pneumoniae was not found in any of the isolates. Our data reveal that anaerobes and Staphylococcus species have replaced S. pneumoniae as the major regional pathogens in surgically treated empyema. In addition, anaerobic isolates were found in higher incidence in CAP than previously reported.

Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo.

The clinical potential of PARP-1 inhibitors has been recognized >10years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problem for their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors. The majority of PARP-1 inhibitors known to date have been developed as NAD competitors. NAD is utilized by many enzymes other than PARP-1, resulting in a trade-off trap between their specificity and efficacy. To circumvent this problem, we have developed a new strategy to blindly screen a small molecule library for PARP-1 inhibitors by targeting a highly specific rout of its activation. Based on this screen, we present a collection of PARP-1 inhibitors and provide their structural classification. In addition to compounds that show structural similarity to NAD or known PARP-1 inhibitors, the screen identified structurally new non-NAD-like inhibitors that block PARP-1 activity in cancer cells with greater efficacy and potency than classical PARP-1 inhibitors currently used in clinic. These non-NAD-like PARP-1 inhibitors are effective against several types of human cancer xenografts, including kidney, prostate, and breast tumors in vivo. Our pre-clinical testing of these inhibitors using laboratory animals has established a strong foundation for advancing the new inhibitors to clinical trials.

Small-molecule collection and high-throughput colorimetric assay to identify PARP1 inhibitors.

During the last few years, poly(ADP-ribose)polymerase (PARP) proteins became a very popular target for anticancer treatment. Many PARP inhibitors have been generated and tested by pharmacological industry. However, most of them were designed to disrupt the DNA-dependent PARP1 protein activation pathway and were based on a competition with NAD for a binding site on PARP molecule and, therefore, on disruption of PARP-mediated enzymatic reaction. This limitation resulted in a discovery of mainly nucleotide-like PARP1 inhibitors which may target not only PARP, but also other pathways involving NAD and other nucleotides. Here, we describe a strategy for the identification of PARP inhibitors that target a different pathway, the histone H4-dependent PARP1 activation. Besides the identification of NAD competitors in a small-molecule collection, this approach allows finding novel classes of PARP inhibitors that specifically disrupt H4-based PARP activation.

Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation in chromatin.

According to the histone code hypothesis, histone variants and modified histones provide binding sites for proteins that change the chromatin state to either active or repressed. Here, we identify histone variants that regulate the targeting and enzymatic activity of poly(ADP-ribose) polymerase 1 (PARP1), a chromatin regulator in higher eukaryotes. We demonstrate that PARP1 is targeted to chromatin by association with the histone H2A variant (H2Av)--the Drosophila homolog of the mammalian histone H2A variants H2Az/H2Ax--and that subsequent phosphorylation of H2Av leads to PARP1 activation. This two-step mechanism of PARP1 activation controls transcription at specific loci in a signal-dependent manner. Our study establishes the mechanism through which histone variants and changes in the histone modification code control chromatin-directed PARP1 activity and the transcriptional activation of target genes.

Nucleosomal core histones mediate dynamic regulation of poly(ADP-ribose) polymerase 1 protein binding to chromatin and induction of its enzymatic activity.

Poly(ADP-ribose) polymerase 1 protein (PARP1) mediates chromatin loosening and activates the transcription of inducible genes, but the mechanism of PARP1 regulation in chromatin is poorly understood. We have found that PARP1 interaction with chromatin is dynamic and that PARP1 is exchanged continuously between chromatin and nucleoplasm, as well as between chromatin domains. Specifically, the PARP1 protein preferentially interacts with nucleosomal particles, and although the nucleosomal linker DNA is not necessary for this interaction, we have shown that the core histones, H3 and H4, are critical for PARP1 binding. We have also demonstrated that the histones H3 and H4 interact preferentially with the C-terminal portion of PARP1 protein and that the N-terminal domain of PARP1 negatively regulates these interactions. Finally, we have found that interaction with the N-terminal tail of the H4 histone triggers PARP1 enzymatic activity. Therefore, our data collectively suggests a model in which both the regulation of PARP1 protein binding to chromatin and the enzymatic activation of PARP1 protein depend on the dynamics of nucleosomal core histone mediation.

Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia.

Animal models of ovarian cancer are crucial for understanding the pathogenesis of the disease and for testing new treatment strategies. A model of ovarian carcinogenesis in the rat was modified and improved to yield ovarian preneoplastic and neoplastic lesions that pathogenetically resemble human ovarian cancer. A significantly lower dose (2 to 5 mug per ovary) of 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the one ovary to maximally preserve its structural integrity. DMBA-induced mutagenesis was additionally combined with repetitive gonadotropin hormone stimulation to induce multiple cycles of active proliferation of the ovarian surface epithelium. Animals were treated in three arms of different doses of DMBA alone or followed by hormone administration. Comparison of the DMBA-treated ovaries with the contralateral control organs revealed the presence of epithelial cell origin lesions at morphologically distinct stages of preneoplasia and neoplasia. Their histopathology and path of dissemination to other organs are very similar to human ovarian cancer. Hormone cotreatment led to an increased lesion severity, indicating that gonadotropins may promote ovarian cancer progression. Point mutations in the Tp53 and Ki-Ras genes were detected that are also characteristic of human ovarian carcinomas. Additionally, an overexpression of estrogen and progesterone receptors was observed in preneoplastic and early neoplastic lesions, suggesting a role of these receptors in ovarian cancer development. These data indicate that this DMBA animal model gives rise to ovarian lesions that closely resemble human ovarian cancer and it is adequate for additional studies on the mechanisms of the disease and its clinical management.