A General Concept for the Electronic and Steric Modification of 1-Metallacyclobuta-2,3-dienes: A Case Study of Group 4 Metallocene Complexes.

The synthesis of group 4 metal 1-metallacyclobuta-2,3-dienes as organometallic analogues of elusive 1,2-cyclobutadiene has so far been limited to SiMe3 substituted examples. We present the synthesis of two Ph substituted dilithiated ligand precursors for the preparation of four new 1-metallacyclobuta-2,3-dienes [rac-(ebthi)M] (M=Ti, Zr; ebthi=1,2-ethylene-1,10-bis(η5-tetrahydroindenyl)). The organolithium compounds [Li2(RC3Ph)] (1 b: R=Ph, 1 c: R=SiMe3) as well as the metallacycles of the general formula [rac-(ebthi)M(R1C3R2)] (2 b: M=Ti, R1=R2=Ph, 2 c: M=Ti, R1=Ph, R2=SiMe3; 3 b: M=Zr, R1=R2=Ph; 3 c: M=Zr, R1=Ph, R2=SiMe3) were fully characterised. Single crystal X-ray diffraction and quantum chemical bond analysis of the Ti and Zr complexes reveal ligand influence on the biradicaloid character of the titanocene complexes. X-band EPR spectroscopy of structurally similar Ti complexes [rac-(ebthi)Ti(Me3SiC3SiMe3)] (2 a), 2 b, and 2 c was carried out to evaluate the accessibility of an EPR active triplet state. Cyclic voltammetry shows that introduction of Ph groups renders the complexes easier to reduce. 13C CPMAS NMR analysis provides insights into the cause of the low field shift of the resonances of metal-bonded carbon atoms and provides evidence of the absence of the ß-C-Ti interaction.

C-H Bond Arylation of Pyrazoles at the ß-Position: General Conditions and Computational Elucidation for a High Regioselectivity.

Direct arylation of most five-membered ring heterocycles are generally easily accessible and strongly favored at the α-position using classical palladium-catalysis. Conversely, regioselective functionalization of such heterocycles at the concurrent ß-position remains currently very challenging. Herein, we report general conditions for regioselective direct arylation at the ß-position of pyrazoles, while C-H α-position is free. By using aryl bromides as the aryl source and a judicious choice of solvent, the arylation reaction of variously N-substituted pyrazoles simply proceeds via ß-C-H bond functionalization. The ß-regioselectivity is promoted by a ligand-free palladium catalyst and a simple base without oxidant or further additive, and tolerates a variety of substituents on the bromoarene. DFT calculations revealed that a protic solvent such as 2-ethoxyethan-1-ol significantly enhances the acidity of the proton at ß-position of the pyrazoles and thus favors this direct ß-C-H bond arylation. This selective pyrazoles ß-C-H bond arylation was successfully applied for the straightforward building of π-extended poly(hetero)aromatic structures via further Pd-catalyzed combined α-C-H intermolecular and intramolecular C-H bond arylation in an overall highly atom-economical process.

Effective Tools for the Metal-Catalyzed Regiodivergent Direct Arylations of (Hetero)arenes.

The direct functionalization of two different C-H bonds of the same organic molecule using different procedures - also called regiodivergent C-H bond functionalization - currently represents an important research topic in organic chemistry, as it demonstrates the versatility of C-H bond functionalization methodology. Over the last decade, the number of tools to control such regiodivergent C-H bond functionalizations has increased significantly. In this account, we will present the various tools that allowed us to arylate different positions of various (hetero)arenes, via a C-H bond functionalization, using palladium or ruthenium catalysis.

Factors that predict 30-day readmission after bariatric surgery: experience of a publicly funded Canadian centre.

Background: Hospital readmissions after bariatric surgery can significantly increase health care costs. Rates of readmission after bariatric surgery have ranged from 0.6% to 11.3%, but the rate of complications and the factors that predict readmission have not been well characterized in Canada. The objective of this study was to characterize readmission rates and the factors that predict 30-day readmission in a Canadian centre. Methods: A retrospective study was performed on all patients who underwent bariatric surgery between 2010 and 2015 in a single Canadian centre. Procedures included laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB). Prospectively collected data were extracted from an administrative database. Multivariable logistic regression analysis was performed to determine which factors predict 30-day readmission. Results: A total of 1468 patients had bariatric surgery (51.0% LRYGB, 40.5% LSG, 8.6% LAGB) during the 6-year study period, with an overall 30-day readmission rate of 7.5%. LRYGB was associated with a higher readmission rate (11.4%) than LSG (3.7%) or LAGB (1.6%). Common reasons for readmission were infection (24.8%), pain (17.4%) and nausea or vomiting (10.1%). Multivariable analysis identified 3 factors that independently predicted readmission: length of stay greater than 4 days (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.03-4.63, p = 0.042), LRYGB (OR 5.21, 95% CI 1.19-22.73, p = 0.028) and acute renal failure (OR 14.10, 95% CI 1.07-186.29, p = 0.045). Conclusion: Readmissions after bariatric surgery were most commonly caused by potentially preventable factors, such as pain, nausea or vomiting. Strategies to identify and address factors associated with readmission may reduce readmissions and health care costs after bariatric surgery in a publicly funded health care system.

Contexte: Les réadmissions hospitalières après la chirurgie bariatrique peuvent accroître significativement le coût des soins de santé. Les taux de ces réadmissions ont varié de 0,6 % à 11,3 %, mais le taux de complications et les facteurs de prédiction des réadmissions n'ont pas été bien caractérisés au Canada. L'objectif de cette étude est de caractériser les taux de réadmissions et les facteurs qui permettent de prédire une réadmission à 30 jours dans un centre canadien. Méthodes: Nous avons étudié rétrospectivement tous les cas de chirurgie bariatrique effectués entre 2010 et 2015 dans un établissement canadien. Les interventions incluaient la dérivation gastrique Roux-en-Y laparoscopique (DGRYL), la gastrectomie en manchon laparoscopique (GML) et la gastroplastie laparoscopique avec anneau ajustable (GLAA). Les données recueillies de manière prospective ont été extraites d'une base de données administrative. Nous avons procédé à une analyse de régression logistique multivariée pour déterminer quels facteurs permettaient de prédire la réadmission à 30 jours. Résultats: En tout, 1468 patients ont subi une chirurgie bariatrique (51,0 % DGRYL, 40,5 % GML et 8,6 % GLAA) durant les 6 années de l'étude, avec un taux global de réadmission à 30 jours de 7,5 %. La DGRYL a été associée un taux de réadmission plus élevé (11,4 %) que la GML (3,7 %) ou la GLAA (1,6 %). Les raisons de réadmission les plus fréquentes ont été infection (24,8 %), douleur (17,4 %) et nausées ou vomissements (10,1 %). L'analyse multivariée a permis de dégager 3 facteurs indépendants de réadmission, soit séjour de plus de 4 jours (rapport des cotes [RR] 2,18, intervalle de confiance [IC] de 95 % 1,03­4,63, p = 0,042), DGRYL (RC 5,21, IC de 95 % 1,19­22,73, p = 0,028) et insuffisance rénale aiguë (RC 14,10, IC de 95 % 1,07­186,29, p = 0,045). Conclusion: Les réadmissions après la chirurgie bariatrique ont le plus souvent été dues à des facteurs évitables, tels que douleur, nausées et vomissements. Des stratégies visant à identifier et à corriger les facteurs de réadmission pourraient réduire ces dernières et le coût des soins de santé après la chirurgie bariatrique dans un système de santé public.

Idiopathic intracranial hypertension and bariatric surgery: a systematic review

Background: Idiopathic intracranial hypertension (IIH) is a rare condition typically affecting women with obesity who are of child-bearing age. Patients commonly present with headaches, visual disturbances, pulsatile tinnitus and papilledema. The association between IIH and obesity has been well established in the literature, suggesting that weight loss may contribute to improving IIH. For patients with severe obesity for whom conservative management is not successful, bariatric surgery is an effective modality for weight loss. We aimed to systematically review the literature to determine the efficacy of bariatric surgery in the treatment of IIH Methods: We conducted a comprehensive search of MEDLINE, Embase, Scopus, the Cochrane Library and Web of Science (limited to studies in humans published in English between January 1946 and July 2015). Results: Twelve primary studies (n = 39 patients) were included in the systematic review. All patients had a preoperative diagnosis of IIH. Preoperative body mass index (BMI) was 47.4 ± 3.6 kg/m2 ; BMI improved to 33.7 ± 2.1 kg/m2 and 33.9 ± 11.6 kg/m2 at 6 and 12 months postoperatively, respectively. Lumbar puncture opening pressures decreased from 34.4 ± 6.9 cmH2O to 14.0 ± 3.6 cmH2O after surgery. Common symptoms of IIH improved after bariatric surgery: headaches (100% preoperatively v. 10% postoperatively), visual complaints (62% v. 44%), tinnitus (56% v. 3%) and papilledema (62% v. 8%). Conclusion: Bariatric surgery appears to lead to considerable improvement in IIH. Idiopathic intracranial hypertension is not a well-publicized comorbidity of obesity, but its presence may be considered as an indication for bariatric surgery.

Contexte: L'hypertension intracrânienne (HTIC) idiopathique est une affection rare qui touche surtout les femmes atteintes d'obésité en âge de procréer. Les symptômes courants sont des maux de tête, des troubles de la vue, des acouphènes pulsatiles et un oedème papillaire. Le lien entre l'HTIC idiopathique et l'obésité est bien établi dans la littérature, ce qui suggère que la perte de poids pourrait améliorer le tableau clinique de l'HTIC. Pour les patients atteints d'obésité sévère pour lesquels le traitement conservateur ne fonctionne pas, la chirurgie bariatrique est un moyen efficace de perdre du poids. Cette revue systématique de la littérature vise à déterminer l'efficacité de la chirurgie bariatrique dans le traitement de l'HTIC idiopathique. Méthodes: Nous avons interrogé MEDLINE, Embase, Scopus, la Bibliothèque Cochrane et Web of Science (limites : études portant sur les humains publiées en anglais entre janvier 1946 et juillet 2015). Résultats: Douze études primaires (n = 39 patients) ont été incluses dans la revue systématique. Tous les patients avaient un diagnostic préopératoire d'HTIC idiopathique. L'indice de masse corporelle (IMC) préopératoire était de 47,4 ± 3,6 kg/m2 ; l'IMC est passé à 33,7 ± 2,1 kg/m2 6 mois après l'opération, puis à 33,9 ± 11,6 kg/m2 12 mois après l'opération. Les pressions d'ouverture des ponctions lombaires sont passées de 34,4 ± 6,9 cmH2O à 14,0 ± 3,6 cmH2O après l'opération. Les symptômes courants de l'HTIC idiopathique se sont améliorés après la chirurgie bariatrique : maux de tête (100% avant opération c. 10% après), troubles de la vue (62% c. 44%), acouphènes pulsatiles (56% c. 3%) et œdème papillaire (62% c. 8%). Conclusion: La chirurgie bariatrique semble améliorer considérablement les symptômes d'HTIC idiopathique. Cette affection n'est pas une comorbidité bien connue de l'obésité, mais sa présence peut être une indication pour la chirurgie bariatrique comme traitement.

Pd/C as Heterogeneous Catalyst for the Direct Arylation of (Poly)fluorobenzenes.

The potential of the heterogeneous catalyst 10 % Pd/C in the direct arylation of (poly)fluorobenzene derivatives with aryl bromides has been investigated. In general, high yields of biaryl derivatives were obtained by using tri-, tetra-, and pentafluorobenzenes, whereas mono- and difluorobenzenes exhibited poor reactivity. The regioselectivities of the arylation reactions were similar to those observed with homogeneous palladium catalysts. Both electron-withdrawing and -donating substituents, such as nitrile, nitro, acetyl, ester, trifluoromethyl, tert-butyl, methoxy, or methyl, on the aryl bromide were tolerated. Unexpectedly, tetrafluoro-substituted [1,1'-biphenyl]-4-ols were obtained from pentafluorobenzene at 150 °C due to a formal regioselective hydroxylation, whereas at lower temperatures the expected pentafluorobiphenyls were obtained. However, no C-F bond cleavage was observed with the other polyfluorobenzene derivatives. These arylation reactions were carried out with only 1 mol % Pd/C as the catalyst and KOAc as an inexpensive base. Therefore, this protocol represents a very attractive access to (poly)fluoro-substituted biphenyls in terms of cost, simplicity, and sustainable chemistry because the Pd/C catalyst can be easily removed at the end of the reaction, there is no contamination with phosphine ligand residues, and the major side-product of the reaction is KOAc⋅HBr.

Late-Stage Diversification of Imidazole-Based Pharmaceuticals through Pd-Catalyzed Regioselective C-H Bond Arylations.

Palladium-catalyzed C-H bond arylation of imidazoles has been applied to pharmaceuticals such as Bifonazole, Climbazole, and Prochloraz. In the presence of phosphine-free Pd(OAc)2 catalyst, aryl bromides are efficiently coupled at the C5-position of the imidazole units, which are widely decorated. Under these conditions, only C-H bond arylation reaction occurred without affecting the integrity of chemical structure of the imidazole-based pharmaceuticals. Moreover, with Bifonazole Pd-catalyzed C-H bond diarylation at the C2- and C5-positions of imidazole unit has also been performed.

Predictive factors for diabetes remission after bariatric surgery

Background: Bariatric surgery has been shown to induce type 2 diabetes mellitus (T2DM) remission in severely obese patients. After laparoscopic Roux-en-Y gastric bypass (LRYGB), diabetes remission occurs early and independently of weight loss. Previous research has identified preoperative factors for remission, such as duration of diabetes and HbA1c. Understanding factors that predict diabetes remission can help to select patients who will benefit most from bariatric surgery. Methods: We retrospectively reviewed all T2DM patients who underwent laparoscopic sleeve gastrectomy (LSG) or LRYGB between January 2008 and July 2014. The primary outcome was diabetes remission, defined as the absence of hypoglycemic medications, fasting blood glucose < 7.0 mmol/L and HbA1c < 6.5%. Data were analyzed using multivariable logistic regression analysis to identify predictive factors of diabetes remission. Results: We included 207 patients in this analysis; 84 (40.6%) had LSG and 123 (59.4%) had LRYGB. Half of the patients (49.8%) achieved diabetes remission at 1 year. Multivariable logistic analysis showed that LRYGB had higher odds of diabetes remission than LSG (odds ratio [OR] 6.58, 95% confidence interval [CI] 2.79­15.50, p < 0.001). Shorter duration of diabetes (OR 0.91, 95% CI 0.83­0.99, p = 0.032) and the absence of long-acting insulin (OR 0.0011, 95% CI < 0.000­0.236, p = 0.013) predicted remission. Conclusion: Type of bariatric procedure (LRYGB v. LSG), shorter duration of diabetes and the absence of long-acting insulin were independent predictors of diabetes remission after bariatric surgery.

Contexte: Il a été démontré que la chirurgie bariatrique provoque une rémission du diabète de type 2 chez les patients gravement obèses. Après la dérivation gastrique Roux-en-Y (DGRY) par laparoscopie, la rémission du diabète se produit tôt et indépendamment de la perte de poids. Des recherches antérieures ont identifié des facteurs préopératoires de rémission, notamment la durée du diabète et l'HbA1c. Comprendre les facteurs prédictifs de la rémission du diabète peut aider à sélectionner les patients qui bénéficieront le plus de la chirurgie bariatrique. Méthodes: Nous avons examiné rétrospectivement les dossiers de tous les patients atteints de diabète de type 2 qui ont subi par laparoscopie une gastrectomie en manchon (GM) ou une DGRY entre janvier 2008 et juillet 2014. Le principal résultat a été la rémission du diabète, définie comme l'absence de médicaments hypoglycémiques, la glycémie à jeun < 7,0 mmol/L et l'HbA1c < 6,5 %. Les données ont été soumises à une analyse de régression logistique multiple pour déterminer les facteurs prédictifs de la rémission du diabète. Résultats: Nous avons inclus 207 patients dans cette analyse; 84 (40,6 %) ont subi une GM et 123 (59,4 %), une DGRY. La moitié des patients (49,8 %) ont obtenu une rémission du diabète à 1 an. L'analyse logistique multiple a montré que la DGRY s'accompagnait de probabilités plus élevées de rémission du diabète que la GM (rapport de cotes [RC] 6,58; intervalle de confiance [IC] de 95 %, 2,79­15,50, p < 0,001). La durée plus courte du diabète (RC 0,91; IC de 95 %, 0,83­0,99, p = 0,032) et absence d'insuline à action prolongée (RC 0,0011; IC de 95 % < 0,000­0,236, p = 0,013) étaient prédicteurs de rémission. Conclusion: Le type d'intervention bariatrique (DGRY c. MG), la durée plus courte du diabète et l'absence d'insuline à action prolongée étaient des prédicteurs indépendants de la rémission du diabète après une chirurgie bariatrique.

Reactivity of 1,2,3- and 1,2,4-Trifluorobenzenes in Palladium-Catalyzed Direct Arylation.

The higher reactivity of the C4-H bond as compared to the C5-H bond of 1,2,3-trifluorobenzene in palladium-catalyzed direct arylation allows the selective synthesis of 4-aryl-1,2,3-trifluorobenzenes in moderate to high yields. In most cases, phosphine-free Pd(OAc)2 catalyst and inexpensive KOAc base were employed. Then, from these 4-aryl-1,2,3-trifluorobenzenes, the palladium-catalyzed C-H bond functionalization of the C6-position allows the synthesis of the corresponding 4,6-diarylated 1,2,3-trifluorobenzenes. We also applied these reaction conditions to the regioselective direct C3-arylation of 1,2,4-trifluorobenzene.

Halo-substituted benzenesulfonyls and benzenesulfinates: convenient sources of arenes in metal-catalyzed C-C bond formation reactions for the straightforward access to halo-substituted arenes.

Palladium-catalyzed reactions using aryl halides as one of the coupling partners represent a very popular method for generating carbon-carbon bonds. However, such couplings suffer from important limitations. As most palladium catalysts are very effective for the cleavage of C-halo bonds (Halo = Cl, Br or I), in many cases, the presence of several halide functional groups on arenes is not tolerated. Since two decades, and especially during the last few years, a new class of coupling partners, benzenesulfonyl and benzenesulfinate derivatives, has emerged as a powerful alternative to aryl halides for the Pd-catalyzed C-C bond formation, as the reactions performed with these substrates generally tolerate C-halo bonds. With these substrates, after a metal-catalyzed desulfitative coupling, a variety of halo-substituted arenes such as biaryls, styrenes, phenylacetylenes, acetophenones, benzonitriles… has been synthesized with high chemoselectivities. The use of these aryl sources allowed the synthesis of molecules containing several halo-substituents including iodo-substituents in only a few steps and provides very simple access to a very wide variety of halo-substituted arenes useful to materials chemists and also to biochemists. In this review, we will summarize the scope of the use of halo-substituted benzenesulfonyls and benzenesulfinates as coupling partners in metal-catalyzed C-C bond formation.

Diagnostic evaluation of sentinel lymph node biopsy using indocyanine green and infrared or fluorescent imaging in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Sentinel node navigation surgery (SNNS) for gastric cancer using infrared visualization of indocyanine green (ICG) is intriguing because it may limit operative morbidity. We are the first to systematically review and perform meta-analysis on the diagnostic utility of ICG and infrared electronic endoscopy (IREE) or near infrared fluorescent imaging (NIFI) for SNNS exclusively in gastric cancer. METHODS: A search of electronic databases MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library using search terms "gastric/stomach" AND "tumor/carcinoma/cancer/neoplasm/adenocarcinoma/malignancy" AND "indocyanine green" was completed in May 2017. Articles were selected by two independent reviewers based on the following major inclusion criteria: (1) diagnostic accuracy study design; (2) indocyanine green was injected at tumor site; (3) IREE or NIFI was used for intraoperative visualization. 327 titles or abstracts were screened. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Ten full text studies were selected. 643 patients were identified with the majority of patients possessing T1 tumors (79.8%). Pooled identification rate, diagnostic odds ratio, sensitivity, and specificity were 0.99 (0.97-1.0), 380.0 (68.71-2101), 0.87 (0.80-0.93), and 1.00 (0.99-1.00), respectively. The summary receiver operator characteristic for ICG + IREE/NIFI demonstrated a test accuracy of 98.3%. Subgroup analysis found improved test performance for studies with low-risk QUADAS-2 scores, studies published after 2010 and submucosal ICG injection. IREE had improved diagnostic odds ratio, sensitivity, and identification rate compared to NIFI. Heterogeneity among studies ranged from low (I2 < 25%) to high (I2 > 75%). CONCLUSIONS: We found encouraging results regarding the accuracy, diagnostic odds ratio, and specificity of the test. The sensitivity was not optimal but may be improved by a strict protocol to augment the technique. Given the number and heterogeneity of studies, our results must be viewed with caution.

Comprehensive geriatric assessment for older people admitted to a surgical service.

BACKGROUND: Aging populations are at increased risk of postoperative complications. New methods to provide care for older people recovering from surgery may reduce surgery-related complications. Comprehensive geriatric assessment (CGA) has been shown to improve some outcomes for medical patients, such as enabling them to continue living at home, and has been proposed to have positive impacts for surgical patients. CGA is a coordinated, multidisciplinary collaboration that assesses the medical, psychosocial and functional capabilities and limitations of an older person, with the goal of establishing a treatment plan and long-term follow-up. OBJECTIVES: To assess the effectiveness of CGA interventions compared to standard care on the postoperative outcomes of older people admitted to hospital for surgical care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two clinical trials registers on 13 January 2017. We also searched grey literature for additional citations. SELECTION CRITERIA: Randomized trials of people undergoing surgery aged 65 years and over comparing CGA with usual surgical care and reporting any of our primary (mortality and discharge to an increased level of care) or secondary (length of stay, re-admission, total cost and postoperative complication) outcomes. We excluded studies if the participants did not receive a complete CGA, did not undergo surgery, and if the study recruited participants aged less than 65 years or from a setting other than an acute care hospital. DATA COLLECTION AND ANALYSIS: Two review authors independently screened, assessed risk of bias, extracted data and assessed certainty of evidence from identified articles. We expressed dichotomous treatment effects as risk ratio (RR) with 95% confidence intervals and continuous outcomes as mean difference (MD). MAIN RESULTS: We included eight randomised trials, seven recruited people recovering from a hip fracture (N = 1583) and one elective surgical oncology trial (N = 260), conducted in North America and Europe. For two trials CGA was done pre-operatively and postoperatively for the remaining. Six trials had adequate randomization, five had low risk of performance bias and four had low risk of detection bias. Blinding of participants was not possible. All eight trials had low attrition rates and seven reported all expected outcomes.CGA probably reduces mortality in older people with hip fracture (RR 0.85, 95% CI 0.68 to 1.05; 5 trials, 1316 participants, I² = 0%; moderate-certainty evidence). The intervention reduces discharge to an increased level of care (RR 0.71, 95% CI 0.55 to 0.92; 5 trials, 941 participants, I² = 0%; high-certainty evidence).Length of stay was highly heterogeneous, with mean difference between participants allocated to the intervention and the control groups ranging between -12.8 and 8.3 days. CGA probably leads to slightly reduced length of stay (4 trials, 841 participants, moderate-certainty evidence). The intervention probably makes little or no difference in re-admission rates (RR 1.00, 95% CI 0.76 to 1.32; 3 trials, 741 participants, I² = 37%; moderate-certainty evidence).CGA probably slightly reduces total cost (1 trial, 397 participants, moderate-certainty evidence). The intervention may make little or no difference for major postoperative complications (2 trials, 579 participants, low-certainty evidence) and delirium rates (RR 0.75, 95% CI 0.60 to 0.94, 3 trials, 705 participants, I² = 0%; low-certainty evidence). AUTHORS' CONCLUSIONS: There is evidence that CGA can improve outcomes in people with hip fracture. There are not enough studies to determine when CGA is most effective in relation to surgical intervention or if CGA is effective in surgical patients presenting with conditions other than hip fracture.

Synthesis of Phenanthrothiazoles and 1,2-Di(heteroaryl)benzenes through Successive Pd-Catalyzed Direct Arylations.

Palladium-catalyzed direct arylation of 4-(2-bromophenyl)-2-methylthiazole proceeds with high efficiency at the thiazolyl C5 position using aryl bromides as the aryl source. This transformation provides simple access to 4-(2-bromophenyl)-2-methyl-5-arylthiazoles, which can be further converted into phenanthrothiazoles via palladium-catalyzed intramolecular direct arylation. When the direct arylation of 4-(2-bromophenyl)-2-methyl-5-arylthiazoles is conducted in the presence of an external heteroarene such as thiazoles, thiophenes, or imidazo[1,2-a]pyridines, the intermolecular arylation of such external heteroarenes proceeds faster than the intramolecular reaction, allowing the formation of 1,2-di(heteroaryl)benzene derivatives.

LINX® magnetic esophageal sphincter augmentation versus Nissen fundoplication for gastroesophageal reflux disease: a systematic review and meta-analysis.

BACKGROUND: The LINX® magnetic sphincter augmentation system (MSA) is a surgical technique with short-term evidence demonstrating efficacy in the treatment of medically refractory or chronic gastroesophageal reflux disease (GERD). Currently, the Nissen fundoplication is the gold-standard surgical treatment for GERD. We are the first to systematically review the literature and perform a meta-analysis comparing MSA to the Nissen fundoplication. METHODS: A comprehensive search of electronic databases (e.g., MEDLINE, EMBASE, SCOPUS, Web of Science and the Cochrane Library) using search terms "Gastroesophageal reflux or heartburn" and "LINX or endoluminal or magnetic" and "fundoplication or Nissen" was completed. All randomized controlled trials, non-randomized comparison study and case series with greater than 5 patients were included. Five hundred and forty-seven titles were identified through primary search, and 197 titles or abstracts were screened after removing duplicates. Meta-analysis was performed on postoperative quality of life outcomes, procedural efficacy and patient procedural satisfaction. RESULTS: Three primary studies identified a total of 688 patients, of whom 273 and 415 underwent Nissen fundoplication and MSA, respectively. MSA was statistically superior to LNF in preserving patient's ability to belch (95.2 vs 65.9%, p < 0.00001) and ability to emesis (93.5 vs 49.5%, p < 0.0001). There was no statistically significant difference between MSA and LNF in gas/bloating (26.7 vs 53.4%, p = 0.06), postoperative dysphagia (33.9 vs 47.1%, p = 0.43) and proton pump inhibitor (PPI) elimination (81.4 vs 81.5%, p = 0.68). CONCLUSION: Magnetic sphincter augmentation appears to be an effective treatment for GERD with short-term outcomes comparable to the more technically challenging and time-consuming Nissen fundoplication. Long-term comparative outcome data past 1 year are needed in order to further understand the efficacy of magnetic sphincter augmentation.

Quality of Follow-up: Systematic Review of the Research in Bariatric Surgery.

OBJECTIVE: We aim to systematically review the bariatric surgery literature with regards to adequacy of patient follow-up, meeting the McMaster criteria of ≥80% follow-up. BACKGROUND: Loss to follow-up is a major concern and can potentially bias the outcome and interpretation of a study. The quality of follow-up in bariatric surgery is quite variable with recent systematic reviews criticizing the field for its lack of overall follow-up. METHODS: A complete search of PubMed was performed. Literature was restricted to a range of 5 years (2007-2012), English language, and publications listed in PubMed. The McMaster Evidence-based Criteria for High Quality Studies was used to assess the follow-up data adequacy and a logistic meta-regression was performed to identify factors associated with high quality follow-up studies. RESULTS: Ninety-nine published manuscripts were included. For follow-up at study end, only 40/99 (40.4%) of papers had adequate patient follow-up, 42/99 (42.4%) failed to meet the McMaster criteria and 17/99 (17.2%) failed to report any follow-up results. On average, 31% were lost to follow-up at the study's end. Only shorter study duration, and if the study was performed in the US, were associated with studies meeting the McMaster criteria. CONCLUSIONS: Only 40% of studies in the bariatric surgery literature meet criteria for adequate follow-up. On average, studies have 30% of patients lost to follow-up at the stated end-point. Identified study characteristics associated with high quality follow-up included shorter study duration and studies performed in the US.

Heated insufflation with or without humidification for laparoscopic abdominal surgery.

BACKGROUND: Intraoperative hypothermia during both open and laparoscopic abdominal surgery may be associated with adverse events. For laparoscopic abdominal surgery, the use of heated insufflation systems for establishing pneumoperitoneum has been described to prevent hypothermia. Humidification of the insufflated gas is also possible. Past studies on heated insufflation have shown inconclusive results with regards to maintenance of core temperature and reduction of postoperative pain and recovery times. OBJECTIVES: To determine the effect of heated gas insufflation compared to cold gas insufflation on maintaining intraoperative normothermia as well as patient outcomes following laparoscopic abdominal surgery. SEARCH METHODS: We searched Cochrane Colorectal Cancer Specialised Register (September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 8), Ovid MEDLINE (1950 to September 2016), Ovid Embase (1974 to September 2016), International Pharmaceutical Abstracts (IPA) (September 2016), Web of Science (1985 to September 2016), Scopus, www.clinicaltrials.gov and the National Research Register (1956 to September 2016). We also searched grey literature and cross references. Searches were limited to human studies without language restriction. SELECTION CRITERIA: Only randomised controlled trials comparing heated (with or without humidification) with cold gas insufflation in adult and paediatric populations undergoing laparoscopic abdominal procedures were included. We assessed study quality in regards to relevance, design, sequence generation, allocation concealment, blinding, possibility of incomplete data and selective reporting. Two review authors independently selected studies for the review, with any disagreement resolved in consensus with a third co-author. DATA COLLECTION AND ANALYSIS: Two review authors independently performed screening of eligible studies, data extraction and methodological quality assessment of the trials. We classified a study as low-risk of bias if all of the first six main criteria indicated in the 'Risk of Bias Assessment' table were assessed as low risk. We used data sheets to collect data from eligible studies. We presented results using mean differences for continuous outcomes and relative risks for dichotomous outcomes, with 95% confidence intervals. We used Review Manager (RevMan) 5.3 software to calculate the estimated effects. We took publication bias into consideration and compiled funnel plots. MAIN RESULTS: We included 22 studies in this updated analysis, including six new trials with 584 additional participants, resulting in a total of 1428 participants. The risk of bias was low in 11 studies, high in one study and unclear in the remaining studies, due primarily to failure to report methodology for randomisation, and allocation concealment or blinding, or both. Fourteen studies examined intraoperative core temperatures among heated and humidified insufflation cohorts and core temperatures were higher compared to cold gas insufflation (MD 0.31 °C, 95% CI, 0.09 to 0.53, I2 = 88%, P = 0.005) (low-quality evidence). If the analysis was limited to the eight studies at low risk of bias, this result became non-significant but remained heterogeneous (MD 0.18 °C, 95% CI, -0.04 to 0.39, I2= 81%, P = 0.10) (moderate-quality evidence).In comparison to the cold CO2 group, the meta-analysis of the heated, non-humidified group also showed no statistically significant difference between groups. Core temperature was statistically, significantly higher in the heated, humidified CO2 with external warming groups (MD 0.29 °C, 95% CI, 0.05 to 0.52, I2 = 84%, P = 0.02) (moderate-quality evidence). Despite the small difference in temperature of 0.31 °C with heated CO2, this is unlikely to be of clinical significance.For postoperative pain scores, there were no statistically significant differences between heated and cold CO2, either overall, or for any of the subgroups assessed. Interestingly, morphine-equivalent use was homogeneous and higher in heated, non-humidified insufflation compared to cold insufflation for postoperative day one (MD 11.93 mg, 95% CI 0.92 to 22.94, I2 = 0%, P = 0.03) (low-quality evidence) and day two (MD 9.79 mg, 95% CI 1.58 to 18.00, I2 = 0%, P = 0.02) (low-quality evidence). However, morphine use was not significantly different six hours postoperatively or in any humidified insufflation groups.There was no apparent effect on length of hospitalisation, lens fogging or length of operation with heated compared to cold gas insufflation, with or without humidification. Recovery room time was shorter in the heated cohort (MD -26.79 minutes, 95% CI -51.34 to -2.25, I2 = 95%, P = 0.03) (low-quality evidence). When the one and only unclear-risk study was removed from the analysis, the difference in recovery-room time became non-significant and the studies were statistically homogeneous (MD -1.22 minutes, 95% CI, -6.62 to 4.17, I2 = 12%, P = 0.66) (moderate-quality evidence).There were also no differences in the frequency of major adverse events that occurred in the cold or heated cohorts.These results should be interpreted with caution due to some limitations. Heterogeneity of core temperature remained significant despite subgroup analysis, likely due to variations in the study design of the individual trials, as the trials had variations in insufflation gas temperatures (35 ºC to 37 ºC), humidity ranges (88% to 100%), gas volumes and location of the temperature probes. Additionally, some of the trials lacked specific study design information making evaluation difficult. AUTHORS' CONCLUSIONS: While heated, humidified gas leads to mildly smaller decreases in core body temperatures, clinically this does not account for improved patient outcomes, therefore, there is no clear evidence for the use of heated gas insufflation, with or without humidification, compared to cold gas insufflation in laparoscopic abdominal surgery.

Endoscopic versus open component separation: systematic review and meta-analysis.

BACKGROUND: The component separation technique (CST) was developed to improve the integrity of abdominal wall reconstruction for large, complex hernias. Open CST necessitates large subcutaneous skin flaps and, therefore, is associated with significant ischemic wound complications. The minimally invasive or endoscopic component separation technique (MICST) has been suggested in preliminary studies to reduce wound complication rates post-operatively. In this study, we systematically reviewed the literature comparing open versus endoscopic component separation and performed a meta-analysis of controlled studies. METHODS: A comprehensive search of electronic databases was completed. All English, randomized controlled trials, non-randomized comparison study, and case series were included. All comparison studies included in the meta-analysis were assessed independently by two reviewers for methodological quality using the Cochrane Risk of Bias tools. RESULTS: 63 primary studies (3,055 patients) were identified; 7 controlled studies and 56 case series. The total wound complication rate was lower for MICST (20.6 %) compared to Open CST (34.6 %). MICST compared to open CST was shown to have lower rates of superficial infections (3.5 vs 8.9 %), skin dehiscence (5.3 vs 8.2 %), necrosis (2.1 vs 6.8 %), hematoma/seroma formation (4.6 vs 7.4 %), fistula tract formation (0.4 vs 1.0 %), fascial dehiscence (0.0 vs 0.4 %), and mortality (0.4 vs 0.6 %.) The open component CST did have lower rates of intra-abdominal abscess formation (3.8 vs 4.6 %) and recurrence rates (11.1 vs 15.1 %). The meta-analysis included 7 non-randomized controlled studies (387 patients). A similar suggestive overall trend was found favoring MICST, although most types of wound complications did not show to significance. MICST was associated with a significantly decreased rate of fascial dehiscence and was shown to be significantly shorter procedure. CONCLUSION: This systematic review and meta-analysis comparing MICST to open CST suggests MICST is associated with decreased overall post-operative wound complication rates. Further prospective studies are needed to verify these findings.

"iBIM"--internet-based interactive modules: an easy and interesting learning tool for general surgery residents.

BACKGROUND: The increased use of information technology supports a resident- centred educational approach that promotes autonomy, flexibility and time management and helps residents to assess their competence, promoting self-awareness. We established a web-based e-learning tool to introduce general surgery residents to bariatric surgery and evaluate them to determine the most appropriate implementation strategy for Internet-based interactive modules (iBIM) in surgical teaching. METHODS: Usernames and passwords were assigned to general surgery residents at the University of Alberta. They were directed to the Obesity101 website and prompted to complete a multiple-choice precourse test. Afterwards, they were able to access the interactive modules. Residents could review the course material as often as they wanted before completing a multiple-choice postcourse test and exit survey. We used paired t tests to assess the difference between pre- and postcourse scores. RESULTS: Out of 34 residents who agreed to participate in the project, 12 completed the project (35.3%). For these 12 residents, the precourse mean score was 50 ± 17.3 and the postcourse mean score was 67 ± 14 (p = 0.020). CONCLUSION: Most residents who participated in this study recommended using the iBIMs as a study tool for bariatric surgery. Course evaluation scores suggest this novel approach was successful in transferring knowledge to surgical trainees. Further development of this tool and assessment of implementation strategies will determine how iBIM in bariatric surgery may be integrated into the curriculum.

CONTEXTE: L'utilisation croissante des technologies de l'information favorise une approche didactique centrée sur les résidents; elle favorise l'autonomie, la flexibilité et une meilleure gestion du temps, en plus d'aider les résidents à évaluer leurs compétences et à améliorer leur conscience d'eux-mêmes. Nous avons conçu un outil d'apprentissage électronique en ligne pour présenter la chirurgie bariatrique aux résidents de chirurgie générale et les évaluer, dans le but d'établir la meilleure stratégie d'application des modules de formation interactive en ligne pour l'enseignement de la chirurgie. MÉTHODES: Des noms d'utilisateurs et des mots de passe ont été assignés aux résidents de chirurgie générale de l'Université de l'Alberta. Ils ont ensuite été orientés vers le site web Obesity101 et invités à répondre à un prétest à choix multiples. Ensuite, ils ont pu accéder aux modules de formation interactive. Les résidents ont pu consulter la documentation du cours aussi souvent qu'ils le souhaitaient avant de répondre à un post-test à choix multiples et de quitter le module. Nous avons utilisé le test t d'échantillons appariés pour mesurer la différence entre les scores du prétest et du post-test. RÉSULTATS: Sur 34 résidents qui ont accepté de participer au projet, 12 l'ont mené à terme (35,3 %). Chez ces 12 résidents, le score moyen au prétest était de 50 ± 17,3 et le score moyen au post-test était de 67 ± 14 (p = 0,020). CONCLUSION: La majorité des résidents qui ont participé à cette étude ont recommandé l'utilisation des modules de formation interactive en ligne comme outil pour l'étude de la chirurgie bariatrique. Les scores d'évaluation du cours donnent à penser que cette approche novatrice a été propice au transfert des connaissances aux résidents de chirurgie. Il faudra perfectionner cet outil et en évaluer les stratégies d'application afin de déterminer de quelle façon intégrer au programme les modules de formation interactive en ligne pour la chirurgie bariatrique.

Outcomes of the adjustable gastric band in a publicly funded obesity program.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is considered a safe and effective treatment for severe obesity and obesity-related comorbidities. We sought to examine the outcome of LAGB delivered through a Canadian publicly funded obesity program. METHODS: We retrospectively analysed the cases of patients who underwent LAGB within a comprehensive, multidisciplinary, publically funded obesity program. RESULTS: A total of 178 patients underwent LAGB. Mean percentage total body weight loss at 1, 2 and 3 years was 15.8%, 20.7% and 20.3%, respectively. The most common short-term complication was postoperative nausea (19%). The medium-term complications included band migration (5.6%) and port site complications, band leakage and incisional hernia at 1% each. The reoperation rate was 4.5%. The mean surgery duration was 56 minutes and the mean length of stay was 1.4 days. The average numbers of clinic visits and band adjustments were highest in the first year. The most common investigation for postoperative symptoms was fluoroscopy (86%). An outcome comparison between the 2 generations of the REALIZE gastric band was inconclusive, requiring further data collection. CONCLUSION: Publicly funded LAGB results in effective weight loss and acceptable safety over the short term. Our patients may represent a distinct population that differs from that in the private system. Long-term data are necessary to determine the cost-effectiveness of this important surgical option for severe obesity.

CONTEXTE: L'anneau gastrique ajustable posé par laparoscopie (AGAL) est considéré comme un traitement sécuritaire et efficace contre l'obésité sévère et les comorbidités connexes. Nous avons cherché à analyser le résultat de la pose d'un AGAL réalisée dans le cadre d'un programme public de lutte contre l'obésité au Canada. MÉTHODES: Nous avons analysé de façon rétrospective les cas de patients qui ont reçu un AGAL dans le contexte d'un programme intégré et multidisciplinaire de lutte contre l'obésité financé par le secteur public. RÉSULTANTS: Au total, 178 patients ont reçu un AGAL. La perte procentuelle moyenne totale de masse corporelle à 1, 2 et 3 ans s'est établie à 15,8 %, 20,7 % et 20,3 % respectivement. Les nausées postopératoires ont constitué la complication à court terme la plus fréquente (19 %). Les complications à moyen terme ont inclus le déplacement de l'anneau (5,6 %) et des complications du côté porte, la fuite au niveau de l'anneau et une hernie à celui de l'incision : elles ont atteint 1 % dans chaque cas. Le taux de répétition de l'intervention a atteint 4,5 %. L'intervention chirurgicale a duré en moyenne 56 minutes et le séjour moyen 1,4 jours. Le nombre moyen de visites à la clinique et celui des rajustements de l'anneau étaient les plus élevés au cours de la première année. Les symptômes postopératoires sont examinés le plus souvent par fluoroscopie (86 %). Une comparaison des résultats entre les 2 générations de l'anneau gastrique REALIZE n'a pas été concluante, ce qui oblige à réunir d'autres données. CONCLUSIONS: La pose d'un AGAL financée par le secteur public entraîne une perte de poids efficace et offre une sécurité acceptable à court terme. Nos patients peuvent représenter une population distincte qui diffère de celle du secteur privé. Il faut des données à long terme pour déterminer la rentabilité de cette option chirurgicale importante en cas d'obésité sévère.

Carbon neutral hydrogen storage and release cycles based on dual-functional roles of formamides.

The development of alternative clean energy carriers is a key challenge for our society. Carbon-based hydrogen storage materials are well-suited to undergo reversible (de)hydrogenation reactions and the development of catalysts for the individual process steps is crucial. In the current state, noble metal-based catalysts still dominate this field. Here, a system for partially reversible and carbon-neutral hydrogen storage and release is reported. It is based on the dual-functional roles of formamides and uses a small molecule Fe-pincer complex as the catalyst, showing good stability and reusability with high productivity. Starting from formamides, quantitative production of CO-free hydrogen is achieved at high selectivity ( > 99.9%). This system works at modest temperatures of 90 °C, which can be easily supplied by the waste heat from e.g., proton-exchange membrane fuel cells. Employing such system, we achieve >70% H2 evolution efficiency and >99% H2 selectivity in 10 charge-discharge cycles, avoiding undesired carbon emission between cycles.