Okmeydanı Eğitim ve Araştırma Hastanesi

Backgrounds and ObjectivesColorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311).Materials and MethodsIn this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups.ResultsA total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848).ConclusionAccording to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Purpose Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with liraglutide has been shown to reduce oxidative stress. Therefore, we evaluated the potential protective effect of liraglutide against GEN-induced nephrotoxicity in rats. Methods Twenty-eight rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus liraglutide (0.6 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis, interstitial fibrosis and inducible nitric oxide synthetase (iNOS) scores were determined histopathologically in a part of kidneys; malondialdehyde (MDA), reduced glutathione (GSH), E-cadherin and transforming growth factor β1 (TGF-β1) levels were determined in other part of kidneys. Results The GSH levels in renal tissue of only GEN-treated rats were significantly lower than others, and administration of liraglutide to rats significantly increased the level of GSH. The group that was given GEN plus liraglutide had significantly lower MDA, TGF - β1 and E - cadherin levels than that given GEN alone. The rats treated with GEN+liraglutide indicated a less severe tubular necrosis, and their glomeruli maintained a better morphology compared to GEN group. iNOS expression was higher in liraglutide administrated group than the group that was applied only GEN. Conclusion Liraglutide exerts protective effects on GEN-induced kidney damage by reducing oxidative stress in rat model.

One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Introduction: There is a lack of evidence of the outcomes in elderly patients advanced stage biliary tract cancer due to the patients aged over 65 years are less than 25% in many prospective trials.We designed a retrospective multicenter study to evaluate the factors affecting treatment and survival in elderly patients with advanced-stage biliary tract cancer.Materials and methods: A total of 116 patients with advanced stage biliary tract cancer aged 65 years were included, and the treatment responses, survival, and toxicity rates were evaluated with respect to age groups Results: There was no significant difference between age and response to treatment, survival, or toxicity.The median progression-free survival and overall survival were 5.3, and 11.8 months respectively.Multivariate analysis indicated that ECOG PS (p<0.001CI95% 1.5-3.7)and PNI (p<0.001CI 95% 0.14-0.41)were significant independent prognostic factors for PFS.The independent prognostic factors for OS were choice of frontline regimen, NLR and PNI (p=0.007CI 95% 0.71 -0.94, p=0.006CI 95% 1.2 -3.1, p=0.001CI 95% 0.35 -0.91, respectively).Discussion: This study confirms the general prognostic relevance of inflammatory parameters and the importance of frontline treatment in elderly patients with advanced-stage biliary tract tumors.Additionally, getting older does not indicate that treatment will be avoided or that they will have a worse prognosis and suffer from more toxicities.

To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC. We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users. Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94-27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9months (95% CI: 7.5-14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use (p = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib. Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib.

In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who were not eligible for surgery and treated with SRS. Between January 2013 and December 2018, 53 patients with cavernomas were treated using SRS with the CyberKnife® system. Patients’ diseases were deeply located or were in subcortical functional brain regions. In addition to bleeding, 23 (43.4%) patients had epilepsy, 12 (22.6%) had neurologic symptoms and 16 patients (30.2%) had severe headaches. The median volume was 741 (range, 421–1351) mm3, and the median dose was 15 (range, 14–16) Gy in one fraction. After treatment, six (50%) of 12 patients with neurologic deficits still had deficits. Rebleeding after treatment developed in only two (3.8%) patients. The drug was completely stopped in 14 (60.9%) out of 23 patients who received epilepsy treatment, and the dose of levetiracetam decreased from 2000 mg to 1000 mg in four (17.3%) of nine patients. Radiologically, complete response (CR) was observed in 13 (24.5%) patients, and partial responses (PR) were observed in 32 (60.2%) patients. Clinical response of CR was observed in 30 (56.6%) patients, PR was observed in 16 (30.2%), stable disease (SD) was observed in three (5.7%) and four (7.5%) patients progressed. In conclusion, SRS applied in the appropriate dose schedule may be an effective and reliable method in terms of symptom control and prevention of rebleeding, especially in patients with inoperable cavernomas.

Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease. To analyse the treatment use by CU patients before, during and after pregnancy as well as outcomes of pregnancy. PREG-CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence network. Data were collected via a 47-item-questionnaire completed by CU patients who became pregnant during their disease course. Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication including standard-dose second generation H1-antihistamines (35.1%), first generation H1-antihistamines (7.6%), high-dose second-generation H1-antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new-borns were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth. Most CU patients used treatment during pregnancy especially second-generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new-borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy.