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OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.
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A highly efficient asymmetric [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones has been developed. This innovative reaction employs an organocatalytic approach, utilizing a hydrogen-bonding bifunctional squaramide-based catalyst. The process enables precise synthesis of chiral polyheterotricyclic oxazolidines and 1,3-oxazinane derivatives, revealing intricate structures with incorporated chiral quaternary centers. Remarkably, this method delivers high yields and exceptional enantioselectivities and diastereoselectivities, achieving up to 99% yield, >20 : 1 dr, and >99% ee.
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The 1,4-benzodiazepine structural framework is a fascinating element commonly found in biologically active and pharmaceutically relevant compounds. A highly efficient method for synthesizing 1,4-benzodiazepin-3-ones is described, involving a [4+3]-cycloaddition reaction between 2-amino-ß-nitrostyrenes and α-bromohydroxamate, with Cs2CO3 used as a base. This process yielded the desired 1,4-benzodiazepines in good yields. Furthermore, an organocatalytic asymmetric [4+3]-cycloaddition was successfully accomplished using a bifunctional squaramide-based catalyst. This approach enabled the enantioselective synthesis of chiral 1,4-benzodiazepines with commendable yields and moderate enantioselectivities, reaching up to 80% yield and 72% ee.
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A highly efficient enantioselective [4 + 2] cycloaddition of 2-amino-ß-nitrostyrenes with cyclic N-sulfonyl ketimines has been developed. This reaction utilizes an organocatalytic approach, employing a multiple-hydrogen-bonding bifunctional squaramide-based catalyst. The process allows for the precise synthesis of chiral polycyclic benzosultams, showcasing intricate structures that incorporate chiral quaternary centers. Noteworthy outcomes of this method include high yields with excellent enantioselectivities and diastereoselectivities (up to 97% yield, 96% ee, and >20:1 dr).
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Ring-fused aminal is an interesting structural skeleton in biologically active and pharmaceutically relevant compounds. A novel and efficient method for synthesizing benzosulfamidate-fused tetrahydroquinazolines is described. By employing the [4+2]-cycloaddition of 2-aminophenyl enones with cyclic N-sulfimines in the presence of DMAP as a base, the desired benzosulfamidate-fused tetrahydroquinazolines were obtained in good yields with high diastereoselectivities. Furthermore, an organocatalytic asymmetric [4+2]-cycloaddition was successfully achieved using a squaramide-based catalyst, enabling the enantioselective synthesis of chiral ring-fused tetrahydroquinazolines with high yields and enantio- as well as diastereoselectivities (up to 89 % yield, 94 % ee, and >30 : 1 dr).
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A novel method for the enantioselective synthesis of spiro N,N-heterocyclic oxindoles has been developed, employing asymmetric [4 + 2]-cycloadditions of 2-aminophenyl enones with isatin-derived ketimines. This method employs an organocatalytic approach, utilizing a bifunctional squaramide-based catalyst. It enables the precise synthesis of chiral spirooxindole-tetrahydroquinazolines with intricate structures, featuring chiral quaternary centers. This process achieves remarkable results, including high yields and exceptional levels of enantioselectivity and diastereoselectivity (up to 96% yield, 95% ee, and >20:1 dr).
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Purpose: The safety of single-incision laparoscopic cholecystectomy (SILC) for acute cholecystitis (AC) has not yet been confirmed. Methods: This single-center retrospective study included patients who underwent laparoscopic cholecystectomy (LC) for AC between April 2010 and December 2020. Propensity scores were used to match patients who underwent SILC with those who underwent conventional multiport LC (CMLC) in the entire cohort and in the two subgroups. Results: A total of 1,876 patients underwent LC for AC, and 427 (22.8%) underwent SILC. In the propensity score-matched analysis of the entire cohort (404 patients in each group), the length of hospital stay (2.9 days vs. 3.5 days, p = 0.029) was shorter in the SILC group than in the CMLC group. No significant differences were observed in other surgical outcomes. In grade I AC (336 patients in each group), the SILC group showed poorer surgical outcomes than the CMLC group, regarding operation time (57.6 minutes vs. 52.4 minutes, p = 0.001) and estimated blood loss (22.9 mL vs. 13.1 mL, p = 0.006). In grade II/III AC (58 patients in each group), there were no significant differences in surgical outcomes between the two groups. Postoperative pain outcomes were also not significantly different in the two groups, regardless of severity. Conclusion: This study demonstrated that SILC had similar surgical and pain outcomes to CMLC in patients with AC; however, subgroup analysis showed that SILC was associated with poor surgical outcomes than CMLC in grade I AC. Therefore, SILC should be carefully performed in patients with AC by experienced hepatobiliary surgeons.
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BACKGROUND: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established. METHODS: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis. RESULTS: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3. CONCLUSION: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC.
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Colecistectomia Laparoscópica , Colecistite Aguda , Neoplasias da Vesícula Biliar , Humanos , Adulto , Feminino , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Masculino , Colecistectomia Laparoscópica/efeitos adversos , Neoplasias da Vesícula Biliar/etiologia , Estudos Retrospectivos , Colecistite Aguda/cirurgia , Resultado do TratamentoRESUMO
An alcohol-induced blackout suggested to be related to a rapid increase in blood alcohol concentration and it is closely related to long-term memory creation. Blackout has been experienced by 35% of the general population and over 50% of university student population. In addition, it has been shown that blackout could be a precursor of injury risk. However, the rate of blackout and blackout related negative consequences in Korean university students have rarely been studied. Therefore, the objective of this study was to determine the blackout experience rate and its negative consequences among students from four universities in Korea. A survey was conducted among university students located in Pusan, Korea in 2013. Demographic and blackout related information were collected through self-report questionnaire, including blackout experience, age of first blackout, and negative consequences of blackout. Descriptive statistical analysis was performed for collected data. Of a total of 470 subjects (Male = 217, Female = 253) surveyed, 190 (40.4%) subjects had experienced a blackout at some points in their lives. The majority (86.3%) of them experienced the first blackout between 20-25 years old. Among those who had experienced a blackout, 57.0% reported that they could not remember how they went home at the end of the night, 8.1%, 7.6%, 3.1%, and 2.2% reported that they had bodily injuries, argument, physical or personal fight, and sexual-related incidences, respectively. This study shows that many Korean university students have experienced blackouts and related negative events. These results suggest that more systematic drinking control strategy is required for Korean university students.
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A novel and streamlined approach to synthesizing benzotriazepin-1-ones has been developed through a hexafluoroisopropanol-promoted decarboxylative cascade reaction between isatoic anhydrides and hydrazonoyl chloride. The [4 + 3] annulation of hexafluoroisopropyl 2-aminobenzoates with nitrile imines, generated in situ, is a key feature of this innovative reaction. This approach has offered a simple and efficient method for synthesizing a broad range of structurally intricate and highly functional benzotriazepinones.
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An innovative and efficient approach has been developed for the synthesis of 5,6-dihydropyrazolo[5,1-a]isoquinolines. This one-pot tandem reaction involves the reaction of C,N-cyclic azomethine imines with α,ß-unsaturated ketones, using K2CO3 as the base and DDQ as the oxidant. The process results in functionalized 5,6-dihydropyrazolo[5,1-a]isoquinolines with good yields. This convenient one-step method encompasses a tandem [3 + 2]-cycloaddition, detosylation, and oxidative aromatization.
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The first base-mediated [4 + 2] annulation of δ-hydroxy-α,ß-unsaturated ketones with azlactones has been developed, through which 3,4-disubstituted 3-amino-δ-lactones were obtained in good yields and with excellent diastereoselectivities. This approach was also applied to the [4 + 2] annulation of δ-sulfonamido-α,ß-unsaturated ketones, which provided a practical protocol for constructing biologically important 3-amino-δ-lactam frameworks.
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Although vitamin D (VD; serum 25 hydroxyvitamin D) deficiency (< 20 ng/mL) is widespread among Japanese women, the VD status among pregnant women is unknown. This study aimed to determine the VD status of pregnant Japanese women during different meteorological seasons and to determine the factors controlling VD status. A total of 309 pregnant Japanese women were recruited at 28 weeks of gestation at the gynecology department of a university hospital in Tokyo between August 2018 and October 2019. Blood samples were collected to measure serum 25(OH)D levels. Two questionnaires were completed: a brief self-administered dietary history questionnaire (BDHQ) and an outdoor exposure history questionnaire to determine skin sunlight exposure and the use of sunscreen. Among the recruited subjects, 268 were included in the statistical analysis. The average VD intake from food was 9.0 µg/day, the average VD synthesis from UV-B was 15.2 µg/day, and the average sum of VD intake and nominal VD synthesis was 24.1 µg/day; this exceeded the recommended 2011 Dietary Reference Intake for the USA and Canada (15.0 µg/day). However, the average serum 25(OH)D level (11.4 ng/mL) was very low, indicating widespread VD deficiency. Serum 25(OH)D and VD synthesis by solar UV-B were significantly correlated only during the high UV-B season. The 25(OH)D level was weakly correlated with the VD intake from food in all seasons. We obtained a statistically significant correlation between serum 25(OH)D level and VD intake from food using the BDHQ. We also obtained a statistically significant correlation between the serum 25(OH)D level and VD synthesis from solar UV-B exposure, especially during the high UV-B season. Our logistic regression analysis model predicted VD deficiency in 88.0% of subjects. Our method might be possible to be used to predict the VD status of pregnant Japanese women, although another validation cohort is needed to verify the ability of the estimation equation.
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Gestantes , Deficiência de Vitamina D , Vitamina D , Feminino , Humanos , Gravidez , Suplementos Nutricionais , População do Leste Asiático , Ingestão de Alimentos , Estações do Ano , Inquéritos e Questionários , Vitamina D/administração & dosagem , Deficiência de Vitamina D/epidemiologia , Vitaminas , Dieta , Luz Solar , Raios UltravioletaRESUMO
1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with γ-NHTs-α,ß-unsaturated ketones were developed to synthesize tricyclic dinitrogen-fused heterocycles. Highly functionalized tricyclic tetrahydroisoquinolines were readily obtained in good to high yields in the [3 + 2]-cycloaddition reaction of N-Bz-protected C,N-cyclic azomethine imines with γ-NHTs-α,ß-unsaturated ketones under mild reaction conditions. Moreover, DABCO-catalyzed cycloaddition of N-Ts-protected C,N-cyclic azomethine imines with γ-NHTs-α,ß-unsaturated ketones followed by cleavage of the tosyl group is a convenient route to synthesize tetrahydropyrazolo [5,1-a]isoquinolines in good yields with excellent diastereoselectivities.
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The first organocatalytic asymmetric [3 + 2]-annulation of γ-sulfonamido-α,ß-unsaturated ketones with cyclic N-sulfimines has been developed, and enantioenriched functionalized polyheterotricyclic imidazolidines were obtained in good yields and with excellent enantioselectivities. This approach was also extended to the asymmetric [3 + 2]-annulation of γ-hydroxy-α,ß-unsaturated ketones, affording enantioenriched polyheterotricyclic oxazolidines. In addition, base-catalyzed [3 + 2]-annulations of γ-sulfonamido/γ-hydroxy-α,ß-unsaturated ketones with cyclic N-sulfimines were re-investigated under mild reaction conditions for the synthesis of racemic polyheterotricyclic imidazolidines and oxazolidines with excellent diastereoselectivities.
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Gastric cancer remains a significant global health concern and its surgical management approaches have undergone significant changes in South Korea and worldwide. Subtotal or total gastrectomy with D2 lymph node dissection is well established as a standard surgical procedure for gastric cancer. With the active implementation of cancer screening in South Korea, the proportion of early gastric cancer cases has significantly increased over the past few decades, leading to a steady increase in the survival rate among patients. Furthermore, recent advances in surgical instruments and techniques have made minimally invasive surgery increasingly prevalent, not only for early but also for advanced gastric cancer. We aim to provide a comprehensive overview of the evolution and current status of gastric cancer surgery in South Korea.
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BACKGROUND: The predictive value of various systemic inflammatory parameters has been reported. However, it is still unclear which inflammatory parameters are the best predictors of prognosis in advanced gastric cancer and what are their mechanisms of action. The aim of this study was to evaluate the association between preoperative systemic inflammatory parameters and overall survival (OS) in patients with advanced gastric cancer. METHODS: This retrospective study included 489 patients with stage II/III advanced gastric cancer treated at the National Cancer Center, Republic of Korea, between January 2012 and December 2015. We divided the patients into survivors and non-survivors and compared their clinicopathological characteristics. Univariate and multivariate analyses using the Cox proportional hazards model were performed to evaluate the prognostic value of inflammatory parameters. RESULTS: The absolute lymphocyte count was significantly higher in survivors (2.07 ± 0.62 × 103/µL vs. 1.88 ± 0.63 × 103/µL, p = 0.001). The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were marginally lower in survivors. Survival analysis revealed that the NLR and PLR were independent prognostic factors for OS. Survival was significantly different depending on NLR and PLR in the same pathologic stages. CONCLUSIONS: NLR and PLR were independent prognostic factors for OS in patients with advanced gastric cancer. Regarding single inflammatory parameters, an elevated lymphocyte count was the only factor associated with a favorable prognosis. These results suggest that the enhanced immune function of patients affects their prognosis more than the increased systemic inflammatory response.
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Purpose: The optimal indications for single-incision laparoscopic cholecystectomy (SILC) have not yet been established. Methods: This single-center retrospective study included consecutive patients who underwent SILC between April 2010 and June 2020. Difficult surgery (DS) (conversion to multiport or open cholecystectomy, adjacent organ injury, operation time of ≥90 minutes, or estimated blood loss of ≥100 mL) and poor postoperative outcome (PPO) (postoperative hospital stay ≥ 7 days or Clavien-Dindo grade ≥ II postoperative complications) were defined to comprehensively evaluate surgical difficulty and postoperative outcomes, respectively. Results: Of 1,405 patients (mean age, 51.2 years; 802 female [57.1%]), 427 (grade I, n = 358; grade II/III, n = 69) underwent SILC for acute cholecystitis (AC), 34 (2.4%) needed conversion to multiport (n = 33) or open cholecystectomy (n = 1), 7 (0.5%) had adjacent organ injury during surgery, and 49 (3.5%) developed postoperative complications. Of the patients, 89 and 52 had DS and PPO, respectively. In the multivariate analysis, grade I AC, grade II/III AC, and body mass index of ≥30 kg/m2 were significant predictors of DS. Age of ≥70 years and DS were significant predictors of PPO. In a subgroup analysis of patients with AC, DS (9.5% vs. 27.5%, p < 0.001) and PPO (5.0% vs. 15.9%, p = 0.001) were more frequent in patients with grade II/III AC than in those with grade I AC. Conclusion: SILC is not recommended in patients with grade II/III AC and should be carefully performed by experienced and well-trained surgeons.
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Purpose: This study was performed to investigate the role of the perioperative neutrophil-to-lymphocyte ratio (NLR) as an early predictor of major postoperative complications after total gastrectomy for gastric cancer. Methods: This single-center, retrospective study reviewed consecutive patients with gastric cancer who underwent total gastrectomy at a single institution from March 2009 to March 2021. The postoperative complications were graded according to the Clavien-Dindo classification. We analyzed the patient demographics and surgical outcomes according to the grade of postoperative complications in the major complications group (≥grade III) and the no major complications group (
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Background: Depending on the location of gastric subepithelial tumors (SETs), surgical access is difficult with a risk of postoperative complications. This study aimed to evaluate the clinicopathological characteristics of small-sized gastric SETs and their surgical outcomes depending on location and provide considering factors for their treatment plans. Methods: This single-center, retrospective study reviewed patients who underwent surgical resection for gastric SETs (size < 5 cm). SETs were divided into benign SETs and gastrointestinal stromal tumors (GISTs) for comparison. The clinicopathological characteristics of SETs in the cardia were compared to those in the other regions. Results: Overall, 191 patients with gastric SETs (135 GISTs, 70.7%; and 56 benign SETs, 29.3%) were included. In multivariate analysis, age > 65 years (odds ratio (OR), 3.183; 95% confidence interval (CI), 1.310−7.735; p = 0.011), and non-cardiac SETs (OR, 2.472; 95% CI, 1.110−5.507; p = 0.030) were associated with a significant risk of malignancy. Compared to SETs in other locations, cardiac SETs showed more complications (3 versus 0; p = 0.000), and open conversion rates (2 versus 0; p = 0.003). However, the proportion of GISTs of SETs in the cardia is not negligible (52.9%). Conclusions: Considering the malignancy risk of SETs, active surgical resection should be considered in old age and/or location in the non-cardiac area. However, in young patients, SETs located in the gastric cardia have a considerably benign nature and are associated with poor short-term surgical outcomes. An individualized surgical approach for asymptomatic small SETs according to the gastric location is warranted.