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Here, we report new radical-polar crossover reactions of α-alkoxy carbon radicals for constructing highly oxygenated molecules with contiguous stereocenters. The method employs a 370 nm UV light-emitting diode (LED) for the photoexcitation of α-alkoxyacyl telluride, and Et3Al as the radical initiator and terminator. First, Et3Al and UV LED promoted radical coupling between the α-alkoxyacyl telluride and cyclopentenone via C-Te bond homolysis, CO expulsion, and C-C bond formation. Second, Et3Al converted the radical species to the corresponding aluminum enolate. Third, the second C-C bond formation occurred via a polar mechanism: intermolecularly with aldehydes/ketones and intramolecularly with epoxide, producing aldol and SN2 adducts, respectively. The present coupling reactions increase the molecular complexity in a single step by stereoselective formation of the two hindered C-C bonds. The devised method is expected to be useful for the expeditious assembly of densely oxygenated natural products.
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The female sex pheromone of Grammodes geometrica (Lepidoptera: Erebidae: Erebinae) was identified as a 2:100:4 mixture of (3Z,6Z,9Z)-3,6,9-icosatriene (T20), (3Z,6Z,9Z)-3,6,9-henicosatriene (T21), and (3Z,6Z,9Z)-3,6,9-tricosatriene (T23) through chemical and electrophysiological analyses of female gland extracts. T23 is a novel sex pheromone component in Erebinae species. Field trapping tests demonstrated optimal male captures in attractant-baited traps when using a 2:100:4 blend of T20, T21 and T23, with a significant decrease in captures observed when T20 or T23 were removed from the full blend. Traps were set in early August, but males began to be captured in early September. The seasonal prevalence showed a bimodal peak, occurring on September 11 and October 9. These findings provide valuable insights into the chemical communication and ecological dynamics of this species within the subfamily Erebinae.
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(3Z,6Z,9Z)-3,6,9-henicosatriene was identified as a major component of female sex pheromone of Bastilla arctotaenia (Lepidoptera: Erebidae), a pest of cultivated roses, by gas chromatograph-electroantennographic detector( GC-EAD) and gas chromatograph/mass spectrometry (GC/MS) analyses. The single (3Z,6Z,9Z)-3,6,9-henicosatriene (1.0 mg/lure) successfully attracted B. arctotaenia males in the field.
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Cromatografía de Gases y Espectrometría de Masas , Lepidópteros , Atractivos Sexuales , Animales , Atractivos Sexuales/química , Atractivos Sexuales/análisis , Femenino , Masculino , Lepidópteros/fisiología , Mariposas Nocturnas/fisiología , Conducta Sexual AnimalRESUMEN
HYPOTHESIS AND BACKGROUND: Total elbow arthroplasty (TEA), categorized into linked and unlinked types, is a commonly reported treatment for rheumatoid arthritis of the elbow. Although unlinked TEA preserves bone, it may result in instability. This study aimed to assess the outcomes of unlinked TEA in rheumatoid arthritis of the elbow beyond 2 years and to identify factors correlating with postoperative valgus instability of unlinked TEA. METHODS: This study included patients who underwent TEA for rheumatoid arthritis of the elbow at our department between August 2009 and January 2017, with a follow-up period exceeding 2 years. Elbow joint range of motion (ROM) and clinical scores were evaluated preoperatively and at the final follow-up. Factors contributing to valgus instability, such as the Larsen grade, sex, age, side, preoperative ROM, postoperative ROM, implant placement, preoperative carrying angle, and the use of biological disease-modifying antirheumatic drugs (bDMARDs), were also assessed. RESULTS: This study encompassed 26 elbows from 23 patients, with a mean patient age at surgery of 64.8 years and a mean follow-up duration of 92.4 months. Significant improvements were observed in the ROM (extension: from -31° preoperatively to -21° postoperatively [P = .02], flexion: from 116° to137° [P < .001]), Japanese Orthopaedic Association-Japan Elbow Society Elbow Function Score (from 45.9 to 86.3 points [P < .001]), and Mayo Elbow Performance Score (from 43.6 to 91.7 points [P < .001]). At the last follow-up, 2 elbows exhibited radiolucent lines around the humeral stem, whereas 7 had valgus instability. Factors correlated with valgus instability included total arc at the final follow-up, preoperative carrying angle, and the use of bDMARDs. DISCUSSION AND CONCLUSION: Unlinked TEA demonstrated favorable midterm outcomes for rheumatoid arthritis of the elbow, albeit with occasional valgus instability. Surgeons should consider preoperative carrying angle and bDMARD use, and exercise caution regarding intraoperative extensions.
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Artritis Reumatoide , Artroplastia de Reemplazo de Codo , Articulación del Codo , Humanos , Codo/cirugía , Resultado del Tratamiento , Estudios de Seguimiento , Articulación del Codo/cirugía , Artritis Reumatoide/complicaciones , Artritis Reumatoide/cirugía , Húmero/cirugía , Rango del Movimiento ArticularRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a public health concern worldwide. Ensitrelvir (S-217622) has been evaluated as an antiviral treatment for COVID-19, targeting SARS-CoV-2 3C-like protease (3CLpro). Ensitrelvir has been reported to have comparable antiviral activity against some of the SARS-CoV-2 variants: alpha, beta, gamma, delta, and omicron (BA.1.18). In this paper, we describe that ensitrelvir is effective against newly emerging SARS-CoV-2 variants and globally prevalent 3CLpro mutations. Ensitrelvir exhibited comparable antiviral activity against SARS-CoV-2 variants, including recently emerging ones: omicron (BA1.1, BA.2, BA.2.75, BA.4, BA.5, BQ.1.1, XBB.1, and XE), mu, lambda, and theta. Genetic surveillance of SARS-CoV-2 3CLpro, the target of ensitrelvir, was conducted using a public database and identified 11 major 3CLpro mutations circulating globally (G15S, T21I, T24I, K88R, L89F, K90R, P108S, P132H, A193V, H246Y, and A255V). The 3CLpro mutation from proline to histidine at amino acid position 132 was especially identified in the omicron variant, with prevalence of 99.69%. Enzyme kinetic assay revealed that these 3CLpro mutants have enzymatic activity comparable to that of the wild type (WT). Next, we assessed the inhibitory effect of ensitrelvir against mutated 3CLpro, with it showing inhibitory effects similar to that against the WT. These in vitro data suggest that ensitrelvir will be effective against currently circulating SARS-CoV-2 variants, including omicron variants and those carrying 3CLpro mutations, which emerging novel SARS-CoV-2 variants could carry.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Péptido Hidrolasas , Cisteína Endopeptidasas/metabolismo , Antivirales/farmacología , Antivirales/química , Inhibidores de Proteasas/farmacologíaRESUMEN
BACKGROUND: Characteristics and prognoses of patients with occult metastases (OM) of pancreatic ductal adenocarcinoma (PDAC) compared with radiologically defined metastases (RM) have been rarely reported. OBJECTIVE: We aimed to clarify the prognosis of OM compared with RM and to establish a treatment strategy for PDAC patients with OM. METHODS: This single-institution, retrospective study evaluated patients with unresectable PDAC between 2008 and 2018. OM was defined as abdominal metastasis that was detected by staging laparoscopy or open laparotomy but not in the initial assessment of radiological images. RESULTS: OM and RM were identified in 135 and 112 patients, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS), neutrophil to lymphocyte ratio (NLR), tumor diameter, and rate of local unresectability were significantly lower in the OM group. Median overall survival (OS) of OM was significantly better than that of RM (13.0 vs 8.9 months, p < 0.001). In multivariate analysis of OS, ECOG PS ≥ 1 (HR 1.64, p = 0.009), NLR ≥5 (HR 1.97, p = 0.004), carbohydrate antigen (CA) 19-9 ≥1000 (HR 1.68, p = 0.001), tumor diameter ≥40 mm (HR 1.40, p = 0.027), conversion surgery (HR 0.12, p < 0.001), and multiple lines of chemotherapy (HR 0.38, p < 0.001) were independent predictors. However, type of metastasis (OM vs RM) not an independent predictor (HR 1.10, p = 0.590). CONCLUSION: The prognosis of PDAC with OM was relatively better than that with RM, but general and nutritional statuses, primary tumor size and CA19-9, conversion surgery and multiple lines of chemotherapy were independent predictors but not tumor burden.
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Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/terapia , Pronóstico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias PancreáticasRESUMEN
Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.
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Traumatismos de los Nervios Periféricos , Activador de Plasminógeno de Tipo Uroquinasa , Axones/fisiología , Humanos , Interleucina-4/farmacología , Macrófagos/fisiología , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/terapia , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genéticaRESUMEN
BACKGROUND: Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry. CASE PRESENTATION: We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain. CONCLUSIONS: This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.
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Amiloidosis , Mieloma Múltiple , Femenino , Humanos , Anciano , Rojo Congo , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Amiloidosis/patología , Inmunoglobulinas , Amiloide , Espectrometría de Masas , Cadenas Ligeras de InmunoglobulinaRESUMEN
Due to the worldwide travel restrictions caused by the 2019 coronavirus disease pandemic, many universities and students lost opportunities to engage in international exchange over the past 2 years. Teleconferencing systems have thus been developed to compensate for severe travel restrictions. Kansai Medical University in Japan and Vilnius University in Lithuania have a collaborative research and academic relationship. The two universities have been conducting an online joint international surgery lecture series for the medical students of both universities. Fifteen lectures were given from October 2021 to May 2022. The lectures focused on gastrointestinal surgery, gastroenterology, radiology, pathology, genetics, laboratory medicine, and organ transplantation. A survey of the attendees indicated that they were generally interested in the content and satisfied with attending this lecture series. Our efforts were successful in providing Japanese and Lithuanian medical students with the opportunity to engage in international exchange through lectures held in each other's countries.
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Estudiantes de Medicina , Humanos , Encuestas y Cuestionarios , Universidades , JapónRESUMEN
BACKGROUND: Anatomical total shoulder arthroplasty (TSA) provides successful long-term outcomes but complications can occur after 10 years that require revision. Computed tomography (CT) is a useful tool for assessing radiolucent lines around the glenoid component of TSA; however, the merits of long-term post-TSA follow up with CT are unclear. The purpose of this study was to evaluate the long-term outcomes after TSA of Japanese population and to identify factors related to radiolucency around the glenoid component using CT. METHODS: A retrospective review was conducted of TSA patients who had completed at least 10 years of clinical follow up. Radiographs and CT images of the affected shoulder obtained at the last follow up were evaluated for radiolucent lines around the stem and each peg, superior inclination and retroversion of the glenoid component, subluxation index, and critical shoulder angle (CSA). Shoulder ROM, Constant-Murley score and UCLA score were compared between the preoperative and last follow up period. RESULTS: Eighteen shoulders in 16 patients met the inclusion criteria. Mean patient age was 61 years, mean follow up period was 137 months, and mean Yian CT score was 19%. CT score was significantly highest in pegs located inferiorly (p < 0.05). Mean glenoid superior inclination was 12.6°, retroversion was -0.3°, subluxation index was 46%, and CSA was 33.7°. Glenoid superior inclination was significantly lower (p = 0.007) in shoulders with possible loosening than in cases with no loosening (5.0° vs 15.6°). Mean Constant score and UCLA score improved significantly after TSA, from 25.8 to 10.7 points preoperatively to 70.1 and 28.9 points postoperatively, respectively. Mean shoulder flexion, internal rotation, and external rotation also showed improvement postoperatively. CONCLUSION: TSA provides good long-term outcomes. Radiolucency was present most frequently around the inferior pegs of the glenoid component. Glenoid superior inclination may affect the formation of radiolucent lines around glenoid pegs. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment study.
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Artroplastía de Reemplazo de Hombro , Cavidad Glenoidea , Luxaciones Articulares , Articulación del Hombro , Humanos , Persona de Mediana Edad , Artroplastía de Reemplazo de Hombro/métodos , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Polietileno , Pueblos del Este de Asia , Tomografía Computarizada por Rayos X , Luxaciones Articulares/cirugía , Estudios Retrospectivos , Cavidad Glenoidea/diagnóstico por imagen , Cavidad Glenoidea/cirugía , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
A 78-year-old woman underwent total gastrectomy with distal pancreatectomy and splenectomy for type 3 gastric cancer and a cystic tumor of the pancreas. Her pathological diagnosis was pT4aN3bM0, pStage â ¢C, and HER2-negative. Capecitabine and oxaliplatin was started as an adjuvant therapy, and capecitabine was administered until 1 year postoperatively. Thirteen months after surgery, she had a recurrence in S3 of the liver and underwent liver resection due to solitary metastasis. The postoperative diagnosis was peritoneal dissemination of gastric cancer with invasion of the falciform ligament. S-1 was started postoperatively. Ten months after surgery, she had a recurrence in S3 of the liver and underwent repeated resection. It invaded into the diaphragm and pericardium, and the final diagnosis was recurrent peritoneal dissemination of gastric cancer. After 5 courses of paclitaxel and ramucirumab, nivolumab was started as a fourth-line therapy for the recurrence of the right supraclavicular lymph nodes, bone, and liver. She had some immune-related adverse events(irAE), including hypothyroidism and hypoadrenocorticism, which required management, but she maintained PR more than 2 years after the initiation of the treatment. Multimodality therapies, including repeated resection and nivolumab, were considered to help her long-term survival.
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Nivolumab , Neoplasias Gástricas , Humanos , Femenino , Anciano , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Capecitabina/uso terapéutico , Ganglios Linfáticos/patología , Ramucirumab , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , GastrectomíaRESUMEN
A 73-year-old woman underwent left nephrectomy for renal cell carcinoma(RCC). The computed tomography(CT)and magnetic resonance imaging(MRI)revealed a 20-mm tumor in the pancreatic tale showing early enhancement in the arterial phase 16 years after surgery. Fluorodeoxyglucose positron emission tomography(FDG-PET)showed slightly uptake (maximum standard uptake value: SUVmax 2.3)and EUS-FNA showed a hyper-vascularized tumor in the pancreatic tail. A single pancreatic metastasis from RCC was diagnosed, and we performed distal pancreatectomy. The histopathological diagnosis was a metastatic pancreatic tumor from RCC. The postoperative course was uneventful and 1 month after surgery, she is alive with no recurrence.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pancreáticas , Femenino , Humanos , Anciano , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/secundario , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Tomografía Computarizada por Rayos X , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/secundario , Nefrectomía , Fluorodesoxiglucosa F18RESUMEN
A 66-year-old man with a history of frequent diarrhea was diagnosed with rectal cancer with obstruction and a pelvic abscess. Following a transverse colostomy, he was referred to our hospital. The initial diagnosis was rectal cancer(cT4a N1bM0, cStage â ¢b)and a pelvic abscess due to tumor perforation. To address this condition, we performed neoadjuvant chemotherapy using a combination of 5-fluorouracil, Leucovorin, oxaliplatin, and irinotecan(FOLFOXIRI). Following 6 courses of FOLFOXIRI, the abscess disappeared and no signs of tumor progression and distant metastases were detected. Subsequently, we performed radical resection with D3LD2 lymph node dissection, leading to a pathological diagnosis of ypT3N1aM0, ypStage â ¢b. The patient then underwent adjuvant chemotherapy with capecitabine and oxaliplatin(CAPOX). No recurrence was observed after 9 months of follow-up.
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Absceso Abdominal , Neoplasias del Recto , Masculino , Humanos , Anciano , Terapia Neoadyuvante , Oxaliplatino/uso terapéutico , Absceso/tratamiento farmacológico , Absceso/etiología , Absceso/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/complicaciones , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéuticoRESUMEN
The gastrointestinal stromal tumor(GIST)guidelines state that the use of neoadjuvant chemotherapy(NAC)for curable GIST is not apparent. However, NAC is performed for massive rectal GIST at our hospital to reduce surgical invasion and improve surgical results. The cases were a 39-year-old man, a 48-year-old man, and a 78-year-old man. The site was Rb in all cases, and the maximum diameters at the rectal GIST diagnosis were respectively 70 mm, 75 mm, and 60 mm, which were massive tumors. Imatinib mesylate(imatinib)was started as NAC. The duration of NAC was respectively 6, 11, and 12 months. The maximum tumor diameter on preoperative CT was smaller than before NAC, and the average reduction rate was 23%. Two cases underwent laparoscopic abdominal perineal resection, and 1 underwent laparoscopic ultra-low anterior resection and ileostomy. No perioperative complications of Clavien-Dindo classification Grade â ¡ or higher were unsettled. All patients were in the high risk group and received imatinib as postoperative adjuvant chemotherapy. Currently, respectively 2 years and 3 months, 1 year and 2 months, and 1 year after surgery, all are alive without recurrence. NAC with imatinib has contributed to minimally invasive and radical surgery for giant rectal GIST.
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Antineoplásicos , Tumores del Estroma Gastrointestinal , Laparoscopía , Neoplasias del Recto , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Mesilato de Imatinib/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Antineoplásicos/uso terapéutico , Terapia Neoadyuvante , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Neoplasias del Recto/patologíaRESUMEN
Light Detection and Ranging (LiDAR) is a widespread technique for 3D ranging and has widespread use in most automated systems that must interact with the external environment, for instance in industrial and security applications. In this work, we study a novel architecture for Single Photon Avalanche Diode (SPAD) arrays suitable for handheld single point rangefinders, which is aimed at the identification of the objects' position in the presence of strong ambient background illumination. The system will be developed for an industrial environment, and the array targets a distance range of about 1 m and a precision of few centimeters. Since the laser spot illuminates only a small portion of the array, while all pixels are exposed to background illumination, we propose and validate through Monte Carlo simulations a novel architecture for the identification of the pixels illuminated by the laser spot to perform an adaptive laser spot tracking and a smart sharing of the timing electronics, thus significantly improving the accuracy of the distance measurement. Such a novel architecture represents a robust and effective approach to develop SPAD arrays for industrial applications with extremely high background illumination.
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Application of laparoscopic surgery(Lap)for colorectal cancer has expanded, and laparoscopic total pelvic exenteration (TPE)of locally advanced rectal cancer(LARC)invading the urogenital organs has been introduced in some institutions. In our institute, we have performed Lap TPE and posterior-TPE(PPE)in a total of 6 LARC patients so far. Here, we report the surgical technique of Lap TPE, and the associated surgical and short-term outcomes. We performed Lap TPE and Lap PPE in 3 patients each. Operation time was approximately 562 min, and the blood loss was 310 mL on an average. No patient developed postoperative complications above Clavien-Dindo Grade â ¢. One patient exhibited recurrence in the liver and another in peritoneum in the Lap PPE group. No recurrence was observed in the Lap TPE group(median follow-up period: 24.5 months). Although Lap TPE and PPE are difficult to perform and time consuming, it is suggested that these procedures may help reduce the intraoperative bleeding volume and shorten the length of postoperative hospital stay compared to open TPE and PPE.
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Laparoscopía , Exenteración Pélvica , Neoplasias del Recto , Humanos , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A 75-year-old woman was treated with TC plus Bev for cancer of unknown primary. During treatment, she presented to the clinic with chief complaints of general malaise and anorexia. On presentation, abdominal distention and upper abdominal tenderness were noted, and sepsis was suspected. A thoracoabdominal CT scan revealed prominent intramural emphysema and mesenteric gas in the ascending colon. An emergency laparotomy was performed for suspected pneumatosis intestinalis non-obstructive intestinal ischemia. However, no intra-abdominal contamination or ischemic changes were observed intraoperatively. Histological examination revealed a small adenocarcinoma on the serous surface of the ascending colon, and immunochemical staining confirmed the diagnosis of serous adenocarcinoma as the patient's primary cancer. This report describes a case in which the patient achieved long-term survival after diagnosis. It also emphasizes the importance of identifying the subset of patients with cancer of unknown primary who have a good prognosis in order to provide appropriate treatment.
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Adenocarcinoma , Neoplasias Primarias Desconocidas , Neumatosis Cistoide Intestinal , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Anciano , Bevacizumab , Femenino , Humanos , Laparotomía , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Neumatosis Cistoide Intestinal/inducido químicamente , Neumatosis Cistoide Intestinal/diagnóstico por imagenRESUMEN
BACKGROUND: Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance. METHODS: This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18-24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model. RESULTS: Ten RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18-24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant). CONCLUSIONS: Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18-24 months) did not experience a relapse.
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Antipsicóticos/administración & dosificación , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: We conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing blonanserin with other antipsychotics (amisulpride, aripiprazole, haloperidol, paliperidone, and risperidone). METHODS: Weighted mean difference (WMD), risk ratio, and number needed to harm (NNH) with 95% confidence intervals (95% CIs) were calculated using random-effects model. RESULTS: Ten RCTs (n=1521) were included in this study. Blonanserin was superior to aripiprazole in improvement of Positive and Negative Syndrome Scale total scores (WMD=-10.62, 95% CI=-17.67 to -3.560, p=0.003). Blonanserin was associated with a higher incidence of all-cause discontinuation (RR=1.373, 95% CI=1.088-1.734, p=0.008, NNH=11), akathisia, extrapyramidal disorder, and agitation/excitement and a lower risk of hyperprolactinemia compared with risperidone + paliperidone. DISCUSSION: The current meta-analytic study did not update the comparison of blonanserin vs. haloperidol because there were no new RCTs. Our results suggest that the efficacy of blonanserin for schizophrenia is comparable with that of other antipsychotics, and blonanserin seems to be well tolerated.
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Antipsicóticos/uso terapéutico , Piperazinas/uso terapéutico , Piperidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/farmacología , Humanos , Piperazinas/farmacología , Piperidinas/farmacologíaRESUMEN
AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.