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1.
Cancers (Basel) ; 16(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38539471

RESUMO

Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3-4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3-4, and any-grade AEs was 2.75% (95%CI: 2.18-3.47), 26.69% (95%CI: 21.60-32.48), and 77.80% (95%CI: 70.91-83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76-5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3-4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs.

2.
Eur J Surg Oncol ; 50(3): 108019, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359725

RESUMO

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.


Assuntos
Tumor do Seio Endodérmico , Neoplasias do Mediastino , Neoplasias Embrionárias de Células Germinativas , Masculino , Adulto , Humanos , Criança , Adulto Jovem , Feminino , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/patologia , Neoplasias do Mediastino/terapia , Neoplasias do Mediastino/patologia , Mediastino/patologia , Terapia Neoadjuvante
3.
European J Pediatr Surg Rep ; 12(1): e26-e32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38351952

RESUMO

We present a simple surgical technique aiming to improve urine outflow through the common urogenital sinus in cloaca and facilitate drainage of existing hydrocolpos. The study included three cases of cloaca with associated hydrocolpos that were operated during the period 2022 through 2023. The patient is placed in the prone position for a standard posterior sagittal anorectoplasty. The distal rectal fistula is severed flush with the vagina/sinus leaving an open defect in the posterior wall of the vagina/sinus. The defect is then widened distally via a vertical incision (∼1 cm) through the posterior wall of the common urogenital sinus toward but not reaching the perineum. This vertical defect is then closed horizontally displacing the posterior vaginal wall downwards toward the perineum (posterior sinuplasty). The postoperative recovery was uneventful in the three cases. Adequate drainage of hydrocolpos was confirmed by imaging at follow-up, as well as improvement of upper urinary tract dilatation. In selected cases of cloaca, posterior sinuplasty is a simple procedure that can be applied during anorectoplasty to provide effective drainage of associated hydrocolpos.

4.
Int J Surg Case Rep ; 110: 108789, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37683513

RESUMO

INTRODUCTION AND IMPORTANCE: Chylolymphatic cysts are benign pathology in lymphatic vessels due to obstruction in the lymphatic system. Their incidence is still unknown. However, they account for approximately 3 % to 9 % of all pediatric lymphangiomas. Most of these lesions are asymptomatic and are discovered accidentally. They can present with non-specific abdominal pain, vomiting and changes in bowel habits. Rarely, Chylolymphatic cysts can cause fatal complications such as intestinal obstruction, volvulus or even torsion. CASE PRESENTATION: A 3-month-old male presented to our unit with manifestations of acute intestinal obstruction. Abdominal examination revealed signs of generalized peritonitis and intestinal obstruction. Abdominal ultrasound revealed minimal turbid intraperitoneal collections and no motility of bowel loops. Plain erect abdominal radiograph revealed multiple small bowel air fluid levels. Abdominal exploration revealed a large Chylolymphatic cyst causing acute intestinal obstruction. Excision of the cysts was done with preservation of adjacent bowel loop. The patient was discharged in good health on the 6th day postoperative. A chylolymphatic cyst with a diameter of 5 cm was identified by histological investigation. CLINICAL DISCUSSION: Mesenteric cyst is a rare intra-abdominal tumor with prevalence of about 1: 20,000 in pediatric age group. They are benign cystic pathology lined with a thin endothelium or mesothelium occur due to gross proliferation of isolated or ectopic lymphatics in mesentery that lack communication with the rest of the lymphatic system. Regarding pathology, mesenteric cysts are classified into four types including type 1 (Pedicled) and type 2 (Sessile), which are limited to the mesentery, hence can be excised completely with or without resection of the involved gut. Type 3 and type 4 are multicentric, so they require complex surgery and often sclerotherapy because of their extension into retroperitoneum. The majority of mesenteric cysts may present as asymptomatic abdominal mass or incidental finding on imaging or during laparotomy for other abdominal conditions. Preoperative diagnosis of mesenteric cyst in most cases is difficult as they have no definite characteristic features. Abdominal ultrasound which is the imaging modality of choice can reveal mesenteric cysts as cystic tumors. Surgical removal of the cyst is the standard treatment for chylolymphatic cysts. CONCLUSION: Most Chylolymphatic cysts in infants are asymptomatic, but they can cause fatal complications such as intestinal obstruction, volvulus or even torsion.

5.
Biomedicines ; 11(9)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37760826

RESUMO

Prostate cancer treatment poses significant challenges due to its varying aggressiveness, potential for metastasis, and the complexity of treatment options. Balancing the effectiveness of therapies, minimizing side effects, and personalizing treatment strategies are ongoing challenges in managing this disease. Significant advances in the use of nanotechnology for the treatment of prostate cancer with high specificity, sensitivity, and efficacy have recently been made. This study aimed to synthesize and characterize a novel Cu/Fe layer double hydroxide (LDH) nanocomposite for use as an anticancer agent to treat prostate cancer. Cu/Fe LDH nanocomposites with a molar ratio of 5:1 were developed using a simple co-precipitation approach. FT-IR, XRD, SEM, TEM, TGA, and zeta potential analyses confirmed the nanocomposite. Moreover, the MTT cell viability assay, scratch assay, and flow cytometry were utilized to examine the prospective anticancer potential of Cu/Fe LDH on a prostate cancer (PC-3) cell line. We found that Cu/Fe LDH reduced cell viability, inhibited cell migration, induced G1/S phase cell cycle arrest, and triggered apoptotic effect in prostate cancer cells. The findings also indicated that generating reactive oxygen species (ROS) formation could improve the biological activity of Cu/Fe LDH. Additionally, Cu/Fe LDH showed a good safety impact on the normal lung fibroblast cell line (WI-38). Collectively, these findings demonstrate that the Cu/Fe LDH nanocomposite exhibited significant anticancer activities against PC-3 cells and, hence, could be used as a promising strategy in prostate cancer treatment.

6.
J Egypt Public Health Assoc ; 98(1): 11, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37271796

RESUMO

BACKGROUND: The steel industry is one of the noisiest industries, which can predispose workers to hearing loss. In Egypt, the demand for steel is increasing due to the construction of new infrastructures as bridges, flyover roads, buildings, and towers; however, little is known about the prevalence of occupational noise-induced hearing loss (NIHL) among steel workers. Understanding the distribution of the affected workers is crucial for planning prevention strategies. This study aimed to estimate the prevalence of occupational NIHL among Egyptian steel workers and identify its correlates. METHODS: This study was conducted at two steel factories in Egypt in November 2021. It involved an initial retrospective review of the factory medical records of the latest periodic medical examination conducted on workers from July to September in the year 2021 representing workers' health status in that year. Then, a case-control approach analysis was carried out. Eligible workers (n = 606) were enrolled and divided into two groups: noise-exposed workers (n = 396) and unexposed workers (n = 210). Univariate and multivariate regression analyses were performed. RESULTS: Occupational exposure to hazardous A-weighted equivalent noise level (> 85 dB) was associated with higher hearing thresholds at all frequencies (highest at 4 kHz followed by 6 kHz), particularly in younger workers below the age of 40 years. Nearly 71% of noise-exposed workers had hearing impairment, and 47% had NIHL compared with unexposed workers (45.7% and 11.9%, respectively). The probability of NIHL in noise-exposed workers was 6.55 times higher than that in unexposed workers (OR = 6.55, 95%CI = 4.13, 10.40; p < 0.001). In noise-exposed workers, age and tinnitus were independent predictors of hearing thresholds, while tinnitus was found to be an independent predictor of NIHL after adjusting for age and job duration (OR = 2.06, 95%CI = 1.01, 4.20; p = 0.045). CONCLUSION: Almost half of noise-exposed workers had NIHL. Tinnitus was found to be an independent predictor of NIHL. Decreasing noise exposure levels in steel plants is recommended to reduce hearing loss. Future research is required to study the effect of tinnitus on audiometry measurements among workers with NIHL.

7.
Sci Rep ; 13(1): 7227, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142660

RESUMO

Clove and green Coffee (g-Coffee) extracts were used to synthesize green iron oxide nanoparticles, which were then used to sorb Cd2+ and Ni2+ ions out of an aqueous solution. Investigations with x-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, nitrogen adsorption and desorption (BET), Zeta potential, and scanning electron microscopy were performed to know and understand more about the chemical structure and surface morphology of the produced iron oxide nanoparticles. The characterization revealed that the main component of iron nanoparticles was magnetite when the Clove extract was used as a reducing agent for Fe3+, but both magnetite and hematite were included when the g-Coffee extract was used. Sorption capacity for metal ions was studied as a function of sorbent dosage, metal ion concentration, and sorption period. The maximum Cd2+ adsorption capacity was 78 and 74 mg/g, while that of Ni2+ was 64.8 and 80 mg/g for iron nanoparticles prepared using Clove and g-Coffee, respectively. Different isotherm and kinetic adsorption models were used to fit experimental adsorption data. Adsorption of Cd2+ and Ni2+ on the iron oxide surface was found to be heterogeneous, and the mechanism of chemisorption is involved in the stage of determining the rate. The correlation coefficient R2 and error functions like RMSE, MES and MAE were used to evaluate the best fit models to the experimental adsorption data. The adsorption mechanism was explored using FTIR analysis. Antimicrobial study showed broad spectrum antibacterial activity of the tested nanomaterials against both Gram positive (S. aureus) (25923) and Gram negative (E. coli) (25913) bacteria with increased activity against Gram positive bacteria than Gram negative one and more activity for Green iron oxide nanoparticles prepared from Clove than g-Coffee one.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Cádmio/análise , Óxido Ferroso-Férrico , Escherichia coli , Staphylococcus aureus , Metais Pesados/química , Ferro/análise , Água , Antibacterianos/química , Nanopartículas Magnéticas de Óxido de Ferro , Adsorção , Cinética , Poluentes Químicos da Água/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Concentração de Íons de Hidrogênio
8.
Risk Manag Healthc Policy ; 16: 537-549, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035269

RESUMO

Purpose: This study aimed to investigate possible association between rotating night shift (RNS) work and anthropometric markers of overall and central adiposity among male workers. Methods: Medical records of workers who underwent medical examination at the Occupational Medicine Unit affiliated with Alexandria Faculty of Medicine were reviewed in December 2021 to extract data about RNS, overall adiposity [body mass index (BMI) from 25 to 29.9 kg/m2 indicated overweight, while BMI ≥30 kg/m2 indicated obesity], central adiposity (waist circumference ≥94 cm). Univariate and multivariate logistic regression were done to model adiposity as a function of potential demographic, lifestyle, and occupational factors. Results: Data of 647 male workers, including daytime workers (26.9%) and RNS workers (73.1%) who spent 1-5 years, 6-9 years, or ≥10 years working RNS, were analyzed. No association was found between RNS work and overall adiposity (BMI ≥30 kg/m2). In multivariate regression, age, residence, and smoking status were predictors of an increased BMI. Compared with young workers (<30 years old), the odds of an increased BMI (BMI ≥25 kg/m2) were 2.6 and 3.01 times higher among workers who were 30-<40, and 40-<50 years old, respectively [95% CI=(1.35, 5.05) and (1.19, 7.56), respectively]. Workers who lived in urban areas were less likely to have had an increased BMI (OR=0.34, 95% CI=0.16, 0.74). The odds of an increased BMI were 2.14 times higher in workers who never smoked compared with current smokers (95% CI=1.12, 4.11). No association was found between RNS and central adiposity. In multivariate regression, age was the sole predictor of central adiposity. Conclusion: The study supports the idea that RNS work might not be associated with overall or central adiposity and highlights a possible association between central adiposity and age and association between BMI and age, residence, and smoking behavior. Longitudinal, larger studies are required to explore the relationship between RNS and adiposity.

10.
Front Vet Sci ; 10: 1139381, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937010

RESUMO

Streptococcus pseudoporcinus (S. pseudoporcinus) is a ß-hemolytic, Gram-positive novel bacterium first identified in 2006. It is a catalase-negative, non-motile coccus arranged in short chains. Furthermore, it has a broad beta-hemolytic reaction on sheep blood agar and cross-reacts with Lancefield group B antigen agglutination reagent. In this study, we report a case of S. pseudoporcinus infection of a surgical wound on the left metatarsus of a dog. The patient is a 9-year-old spayed female Great Dane dog with a brief history of multiple cutaneous masses being removed. Post-surgery, the post-surgical site on the left metatarsus became infected and discharged purulent material with a fetid odor. Upon preliminary diagnostic testing, we detected catalase-negative Gram-positive cocci exhibiting beta-hemolytic growth on sheep blood agar. A VITEK® 2 Compact machine from bioMérieux identified the bacterium as S. pseudoporcinus. Furthermore, antibiotic testing revealed multidrug resistance. Therefore, we document a multidrug-resistant S. pseudoporcinus isolate as a cause of canine post-surgical wound infection. Furthermore, it was the only isolate detected from the sample; hence, it is the cause of the infection. To our knowledge, this case is the first report of S. pseudoporcinus in a dog.

11.
Front Oncol ; 13: 1071770, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761976

RESUMO

Introduction: Primary malignant cardiac tumors (PMCTs) are rare. Geographical distribution has been demonstrated to affect cancer outcomes, making the reduction of geographical inequalities a major priority for cancer control agencies. Geographic survival disparities have not been reported previously for PMCT and the aim of this study is to compare the prevalence and the long-term survival rate with respect to the geographic location of PMCTs using the Surveillance, Epidemiology, and End Results (SEER) research plus data 17 registries between 2000 and 2019. Methods: The SEER database was queried to identify geographic variation among PMCTs. We classified the included states into 4 geographical regions (Midwest, Northeast, South and West regions) based on the U.S. Census Bureau-designated regions and divisions. Different demographic and clinical variables were analyzed and compared between the four groups. Kaplan Meier curves and Cox regression were used for survival assessment. Results: A total of 563 patients were included in our analysis. The median age was 53 years (inter-quartile range (IQR): 38 - 68 years) and included 26, 90, 101, and 346 patients from the Midwest, Northeast, South, and West regions respectively. Sarcoma represented 65.6% of the cases, followed by hematological tumors (26.2%), while mesothelioma accounted for 2.1%. Treatment analysis showed no significant differences between different regions. Median overall survival was 11, 21, 13, and 11 months for Midwest, Northeast, South and West regions respectively and 5-year overall survival was 22.2%, 25.4%, 14.9%, and 17.6% respectively. On multivariate Cox regression, significant independent predictors of late overall mortality among the entire cohort included age (Hazard Ratio [HR] 1.028), year of diagnosis (HR 0.967), sarcoma (HR 3.36), surgery (HR 0.63) and chemotherapy (HR 0.56). Conclusion: Primary malignant cardiac tumors are rare and associated with poor prognosis. Sarcoma is the most common pathological type. Younger age, recent era diagnosis, surgical resection, and chemotherapy were the independent predictors of better survival. While univariate analysis revealed that patients in the South areas had a worse survival trend compared to other areas, geographic disparity in survival was nullified in multivariate analysis.

13.
Ann Surg Oncol ; 30(7): 4030-4039, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36820939

RESUMO

BACKGROUND: Minimally invasive surgery is an expanding field of surgery that has replaced many open surgical techniques. Surgery remains a cornerstone in the treatment of esophageal cancer, yet it is still associated with significant morbidity and technical difficulties. Mediastinoscope-assisted esophagectomy is a promising technique that aims to decrease the surgical burden and enhance recovery. METHODS: PubMed, MEDLINE, and EMBASE databases were searched for publications on mediastinoscope-assisted esophagectomies for esophageal cancer. The primary endpoint was a postoperative anastomotic leak, while secondary endpoints were assessment of harvested lymph nodes (LNs), blood loss, chyle leak, hospital length of stay (LOS), operative (OR) time, pneumonia, wound infection, mortality, and microscopic positive margin (R1). The pooled event rate (PER) and pooled mean were calculated for binary and continuous outcomes respectively. RESULTS: Twenty-six out of the 2274 searched studies were included. The pooled event rate (PER) for anastomotic leak was 0.145 (0.1144; 0.1828). The PERs for chyle leak, recurrent laryngeal nerve injury/hoarseness, postoperative pneumonia, wound infection, early mortality, postoperative morbidity, and microscopically positive (R1) resection margins were 0.027, 0.185, 0.09, 0.083, 0.020, 0.378, and 0.037 respectively. The pooled means for blood loss, hospital stay, operative time, number of total harvested LNs, and number of harvested thoracic LNs were 159.209, 15.187, 311.116, 23.379, and 15.458 respectively. CONCLUSIONS: Mediastinoscopic esophagectomy is a promising minimally invasive technique, avoiding thoracotomy, patient repositioning, and lung manipulation; thus allowing for shorter surgery, decreased blood loss, and decreased postoperative morbidity. It can also be reliable in terms of oncological safety and LN dissection.


Assuntos
Neoplasias Esofágicas , Laparoscopia , Pneumonia , Humanos , Esofagectomia , Mediastinoscópios , Fístula Anastomótica/cirurgia , Neoplasias Esofágicas/patologia , Tempo de Internação , Pneumonia/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/cirurgia , Laparoscopia/métodos , Resultado do Tratamento
14.
Br J Neurosurg ; 37(5): 1271-1272, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33241950

RESUMO

We present a case of extradural hematoma resulting from a relatively minor closed injury over the vertex where a plasma cell tumour had invaded the superior sagittal sinus. The patient underwent an emergency craniotomy and evacuation of the hematoma. Hemostasis and prevention of recollection of the hematoma were hampered by the erosion of the sagittal sinus making its direct repair impossible. This was achieved by hitching up the dura lateral to the sinus to become its lateral wall reinforced by hemostatic agents. The patient made a full recovery. Malignant tumours invading the dural venous sinuses and eroding the skull can cause life-threatening intracranial bleeding after relatively minor trauma.


Assuntos
Hematoma Epidural Craniano , Fraturas Cranianas , Neoplasias Cranianas , Humanos , Cavidades Cranianas/cirurgia , Craniotomia/métodos , Hematoma Epidural Craniano/diagnóstico por imagem , Hematoma Epidural Craniano/etiologia , Hematoma Epidural Craniano/cirurgia , Crânio/cirurgia , Fraturas Cranianas/cirurgia , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/cirurgia , Masculino , Adulto
16.
Rep Biochem Mol Biol ; 12(2): 251-258, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38317821

RESUMO

Background: Vitamin D (vit D) controls inflammation and immunity. In Behçet's disease (BD), microRNA-155 is recognized as a significant immune response regulator. We aimed to investigate the role of vit D on immunomodulation and downregulation of inflammatory pathways associated with BD and detect the role of miRNA-155 in BD. Methods: miRNA-155 expression by Real Time -Polymerase Chain Reaction (RT-PCR), and vit D, nuclear factor Kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor necrosis fact of TNF-α) expression by Enzyme Linked Immunosorbent Assay (ELISA) were assessed. Results: BD patients had a significantly higher relative expression of microRNA-155 (P< 0.001), it was significantly related to vascular manifestations (P< 0.001). Vit D relative expression was significantly low in BD (P< 0.001). There was a significant rise in miRNA-155 in the active group compared to the inactive group (P< 0.001). A significant decrease in vit D levels (IU) was found in inactive and active individuals suffering from BD when compared to controls (P< 0.001). A significant rise was found in vit D levels in inactive BD cases (P< 0.001). A significant positive correlations were found between miRNA-155, NF-κB, TNF-α, and negative correlations with vit D relative expression in BD patients. Conclusions: miRNA-155 relative expression is higher in BD is significantly related to vascular manifestations. It may have a relationship to disease activity. Vitamin D relative expression is significantly low in BD patients, which can significantly influence immunomodulatory BD therapy. Vitamin D deficiency linked to active BD.

18.
J Clin Med ; 11(16)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36013139

RESUMO

Data concerning age-related populations affected with primary malignant cardiac tumors (PMCTs) are still scarce. The aim of the current study was to analyze mortality differences amongst different age groups of patients with PMCTs, as reported by the National Cancer Database (NCDB). The NCDB was retrospectively reviewed for PMCTs from 2004 to 2017. The primary outcome was late mortality differences amongst different age categories (octogenarian, septuagenarian, younger age), while secondary outcomes included differences in treatment patterns and perioperative (30-day) mortality. A total of 736 patients were included, including 72 (9.8%) septuagenarians and 44 (5.98%) octogenarians. Angiosarcoma was the most prevalent PMCT. Surgery was performed in 432 (58.7%) patients (60.3%, 55.6%, and 40.9% in younger age, septuagenarian, and octogenarian, respectively, p = 0.04), with a corresponding 30-day mortality of 9.0% (7.0, 15.0, and 38.9% respectively, p < 0.001) and a median overall survival of 15.7 months (18.1, 8.7, and 4.5 months respectively). Using multivariable Cox regression, independent predictors of late mortality included octogenarian, governmental insurance, CDCC grade II/III, earlier year of diagnosis, angiosarcoma, stage III/IV, and absence of surgery/chemotherapy. With increasing age, patients presented a more significant comorbidity burden compared to younger ones and were treated more conservatively. Early and late survival outcomes progressively declined with advanced age.

19.
J Med Chem ; 65(17): 11726-11744, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-35993890

RESUMO

A novel approach for the dual inhibition of steroid sulfatase (STS) and 17ß-hydroxysteroid dehydrogenase type 1(17ß HSD1) by a single drug was explored, starting from in-house 17ß HSD1 inhibitors via masking their phenolic OH group with a sulfamate ester. The sulfamates were intentionally designed as drugs for the inhibition of STS and, at the same time, prodrugs for 17ß-HSD1 inhibition ("drug-prodrug approach"). The most promising sulfamates 13, 16, 18-20, 22-24, 36, and 37 showed nanomolar IC50 values for STS inhibition in a cellular assay and their corresponding phenols displayed potent 17ß-HSD1 inhibition in cell-free and cellular assays, high selectivity over 17ß-HSD2, reasonable metabolic stability, and low estrogen receptor α affinity. A close relationship was found between the liberation of the phenolic compound by sulfamate hydrolysis and 17ß-HSD1 inactivation. These results showed that the envisaged drug-prodrug concept was successfully implemented. The novel compounds constitute a promising class of therapeutics for the treatment of endometriosis and other estrogen-dependent diseases.


Assuntos
Endometriose , Pró-Fármacos , 17-Hidroxiesteroide Desidrogenases , Endometriose/tratamento farmacológico , Inibidores Enzimáticos/metabolismo , Feminino , Humanos , Fenóis/farmacologia , Pró-Fármacos/farmacologia , Esteril-Sulfatase , Relação Estrutura-Atividade
20.
Int J Surg ; 104: 106739, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35764254

RESUMO

BACKGROUND: In the modern era, minimally invasive surgery is rapidly evolving and even replacing conventional open techniques in many surgical fields. Thyroidectomy was not an exception, with the introduction of multiple endoscopic thyroidectomy techniques. Trans-oral endoscopic trans-vestibular thyroidectomy (TOT) is a novel technique with promising outcomes. We conducted this meta-analysis to compare surgical outcomes and learning curves for TOT and other endoscopic thyroidectomy techniques. METHODS: A systematic review in PubMed, MEDLINE, and EMBASE databases was conducted searching for publications on TOT versus trans-axillary thyroidectomy (TAT). The primary endpoint was operative (OR) time. Secondary endpoints were number of harvested lymph nodes (LNs), estimated blood loss (EBL), recurrent laryngeal nerve (RLN) injury, hoarseness, seroma, infection, chyle leak, hypocalcemia, hospital length of stay (LOS), and Cost. We also investigated the learning curve for each technique. Leave-out-out analysis, meta-regression, and subgroup analysis were used. Random effect inverse variance method was utilized. RESULTS: Among 3820 retrieved studies, 15 studies (10 unmatched and 5 matched), with 2173 (TOT: 1024(47.12%) and TAT:1149(52.87%)) patients, met the inclusion criteria. The operative time and harvested L. Ns number were higher in TOT versus TAT (standard mean difference (SMD) = 0.72 [95%CI 0.07; 1.37], P = 0.029 and SMD = 0.32 [95%CI 0.02; 0.62], P = 0.036 respectively) while less EBL in TOT versus TAT (SMD = -0.26 [-0.43; -0.09], P = 0.0018). All other outcomes showed no significant difference between both groups. Weighted mean values for TOT and TAT were 158.03 vs 144.97 min for OR time, 6.33 vs 5.16 for harvested LNs, and $5,919.05 vs $6,253.79 for the cost. Statistical significance in learning curve development was noticed ranging between 6 and 15 annual cases. CONCLUSION: Trans-oral thyroidectomy is a safe and reliable technique with outcomes comparable to other endoscopic techniques. It provides better access to the central compartment with a more feasible LN dissection. Improvement in surgical outcomes is expected with growing learning curve and technique mastery.


Assuntos
Curva de Aprendizado , Neoplasias da Glândula Tireoide , Axila , Endoscopia , Humanos , Duração da Cirurgia , Tireoidectomia
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