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Fetal ovarian torsion is quite a rare event during the antenatal period and usually seen because of an ovarian cyst complication. In this case report, we present a case of fetal ovarian torsion without any ovarian cyst or underlying detectable causes. A 27-year-old primigravid woman with no significant past medical history had a routine prenatal ultrasound at 30 weeks' gestation. The ultrasound showed abdominal ascites and a 47×42-cm intraabdominal solid diffuse mass at the left side under the stomach. Doppler examination showed no blood flow on the mass. Paracentesis was performed, cytological examination reported no abnormality. Based on these findings, the diagnosis was thought to be fetal ovarian torsion. There is lack of consistent recommendations to guide the prenatal and the postnatal management of cases with in-utero diagnosis of ovarian torsion. A "wait-and-see" policy is usually preferred, as in our case., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: The impact of body mass index (BMI) on outcomes in respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) has been poorly described. We aimed to assess: (i) whether adults with class II obesity or more (BMI ≥ 35 kg/m 2 ) have worse outcomes than lean counterparts, (ii) the form of the relationship between BMI and outcomes, (iii) whether a cutoff marking futility can be identified., Methods: A retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry from 1/1/2010 to 31/12/2020 was conducted. Impact of BMI ≥ 35 kg/m 2 was assessed with propensity-score (PS) matching, inverse propensity-score weighted (IPSW) and multivariable models (MV), adjusting for a priori identified confounders. Primary outcome was in-hospital mortality. The form of the relationship between BMI and outcomes was studied with generalized additive models. Outcomes across World Health Organisation (WHO)-defined BMI categories were compared., Results: Among 18,529 patients, BMI ≥ 35 kg/m 2 was consistently associated with reduced in-hospital mortality [PS-matched: OR: 0.878(95%CI 0.798-0.966), p = 0.008; IPSW: OR: 0.899(95%CI 0.827-0.979), p = 0.014; MV: OR: 0.900(95%CI 0.834-0.971), p = 0.007] and shorter hospital length of stays. In patients with BMI ≥ 35 kg/m 2 , cardiovascular (17.3% versus 15.3%), renal (37% versus 30%) and device-related complications (25.7% versus 20.6%) increased, whereas pulmonary complications decreased (7.6% versus 9.3%). These findings were independent of confounders throughout PS-matched, IPSW and MV models. The relationship between BMI and outcomes was non-linear and no cutoff for futility was identified., Conclusion: Patients with obesity class II or more treated with ECMO for respiratory failure have lower mortality risk and shorter stays, despite increased cardiovascular, device-related, and renal complications. No upper limit of BMI indicating futility of ECMO treatment could be identified. BMI as single parameter should not be a contra-indication for respiratory ECMO., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: 18 F-FDG PET/CT is a valuable diagnostic tool in infective endocarditis (IE). However, the prognostic value is unclear. This study aims to evaluate the prognostic performance of 18 F-FDG PET/CT in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE)., Methods: We retrospectively included 76 patients treated for definite IE (NVE and PVE) that underwent 18 F-FDG PET/CT between January 2016 and December 2018. Clinical, echocardiographic and 18 F-FDG PET/CT (pathologic valvular 18 F-FDG uptake, extracardiac complications (ECC)) data were collected. The primary endpoint was defined as mortality or recurrence of IE at a one-year follow-up., Results: Pathologic valvular 18 F-FDG uptake was detected in 32 of 57 (56.1%) patients, 30% (9/30) in NVE and 85.2% (23/27) in PVE group. Atrial fibrillation (OR 3.90, 95% CI = 1.14-16.3), prior anticoagulation treatment (OR 6.37, 95% CI = 1.89-26.7), large vegetation (≥ 10 mm) (OR 4.05, 95% CI = 1.14-16.1), perivalvular complications (OR 7.22, 95% CI = 1.68-55.1) and abscess (OR 10.9, 95% CI = 1.84-283) were associated with positive PET/CT. Extracardiac complications were found in 27 of 76 (35.5%) patients, 42.9% (18/42) in the NVE and 26.5% (9/34) in the PVE group. Pathological valvular tracer uptake (HR 1.20, 95% CI = 0.43-3.37) or extracardiac complications (HR 0.58, 95% CI = 0.21-1.62) were not associated with the occurrence of the primary endpoint., Conclusion: Our study could not demonstrate a prognostic value of 18 F-FDG PET/CT in IE, but confirms high diagnostic performance, which may compromise prognostic significance by accelerated optimal treatment because of earlier diagnostic certainty.

Background: New oncological treatments improved survival but also increased awareness of cardiovascular side-effects during and after cancer therapy., Methods: We report the experience of the cardio-oncology clinic at a large Belgian tertiary care center and investigated the predictability of cardiotoxicity based on referring department, cardiovascular risk factors, cancer treatment and existing risk scores of the American Society of Clinical Oncologists (ASCO) and Mayo Clinic. Cardiotoxicity was defined as a 10% reduction in Left Ventricular Ejection Fraction (LVEF) compared to the baseline transthoracic echocardiography (TTE) in asymptomatic patients or 5% in symptomatic patients., Results: Of the 324 patients included, 14.5% died during follow-up. Most deaths were oncological, yet 19% of deaths were attributable to cardiovascular diseases. Models based on cardiovascular risk factors alone and cardiovascular risk factors combined with cardiotoxic medication poorly predicted cardiotoxicity. Existing risk scores from ASCO and Mayo Clinic also poorly predicted cardiotoxicity. A weighed model based on the Mayo Clinic cardiotoxicity risk score was the best risk assessment tool with still a limited predictive value with an Area Under the Receiver Operating Characteristic curve of 0.654 (CI 95%: 0.601-0.715)., Conclusion: Cardiovascular morbidity and mortality are common in cancer patients and survivors and stress the unmet need of adequate risk prediction tools for systematic screening and rigorous cardiovascular follow-up. In our outpatient cohort, cardiotoxicity risk could not be adequately predicted by cancer type, using classic cardiovascular risk factors, nor by the combination of cardiovascular risk factors and the proposed cancer treatment. Furthermore, we showed that existing cardiotoxicity risk scores are suboptimal and should thus be interpreted with caution., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a critical component of the kallikrein-kinin system. Its dysregulation may lead to increased vascular permeability and release of inflammatory chemokines. Interactions between the kallikrein-kinin and the coagulation system might further contribute to thromboembolic complications in COVID-19., Methods: In this observational study, we measured plasma and tissue kallikrein hydrolytic activity, levels of kinin peptides, and myeloperoxidase (MPO)-DNA complexes as a biomarker for neutrophil extracellular traps (NETs), in bronchoalveolar lavage (BAL) fluid from patients with and without COVID-19., Findings: In BAL fluid from patients with severe COVID-19 (n = 21, of which 19 were mechanically ventilated), we observed higher tissue kallikrein activity (18·2 pM [1·2-1535·0], median [range], n = 9 vs 3·8 [0·0-22·0], n = 11; p = 0·030), higher levels of the kinin peptide bradykinin-(1-5) (89·6 [0·0-2425·0], n = 21 vs 0·0 [0·0-374·0], n = 19, p = 0·001), and higher levels of MPO-DNA complexes (699·0 ng/mL [66·0-142621·0], n = 21 vs 70·5 [9·9-960·0], n = 19, p < 0·001) compared to patients without COVID-19., Interpretation: Our observations support the hypothesis that dysregulation of the kallikrein-kinin system might occur in mechanically ventilated patients with severe pulmonary disease, which might help to explain the clinical presentation of patients with severe COVID-19 developing pulmonary oedema and thromboembolic complications. Therefore, targeting the kallikrein-kinin system should be further explored as a potential treatment option for patients with severe COVID-19., Funding: Research Foundation-Flanders (G0G4720N, 1843418N), KU Leuven COVID research fund., Competing Interests: Declaration of interests M.V., B.N., H.C., and J.H.M.F. are employees of Oxurion NV. Oxurion NV and KU Leuven LRD submitted a patent on kallikrein inhibitors. K.M. is an inventor on the granted patent US9642822 awarded to Children's Medical Center Corporation covering the targeting of NETs in thrombosis and lung injury and the pending patent WO20180271953A1. She reports issued patent US9642822B2 and pending patents US2019167680A1. K.M. also reports consulting fees from PEEL Therapeutics. She holds a grant from Flanders Research Foundation (FWO) and a Horizon 2020 grant, as well as a grant from the International Society on Thrombosis and Haemostasis. T.V. is a board member and vice-president of the Belgian Society for Thrombosis and Haemostasis. P.V. and T.V. are co-holders of a research chair for clinical research with Trasylol (DAWN-AntiCo). P.V. holds an institutional grant funded by Bayer AG and by BMS/Pfizer. He reports consulting fees from Anthos Therapeutics, Bayer AG, Boehringer,BMS, Pfizer, Daiichi Sankyo, and Portola/Actelion, and honoraria as a speaker from Bayer, BMS, Pfizer, Daiichi Sankyo, and Leo Pharma. P.V. has participated in a DSMB for clinical trials sponsored by Bayer and Boehringer Ingelheim. R.V. and A.V. report participation in advisory board for Takeda and involvement in ERS, ESOT/ECTTA boards. J.W. is a holder of research grants funded by MSD, Pfizer, and Gilead. He reports speakers fees and support for attending meetings from Gilead, MSD, and Pfizer, and participation on an advisory board for Gilead. He has received study medication for clinical trials from MSD. The other authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Prostate cancer (PCa) is one of the most common cancers and one of the leading causes of death worldwide. Thus, one major issue in PCa research is to accurately distinguish between indolent and clinically significant (csPCa) to reduce overdiagnosis and overtreatment. In this study, we aim to validate the usefulness of diagnostic nomograms (DN) to detect csPCa, based on previously published urinary biomarkers., Methods: Capillary electrophoresis/mass spectrometry was employed to validate a previously published biomarker model based on 19 urinary peptides specific for csPCa. Added value of the 19-biomarker (BM) model was assessed in diagnostic nomograms including prostate-specific antigen (PSA), PSA density and the risk calculator from the European Randomized Study of Screening. For this purpose, urine samples from 147 PCa patients were collected prior to prostate biopsy and before performing digital rectal examination (DRE). The 19-BM score was estimated via a support vector machine-based software based on the pre-defined cutoff criterion of - 0.07. DNs were subsequently developed to assess added value of integrative diagnostics., Results: Independent validation of the 19-BM resulted in an 87% sensitivity and 65% specificity, with an AUC of 0.81, outperforming PSA (AUC  PSA : 0.64), PSA density (AUC  PSAD : 0.64) and ERSPC-3/4 risk calculator (0.67). Integration of 19-BM with the rest clinical variables into distinct DN, resulted in improved (AUC range: 0.82-0.88) but not significantly better performances over 19-BM alone., Conclusion: 19-BM alone or upon integration with clinical variables into DN, might be useful for detecting csPCa by decreasing the number of biopsies., (© 2022. The Author(s).)

Background: Aortic stenosis and coronary artery disease (CAD) frequently coincide. However, the management of coexisting CAD in patients undergoing transcatheter aortic valve replacement (TAVR) remains controversial., Objectives: This study sought to determine whether the presence of CAD, its complexity, and angiography-guided percutaneous coronary intervention (PCI) are associated with outcomes after TAVR., Methods: All patients undergoing TAVR at a tertiary referral center between 2008 and 2020 were included in a prospective observational study. Baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) and, whenever applicable, a residual SS after PCI were calculated. A multivariate analysis was performed to determine the effect of CAD, stratified according to complexity, and PCI on 5-year outcomes., Results: In 604 patients, the presence of CAD and its complexity were significantly associated with worse 5-year survival (SS 0: 67.9% vs SS 1-22: 56.1% vs SS >22: 53.0%; log-rank P = 0.027) and increased cardiovascular mortality (SS 0: 15.1% vs SS 1-22: 24.0% vs SS >22: 27.8%; log-rank P = 0.024) after TAVR. Having noncomplex CAD (SS 1-22) was an independent predictor for increased all-cause mortality (HR: 1.43; P = 0.046), while complex CAD (SS >22) increased cardiovascular mortality significantly (HR: 1.84; P = 0.041). Angiography-guided PCI or completeness of revascularization was not associated with different outcomes., Conclusions: The presence of CAD and its anatomical complexity in patients undergoing TAVR are associated with significantly worse 5-year outcomes. However, angiography-guided PCI did not improve outcomes, highlighting the need for further research into physiology-guided PCI., Competing Interests: Funding Support and Author Disclosures Dr Minten is supported by the Research Foundation Flanders Grant 1194521 N. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The impact of sex on ICD implantation practice and survival remain a topic of controversy. To assess sex-specific differences in ICD implantation practice we compared clinical characteristics and survival in women and men., Methods: From a nationwide registry, all new ICD implantations performed between 01/02/2010 and 31/01/2019 in Belgian patients were analyzed retrospectively. Baseline characteristics and survival rates were compared between sexes. To identify predictors of mortality, multivariable Cox regression was performed., Results: Only 3096 (20.9%) of 14,787 ICD implantations were performed in women. Within each type of underlying cardiomyopathy, the proportion women were lower than men. The main indication in men was ischemic vs dilated cardiomyopathy in women. Women were overall younger (59.1 ± 15.1 vs 62.6 ± 13.1 years; p < 0.001) and had less comorbidities except for oncological disease. More women functioned in NYHA-class III (33.6% vs 27.9%; p < 0.001) and had a QRS > 150 ms (29.4% vs 24.3%; p < 0.001), consistent with a higher use of CRT-D devices (31.7% vs 25.1%; p < 0.001). Women had more complications, reflected by the need to more re-interventions within 1 year (4.3% vs 2.7%, p < 0.001). After correction for covariates, sex-category was not a significant predictor of mortality (p = 0.055)., Conclusion: There is a significant sex-disparity in ICD implantation rates, not fully explained by epidemiological differences in the prevalence of cardiomyopathies, which could imply an undertreatment of women. Women differ from men in baseline characteristics at implantation suggesting a selection bias. Further research is necessary to evaluate if women receive equal sudden cardiac death prevention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Vitamin D status is influenced by well-known determinants, but factors associated with low 25-hydroxyvitamin D levels in the cutaneous melanoma population are not well defined. The aim of this study was to confirm the well-known determinants and to assess new determinants for 25-hydroxyvitamin D levels in a cutaneous melanoma population. In a prospectively included cohort of 387 patients with cutaneous melanoma the association of 25-hydroxyvitamin D levels with sex, age, body mass index, time of blood withdrawal, Fitzpatrick phototype, vitamin D supplementation, score for intensity of lifetime sun exposure, smoking, education level, hair and skin colour, eye colour, total number of benign naevi, freckles and parameters of chronic sun damage was investigated. In addition, 25-hydroxyvitamin D levels were correlated with pathological parameters of the primary tumour and melanoma stage (8th edition of the American Joint Committee on Cancer (AJCC). Univariate and multivariate logistic regressions were performed using R software. The following factors had a significant effect on vitamin D status: body mass index, seasonal time of blood sampling, vitamin D supplementation, and a subtype of skin, and hair colour.

Background: Venous thromboembolism (VTE) frequently occurs in hospitalized patients with coronavirus disease 2019 (COVID-19). The optimal dose of anticoagulation for thromboprophylaxis in COVID-19 is unknown., Aims: To report VTE incidence and bleeding before and after implementing a hospital-wide intensified thromboprophylactic protocol in patients with COVID-19., Methods: On March 31, 2020, we implemented an intensified thromboprophylactic protocol consisting of 50 IU anti-Xa low molecular weight heparin (LMWH)/kg once daily at the ward, twice daily at the intensive care unit (ICU). We included all patients hospitalized in a tertiary care hospital with symptomatic COVID-19 between March 7 and July 1, 2020. The primary outcome was the incidence of symptomatic or subclinical VTE and major bleeding during admission. Routine ultrasound screening for VTE was performed whenever logistically possible., Results: We included 412 patients, of which 116 were admitted to the ICU. Of 219 patients with standard a prophylactic dose of LMWH, 16 (7.3%) had VTE, 10 of which were symptomatic (4.6%). Of 193 patients with intensified thromboprophylaxis, there were no symptomatic VTE cases, three incidental deep venous thrombosis cases (1.6%), and one incidental pulmonary embolism (0.5%). The major bleeding rate was 1.2% in patients with intensified thromboprophylaxis and 7.7% when therapeutic anticoagulation was needed., Conclusion: In hospitalized patients with COVID-19, there were no additional symptomatic VTEs and a reduction in incidental deep vein thrombosis after implementing systematic thromboprophylaxis with weight-adjusted prophylactic (ward) to intermediate (ICU), but not therapeutic dosed anticoagulation. This intensified thromboprophylaxis was associated with a lower risk of major bleeding compared with therapeutic dosed anticoagulation., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Study Question: Does direct kisspeptin signaling in the oocyte have a role in the control of follicular dynamics and ovulation?, Summary Answer: Kisspeptin signaling in the oocyte plays a relevant physiological role in the direct control of ovulation; oocyte-specific ablation of kisspeptin receptor, Gpr54, induces a state of premature ovulatory failure in mice that recapitulates some features of premature ovarian insufficiency (POI)., What Is Known Already: Kisspeptins, encoded by the Kiss1 gene, are essential for the control of ovulation and fertility, acting primarily on hypothalamic GnRH neurons to stimulate gonadotropin secretion. However, kisspeptins and their receptor, Gpr54, are also expressed in the ovary of different mammalian species, including humans, where their physiological roles remain contentious and poorly characterized., Study Design, Size, Duration: A novel mouse line with conditional ablation of Gpr54 in oocytes, named OoGpr54-/-, was generated and studied in terms of follicular and ovulatory dynamics at different age-points of postnatal maturation. A total of 59 OoGpr54-/- mice and 47 corresponding controls were analyzed. In addition, direct RNA sequencing was applied to ovarian samples from 8 OoGpr54-/- and 7 control mice at 6 months of age, and gonadotropin priming for ovulatory induction was conducted in mice (N = 7) from both genotypes., Participants/materials, Setting, Methods: Oocyte-selective ablation of Gpr54 in the oocyte was achieved in vivo by crossing a Gdf9-driven Cre-expressing transgenic mouse line with a Gpr54 LoxP mouse line. The resulting OoGpr54-/- mouse line was subjected to phenotypic, histological, hormonal and molecular analyses at different age-points of postnatal maturation (Day 45, and 2, 4, 6 and 10-11 months of age), in order to characterize the timing of puberty, ovarian follicular dynamics and ovulation, with particular attention to identification of features reminiscent of POI. The molecular signature of ovaries from OoGpr54-/- mice was defined by direct RNA sequencing. Ovulatory responses to gonadotropin priming were also assessed in OoGpr54-/- mice., Main Results and the Role of Chance: Oocyte-specific ablation of Gpr54 caused premature ovulatory failure, with some POI-like features. OoGpr54-/- mice had preserved puberty onset, without signs of hypogonadism. However, already at 2 months of age, 40% of OoGpr54-/- females showed histological features reminiscent of ovarian failure and anovulation. Penetrance of the phenotype progressed with age, with >80% and 100% of OoGpr54-/- females displaying complete ovulatory failure by 6- and 10 months, respectively. This occurred despite unaltered hypothalamic Gpr54 expression and gonadotropin levels. Yet, OoGpr54-/- mice had decreased sex steroid levels. While the RNA signature of OoGpr54-/- ovaries was dominated by the anovulatory state, oocyte-specific ablation of Gpr54 significantly up- or downregulated of a set of 21 genes, including those encoding pituitary adenylate cyclase-activating polypeptide, Wnt-10B, matrix-metalloprotease-12, vitamin A-related factors and calcium-activated chloride channel-2, which might contribute to the POI-like state. Notably, the anovulatory state of young OoGpr54-/- mice could be rescued by gonadotropin priming., Large Scale Data: N/A. ., Limitations, Reasons for Caution: Conditional ablation of Gpr54 in oocytes unambiguously caused premature ovulatory failure in mice; yet, the ultimate molecular mechanisms for such state of POI can be only inferred on the basis of RNAseq data and need further elucidation, since some of the molecular changes observed in OoGpr54-/- ovaries were secondary to the anovulatory state. Direct translation of mouse findings to human disease should be made with caution since, despite the conserved expression of Kiss1/kisspeptin and Gpr54 in rodents and humans, our mouse model does not recapitulate all features of common forms of POI., Wider Implications of the Findings: Deregulation of kisspeptin signaling in the oocyte might be an underlying, and previously unnoticed, cause for some forms of POI in women., Study Funding/competing Interest(s): This work was primarily supported by a grant to M.P. and M.T.-S. from the FiDiPro (Finnish Distinguished Professor) Program of the Academy of Finland. Additional financial support came from grant BFU2017-83934-P (M.T.-S.; Ministerio de Economía y Competitividad, Spain; co-funded with EU funds/FEDER Program), research funds from the IVIRMA International Award in Reproductive Medicine (M.T.-S.), and EFSD Albert Renold Fellowship Programme (S.T.R.). The authors have no conflicts of interest to declare in relation to the contents of this work., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Patients treated in intensive care units (ICUs) experience life-threatening medical conditions but some external factors in ICUs do not help or even adversely affect and complicate their evolution. Among others, such factors include noise pollution due to alarms and medical clinical equipment, as well as the activities of the health care personnel themselves., Aim: This study aimed to evaluate the influence of elevated sound levels on physiological variables and the consciousness state of patients treated in a cardiovascular area in an ICU., Design: A longitudinal study with several observations was carried out during 1 month in the cardiovascular area of an ICU of a third-level hospital in southern Spain., Methods: Sound levels were monitored in different work shifts and patients' physiological data and consciousness status were recorded. Generalized additive mixed models (GAMMs) were developed to detect the variability of the sound levels together with the vital parameters of the patients in the ICU., Results: Thirty-eight patients were included. The mean sound level was 54.09 dBA. The GAMM sound levels analysis showed a significant increase in sound levels from 4:30 p.m. to 8:00 p.m. (1.83 dBA; P < .001) and 8:00 p.m. to 11:30 p.m. (3.06 dBA; P < .001). An increase in heart rate (3.66 bpm; P < .001), respiratory rate (2.62 rpm; P < .001) and the Glasgow Coma Scale (0.50 units; P = .002) was detected during the 4:30 p.m.-8:30 p.m., Conclusions: Elevated sound levels in cardiovascular ICUs seem to influence positively the physiological and consciousness status of patients. Given the importance of the findings for patient safety, future intervention studies are recommended., Relevance to Clinical Practice: The finding of this study could translate into structural changes in ICU facilities, as well as the development of clinical practice guidelines that influence the behaviour of health care professionals., (© 2022 The Authors. Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Objectives: Adipose tissue-derived mesenchymal stromal cells (ASCs) are useful in cell-based therapy. However, it is well known that diabetes mellitus (DM) alters ASCs' functionality. The majority of in vitro studies related to ASCs are developed under non-physiological oxygen conditions. Therefore, they may not reflect the full effects of DM on ASCs, in vivo . The main aim of the current study is to identify molecular pathways and underlying biological mechanisms affected by diabetes on ASCs in physiological oxygen conditions., Materials and Methods: ASCs derived from healthy (ASCs-C) and diabetic (ASCs-D) rats were expanded under standard culture conditions (21% O 2 ) or cultured in physiological oxygen conditions (3% O 2 ) and characterized. Differential gene expressions (DEGs) of ASCs-D with respect to ASCs-C were identified and analyzed with bioinformatic tools. Protein-protein interaction (PPI) networks, from up- and down-regulated DEGs, were also constructed., Results: The bioinformatic analysis revealed 1354 up-regulated and 859 down-regulated DEGs in ASCs-D, with 21 and 78 terms over and under-represented, respectively. Terms linked with glycosylation and ribosomes were over-represented and terms related to the activity of RNA-polymerase II and transcription regulation were under-represented. PPI network disclosed RPL11-RPS5 and KDR-VEGFA as the main interactions from up- and down-regulated DEGs, respectively., Conclusion: These results provide valuable information about gene pathways and underlying molecular mechanisms by which diabetes disturbs ASCs biology in physiological oxygen conditions. Furthermore, they reveal, molecular targets to improve the use of ASCs in autologous transplantation., Competing Interests: The authors declare there are no conflicts of interest.

Introduction: Thyroid autoimmunity (TAI) is the most common autoimmune disorder. Patients with TAI are usually euthyroid, and the presence of anti-thyroid peroxidase (anti-TPO) in patients with or without thyroid dysfunction is associated with infertility, recurrent embryo implantation failure, and early pregnancy loss. We aimed to investigate the relationship between low ovarian reserve, pregnancy outcomes, and TAI., Material and Methods: This retrospective cohort study was conducted in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients between 2010 and 2018. All patients (n = 1400) for whom thyroid autoantibody testing was requested were detected. A study group was formed from patients with anti-TPO positivity (n = 363). The control group (n = 555) comprised euthyroid anti-TPO negative patients matched to the study group regarding age and body mass index (BMI)., Results: Mean serum TSH value was 2.35 ± 1.70 mIU/mL in anti-TPO-positive patients and 1.81 ± 1.2 mIU/mL in controls, and the difference was significant (p < 0.05). Total dose of gonadotropins used in ovulation induction in anti-TPO-positive and control patients were 3000 IU and 2700 IU, respectively, and the difference was statistically significant (p < 0.05). The number of metaphase 2 oocytes was significantly lower in the anti-TPO-positive group (p < 0.05). Embryo transfer number and embryo grade were significantly lower in the anti-TPO-positive group (p < 0.01). Poor ovarian response was significantly higher in anti-TPO-positive patients (40%) as compared to anti-TPO-negative controls (30%) (p < 0.01). Clinical pregnancy rate was significantly lower in the anti-TPO-positive group (29.2%), as compared to the antibody-negative group (38.4%) (p < 0.01)., Conclusions: There are controversial data regarding the impact of antithyroid antibodies on ovarian reserve and pregnancy outcome after IVF treatment. The results of this study indicate that there was a relationship between TAI and poor ovarian response, and that TAI adversely affects IVF outcomes. Further investigations are required to explore the mechanism behind these effects.

Aim: The aim is to identify the chronic endometritis (CE) incidence in recurrent implantation failure (RIF) patients undergoing in vitro fertilization (IVF) treatment and compare the IVF outcomes of RIF patients with CE following antibiotic therapy with RIF patients without CE. Another purpose is to compare the IVF outcomes of described RIF patients with patients undergoing the first cycle of IVF., Methods: In this retrospective cohort study, CE was diagnosed with CD-138 immunohistochemical staining. Among RIF patients, two groups were formed as group 1, including patients diagnosed with CE and treated by antibiotics (n = 129), and group 2, including patients without CE (n = 103). Patients with the first IVF cycle having similar infertility etiologies with RIF patients were reviewed as group 3 (n = 932)., Results: CE was diagnosed in 55.6% of RIF patients. The number of oocytes retrieved was not different between groups. Implantation rates (IR) were similar after antibiotic treatment in RIF patients with or without CE. However, Group 3 had a higher IR (41.1%) than group 1 and 2 (23.1% and 30.1%, respectively) (p < 0.001). Clinical pregnancy (CPR) and live birth rates (LBR) were comparable between RIF groups. However, CPR and LBR were significantly higher in group 3 (48.6% and 40.5%) than group 1 (36.4% and 27.9%), and group 2 (37.9% and 30.1%) (p = 0.007 and p = 0.005, respectively)., Conclusion: Unidentified endometrial factors except CE may also affect the implantation process, although CE is a frequent finding in patients with RIF. Reproductive outcomes may not be improved only with antibiotics in RIF patients with CE., (© 2021 Japan Society of Obstetrics and Gynecology.)

Context: Recent studies emphasize the importance of considering the metabolic status to develop personalized medicine approaches. This is especially relevant in prostate cancer (PCa), wherein the diagnostic capability of prostate-specific antigen (PSA) dramatically drops when considering patients with PSA levels ranging from 3 to 10 ng/mL, the so-called grey zone. Hence, additional noninvasive diagnostic and/or prognostic PCa biomarkers are urgently needed, especially in the metabolic-status context., Objective: To assess the potential relation of urine In1-ghrelin (a ghrelin-splicing variant) levels with metabolic-related/pathological conditions (eg, obesity, diabetes, body mass index, insulin and glucose levels) and to define its potential clinical value in PCa (diagnostic/prognostic capacity) and relationship with PCa risk in patients with PSA in the grey zone., Methods: Urine In1-ghrelin levels were measured by radioimmunoassay in a clinically, metabolically, pathologically well-characterized cohort of patients without (n = 397) and with (n = 213) PCa with PSA in the grey zone., Results: Key obesity-related factors associated with PCa risk (BMI, diabetes, glucose and insulin levels) were strongly correlated to In1-ghrelin levels. Importantly, In1-ghrelin levels were higher in PCa patients compared to control patients with suspect of PCa but negative biopsy). Moreover, high In1-ghrelin levels were associated with increased PCa risk and linked to PCa aggressiveness (eg, tumor stage, lymphovascular invasion). In1-ghrelin levels added significant diagnostic value to a clinical model consisting of age, suspicious digital rectal exam, previous biopsy, and PSA levels. Furthermore, a multivariate model consisting of clinical and metabolic variables, including In1-ghrelin levels, showed high specificity and sensitivity to diagnose PCa (area under the receiver operating characteristic curve = 0.740)., Conclusions: Urine In1-ghrelin levels are associated with obesity-related factors and PCa risk and aggressiveness and could represent a novel and valuable noninvasive PCa biomarker, as well as a potential link in the pathophysiological relationship between obesity and PCa., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Polycystic ovary syndrome (PCOS) is diagnosed based on the clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, such as obesity and insulin resistance. miRNA have recently emerged as putative pathophysiological and diagnostic factors in PCOS. However, no reliable miRNA-based method for molecular diagnosis of PCOS has been reported. The aim of this study was to develop a tool for accurate diagnosis of PCOS by targeted miRNA profiling of plasma samples, defined on the basis of unbiased biomarker-finding analyses and biostatistical tools., Methods: A case-control PCOS cohort was cross-sectionally studied, including 170 women classified into four groups: non-PCOS/lean, non-PCOS/obese, PCOS/lean, and PCOS/obese women. High-throughput miRNA analyses were performed in plasma, using NanoString technology and a 800 human miRNA panel, followed by targeted quantitative real-timePCR validation. Statistics were applied to define optimal normalization methods, identify deregulated biomarker miRNAs, and build classification algorithms, considering PCOS and obesity as major categories., Results: The geometric mean of circulating hsa-miR-103a-3p, hsa-miR-125a-5p, and hsa-miR-1976, selected among 125 unchanged miRNAs, was defined as optimal reference for internal normalization (named mR3-method). Ten miRNAs were identified and validated after mR3-normalization as differentially expressed across the groups. Multinomial least absolute shrinkage and selection operator regression and decision-tree models were built to reliably discriminate PCOS vs non-PCOS, either in obese or non-obese women, using subsets of these miRNAs as performers., Conclusions: We define herein a robust method for molecular classification of PCOS based on unbiased identification of miRNA biomarkers and decision-tree protocols. This method allows not only reliable diagnosis of non-obese women with PCOS but also discrimination between PCOS and obesity., Capsule: We define a novel protocol, based on plasma miRNA profiling, for molecular diagnosis of PCOS. This tool not only allows proper discrimination of the condition in non-obese women but also permits distinction between PCOS and obesity, which often display overlapping clinical presentations.

Objectives: To assess the predictive power of scores used in hospital emergency departments (EDs) to give early warning of risk for mortality and hospital ward or intensive care unit (ICU) admission., Material and Methods: Systematic review and meta-analysis. We searched MEDLINE, Embase, the Web of Science, and the Cochrane Library. Observational studies and clinical trials published between January 1, 1950, and June 12, 2020 that used early-warning scores in hospital EDs were included. The main outcomes were mortality (at 24, 48, and more than 72 hours), hospital admission, and ICU admission., Results: Nine studies entered into the systematic review; 4 of them, with 165 580 patients, were included in the meta-analysis. The studies were heterogeneous with respect to the scores used. The one used most often was the National Early Warning Score (NEWS). The meta-analysis of studies using the NEWS scale showed that it had good predictive power for mortality: the area under the curve (AUC) of the receiver operating characteristic was 0.88 (95%, CI, 0.87-0.89; P .001, I2 = 0%) at 24 hours and 0.86 (0.84-0.88; P .001; I2 = 49.3%) at 48 hours. The AUC for inhospital mortality was 0.77 (95% CI, 0.74-0.80; P .001; I2 = 96.2%). The NEWS score had adequate power for predicting risk of hospital ward and ICU admission., Conclusion: Early warning scores used in hospital EDs are able to predict risk of early and in-hospital mortality.

Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms.

Objective: Management of ovarian endometrioma before IVF treatment is still challenging. We aimed to assess the effect of the pre-cycle surgical removal of endometriomas on IVF outcomes in a large number of cycles in patients undergoing IVF/ICSI treatment. Besides this, we also proposed to compare the cycle outcomes within both normo and poor responder patients to evaluate the impact of endometrioma and its surgery., Study Design: A retrospective cohort study was conducted in a private IVF clinic between September 2014 and December 2018. A total of 2438 IVF/ICSI cycles of 1936 patients were reviewed. Patients who had previous endometrioma surgery (Group 1), patients with non-operated endometrioma (Group 2), and patients without endometriosis, including tubal factor infertility confirmed by laparoscopy and unexplained infertility without endometrioma (Group 3) were analyzed in this study., Results: Total dose of gonadotropins was significantly higher in group 1 than others (p < 0.05). However, antral follicle counts, estradiol levels on the day of hCG trigger, the number of retrieved and metaphase II oocytes were significantly lower in group 1 than in other groups (p < 0.05). Poor response to gonadotropins was more frequent in group 1 as compared to other groups (47.9%, 34.3%, 35.5%, respectively) (p < 0.05). Cycle cancellation rates were significantly higher in group 1 than in other groups (6.7%, 1.4%, and 2.8%, respectively) (p < 0.05). Clinical pregnancy (CPR) and live birth rates (LBR) per cycle and embryo transfer were not different among groups. However, CPR per cycle and embryo transfer were significantly higher in the operated endometrioma group within unexpected poor responders (p = 0.023, p = 0.010, respectively). CPR and LBR per cycle and per embryo transfer were similar within normo-responder patients. Multiple logistic regression analysis revealed that female age and poor response to gonadotropins were the significant variables in predicting live birth (OR: 0.946, CI: 0.926-0.966, p < 0.001 and OR: 3.294, CI: 2.336-4.645, p < 0.001, respectively)., Conclusion: Pre-cyle removal of endometrioma may have an adverse impact on ovarian reserve, and pregnancy outcomes seem to be similar with or without surgery in patients undergoing IVF treatment. However, endometrioma surgery may be considered in the subsequent IVF cycles of patients with lower than expected ovarian response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background:  Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis., Methods:  Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation-perfusion (V/Q) scan to screen for incidental pulmonary embolism., Results:  Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported., Conclusion:  In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective., Competing Interests: J.W. reports grants and personal fees from Pfizer, MSD, Gilead, outside the submitted work. C.V. reports grants from Belgian Fund for Cardiothoracic Surgery, grants from Abiomed, outside the submitted work. T.V. reports personal fees from Bayer AG, personal fees from Boehringer Ingelheim, personal fees from Daiichi Sankyo, personal fees from BMS/Pfizer, personal fees from Leo Pharma, personal fees from Sanofi Aventis, outside the submitted work. R.V. reports grants from Research Foundation-Flanders (FWO), outside the submitted work. P.V. reports grants and personal fees from Bayer, grants and personal fees from Boehringer Ingelheim, grants and personal fees from BMS, grants and personal fees from Pfizer, grants from Nordic Pharma, grants and personal fees from Daiichi-Sankyo, outside the submitted work. M.J. reports grants from Bayer, grants from Takeda, grants from Instrumentation Laboratory, grants from Thrombogenics, outside the submitted work., (Thieme. All rights reserved.)

Objective: To compare the IVF outcome of patients assumed to be poor responders before their first cycle treated by microdose flare-up or GnRH antagonist protocols with patients who had a poor ovarian response after their first cycle stimulated with long GnRH protocol., Study Design: Observational cohort study., Place and Duration of Study: Department of Obstetrics and Gynecology, IVF Unit of Gazi University Faculty of Medicine, from September 2014 to February 2019., Methodology: Patients treated with the first cycle of IVF and diagnosed as poor responders after ovarian stimulation were evaluated according to the treatment protocol, including microdose flare-up (Group 1: 136 patients), GnRH antagonist (Group 2: 105 patients), and long GnRH agonist (Group 3: 77 patients)., Results: Basal FSH level was significantly lower in group 3 compared to other groups (p<0.05). The number of oocytes retrieved, the number of metaphase II oocytes were similar between groups, although the mean AFC was significantly higher in group 3 than in group1 and 2 (p<0.05). Clinical pregnancy rates per patient were higher in group 3 (20.8%) than in group 1 (12.5%) and group 2 (13.3%), but the difference was not statistically significant (p=0.230). The live birth rate per patient was statistically higher in group 3 (19.5%) as compared to other groups (8.8%, 9.5%, respectively; p<0.05)., Conclusion: Long protocol may be an option in poor responders undergoing IVF. Ovarian reserve markers are essential factors with stimulation protocol for the success of IVF in poor responder patients. Key Words:  Infertility, Ovulation ınduction, Ovarian reserve, Fertilisation in-vitro, Oocyte retrieval, Pregnancy outcome, Reproductive techniques, Assisted.

Background: The objective of this study was to explore telomere-associated variables (TAV) as complementary biomarkers in the early diagnosis of prostate cancer (PCa), analyzing their application in risk models for significant PCa (Gleason score > 6)., Methods: As part of a larger prospective longitudinal study of patients with suspicion of PCa undergoing prostate biopsy according to clinical practice, a subgroup of patients (n = 401) with PSA 3-10 ng/ml and no prior biopsies was used to evaluate the contribution of TAV to discern non-significant PCa from significant PCa. The cohort was randomly split for training (2/3) and validation (1/3) of the models. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate TAV in peripheral blood mononucleated cells. Models were generated following principal component analysis and random forest and their utility as risk predictors was evaluated by analyzing their predictive capacity and accuracy, summarized by ROC curves, and their clinical benefit with decision curves analysis., Results: The median age of the patients was 63 years, with a median PSA of 5 ng/ml and a percentage of PCa diagnosis of 40.6% and significant PCa of 19.2%. Two TAV-based risk models were selected (TAV models 1 and 2) with an AUC ≥ 0.83 in the full study cohort, and AUC > 0.76 in the internal validation cohort. Both models showed an improvement in decision capacity when compared to the application of the PCPT-RC in the low-risk probabilities range. In the validation cohort, with TAV models 1 and 2, 33% /48% of biopsies would have been avoided losing 0/10.3% of significant PCa, respectively. The models were also tested and validated on an independent, retrospective, non contemporary cohort., Conclusions: Telomere analysis through TAV should be considered as a new risk-score biomarker with potential to increase the prediction capacity of significant PCa in patients with PSA between 3-10 ng/ml.

The aim of this study was to investigate the functional results of glass ionomer cement (GIC) and incus transposition (IT) used for treatment of incus long process defects in pediatric patients. The medical records of 40 patients, aged 10 to 16 years, who underwent ossicular reconstruction due to incus long process defect between January 2010 and July 2017 were reviewed for age and gender, types of ossiculoplasty technique, types of graft used for tympanic membrane repair, preoperative-postoperative audiological examinations, and length of follow-up. The mean preoperative air-bone gap (ABG) was 29.40 (8.47) dB, the mean postoperative ABG was 15.25 (8.55) dB in the entire group, and the difference was statistically significant ( P < .001). The functional outcome (ABG ≤ 20 dB) was 80% (32 patients) in the entire group. The mean hearing gain was 18.83 (9.43) dB and postoperative mean ABG was 20 dB or better in 17 (94.4%) patients in the GIC group. The mean hearing gain was 10.31 (9.44) dB, and postoperative mean ABG was 20 dB or better in 14 (63.6%) patients in the IT group. The mean hearing gain was significantly higher in the GIC group than in the IT group ( P = .026), and the postoperative mean ABG was significantly higher in the IT group than in the GIC group ( P = .045). The functional success rates were significantly higher in GIC group than in IT group ( P = .020). There were no statistically significant differences between groups in terms of postoperative speech reception threshold and word recognition scores ( P = .628, P = .260, respectively). The graft success rates were 94.4% (17 patients) in the GIC group and 90.9% (20 patients) in the IT groups. There was no statistically significant difference between groups in operated side ( P = 1.000). Reconstruction of small incus long process defects using GIC is a valuable technique and can be safely used in pediatric patients. The hearing outcomes are significantly better in GIC rebridging technique when compared with a sculpted IT technique.

Scope: It is hypothesized that decreased advanced glycation end products (AGEs) levels could affect type 2 diabetes mellitus (T2DM) remission in newly diagnosed patients through the consumption of two healthy diets., Methods and Results: Patients from CORDIOPREV study, all with previous cardiovascular events, with T2DM at the beginning of the study are included. Patients are randomized to a Mediterranean or a low-fat diet for five years. No different diabetes remission rates are found among diets. Serum methylglioxal (MG) and carboximethyllysine (CML), levels dietary AGE, as well as gene expression of AGER1 and RAGE are measured. Serum MG decreases only after the consumption of the Mediterranean diet. Moreover, a COX regression analysis shows that each SD decrease in the MG, occurring after the Mediterranean diet, increases the probability of T2DM remission with HR:2.56(1.02-6.25) and p = 0.046 and each SD increase in disposition index at baseline increases the probability of remission with HR:1.94(1.32-2.87) and p = 0.001., Conclusions: It is demonstrated that the reduction of serum AGEs levels and the modulation of its metabolism, occurring after the consumption of a Mediterranean diet, might be involved in the molecular mechanism underlying the T2DM remission of newly diagnosed patients with coronary heart disease., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: The differences between the baseline gut microbiota of patients who developed type 2 diabetes (T2D) consuming a low-fat (LF) or a Mediterranean (Med) diet are explored and risk scores are developed to predict the individual risk of developing T2D associated with the consumption of LF or Med diet., Methods and Results: All the patients from the CORDIOPREV study without T2D at baseline (n = 462) whose fecal sample are available, are included. Gut microbiota is analyzed by 16S sequencing and the risk of T2D after a median follow-up of 60 months assessed by Cox analysis. Linear discriminant analysis effect size (LEfSe) analysis shows a different baseline gut microbiota in patients who developed T2D consuming LF and Med diets. A higher abundance of Paraprevotella, and lower Gammaproteobacteria and B. uniformis are associated with T2D risk when an LF diet is consumed. In contrast, higher abundances of Saccharibacteria, Betaproteobacteria, and Prevotella are associated with T2D risk when a Med diet is consumed., Conclusion: The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of T2D development, which may be used for selecting personalized dietary models to prevent T2D., (© 2020 Wiley-VCH GmbH.)

The aim of this paper is to identify risk factors associated with the development of osteosynthesis plates' related complications in fibula free flap reconstructions. This is a case series study of consecutive fibula free flaps. Clinical and radiological variables were recorded. Patient outcomes were evaluated with special attention to osteosynthesis plates' related complications; these included plate exposure, plate fracture, loosening of screws, non-union, bone resorption, oro-cutaneous fistulas, and bone exposure. We have done a descriptive analysis, univariate analysis, and multivariate logistic regression model to explore possible risk factors for osteosynthesis plates' related complications. Data analysis was performed using R software (version 3.5.0). 111 fibula free flaps were studied. 29 patients (26.1%) developed osteosynthesis plates' related complications. The mean time to osteosynthesis plates' related complications was 22 months; range (1-120); the median and mode were 12 months. Patients with preoperative radiotherapy (34% vs 14%, p = 0.021), and secondary reconstruction (31% vs 15%, p = 0.053) had a higher incidence of osteosynthesis plates' related complications. In the univariate analysis, "preoperative radiotherapy" (OR 3.07, 95%CI = 1.139-8.242, p = 0.025) and "extraoral soft-tissue defect" (OR 2.907, 95%CI = 1.032-8.088, p = 0.042) were risk factors for osteosynthesis plates' related complications. We have observed an interaction effect: patients with mandibular Brown's classes III + IV and "secondary reconstruction" have a higher risk for osteosynthesis plates' related complications; more than 47.30 times compared to Brown's class I and "primary reconstruction" (p = 0.026). Different factors may contribute to the development of osteosynthesis plates' related complications. Our study adds important information about these. Patients with higher risk of developing complications should be informed that a second intervention to remove the plates might be necessary., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Tumor budding has been found to be of prognostic significance for several cancers, including colorectal cancer (CRC). Additionally, the molecular classification of CRC has led to the identification of different immune microenvironments linked to distinct prognosis and therapeutic response. However, the association between tumor budding and the different molecular subtypes of CRC and distinct immune profiles have not been fully elucidated. This study focused, firstly, on the validation of derived xenograft models (PDXs) for the evaluation of tumor budding and their human counterparts and, secondly, on the association between tumor budding and the immune tumor microenvironment by the analysis of gene expression signatures of immune checkpoints, Toll-like receptors (TLRs), and chemokine families. Clinical CRC samples with different grades of tumor budding and their corresponding PDXs were included in this study. Tumor budding grade was reliably reproduced in early passages of PDXs, and high-grade tumor budding was intimately related with a poor-prognosis CMS4 mesenchymal subtype. In addition, an upregulation of negative regulatory immune checkpoints (PDL1, TIM-3, NOX2, and IDO1), TLRs (TLR1, TLR3, TLR4, and TLR6), and chemokine receptors and ligands (CXCR2, CXCR4, CXCL1, CXCL2, CXCL6, and CXCL9) was detected in high-grade tumor budding in both human samples and their corresponding xenografts. Our data support a close link between high-grade tumor budding in CRC and a distinctive immune-suppressive microenvironment promoting tumor invasion, which may have a determinant role in the poor prognosis of the CMS4 mesenchymal subtype. In addition, our study demonstrates that PDX models may constitute a robust preclinical platform for the development of novel therapies directed against tumor budding in CRC., (Copyright © 2020 Guil-Luna, Mena, Navarrete-Sirvent, López-Sánchez, Khouadri, Toledano-Fonseca, Mantrana, Guler, Villar, Díaz, Medina-Fernández, De la Haba-Rodríguez, Aranda and Rodríguez-Ariza.)

Cisplatin, a pharmacological agent widely used for treating many cancers, may cause serious side effects including ototoxicity, nephrotoxicity, and peripheral neuropathy. The present study aimed to investigate whether platelet-rich plasma (PRP) protects against cisplatin ototoxicity. Eight rats (16 ears) were divided into 2 groups: control group (4 rats, 8 ears) that received intratympanic saline and study group (4 rats, 8 ears) that received intratympanic PRP. Cisplatin (10 mg/day intraperitoneally) or vehicle was administered 2 times per day to the animals. Auditory brainstem responses were recorded preoperatively and postoperatively on day 4 and at week 3. The authors compared the morphological appearances of spiral ganglion cells and the organ of Corti and the density of spiral ganglion cells between treatment groups. The number of outer hair cells in the organ of Corti significantly decreased in the control group compared with that in the PRP group. Although no statistically significant difference was observed between the groups regarding ABR thresholds on day 4 (P = 0.083, a statistically significant difference was observed between groups at week 3 (P = 0.038). Our results suggest that PRP can prevent cisplatin-induced ototoxicity.

Aim: To evaluate whether the duration of sexual abstinence has impact on oxidative stress in semen samples., Methods: Oxidative reaction was tested for different levels of reactive oxygen species (ROS) by nitro blue tetrazolium assay in 90 patients with the diagnosis of unexplained or male factor infertility that were grouped into 3 groups as 0-2 (group 1), 3-4 (group 2) and >4 days (group 3) of duration of sexual abstinence. Subsequently, the remaining semen was prepared by gradient method for ovarian stimulation and intrauterine insemination (IUI) cycles to compare pregnancy rates in terms of different levels of ROS and different abstinence periods., Results: Increased staining pigment intensity was related to higher level of ROS in >4 days' group as compared to groups 0-2 and 3-4 days (70% vs 43.3% and 50%, P = 0.013 and P = 0.014, respectively). Pregnancy rates significantly decrease with prolonged abstinence period (26.7%, 16.7% and 6.7% in groups 1, 2 and 3, respectively, P = 0.039). Progressive motile sperm count after gradient method of sperm preparation for IUI was highest in 3-4 days of abstinence period than shorter and longer abstinence groups., Conclusion: Longer duration of sexual abstinence causes higher oxidative stress and decreases pregnancy rates in IUI cycles., (© 2020 Japan Society of Obstetrics and Gynecology.)

Aim: Mammary serine protease inhibitor (maspin) acts as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are increased in some types of malignant cells. The aim of this study was to investigate the maspin expression in cervical dysplasia and cervical cancer, and to analyze its' relation with survival., Methods: Maspin expression was detected by immunohistochemistry using labeled streptavidin biotin method to determine cytoplasmic and nuclear maspin expressions in cervical intraepithelial neoplasia grade 1 (CIN1), cervical intraepithelial neoplasia grade 2 (CIN2), cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer., Results: A total of 89 patients with CIN (29 cases of CIN1, 30 cases of CIN2 and 30 cases of CIN3), and 27 patients with cervical cancer were included to the study. 7.8% of the patients with CIN had maspin staining positivity. On the other hand maspin staining was positive in 20 of 27 patients (74.1%) with cervical carcinoma (P = 0.001). Of these patients 20 (100%) had cytoplasmic, and 8 (40%) had nuclear maspin staining positivity. Cytoplasmic maspin immunoreactive scores were found to be significantly higher in carcinoma group when compared to the patients with CIN1/3 (respectively; P = 0.01, P = 0.02). No difference was noted for nuclear maspin expression. Significant overall survival advantage was detected for patients with nuclear maspin staining (P = 0.03)., Conclusion: The current study shows that nuclear maspin expression is related with better overall survival in cervical cancer. Maspin staining can be a useful diagnostic marker to discriminate cervical intraepithelial neoplasia from cervical carcinoma., (© 2020 Japan Society of Obstetrics and Gynecology.)

Purpose: Many anatomical factors are known to cause obstructive sleep apnea syndrome (OSAS), but only few studies have examined the relationship between the morphology of pterygoid hamulus (PH), upper airway, and OSAS severity. This study aimed to investigate the relationship between the severity of OSAS and PH morphology and other anatomical variations of the upper airway., Methods: The data of the patients who underwent polysomnography and diagnosed with OSAS were retrospectively reviewed, and those who underwent paranasal sinus computed tomography were determined. The patients were divided into three groups according to the apnea-hypopnea index (AHI) scores obtained from the polysomnography (mild, moderate, and severe). The relationship between PH thickness, length and interpterygoid distance, and the severity of AHI was investigated., Results: Seventy-four patients were included in the study. In patients with severe OSAS (1.83 ± 0.29 mm), the PH bone thickness was significantly thicker compared to those with mild OSAS (1.59 ± 0.36 mm) (p = 0.03). When the interpterygoid distance and its ratio to the velopharyngeal length were examined, it was found significantly shorter in patients with severe OSAS than mild cases (p < 0.001; p = 0.045, respectively)., Conclusion: Our results showed that OSAS severity was associated with hamulus thickness, interpterygoid distance, and the ratio of interpterygoid distance to VL. Our study provides further insight into the pathophysiology of sleep apnea, suggesting that morphometric evaluation of the pterygoid hamulus and upper airway measurements can assist clinicians in stratifying and determining the best treatment options for patients with OSAS.

Objective: The inflammatory and vascular disorders have been proposed in the pathogenesis of Bell's palsy (BP). Several studies investigated the role of inflammation and ischemia in BP using white blood cell (WBC) count and its subtypes. Here, we aimed to investigate lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet-lymphocyte ratio (PLR) in BP., Methods: The study was conducted on 76 patients with BP and 60 healthy controls. The comparison of LDH, NLR, MPV, and PLR was made between groups. The relationships between LDH, NLR, MPV, and PLR were also investigated., Results: The mean LDH concentrations and NLR were significantly high in BP group than in control group (p < 0.01, p < 0.05, respectively). There was no significant difference between groups in MPV and PLR (p = 0.195, p = 0.263, respectively)., Conclusion: Our results support the diagnostic value of high LDH concentrations in BP patients. Further studies are needed to investigate the relationship between LDH and the severity and prognosis of BP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Baklacı et al.)

Objective This study aimed to investigate the abnormal high-resolution computed tomography (HRCT) findings in cholesteatomatous chronic otitis media (CCOM) patients preoperatively and the coexistence of abnormal HRCT findings with facial canal dehiscence (FCD) observed intraoperatively to identify the predictive factors associated with FCD. Methods The medical records of 151 CCOM patients who had undergone tympanomastoidectomy at our center were retrospectively examined in terms of the patients' age and gender, preoperative HRCT findings [scutum defect, posterior wall of external auditory canal (PWEAC) defect, lateral semicircular canal (LSSC) defect, tegmen defect, and sigmoid plate erosion]. Operation records containing information about FCD were also analyzed. Results The prevalence of FCD was found to be 33.8% (51/151). There was a significant correlation between the presence of scutum, PWEAC, LSSC, and tegmen defects and the presence of FCD. However, no statistically significant correlation was found between the presence of sigmoid plate erosion and the presence of FCD. The results of regression analysis of the coexisting pathologic findings for FCD showed that the risk of FCD was highest in patients with LSSC + scutum defects (34.3-fold increase), followed by LSSC + PWEAC defects (31.6-fold increase). Conclusion Our study revealed that the presence of scutum, PWEAC, LSSC, and tegmen defects on HRCT indicates a higher risk of FCD preoperatively. This risk is even greater when multiple abnormal findings coexist., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Baklacı et al.)

The goal of this study was to investigate the association between various sinonasal anatomical variations and the morphological features of lateral nasal bone, using paranasal computerized tomography (PNCT) sections. Two hundred and fifty patients who underwent a PNCT scan because of a prediagnosis of nasal septum deviation or sinusitis were included in the study. For each patient, presence of the following anatomical variations was determined on CT sections: length and thickness of nasal bone, thickness of intermediate nasal bone, pneumatized middle turbinate, paradox middle turbinate, Agger nasi cell, Haller cell, Onodi cell, supraorbital cell, pneumatized uncinate process, and nasal septal deviation. The effect of each anatomical variation on the length and thickness of the lateral nasal bone was investigated. The patients with bilateral pneumatized middle turbinate and the patients with bilateral Agger nasi cell had a thinner lateral nasal bone both on the right and the left sides compared to those without. The patients with bilateral Onodi cell and Agger nasi cell had a longer lateral nasal bone both on the right and the left sides compared to those without. The nasal bone thickness was significantly thicker on the deviation side than the contralateral nasal bone. The nasal bone length was significantly longer on the side of the septum deviation. In this study, we found that sex, presence of Agger nasi and Onodi cells, pneumatization of middle turbinate, and direction of nasal septal deviation influenced the morphology of the nasal bone. For successful nasal surgery, careful examination of preoperative anatomical variations is very important.

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2 / CDK6 / CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.

Objective Programmed cell death protein-1 (PD-1) inhibitors that have been recently introduced for the systemic treatment of head and neck cancers offer the advantage of fewer side effects and more effective treatment than chemotherapy drugs. A review of the literature shows that the ototoxic side effects of the PD-1 inhibitor have not yet been fully elucidated. In this study, we aimed to investigate whether the PD-1 inhibitor has ototoxic activity using both electrophysiological and histopathological methods. Methods A total of 24 rats, 12 for the study group, and 12 for the control group were included in the study. The study group was administered the PD-1 inhibitor. The auditory brainstem responses (ABR) of the study and control groups were evaluated. At the end of the study, all animals were sacrificed, and their cochleae were examined by immunohistochemical staining. Results In the study group, the ABR values ​​were 13.95 ± 2.70 before treatment, 15.83 ± 1.94 at week 4 of treatment (p=0.024), and 15.00 ± 1.06 at week 7 (p=0.157). Furthermore, according to immunohistochemical staining, the cochlear hair cells were reduced in the study group compared to the control group. Conclusion It was determined that the PD-1 inhibitor showed ototoxic activity during the course of treatment, but this was spontaneously resolved during follow-up. The clinical significance of these findings should be supported by human studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Kuzucu et al.)

Introduction : Metastatic colorectal cancer (CRC) remains a dilemma for cancer researchers with an increasing incidence in the younger patient population. Until the last decade, limited therapeutic options were available for metastatic CRC patients leading to relatively poor clinical outcomes. Areas covered : With advances in genome sequencing technology and reductions in the cost of next-generation sequencing, molecular profiling has become more accessible for cancer researchers and clinical investigators, which has furthered our understanding of the molecular behavior of CRC. This progress has recently translated into significant advances in molecular-based therapeutics and led to the development of new target-specific agents in metastatic CRC patients. In this review article, we extensively elaborate on genomic alterations seen in CRC patients including, but not limited to, EGFR, MMR, BRAF, HER2, NTRKs, FGFR, BRCA1/2, PALB2, POLE, and POLD1 genes, all of which are potentially actionable by either an FDA-approved agent or in a clinical trial setting. Expert opinion : We strongly recommend molecular profiling in metastatic CRC patients during the early course of their disease, as this may provide therapeutic and prognostic information that can guide clinicians to practice precision medicine. Patients with potentially actionable genes should be considered for targeting agents based on molecular alterations.

Purpose: We aimed to determine the position and size of the sphenoid sinus (SS) in our study and compare the results of the measurements relative to age, gender, and the presence of pituitary adenoma using multidetector computerized tomography (MDCT)., Methods: We retrospectively evaluated the paranasal sinus computerized tomography (CT) images of 200 individuals (age range of all the individuals 4-84 years; 101 females, 99 males; age range of individuals with pituitary adenoma 15-63 years; 15 females, 9 males) with 24 pituitary adenomas. The shape of SS were identified and classified, volume were measured by MDCT also for individuals with pituitary adenoma., Results: It was determined that the volume averages were significantly affected by the type of SS. Among all the individuals studied, the sellar type of SS was most frequently observed (41.5%), followed by the postsellar type (38.5%), and the least observed was the presellar type (9%). The volume of the SS is bigger in males than females although the volume is not affected by the presence of pituitary adenomas. The development of the SS continues until the age of nine., Conclusion: The morphology and morphometry of the SS show individual differences. These anatomic variations are important for decision making and application for surgical interventions (especially transsphenoidal surgery).

Humoral alloimmunity, particularly that triggered by preformed antibodies against human leukocyte antigens (HLA), is associated with an increased prevalence of rejection and reduced transplant survival. The high sensitivity of solid phase assays, based on microbeads coated with single antigens (SAB), consolidated them as the gold-standard method to characterize anti-HLA antibodies, ensuring a successful allograft allocation. Mean fluorescence intensity (MFI) provided by SAB is regularly used to stratify the immunological risk, assuming it as a reliable estimation of the antibody-level, but it is often limited by artifacts. Beyond MFI, other properties, such as the complement-binding ability or the IgG1-4 subclass profile have been examined to more accurately define the clinical relevance of antibodies and clarify their functional properties. However, there are still unresolved issues. Neat serum-samples from 20 highly-sensitized patients were analyzed by SAB-panIgG, SAB-IgG1-4 subclass and SAB-C1q assays. All 1:16 diluted serum-samples were additionally analyzed by SAB-panIgG and SAB-IgG1-4 subclass assays. A total of 1,285 anti-HLA antibodies were identified as positive, 473 (36.8%) of which were C1q-binding. As expected, serum-dilution enhanced the correlation between the C1q-binding ability and the antibody-strength, measured as the MFI (r neat = 0.248 vs. r diluted = 0.817). SAB-subclass assay revealed at least one IgG1-4 subclass in 1,012 (78.8%) positive antibody-specificities. Among them, strong complement-binding subclasses, mainly IgG1, were particularly frequent (98.9%) and no differences were found between C1q- and non-C1q-binding antibodies regarding their presence (99.4 vs. 98.5%; p = 0.193). In contrast, weak or non-C1q-binding subclasses (IgG2/IgG4) were more commonly detected in C1q-binding antibodies (78.9 vs. 38.6%; p < 0.001). Interestingly, a strong association was found between the C1q-binding ability and the IgG1 strength (r IgG1dil = 0.796). Though lower, the correlation between the IgG2 strength and the C1q-binding ability was also strong (r IgG2dil = 0.758), being both subclasses closely related (r IgG1-IgG2 = 0.817). We did not find any correlation with the C1q-binding ability considering the remaining subclasses. In conclusion, we demonstrate that a particular profile of IgG subclasses (IgG1/IgG3) itself does not determine at all the ability to bind complement of anti-HLA antibodies assessed by SAB-C1q assay. It is the IgG subclass strength, mainly of IgG1, which usually appears in combination with IgG2, that best correlates with it.

Purpose: To investigate the relationship between mastoid pneumatization and the conformation and depth of the sinus tympani (ST) in patients with chronic otitis media (COM), based on the high-resolution computed tomography (HRCT) scans., Methods: Two hundred and two patients affected by COM were included in the study. The patients were divided into three groups according to the extent of mastoid pneumatization on HRCT scans; pneumatized (group 1), diploic (group 2) or sclerotic (group 3). The variation in the ST area (types A, B, C) was assessed using a radiomorphological classification based on the relationship between the medial boundary of the ST and the third portion of the facial nerve. Depth of the ST was calculated by measuring the distance between the medial boundary of the ST and medial boundary of the third portion of the facial nerve RESULTS: There was a statistically significant difference between the groups in terms of the type of ST (p < 0.001). The mean depths of the ST were 1.59 ± 0.82 mm (0.00-2.80 mm) in group 1, 1.10 ± 0.79 mm (0.00-3.00 mm) in group 2 and 0.53 ± 0.63 mm (0.00-2.60 mm) in group 3. The groups were significantly different in terms of the depth of the ST (p < 0.001)., Conclusion: A well-pneumatized mastoid is highly associated with a deep and posteriorly positioned ST with respect to the facial nerve. The preoperative HRCT scans of patients with cholesteatoma should be carefully evaluated to determine the conformation and depth of the ST.

Objective: To investigate the success rates and hearing outcomes of temporalis fascia and tragal cartilage grafts used for type-1 tympanoplasty in the elderly (³65 years) METHODS: The medical records of 73 elderly patients who underwent type-1 tympanoplasty at our center between January 2010 and June 2017 were retrospectively reviewed for age, gender, perforation side, presence of contralateral perforation, type and location of perforation, graft material types, preoperative and postoperative hearing levels, and length of follow-up., Results: The graft success rate was 83.5% (61 patients) for the entire group, 76.2% (32 patients) for the fascia group, and 93.5% (29 patients) for the cartilage group. The success rate for the cartilage group was significantly higher than that for the fascia group (P=0.048). The mean hearing gain was 12.5±7.6 and 8.9±6.1dB in the fascia and cartilage groups, respectively, and postoperative ABG was 10 dB or better in 29 (69.0%) and 19 (61.3%) patients, respectively. The mean hearing gain was significantly higher in the fascia group than in the cartilage group (P=0.028), whereas the mean ABG was significantly higher in the cartilage group than in the fascia group (P=0.009). The functional success rates were similar in both groups (P=0.490)., Conclusion: Tympanoplasty is a safe and effective procedure in elderly patients with a 83.5% of graft success rate. Tragal cartilage may be the first choice of graft material due to its high success rates. The functional outcomes did not show significant differences between the fascia and cartilage groups., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction and Objectives: The worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity. Liraglutide (LRG), a glucagon-like peptide-1 receptor agonist, can reduce body weight. This study assessed the metabolic efficacy of LRG in real-world clinical practice., Methods: An observational, retrospective cohort study including patients treated with LRG for at least one year (187 patients). Anthropometric and metabolic variables, a composite endpoint, factors predicting response to LRG, and cardiovascular risk over time were assessed. A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values., Results: HbA1c levels and weight significantly decreased in the first 12 weeks, and the decrease persisted at 12 and 24 months in all subgroups studied. Mean weight and HbA1c decreases after 24 months were 8.5kg and 1.7% respectively. HbA1c values <7% were achieved by 42% of patients at 12 months and by 40% at 24 months. Treatment with LRG allowed for reduction in insulin dose. No serious adverse events were noted. Cardiovascular risk decreased from high to moderate-low., Conclusions: Under standard clinical practice conditions, LRG achieved a better metabolic response than seen in clinical trials. Efficacy at 12 weeks of treatment is a good predictor of response. LRG allows for delaying or reducing insulin dose by improving both weight and glucose control. Cardiovascular risk improved., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: Smoking cessation in subjects with a severe mental illness (SMI) is a challenging but attainable goal. Furthermore, the identification of variables involved in the quitting process is a highly relevant factor in clinical practice. This study aimed to analyze the influence of smokers' motivation in smoking reduction and cessation and select the most suitable way of measuring motivation., Methods: This is a secondary analysis of a 9-month, multicenter trial examining a Multicomponent Smoking Cessation Program in 82 adult outpatients with SMI. At the end of the preparation stage, the smokers' motivational level was evaluated with the University of Rhode Island Change Assessment Scale. This allowed us to rate subjects using a continuous measure ("Readiness to Change," RTC) and group them in "Stages of Change" (SOC). Regression analyses were carried out to identify predictors of the efficacy outcomes: a reduction in at least 50% of the cigarettes smoked per day (CPD), a reduction in the expired carbon monoxide (CO), and complete abstinence from smoking., Results: We studied differences in measurements of motivational levels independently (RTC and SOC) for patients who had a reduction in at least 50% of the CPD and for patients who achieved complete abstinence from smoking. However, these differences did not reach statistical significance during the follow-up study with a logistic mixed-effects model. In a linear mixed-effects model, the reduction of expired CO was significantly associated with RTC, at the end of the active treatment phase and during follow-up (β: -1.51; SD 0.82; p < 0.01)., Conclusion: The motivation level achieved in the preparation phase predicted the reduction of expired CO over a given period when calculated by a continuous measure (RTC)., (© 2019 S. Karger AG, Basel.)

Background: The aim of this study was to investigate the success of type 1 tympanoplasty in pediatric patients with chronic otitis media, and to evaluate the prognostic factors that may influence its success., Materials and Methods: Medical records of 102 children aged between 8 and 18 years (46 female, 56 male) who underwent type 1 tympanoplasty for chronic tympanic membrane perforation between January 2010 and July 2017 were reviewed. Age, gender, condition of contralateral ear (unilateral, bilateral), type (central, marginal) and location of perforation (anterior, posterior, inferior), graft material (fascia, cartilage), pre- and post-operative hearing levels, mean air-bone gap (ABG), surgical approach (postauricular, endaural) and length of follow up were recorded., Results: Anatomical and functional success (ABG < 20 dBHL) rates were 86.3% (88 patients) and 74.5% (76 patients) after a mean follow-up of 32 ± 16.55 months, respectively. The mean hearing improvement was 10.77 ± 10.45 dBHL. The graft success rates were significantly higher in tragal cartilage group (95.1%) than in temporalis fascia group (80.3%) (p = 0.033). Graft success was negatively affected by contralateral perforation (p = 0.003). All patients with bilateral perforations and graft failure were in temporalis fascia group. Age, type and location of perforation and surgical approach did not influence graft success (p > 0.05)., Conclusion: Our results showed that type 1 tympanoplasty can be performed effectively in pediatric population regardless of age, location and type of perforation and surgical approach. Bilateral perforations are prone to reperforation, and should be treated with cartilage graft.

Aims: To study the response of clinical variables (HbA 1c , body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real-world clinical setting, and to describe the evolution of HbA 1c and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs)., Methods: We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0-12.0) months., Results: Individuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m 2 ), with inadequate HbA 1c (68 mmol/mol [8.4%]), blood pressure and lipid levels. Upon liraglutide treatment, HbA 1c , body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA 1c response, whereas higher baseline HbA 1c , longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA 1c response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response., Conclusions: In this real-world study, we showed the effectiveness of liraglutide in improving body weight, HbA 1c , mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA 1c and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide., (© 2018 Diabetes UK.)

Purpose: We aimed to research in detail the morphology of the facet orientation (FO) and tropism (FT) in degenerative diseases., Method: This study consisted of patients with disc degeneration (DD) and with lumbar spondylolisthesis (LS) as well as a control group without these two diseases. The group of patients with DD was separated by DD grades. Vertebral body and intervertebral discs' (IVDs) morphometric values, facet joint osteoarthritis (OA) grading, FO and FT were examined in all the groups. All measurements were applied to MRIs of 353 patients., Result: There was a significant difference in facet angle values between the groups at L4-L5 (FO: p = 0.001). There was a significant negative correlation between FO at L4-L5 and L4 vertebral body anterior posterior diameter and L5 mid-vertebral body height, in 353 patients (p = 0.003; p = 0.010). Facet joint OA grading scores were lower in the control group than in the disc degeneration patient (DDP) and LS groups (p < 0.05). Sagittal FO was seen with the increase of facet joint OA scores at L4-L5 in the control and DDP groups (control: p = 0.001; DDP: p = 0.40)., Conclusion: Facet joints can show different orientation values in LS and DDP groups at L4-L5. The presence of FT is a risk factor for an LS patient at L4-L5. Sagittal FO is seen with vertebral slip at L5-S1. FO is affected by the morphometric changes of the vertebral body at L4-L5. Discussions in this regard need to be resolved through further research.