De-epimerizing DyKAT of ß-lactones generated by isothiourea-catalysed enantioselective [2 + 2] cycloaddition.

An enantioselective isothiourea-catalysed [2 + 2] cycloaddition of C(1)-ammonium enolates with pyrazol-4,5-diones is used to construct spirocyclic ß-lactones in good yields, excellent enantioselectivity (99 : 1 er) but with modest diastereocontrol (typically 70 : 30 dr). Upon ring-opening with morpholine or alternative nucleophilic amines and alcohols ß-hydroxyamide and ß-hydroxyester products are generated with enhanced diastereocontrol (up to >95 : 5 dr). Control experiments show that stereoconvergence is observed in the ring-opening of diastereoisomeric ß-lactones, leading to a single product (>95 : 5 dr, >99 : 1 er). Mechanistic studies and DFT analysis indicate a substrate controlled Dynamic Kinetic Asymmetric Transformation (DyKAT) involving epimerisation at C(3) of the ß-lactone under the reaction conditions, coupled with a hydrogen bond-assisted nucleophilic addition to the Si-face of the ß-lactone and stereodetermining ring-opening. The scope and limitations of a one-pot protocol consisting of isothiourea-catalysed enantio-determining [2 + 2] cycloaddition followed by diastereo-determining ring-opening are subsequently developed. Variation within the anhydride ammonium enolate precursor, as well as N(1) and C(3) within the pyrazol-4,5-dione scaffold is demonstrated, giving a range of functionalised ß-hydroxyamides with high diastereo- and enantiocontrol (>20 examples, up to >95 : 5 dr and >99 : 1 er) via this DyKAT.

Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution of Tetra-substituted Morpholinone and Benzoxazinone Lactols.

The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) of tetra-substituted lactols is a recognised synthetic challenge. In this manuscript, a highly enantioselective isothiourea-catalysed acylative DKR of tetra-substituted morpholinone and benzoxazinone-derived lactols is reported. The scope and limitations of this methodology have been developed, with high enantioselectivity and good to excellent yields (up to 89%, 99:1 er) observed across a broad range of substrate derivatives incorporating substitution at N(4) and C(2), di- and spirocyclic substitution at C(5)- and C(6)-position, as well as benzannulation (>35 examples in total). The DKR process is amenable to scale-up on a 1 g laboratory scale. The factors leading to high selectivity in this DKR process have been probed through computation, with an N-C=O•••isothiouronium interaction identified as key to producing ester products in highly enantioenriched form.

Enantioselective Synthesis of Tetra-substituted 3-Hydroxyphthalide Esters by Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution.

A general and highly enantioselective method for the preparation of tetra-substituted 3-hydroxyphthalide esters via isothiourea-catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)-HyperBTM (5 mol%) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99%, 99:1 er). Substitution of the aromatic core within the 3-hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3)-, is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computation, with a key substrate heteroatom donor O•••acyl-isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination.

Enantioselective Synthesis in Continuous Flow: Polymer-Supported Isothiourea-Catalyzed Enantioselective Michael Addition-Cyclization with α-Azol-2-ylacetophenones.

A packed reactor bed incorporating a polymer-supported isothiourea HyperBTM catalyst derivative has been used to promote the enantioselective synthesis of a range of heterocyclic products derived from α-azol-2-ylacetophenones and -acetamides combined with alkyl, aryl, and heterocyclic α,ß-unsaturated homoanhydrides in continuous flow via an α,ß-unsaturated acyl-ammonium intermediate. The products are generated in good to excellent yields and generally in excellent enantiopurity (up to 97:3 er). Scale-up is demonstrated on a 15 mmol scale, giving the heterocyclic product in 68% overall yield with 98:2 er after recrystallization.

α-Functionalisation of Cyclic Sulfides Enabled by Lithiation Trapping.

A general and straightforward procedure for the lithiation trapping of cyclic sulfides such as tetrahydrothiophene, tetrahydrothiopyran and a thiomorpholine is described. Trapping with a wide range of electrophiles is demonstrated, leading to more than 50 diverse α-substituted saturated sulfur heterocycles. The methodology provides access to a range of α-substituted cyclic sulfides that are not easily synthesised by the currently available methods.

Disparate potential for readmission prevention exists among inpatient and outpatient procedures in a minimally invasive surgery practice.

BACKGROUND: Administrators have focused on decreasing postoperative readmissions for cost reduction without fully understanding their preventability. This study describes the development and implementation of a surgeon-led readmission review process that assessed preventability. METHODS: A gastrointestinal surgical group at a tertiary referral hospital developed and implemented a template to analyze inpatient and outpatient readmissions. Monthly stakeholder assessments reviewed and categorized readmissions as potentially preventable or not preventable. Continuous variables were examined by the Student's t test and reported as means and standard deviations. Categorical variables were examined by the Pearson χ2 statistic and Fisher's exact test. RESULTS: There were 61 readmission events after 849 inpatient operations (7.2%) and 16 after 856 outpatient operations (1.9%), the latter of which were all classified as potentially preventable. Colorectal procedures represented 65.6% of readmissions despite being only 37.2% of all cases. The majority (67.2%) of readmission events were not preventable. Compared to the not-preventable group, the potentially preventable group experienced more dehydration (30.0% vs 9.8%, P = .045) and ileostomy creation (78.6% vs 33.3%, P = .017). The potential for outpatient management to prevent readmission was significantly higher in the potentially preventable group (40.0% vs 0.0%, P < .001), as was premature discharge prevention (35.0% vs 0.0%, P < .001). CONCLUSION: The use of the standardized template developed for analyzing readmission events after inpatient and outpatient procedures identified a disparate potential for readmission prevention. This finding suggests that a singular focus on readmission reduction is misguided, with further work needed to evaluate and implement appropriate quality-based strategies.

Understanding divergent substrate stereoselectivity in the isothiourea-catalysed conjugate addition of cyclic α-substituted ß-ketoesters to α,ß-unsaturated aryl esters.

The development of enantioselective synthetic methods capable of generating vicinal stereogenic centres, where one is tetrasubstituted (such as either an all-carbon quaternary centre or where one or more substituents are heteroatoms), is a recognised synthetic challenge. Herein, the enantioselective conjugate addition of a range of carbo- and heterocyclic α-substituted ß-ketoesters to α,ß-unsaturated aryl esters using the isothiourea HyperBTM as a Lewis base catalyst is demonstrated. Notably, divergent diastereoselectivity is observed through the use of either cyclopentanone-derived or indanone-derived substituted ß-ketoesters with both generating the desired stereodefined products with high selectivity (>95 : 5 dr, up to 99 : 1 er). The scope and limitations of these processes are demonstrated, alongside application on gram scale. The origin of the divergent substrate selectivity has been probed through the use of DFT-analysis, with preferential orientation driven by dual stabilising CH⋯O interactions. The importance of solvation with strongly polar transition-states is highlighted and the SMD solvation model is demonstrated to capture solvation effects reliably.

A resident robotic curriculum utilizing self-selection and a web-based feedback tool.

To describe an obstetrics and gynecology residency robotic curriculum, facilitated by a web-based feedback and case-tracking tool, allowing for self-selection into advanced training. Phase I (Basic) was required for all residents and included online training modules, online assessment, and robotic bedside assistant dry lab. Phase II (Advanced) was elective console training. Before live surgery, 10 simulation drills completed to proficiency were required. A web-based tool was used for surgical feedback and case-tracking. Online assessments, drill reports, objective GEARS assessments, subjective feedback, and case-logs were reviewed (7/2018-6/2019). A satisfaction survey was reviewed. Twenty four residents completed Phase I training and 10 completed Phase II. To reach simulation proficiency, residents spent a median of 4.1 h performing required simulation drills (median of 10 (3, 26) attempts per drill) before live surgery. 128 post-surgical feedback entries were completed after performance as bedside assistant (75%, n = 96) and console surgeon (5.5%, n = 7). The most common procedure was hysterectomy 111/193 (58%). Resident console surgeons performed portions of 32 cases with a mean console time of 34.6 ± 19.5 min. Mean GEARS score 20.6 ± 3.7 (n = 28). Mean non-technical feedback results: communication (4.2 ± 0.8, n = 61), workload management (3.9 ± 0.9, n = 54), team skills (4.3 ± 0.8, n = 60). Residents completing > 50% of case assessed as "apprentice" 38.5% or "competent" 23% (n = 13). After curriculum change, 100% of surveyed attendings considered residents prepared for live surgical training, vs 17% (n = 6) prior to curriculum change [survey response rate 27/44 (61%)]. Attendings and residents were satisfied with curriculum; 95% and recommended continued use 90% (n = 19).This two-phase robotic curriculum allows residents to self-select into advanced training, alleviating many challenges of graduated robotic training.

Unseen Burden of Injury: Post-Hospitalization Mortality in Geriatric Trauma Patients.

BACKGROUND/OBJECTIVES: Older adults are at risk for adverse outcomes after trauma, but little is known about post-acute survival as state and national trauma registries collect only inpatient or 30-day outcomes. This study investigates long-term, out-of-hospital mortality in geriatric trauma patients. METHODS: Level I Trauma Center registry data were matched to the US Social Security Death Index (SSDI) to determine long-term and out-of-hospital outcomes of older patients. Blunt trauma patients aged ≥65 were identified from 2009 to 2015 in an American College of Surgeons Level 1 Trauma Center registry, n = 6289 patients with an age range 65-105 years, mean age 78.5 ± 8.4 years. Dates of death were queried using social security numbers and unique patient identifiers. Demographics, injury, treatments, and outcomes were compared using descriptive and univariate statistics. RESULTS: Of 6289 geriatric trauma patients, 505 (8.0%) died as an inpatient following trauma. Fall was the most common mechanism of injury (n = 4757, 76%) with mortality rate of 46.5% at long-term follow-up; motor vehicle crash (MVC) (n = 1212, 19%) had long-term mortality of 27.6%. Overall, 24.1% of patients died within 1 year of trauma. Only 8 of 488 patients who died between 1 and 6 months post-trauma were inpatient. Mortality rate varied by discharge location: 25.1% home, 36.4% acute rehabilitation, and 51.5% skilled nursing facility, P < .0001. CONCLUSION: Inpatient and 30-day mortality rates in national outcome registries fail to fully capture the burden of trauma on older patients. Though 92% of geriatric trauma patients survived to discharge, almost one-quarter had died by 1 year following their injuries.

Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins.

Enantioselective [2 + 2] cycloaddition of C(1)-ammonium enolates generated catalytically using the isothiourea HyperBTM with N-alkyl isatins gives spirocyclic ß-lactones. In situ ring opening with an amine nucleophile generates isolable highly enantioenriched products in up to 92:8 dr and in >99:1 er.

A core outcome set for damage control laparotomy via modified Delphi method.

OBJECTIVES: Damage control laparotomy (DCL) remains an important tool in the trauma surgeon's armamentarium. Inconsistency in reporting standards have hindered careful scrutiny of DCL outcomes. We sought to develop a core outcome set (COS) for DCL clinical studies to facilitate future pooling of data via meta-analysis and Bayesian statistics while minimizing reporting bias. METHODS: A modified Delphi study was performed using DCL content experts identified through Eastern Association for the Surgery of Trauma (EAST) 'landmark' DCL papers and EAST ad hoc COS task force consensus. RESULTS: Of 28 content experts identified, 20 (71%) participated in round 1, 20/20 (100%) in round 2, and 19/20 (95%) in round 3. Round 1 identified 36 potential COS. Round 2 achieved consensus on 10 core outcomes: mortality, 30-day mortality, fascial closure, days to fascial closure, abdominal complications, major complications requiring reoperation or unplanned re-exploration following closure, gastrointestinal anastomotic leak, secondary intra-abdominal sepsis (including anastomotic leak), enterocutaneous fistula, and 12-month functional outcome. Despite feedback provided between rounds, round 3 achieved no further consensus. CONCLUSIONS: Through an electronic survey-based consensus method, content experts agreed on a core outcome set for damage control laparotomy, which is recommended for future trials in DCL clinical research. Further work is necessary to delineate specific tools and methods for measuring specific outcomes. LEVEL OF EVIDENCE: V, criteria.

Complicated Diverticular Disease.

The modern management of colonic diverticular disease involves grouping patients into uncomplicated or complicated diverticulitis, after which the correct treatment paradigm is instituted. Recent controversies suggest overlap in management strategies between these two groups. While most reports still support surgical intervention for the treatment of complicated diverticular disease, more data are forthcoming suggesting complicated diverticulitis does not merit surgical resection in all scenarios. Given the significant risk for complication in surgery for diverticulitis, careful attention should be paid to patient and procedure selection. Here, we define complicated diverticulitis, discuss options for surgical intervention, and explain strategies for avoiding operative pitfalls that result in early and late postoperative complications.

Twelve years of component separation technique in abdominal wall reconstruction.

BACKGROUND: Component separation technique involves incision of abdominal muscle and its aponeurosis, which generates a myofascial advancement flap to assist with fascial closure in abdominal wall reconstructions. This tissue mobilization allows for musculo-fascial approximation of much larger abdominal wall defects than would otherwise be possible. With extensive tissue mobilization, however, there is concern for significant wound and systemic complications. METHODS: A prospective, single institution hernia database was queried for patients undergoing component separation from January 2006 to May 2018. Emergency operations were excluded. Anterior component separation (external oblique release with posterior rectus sheath release) and posterior component separation (transversus abdominus release and posterior rectus sheath release) were examined. RESULTS: Of the 775 component separation, 33.4% included anterior component separation and 66.6% posterior component separation. Mean age was 58.8 ± 11.5 years, mean body mass index was 33.6 ± 7.1 (kg/m2), and 27.9% of patients were diabetic. Hernias were large (280.0 ± 220.9 cm2) and often complex (recurrent: 62.6%, incarcerated: 41.5%, concomitant panniculectomy: 39.1%, and contaminated: 37.0%). Defect size was larger in anterior component separation group compared with posterior component separation (379.5 ± 265.2 vs 230.0 ± 175.0 cm2, P < .001). There was a 35.1% wound complication rate with 32 recurrences (4.1%) during a mean follow-up of 23.3 ± 25.1 months. Complete fascial closure and lack of wound complications significantly improved outcomes (P < .01). Patients undergoing anterior component separation demonstrated more wound complications (42.9% vs 31.2%, P < .001) and recurrences (7.0% vs 2.7%, P = .005). In multivariate analysis, anterior component separation was associated with increased risk of wound complications (odds ratio 1.660; confidence interval, 1.125-2.450), but not recurrence (odds ratio 2.95; confidence interval, 0.72-12.19). Since 2013, prehabilitation and perforator sparing techniques reduced anterior component separation wound complications to 19.6% (P = .008). CONCLUSION: Both anterior component separation and posterior component separation are associated with low recurrence rates, but anterior component separation is associated with higher wound complications. Prehabilitation and operative techniques improve outcomes of component separation.

Outcomes of open abdomen versus primary closure following emergent laparotomy for suspected secondary peritonitis: A propensity-matched analysis.

BACKGROUND: Optimal management following index laparotomy is poorly defined in secondary peritonitis patients. Although "open abdomen" (OA), or temporary abdominal closure with planned relaparotomy, is used to reassess bowel viability or severity of contamination, recent studies demonstrate comparable morbidity and mortality with primary abdominal closure (PC). This study evaluates differences between OA and PC following emergent laparotomy. METHODS: Using the Premier database at a quaternary care center (2012-2016), nontrauma patients with secondary peritonitis requiring emergent laparotomy were identified (N = 534). Propensity matching for PC (n = 331; 62%) or OA (n = 203; 38%) was performed using variables: Mannheim Peritonitis Index, lactate, and vasopressor requirement. One hundred eleven closely matched pairs (PC:OA) were compared. RESULTS: Five hundred thirty-four patients (55.0% female; mean age, 59.6 ± 15.5 years) underwent emergent laparotomy. Of the OA patients, 136 (67.0%) had one relaparotomy, while 67 (33.0%) underwent multiple reoperations. Compared to daytime cases, laparotomies performed overnight (6 pm-6 am) had more temporary closures with OA (42.8% OA vs. 57.2% PC, p = 0.04). When assessing by surgeon type, PC was performed in 78.7% of laparotomies by surgical subspecialties compared to 56.7% (p < 0.0001) of acute care surgeons. After propensity matching, OA patients had increased postoperative complications (71.2% vs. 41.4%, p < 0.0001), mortality (22.5% vs. 11.7%, p = 0.006), and longer median length of stay (13 vs. 9 days, p = 0.0001). CONCLUSION: Open abdomen was performed in 38.0% of patients, with one-third of those requiring multiple reoperations. Complications, mortality rates, and costs associated with OA were significantly increased when compared to PC. Given these findings, future studies are needed to determine appropriate indications for OA. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Trauma Recidivism and Mortality Following Violent Injuries in Young Adults.

BACKGROUND: Trauma recidivism accounts for approximately 44% of emergency department admissions and remains a significant health burden with this patient cohort carrying higher rates of morbidity and mortality. METHODS: A level 1 trauma center registry was queried for patients aged 18-25 y presented between 2009 and 2015. Patients with nonaccidental gunshot wounds, stab wounds, or blunt assault-related injuries were categorized as violent injuries. Primary outcomes included mortality and recidivism, which were defined as patients with two unrelated traumas during the study period. Hospital records and the Social Security Death Index were used to aid in outcomes. RESULTS: A total of 6484 patients presented with 1215 (18.7%) sustaining violent injuries (87.4% male, median age 22.2 y). Mechanism of violent injuries included 64.4% gunshot wound, 21.1% stab, and 14.8% blunt assault. Compared with nonviolent injuries, violent injury patients had increased risk of mortality (9.3% versus 2.1%, P < 0.0001). Out-of-hospital mortality was 2.6% (versus 0.5% nonviolent, P < 0.0005), with an average time to death being 6.4 mo from initial injury. Recidivism was 24.9% with mean time to second violent injury at 31.9 ± 21.0 mo; 14.9% had two trauma readmissions, and 8.0% had ≥3. Ninety percent of subsequent injuries occurred within 5 y, with 19.1% in the first year. CONCLUSIONS: The burden of injury after violent trauma extends past discharge as patients have significantly higher mortality rates following hospital release. Over one-quarter present with a second unrelated trauma or death. Improved medical, psychological, and social collaborative treatment of these high-risk patients is needed to interrupt the cycle of violent injury.

Diagnosis and Management of Parastomal Hernias.

CASE SUMMARY: A 63-year-old woman with history of stage II rectal adenocarcinoma status postneoadjuvant chemoradiation and subsequent abdominoperineal resection presented with worsening bulge and inability to pouch stoma. CT scan revealed a 4-cm parastomal hernia. After discussion with the patient regarding management options, she elected to undergo repair of hernia defect. A robot-assisted laparoscopic parastomal hernia repair with synthetic mesh via the Sugarbaker technique was performed. After a short stay in the hospital, the patient recovered well and reported no recurrent symptoms.

Prophylactic Ureteral Catheters for Colectomy: A National Surgical Quality Improvement Program-Based Analysis.

BACKGROUND: Despite improvement in technique and technology, using prophylactic ureteral catheters to avoid iatrogenic ureteral injury during colectomy remains controversial. OBJECTIVE: The aim of this study was to evaluate outcomes and costs attributable to prophylactic ureteral catheters with colectomy. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: The colectomy-targeted American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2014 was queried. MAIN OUTCOME MEASURES: The primary end point was the rate of 30-day ureteral injury after colectomy. Univariate and multivariate analyses determined factors associated with ureteral injury and urinary tract infection in patients undergoing colectomy. RESULTS: A total of 51,125 patients were identified with a mean age of 60.9 ± 14.9 years and a BMI of 28.4 ± 6.7 k/m; 4.90% (n = 2486) of colectomies were performed with prophylactic catheters, and 333 ureteral injuries (0.65%) were identified. Prophylactic ureteral catheters were most commonly used for diverticular disease (42.2%; n = 1048), with injury occurring most often during colectomy for diverticular disease (36.0%; n = 120). Univariate analysis of outcomes demonstrated higher rates of ileus, wound infection, urinary tract infection, urinary tract infection as reason for readmission, superficial site infection, and 30-day readmission in patients with prophylactic ureteral catheter placement. On multivariate analysis, prophylactic ureteral catheter placement was associated with a lower rate of ureteral injury (OR = 0.45 (95% CI, 0.25-0.81)). LIMITATIONS: This was a retrospective study using a clinical data set. CONCLUSIONS: Here, prophylactic ureteral catheters were used in 4.9% of colectomies and most commonly for diverticulitis. On multivariate analysis, prophylactic catheter placement was associated with a lower rate of ureteral injury. Additional research is needed to delineate patient populations most likely to benefit from prophylactic ureteral stent placement. See Video Abstract at http://links.lww.com/DCR/A482.

Trainee-associated outcomes in laparoscopic colectomy for cancer: propensity score analysis accounting for operative time, procedure complexity and patient comorbidity.

BACKGROUND: Surgical trainee association with operative outcomes is controversial. Studies are conflicting, possibly due to insufficient control of confounding variables such as operative time, case complexity, and heterogeneous patient populations. As operative complications worsen long-term outcomes in oncologic patients, understanding effect of trainee involvement during laparoscopic colectomy for cancer is of utmost importance. Here, we hypothesized that resident involvement was associated with worsened 30-day mortality and 30-day overall morbidity in this patient population. METHODS: Patients undergoing laparoscopic colectomy for oncologic diagnosis from 2005 to 2012 were assessed using the American College of Surgeons National Surgical Quality Improvement Program dataset. Propensity score matching accounted for demographics, comorbidities, case complexity, and operative time. Attending only cases were compared to junior, middle, chief resident, and fellow level cohorts to assess primary outcomes of 30-day mortality and 30-day overall morbidity. RESULTS: A total of 13,211 patients met inclusion criteria, with 4075 (30.8%) cases lacking trainee involvement and 9136 (69.2%) involving a trainee. Following propensity matching, junior (PGY 1-2) and middle level (PGY 3-4) resident involvement was not associated with worsened outcomes. Chief (PGY 5) resident involvement was associated with worsened 30-day overall morbidity (15.5 vs. 18.6%, p = 0.01). Fellow (PGY > 5) involvement was associated with worsened 30-day overall morbidity (16.0 vs. 21.0%, p < 0.001), serious morbidity (9.3 vs. 13.5%, p < 0.001), minor morbidity (9.8 vs. 13.1%, p = 0.002), and surgical site infection (7.9 vs. 10.5%, p = 0.006). No differences were seen in 30-day mortality for any resident level. CONCLUSION: Following propensity-matched analysis of cancer patients undergoing laparoscopic colectomy, chief residents, and fellows were associated with worsened operative outcomes compared to attending along cases, while junior and mid-level resident outcomes were no different. Further study is necessary to determine what effect the PGY surgical trainee level has on post-operative morbidity in cancer patients undergoing laparoscopic colectomy in the context of multiple collinear factors.

Enantioselective Synthesis of ß-Fluoro-ß-aryl-α-aminopentenamides by Organocatalytic [2,3]-Sigmatropic Rearrangement.

The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of ß-fluoro-ß-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the ß-fluoro-ß-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.