Identification of a growth factor for primary murine stroma as macrophage colony-stimulating factor

Knowledge of the stromal microenvironment is crucial for understanding the hematopoietic system. We took advantage of an assay that permits analysis of primary stroma-initiating cells (SICs) on the clonal level, and further characterized SICs and the factors that regulate SICs. Stroma formation in this assay is dependent on a high-molecular-weight factor secreted by the stromal cell line AC3.U. Here we show that this factor is identical to macrophage colony-stimulating factor (M-CSF), and that purified M-CSF is sufficient for induction of stroma formation. M-CSF, isolated from the line AC3.U, as well as from L929 cells and COS cells transfected with an expression vector encoding M- CSF, migrated in two peaks as 160- and 650-kD species after gel filtration. These molecular-weight species encompassed all stroma- inducing activity, and both stimulated macrophage colony formation. Affinity chromatography and blocking studies with antibodies specific for M-CSF and c-fms confirmed M-CSF as the sole factor in the supernatant of the stromal cell line AC3.U that promotes stroma formation. Culture of marrow, for as little as 1 week, depleted M-CSF- dependent SIC while increasing the incidence of replatable, factor- independent SIC. This suggests that culture changes the properties of SICs, perhaps by inducing differentiation into mature stromal cells. Thus, our results show a novel function of M-CSF as an important modulator of stroma formation.     

Heterogeneity and Classification of Recent Onset Psychosis and Depression: A Multimodal Machine Learning Approach

Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of depression and psychosis to investigate their heterogeneity, with common, comorbid transdiagnostic symptoms. Analyzing clinical/neurocognitive and grey matter volume (GMV) data from the PRONIA database, we generated prototypic models of recent-onset depression (ROD) vs. recent-onset psychosis (ROP) by training support-vector machines to separate patients with ROD from patients with ROP, who were selected for absent comorbid features (pure groups). Then, models were applied to patients with comorbidity, ie, ROP with depressive symptoms (ROP+D) and ROD participants with sub-threshold psychosis-like features (ROD+P), to measure their positions within the affective-psychotic continuum. All models were independently validated in a replication sample. Comorbid patients were positioned between pure groups, with ROP+D patients being more frequently classified as ROD compared to pure ROP patients (clinical/neurocognitive model: χ² = 14.874; P < .001; GMV model: χ² = 4.933; P = .026). ROD+P patient classification did not differ from ROD (clinical/neurocognitive model: χ² = 1.956; P = 0.162; GMV model: χ² = 0.005; P = .943). Clinical/neurocognitive and neuroanatomical models demonstrated separability of prototypic depression from psychosis. The shift of comorbid patients toward the depression prototype, observed at the clinical and biological levels, suggests that psychosis with affective comorbidity aligns more strongly to depressive rather than psychotic disease processes. Future studies should assess how these quantitative measures of comorbidity predict outcomes and individual responses to stratified therapeutic interventions.     

Surgical Approach for Polycystic Ovarian Syndrome in Management of Infertility

Background

In patients with Polycystic Ovarian Syndrome (PCOS), resolution of infertility is an important goal of treatment. Wedge resection of the ovaries described as a means to achieve this was practiced in the middle of twentieth century. With the advent of endoscopic surgery, surgical approach for the same condition has been modified. Multi point biopsy, multiple needle puncture, electofulguration and laser fulguration are being tried in the context of PCOS. This project was taken up to evaluate the scope of electo fulguration in clomiphene resistant PCOS.

Methods

Forty patients who did not show sonographic evidence of ovulation with clomiphene citrate (CC) 100mg OD for 05 days in two cycles were subjected to laparoscopy. The patients who did not show any pelvic factor for infertility were alternately assigned to electro - fulguration treatment of ovaries or no fulguration during laparoscopy. These were designated as ‘Lap EC’ & ‘Only CC’ group respectively. For ‘Only CC’ group’ stimulation with CC was continued for four cycles with a higher dose 150 mg OD for 05 days. Lap EC group were subjected to CC 100mg OD for 5 days for two cycles in case of non achievement of ovulation in the first two drug free cycles following EC. Folliculometry, HCG administration and Intra Uterine Insemination (IUI) was performed for both groups.

Results

Total percentage of ovulatory cycles were 51.8% in EC group compared to 5.26% in the CC group. Overall pregnancy rate of 30% was achieved in the Lap EC group as compared to only 10% in the CC group (p<0.05).

Conclusion

Laparoscopic electrofulguration of ovaries increases the chances of ovulation and conception. This being a cheaper one time procedure as compared to other expensive ovulation inducing agents, should be the preferred mode and the primary procedure wherever polycystic ovaries are encountered while evaluating a case of infertility by laparoscopy.Key Words: Infertility, PCOS, Electrofulguration     

The relation between staging fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters and tumor necrosis rate in pediatric osteosarcoma patients

Background/aimThe aim of this study was to investigate the contribution of fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in staging of pediatric osteosarcoma patients and also to evaluate the ability of metabolic parameters from the primary tumor to predict tumor necrosis rate (TNR).Material and methodsF-18 FDG-PET/CT imaging was performed in staging 37 pediatric osteosarcoma patients. The metabolic parameters SUVmax (maximum standardised uptake value), MTV (metabolic tumour volume), and TLG (total lesion glycolysis) were measured from the primary tumor. TNR level of the primary tumor was histopathologically measured after standard neoadjuvant chemotherapy treatment. The contribution of F-18 FDG-PET/CT to staging of pediatric osteosarcoma patients and the accuracy of metabolic parameters of the primary tumor to predict TNR were analized by regression analysis.Results MTV and TLG of the primary tumor were found to efficiently predict histopathologic TNR, whereas SUVmax was not (P = 0.012, P = 0.027, P = 0.25, respectively). Also 5 of 12 patients (41.6%) who were initially defined as localised osteosarcoma were upstaged in consequence of staging F-18 FDG-PET/CT findings. Conclusion F-18 FDG-PET/CT staging in pediatric osteosarcoma patients can effectively distinguish metastatic-localised disease. MTV and TLG values are important parameters, which can efficiently be used to predict TNR.     

Parent and teacher perceptions of child behaviour following cardiac surgery

To determine if parents whose children had undergone successful cardiac surgery perceived their children any differently from parents of children who had not undergone surgery, we used the Achenbach Child Behaviour Checklist (CBCL) to compare parent and teacher perceptions in these two groups. Subjects included 168 children who had undergone cardiac surgery 4 to 8 years previously and 51 controls. On the behaviour scale of the CBCL, the teachers' mean t scores showed no significant difference bctween the cardiac and control groups, in contrast to the parents' scores where parents perceived a higher degree of behavioural problems in children who had undergone cardiac surgery. On the Social competence scale of the CBCL, the parents scored their children who had undergone cardiac surgery as less Socially competent than did the parents of the controls. Teachers' scores showed no difference between groups.     

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aimWe aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH).Materials and methods Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system.Results There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status.Conclusion In this study, the CIMT values of CAH cases were similar to those of healthy subjects.     

Risk factors associated with mortality in ıntensive care COVID-19 patients: the importance of chest CT score and intubation timing as risk factors

Background/aim Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the predictors of mortality in critically ill patients admitted to the intensive care unit (ICU) are not yet well understood. In this study, we aimed to investigate the risk factors associated with ICU mortality in our hospital.Materials and methods In this single-centered retrospective study, we enrolled 86 critically ill adult patients with COVID-19 admitted to ICU of Dokuz Eylül UniversityHospital (İzmir, Turkey) between 18 March 2020 and 31 October 2020. Data on demographic information, preexisting comorbidities, treatments, the laboratory findings at ICU admission, and clinical outcomes were collected. The chest computerized tomography (CT) of the patients were evaluated specifically for COVID-19 and CT score was calculated. Data of the survivors and nonsurvivors were compared with survival analysis to identify risk factors of mortality in the ICU.Results The mean age of the patients was 71.1 ± 14.1 years. The patients were predominantly male. The most common comorbidity in patients was hypertension. ICU mortality was 62.8%. Being over 60 years old, CT score > 15, acute physiology and chronic health evaluation (APACHE) II score ≥ 15, having dementia, treatment without favipiravir, base excess in blood gas analysis ≤ –2.0, WBC > 10,000/mm³, D-dimer > 1.6 µg/mL, troponin > 24 ng/L, Na ≥ 145 mmol/L were considered to link with ICU mortality according to Kaplan–Meier curves (log-rank test, p < 0.05). The APACHE II score (HR: 1.055, 95% CI: 1.021–1.090) and chest CT score (HR: 2.411, 95% CI:1.193–4.875) were associated with ICU mortality in the cox proportional-hazard regression model adjusted for age, dementia, favipiravir treatment and troponin. Howewer, no difference was found between survivors and nonsurvivors in terms of intubation timing.ConclusionsCOVID-19 patients have a high ICU admission and mortality rate. Studies in the ICU are also crucial in this respect. In our study, we investigated the ICU mortality risk factors of COVID-19 patients. We determined a predictive mortality model consisting of APACHE II score and chest CT score. It was thought that this feasible and practical model would assist in making clinical decisions.     

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

BackgroundTo date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality.Materials and MethodsIn this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study.ResultsA total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66–81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96–58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55–14.46,p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84–51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality.ConclusionEarly detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.