Factors affecting prognosis and treatment strategies in metastatic soft tissue sarcomas: twenty years of experience.

OBJECTIVE: In this study, we aimed to reveal the general clinicopathological features, treatment features, and factors that could predict overall survival in metastatic soft tissue sarcomas, a very rare and heterogeneous disease group. PATIENTS AND METHODS: This study was a retrospective cohort study. Patients monitored with metastatic soft tissue sarcoma between January 2001 and January 2021 were evaluated retrospectively. Patients aged 18 years and over, histopathologically diagnosed with metastatic STS, and unsuitable for operations, such as local curative surgery or metastasectomy, were included in the study. RESULTS: A total of 179 patients in the metastatic stage and monitored in our center were included in the study. The median follow-up period was 8.4 months (IQR, 3.4-14.4). 58 (32.4%) patients were de-novo metastatic, and 121 (67.6%) patients developed metastasis later. The median age was 53.2 (Range: 18.8-87.6 years), and 101 (56.4%) patients were male. The most common primary location was the lower extremity (87) (48.6%). The most common histological subtypes were synovial sarcoma (38) (21.2%), pleomorphic sarcoma (37) (20.7%), and liposarcoma (26) (14.5%). The majority were grade 3 tumors (n=131, 73.2%). Having ECOG PS 2-3 (HR=2.829, 95% CI 1,667-4.800, p<0.001), having tumor grade as 3 (HR=1.748, 95% CI 1.150-2.656, p<0.009), receiving palliative chemotherapy (HR=0.294, 95% CI 0.144-0.600, p<0.001), and receiving two or more lines of chemotherapy among those palliative receivers (HR=2.505 95% CI 1.696-3.700, p<0.001) were independent predictive factors of mortality. CONCLUSIONS: Survival in metastatic soft tissue sarcoma is better in patients with good ECOG performance status, low tumor grades, and who have received palliative chemotherapy. Receiving more than one line of palliative systemic treatment for progressive disease improves survival.

Diagnostic yield of microarrays in individuals with non-syndromic developmental delay and intellectual disability.

BACKGROUND: Intellectual disability (ID), or developmental delay (DD) when the individual is yet under 5 years of age, is evident before 18 years of age and is characterised by significant limitations in both intellectual functioning and adaptive behaviour. ID/DD may be clinically classified as syndromic or non-syndromic. Genomic copy number variations (CNVs) constitute a well-established aetiological subgroup of ID/DD. Overall diagnostic yield of microarrays is estimated at 10-25% for ID/DD, especially higher when particular clinical features that render the condition syndromic accompany. METHODS: In this study, we aimed to investigate the diagnostic yield of microarrays in the subgroup of individuals with non-syndromic ID/DD (NSID/NSDD). A total of 302 NSID/NSDD individuals who have undergone microarray analysis between October 2013 and April 2020 were included. Accompanying clinical data, including head circumference, delayed developmental areas, seizures and behavioural problems were collected and analysed separately in NSID and NSDD subgroups. RESULTS: The diagnostic yield of microarray analyses in NSID/NSDD was determined as 10.9% in NSID (10.7%) and in NSDD (11.1%). Presence of behavioural and epileptic problems did not contribute to the diagnostic yield. However, in the presence of macrocephaly, the contribution to diagnostic yield was statistically significant particularly in NSDD group. The most common pathogenic CNVs involved chromosomes 16, 15 and X. Lastly, we propose a Xq21.32q22.1 deletion as likely pathogenic in a child with isolated language delay and accompanying seizures. CONCLUSIONS: Particularly in neurodevelopmental diseases, microarrays are useful for establishing the diagnosis and detecting novel susceptibility regions. Future studies would accurately classify the herein presented variants of uncertain significance CNVs as pathogenic or benign.

Relationship Between the Fibrinogen-to-Albumin Ratio and SYNTAX Score in Patients with Non-St-Elevation Myocardial Infarction

ABSTRACT Background: Despite the association of fibrinogen-to-albumin ratio (FAR) with the extent, severity, and complexity of coronary artery disease (CAD) in patients with ST-elevation myocardial infarction (STEMI) and stable CAD, no studies to date have specifically addressed this issue in patients with non-STEMI (NSTEMI). Objectives: This study aimed to evaluate whether a relationship exists between FAR and the SYNergy between Percutaneous Coronary Intervention with TAXus (SYNTAX) score in patients with NSTEMI. Methods: In this prospective cross-sectional study, 330 patients with NSTEMI who had undergone coronary angiography in an academic medical center were divided into two groups: those with an intermediate/high (≥23) SYNTAX score (241 patients) and those with a low SYNTAX score <23 (89 patients). SYNTAX score was computed by two highly experienced cardiologists (who were blinded to the study data) using an online SYNTAX calculator. Fibrinogen and albumin levels were measured in all patients, and FAR was calculated. Results: Multivariate logistic regression analysis showed that FAR (odds ratio [OR]: 1.478, 95% confidence interval [CI]: 1.089-2.133, p = 0.002), low-density lipoprotein (OR: 1.058, 95% CI: 1.008-1.134, p = 0.026), and troponin I (OR: 1.219, 95% CI: 1.015-1.486, p = 0.031) were independent predictors of the SYNTAX score. In a receiver operating characteristics analysis, a cutoff FAR value of 95.3 had an 83% sensitivity and an 86% specificity (area under the curve [AUC]: 0.84, p < 0.001) for the prediction of SYNTAX scores ≥23 in NSTEMI patients. Conclusion: These results indicate that FAR is a useful tool to predict intermediate-high SYNTAX scores in NSTEMI patients.

Early and late aortic propagation velocity values in STEMI patients after successful primary PCI and their relationship with neutrophil to lymphocyte ratio.

OBJECTIVE: Atherosclerosis leads to increased arterial resistance through thickening and stiffening of the arterial wall, a phenomenon largely known as arterial stiffness. M-mode propagation velocity of the descending thoracic aorta, named aortic velocity propagation (AVP) is a novel method for the measurement of the aortic stiffness. We aimed to investigate the difference between early and late values of AVP after successful primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. PATIENTS AND METHODS: A total of 103 (70 male, 67.9%) consecutive patients without a previous history of coronary artery disease, who presented with STEMI without hemodynamic compromise and underwent successful primary PCI were enrolled. Transthoracic echocardiography was performed in all patients after primary PCI at 12-24 hour in Intensive Care Unit (early measurements) and three months after the discharge during follow-up (late measurements). Doppler echocardiography, 2D and aortic M-mode propagation velocity measurements were recorded. Haematological and serum biochemical parameters of the study group were recorded. RESULTS: There were no statistically significant differences in 2D echocardiography measurements between early and late evaluations. AVP values increased during 3 months follow-up in all patients. Mean AVP values were 33.7± 11.6 cm/sn and 44.4±10.5 cm/sn at early and late measurements, respectively (p<0.001). There were significant correlations between differences of AVP and neutrophil-lymphocyte ratio between early and late measurements. CONCLUSIONS: We demonstrated for the first time that AVP values could improve after successful treatment in STEMI patients. The increment in AVP values was closely correlated with a decrement in neutrophil lymphocyte ratio. It can be postulated that AVP has strong correlations with the inflammatory markers.

Effect of sildenafil on intestinal adaptation parameters in a rat model of short bowel syndrome.

OBJECTIVE: We aimed to evaluate the effect of sildenafil on the intestinal adaptation in short bowel syndrome (SBS). MATERIALS AND METHODS: Forty-eight male Wistar-albino rats (weight, 231-390 g) were randomly divided into four groups with 12 rats in each. Group TA had only ileal transection+anastomosis, Group TA+S was given sildenafil after ileal transection+anastomosis, Group RA had a resection of 75% of the small bowel+anastomosis, Group RA+S was given sildenafil after small bowel resection+anastomosis. Sildenafil was injected subcutaneously at 60 mg/kg/day dose throughout 3-21 days postoperatively. Bowel and mucosal weights, villus height, crypt depth, DNA and protein concentrations were determined. RESULTS: Jejunal bowel weight was lower in TA and TA+S groups than RA and RA+S groups (p < 0.05). RA+S group had higher ileal and jejunal mucosal weights than RA and TA+S groups (p < 0.05). Villus height was highest in RA+S group both in ileum and jejunum (466.1 ± 38.6 µm and 648.1 ± 65.7 µm, respectively). Jejunal crypt depth was highest in RA+S group (255.1 ± 21.9 µm) compared to other groups (p < 0.05). There was no significant difference in ileal and jejunal protein concentration between TA and TA+S groups and in ileal protein concentration between RA ve RA+S groups (p > 0.05). Ileal DNA concentration was higher in TA+S group, and jejunal DNA concentration was higher in RA and RA+S groups than TA and TA+S groups (p < 0.05). CONCLUSIONS: Sildenafil has a positive effect on intestinal adaptation parameters, particularly in jejunum in a rat SBS model. Thus, its role in the treatment of SBS should be further investigated with clinical studies.

Neurochemical evaluation of brain function with 1H magnetic resonance spectroscopy in patients with fragile X syndrome.

Fragile X syndrome (FXS) is the most common hereditary disorder of intellectual disability. Cognitive deficits involve executive function, attention, learning and memory. Advanced neuroimaging techniques are available, and (1)H magnetic resonance spectroscopy (MRS) can be used as a complementary method to MR imaging to understand disease processes in brain, by in vivo demonstration of brain metabolites. MRS was performed in 13 male patients with FXS full mutation, and 13 age- and sex-matched healthy controls. FXS diagnosis was based on clinical evaluation, followed by detection of FMR1 full mutation. Axial T2 TSE, sagittal T1 SE and coronal 3D MPRAGE images were obtained for both morphological imaging and voxel localization. Following evaluation of conventional images, multivoxel MRS (CSI) through supraventricular white matter and single voxel MRS (svs) with an intermediate echo time (TE:135 ms) from the cerebellar vermis were performed. Choline/Creatine (Cho/Cr), N-acetyl aspartate/Creatine (NAA/Cr), and Choline/N-acetyl aspartate (Cho/NAA) ratios were examined at right frontal (RF), left frontal (LF), right parietal (RP), left parietal (LP), and cerebellar vermian (C) white matter. Statistical analyses were done using t-test and Mann-Whitney U tests. A statistically significant difference was observed in RP Cho/NAA ratio (cell membrane marker/neuroaxonal marker), FXS patients having lower levels than controls (P = 0.016). The results should be evaluated cautiously in parallel to consequences in brain metabolism leading to alterations in neurotransmitter levels, osmoregulation, energy metabolism and oxidative stress response described in animal models. MRS may serve to define a metabolic signature and biomarkers associated with FXS.

Duration of anti-HER2 blockage therapy may improve survival in HER2 positive metastatic breast carcinoma patients.

PURPOSE: The duration of anti-HER2 blockage therapy in metastatic breast cancer patients is still unclear. We aimed to evaluate the effect of the anti-HER2 blockage therapy duration and other factors on survival in HER2 positive metastatic breast carcinoma (MBC) patients. METHODS: The medical records of 193 HER2 positive MBC patients, who did not have the opportunity to receive adjuvant trastuzumab therapy but had received trastuzumab in the metastatic setting were retrospectively evaluated. RESULTS: The median age at diagnosis was 45.0 years (range 21-83). Ninety-two (47.7%) patients received palliative trastuzumab < 6 months median, whereas 101 patients received trastuzumab ≥ 6 months median. The median number of trastuzumab cycles was 8 (range 1-51). Median survival after breast cancer recurrence was 31.0 months (range 24.3-37.7). The duration of trastuzumab therapy had a significant impact on the prognosis of recurrent breast cancer (22.0 vs 49.0 months, for ≤ 6 months of treatment duration, respectively; p<0.0001). Survival after breast cancer recurrence for the patients who received lapatinib plus capecitabine vs those who did not was significantly different (59 patients, p=0.005). Moreover, there was a statistically significant relationship between prolonged lapatinib plus capecitabine combination therapy and improved survival after disease recurrence (p=0.022). In the multivariate Cox regression analysis, treatment with trastuzumab > 6 months (p=0.003) was the only independent prognostic factor for survival after breast cancer recurrence. CONCLUSION: The duration of anti-HER2 blockage therapies, especially with trastuzumab, seems to improve survival of HER2-positive metastatic breast cancer patients who were not previously treated with adjuvant trastuzumab, regardless of other therapies.

Alternative methods for the screening of retinopathy of prematurity: binocular indirect ophthalmoscopy vs wide-field digital retinal imaging.

PURPOSE: To compare the diagnostic efficacy of wide-field digital retinal imaging (WFDRI) with binocular indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP) screening. METHODS: Premature infants admitted for ROP screening were included in this prospective, randomized and double-blind comparative study. They were examined by using BIO and WFDRI. RESULTS: A total of 58 infants were enrolled in the study. The sensitivities of WFDRI in detecting any stage of ROP, treatment-requiring ROP and plus disease were 58.6, 100, and 100% respectively, with a specificity of 100% for all. The proportional agreement between WFDRI and BIO was 0.903 for detection of any stage of ROP, 1.0 for treatment-requiring ROP, and 1.0 for plus disease. CONCLUSION: The sensitivity and specificity of WFDRI was excellent for the diagnosis of severe and treatment-requiring ROP. However, BIO was superior in mild ROP particularly for the ones in retinal periphery.

Amblyopia and sensory features at initial presentation of Brown syndrome: an issue to recognize.

PURPOSE: To investigate the frequency of amblyopia and sensory features at initial presentation in patients who had unilateral congenital Brown syndrome (BS) and to identify the potential risk factors for amblyopia in BS. METHODS: The study conducted with patients who had unilateral congenital BS. Patient demographics, visual acuity, refractive errors, amount of horizontal and vertical deviations, abnormal head position, fusion, and stereopsis were all reviewed. The main outcome measure was the frequency of amblyopia at initial presentation. RESULTS: The review identified 44 patients with BS (median age 5 years). The frequency of amblyopia was 15.9% (seven patients) in BS at initial presentation. Patient age (P=0.297), ocular alignment at primary position (P=0.693), anisometropia (P=0.184), and stereoacuity (P=0.061) were found to have no significant relation with amblyopia. The main associated risk factor was the absence of sensory fusion (P=0.013). CONCLUSIONS: Amblyopia may be encountered among patients with BS, and may be related to binocularity of the patient. Its recognition may be a critical step during the treatment planning and may determine presumably the success of future therapies.

ABO and Rh blood groups frequency in women with HER2 positive breast cancer.

PURPOSE: The role of genetic factors in the development of cancer is widely accepted. Data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. The aim of this study was to investigate the presence of a possible association between HER2 (+) breast cancer in Turkish women and ABO blood groups and Rh factor. METHODS: In 294 female patients with HER2 (+) breast cancer, ABO blood groups and Rh factor were examined. The relationship of blood groups with age, menopausal status, and family history of cancer, estrogen receptor (ER), progesterone receptor (PR) and HER2 status of these patients was evaluated. Blood groups distribution of 22,821 healthy blood donors was also assessed and compared with the patients' blood groups distribution. RESULTS: The median patient age was 47 years (range 20-80) and 56% of the patients were premenopausal. ER and PR were positive in 50 and 60% of the patients, respectively. Overall, the ABO blood group distribution of the 294 HER2 (+) breast cancer patients was similar to that of the healthy blood donors (p=0.36). Likewise there was no correlation between blood type and ER, PR and menopausal status. Rh (-) patients had more frequent family cancer history and this difference was significant for patients with blood group B Rh (-) and O Rh (-) (p = 0.04). CONCLUSION: In the present study we didn't find any relationship between HER2 status and ABO blood group and Rh factor. However, further studies with larger number of patients are needed to establish the role (if any) of blood groups in patients with breast cancer.

Concomitant Hodgkin's lymphoma and gastric adenocarcinoma: a rare coincidence.

Gastric adenocarcinomas may be seen together with colon, prostate, breast, liver, lung and gynecological malignancies as synchronous or metachronous cancer. However, Hodgkin's lymphoma (HL) is rarely diagnosed with solid tumors. Herein, a 72-year-old man with both gastric adenocarcinoma and HL has been presented. Mass lesions far away from the primary tumor in cancer patients can be not only the sign of distant metastasis but also another primary malignancy. In the English literature, synchronous gastric adenocarcinoma and HL has been rarely reported, and as far as we know, this is the third case to be reported.

Molecular epidemiology of vancomycin-resistant Enterococcus faecium strains isolated from haematological malignancy patients in a research hospital in Turkey.

Infections and outbreaks of vancomycin-resistant enterococci (VRE) still appear to be rare in Turkey. In the present study, VRE strains isolated during an outbreak in a haematology unit of a training and research hospital in Turkey were typed and their antimicrobial-resistance patterns were characterized by molecular methods. Twelve vancomycin-resistant Enterococcus faecium strains isolated from patients with haematological malignancies were investigated by PCR for the presence of genes encoding resistance to vancomycin, tetracycline, chloramphenicol, gentamicin and erythromycin. Their clonal relationship was evaluated by PFGE and multilocus sequence typing. All strains were resistant to vancomycin and erythromycin, and had the vanA and ermB genes, respectively. PFGE was used to determine the presence of two pulsotypes and determine their subtypes. Pulsotype A belonged to sequence type (ST) 17 and pulsotype B belonged to ST 78. All strains with the vanA gene were not the same clone, indicating multiple acquisitions of resistant isolates, even over such a short time period.

Relationship between N-terminal pro-B type natriuretic peptide and extensive echocardiographic parameters in mild to moderate aortic stenosis.

CONTEXT: The N-terminal pro-B type natriuretic peptide levels (NT pro-BNP) are increased in cases of volume or pressure overload. AIMS: To examine NT pro-BNP levels and enclose whether any relationship is present between the levels of NT pro-BNP and extensive echocardiographic parameters in asymptomatic patients with mild to moderate aortic stenosis (AS). SETTINGS AND DESIGN: A cross-sectional study about the NT pro-BNP levels was conducted in 37 asymptomatic AS patients and compared with 40 controls. METHODS: Patients < 70 years old with mild to moderate AS with a peak transaortic gradient > 20 mm Hg in transthoracic echocardiogram were included in our study. Extensive echocardiographic parameters and NT pro-BNP levels were obtained from these patients and these indices were compared with the control population selected from the patients who had similar clinical characteristics with the AS patients. STATISTICAL ANALYSIS: NT-proBNP values were found to be distribution free. Spearman correlation coefficient was used for correlation analysis. Mean values were compared by the Kruskal-Wallis test. RESULTS: The NT pro-BNP levels were increased in patients with AS (median; interquartiles range: 686 [449-855] pg/mL vs. 140 [116-150] pg/mL, P < 0.001). Among patients with AS, when correlation analysis was performed mean transaortic gradient, aortic valve area index, myocardial performance index, E(m)/A(m) ratio, left-ventricular mass index (LVMI) and E/E(m) ratio had correlations (r=0.38, P = 0.026; r=-0.46, P =0.008; r=0.19, P =0,049; r=-0.22, P =0.04, r=0.49, P =0.003 and r=0.53, P <0.001 respectively) with plasma NT pro-BNP levels. The LVMI (r = 0.49, P = 0.003) and E/E(m) ratio (r = 0.53 P < 0.001) have the strongest correlations when compared to other parameters. CONCLUSION: Plasma NT pro-BNP levels are increased in even asymptomatic patients with AS and correlated with several echocardiographic parameters related to severity of AS and degree of diastolic dysfunction. As a result, NT pro-BNP levels may be used in the follow-up of asymptomatic patients having mild to moderate AS.

Relationship between short wavelength perimetry and central corneal thickness values in ocular hypertensive subjects.

PURPOSE: To evaluate the results of short wavelength perimetry (SWAP) of ocular hypertensive (OHT) patients and correlate these findings with central corneal thickness (CCT) measurements. METHODS: Thirty-seven OHT patients with a mean age of 50.2+/-8.2 (SD) years and 30 control subjects with a mean age of 50.3+/-8.5 (SD) years were included in this study. A questionnaire was applied to patients to evaluate the demographic risk factors that may predict glaucoma development. After a detailed ophthalmologic examination, achromatic and short wavelength perimetries and ultrasonic pachymetry were performed and the results were compared between the two groups with Student t test and Mann-Whitney U test. A p value<0.05 is considered as statistically significant. RESULTS: Mean CCT was higher in the OHT group (right eye; 558.13+/-28.39 microm and left eye; 558.94+/-27.30 microm) when compared with the control subjects (524.66+/-30.53 microm and 525.86+/-30.46 microm, respectively) (p<0.01). A significant positive correlation was found between CCT measurements and intraocular pressure (r=0.5, p<0.001). Four right eyes (10.8%) and five left eyes (13.5%) of OHT patients had defects in SWAP. OHT patients with SWAP abnormalities had significantly lower CCT measurements in right (527.25+/-17.34 microm) and left eye (528.80+/-13.60 microm) when compared with OHT patients without SWAP defects (561.87+/-27.29 microm and 563.65+/-25.92 microm, respectively) (p<0.05). Significant correlations were found between CCT and SWAP MD, PSD, and CPSD (p<0.05). CONCLUSIONS: OHT patients with SWAP abnormalities had significantly lower CCT measurements than those without. CCT is considered as a risk factor for the development of glaucomatous damage in OHT patients.

Comparing the accuracy of panoramic and intraoral radiography in the diagnosis of proximal caries.

OBJECTIVES: The purpose of this study was to compare the diagnostic accuracy of panoramic and intraoral radiographic surveys in the diagnosis of proximal caries according to the different dental regions (maxillary and mandibular incisor, canine, premolar and molar). METHODS: In this study, full mouth series and panoramic radiographs of 79 patients were used. The radiographs were evaluated for proximal caries by three observers. The diagnostic accuracy of radiographic surveys for each dental region was assessed by means of receiver operating characteristic (ROC) curve analysis. RESULTS: Full mouth series was the most efficient method in the diagnosis of caries for incisor and canine teeth. However, full mouth series and combination of panoramic plus bitewings had similar diagnostic accuracy for premolar and molar teeth. CONCLUSIONS: Panoramic survey alone was not sufficient for the diagnosis of proximal caries for the entire dentition. The combination of panoramic plus bitewing plus anterior periapical survey exhibited a diagnostic accuracy for proximal caries that was comparable with full mouth series.

Blood viscosity in patients with diffuse large B cell non-Hodgkin's lymphoma.

UNLABELLED: The aim of the study was to evaluate blood viscosity as possible marker of disease progression in patients with newly diagnosed non-Hodgkin's lymphoma (NHL). METHODS: The viscosity of blood samples from 20 patients with newly diagnosed aggressive NHL (stage I, n=7; stage II, n=4; stage III, n=7; stage IV, n=2) was analyzed using Brookfield DV-II + (USA) machine. RESULTS: Blood viscosity in NHL patients (median: 5.5+/-1.46 miliPascal) inversely correlated with lactatdehydrogenase (LDH) level, international prognostic index (IPI) score, and stage (p=0.02, r=-0.51; p=0.03, r=-0.63; and p=0.04, r=-0.45, respectively) and positively correlated with hemoglobin level (p=0.02, r=0.65)). CONCLUSION: According to our data, blood viscosity may be considered as a follow up marker in NHL patients along with LDH level or sedimentation rate.