A Associação de TWEAK com Calcificação da Artéria Coronária em Pacientes com Doença Renal Crônica

BackgroundThe soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is a member of the TNF superfamily that plays a critical role in proliferation and inflammation in the arterial circulation.ObjectivesThis prospective study aimed to show the relationship between the sTWEAK levels and coronary artery calcification (CAC) in patients with chronic kidney disease (CKD).MethodsThis prospective study included 139 consecutive patients undergoing computed coronary angiography for any reason except for acute coronary syndromes from August 2020 to February 2021. A total of 12 patients were excluded from the study due to exclusion criteria. Patients were divided into two groups with regard to having a CAC score of less than 400 (n=84) and 400 or more (n=43). Significance was assumed at a 2-sided p<0.05.ResultsAs the CAC score increased, sTWEAK levels presented a statistically significant decrease, and a strong relationship between sTWEAK levels and the CAC score (r: -0.779, p<0.001) was observed. The ROC analysis revealed that the optimal cut-off level of sTWEAK for predicting the CAC score of 400 was 761 pg/mL with a sensitivity of 71% and a specificity of 73% (AUC: 0.78; 95% CI:0.70-0.85; p < 0.001)ConclusionsEven though the large-scale studies showed a positive correlation between eGFR and the sTWEAK levels, some studies found the increased sTWEAK levels to be associated with mortality and the severity of the coronary artery system in patients with CKD. Our results support our hypothesis that the sTWEAK level shows coronary calcification rather than other types of atherosclerotic plaques.     

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats

Background:Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats.Methods:he animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion + uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion + uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes.Results:In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups.Conclusion:Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.     

Clinical results of free vascularized fibula graft in the management of precollapse osteonecrosis of the femoral head: A retrospective clinical study

Objective:This study aimed to evaluate clinical results, femoral head survival, and the need for total hip arthroplasty (THA) in patients with precollapse osteonecrosis of the femoral head (OFH) (Steinberg stage II and III) treated by free vascularized fibula graft (FVFG) application.Methods:We retrospectively reviewed 54 hips of 47 patients (39 males, eight females; mean age 36 ± 14 years) who underwent FVFG due to OFH, with at least two years of follow-up. The patient data, including Harris Hip Score (HHS), Visual Analogue Scale (VAS), and conversion to THA, were documented.Results:The right hip of 26 patients and the left hip of 28 patients were involved. Bilateral FVFG surgery was performed on seven patients due to bilateral OFH. The mean follow-up time was 5.5 (range 2-14) years. Survival of the femoral head was observed in 39 hips (72.2%), while the femoral head collapse was observed in 15 femoral heads (27.8%). The mean preoperative HHS increased from 46.5 (range = 12-85) to 86.5 (range = 33-100) postoperatively (P < 0.001). The mean preoperative VAS score improved from 8.2 (range = 2-10) to 1.3 (range = 0-10) postoperatively (P < 0.001). THA was performed on seven hips at a mean follow-up time of 1.8 years (range = 0.7–3.3). There was no significant difference in the collapse rate between unilateral or bilateral OFH (P = 0.175). A higher survival rate was observed in the Steinberg stage II femoral head patients compared to the stage III femoral head (P = 0.021).Conclusion:This study has shown that FVFG surgery can be a good option for managing patients with Steinberg stage II and III precollapse OFH to prevent femoral head collapse and joint function.     

Survival Outcomes of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

BackgroundThe survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB).Patients and MethodsPatients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS).ResultsAmong 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size >4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P < .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P < .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P < .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P < .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of >2 were associated with worse OS (P < .05).ConclusionsAny adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged >76 years.     

Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study

BackgroundAbout 10–20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa.MethodsData were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS).ResultsA total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55–0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24–1.67; P<0.001), age >70 years (HR 1.28; 1.02–1.62; P=0.034), lack of health insurance (HR 1.32; 1.02–1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43–11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48–2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29–0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55–0.79; P<0.001) were associated with improved OS.ConclusionsIn addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.     

Tuberculous and non‐tuberculous cervical lymphadenopathy incidence and distribution in Somalia from 2016 to 2020: A review of 241 cases

ObjectiveTo determine the incidence of tuberculous lymphadenitis (TBL) and other pathologies in cervical lymphadenopathies in Somalia and accompanying radiological findings.MethodsIn this hospital‐based retrospective study, the demographic characteristics, pathology results and radiological findings of 263 patients who underwent ultrasound (US)‐guided cervical lymph node biopsy between January 2016 and February 2020 were analyzed.ResultsOf 241 patients 118 men and 123 women (mean age 27.9 ± 18.1 years) included in the study, 46.1% (n = 111) were diagnosed as necrotizing granulomatous lymphadenitis (caseified, consistent with TBL) and 21.6% (n = 12, atypical lymphoid cells and n = 40, metastases) as malignancy. The most common type of metastasis was squamous cell cancer (n = 31), and the primary source of most of them was esophageal cancer (16/31, 51.6%). The age of patients with TBL was significantly lower than that of non‐TBL (21.9 ± 14.6 vs. 41.9 ± 24.6, P = 0.003) and the incidence of TBL in pediatric patients was statistically higher (58.0% vs. 21.5%, P = 0.019). The rate of patients with TBL being localized at level 4 and level 5 was significantly more than non‐TBL patients (18.0% vs. 10.0% and 23.4% vs. 10.8%, respectively, P = 0.01). Half of patients with TBL who have chest radiography had pathological findings; consolidation and bronchopneumonia were present in 52.6% of them. There were 2 patients with paravertebral abscess and one patient with gastrointestinal tuberculosis.ConclusionIn Somalia, in the presence of cervical lymphadenopathy, after diagnosis by using US‐guided biopsy; primarily considering of TBL and malignancy, thoracic involvement should be investigated, and esophageal carcinoma must be excluded in terms of metastatic lymph node.     

Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats

Carvacrol is a dietary polyphenol from Lamiaceae plants that has been shown to possess a wide range of biological activities including antioxidant and antitumor effects. This study aimed to investigate its anti-inflammatory and antioxidant effects on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Forty-nine rats were randomly assigned to four treatment and three control groups. Over 60 days, MNNG (200 mg/kg BW) was orally applied to animals of groups 1–5 while the rats in groups 2–5 also received different doses of carvacrol (10, 25, 50, and 100 mg/kg BW, respectively) until the end of the experiment. Group 6 rats were treated with 100 mg/kg BW carvacrol and no MNNG whereas group 7 was the control group without any treatment. After the euthanasia of all rats, the inflammatory cytokines and oxidative stress parameters were assessed in the blood and tissues. The expression of caspase 9, Bax, and Bcl-2 proteins in the stomach tissues were investigated through histopathological examinations. Statistically significant differences were observed in the body weight, oxidative stress, and inflammation parameters of groups 1 to 6 compared to group 7 (p ≤ 0.001). Animals in MNNG groups 2 and 3 treated with the low dose carvacrol (10 and 25 mg/kg BW) showed significantly reduced oxidative stress, inflammation, and apoptotic effect compared to animals of the MNNG groups receiving increased doses of carvacrol (50 and 100 mg/kg BW) or no carvacrol. Rats exposed to MNNG exhibited gastric cancer cells in several areas. In the MNNG group receiving 100 mg/kg BW carvacrol, the inflammatory cell infiltration was observed in gastric mucosal and submucosal areas whereas MNNG rats supplemented with 10 and 25 mg/kg BW carvacrol showed no pathological alterations of the gastric cells. The results of this study indicate that significant antioxidant and anti-inflammatory effects induced by carvacrol at doses of 10 and 25 mg/kg BW interfered with gastric carcinogenesis induced by MNNG in Wistar rats as well as provide hepatoprotection. However, high doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis.     

Composition,antimicrobial activity and in vitro cytotoxicity of essential oil from Cinnamomum zeylanicum Blume (Lauraceae)

The essential oil from the bark of Cinnamomum zeylanicum Blume was analyzed by GC–MS and bioassays were carried out. Nine constituents representing 99.24% of the oil were identified by GC–MS. The major compounds in the oil were (E)-cinnamaldehyde (68.95%), benzaldehyde (9.94%) and (E)-cinnamyl acetate (7.44%). The antimicrobial activity of the oil was investigated in order to evaluate its efficacy against 21 bacteria and 4 Candida species, using disc diffusion and minimum inhibitory concentration methods. The essential oil showed strong antimicrobial activity against all microorganisms tested. The cytotoxic and apoptotic effects of the essential oil on ras active (5RP7) and normal (F2408) fibroblasts were examined by MTT assay and acridine orange/ethidium bromide staining, respectively. The cytotoxicity of the oil was quite strong with IC₅₀ values less than 20 μg/mL for both cell lines. 5RP7 cells were affected stronger than normal cells. Morphological observation of apoptotic cells indicated the induction of apoptosis at the high level of the oil, especially in 5RP7 cells. The present study showed the potential antimicrobial and anticarcinogenic properties of the essential oil of cinnamon bark, indicating the possibilities of its potential use in the formula of natural remedies for the topical treatment of infections and neoplasms.     

Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis

The goal of this investigation was to study the protective effects of thymoquinone (TQ) and methotrexate (MTX) on collagen-induced arthritis (CIA) in rats. On day 0 under ether anesthesia, the experimental groups were immunized with 0.5 mg native chick collagen II (CII) solubilized in 0.1 M acetic acid and emulsified in Freund's incomplete adjuvant. Control rats were gavaged with vehicle, whereas CII was administered intradermally. In addition, arthritis treated with TQ group received TQ (10 mg kg(-1) bw by gavage once a week for 3 weeks starting on day 0); and arthritis treated with MTX group received MTX (MTX was suspended in corn oil and administered by gavage at 1 mg kg (-1) bw once a week for 3 weeks starting on day 0). A significant decrease in the incidence and severity of arthritis by clinical and radiographic assessments was found in recipients of therapy, compared with that of controls. The MTX treatment significantly (P<0.01) decreased the elevated serum NO, urea and creatinine in arthritic rats. Likewise, TQ treatment was also able to reduce significantly (P<0.05) serum NO, urea and creatinine levels, but to lesser extent than MTX. The histopathologic abnormalities are consistent with the hydropic epithelial cell degenerations and moderate tubular dilatation in the some proximal and distal tubules. The severity of the degenerative changes in most of the shrunken glomerules and vascular congestion were also observed in arthritic animals. Preventive treatment of TQ and especially MTX significantly inhibited kidney dysfunction and this histopathologic alterations. These studies indicate that TQ can be used similar to MTX as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.