The spectrum of side effects associated with COVID-19 vaccines in patients with inborn errors of immunity.

OBJECTIVE: COVID-19 immunization was implemented with emergency-use authorization. We had concerns/lack of information on mRNA vaccine side effects in different inborn errors of immunity (IEI) types. METHODS: We enrolled 141 patients (IEIP) and 151 healthy controls(HC) who received SARS-CoV-2 vaccine/s(Sinovac and/or Pfizer-BioNTech(mRNA vaccine), one to five doses), questioned them for side-effects, evaluated in three groups according to the vaccine/s they received; only Sinovac, only Pfizer-BioNTech, and both vaccines. RESULTS: Arm pain, generalized weakness, myalgia, and fever were common side effects in IEI-P and HC groups. Generalized weakness/fatigue, fever, and palpitation were significantly frequent in IEI-P who experienced COVID-19 compared to those who did not (p = 0.021, p = 0.047, and p = 0.024, respectively). Severe symptoms after vaccination, new-onset splenomegaly and pancytopenia, urticaria, herpes simplex virus (HSV), and varicella zoster virus (VZV) reactivation were seen in four IEI-P (2.8%). CONCLUSION: IEI-P mRNA vaccination is relatively safe compared to the conventional vaccine. Individuals who experience uncommon side effects should undergo immunological screening.

Biomarker detection using corrected degree of domesticity in hybrid social network feature selection for improving classifier performance.

BACKGROUND: Dimension reduction, especially feature selection, is an important step in improving classification performance for high-dimensional data. Particularly in cancer research, when reducing the number of features, i.e., genes, it is important to select the most informative features/potential biomarkers that could affect the diagnostic accuracy. Therefore, researchers continuously try to explore more efficient ways to reduce the large number of features/genes to a small but informative subset before the classification task. Hybrid methods have been extensively investigated for this purpose, and research to find the optimal approach is ongoing. Social network analysis is used as a part of a hybrid method, although there are several issues that have arisen when using social network tools, such as using a single environment for computing, constructing an adjacency matrix or computing network measures. Therefore, in our study, we apply a hybrid feature selection method consisting of several machine learning algorithms in addition to social network analysis with our proposed network metric, called the corrected degree of domesticity, in a single environment, R, to improve the support vector machine classifier's performance. In addition, we evaluate and compare the performances of several combinations used in the different steps of the method with a simulation experiment. RESULTS: The proposed method improves the classifier's performance compared to using the whole feature set in all the cases we investigate. Additionally, in terms of the area under the receiver operating characteristic (ROC) curve, our approach improves classification performance compared to several approaches in the literature. CONCLUSION: When using the corrected degree of domesticity as a network degree centrality measure, it is important to use our correction to compare nodes/features with no connection outside of their community since it provides a more accurate ranking among the features. Due to the nature of the hybrid method, which includes social network analysis, it is necessary to investigate possible combinations to provide an optimal solution for the microarray data used in the research.

Prognostic factors of overall and prostate-specific antigen-progression-free survival in metastatic castration-resistant prostate cancer patients treated with 177 Lu-PSMA-617. A single-center prospective observational study.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with 177 Lutetium labeled PSMA-617 therapy (PSMA-RLT), as well as baseline and therapy-related parameters associated with survival. METHODS: This prospective study included 52 patients who received two to six cycles of PSMA-RLT. Primary endpoints were overall survival (OS) and prostate-specific antigen (PSA)-progression-free survival (PFS). 18 F-Fluorodeoxyglucose (FDG) and 68 Ga-PSMA (PSMA) Positron Emission Tomography/Computer Tomography (PET/CT) scans were performed for a comprehensive assessment of tumor burden and heterogeneity. Biochemical, imaging, clinical, and therapy-related parameters were analyzed with the Kaplan-Meier, log-rank, and Cox regression analyses to predict OS and PFS. RESULTS: Median OS and PSA-PFS were 17.7 (95% confidence interval [CI]: 15.2-20.2) and 6.6 months (95% CI: 4.5-8.8), respectively. Primary resistance to PSMA-RLT (hazard ratio [HR]: 12.57, 95% CI: 2.4-65.2, p: 0.003), <30% PSA response rate after first cycle of PSMA-RLT (HR: 1.016, 95% CI: 1.006-1.03, p: 0.003), FDG > PSMA disease (HR: 4.9, 95% CI: 1.19-20.62, p: 0.03), PSA doubling time (PSA DT) of ≤2.4 months (HR: 15.7, 95% CI: 3.7-66.4, p: <0.0001), and low hemoglobin levels (HR: 0.59, 95% CI: 0.41-0.83, p: 0.003) were correlated with poor OS in the multivariate analysis. Bone scintigraphy > PSMA disease (HR: 5.6; 95% CI: 1.8-17, p: 0.002) and high C-reactive protein (HR: 1.4, 95% CI: 1.1-1.7, p: 0.001) were significant predictive biomarkers for PFS in the multivariate analysis. CONCLUSION: PSA response rate and pattern to PSMA-RLT are the most important predictors of survival in patients receiving PSMA-RLT. Being a strong predictive biomarker, combined FDG and PSMA PET can be helpful for the decision of PSMA-RLT eligibility.

Evaluation of periodontal status and cytokine response in children with familial Mediterranean fever or systemic juvenile idiopathic arthritis.

OBJECTIVES: Familial Mediterranean fever (FMF) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases and anti-inflammatory agents are used in their treatment. This study evaluates the periodontal status and cytokine response in pediatric patients with FMF or sJIA. MATERIALS AND METHODS: Forty-eight FMF/sJIA patients were under treatment/control and in attack-free period; 20 systemically healthy children participated in the study. FMF/sJIA patients were divided into two subgroups based on the treatment they received: receiving anti-IL-1 therapy (anti-IL-1 ( +)) and not receiving anti-IL-1 therapy (anti-IL-1 ( -)). The clinical periodontal indices were recorded. Gingival crevicular fluid (GCF) and serum samples were collected. Cytokine levels (IL-1ß, IL-1α, TNF-α, IL-6, IL-8, IL-10, IL-17, IL-33) in GCF and serum were measured using ELISA kits. RESULTS: There was no significant difference between the groups in terms of GCF IL-1ß and IL-1α levels although, BoP and GI were significantly lower in the anti-IL-1 ( +) group compared to the control group. GCF IL-10 level was higher in the anti-IL-1 ( -) group than in the control group; GCF IL-8 levels were lower in both FMF/sJIA subgroups versus controls. There was no significant difference between serum cytokine levels of FMF/sJIA subgroups. CONCLUSIONS: Considering the significant decrease in GI, BoP, and GCF IL-8 levels in the anti-IL-1 ( +) group, it can be concluded that anti-IL-1 medications may suppress periodontal inflammation clinically and immunologically. CLINICAL RELEVANCE: Anti-IL agents are not currently used in periodontal therapy. However, this study demonstrated the positive effect of anti-IL-1 medications on periodontal inflammation in pediatric patients with FMF or sJIA.

In vitro comparison of nanofibrillar and macroporous-spongious composite tissue scaffolds for periodontal tissue engineering.

PURPOSE/AIM OF THE STUDY: The ultimate goal of periodontal treatment is to regenerate the lost periodontal tissues. The interest in nanomaterials in dentistry is growing rapidly and has focused on improvements in various biomedical applications, such as periodontal regeneration and periodontal tissue engineering. To enhance periodontal tissue regeneration, hydroxyapatite (HA) was used in conjunction with other scaffold materials, such as Poly lactic-co-glycolic-acid (PLGA) and collagen (C). The main target of this study was to compare the effects of nano and macrostructures of the tissue scaffolds on cell behavior in vitro for periodontal tissue engineering. MATERIALS AND METHODS: Nanofibrillar and macroporous-spongious composite tissue scaffolds were produced using PLGA/C/HA. Subgroups with BMP-2 signal molecule and without HA were also created. The scaffolds were characterized by FTIR, SEM/EDX techniques, and mechanical tests. The scaffolds were compared in the periodontal ligament (PDL) and MCT3-E1 cell cultures. The cell behaviors; adhesions by SEM, proliferation by WST-1, differentiation by ALP and mineralization with Alizarin Red Tests were determined. RESULTS: Cell adhesion and mineralization were higher in the nanofibrillar scaffolds compared to the macroporous-spongious scaffolds. Macroporous-spongious scaffolds seemed better for the proliferation of PDL cells and differentiation of MC3T3-E1-preosteoblastic cells, while nanofibrillar scaffolds were more convenient for the differentiation of PDL cells and proliferation of MC3T3-E1-preosteoblastic cells. CONCLUSIONS: In general, nanofibrillar scaffolds showed more favorable results in cell behaviors, compared to the macroporous-spongious scaffolds, and mostly, BMP-2 and HA promoted the activities of the cells.

Efficacy of platelet-rich fibrin and connective tissue graft in papilla reconstruction.

PURPOSE: To evaluate efficacy of platelet-rich fibrin (PRF) or connective tissue graft (CTG) in papilla reconstruction (PR) with the semilunar incision (SI) technique. MATERIALS AND METHODS: The analysis consisted of 55 sites (27 CTG and 28 PRF) from 20 patients who underwent PR with either PRF or CTG placed in the maxillary anterior region with SI technique. Baseline (BL) and follow-up (T1 , first month, T3 , third month, T6 , sixth month) clinical data including periodontal evaluations (gingival index (GI), plaque index (PI), pocket depth (PD), keratinized tissue width (KTW), gingival recession), papilla-associated recordings (alveolar crest-interdental contact point [AC-IC], alveolar crest-papilla tip [AC-PT], papilla tip-interdental contact point [PT-IC], papilla height loss [PHL], interdental tissue stroke [ITS] and papilla presence index [PPI]) and patient satisfaction were analyzed. RESULTS: CTG provided better PR outcomes. GI, PI, and PD showed a slight increase at T1 and then, turned to their BL levels. The other periodontal parameters showed significant improvement after both treatment modalities. No inter-group difference was found except for KTW, which was in favor of CTG. CONCLUSION: Based on the results, CTG is recommended over PRF in PR treatment due to its superior outcomes with less recurrence risk. CLINICAL SIGNIFICANCE: Connective tissue graft provides superior results than platelet-rich fibrin in papilla reconstruction with the semilunar incision technique.

A Quality Improvement Study on Delirium Awareness Day: In Pursuit of Missed Delirium Diagnoses.

The current study aimed to screen for delirium in hospitalized older adults and assess the validity of the Turkish version of the 4A's Test (4AT-TR) as a feasible tool to integrate in routine patient care. The point prevalence of delirium according to clinical evaluation in routine practice was detected among all patients aged ≥60 years in 12 pilot wards. Delirium screening was then conducted by two arms: (a) nurses using the 4AT-TR and (b) geriatricians according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria. Prevalence of delirium according to clinical impression was 3.3% (n = 4), whereas prevalence was 12.4% (n = 17) according to DSM-5 criteria and 13.8% (n = 17) according to the 4AT-TR. The 4AT-TR performed by nurses had a sensitivity of 66.6% and specificity of 93.5%. Area under the receiver operating characteristic curve for delirium diagnosis was 0.819 (p < 0.001). Most delirium cases remain undetected unless a routine and formal delirium assessment is integrated in hospital care of high-risk patients. The 4AT-TR performed by nurses seems to be a valid tool for determining delirium in hospitalized older adults. [Journal of Gerontological Nursing, 48(8), 43-51.].

Investigation of the validity and reliability of the Turkish version of the Functional Assessment of Cancer Therapy-Cognitive Function in cancer patients.

OBJECTIVE: The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a questionnaire that is used to evaluate the quality of life and cognitive functions according to individual self-reports. The aim of this study was to investigate the validity and reliability of the Turkish version of the FACT-Cog. METHODS: Cancer patients who were treated with chemo or radiotherapy and had a score of 24/30 and more in Mini-Mental State Examination (MMSE) were included in this study. Cognitive functions assessed with the FACT-Cog and the European Organization of Research and Treatment of Cancer Quality of Life Core Questionnaire Core 30: Cognitive Function subscale (EORTC QLQ-CF). RESULTS: One hundred and forty cancer patients [female = 87 (62.1%), male = 53 (37.9%)] were included. The mean age of the participants was 47.93 ± 11.90 years. The Cronbach's α of the FACT-Cog scale was 0.82. Test-retest intraclass correlation coefficient values of the FACT-Cog questionnaire were varied from 0.855 to 0.954. There were found low correlations between the total score of the FACT-Cog and the MMSE (r = 0.26, p = 0.002), and moderate correlations between the EORTC QLQ-CF subscale and the FACT-Cog (r = -0.43; p < 0.001). SIGNIFICANCE OF RESULTS: It showed the validity and reliability of the Turkish version of the FACT-Cog questionnaire for cancer patients. It may be beneficial to use this questionnaire for the effects of cancer treatment.

Klotho gene G395A and C1818T polymorphisms in acromegaly: Association with clinical presentation and comorbidities.

BACKGROUND: Klotho is a new identified anti-ageing gene with tumour suppressor activities. Current data suggest that there is a tight relationship between Klotho protein and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. PURPOSE: This study aimed to investigate the possible association of Klotho gene polymorphisms with acromegaly and to assess whether these polymorphisms contribute to clinical characteristics, comorbidities and biochemical variables in these patients. METHODS: The study included 52 patients with acromegaly and 52 unrelated healthy subjects. The Klotho G395A and C1818T polymorphisms were assessed by Sanger sequencing. Serum levels of sKlotho were determined by ELISA method. RESULTS: Subjects carrying GA genotype of Klotho G395A polymorphism had 3.27 times higher risk of developing acromegaly [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.37-7.81; p = .023]. The A allele of G395A was significantly associated with acromegaly risk (OR, 2.27; 95% CI: 1.1-4.72; p = .022). No association was observed between the studied polymorphisms and disease characteristics including age at acromegaly diagnosis, size of adenoma, baseline GH and IGF-1 concentrations, and final outcome. G395A polymorphism was associated with the presence of malignancy (OR, 2.24, 95% CI: 1.63-3.08; p = .019) and colorectal polyps (OR, 1.99; 95% CI: 1.02-3.88; p = .047) in patients with acromegaly. Serum sKlotho levels were significantly higher and correlated with GH and IGF-1 levels among acromegaly patients. There was no association between the studied polymorphisms and sKlotho levels. CONCLUSIONS: Klotho G395A polymorphism is associated with acromegaly susceptibility and increased risk of malignancy and colorectal polyps in these patients.

The role of adverse childhood experience and social support type in postpartum depression in Turkey.

BACKGROUND: Improved knowledge of causal and protective factors is crucial for Postpartum depression (PPD) prevention and management. AIMS: To investigate the relationship between adverse childhood experience (ACE), perceived social support and PPD in a middle-income non-Western country, and to investigate which type of ACE and which sources of social support were associated with PPD. METHODS: The study was cross-sectional study and conducted in a one center from Turkey during March-June 2019. Women up to 1-week postpartum were included in the study. The Edinburgh Postpartum Depression Scale (EPDS), a validated ACE questionnaire, and the Multidimensional Scale of Perceived Social Support were completed. RESULTS: Nine hundred women took part in the study. The proportion identified with PPD and ACE were 10% and 8.8%, respectively. In bivariate analysis, having previous PPD, unwanted pregnancy, insufficient antenatal care, low family income, history of ACE, and perception of low social support were associated with PPD (p < 0.05). Family support was perceived as beneficial, in both women with no history or ≥2 instances of ACE. However, perceived support from friends and/or a special person was lowest in the ≥2 ACE group (p < 0.05). In logistic regression, unwanted pregnancy, emotional abuse, and neglect, incarceration of a household member, and poor special person support were factors significantly associated with developing PPD (p = 0.005). CONCLUSIONS: Emotional abuse, neglect, household dysfunction, and perceived poor support from a special person were risk factors for PPD. A history of maternal childhood trauma and poor social support might indicate the need for early PPD interventions.

Topical co-delivery of platelet rich fibrin and tranexamic acid does not decrease blood loss in primary total knee arthroplasty compared to the standard of care: a prospective, randomized, controlled trial.

PURPOSE: The purpose of this study was to evaluate the efficacy of intra-operative co-administration of tranexamic acid (TA) and platelet rich fibrin (PRF) using a proprietary co-delivery system on the amount of blood loss, early functional outcomes and wound complications after primary total knee arthroplasty (TKA). The intervention was compared to the standard of care (combined intravenous & topical TA) in a prospective, randomized, blinded setting. METHODS: 80 patients undergoing primary cemented TKA without tourniquet were prospectively randomized into control (combined intravenous and topical TA) and PRF (intra-venous TA and co-delivery of topical PRF and TA) groups after informed consent. Total blood loss, drainage blood loss, knee range of motion, VAS pain scores, length of stay and wound complications were analysed. Data collection was performed in a double blind manner on days 1, 3 and 21. RESULTS: There was no statistically significant difference in drainage blood loss (550 ml vs. 525 ml, p = 0.643), calculated total blood loss on day 1 (401 ml vs. 407 ml, p = 0.722), day 3 (467 ml vs 471 ml, p = 0.471) and day 21 (265 ml vs. 219 ml, p = 0.082) between the PRF and control groups respectively. The PRF group had a small but statistically significant increase in median knee extension in the early post-operative period, however this difference evened out at 3 weeks. No significant difference could be demonstrated between the PRF and control groups in length of stay, VAS pain scores, narcotic usage, wound complications and knee flexion at all time points. CONCLUSIONS: The topical co-delivery of PRF and TA does not significantly decrease blood loss in primary TKA compared to the standard of care. Slightly better active knee extension in the first 3 postoperative days can be achieved, however this benefit is not clinically relevant. LEVEL OF EVIDENCE: I, Therapeutic study.

FTO gene-lifestyle interactions on serum adiponectin concentrations and central obesity in a Turkish population.

The aim of the study was to investigate whether lifestyle factors modify the association between fat mass and obesity-associated (FTO) gene single nucleotide polymorphisms (SNPs) and obesity in a Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed using FTO SNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated with FTO SNP rs9939609 (p = 0.001 and p = 0.002, respectively) and GRS (p = 0.002 and p = 0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (Pinteraction = 0.027 and Pinteraction = 0.044, respectively). Our study has demonstrated that the association between FTO SNPs and central obesity might be modified by lifestyle factors in this Turkish population.

Evaluation of periodontal status and cytokine/chemokine profile of GCF in patients with severe congenital neutropenia.

Severe congenital neutropenia (SCN) is a primary immunodeficiency characterized by defect in neutrophil count. Increased risk of infections in addition to periodontal problems, such as ulcerations of oral mucosa, gingival inflammation, and rapid loss of attachment are common in the course of the disease. The aim of the present study is to define the causal relationship between the severity of periodontal inflammation and severe congenital neutropenia through identification of cytokine profile in gingival crevicular fluid (GCF). A case-control study was performed in patients diagnosed with SCN and healthy controls. Demographic data, the molecular defect, laboratory work-up were gathered from the hospital registry. Periodontal indices were recorded and GCF samples were analyzed using multiplex analysis for the simultaneous measurements of the particular cytokines and chemokines. The present study included 14 patients and 22 control subjects. Both groups were comparable in terms of age and sex. Severity of gingival inflammation measured by the criteria of Löe was higher in the SCN cases (p < 0.05). Moreover, GCF levels of IFN-α, TNF-α, IL-10, IL-13, IL-15, IL-17, IL-2, IL-7, IL-33, IP-10, MIG, MIP-1ß were significantly higher in the controls. Decreased cytokine secretion seems to correlate with the decrease in neutrophil counts. The severity of gingival inflammation in SCN patients may be due to the bacterial overgrowth and the change in the content of the oral flora due to the decreased neutrophil counts. Therefore, regular periodontal examinations, the motivation of oral hygiene as well as the compliance with therapy in SCN patients contribute to the periodontal health.

Effects of intraoperative blood loss during liver resection on patients' outcome: a single- center experience

Background/aim: Operative bleeding is one of the major determinants of outcome in liver surgery. This study aimed to describe the impact of intraoperative blood loss on the postoperative course of liver resection (LR). Materials and methods: The data of 257 patients who were treated with LR between January 2007 and October 2018 were retrospectively analyzed. LRs were performed via intermittent portal triad clamping (PTC) under low central venous pressure. Results: LRs were performed for 67.7% of patients with a malignant disease and 32.3% of patients with a benign disease. Major LR was performed in 89 patients (34.6%). The mean PTC period was 20.32 min (±13.7). The median intraoperative bleeding amount was 200 mL (5­3500 mL), the 30-day mortality rate was 4.3%, and the morbidity rate was 31.9%. The hospital stay (p = 0.002), morbidity (p = 0.009), and 30-day mortality (p = 0.041) of patients with a bleeding amount of more than 500 mL significantly increased. Conclusion: Surgeons should consider the adverse effects of intraoperative bleeding during liver resection on patients' outcome. Favorable outcomes would be obtained with diligent postoperative care.

Quasi-least squares regression method with dentistry data.

BACKGROUND: In dentistry, single-jaw surgery or double-jaw surgery is performed depending on the patient's need to correct severe skeletal malocclusions. The effect of these surgical methods used in treatment is to be investigated with quasi-least squares regression (QLS), which is a new data analysis method for correlated data obtained by extending generalized estimating equations (GEE). AIM: The aim of this study is to investigate whether jaw surgery methods (single jaw and double jaw) and time are effective on some outcome variables (C point menton distance, cervical plane angle, distance from point C to pogonion perpendicular, angle between cervical plane and facial plane) using QLS method. METHODS: In application, 114 measurements were performed on the lateral cephalometric radiographs of 34 patients aged 18 years and older who received orthodontic treatment and underwent surgery in the period of 2000-2018. The effects of time and group variables on four dependent variables were investigated and evaluated using QLS and GEE methods. RESULTS: Single-jaw surgery and double-jaw surgery as a group variable on all outcome variables were not significant. Among the working correlation structures used in QLS, the highest correlation value was obtained by "Markov" working correlation structure. CONCLUSION: Single-jaw surgery and double-jaw surgery were found to be statistically insignificant for outcome variables examined. QLS is superior to GEE in cases where repeated measurements are performed at unequal time intervals and there are missing observations.

Injectable conductive hydrogel restores conduction through ablated myocardium.

INTRODUCTION: Therapies for substrate-related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. METHODS: A nanocellulose carbon nanotube-conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. RESULTS: The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The direct current conductivity under aqueous conduction was 4.3 × 10-1 S/cm. In four canine hearts, when compared with the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of the conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation restored through the ablated tissue. Gross specimen examination demonstrated retention of the hydrogel within the tissue. CONCLUSIONS: This proof-of-concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long-term retention and biocompatibility of the hydrogel through in vivo experimentation.

Levels of pro- and anti-inflammatory cytokines in cystic fibrosis patients with or without gingivitis.

BACKGROUND: Inflammatory periodontal diseases are caused by interaction between gram negative, anaerobic bacteria and host response. Persistent infection of Pseudomonas aeruginosa in cystic fibrosis (CF) patients also cause increased pro-inflammatory response and the imbalance of pro- and anti-inflammatory response in brochoalveolar lavage fluid which leads to destruction of lungs. The aim of this study is to evaluate periodontal status of CF patients, to measure level of cytokines and biochemical molecules in gingival crevicular fluid (GCF), and to detect presence of P. aeruginosa in dental plaque samples. MATERIALS AND METHODS: GCF samples were collected from 41 CF patients and 39 healthy (non-CF) subjects. Interleukin (IL)-1ß, IL-17, IL-10, human neutrophil elastase (HNE), cystic fibrosis transmembrane regulator (CFTR) protein, and human ß-defensin-1 (HBD1) in GCF were evaluated by ELISA method. Dental plaque samples were collected from 18 CF patients with history of P. aeruginosa colonization and 15 non-CF subjects. Presence of P. aeruginosa was evaluated by using conventional culture methods and molecular methods. RESULTS: Levels of IL-1ß, HNE, and HBD1 in CF patients were significantly higher than non-CF subjects. However, IL-10 level was significantly lower in CF patients. Increased pro-inflammatory (IL-1ß) and decreased anti-inflammatory (IL-10) cytokine levels were observed in GCF samples from CF patients, irrespective of their periodontal status. P. aeruginosa were detected in four samples of 18 CF patients, and all were negative in non-CF group. CONCLUSIONS: As a result of this study, CF coexists increasing pro-inflammatory and decreasing anti-inflammatory response locally. Due to increasing pro-inflammation, CF patients should be followed-up more often than non-CF children.

Retinal degeneration is associated with brain volume reduction and prognosis in radiologically isolated syndrome.

BACKGROUND: The extent of neurodegeneration in the earliest stages of central nervous system (CNS) demyelination is not known. Optical coherence tomography (OCT) is a powerful tool to study neurodegeneration in demyelinating disorders. OBJECTIVES: To study neuroaxonal loss in the retina of individuals with radiologically isolated syndrome (RIS) and investigate whether OCT measurements are associated with brain volumetrics and clinical conversion to multiple sclerosis (MS). METHODS: Subjects fulfilling the Okuda criteria for RIS (n = 15 patients, 30 eyes) and age- and sex-matched healthy controls (HC) underwent spectral-domain OCT and magnetic resonance imaging for volumetric measurement of brain structures. RESULTS: Macular ganglion cell-inner plexiform layer (mGCIPL), macular retinal nerve fiber layer (mRNFL), and temporal peripapillary RNFL (pRNFL) thickness; normalized total brain volume (nTBV); and normalized thalamic volume (nTV) were reduced in RIS compared to HC. mGCIPL, mRNFL, and pRNFL measurements were associated with nTBV, nTV, and normalized gray and white matter volumes in the RIS group. pRNFL was thinner in individuals with RIS who converted to MS in 5 years. CONCLUSIONS: Retinal neurodegeneration can be detected in the papillomacular region in the earliest stages of CNS demyelination and reflects global disease processes in the brain. OCT can be potentially useful for predicting prognosis in RIS.

Evaluation of gingival crevicular fluid and peri-implant crevicular fluid levels of sclerostin, TWEAK, RANKL and OPG.

BACKGROUND: The combination of local and systemic factors play role in the pathogenesis of periodontal and peri-implant diseases. Host-derived enzymes, cytokines and other proinflammatory mediators play an integral role in this destruction. The aim of this study is to evaluate gingival crevicular fluid (GCF) and peri-implant crevicular (PICF) fluid levels of sclerostin, TNF-related weak inducer of apoptosis (TWEAK), receptor activator of nuclear factor kappa-beta ligand (RANKL) and osteoprotegerin OPG in periodontal and peri-implant tissues in disease and health conditions and also to assess the potential for use as biomarkers. MATERIALS AND METHODS: The study population was consisted of 50 women and 41 men, in the total of 91 individuals, with a mean age of 51.84 ±â€¯14.05. Periodontitis (n = 22), periodontal health (n = 17), peri-implantitis (n = 27) and peri-implant health (n = 25) groups were established according to clinical and radiographic examination results of 39 teeth and 52 implants restored with fixed prosthetic restorations. In all groups, periodontal and peri-implant parameters (probing depth, gingival recession, gingival bleeding time index, gingival index, and plaque index) were recorded and GCF and PICF samples were also collected. Sclerostin, TWEAK, RANKL and OPG levels in GCF and PICF were measured with ELISA tests. RESULTS: Peri-implantitis group presented significantly higher levels of Sclerostin (p = 0.002), TWEAK(p < 0.0001), RANKL(p < 0.0001), and OPG (p = 0.037) compared to peri-implant health group. Similarly, significantly higher levels of TWEAK (p = 0.001), RANKL(p < 0.0001), and OPG(p = 0.025) were detected in periodontitis group when compared to periodontal health group. Statistically significant correlations were also noted between biochemical parameters and clinical parameters. CONCLUSION: Findings of this study evaluating four different bone metabolism related proteins at the same time, suggests levels of sclerostin may be a biomarker for peri-implant disease presenting significantly higher levels in the peri-implantitis group than in the peri-implant health group. Moreover, levels of TWEAK can be a good indicator for both periodontal and peri-implant disease, due to the correlations with periodontal clinical parameters and the higher levels of TWEAK in diseased sites compared to the healthy sites for both dental implants and teeth.

68Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer.

BACKGROUND: 68Ga-PSMA Positron Emission Tomography/Computerized Tomography (PET/CT) has shown promising results for the detection of recurrent prostate cancer (RPCa). However, the diagnostic value of this method is yet to be validated. The aim of this study was to determine the influence of clinical and biochemical variables on the detection rate of 68Ga-PSMA PET/CT in patients with RPCa. METHODS: This is a prospective study of 121 patients who underwent 68Ga-PSMA-PET/CT and conventional imaging (CI) for RPCa. Detection rates were analyzed and correlated with various clinical and biochemical variables such as Gleason score GS), androgen deprivation therapy (ADT), trigger PSA (tPSA), PSA doubling-time (PSAdt) and PSA velocity (PSAv). RESULTS: 68Ga-PSMA-PET/CT showed at least one focus of pathological 68Ga-PSMA uptake in 92/121 (76%) of patients. Nodal metastases (in 47% of patients) were the most common site of recurrent disease followed by bones (36%) and prostate (32%). Out of 121 patients, 57 (47%) had only positive findings on PSMA scan verified by biopsy or follow-up. The majority of these lesion were located in the lymph nodes (31/57, 54,5%), which were below the detection limit of CT. Univariate analysis showed higher detection rate of PET/CT with increasing tPSA, PSAv and short PSAdt. Best cutoff for tPSA, PSAv and PSAdt was 0.5 ng/ml, 2.25 ng/ml/year and 8.65 months, respectively. The detection rate of PSMA-PET/CT was higher in patients with high grade tumors (GS > 7, 23.7% vs 76.3%) and in patients who were on ADT during of PSMA scan (76.3% vs 96%). In multiple logistic regression analysis, PSAdt and concurrent ADT were identified as predictors of positive 68Ga-PSMA-PET/CT. CONCLUSION: 68Ga-PSMA-PET/CT is useful for re-staging patients with RPCa and has improved performance compared with CI for disease detection. Detection rates are improved in patients on ADT and with short PSAdt.