Efficacy and safety of infliximab in patients with autoimmune hepatitis.

BACKGROUND AND AIMS: A limited number of drugs are used as standard or alternative therapies in autoimmune hepatitis (AIH). No specific recommendations are available for patients failing to respond to these therapies. We analyzed the efficacy and safety of infliximab in patients with AIH. APPROACH AND RESULTS: We performed a retrospective study of 42 patients with AIH who received infliximab at 21 liver centers in 12 countries. Patients were categorized according to the reason for infliximab therapy. Patients in group 1 (n=20) had failed standard, second-line (mycophenolate mofetil and 6-mercaptopurine) or third-line (tacrolimus or cyclosporine) therapy. In group 2 (n=22), infliximab was given for treatment of concomitant extrahepatic autoimmune diseases. Patients received a median of 17 (range: 3-104) infliximab infusions. Complete biochemical response (CR) was achieved or maintained in 33 (78%) patients during infliximab therapy. In group 1, infliximab induced CR in 11 of 20 (55%) patients. In group 2, 16 patients with CR prior to infliximab maintained remission, and the remaining 6 patients with active AIH (5 on standard and 1 on both second-line and third-line therapy) showed CR following infliximab therapy. Infliximab led to CR in 75% (6/8) of nonresponders to second-line and in 46% (6/13) of failing third-line therapy. Overall, 65% (17/26) of the patients with active AIH achieved CR on infliximab. Infliximab was discontinued in 3 patients of group 1. One patient had a severe allergic reaction and 2 developed anti-infliximab autoantibodies. CONCLUSIONS: Our study suggests that infliximab may be an effective and safe rescue therapy in AIH.

The effect of incidental dose to pelvic nodes in bladder-only irradiation in the era of IMRT: a dosimetric study.

PURPOSE: While three-dimensional radiotherapy (RT) causes high incidental nodal doses in bladder-only irradiation for muscle-invasive bladder cancer (MIBC), the impact on pelvic lymphatics is unclear in the era of intensity-modulated RT (IMRT). This study evaluates incidental doses to pelvic lymphatics in MIBC patients treated with IMRT. METHODS: The data of 40 MIBC patients treated with bladder-only IMRT and concurrent chemotherapy were retrospectively evaluated. The pelvic lymphatics were contoured on initial simulation images and incidental nodal doses were evaluated. The Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was used for statistics. RESULTS: Median RT dose to the bladder was 60 Gy in 30 fractions. In dosimetric analysis, median values of mean dose (Dmean) of the obturator, presacral, external iliac, internal iliac, and distal common iliac lymphatics were 33 Gy (range 4-50 Gy), 3 Gy (range 1-28 Gy), 9.5 Gy (range 3-41 Gy), 7.5 Gy (range 2-14 Gy), and 1 Gy (range 0-15 Gy), respectively. The Dmean of the obturator lymphatics was significantly higher (p < 0.001) and the Dmean of the distal common iliac lymphatics was significantly lower (p < 0.001) than all remaining lymphatic stations. The Dmean of the external iliac lymphatics was significantly higher than that of the presacral lymphatics (p < 0.001), but the difference with the internal iliac lymphatics was not statistically significant (p = 0.563). CONCLUSION: The incidental nodal doses with bladder-only IMRT are heterogeneous and remain below the generally accepted doses for microscopic disease eradication for bladder cancer.

Analysis of patients with parotid recurrence after parotid-sparing IMRT for nasopharyngeal carcinoma: case series and review of the literature.

PURPOSE: Intensity-modulated radiotherapy (IMRT) is the standard treatment approach for nasopharyngeal cancer (NPC). IMRT enables effective sparing of the parotid glands and reduces the risk of xerostomia, a common complication of head and neck irradiation. Nevertheless, it is essential to determine whether the parotid-sparing IMRT (ps-IMRT) technique yields increased intra-/periparotid recurrence rates, which constitutes the main purpose of this study. METHODS: Patients with a diagnosis of NPC that received definitive chemoradiotherapy/radiotherapy (CRT/RT) between 1991 and 2021 were evaluated retrospectively. Patients with intra-/periparotid recurrence were detected and prognostic factors for recurrence were sought. RESULTS: A total of 746 patients were evaluated. Two-dimensional (2D)-RT was applied to 541, 3D conformal RT (3D-CRT) to 10, and ps-IMRT to 195 patients. After a median 85-month follow-up, one (0.18%) patient who received 2D-RT and four (2%) patients who received ps-IMRT experienced an intra-/periparotid recurrence. The median time to intra-/periparotid recurrence was 11.9 months. All patients had been diagnosed with a metastatic lymph node > 2 cm at level II of the ipsilateral neck. In addition, all recurrences occurred on the same side as the positive neck at the time of diagnosis. The 3­year overall survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 80%, 40%, and 60%, respectively. CONCLUSION: Intra-/periparotid recurrence is extremely rare in NPC. However, it is still possible to identify and characterize particular risk factors, which include a metastatic lymph node at level II, particularly > 2 cm, and multinodal disease at the time of diagnosis.

The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer.

BACKGROUND: Ceranib-2, an acid ceramidase (AC) inhibitor, can inhibit cancer cell proliferation and tumor development. However, poor water solubility and low cellular bioavailability limit its efficacy in cancer treatment. METHODS AND RESULTS: This study aimed to investigate the cell death induced by ceranib-2 and its solid lipid nanoformulation (ceranib-2-SLN) produced by the hot homogenization technique and the synergistic relationship between ceramide and telomerase in vitro and in silico. Furthermore, this study proved the possible mechanism of ceranib-2-induced AC inhibition by in silico studies. The effective cytotoxic concentrations of ceranib-2, telomerase level, and changes in ceramide levels were measured by MTT colorimetric cytotoxicity assay, ELISA, and LC/MS/MS methods, respectively. TEM results showed that ceranib-2-SLN was 13-fold smaller than the size of ceranib-2. Ceranib-2 and ceranib-2-SLN had IC50 concentrations of 31.62 (± 2.1) and 27.69 (± 1.75) µM in A549, and 48.79 (± 1.56) and 67.98 (± 2.33) in Beas-2B cells. These compounds simultaneously increased ceramide levels and decreased telomerase levels in A549 cells. Ceranib-2 increased telomerase levels while decreasing ceramide levels in Beas-2B cells. It was shown how the synergistic impact of ceranib-2-induced ceramide production and ceramide-induced telomerase level reduction on cytotoxicity in A549 cells. CONCLUSIONS: Ceranib-2-SLN was discovered to be more cytotoxic on cancer cells than ceranib-2, suggesting that it could be a promising option for the development of a new anti-cancer agent.

Esophageal Carcinoma in Children: Report of 2 Cases and a Review of the Literature.

Esophageal carcinoma in children and adolescents is extremely rare. Here, we report 2 cases of pediatric esophageal carcinoma presenting with progressive dysphagia. There was not any underlying specific risk factor in our cases. The histopathological subtypes were adenocarcinoma in one and squamous cell carcinoma in another case. Response to combined modality treatment was good in the case of adenocarcinoma, while the patient with squamous cell carcinoma was unresponsive to treatment and died of the progressive disease. We reviewed the pediatric cases of esophageal carcinoma reported in the literature. Progressive dysphagia was observed in 89% of these cases. One third of pediatric cases had underlying risk factors. Squamous cell carcinoma is a more common type of childhood esophageal carcinoma. In contrast to adults, pediatric esophageal squamous cell carcinoma may distribute throughout the esophagus. Esophageal adenocarcinoma was seen in the distal esophagus in pediatric cases. Metastatic disease was found in 48% of pediatric patients at presentation, and the prognosis is poor. Collaborative efforts are needed for success in the treatment of esophageal carcinoma.

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome.

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. CONCLUSIONS: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

The association between pan-immune-inflammation value and survival in head and neck squamous cell carcinoma.

PURPOSE: A significant portion of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) relapse despite multimodality treatment denoting the need for biomarkers. The pan-immune-inflammation value (PIV) is a recently developed blood count-based prognostic biomarker. We evaluated the relationship between PIV and survival in locally advanced HNSCC patients treated with chemoradiotherapy (CRT). METHODS: A total of 199 patients who underwent CRT at Hacettepe University Oncology Hospital were included. The relationship between clinical and laboratory parameters with overall survival (OS) and disease-free survival (DFS) was analyzed by multivariate analyses. RESULTS: The median age was 59 years and 90.5% of the patients were male. 66.8% of the patients had laryngeal primaries, and 78.9% had T3-T4 disease. 84.9% of the patients received CRT with cisplatin. The optimal PIV threshold value was calculated as 404 in ROC analyses. This PIV value had 75.8% sensitivity and 70.4% specificity for OS prediction (AUC 0.781; 95% CI 0.715-0.846; p < 0.001). In multivariate analyses, high PIV levels (≤ 404 vs. > 404, HR 2.862; 95% CI 1.553-5.276; p = 0.001), higher NLR (≤ 2.5 vs. > 2.5, HR 1.827; 95% CI 1.017-3.281; p = 0.044) levels and ECOG performance score of 2 (HR 2.267; 95% CI 1.385-3.711; p = 0.001) were associated with shorter OS. These factors were associated with shorter DFS also (HR for PIV 2.485, 95% CI 1.383-4.467, p = 0.002). CONCLUSIONS: We observed shorter OS and DFS in locally advanced HNSCC patients with high PIV levels. If prospective studies support our findings, the PIV score could be a prognostic biomarker in HNSCC.

SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis.

BACKGROUND: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS: We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.

Do grape and black mulberry molasses have an effect on oral mucositis and quality of life in patients with head and neck cancer?

OBJECTIVE: We aimed to investigate the effect of black mulberry and grape molasses on the prevention and treatment of oral mucositis and quality of life (QoL) in patients with head and neck cancer (HNC). METHODS: Patients treated for HNC between 2010 and 2018 in our department were divided into three groups (group 1 = control (n = 14), group 2 = grape molasses (n = 40), and group 3 = black mulberry molasses (n = 40)). Oral mucositis, pain scoring, and weight loss were evaluated weekly. The European Organization for Research and Treatment of Cancer (EORTC) General QoL Questionnaire (QLQ-C30) and EORTC Head and Neck Cancer QoL Module (QLQ-HN35) were used to evaluate QoL. RESULTS: The mean body weight, scores of oral mucositis, and pain were similar among the groups throughout the treatment. Both groups 2 and 3 were associated with improved outcomes for swallowing, opening mouth, and weight loss in the EORTC HN35, and these parameters were not significantly different between groups 2 and 3. Global health score was higher in group 3 at the 6th week of RT compared to that of group 2. Both groups 2 and 3 had improved scores for role functioning, emotional and social functioning, fatigue, appetite loss, and pain throughout the treatment compared to group 1. CONCLUSIONS: Both grape and black mulberry molasses improved the QoL in HNC patients. No significant difference between black mulberry and grape molasses was found with regard to the healing of oral mucositis.

Decreased Na+/K+ pump activity in the erythrocyte membrane due to malondialdehyde in rheumatoid arthritis: an in vivo and in silico study.

Apart from demonstrating the interaction behavior of malondialdehyde (MDA) with Na+/K+-ATPase using in silico, the current study aims to investigate the effect of rheumatoid arthritis-related oxidative stress on Na+/K+-ATPase activity that is present in the erythrocyte cell membrane, which is rich in proteins vulnerable to damage from MDA and other free radicals. The target population of this study consists of 28 rheumatoid arthritis patients and 20 healthy volunteers whose MDA levels and Na+/K+-ATPase activity were determined. It was shown that MDA levels of rheumatoid arthritis patients increased (p < 0.001) and their Na+/K+-ATPase activity noticeably decreased when compared to those of healthy individuals. Also, according to this in silico modeling, MDA decreased Na+/K+-ATPase activity in line with the correlation analyses. Consequently, while elevated levels of MDA in the rheumatoid arthritis group were suggestive of oxidative stress, a decreased Na+/K+-ATPase-activity led us to speculate that the cellular membrane had sustained injury. Therefore, our results could be useful in explaining how MDA affects Na+/K+-ATPase activity in the interior of a specific molecular pathway.

Escin attenuates oxidative damage, apoptosis and lipid peroxidation in a model of cyclophosphamide-induced liver damage.

To investigate the effects of escin (ES) on acute damage induced by alkylating agent, experimental rats were injected with cyclophosphamide (CPM) to cause liver damage. The animals were divided into four groups: Control Group, CPM (200 mg/kg), ES (10 mg/kg), CPM, and ES Groups. Immunohistopathological, hepatic histopathological, and biochemical changes were analyzed. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), malondyaldehyde (MDA), glutathion (GSH), total oxidant status (TOS) and total antioxidant status (TAS) in serum were all determined. Serum and immunohistopathology analysis revealed that MDA, ALT, AST, LDH, TOC and OSI, caspase-3 and Bax levels had increased while GSH, TAC, Bcl- 2 and OSI levels decreased in CPM Group when compared to Control Group. These findings appear to account for the severe damage detected. In the CPM + ES treated group, positive improvements were found in biochemical parameters as well as in cell-death and tissue-related damage parameters.The results show that ES considerably protects the rat liver against CPM-induced hepatotoxicity thanks to because of its anti-oxidant and anti-apoptotic properties.

Investigation into the protective effects of Hypericum Triquetrifolium Turra seed against cyclophosphamide-induced testicular injury in Sprague Dawley rats.

For centuries, Turkey has been a significant location here around 80 species of Hypericum with differing names widely occur, which is also known as Turkish folk medicine in treating some bacterial diseases as well as stomach and intestine inflammation. Recent studies have reported this herb family to contain numbers of bioactive compound contents. The study aims to investigate the protective effects of Hypericum triquetrifolium Turra (HT) upon oxidative stress and apoptosis in a rat model in which testes injury was induced by CP. The testicular injury was caused using CP (150 mg/kg). The rats were treated with a single dose (100 mg/kg) of methanol extract of HT to investigate various biochemical markers in the serum and plasma of blood samples apart from assessing the prognosis of CP-induced testicular damage. Added to that, histological analyses were performed to identify possible structural changes and apoptotic indicators, like Bax, Caspase-3, and Bcl-2. In CP Group, there was a rise in the levels of total oxidant status (TOS), malondialdehyde (MDA), oxidative stress index (OSI), Caspase-3, and Bax while superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), Bcl-2, and total antioxidant capacity (TAC) all decreased. Also, our histological analysis showed damaged testes. On the other hand, neither biochemical nor histological analysis showed testicular damage in HT Alone Group. In CP + HT Group, a significant number of the negatives changes due to CP were observed to have improved remarkably following an HT treatment. This study results suggest that HT could help improve CP-induced testicular injury thanks to its anti-oxidative and anti-apoptotic properties.

Stereotactic body radiotherapy optimization to reduce the risk of carotid blowout syndrome using normal tissue complication probability objectives.

PURPOSE: To determine the possibility of further improving clinical stereotactic body radiotherapy (SBRT) plans using normal tissue complication probability (NTCP) objectives in order to minimize the risk for carotid blowout syndrome (CBOS). METHODS: 10 patients with inoperable locally recurrent head and neck cancer, who underwent SBRT using CyberKnife were analyzed. For each patient, three treatment plans were examined: (1) cone-based without delineation of the ipsilateral internal carotid (clinical plan used to treat the patients); (2) cone-based with the carotid retrospectively delineated and spared; and (3) Iris-based with carotid sparing. The dose-volume histograms of the target and primary organs at risk were calculated. The three sets of plans were compared based on dosimetric and TCP/NTCP (tumor control and normal tissue complication probabilities) metrics. For the NTCP values of carotid, the relative seriality model was used with the following parameters: D50 = 40 Gy, γ = 0.75, and s = 1.0. RESULTS: Across the 10 patient plans, the average TCP did not significantly change when the plans were re-optimized to spare the carotid. The estimated risk of CBOS was significantly decreased in the re-optimized plans, by 14.9% ± 7.4% for the cone-based plans and 17.7% ± 7.1% for the iris-based plans (p = 0.002 for both). The iris-based plans had significant (p = 0.02) reduced CBOS risk and delivery time (20.1% ± 7.4% time reduction, p = 0.002) compared to the cone-based plans. CONCLUSION: A significant improvement in the quality of the clinical plans could be achieved through the delineation of the internal carotids and the use of more modern treatment delivery modalities. In this way, for the same target coverage, a significant reduction in the risk of CBOS could be achieved. The range of risk reduction varied depending on the proximity of carotid artery to the target.

Alternations in nuclear factor kappa beta activity (NF-kB) in the rat brain due to long-term use of atomoxetine for treating ADHD: In vivo and in silico studies.

Attention Deficit Hyperactivity Disorder (ADHD) is the most common psychiatric disorder reported particularly in children. Long-term use of antipsychotic drugs used in the treatment of ADHD has been shown to exert toxic effects on the brain. However, not enough research has been carried out on the neurotoxic effects of these drugs on the brain tissue. Atomoxetine (ATX) is the most widely used antipsychotic drug that has gained approval for ADHD treatment. The present study aims to determine the damage induced by long-term use of three different doses of ATX in the brain tissue of experimental rats. 24 rats were divided into Control group (0.5 mL saline), Group 2 (0.5 mg/mL ATX), Group 3 (1.0 mg/mL ATX), and Group 4 (2.0 mg/mL ATX), each group having 6 members. Their brain tissues were taken for stereological, histological, and nuclear factor kappa-B (NF-kB) protein expression analysis. ATX was determined to have caused a few alterations in the brain tissue, such as disruption in the endothelial epithelium of capillaries, a couple of large astrocyte nuclei, and mitotic astrocytes. Moreover, a significant difference was observed in Group 4 compared to Control Group in terms of astrocyte counts in the brain sections. As for Groups 3 and 4, there were differences in terms of oligodendrocyte counts in the incisions cultivated from the brain tissues of the animals. On the other hand, NF-kB positive astrocytes of Groups 3 and 4 differed significantly from those of Control and Group 2. The results of molecular dockings of the present study are in line with the in-vivo results. Therefore, it was concluded that the higher the dose of ATX was, the more damage the brain tissue sustained.

Molecular docking analyses of Escin as regards cyclophosphamide-induced cardiotoxicity: In vivo and in Silico studies.

This study aims to investigate whether Escin (ES) can protect against Cyclophosphamide (CPM)-induced cardiac damage. The experimental rats were categorized as Control, CPM (200 mg/kg), ES (10 mg/kg), and CPM + ES Groups, each having 6 members. Their heart tissues were stained with Hematoxylin and Eosin and the structural changes were investigated under the light microscope. The biochemical markers of ischemia modified albumin (IMA), creatine kinase (CK-MB), antioxidant activity indicators Catalase (CAT), and superoxide dismutase (SOD) activities were measured using blood samples. Besides, the effects of CPM, ES, and CPM + ES upon CAT and SOD activities were shown via molecular docking studies. In the Single-Dose CPM group, CK-MB and IMA levels significantly increased while SOD and CAT levels significantly decreased. However, the heart tissues were damaged. CK-MB and IMA levels significantly decreased in CP+ ES Group. On the other hand, SOD, and CAT levels significantly increased and reduced the damage remarkably. Our findings showed that ES treatment successfully reduced the toxic effects upon the rats. The conclusion is that ES treatment can help protect the heart tissue against CPM-induced toxicity. Both in-vivo results and molecular modeling studies showed that the negative effects of CPM upon SOD activity were bigger than that of CAT.

Radiotherapy-induced alterations in vitreous humor: A new potential critical structure.

Vitreous humor (VH) is not considered as a critical structure in the radiotherapy planning process. In the present study, an experimental animal model was performed to examine the effects of radiotherapy on VH. The right eyes of twelve New Zealand rabbits were irradiated to 60 Gy in 3 fractions in accordance with the scheme used in the treatment of uveal melanoma in our clinic, and contralateral (left) eyes were considered as control. Weekly ophthalmologic examination was performed after irradiation, for three months. At the end of the third month, enucleation and vitreous collection were conducted. The vitreous samples were subjected to metabolomic analyses, ELISA analyses, viscosity measurements, and electron microscopic examination. In control and experimental vitreous samples, 275 different metabolites were identified, and 34 were found to differ significantly between groups. In multivariate analyzes, a clear distinction was observed between control and irradiated vitreous samples. Pathway analysis revealed that nine pathways were affected, and these pathways were mainly related to amino acid metabolism. A significant decrease was observed in the expressions of type II, V, and XI collagens in protein level in the ELISA. There was a non-significant decrease in type IX collagen and viscosity. Electron microscopic examination revealed disrupted collagen fibrillar ultra-structure and dispersed collagen fragments in the experimental vitreous. An intact vitreous is essential for a healthy eye. In this study, we observed that radiation causes changes in the vitreous that may have long-term consequences.

Serum Biglycan as a Diagnostic Marker for Non-Alcoholic Steatohepatitis and Liver Fibrosis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has risen in prevalence substantially through the years. Although course and progression of the disease are variable, fibrosis is the most important factor. We intended to explore utility of serum biglycan (BGN) in NASH and its capacity in anticipating liver fibrosis. METHODS: Serum tests of consecutive patients with biopsy-confirmed NASH and age, gender-matched healthy volunteers were utilized to evaluate serum BGN levels using ELISA kits. The correlation between BGN and histopathological highlights of NASH was examined. While patients with fibrosis scores < 2 were assembled in mild and scores of (≥ 2) were in significant fibrosis groups. Univariate/multivariate regression analyses were performed to assess the independent predictive variables of liver fibrosis. Receiver operating characteristics (ROC) were applied to locate the best cutoff values of BGN for NASH and fibrosis. RESULTS: Seventy patients with NASH and 70 controls were recruited in the study. BGN levels were lower in NASH patients contrasted with controls 137.70 ± 33.12 pg/mL vs. 259.61 ± 187.34 pg/mL, respectively, and p < 0.001. In correlation, serum BGN was related to liver fibrosis and inflammation. The comparison between mild and significant fibrosis groups regarding BGN was as follows 155.92 ± 49.97 pg/mL vs. 390.07 ± 214.746 pg/mL, respectively, (p < 0.001). In multivariate analyses, BGN was an independent predictive factor of significant fibrosis (OR, 1.030; 95% CI: 1.011 - 1.048; p < 0.001). ROC analysis revealed that BGN was statistically significant in determination of significant fibrosis (AUROC, 0.955; 95% CI, 0.877 - 0.990; p < 0.001). Best cutoff value was 189.58 pg/mL with the best sensitivity (93.55%) and specificity (87.18%). CONCLUSIONS: Serum BGN may be a new non-invasive indicative marker for the presence of NASH, significant fibrosis, and a treatment goal in the disease process.

Factors affecting post-treatment radiation-induced lung disease in patients receiving stereotactic body radiotherapy to lung.

The aim of the study is to investigate factors that may cause radiation-induced lung disease (RILD) in patients undergoing stereotactic body radiotherapy (SBRT) for lung tumors. Medical records of patients treated between May 2018 and June 2019 with SBRT were retrospectively evaluated. All patients should have a diagnosis of either primary non-small cell lung cancer (NSCLC) or less than three metastases to lung from another primary. The median treatment dose was 50 Gy in 4-5 fractions. Tumor response and RILD were evaluated in thoracic computer tomography (CT) using RECIST criteria. 82 patients with 97 lung lesions were treated. The median age was 68 years (IQR = 62-76). With a median follow-up of 7.2 months (3-18 months), three patients had grade 3 radiation pneumonitis (RP). RILD was observed in 52% of cases. Patients who had RILD had a higher risk of symptomatic RP (p = 0.007). In multivariate analyses older age, previous lung radiotherapy history, and median planning treatment volume (PTV) D95 value of ≥ 48 Gy were associated with RILD. Local recurrence (LR) was observed in 5.1% of cases. There was no difference in overall survival and LR with the presence of RILD. Older age, previous lung radiotherapy history, and median PTV D95 value of ≥ 48 Gy seems to be associated with post-SBRT RILD.

Stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer: Does beam-on time matter?

PURPOSE: Stereotactic body radiotherapy (SBRT) is an effective treatment option for patients with early-stage non-small cell lung cancer (NSCLC). In this study, we evaluated the treatment results using two different SBRT techniques and the effect of beam-on time (BOT) on treatment outcomes. METHODS: Between July 2007 and January 2018, 142 patients underwent SBRT for primary NSCLC. We have delivered SBRT using either respiratory tracking system (RTS) or internal-target-volume (ITV)-based motion management techniques. The effect of age, tumor size, pretreatment tumor SUVmax value, presence of tissue diagnosis, histopathological subtype, operability status, tumor location, motion management technique, BED10 value, BOT on overall survival (OS), loco-regional control (LRC), event-free survival (EFS) and primary tumor control (PTC) were evaluated. RESULTS: Median age of the patients was 70 years (range, 39-91 years). Most of the patients were inoperable (90%) at the time of SBRT. Median BED10 value was 112.5 Gy. With a median follow-up of 25 months, PTC was achieved in 91.5% of the patients. Two-year estimated OS, LRC, PTC and EFS rates were 68, 63, 63 and 53%, respectively. For the entire group, OS was associated with BOT (P = 0.027), and EFS was associated with BOT (P = 0.027) and tumor size (P = 0.015). For RTS group, OS was associated with age (P = 0.016), EFS with BOT (P = 0.05) and tumor size (P = 0.024), LRC with BOT (P = 0.008) and PTC with BOT (P = 0.028). The treatment was well tolerated in general. CONCLUSION: SBRT is an effective and safe treatment with high OS, LRC, EFS and PTC rates in patients with primary NSCLC. Protracted BOT might deteriorate SBRT outcomes.

Stereotactic ablative radiotherapy for bone metastasis of gastrointestinal stromal tumor: Case report and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors are rare and only make bone metastases at a rate of 5%. CASE SUMMARY: A 31-year-old male with a GIST presented with solitary bone metastasis at the right iliac bone. We performed stereotactic ablative radiotherapy (SABR) and achieved excellent local control. Herein, our case is presented, and a short review of the literature is carried out. CONCLUSION: SABR should be considered as a treatment option in GIST with bone metastasis.