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INTRODUCTION: Obesity is frequent among organ transplant recipients, increasing the risk of acute graft rejection and overall morbimortality. Laparoscopic sleeve gastrectomy (LSG) effectively improves graft survival and associated comorbidities. We first compared 30-d outcomes between chronic immunosuppressed (CI) and nonchronic immunosuppressed (non-CI) patients. Then, between organ transplant and non-organ transplant CI patients who underwent LSG. METHODS: Patients who underwent LSG within the metabolic and bariatric surgery accreditation and quality improvement program 2017-2019 were included. Using 1:1 and 1:4 propensity score matching analysis, the cohorts were matched for 30 characteristics. We then compared 30-d outcomes between CI and non-CI (analysis 1) and between organ transplant and non-organ transplant CI patients who underwent LSG (analysis 2). RESULTS: A total of 486,576 patients were included. The matched cohorts in analysis 1 (n = 8978) and analysis 2 (n = 1152, n = 371) had similar preoperative characteristics. Propensity score matching in analysis 1 showed that patients in the CI group had significantly higher rates of renal complications (0.4% versus 0.2%, P = 0.006), unplanned intensive care unit admission (1.1% versus 0.7%, P = 0.003), blood transfusions (1.1% versus 0.7%, P = 0.003), readmissions (4.6% versus 3.5%, P < 0.001), reoperations (1.4% versus 1.0%, P = 0.033), interventions (1.3% versus 1.0%, P = 0.026), and postoperative bleeding (0.6% versus 0.4%, P = 0.013). In analysis 2, patients with organ transplant CI had a higher rate of pulmonary complications (1.1% versus 0.3%, P = 0.043), renal complications (2.4% versus 0.2%, P < 0.001), blood transfusions (6.5% versus 1.3%, P < 0.001), and readmissions (10.0% versus 4.6%, P < 0.001). CONCLUSIONS: Patients with transplant-related CI who underwent LSG have higher 30-d postoperative complication rates compared to nontransplant-related CI patients; however, there were no differences in terms of mortality, intensive care unit admissions, staple line leaks, or bleeding. LSG is safe and feasible in this high-risk population.
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Gastrectomia , Transplante de Órgãos , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Gastrectomia/efeitos adversos , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Transplante de Órgãos/efeitos adversos , Pontuação de Propensão , Resultado do Tratamento , Laparoscopia/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Sobrevivência de Enxerto , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/etiologiaRESUMO
BACKGROUND: Sleeve gastrectomy is the most common bariatric procedure and its long-term complications include inadequate weight loss, weight regain, and de novo GERD, often requiring revisional surgery. Revisions, notably re-sleeve and conversion to Roux-en-Y gastric bypass (RYGB), are frequently performed, but safety data is limited. Herein, we used the MBSAQIP database to compare 30 day outcomes of primary sleeve gastrectomy (SG) with re-sleeve (RS) and SG to RYGB conversion. METHODS: Patients who underwent primary SG, RS, and SG to RYGB conversion within the MBSAQIP data registry from January 1, 2020 to December 31, 2022 were included in this study. Using Propensity Score Matching analysis, the cohorts were matched for 23 preoperative characteristics. We then compared 30 day postoperative outcomes and bariatric-specific complications between primary SG and RS (analysis 1) and between RS and SG to RYGB conversion (analysis 2). RESULTS: A total of 302,961 were included. The matched cohorts in analysis 1 (n = 1630) and analysis 2 (n = 1633) had similar pre-operative characteristics. Propensity-matched outcomes in analysis 1 showed that patients in the RS group had significantly higher staple line leak (1.3% vs. 0.1%, p < 0.001) when compared to primary SG. Similarly, longer operative times (90.16 ± 51.90 min vs. 68.32 ± 37.54 min, p < 0.001) and higher rates of readmissions (5.5% vs. 2.1%, p < 0.001), reoperations (2.3% vs. 0.6%, p < 0.001), interventions (2.5% vs. 0.4%, p < 0.001) were found in those who underwent RS. In analysis 2, RS showed higher leak rates (1.3% vs. 0.5%, p = 0.015) when compared to conversion from SG to RYGB. CONCLUSION: The RS group has a higher risk of staple line leaks compared to primary SG and conversion from SG to RYGB. In our study, there was a 2.6-fold increase in staple line leak after re-sleeve compared to RYGB conversion and a 13-fold increase compared to primary SG.
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Fístula Anastomótica , Gastrectomia , Derivação Gástrica , Obesidade Mórbida , Reoperação , Humanos , Derivação Gástrica/métodos , Derivação Gástrica/efeitos adversos , Gastrectomia/métodos , Gastrectomia/efeitos adversos , Feminino , Masculino , Reoperação/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Obesidade Mórbida/cirurgia , Grampeamento Cirúrgico/métodos , Pontuação de Propensão , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: The evolution of minimally invasive surgery has transformed inguinal hernia repair (IHR). The innovative single-port technique reduces the number of surgical incisions. However, the benefits of single-port IHR remain controversial. Our systematic review and network meta-analysis assess the efficacy and clinical outcomes of single-port laparoscopic inguinal hernia repair (SPL-IHR), multi-port laparoscopic inguinal hernia repair (MPL-IHR), single-port robotic inguinal hernia repair (SPR-IHR), and multi-port robotic inguinal hernia repair (MPR-IHR). METHODS: A comprehensive search was conducted in PubMed, EMBASE, Cochrane, and Ovid for articles published before January 2024, focusing on complication rates, recurrence, seroma, hematoma, operative time, post-operative pain, and cosmetic outcomes of laparoscopic or robotic IHR. Both extraperitoneal (TEP) and transabdominal (TAPP) approaches were analyzed using MetaInsight. MPL-TAPP was used as the standard for comparison. RESULTS: Thirty-seven studies, including 5,038 patients, 36.92% (1,860 patients) underwent MPL-TEP, 23.64% (1,191 patients) SPL-TEP, 22.23% (1,120 patients) MPR-TAPP, 10.08% (508 patients) MPL-TAPP, 5.40% (272 patients) SPL-TAPP, and 1.73% (87 patients) SPR-TAPP. There were no significant differences in the rates of post-operative complications, hernia recurrence, hematoma, or seroma among the techniques when compared to MPL-TAPP. For secondary outcomes, MPR-TAPP significantly increased the operative time for unilateral hernia repair by a mean difference (MD) of 10.60 min [95% CI: 2.16-19.04]. Conversely, for bilateral hernia repair, there was no significant difference. Post-operative pain was significantly higher for MPL-TEP and SPL-TEP, with MDs of 1.44 [95% CI: 0.43 to 2.44] and 1.22 [95% CI: 0.18 to 2.26], respectively. SPL-TEP was significantly favored in cosmetic outcomes over MPL-TEP, with an MD of 0.65 [95% CI: 0.07 to 1.24]. CONCLUSION: In our network meta-analysis, the risk of post-operative complications, including recurrence, hematoma, and seroma, does not significantly vary among single-port and multi-port laparoscopic or robotic techniques. This suggests that surgical technique selection can rely on surgeon expertise and resource availability, without compromising outcomes.
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BACKGROUND: Obesity is a risk factor for the development of ventral hernias. Approximately eight percent of patients undergoing bariatric surgery have a concomitant ventral hernia. However, the optimal timing of hernia repair in these patients is debated. Concerns regarding mesh insertion in a potentially contaminated field are often cited by opponents of a combined approach. Our study compares 30-day outcomes of bariatric surgery with concurrent ventral hernia repair with mesh versus bariatric surgery alone. METHODS: Using the 2015-2022 MBSAQIP database, patients aged 18-65 years who underwent minimally invasive sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with or without concurrent ventral hernia repair with mesh (VHR-M) were identified. 30-day postoperative outcomes were compared between patients who underwent SG or RYGB with VHR-M versus SG or RYGB alone. 1:1 propensity score matching was performed using 26 preoperative characteristics to adjust confounders. RESULTS: Among 1,236,644 patients who underwent SG (n = 871,326) or RYGB (n = 365,318), 3,121 underwent SG + VHR-M and 2,321 RYGB + VHR-M. The concurrent approach had longer operative times, in SG + VHR-M (86.06 ± 42.78 vs. 73.80 ± 38.45 min, p < 0.001), and in RYGB + VHR-M (141.91 ± 58.68 vs. 128.47 ± 62.37 min, p < 0.001). The RYGB + VHR-M cohort had higher rates of reoperations (3.2% vs. 2.1%, p = 0.024). Overall, 30-day outcomes, and bariatric-specific complications such as mortality, unplanned ICU admissions, surgical site complications, cardiac, pulmonary, renal complications, anastomotic leaks, postoperative bleeding, and intestinal obstruction were similar between SG + VHR-M or RYGB + VHR-M groups versus SG or RYGB alone. CONCLUSION: Bariatric surgery performed concurrently with VHR-M is safe and feasible and does not excessively prolong operative times. However, patients undergoing RYGB with VHR-M do have a higher rate of reoperations, therefore a staged VHR is recommended. On the other hand, concurrent SG and VHR-M may benefit after an appropriate individualized risk stratification assessment.
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BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) in patients with BMI ≥ 60 presents technical challenges, that might be overcome by robotic surgery, but its effectiveness has not been rigorously evaluated. We compared the 30-day outcomes of LSG and robotic sleeve gastrectomy (RSG) in patients with BMI < 60 versus ≥ 60 and between LSG and RSG in patients with BMI ≥ 60. METHODS: Patients aged 18-65 years who underwent sleeve gastrectomy were included using the 2019-2022 MBSAQIP database. We performed a Propensity Score Matching analysis, with 21 preoperative characteristics. We compared 30-day postoperative outcomes for patients with BMI < 60 versus ≥ 60 using either a laparoscopic (Analysis 1) or robotic approach (Analysis 2) and compared LSG versus RSG in patients with BMI ≥ 60 (Analysis 3). RESULTS: 297,250 patients underwent LSG and 81,008 RSG. Propensity-matched¸ outcomes in analysis 1 (13,503 matched cases), showed that patients with BMI ≥ 60 had higher rates of mortality (0.1% vs. 0.0%, p = 0.014), staple line leak (0.3% vs. 0.2%, p = 0.035), postoperative bleeding (0.2% vs 0.1%, p = 0.028), readmissions (3.5% vs. 2.4%, p < 0.001), and interventions (0.7% vs. 0.5%, p = 0.028) when compared to patients with BMI < 60. In analysis 2 (4350 matched cases), patients with BMI ≥ 60 demonstrated longer operative times, length of stay, and higher rates of unplanned ICU when compared to patients with BMI < 60. In analysis 3 (4370 matched cases), patients who underwent RSG had fewer readmissions (2.9% vs. 3.7%, p = 0.037), staple line leaks (0.1% vs. 0.3%, p = 0.029), and postoperative bleeding (0.1% vs. 0.3%, p = 0.045), compared to LSG. Conversely, a longer operative time (92.74 ± 38.65 vs. 71.69 ± 37.45 min, p < 0.001) was reported. CONCLUSION: LSG patients with BMI ≥ 60 have higher rates of complications compared to patients with a BMI < 60. Moreover, some outcomes may be improved with the robotic approach in patients with BMI ≥ 60. These results underscore the importance of considering a robotic approach in this super super obese population.
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Gastrectomia , Laparoscopia , Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Laparoscopia/métodos , Idoso , Adulto Jovem , Adolescente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Bases de Dados Factuais , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricos , Índice de Massa Corporal , Pontuação de Propensão , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: While laparoscopic gastrectomy is a prominent therapeutic approach for distal gastric cancer, the clinical benefits of 3D laparoscopy over 2D laparoscopy remain unclear. We aimed to compare the clinical outcomes of 3D laparoscopy and 2D laparoscopy for distal gastric cancer resection through a systematic review and meta-analysis. METHODS: We searched PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published from inception through January 2023, according to the PRISMA guidelines. The MD or RR was used to compare 3D and 2D distal gastrectomy. Random-effects meta-analysis was estimated using the inverse variance and Mantel-Haenszel method for binary outcomes and the DerSimonian-Laird estimator for continuous outcomes. RESULTS: After reviewing 559 studies, 6 manuscripts met the inclusion criteria. The analysis included 689 patients, with 348 (50.5%) in the 3D group and 341 (49.5%) in the 2D group. 3D laparoscopic gastrectomy reduces the operative time (WMD - 28.57 min, 95% CI - 50.70 to - 6.44, p = 0.011), intraoperative blood loss (WMD - 6.69 mL, 95% CI - 8.09 to - 5.29, p < 0.001), and postoperative hospital stay (WMD - 0.92 days, 95% CI - 1.43 to - 0.42, p < 0.001). There were no significant differences in time to first postoperative flatus (WMD - 0.22 days, 95% CI - 0.50 to 0.05, p = 0.110), postoperative complications (Relative Risk 0.56, 95% CI 0.22 to 1.41, p = 0.217), and the number of retrieved lymph nodes (WMD 1.25, 95% CI - 0.54 to 3.03, p = 0.172) between 3 and 2D laparoscopic distal gastrectomy. CONCLUSION: Our study highlights the potential advantages of 3D laparoscopy in distal gastrectomy, including shorter operative time, postoperative hospital stay, and decreased intraoperative blood loss.
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Laparoscopia , Neoplasias Gástricas , Humanos , Perda Sanguínea Cirúrgica , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Resultado do Tratamento , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Gastrectomia/métodosRESUMO
BACKGROUND: Idiopathic granulomatous mastitis (IGM) is mostly described as an autoimmune disease with higher prevalence among Middle Eastern childbearing-age women. This study aimed to evaluate the best treatment of choice in patients with resistant or recurrent IGM. STUDY DESIGN: Patients with established recurrent or resistant IGM who were referred to the Breast Cancer Research Center from 2017 to 2020 were randomly assigned to either one of the following treatment groups: A (best supportive care), B (corticosteroids: prednisolone), and C (methotrexate and low-dose corticosteroids). This adaptive clinical trial evaluated radiological and clinical responses, as well as the potential side effects, on a regular basis in each group, with patients followed up for a minimum of 2 years. RESULTS: A total of 318 participants, with a mean age of 33.52 ± 6.77 years, were divided into groups A (10 patients), B (78 patients), and C (230 patients). In group A, no therapeutic response was observed; group B exhibited a mixed response, with 14.1% experiencing complete or partial responses, 7.7% maintaining stability, and 78.2% experiencing disease progression. Accordingly, groups A and B were terminated due to inadequate response. In group C, 94.3% achieved complete response, 3% showed partial remission, and 2.7% had no response to therapy. Among the entire patient cohort, 11.6% tested positive for antinuclear antibodies, 3.5% for angiotensin-converting enzyme, and 12.3% for erythema nodosum. Notably, hypothyroidism was a prevalent condition among the patients, affecting 7.2% of the cohort. The incidence of common side effects was consistent across all groups. CONCLUSIONS: The most effective treatment option for patients with recurrent or resistant IGM is a combination therapy involving steroids and disease-modifying antirheumatic drugs such as methotrexate.
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Mastite Granulomatosa , Metotrexato , Recidiva , Humanos , Feminino , Mastite Granulomatosa/tratamento farmacológico , Mastite Granulomatosa/diagnóstico , Adulto , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Quimioterapia Combinada , Resultado do Tratamento , Glucocorticoides/uso terapêutico , Glucocorticoides/administração & dosagemRESUMO
Lymph node (LN) status is an essential prognostic factor in breast cancer (BC) patients, with an important role in the surgical and therapeutic plan. Recently, we have been developed a novel system for real-time intra-operative electrical LN scanning in BC patients. The ELS scores were calibrated by pathological evaluation of the LNs. Herein, we evaluated the efficacy of ELS in a prospective study for non-chemo-treated breast cancer patients. This is a prospective study in which ELS scores are blind for pathologists who declare the clearance or involvement of LNs based on permanent pathology as the gold standard. ELS and frozen-section (FS) pathology results were achieved intra-operatively, and samples were sent for the permanent pathology. The score of ELS did not affect the surgeons' decision, and the treatment approach was carried out based on FS pathology and pre-surgical data, such as imaging and probable biopsies. Patients were recruited from October 2021 through November 2022, and 381 lymph nodes of 97 patients were included in the study. In this study we recruited 38 patients (39.2%) with sentinel lymph node biopsy (SLNB) and 59 patients (60.8%) with ALND. Of the 381 LNs scored by ELS, 329 sentinel LNs underwent routine pathology, while others (n = 52) underwent both FS and permanent pathology. ELS showed a sensitivity of 91.4% for node-positive patients, decreasing to 84.8% when considering all LNs. Using ROC analysis, ELS diagnosis showed a significant AUC of 0.878 in relation to the permanent pathology gold standard. Comparison of ELS diagnosis for different tumor types and LN sizes demonstrated no significant differences, while increasing LN size correlated with enhanced ELS sensitivity. This study confirmed ELS's efficacy in real-time lymph node detection among non-chemo-treated breast cancer patients. The use of ELS's pathological scoring for intra-operative LN diagnosis, especially in the absence of FS pathology or for non-sentinel LN involvement, could improve prognosis and reduce complications by minimizing unnecessary dissection.
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Axila , Neoplasias da Mama , Linfonodos , Metástase Linfática , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Pessoa de Meia-Idade , Linfonodos/patologia , Estudos Prospectivos , Idoso , Adulto , Biópsia de Linfonodo Sentinela/métodos , Excisão de Linfonodo/métodosRESUMO
Introduction: This study aimed to study the trend, histologic pattern, geographical distribution, and characteristics of nasopharyngeal carcinoma (NPC) and nasopharyngeal neoplasms (NPN) from 2003 to 2017 in Iran. Materials and Methods: The Ministry of Health and Medical Education collected NPN cases from the corresponding university in each province and stored them in Iran National Cancer Registry (INCR) database. The Joinpoint program calculated the average annual percent change (AAPC) and its 95% confidence interval (CI). The jump model minimized the interfering effect of INCR transformation. Results: 3653 NPN cases were reported between 2003-2010 and 2014-2017, with a mean age of 49.04 ± 18.31 years and a male-to-female ratio of 2.15. The age-standardized incidence rate (ASIR) per 100,000 person-years was 0.30 for females and 0.68 for males in 2017. Although the ASIR/100,000 of NPN raised from 0.35 to 0.49 during 2003-2017, the trend was constant with an AAPC of -2% (95% CI: -4.8% to 0.9%). The age-specific incidence rate was highest in the older than 70 population (1.56/100,000). NPC formed 77.1% of NPNs and showed a constant pattern (AAPC CI: -5.7% to 0.2%), in contrast to the significant increase of non-keratinizing squamous cell carcinoma (AAPC CI: 2.3%to 24.5%). Conclusions: Nasopharynx cancer is rare in Iran, and NPC incidence remained constant from 2003 to 2017, unlike previously reported rising trend. However, non-keratinizing squamous cell carcinoma exhibited a significant increase, and future studies are needed to examine the role of the Epstein-Barr virus on this growth rate.
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HER2 is an important prognostic marker in breast cancer (BC) patients, which also plays a crucial role in their therapeutic plan. Consequently, a great desire is to thoroughly assess the patients based on their HER2 status. In the current study, we aimed to evaluate HER2-low breast cancer as a new subtype in the standard classification of BC patients and review its characteristics and survival rate in a tertiary center in Iran. We retrospectively evaluated disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of BC patients referred to the Cancer Research Center in Tehran, Iran from 1991 to 2022. Patients' clinical characteristics, including HER2 status, which is classified as HER2-low, HER2-positive, or HER2-negative, were obtained from prospectively maintained registries. Among the total 3582 recruited patients, 60.2%, 13.6%, and 26.2% were HER2-negative, HER2-low, and HER2-positive, respectively. HER2-positive patients showed a significantly higher Hazard Ratio (HR) for DFS (HR 1.44, 95% CI 1.01-2.05) and OS (HR 2.05, 95% CI 1.31-3.20), compared to HER2-low. Moreover, HER2-low and HER2-negative were found to show the same proportion of high-grade tumors (28 and 28.4%), while 40% of the HER2-positive tumors were high-grade. Accordingly, HER2-low patients had a lower metastasis risk than the others (P-value = 0.01). The Ki67 percentage was significantly lower in the HER2-low group compared to the HER2-positive (P-value < 0.001). HER2-low, a new subtype of HER2-status classification with distinct biological and clinicopathological traits, represented the highest survival rate and less invasive characteristics. This difference was statistically significant when compared to HER2-positive, but not when compared to HER2-negative.Research registration unique identifying number: NCT05754047.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Receptor ErbB-2 , Prognóstico , Taxa de Sobrevida , Irã (Geográfico)RESUMO
Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg-1 ] versus DLNs-based chemotherapy [0.75 mg kg-1 ]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.
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Antineoplásicos , Nanopartículas , Neoplasias , Camundongos , Ratos , Animais , Sistemas de Liberação de Medicamentos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Eletricidade Estática , Antineoplásicos/química , Polímeros/uso terapêutico , Neoplasias/tratamento farmacológico , Nanopartículas/química , Portadores de Fármacos/química , Liberação Controlada de FármacosRESUMO
BACKGROUND: Coronavirus infection can induce the production of inflammatory cytokines leading to acute respiratory distress syndrome (ARDS) and death. It is well-established that interferons (IFNs) are essential in regulating the immune response, thus their effects of IFNs on COVID-19 patients should be subject to investigation. This study aimed to investigate the effects of IFN-α alone or in combination with remdesivir in hospitalized COVID-19 patients. MATERIAL AND METHODS: A multicentre, retrospective study was conducted on COVID-19 patients admitted to three hospitals in Tehran, Iran, from March 20, 2020, to March 18, 2021. The unadjusted and adjusted effects of IFN-α on COVID-19 outcomes were investigated through propensity score matching (PSM) to achieve a 1:1 balanced dataset. RESULTS: Among 4,782 patients, 3,764 were eligible for the study, including 1,704 patients (45.27%) receiving at least one treatment with IFN-α and 2,060 controls not receiving IFN-α. After PSM, 851 IFN-α patients and 851 controls were recruited in the PSM analysis with a median age of 60.8 (standard deviation [SD]: 16.2 and 60.9 [SD: 17.4]), respectively. The PSM results showed no significant difference between the survival curves of the IFN-α group and the control group (p=0.340). However, the unadjusted impact of IFN-α on the risk of mortality was statistically significant (p=0.043, hazard-ratio: 0.86; 95% confidence interval [CI]: 0.75-0.99). Also, the combination of IFN-α and remdesivir had no significant benefit (HR: 89, 95% CI: 0.74-1.34). CONCLUSION: Our findings indicate that subcutaneous administration of IFN-α, with or without remdesivir, does not have any significant impact on COVID-19 mortality and ICU admission. Future clinical trials considering the time, subtype, and form of IFN-α administration are warranted to investigate the potential therapeutic effects of IFN-α on COVID-19.
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COVID-19 , Interferon-alfa , Humanos , Interferon-alfa/uso terapêutico , Mortalidade Hospitalar , Pontuação de Propensão , Estudos Retrospectivos , Irã (Geográfico)/epidemiologiaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) frequently presents with metastasis, but the molecular programs in human PDAC cells that drive invasion are not well understood. Using an experimental pipeline enabling PDAC organoid isolation and collection based on invasive phenotype, we assessed the transcriptomic programs associated with invasion in our organoid model. We identified differentially expressed genes in invasive organoids compared with matched noninvasive organoids from the same patients, and we confirmed that the encoded proteins were enhanced in organoid invasive protrusions. We identified 3 distinct transcriptomic groups in invasive organoids, 2 of which correlated directly with the morphological invasion patterns and were characterized by distinct upregulated pathways. Leveraging publicly available single-cell RNA-sequencing data, we mapped our transcriptomic groups onto human PDAC tissue samples, highlighting differences in the tumor microenvironment between transcriptomic groups and suggesting that non-neoplastic cells in the tumor microenvironment can modulate tumor cell invasion. To further address this possibility, we performed computational ligand-receptor analysis and validated the impact of multiple ligands (TGF-ß1, IL-6, CXCL12, MMP9) on invasion and gene expression in an independent cohort of fresh human PDAC organoids. Our results identify molecular programs driving morphologically defined invasion patterns and highlight the tumor microenvironment as a potential modulator of these programs.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Transcriptoma , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/metabolismo , Organoides/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Microambiente Tumoral/genéticaRESUMO
Background: Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy. Methods: In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient's signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study. Results: Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients' lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates. Conclusion: PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.
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Background and Objectives: We compared two common antibiotic regimens for the treatment of mild to moderate CAP: levofloxacin versus ß-lactam and macrolide combination; in terms of their efficacy and side effects. Materials and Methods: Patients with mild to moderate CAP were randomized into two groups. Group I received a combination of 1 gram ceftriaxone daily and 500 mg azithromycin daily for 5-7 days. Group II received levofloxacin 750 mg daily for five days. The signs and symptoms, hospitalization length, and the side effects were investigated. Results: There were 77 and 74 patients in groups I and II. The vital signs of group II were significantly better on the 3rd day of admission, except for the temperature (P=0.09). The O2 saturation of group II was markedly improved on the 5th day of admission (P=0.0061). In terms of clinical symptoms and hospitalization length, group II was considerably better. However, the rate of side effects in both groups was similar (P=0.885). Conclusion: Hospitalized patients with mild to moderate CAP might take more advantage of fluoroquinolone administration. It could improve the patients' signs and symptoms and reduce hospitalization length, compared with the combination of macrolide and cephalosporin, with the same rate of side effects.
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Background & Objective: Various studies showed the use of epidermal growth factor receptors (EGFRs) gene mutations in the therapeutic plan of patients with advanced lung cancer. This study aimed to investigate the frequency and types of EGFR gene mutations among Iranian patients with lung adenocarcinoma referred to a specialized lung diseases hospital from 2014 to 2019. Methods: The data of all patients with lung adenocarcinoma referred to the Molecular Department of Masih Daneshvari Hospital Laboratory (National Research Institute of Tuberculosis and Lung Diseases) from 2014 to 2019 for EGFR mutation tests were collected. Patients' characteristics data and information on the frequency and types of EGFR gene mutations were obtained from the hospital information system (HIS). The collected data were analyzed using SPSS 25. Results: A total of 570 individuals (Mean age of 58.74, 51.6% Male) were included in the study; 113 out of 570 patients (19.8%) were diagnosed with gene mutation. In terms of the type of mutation, 65 participants (57%) showed deletion, 48 patients (42.1%) were diagnosed with replacement, and one (0.9%) case demonstrated both. Notably, the mutation rate detected among the female patients was significantly higher than the male ones (P=0.001); in particular, deletion type of mutation was found more among women, although both genders were the same in terms of the replacement frequency. However, the age had no effect on the mutation in this study (P=0.05). Conclusion: Among Iranian patients with lung adenocarcinoma, 19.8% harbored EGFR gene mutation. This mutation was found in association with lung cancer and could affect the patient's therapeutic plan.
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Background and aims: Inflammatory bases lead to a simultaneous flourishing of cardiovascular complications with inflammatory bowel disease (IBD). As a released cytokine, tumor necrosis factor-α (TNF-α) can either disrupt or preserve cardiovascular performance. Due to this controversy, this study aimed to appraise the short-term anti-TNF (adalimumab [ADA]) relics on cardiac function by gauging the echocardiography indexes in patients with immunosuppressant refractory ulcerative colitis (UC). Methods: All cases with a definite diagnosis of UC were included based on providing written informed consent and owning the severe form of active disease (Mayo score ≥7), which did not dampen with immunosuppressant. Patients were excluded in the case of previous cardiac ailments/risk factors and prior related surgical or pharmaceutical intervention. Transthoracic echocardiography (TTE) was carried out before and 3 months after biological regimen allocation and changes in indexes [ejection fraction (EF), left ventricular end-diastolic volume (LVEDV)/left ventricular end-systolic volume (LVESV), and global longitudinal strain (GLS) in standard parasternal short axis from mid-ventricular level, two-, three-, and four-chamber apical long axes] were compared via statistical analyses. Results: The study consisted of 13 (65%) men and 7 (35%) women, with a mean age of 36.54 ± 11.3 years. Participants mainly possessed Montreal class I (45%) and an average of 3.25 years of disease duration. The intervention significantly controlled inflammation [endoscopic Mayo score (P = 0.001), partial Mayo score (P = 0.001), and C-reactive protein (P = 0.001)]. Endoscopic and clinical remission was obtained in 7 (35%) and 9 (45%) patients, respectively; however, no significant discrepancy related to the LVEDV (P = 0.86), LVESV (P-value = 0.25), EF (P-value = 0.06), and GLS in standard parasternal short axis (P = 0.73), long axis [apical 2-chamber (P-value = 0.61), apical 3-chamber (P-value = 0.15), and apical 4-chamber (P-value = 0.19) views] was observed before and after the intervention. Furthermore, no statistically significant correlation between disease activity and cardiac function was found, neither before nor after ADA administration. Conclusion: The present perusal found no deterioration in left ventricular function indexes with ADA intervention among patients with IBD without cardiac ailment. Thus, prescribing the anti-TNF to alleviate the inflammation can be carried out with less concern about cardiac consequences and considering other adverse traces in the target group.
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For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high-risk and neoplastic cells, especially in surgical cavity margins, is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non-fixed tissues prevents us from achieving a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still real-time detection of neoplastic lesions is crucial to improving diagnostic quality. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer/atypical cells through reverse Warburg effect and hypoxia assisted glycolysis pathways in a quantitative electrochemical manner. The study was carried out on cell lines, 57 in vivo mice models with breast cancer, and 258 fresh in vitro samples of breast cancer tumors. A real-time electrotechnical system, named cancer diagnostic probe (CDP) (US Patent Pub. No.: US 2018/02991 A1, US 2021/0007638 A1, and US 2021/0022650 A1 [publications], and US 10,786,188 B1 [granted]), has been developed to find pre-neoplastic/neoplastic cells in vivo in a quantitative electrochemical manner by tracing hypoxia glycolysis byproducts. Matched pathological evaluations with response peaks of CDP were found based on the presence of neoplasia (from atypia to invasive carcinoma) in live breast tissues. The ability of CDP to find neoplastic lesions in mice models in vivo and fresh breast tumors in vitro was verified with sensitivity and specificity of 95% and 97%, respectively. The system may help a surgeon assistant system for usage in the operating room after passing many trials and standard examinations in the future.
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BACKGROUND: Cancer diagnostic probe (CDP) had been developed to detect involved breast cavity side margins in real-time (Miripour et al. Bioeng Transl Med. e10236.). Here, we presented the results of the in vivo human model CDP studies on non-neoadjuvant cases. METHODS: This study is a prospective, blind comparison to a gold standard, and the medical group recruited patients. CDP and frozen data were achieved before the permanent pathology experiment. The main outcome of the study is surgical margin status. From November 2018 to April 2020, 202 patients were registered, and 188 were assigned for the study. Breast-conserving surgery at any age or gender, re-surgery due to re-currency, or involved margins are acceptable. Patients must be non-neoadjuvant. The reliability of CDP scoring had been evaluated by the pathology of the scored IMs. Then, three models of the study were designed to compare CDP with the frozen sections. Receiver operating characteristic (ROC) curves and AUC were measured based on the permanent postoperative pathology gold standard. RESULTS: A matched clinical diagnostic categorization between the pathological results of the tested IMs and response peaks of CDP on 113 cases, was reported (sensitivity = 97%, specificity = 89.3%, accuracy = 92%, positive predictive value (PPV) = 84.2%, and negative predictive value (NPV) = 98%). Study A showed the independent ability of CDP for IM scoring (sensitivity = 80%, specificity = 90%, accuracy = 90%, PPV = 22.2%, and NPV = 99.2%). Study B showed the complementary role of CDP to cover the missed lesions of frozen sections (sensitivity = 93.8%, specificity = 91%, accuracy = 91%, PPV = 55.6%, and NPV = 99.2%). Study C showed the ability of CDP in helping the pathologist to reduce his/her frozen miss judgment (specificity = 92%, accuracy = 93%, PPV = 42.1%, and NPV = 100%). Results were reported based on the post-surgical permanent pathology gold standard. CONCLUSION: CDP scoring ability in intra-operative margin detection was verified on non-neoadjuvant breast cancer patients. Non-invasive real-time diagnosis of IMs with pathological values may make CDP a distinct tool with handheld equipment to increase the prognosis of breast cancer patients.