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Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging as they show overlapping histomorphological and immunohistochemical features. Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary [25 primary ovarian mucinous carcinomas (POMCs) and 28 mucinous borderline tumors (MBTs)] and 27 secondary (12 of colonic origin, 7 of appendiceal origin, and 8 of gastric origin). Expression was correlated with different clinicopathologic parameters. PAX8-positive immunostaining was detected in 38 out of 53 cases (71.69%) of primary ovarian mucinous neoplasms (POMNs) with null positivity in the secondary ovarian mucinous tumors (0/27). SATB2-positive expression was detected in 16 out of 27 cases (59.26%) of the secondary ovarian mucinous tumors. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). A profile of SATB2-/PAX8+ and SATB2+/PAX8- can be used to differentiate POMNCs from secondary ovarian mucinous tumors of GI origin, respectively, with 100% specificity. PAX8 expression is associated with some clinicopathologic parameters providing the basis for the possible usage of PAX8 as prognostic marker.
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OBJECTIVES: To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). MATERIALS AND METHODS: Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale. RESULTS: This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001). CONCLUSIONS: Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.
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Terapia Antiplaquetaria Doble , Fibrinolíticos , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/mortalidad , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Fibrinolíticos/efectos adversos , Fibrinolíticos/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Resultado del Tratamiento , Terapia Antiplaquetaria Doble/efectos adversos , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Riesgo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Medición de Riesgo , Evaluación de la Discapacidad , Administración Intravenosa , Recuperación de la Función , Estudios Observacionales como Asunto , Anciano de 80 o más AñosRESUMEN
Programmed cell death protein-1 (PD-1) is an immune checkpoint protein, PD-1 interaction with PD ligand-1 (PD-L1) is essential for maintaining immunological tolerance. The study aimed to study and compare the levels of PD-1 and PD-L1 in lesional and nonlesional skin of lichen planus (LP) patients and compare these levels to normal healthy controls to assess their role in the pathogenesis of LP. This case-control study involved 30 patients with LP and 30 healthy age-and sex-matched controls. After clinical assessment of the severity by LP severity index score (LPSI), skin biopsies were taken from lesional and nonlesional skin of LP patients and from normal skin in healthy controls for assessment of the tissue levels of PD-1 and PD-L1 by ELISA. The tissue levels of both PD-1 and PD-L1 were significantly higher in healthy controls than in both lesional and nonlesional skin of LP patients (P < 0.001). Also, significantly higher PD-l and PD-L1 levels in nonlesional skin than in lesional skin of LP patients were reported (P < 0.001). No significant correlations were found between lesional and nonlesional PD-1, PD-L1 levels, or LPSI score. Based on the fact that PD-1/PD-L1 interaction is important to maintain tolerance and protection against autoimmune diseases, in addition to our study results that revealed lower levels of PD-1/PD-L1 in LP skin than in healthy skin, we can conclude that PD-1/PDL-1 may be incriminated in the pathogenesis of LP. ClinicalTrials.govID: NCT04892381.
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Antígeno B7-H1 , Liquen Plano , Humanos , Antígeno B7-H1/metabolismo , Estudios de Casos y Controles , Liquen Plano/metabolismo , Ligandos , Receptor de Muerte Celular Programada 1RESUMEN
RATIONALE: Respiratory culture screening is mandatory for all potential lung transplant donors. There is limited evidence on the significance of donor multidrug-resistant (MDR) bacteria on transplant outcomes. Establishing the safety of allografts colonized with MDR bacteria has implications for widening an already limited donor pool. OBJECTIVES: We aimed to describe the prevalence of respiratory MDR bacteria among our donor population and to test for associations with posttransplant outcomes. METHODS: This retrospective observational study included all adult patients who underwent lung-only transplantation for the first time at King Faisal Specialist Hospital & Research Centre in Riyadh from January 2015 through May 2022. The study evaluated donor bronchoalveolar lavage and bronchial swab cultures. MAIN RESULTS: Sixty-seven of 181 donors (37%) had respiratory MDR bacteria, most commonly MDR Acinetobacter baumannii (n = 24), methicillin-resistant Staphylococcus aureus (n = 18), MDR Klebsiella pneumoniae (n = 8), MDR Pseudomonas aeruginosa (n = 7), and Stenotrophomonas maltophilia (n = 6). Donor respiratory MDR bacteria were not significantly associated with allograft survival or chronic lung allograft dysfunction (CLAD) in adjusted hazard models. Sensitivity analyses revealed an increased risk for 90-day mortality among recipients of allografts with MDR Klebsiella pneumoniae (n = 6 with strains resistant to a carbapenem and n = 2 resistant to a third-generation cephalosporin only) compared to those receiving culture-negative allografts (25.0% versus 11.1%, p = 0.04). MDR Klebsiella pneumoniae (aHR 3.31, 95%CI 0.95-11.56) and Stenotrophomonas maltophilia (aHR 5.35, 95%CI 1.26-22.77) were associated with an increased risk for CLAD compared to negative cultures. CONCLUSION: Our data suggest the potential safety of using lung allografts with MDR bacteria in the setting of appropriate prophylaxis; however, caution should be exercised in the case of MDR Klebsiella pneumoniae.
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Trasplante de Pulmón , Staphylococcus aureus Resistente a Meticilina , Stenotrophomonas maltophilia , Adulto , Humanos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Klebsiella pneumoniae , Donantes de TejidosRESUMEN
INTRODUCTION: Our systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of Rucaparib, a PARP inhibitor (PARPi), in patients with ovarian cancer and BRCA mutation. METHODS: Online databases were comprehensively searched for all phase III Randomized trials that used Rucaparib therapy for ovarian cancer patients and patients having BRCA mutation. Efficacy results are progression-free survival and overall response rate in addition to addressing its safety concerns. RESULTS: After pooling data from 4 clinical trials, the analysis showed a significant improvement in PFS among ovarian cancer patients and for the maintenance therapy with a hazard ratio (HR) of 0.49 (95% CI 0.34-0.73, p = 0.0003) and 0.42 (95% CI 0.29-0.62, p < 0.0001), respectively. For patients with BRCA mutations, the PFS showed significant improvement with a (HR) of 0.42 (95% CI 0.25-0.71, p < 0.001). A difference was observed in the risk of grade ≥ 3 TEAEs between the two groups (RR = 2.48; 95% CI 1.40-4.37). CONCLUSION: Rucaparib demonstrated significant efficacy in improving PFS and ORR in ovarian cancer patients, particularly those having BRCA mutations. However, they should be closely monitored due to the greater risk of various adverse effects.
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Neoplasias Ováricas , Humanos , Femenino , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Indoles/efectos adversos , Mutación , Ensayos Clínicos Fase III como AsuntoRESUMEN
A negative impact of finasteride on fertility has been reported, in which over production of reactive oxygen species and apoptosis were implicated. Hesperidin, a plant-derived bioflavonoid with antioxidant and anti-apoptotic effects, may mitigate these adverse effects. In order to investigate the possible protective role of hesperidin against finasteride-induced seminiferous tubules toxicity in adult male Wistar rats, 60 rats were randomized into five groups (I-V) receiving distilled water, 0.5% sodium carboxymethylcellulose solution, hesperidin, finasteride, and combined hesperidin and finasteride respectively. Testicular weight, sperm count and motility were determined. Testicular tissue homogenates were prepared to measure the level of malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH) and the gene expression of caspase-3 and B-cell lymphoma 2 (Bcl2). Testes were processed for light and electron microscopic evaluation. Johnsen score was calculated. Administration of finasteride resulted in significantly decreased testicular weights, sperm count and motility, Johnsen score, tissue levels of TAC and GSH together with significant increase in tissue MDA. Gene expression revealed significantly increased caspase-3 and decreased Bcl2. Furthermore, finasteride disrupted the seminiferous tubules, causing degenerative changes affecting Sertoli cells and spermatogenic cells. Co-administration of hesperidin with finasteride resulted in improvement in testicular weights, TAC, GSH, Bcl2, Johnsen score, sperm count and motility as well as preservation of the structure of the seminiferous tubules. To conclude, hesperidin was found to have a protective potential on finasteride-induced oxidative stress, apoptosis and testicular structural damage.
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Hesperidina , Testículo , Masculino , Ratas , Animales , Ratas Wistar , Hesperidina/metabolismo , Hesperidina/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Finasterida/toxicidad , Finasterida/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Semen/metabolismo , Túbulos Seminíferos , Espermatozoides , Estrés Oxidativo , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
BACKGROUND: Transplanting lungs from donors with positive blood cultures has not been shown to adversely affect survival. There is limited evidence for potential effects on other outcomes, such as hospital course, graft function, and transmission of infection. METHODS: This retrospective cohort study included adult patients who underwent lung-only transplantation for the first time between March 2010 and December 2022. Outcomes of patients whose donors had positive blood cultures within 72 h of transplant were compared to patients whose donors had negative blood cultures. RESULTS: Twenty-five (10.8%) of 232 donors had positive blood cultures, including a single, unexpected case with candidemia. The most commonly isolated bacteria were Enterobacter cloacae (n = 5), Klebsiella pneumoniae (n = 5), Acinetobacter baumannii (n = 3), Pseudomonas aeruginosa (n = 3), and Staphylococcus aureus (n = 3). Eleven donors had identical bacteria in their respiratory cultures. All patients who were transplanted from donors with positive blood cultures survived beyond 90 days. Positive donor blood cultures were not associated with longer hospital stay, in-hospital complications, acute cellular rejection, or the achievement of 80% predicted forced expiratory volume in the first second. Probable transmission of donor bacteremia occurred in only two cases (both with S. aureus). These two donors had positive respiratory cultures with the same organism. CONCLUSION: The study did not find an increased risk of adverse events when transplanting lungs from donors with positive blood cultures. Allograft cultures may be more predictive of the risk of transmitting infections.
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Trasplante de Pulmón , Staphylococcus aureus , Adulto , Humanos , Estudios Retrospectivos , Cultivo de Sangre , Donantes de Tejidos , Trasplante de Pulmón/efectos adversos , Donantes de Sangre , BacteriasRESUMEN
BACKGROUND AND OBJECTIVE: One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases. CONCLUSION: S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.
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Colitis Ulcerosa , Lisofosfolípidos , Moduladores de los Receptores de fosfatos y esfingosina 1 , Esfingosina/análogos & derivados , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Receptores de Esfingosina-1-Fosfato/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Vital pulp therapy, based on the use of stem cells, has promising research and therapeutic applications in dentistry. It is essential to understand the direct effect of capping materials on the dental pulp stem cells of primary teeth, which contribute to the healing powers of the tooth. The aim of this study is to evaluate the effect of different capping materials (Calcium Hydroxide (DyCal®) - Glass Ionomer (Fuji IX®) and light-cured resin modified calcium silicate (TheraCal LC®)) on the viability, proliferation, and differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). METHODS: SHEDs were isolated from extracted primary teeth, then divided into four groups and each of the capping materials were applied to the stem cells as follows: group I the controls, group II with Ca(OH)2, group III with the GIC, and group IV with the Theracal LC. For all groups assessment of viability and proliferation rate was done using the MTT cell proliferation assay. Also, Differentiation was evaluated by measuring the gene expression of Alkaline phosphatase enzyme activity (ALP) and Dentin matrix protein-1 (DMP1) through quantitative real-time PCR. Morphological assessment was conducted using Alizarin Red S staining. All evaluations were performed after 7 and 14 days of culture. RESULTS: TheraCal LC showed the highest values of proliferation, which was significant only compared to the control group after 2 weeks (p = 0.012). After one week, TheraCal LC showed the highest significant values of ALP and DMP1 compared to all other groups (p < 0.001). CONCLUSION: The three materials under study are biocompatible, maintain viability, and stimulate the proliferation and differentiation of SHEDs. However, TheraCal LC allows better proliferation of SHEDs than Dycal Ca(OH)2 and Fuji IX GIC.
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Compuestos de Calcio , Hidróxido de Calcio , Humanos , Hidróxido de Calcio/farmacología , Hidróxido de Calcio/uso terapéutico , Compuestos de Calcio/farmacología , Silicatos/farmacología , Diferenciación Celular , Células Madre , Diente Primario , Proliferación Celular , Pulpa DentalRESUMEN
INTRODUCTION: We aimed to describe the clinical efficacy and safety of tislelizumab, a new (PD-1) inhibitor, in patients with malignant solid tumors. METHODS: We searched relevant databases for phase III randomized controlled trials, including patients with solid tumors. The following outcomes are of interest: overall response rate (OS), overall survival (ORR), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events (TRAE). We conducted subgroup analyses based on the line of therapy, type of solid tumor, and tislelizumab alone or combined with chemotherapy. RESULTS: Seven phase III RCTs with 3478 were included in the meta-analysis. Pooled analysis demonstrated that tislelizumab significantly improved ORR and DCR with (OR) of 2.59 (95% (CI) = 2.15-3.12, p < 0.00001) and 1.78 (95% CI = 1.43-2.21, p > 0.00001), respectively. Pooled HRs for OS and PFS were 0.71 (95% CI = 0.65-0.78, p > 0.00001) and 0.68 (95% CI = 0.54-0.84, p = 0.0005), respectively. CONCLUSION: Overall, based on this meta-analysis, the available data strongly supports the utilization of tislelizumab in the treatment of malignant solid tumors. PROSPERO REGISTRATION NUMBER: CRD42023408815.
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Neoplasias , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Perioperative analgesia is very important during an abdominal hysterectomy. Determining the impact of the erector spinae plane block (ESPB) on patients undergoing an open abdominal hysterectomy while under general anesthesia was our aim. METHODS: In order to create equal groups, 100 patients who underwent elective open abdominal hysterectomies under general anesthesia were enlisted. The preoperative bilateral ESPB with 20 ml of bupivacaine 0.25% was administered to the ESPB group (n = 50). The same procedure was performed on the control group (n = 50), but they received a 20-ml saline injection instead. The primary outcome is the total amount of fentanyl consumed during surgery. RESULTS: We found that the mean (SD) intraoperative fentanyl consumption was significantly lower in the ESPB group than in the control group (82.9 (27.4) g vs. 148.5 (44.8) g, with a 95% CI = -80.3 to -50.8; p 0.001). Likewise, mean (SD) postoperative fentanyl consumption was significantly lower in the ESPB group than in the control group (442.4 (17.8) g vs. 477.9 (10.4) g, with a 95% CI = -41.3 to -29.7; p 0.001). On the other hand, there is no statistically significant difference between the two study groups regarding sevoflurane consumption (89.2 (19.5) ml vs. 92.4 (15.3) ml, with a 95% CI = -10.1 to 3.8; p 0.4). We documented that during the post-operative period (0-24 h), VAS scores at rest were, on average, 1.03 units lower in the ESPB group (estimate = -1.03, 95% CI = -1.16-(-0.86), t = -14.9, p-value 0.001), and VAS scores during cough were, on average, 1.07 units lower in the ESPB group (estimate = -1.07, 95% CI = -1.21-(-0.93), t = -14.8, p-value 0.001). CONCLUSION: Bilateral ESPB can be utilized as an adjuvant method to reduce intraoperative fentanyl consumption and enhance postoperative pain control in patients undergoing open total abdominal hysterectomy under general anesthesia. It is effective, secure, and little obtrusive. TRIAL REGISTRATION: No protocol revisions or study amendments have been made since the trial's inception, according to the information on ClinicalTrials.gov (NCT05072184; principal investigator: Mohamed Ahmed Hamed; date of registration: October 28, 2021).
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Bloqueo Nervioso , Proyectos de Investigación , Femenino , Humanos , Anestesia General , Fentanilo , Histerectomía , Dolor Postoperatorio/prevención & control , Ultrasonografía IntervencionalRESUMEN
Background and Aims: The viral agent of the novel coronavirus disease 2019 (COVID-19) continues to spread worldwide, leading to a global pandemic. this may negatively affect students' mental health who have to maintain their learning efforts. Therefore, we aimed to assess students' perceptions of the online learning programs designed for university students in Arab countries during the COVID-19 pandemic. Methods: This cross-sectional study was conducted on university students using a self-administered online questionnaire in 15 Arab countries, including 6779 participants. The actual sample size was calculated using the EpiInfo program calculator. The validated, piloted questionnaire assessed the effectiveness of internet-based distance learning applications used in these countries during the pandemic. The SPSS version 22 was used. Results: Among the 6779 participants, 26.2% believed that their teachers diversify learning methods, 22.0% thought that their teachers were able to treat the weakness the students have, and 30.7% agreed that their teachers efficiently communicate with them through COVID-19 internet-based learning process. Around 33% of students participated in lectures effectively, 47.4% submitted their homework within accepted deadlines, and 28.6% thought that their colleagues did not cheat during exams and homework. Around 31.3% of students believed that online-based learning had a role in directing them towards research, and 29.9% and 28.9%, respectively, believed that online learning had a role in developing analytical thinking and synthesis skills. Participants reported many suggestions to enhance the process of internet-based distance learning in the future. Conclusion: Our study suggests that online-based distance learning in Arab countries still needs more improvement as students still are more inclined toward face-to-face teaching. However, exploring the factors that influence students' perceptions of e-learning is vital for improving the quality of online-based distance learning. We recommend exploring the perceptions of educators regarding their experience towards online-based distance learning during COVID-19 lockdown.
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OBJECTIVE: To evaluate the clinical efficacy and safety of Capivasertib on patients with solid tumors. METHODS: Data from four RCTs were pooled to create a systematic review and meta-analysis focusing on Capivasertib-treated patients with solid tumor. Progression-free survival (PFS) and adverse events (AE) were the primary outcomes. RESULTS: A total of 540 individuals from four RCTs were included. The analysis showed that Capivasertib improved PFS for the ITT population with an HR of 0.75 (95% CI = 0.62-0.90, p = 0.002), whereas it did not show improvement in PFS of the PI3K/AKT/PTEN-altered group with an HR = 0.61 (95% CI = 0.32-1.16, p = 0.13). The analysis also showed that Capivasertib improved OS for the ITT population with an HR = 0.61 (95% CI = 0.47-0.78, p = 0.0001). For safety, four studies were included; statistical differences between Capivasertib and placebo were found in discontinuation of Capivasertib due to toxicity or AE (RR = 2.37, 95% CI = 1.37-4.10, p = 0.002). CONCLUSION: Capivasertib plus chemotherapy or hormonal therapy combination has shown promising antitumor efficacy and promising safety profile in the treatment of individuals with solid tumor.
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Neoplasias , Fosfatidilinositol 3-Quinasas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias/tratamiento farmacológicoRESUMEN
Background: Current guidelines recommend a body mass index (BMI) of 16 kg/m2 as the minimum threshold for lung transplantation, despite mixed evidence on outcomes in underweight patients. The current study aimed to describe survival outcomes of underweight patients who underwent lung transplantation at a single center. Methods: This retrospective observational study included adult lung transplant recipients who underwent transplantation for the first time between March 2010 and March 2022 at King Faisal Specialist Hospital and Research Center and excluded patients with obesity. We defined an underweight status as a BMI <17 kg/m2. Results: Forty-eight of the 202 lung transplant recipients were underweight at the time of surgery. The underweight patients had similar lengths of hospital (p = 0.53) and intensive care unit (p = 0.81) stays compared to other patients. Thirty-three percent of underweight patients had died within 5-year follow-up, compared to 34% of patients who were not underweight. There was no significant difference in mortality risk between underweight patients and patients with normal BMIs in our multivariable Cox regression model (adjusted HR 1.57, 95%CI: 0.77-3.20, p = 0.21). Exploratory analyses revealed that a pre-transplant BMI <13 kg/m2 was associated with a trend towards increased 5-year mortality (adjusted HR 4.00, 95%CI: 0.87-18.35, p = 0.07). Conclusions: Our findings suggest that patients with BMIs of 13-17 kg/m2 may be candidates for lung transplantation. Large multi-center cohort studies are needed to confirm the lower BMI limit for safely transplanting patients.
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This study aims to design and optimize chitosan-coated bilosomal formulations loaded with psoralidin (Ps-CS/BLs) with improved physicochemical properties, oral bioavailability, and boosted apoptotic and necrotic effects. In this regard, uncoated bilosomes loaded with Ps (Ps/BLs) were nanoformulated using the thin-film hydration technique using different molar ratios of phosphatidylcholine (PC), cholesterol (Ch), Span 60 (S60), and sodium deoxycholate (SDC) (1:0.4:0.2:0.125, 1:0.4:0.2:0.25, and 1:0.4:0.2:0.5, respectively). The best-optimized formulation with respect to size, PDI, zeta potential, and EE% was selected and then coated with chitosan at two different concentrations (0.125 and 0.25 w/v%), forming Ps-CS/BLs. The optimized Ps/BLs and Ps-CS/BLs showed a spherical shape and relatively homogenous size with negligible apparent agglomerations. Additionally, it was demonstrated that coating Ps/BLs with chitosan has significantly increased the particle size from 123.16 ± 6.90 in the case of Ps/BLs to 183.90 ± 15.93 nm in the case of Ps-CS/BLs. In addition, Ps-CS/BLs exhibited higher zeta potential (+30.78 ± 1.44 mV) as compared to Ps/BLs (-18.59 ± 2.13 mV). Furthermore, Ps-CS/BL showed enhanced entrapment efficiency (EE%) of 92.15 ± 7.20% as compared to Ps/BLs (68.90 ± 5.95%). Moreover, Ps-CS/BLs exhibited a more sustained release behavior of Ps compared to Ps/BLs over 48 h, and both formulations were best obeying the Higuchi diffusion model. More importantly, Ps-CS/BLs displayed the highest mucoadhesive efficiency% (74.89 ± 3.5%) as compared to Ps/BLs (26.78 ± 2.9%), indicating the ability of the designed nanoformulation to improve oral bioavailability and extend the residence time inside the gastrointestinal tract upon oral administration. Moreover, upon evaluating the apoptotic and necrotic effects of free Ps and Ps-CS/BLs on human breast cancer cell lines (MCF-7) and human lung adenocarcinoma cell lines (A549), there was a dramatic increase in the percentages of the apoptotic and necrotic cell compared to the control and free Ps. Our findings suggest the possible oral use of Ps-CS/BLs in hampering breast and lung cancers.
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BACKGROUND: Management of postoperative pain after shoulder arthroscopy is an important issue. Dexmedetomidine, as an adjuvant, improves nerve block efficacy and decreases postoperative consumption of opioids. As a result, we designed this study to determine if adding dexmedetomidine to an erector spinae plane block (ESPB) that is guided by ultrasound (US) is beneficial for treating immediate postoperative pain following shoulder arthroscopy. METHODS: This randomized controlled double-blind trial recruited 60 cases 18-65 years old of both sexes, American Society of Anesthesiologists (ASA) physical status I-II, scheduled for elective shoulder arthroscopy. Random allocation of 60 cases was done equally into two groups according to the solution injected in US-guided ESPB at T2 before general anesthetic induction. Group (ESPB): 20 ml 0.25% bupivacaine. Group (ESPB + DEX): 19 ml bupivacaine 0.25% + 1 mL dexmedetomidine 0.5 µg/kg. The primary outcome was The total rescue morphine consumption in the first 24 postoperative hours. RESULTS: The mean intraoperative fentanyl consumption was significantly lower in the group (ESPB + DEX) compared to the group (ESPB) (82.86 ± 13.57 versus 100.74 ± 35.07, respectively, P = 0.015). The median (IQR) time of the 1st rescue analgesic request was significantly delayed in the group (ESPB + DEX) compared to group (ESPB) [18.5 (18.25-18.75) versus 12 (12-15.75), P = 0.044]. The number of cases that required morphine was significantly lower in the group (ESPB + DEX) than in the group (ESPB) (P = 0.012). The median (IQR) of total postoperative morphine consumption in 1st 24 h was significantly lower in the group (ESPB + DEX) compared to the group (ESPB) [0 (0-0) versus 0 (0-3), P = 0.021]. CONCLUSION: The dexmedetomidine as an adjuvant to bupivacaine in ESPB produced adequate analgesia by reducing the intraoperative and postoperative opioid requirements in shoulder arthroscopy. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT05165836; principal investigator: Mohammad Fouad Algyar; registration date: 21/12/ 2021).
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Analgesia , Dexmedetomidina , Bloqueo Nervioso , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Artroscopía , Hombro , Bupivacaína , Dolor Postoperatorio/prevención & control , Analgésicos Opioides , Morfina , Ultrasonografía IntervencionalRESUMEN
Aim: The aim was to investigate the expression profile of miR-516a-3P and its correlation with the PNPLA3 rs738409 polymorphism in Egyptian hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) patients. Materials & methods: miR-516a-3P was quantified and rs738409 was genotyped by quantitative reverse transcription PCR. Results: miR-516a-3P was significantly upregulated in HCC patients compared with HCV patients (p = 0.001). Receiver operating characteristic curve analysis confirmed that miR-516a-3P discriminates HCC from HCV (p = 0.001). A significant (p = 0.015) correlation between miR-516a-3p level and PNPLA3 rs738409 genotypes was recorded in HCV patients, yet it was not recorded in either healthy individuals or HCC patients. miR-516a-3p level was significantly (p = 0.001) higher in HCV patients carrying the rs738409 GG genotype than in those carrying the CC genotype. Conclusion: miR-516a-3P is a potential biomarker in HCC. PNPLA3 rs738409 GG carriers affect miR-516a-3P expression in HCV, and this may highlight a new mechanism in liver disease.
In the past decade, miRNAs were established as biomarkers in various cancers, including liver cancer. Information about the deregulation of miR-516a-3p and its efficiency as a biomarker in hepatitis C virus (HCV) and liver cancer patients is lacking globally and in Egypt. This study proved for the first time that miR-516a-3p is differentially expressed in HCV and liver cancer patients and is statistically efficient in discriminating between them, so it might be used for early detection of HCC. Genetic variants that affect expression levels of genes are called expression quantitative trait loci (eQTL), and those acting on genes on other chromosomes are called trans-eQTL. The authors speculate that rs738409 is a genetic variant that might have a trans-eQTL effect on the miR-516a-3p gene in HCV patients.
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Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , MicroARNs , Fosfolipasas A2 Calcio-Independiente , Humanos , Biomarcadores , Carcinoma Hepatocelular/genética , Hepatitis C/genética , Lipasa/genética , Neoplasias Hepáticas/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genética , Fosfolipasas A2 Calcio-Independiente/genética , Aciltransferasas/genéticaRESUMEN
BACKGROUND: Tobacco use is one of the major public health threats globally. Community pharmacists are uniquely positioned to offer tobacco cessation services owing to their easy accessibility by the public. To prepare Qatar community pharmacists to develop the competencies and skills required to offer smoking cessation services, an intensive tobacco control education program was designed and implemented. The study aimed to assess the impact of the tobacco education program on the pharmacists' skills and competence. METHODS: A random sample of community pharmacists in Qatar was chosen for participation in the program. Consenting participants were randomly assigned to either intervention or control groups. The intervention group received an intensive education program on treatment of tobacco-use disorder, while a short didactic session on a non-tobacco-related topic was delivered to the control group. The pharmacists' tobacco cessation skills and competencies were assessed using an Objective Structured Clinical Examination (OSCE). RESULTS: A total of 54 and 32 community pharmacists in the intervention group and the control group, respectively, completed the OSCE. The intensive tobacco education group achieved significantly higher total scores than the control group in all the OSCE cases. Specifically, the mean total scores for the intervention group were 15.2, 15.3, 14.2, 14.6, 16.3, and 15.2 compared to 8.8, 6.2, 7.7, 9.2, 8.3, and 11.3 for the control group (p < 0.001) for cases one to six respectively. CONCLUSION: The study demonstrated that an intensive tobacco cessation education program can improve pharmacists' tobacco cessation skills and increase their tobacco cessation counseling abilities. TRIAL REGISTRATION: Clinical Trials NCT03518476 ( https://clinicaltrials.gov/ct2/show/NCT03518476 ) Registration date: May 8, 2018.
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Servicios Comunitarios de Farmacia , Cese del Hábito de Fumar , Tabaquismo , Consejo , Humanos , Farmacéuticos/psicología , Tabaquismo/terapiaRESUMEN
BACKGROUND: Association studies identified genetic polymorphisms as predictive risk factors of rapid fibrosis progression in chronic hepatitis C (CHC). This study aims to assess the impact of IL28B rs8099917 polymorphism on CHC genotype 4 (G4) susceptibility and liver fibrosis progression individually; and in combination with PNPLA3 rs738409. PATIENTS AND METHODS: IL28B rs8099917 and PNPLA3 rs738409 were genotyped in 150 Egyptian CHC patients and 175 healthy controls using real-time PCR. RESULTS: IL28B rs8099917 genotype distribution significantly differs in healthy individuals versus CHC patients (p = .018); and in low versus advanced fibrosis IL28B (p = .013). The haplotype CC -GG (PNPLA3-IL28B) is considered a high-risk signature for susceptibility to CHC infection. Similarly, GG-GG (PNPLA3-IL28B) is considered a high-risk signature for higher degree of fibrosis. CONCLUSION: IL28B rs8099917 and PNPLA3 rs738409 introduce genetic signature to identify patients at higher risk for CHC susceptibility and fibrosis progression in CHC G4.