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BACKGROUND: Although scleroatrophic gallbladder is a rare condition, it presents significant clinical challenges in diagnosis and management. More agreement is needed on this disorder's diagnostic criteria and optimal management approach. We will conduct a systematic review to summarise the scleroatrophic gallbladder's preoperative diagnostic criteria, including imaging modalities. METHODS: A systematic review will be undertaken using the PRISMA guidelines. The protocol has been registered in PROSPERO (CRD42024503701). We will search in Medline (via PubMed), Embase, SCOPUS, the Cochrane Library, and Web of Science to find original studies reporting about scleroatrophic gallbladder or synonymous. Two reviewers will independently screen the titles and abstracts following the eligibility criteria. We will include all types of studies that describe any diagnostic criteria or tools. After retrieving the full text of the selected studies, we will conduct a standardised data extraction. Finally, a narrative synthesis will be performed. The quality of the identified studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies- 2 tool. DISCUSSION: This systematic review will provide information on the preoperative diagnostic criteria of the scleroatrophic gallbladder and the value of imaging studies in its diagnosis. In addition, this work will aid doctors in the decision-making process for diagnosing scleroatrophic gallbladder and propose treatment approaches to this condition. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered in PROSPERO (CRD42024503701).

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BACKGROUND: Sodium oxybate (Xyrem®), approved by the European Medicines Agency (EMA) for narcolepsy with cataplexy, is only available through risk mitigation programs due to potential adverse effects including respiratory and central nervous system depression, neuropsychiatric events, and misuse. OBJECTIVE: We report findings from a survey evaluating effectiveness of the European Union Xyrem® Risk Management Plan (RMP). PATIENTS AND METHODS: A cross-sectional, online, multiple-choice survey was distributed to randomly selected healthcare professionals (HCPs) from six European countries (April 2016-May 2018). Eligibility criteria: current/potential Xyrem® prescriber and/or sleep disorder specialist; contact information available; on the Xyrem® RMP educational materials mailing list. PRIMARY OUTCOME: proportion of respondents answering each question correctly (< 50% responses correct = unsatisfactory comprehension, 50% to < 70% = satisfactory, ≥ 70% = excellent), with precision assessed using 95% confidence intervals (CIs). RESULTS: Of the 709 HCPs contacted, 601 did not agree to take part, 108 were screened with 35/108 eligible for inclusion; 31 HCPs completed the survey. Of the 31 respondents, 29 (93.5%; 95% CI 84.4-100.0) reported receiving Xyrem® safety information, commonly from a sales representative, EMA Summary of Product Characteristics (SmPC), or educational meeting; only 9/31 (31.0%; 14.3-50.0) recalled receiving mailed educational materials. The number of HCPs answering dosing-related questions correctly ranged from 24/31 to 31/31. All Xyrem® contraindications were correctly identified by 26/31 (83.9%; 70.0-96.7) respondents. All respondents 'always' or 'sometimes' completed SmPC recommended activities upon treatment initiation. The majority indicated signs of abuses/misuse/diversion (23/31; 74.2%; 58.6-88.0) and criminal use (23/31; 74.2%; 59.4-89.3) should be monitored at follow-up. CONCLUSIONS: These data demonstrate the importance of providing a range of educational materials. However, the low sample size limits interpretation; increased HCP engagement would improve understanding of how best to develop educational materials. EUROPEAN POST-AUTHORIZATION STUDY (PAS) REGISTER NUMBER: EUPAS15024.

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BACKGROUND: Prognostication for esophageal cancer has traditionally relied on postoperative tissue specimens. This study aimed to use a histologically homogenous cohort to investigate the relationship between clinical, pathological or radiological variables and overall survival in patients undergoing esophagectomy for adenocarcinoma. METHODS: A single-centre study of patients who underwent esophagectomy for adenocarcinoma over 10 years in a tertiary centre was performed. By regression analysis, variables available preoperatively and postoperatively were studied for prognostication. The primary outcome was overall survival. RESULTS: 254 cases were analyzed. Over a median follow-up period of 31.8 months (IQR = 42.5), overall survival was 51.5 months (95% confidence interval: 33.0-69.9). According to hazard ratios (HR) for all-cause death, adverse prognostic factors included: a higher postoperative N-stage (HR ≥ 1.29; p ≤ 0.024), histopathological tumor length ≥25 mm (HR = 2.04; p = 0.03), poorer tumor differentiation (HR ≥ 2.86; p ≤ 0.042), and R1 status (HR = 2.33; p = 0.02). A lymph node yield ≥35 was a favorable prognostic factor (HR = 0.022; p < 0.001). Demographic and radiological variables, preoperative TNM stages, postoperative T-stage, and neoadjuvant/adjuvant treatment were not associated with overall survival. CONCLUSIONS: This study identifies several postoperatively factors which are available for the prognostication and identifies factors that should not be used to exclude patients from curative surgery.

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Study Objectives: To evaluate adherence to sodium oxybate prescribing information for indication and dosage, patients' compliance with instructions for use, safety/tolerability in routine clinical practice, and abuse potential. Methods: A postauthorization, noninterventional surveillance study (NCT00244465) in patients who were prescribed sodium oxybate according to current practice by sleep disorders specialists. Patients were monitored for ≤18 months. Results: Overall, 749 patients were enrolled; 730 included in the intent-to-treat population (narcolepsy type 1 n = 670, other indications n = 60). We report on patients with narcolepsy type 1 (female 47.9%, mean age 39.4 years); 495/670 (73.9%) completed the study. Median dose: at start of study 4.5 g per night, 6 g per night throughout study, in two equal doses. According to the treatment compliance checklist, 35.5 per cent of patients consumed alcohol, 19.3 per cent took the medication <2 hr after food, and 27.1 per cent did not adhere to recommended time schedule, with few associated treatment-emergent adverse events (TEAEs). Incidences of higher-than-recommended doses, difficulty in preparing doses, and abuse were low. TEAEs were reported by 67.3 per cent, most frequently headache (11.6%) and nasopharyngitis (6.4%). Discontinuation due to TEAEs: 8.8 per cent. Serious TEAEs: 6.4 per cent. There were no reports of respiratory depression. No particular safety concerns were identified in pediatric or elderly patients, or those with underlying sleep apnea. Conclusions: In this large postauthorization safety study of sodium oxybate use, indication and dosage prescribing recommendations were generally followed, and most patients complied with instructions, with deviations around alcohol consumption, eating before dosing and timing. The overall safety profile was consistent with previous observations; incidence of abuse was low. Section: Neurological disorders. Clinical Trial: Postauthorization, noninterventional, surveillance, pharmacoepidemiology study to evaluate long-term safety, tolerability, and compliance in administration of Xyrem (sodium oxybate) oral solution in patients who receive treatment with this medication in regular clinical practice. https://clinicaltrials.gov/ct2/show/NCT00244465, ClinicalTrials.gov: NCT00244465.

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Chronic venous disease (CVeD) is a prevalent condition with a significant socioeconomic burden, yet the pathophysiology is only just beginning to be understood. Previous studies concerning the dysregulation of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) within the varicose vein wall are inconsistent and disregard clinical progression. Moreover, it is highly plausible that MMP and TIMP expression/activity is affected by transforming growth factor (TGF)-ß1 and its signaling receptors (TGFßRs) expression/activity in the vein wall. A case-control study was undertaken to analyze genetic and immunohistochemical differences between healthy (n = 13) and CVeD (early stages: n = 19; advanced stages: n = 12) great saphenous vein samples. Samples were grouped based on anatomic harvest site and subjected to quantitative polymerase chain reaction for MMP1, MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGFßR1, TGFßR2, and TGFßR3 gene expression analysis, and then to immunohistochemistry for immunolocalization of MMP2, TIMP2, and TGFßR2. Decreased gene expression of MMP12, TIMP2, TIMP3, TIMP4, and TGFßR2 was found in varicose veins when compared to controls. Regarding CVeD clinical progression, two facts arose: results across anatomical regions were uneven; decreased gene expression of MMP9 and TGFßR3 and increased gene expression of MMP2 and TIMP3 were found in advanced clinical stages. Most immunohistochemistry results for tunica intima were coherent with qPCR results. In conclusion, decreased expression of TGFßRs might suggest a reduction in TGF-ß1 participation in the MMP/TIMP imbalance throughout CVeD progression. Further studies about molecular events in the varicose vein wall are required and should take into consideration the venous anatomical region and CVeD clinical progression.

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Chronic venous insufficiency and varicose veins occur commonly in affluent countries and are a socioeconomic burden. However, there remains a relative lack of knowledge about venous pathophysiology. Various theories have been suggested, yet the molecular sequence of events is poorly understood. Transforming growth factor-beta one (TGF-ß1) is a highly complex polypeptide with multifunctional properties that has an active role during embryonic development, in adult organ physiology and in the pathophysiology of major diseases, including cancer and various autoimmune, fibrotic and cardiovascular diseases. Therefore, an emphasis on understanding its signaling pathways (and possible disruptions) will be an essential requirement for a better comprehension and management of specific diseases. This review aims at shedding more light on venous pathophysiology by describing the TGF-ß1 structure, function, activation and signaling, and providing an overview of how this growth factor and disturbances in its signaling pathway may contribute to specific pathological processes concerning the vessel wall which, in turn, may have a role in chronic venous insufficiency.

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Objectives Transforming growth factor-beta1 (TGF-ß1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-ß1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-ß1 receptors. Methods Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein. Each vein sample was divided into two segments, which were cultivated separately in vitro (one of the segments had TGF-ß1 added) and then submitted to gene expression analysis. Results In the TGF-ß1 supplemented group, there was a general increase in the mean gene expression. Specifically, expression of MMP9, MMP12, TIMP1 and TIMP2 were statistically significant. Conclusion The results of this study demonstrate that the gene expression of MMP9, MMP12, TIMP1 and TIMP2 was influenced by the addition of TGF-ß1. These results may be translated to chronic venous insufficiency framework and suggest involvement of TGF-ß1 in the vein wall pathology.

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Splenic hemorrhage secondary to retching and vomiting from incarceration of paraesophageal hernia is a rare but life-threatening complication. Clinicians need to be aware of this complication in the event of sudden unexplained hemodynamic instability. Surgical intervention for the hernia is best performed as soon as possible once the patient is stabilized, before complications such as perforation or further bleeding occur. We report two cases of splenic rupture and intraperitoneal bleeding resulting from traction of the gastrosplenic pedicle associated with retching and vomiting from a giant paraesophageal hernia.

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This study aimed to develop a protocol of semen cryopreservation of the mutton snapper Lutjanus analis. The interaction between three extenders ( pH 6.1; 7.8 and 8.2) , two concentrations of dimethyl sulfoxide ( DMSO, 5 and 10%) and three cooling rates ( -90; -60 and -30°C.min-1) on the sperm motility rate and motility time were analyzed by a factorial experiment. A sample of 30 fishes ( 1,261 ± 449 g) collected in the nature was kept in floating net cages. The semen was frozen by using cryogenic straws, in nitrogen vapour and transferred, later, to liquid nitrogen. Fertilization test was accomplished to evaluate the viability of the cryopreserved sperm. The highest sperm motility rate and motility time ( P < 0.05) was achieved by combining extender C ( pH 8.2) with DMSO ( 10%) and cooling rate of -60°C.min-1 ( P < 0.05) . The use of cryopreserved sperm presented fertilization rates higher than 59% validating the present protocol for mutton snapper.

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A study of 701 primary adenocarcinomas of the lung was made at the Department of Pathology of the Hospital da Universidade de Coimbra for a period of fifteen years, between 1990 and 2004. In the same period 382 metastases were diagnosed, mainly from colon (119) and breast (66). The incidence of primary adenocarcinomas varied from 16 cases in 1990 to 49 cases in men and from 12 to 37 cases in women in that period. From 2001 onwards, the incidence was almost coincident in both genders. In the last four years, since 2001, patients were in the seventies at the time of diagnosis and a considerable number of cases were diagnosed after 80 years of age. The criteria defined by the WHO classification of Tumours of the Lung, Pleura, Thymus and Heart 2004 were applied to the primary adenocarcinomas of the lung and as was expected, bronchioloalveolar carcinomas had its incidence in women while acinar adenocarcinomas were diagnosed mainly in men. These conclusions were obtained via surgical specimens and when surgical biopsies were representative and those were mainly in stage IIB and IIIA. A number of 109 cases had the final diagnosis of adenocarcinoma of the lung based on morphology and immunohistochemistry criteria.

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A espécie Centropomus parallelus, conhecida como robalo nas regiöes Sudeste e Sul e como camorim no Nordeste e Norte, foi submetida à reproduçäo induzida com hCG (human chorionic gonadotropin), no Laboratório de Maricultura do Instituto de Pesca, em Cananéia, SP (25§ 01' S; 47§ 57' W). Em novembro e dezembro de 1996 e janeiro de 1997, fêmeas dessa espécie pesando entre 210 g e 1.740 g e medindo entre 25,7 cm e 56,0 cm foram selecionadas levando-se em consideraçäo o valor médio do diâmetro dos ovócitos, o padrao de distribuiçäo porcentual dos valores do diâmetro e a localizaçäo da vesícula germinativa na célula. Foram utilizadas doses únicas de 1, 2 ou 5 UI de hCG por grama de peso corporal em vinte e seis fêmeas que apresentaram ovócitos com diâmetro médio ao redor de 400 µm e distribuiçäo de freqüência porcentual de valores dos diâmetros unimodal, com moda em 435,6 µm. Como controle, foram utilizadas quatro fêmeas, que receberam 1 ml de soluçäo salina a 0,9 por cento. Aproximadamente 35 horas após a aplicaçäo do hormônio, as fêmeas iniciaram a liberaçäo dos óvulos. Neste momento, os óvulos apresentaram o diâmetro médio superior a 600 µm, uma única gota de óleo e vesícula germinativa quebrada. Foi feita extrusäo dos óvulos para fertilizaçäo a seco. Os machos näo foram submetidos a tratamento hormonal, sendo selecionados pela quantidade e viscosidade do sêmen e motilidade dos espermatozóides. A taxa de fertilizaçao variou de 70 a 90 por cento. A eclosäo das larvas ocorreu 18 horas após a fertilizaçäo. Durante a incubaçäo dos ovos e eclosäo das larvas, a temperatura da água foi de 25 ñ 1§C e a salinidade variou de 29 a 35 por cento

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