Anodic Cyclizations, Densely Functionalized Synthetic Building Blocks, and the Importance of Recent Mechanistic Observations.

Anodic cyclization reactions can provide a versatile method for converting newly obtained chiral lactols to densely functionalized cyclic building blocks. The method works by first converting the lactol into an electron-rich olefin and then oxidatively generating a radical cation that is trapped by a nucleophile. Historically, such reactions have benefited from the use of less polar radical cations when the trapping nucleophile is a heteroatom and more polar radical cations when the reaction forms C-C bonds. This forced one to optimize underperforming reactions by resynthesizing the substrate. Here, we show that by taking advantage of methods that serve to drive a reversible initial cyclization reaction toward the product, this dichotomy and need to manipulate the substrate can be avoided. Two such methods were utilized: a faster second oxidation step and a mediated electrolysis. Both led to successful cyclizations using a polar radical cation and heteroatom nucleophiles.

Heart development in two populations of Atlantic killifish (Fundulus heteroclitus) following exposure to a polycyclic aromatic hydrocarbon mixture.

Historic industrial pollution of the Elizabeth River, Virginia resulted in polycyclic aromatic hydrocarbon (PAH) contamination in sediments. Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood (AW) industrial site adapted to complex PAH mixture at this Superfund site. Their embryos have proved highly resistant to cardiac abnormalities indicative of PAH toxicity. In this study, embryos spawned from adults collected at AW and King's Creek (KC), a reference site, were exposed at 24 h post fertilization (hpf) to Elizabeth River Sediment Extract (ERSE), a complex PAH mixture, in a range of concentrations (0, 5.04, 50.45, 100.90, 151.35, or 252.25 µg/L total PAHs). Embryos were processed for histology at 144 hpf to enable evaluations of hearts at tissue and cellular levels. Morphometry and severity scoring were used to evaluate the extent of alterations. Unexposed embryos were similar in both populations. ERSE exposure resulted in multiple changes to hearts of KC embryos but not AW. Alterations were particularly evident in KC embryos exposed to concentrations above 1% ERSE (50.45 µg/L), which had thinner ventricular walls and larger pericardial edema. Individuals with moderate pericardial edema maintained arrangement and proximity of heart chambers, but changes were seen in ventricular myocytes. Severe pericardial edema was prevalent in exposed KC embryos and typically resulted in tube heart formation. Ventricles of tube hearts had very thin walls composed of small, basophilic cells and lacked trabeculae. Edematous pericardial fluid contained small amounts of proteinaceous material, as did controls, and was free of cells. This fluid was primarily unstained, suggesting water influx due to increased permeability. The use of histological approaches provided more specific detail for tissue and cellular effects in hearts of embryos exposed to PAHs and enabled understanding of potential links to later life effects of early life exposure.

NIHSS 24 h After Mechanical Thrombectomy Predicts 90-Day Functional Outcome.

BACKGROUND: Mechanical thrombectomy (MT) for large vessel occlusion (LVO) ischemic stroke is a safe and effective treatment modality. The National Institute of Health Stroke Scale (NIHSS) 24 h after MT (24 h-NIHSS) was shown to serve as the strongest surrogate for 90-day functional outcome. Here, we seek to externally validate 24 h-NIHSS as predictor for 90-day functional outcome and explore additional variables in this context. METHODS: Patients treated for anterior LVO between February 2016 and August 2020 with premorbid mRS < 3 were included. Receiver operating characteristics were used to compare different NIHSS-related surrogates, such as baseline (B) NIHSS, 24 h-NIHSS, Δ­NIHSS and percent (%) change NIHSS to predict favorable function outcome (mRS 0-2). Additional analysis was performed to assess predictors associated with poor outcome despite reaching the best predictor threshold. RESULTS: A total of 337 eligible cases were identified. The 24 h-NIHSS outperformed B­NIHSS, Δ­NIHSS, and %­NIHSS in terms of 90-day mRS 0-2 prediction. A 24-NIHSS ≤ 8 was identified as the optimal binary threshold. Multivariable analysis demonstrated that 24-NIHSS ≤ 8 and younger patient age were independently associated with mRS 0-2. Despite achieving 24 h-NIHSS ≤ 8, 23/143 (16.1%) cases experienced poor outcome (mRS 4-6). Older age, higher baseline NIHSS, coexisting chronic kidney disease, and longer hospital stay were independent predictors for poor outcome despite achieving 24 h-NIHSS ≤ 8. CONCLUSION: An NIHSS of 8 or less 24 h after MT was validated to serve as an independent, strong surrogate for favorable functional outcome; however, cofactors such as older age, higher baseline NIHSS and coexisting comorbidities appear to mitigate this clinical adjunct.

Mechanical Thrombectomy for Anterior versus Posterior Circulation Large Vessel Occlusion Stroke with Emphasis on Posterior Circulation Outcomes.

PURPOSE: Although there is class I evidence for mechanical thrombectomy (MT) for anterior circulation large vessel occlusion (LVO) stroke, no high-class evidence exists for the posterior circulation. Here, we sought to compare clinical features of anterior versus posterior LVO as well as predictors of a posterior LVO MT outcome. METHODS: Patients with acute ischemic stroke who underwent MT for anterior and posterior LVO stroke between February 2016 and August 2020 from 2 comprehensive stroke centers were reviewed. Anterior and posterior LVO strokes were compared. In addition, predictors for a favorable outcome (modified Rankin scale [mRS] 0-3), death (mRS 6), and futile revascularization (mRS 4-6 despite TICI 2b/3 revascularization) for posterior LVO were analyzed. RESULTS: Collectively, 813 LVO thrombectomy cases were analyzed, and 77 of 813 cases (9.5%) were located in the posterior circulation. Although favorable 90-day functional outcome rates did not differ between anterior and posterior LVO (P = 0.093), death was significantly more frequent among posterior LVO cases (P = 0.013). In the posterior LVO subgroup, a primary aspiration technique and successful revascularization TICI 2b/3 irrespective of time to the intervention were independently associated with achieving a favorable outcome. Primary aspiration was identified to inversely associate with futile revascularization. CONCLUSION: Anterior and posterior circulation MT patients have distinct clinical profiles. The use of primary aspiration appears fundamental for beneficial outcomes in posterior circulation MT.

Outcome Following Mechanical Thrombectomy for Anterior Circulation Large Vessel Occlusion Stroke in the Elderly.

BACKGROUND: Pooled data of randomized controlled trials investigating mechanical thrombectomy (MT) to treat anterior circulation large vessel occlusion have demonstrated safety and effectiveness across all age groups, including ≥ 80 years of age; however, only a few nonagenarians were in the ≥ 80 years subgroup. Therefore, the benefit of MT in nonagenarians is mostly unknown. METHODS: Two comprehensive stroke centers retrospectively reviewed all acute ischemic stroke patients who underwent MT for anterior circulation large vessel occlusion (LVO) stroke between February 2016 and August 2020. Revascularization TICI2b/3, symptomatic intracranial hemorrhage (ICH), and functional outcome using modified Rankin scale (mRS) were assessed for cases aged < 80 years, 80-89 years, and 90-99 years. Favorable functional outcome was defined as mRS 0-2 or reaching the prestroke mRS and moderate as mRS 0-3. RESULTS: The final data set comprised a total of 736 cases. Of these, 466 aged < 80 years, 219 aged 80-89 years, and 51 aged 90-99 years. In nonagenarians, TICI 2b/3 revascularization was observed in 84.3% while symptomatic ICH was observed in 4%. These rates were similar to 80-89 years and < 80 years age groups. Favorable and moderate functional outcome as well as death rates differed significantly between nonagenarians and < 80 years (19.6%, 29.4%, 51.0% vs 47.9%, 60.7%, 18.7%, respectively, p < 0.001), but were similar between nonagenarians and octogenarians (29.7%, 38.8%, 38.8%, p = 0.112-0.211). CONCLUSION: A moderate outcome among nonagenarians was observed in about 30%, while mortality rates were about 50%. Withholding mechanical thrombectomy does not appear justifiable, although the absolute treatment effect among nonagenarians remains unknown.

A new technique of direct intra-abdominal pressure measurement: a preliminary study.

OBJECTIVE: The purpose of this study was to determine if a 14-F polyvinyl chloride (PVC) round drain is a reliable tool for direct intra-abdominal pressure measurement. DESIGN: A prospective interventional study. SETTING: Department of Surgery B, intensive care unit, recovery room, Hillel-Yaffe level II trauma center. METHODS: Forty patients undergoing abdominal surgery and treated postoperatively with intraperitoneal drains and intravesical catheters were included in this study. The indication for insertion of intraperitoneal drains and intravesical catheters was strictly medical. The decision of placing urinary bladder catheter and PVC round drain was done by a senior surgeon. Intra-abdominal pressures were measured simultaneously through the intraperitoneal drain and the urinary catheter. Using a sterile technique, the intraperitoneal drain was disconnected from the drainage bulb and connected to an invasive blood pressure monitoring system. Intravesical pressures were measured by inserting 50 mL into the bladder, and then the urinary catheter was connected to an invasive blood monitoring system. Measurements were done twice a day for 3 days or less if earlier removal of either the intraperitoneal drain or urinary catheters were medically indicated. RESULTS: Two hundred twenty-even simultaneous measurements were performed. Pressures as measured through the intraperitoneal drain were found to be significantly correlated to pressures as measured intravesically (r = 0.962). CONCLUSIONS: Direct measurement of the intra-abdominal pressure via a 14-F PVC round drain is a newly described technique. Our method is simple, safe, and credible. Future investigation is needed to confirm the reliability of this method for continuous postoperative measurement of the intra-abdominal pressure in selected patients.

New technique of direct intra-abdominal pressure measurement.

OBJECTIVE: To determine the efficacy of 14-Fr PVC round drain in the direct measurement of intra-abdominal pressure. METHODS: Fifty consecutive patients undergoing elective laparoscopic surgery in a tertiary teaching hospital were included in this pilot study. Patients underwent laparoscopic cholecystectomy, appendectomy, splenectomy, colectomy and Nissen fundoplication. After creation of pneumoperitoneum and insertion of the trocars as indicated by the operation, a 14-Fr PVC round drain was inserted into the abdominal cavity via one of the laparoscopic ports. It was then connected under sterile conditions to the invasive blood pressure measurement system. Intra-abdominal pressure was gradually increased. Intra-abdominal pressures as measured through the round PVC drain were compared to those measured by the laparoscopic insufflator at 5, 8, 12 and 24 mmHg. RESULTS: Two hundred measurements using each of the two methods were performed and correlated. The correlation coefficient was 0.996. No complications were observed with this new technique. CONCLUSION: Direct measurement of intra-abdominal pressure using 14-Fr PVC round drain is a newly described technique that is simple, fast and credible. Future investigation will be needed to confirm the reliability of this method during postoperative follow-up of intra-abdominal pressures in selected patients.

Mesh wrap in severe pediatric liver trauma.

PURPOSE: This study reviews the authors' experience in treating severe pediatric liver injuries with absorbable mesh wrapping. The authors found this relatively new therapeutic method very useful in selected cases, although its use is not very common in children. The authors analyze the indication describe some technical aspects, and discuss the advantages and the pitfalls of the method. METHODS: In a 10-year period between 1990 and 2000, 181 children were admitted to Hillel-Yaffe Medical Center with blunt hepatic trauma. A total of 132 children were treated conservatively, and 49 (27%) were operated on. The operated group included 35 cases of isolated liver injuries and 14 cases of additional intraabdominal injuries. Thirty-four children were operated on between 1990 and 1995 (36% of 96 children), whereas between 1995 and 2000, 15 children were operated on (17% of 85 children), including 4 children aged 18 months to 15 years with massive liver bleeding who were treated with mesh wrap technique. The retrospective analysis of these 4 cases indicates a progressive policy in the recognition of cases suitable for mesh wrapping and gallbladder conservation. RESULTS: The perihepatic mesh wrap technique controlled the bleeding in all children. In 3 of them the right lobe was wrapped, and, in 1 case, total liver wrapping was performed. Hepatic enzymes and bilirubin levels were elevated in the first 3 to 7 days and declined gradually to normal levels. The perihepatic mesh was not an obstacle to a transcutaneous drainage of an intrahepatic biloma. All 4 children returned to normal physical activities. CONCLUSIONS: Liver mesh wrap is a simple, effective, and rapid way to obtain hemostasis and to conserve parenchyma in severe traumatized liver. The decision to wrap the liver should be done early to prevent acidosis and hypothermia. Cholecystectomy is not an integral part of the procedure in children. The morbidity is low, and most of the complications can be treated nonsurgically.