Genetic dependencies associated with transcription factor activities in human cancer cell lines.

Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

The Effect of Intraoperative Patient Positioning on the Success of Intertrochanteric Fracture Surgery in Older Patients.

Background and Objectives: The incidence of hip fractures in people of advanced ages is increasing due to our aging society. Patient positioning for the intertrochanteric fractures of the femur can be performed in various ways. The aim of this study is to clinically and radiologically compare the use of the supine hemilithotomy position, the lateral decubitus position, and the traction table when performing proximal femoral nail (PFN) surgery for femoral intertrochanteric fractures in the geriatric age group. Materials and Methods: A total of 170 elderly patients with femoral intertrochanteric fractures were included in this cross-sectional study. The patients were divided into three groups (the supine hemilithotomy group, the lateral decubitus group, and the fracture table group). For the postoperative period, complications, length of stay in the intensive care unit, and length of stay in hospital were examined, while in postoperative radiographs, tip-apex distances (TADs), collodiaphyseal angles (CDAs), and Cleveland-Bosworth quadrants were examined to evaluate the placement of the lag screw in the femoral head. The quality of fracture reduction was evaluated according to the modified Baumgaertner criteria. Results: The mean age of the patients was 77.8 ± 8.8; 57.6% of patients were female. According to the modified Baumgaertner criteria, it was determined that patients with 'poor' reduction quality had an approximately ten times higher risk of cut-out than those with 'good' reduction quality (OR = 10.111, p = 0.002, 95% confidence interval; 2.313-44.207). The operative time for patients in the fracture table group was longer than that of the other groups Additionally, the CDA in the supine hemilithotomy position group was longer. Conclusions: Although PFN surgery using the traction table is longer in terms of surgical time compared to surgery performed in the lateral decubitus position and the supine hemilitotomy position, it is advantageous in terms of better TAD and CDA values and lower complication rates.

Calcaneus as a Rare Location of Solitary Osteochondromas: Two Case Reports.

Osteochondromas are the most common benign bone tumors, with an incidence of 36% to 41% among benign bone tumors. They can be caused by genetics, trauma, and growth defects. The incidence of all osteochondromas in the hands and feet is approximately 10%, and they are extremely rare in the calcaneus. They generally arise from the metaphysis and metaphyseal-diaphyseal region of the long bones. Osteochondromas, which are generally painless, are noted with signs of inflammation in the bursa, vascular and nerve compression, pain caused by joint deterioration, swelling in the subcutaneous tissue, or gait disturbance. The incidence of malignant transformation of solitary osteochondromas is 1%. We present two cases, an 11-year-old male patient and a 32-year-old male patient, diagnosed with osteochondroma in the calcaneus.

Assessment and feedback of the COVID-19 pandemic's effects on physicians' day-to-day practices: good knowledge may not predict good behavior.

The importance of doctors' knowledge and awareness of infectious diseases was felt worldwide during the COVID-19 pandemic. With this study, we aimed to evaluate the effect of the long and dynamic pandemic process on resident physicians' knowledge and protective behaviors for infection control in a tertiary hospital setting and protective behaviors for infection control in a tertiary hospital setting. The population of this cross-sectional study consisted of assistant physicians working at Suleyman Demirel University Faculty of Medicine Training and Research Hospital. A questionnaire evaluating information and protective practices for COVID-19 was applied to the participants through face-to-face interviews using the convenience sampling method, with an interval of one year. In the second year of the pandemic, resident physicians' awareness of the correct use of personal protective equipment decreased (p = 0.001). Despite the continuous training, it was determined that the residents preferred masks with high protection at a lower rate when they encountered patients who received oxygen support of 5 lt/min and above (p < 0.001). To prevent the spread of COVID-19 infection in the hospital as the pandemic progresses, it has been determined that resident physicians are less prone to evaluate possible infection symptoms in patients hospitalized for non-COVID-19 reasons (p = 0.013). As a result, the data we obtained showed that despite the regular training during the pandemic and the death of many health workers, the residents' adherence to infection control and prevention practices, which also protect them, decreased significantly in the second year of the pandemic. These valuable data showed us that good knowledge does not predict good infection control and prevention practices. Our findings show that physicians need a new education system that motivates them. In addition, psychosocial determinants, physical and mental fatigue, and institutional control factors contributing to these results and affecting individual risk perception should be recognized and prevented.

Fluoroscopy guided without contrast injection for ganglion impar blockade in traumatic coccydynia: Description a modified approach and 1-year results.

BACKGROUND: This study presents a new fluoroscopy-controlled approach in patients with chronic traumatic coccydynia by applying ganglion impar block using the needle-inside-needle technique from the intercoccygeal region without the administration of contrast material. With this approach, the cost and possible side effects of using contrast material can be prevented. In addition, we examined the long-term effect of this method. METHODS: The study was designed retrospectively. The marked area was entered with a 21-gauge needle syringe, and 3 cc of 2% lidocaine was administered subcutaneously by local infiltration. A 25-gauge 90 mm spinal needle was inserted into the guide 21-gauge 50 mm needle tip. The location of the needle tip was controlled under fluoroscopy, and 2 mL of 0.5% bupivacaine and 1 mL of be-tamethasone acetate were mixed and administered. RESULTS: A total of 26 patients with chronic traumatic coccydinia participated in the study between 2018 and 2020. The average procedure time was approximately 3.19 min. The mean time of pain relief of more than 50% was 1.25±1.22 (1st min-72 h) min. The mean Numerical pain rating scale scores were 2.38±2.26 at 1 h, 2.50±2.30 at 6 h, 2.50±2.21 at 24 h, 3.73±2.20 at 1 month, 4.46±2.14 at 6 months 1 and 5.23±2.52 at 1 year. CONCLUSION: Our study shows that as an alternative in patients with chronic traumatic coccydynia, the long-term results of the needle-inside-needle method from the intercoccygeal region without contrast material are safe and feasible.

Evaluation of combination therapies with colistin in an experimental mouse pneumonia model induced by carbapenem-resistant Acinetobacter baumannii strain.

The treatment options are limited in Acinetobacter baumannii infections. In this study, the effectiveness of colistin monotherapy and combinations of colistin with different antibiotics were investigated in an experimental pneumonia model induced by carbapenem-resistant A. baumannii strain. Mice in the study were divided into five groups as control (no treatment), colistin monotherapy, colistin + sulbactam, colistin + imipenem, and colistin + tigecycline combinations. The modified experimental surgical pneumonia model of Esposito and Pennington was applied to all groups. The presence of bacteria in blood and lung samples was investigated. Results were compared. In blood cultures, while there was no difference between the control and colistin groups, there was a statistical difference between the control and the combination groups (P = 0.029). When the groups were compared in terms of lung tissue culture positivity, there was a statistical difference between the control group and all treatment groups (colistin, colistin + sulbactam, colistin + imipenem, and colistin + tigecycline) (P = 0.026, P < 0.001, P < 0.001, and P = 0.002, respectively). The number of microorganisms that grew in the lung tissue was found to be statistically significantly lower in all treatment groups in comparison with the control group (P = 0.001). Both monotherapy and combination therapies of colistin were found to be effective in the treatment of carbapenem-resistant A. baumannii pneumonia, but the superiority of combination therapies over colistin monotherapy has not been demonstrated.

Reconstruction of critical size segmental femoral diaphyseal defects of New Zealand rabbits by using combined titanium mesh cage and induced membrane technique.

PURPOSE: Long bone defects due to fractures resulting from high-energy trauma, infections and tumor resections are problems that orthopedic surgeons commonly face. We investigated the effects of a titanium mesh cage on bone healing with an induced membrane technique. METHODS: Three groups, each composed of eight rabbits, were formed. Extraarticular diaphyseal bone defects were created. Femora of the first group were fixed with an empty titanium mesh cage and two K-wires. After formation of the defect, polymethylmethacrylate was inserted and fixed with a K-wire in the second group. At the third week, the cement was removed, a sterilized cancellous graft-filled titanium mesh cage was placed into the defect, and the membrane that was previously formed over the cement was placed on the cage and repaired. In the third group, sterilized cancellous grafts were filled into the titanium mesh cage, and the titanium mesh cage was fitted into the bone defect area. RESULTS: At the end of the third month, all subjects were killed. Radiological data revealed that the healing of the bone in the second and third groups was significantly better than that in the first group. There was no difference between the second and third groups. A histological evaluation of the healing status, such as fibrous tissue, cartilage tissue and mature or immature bone formation, was performed. Histological healing in the second and third groups was also significantly better than that in the first group. CONCLUSION: We concluded that the combination of membrane-induced bone healing and graft-filled titanium mesh cages expedites osteogenesis in extraarticular bone defects.

Mortality-associated factors of candidemia: a multi-center prospective cohort in Turkey.

Candidemia may present as severe and life-threatening infections and is associated with a high mortality rate. This study aimed to evaluate the risk factors associated with 30-day mortality in patients with candidemia. A multi-center prospective observational study was conducted in seven university hospitals in six provinces in the western part of Turkey. Patient data were collected with a structured form between January 2018 and April 2019. In total, 425 episodes of candidemia were observed during the study period. Two hundred forty-one patients died within 30 days, and the 30-day crude mortality rate was 56.7%. Multivariable analysis found that SOFA score (OR: 1.28, CI: 1.154-1.420, p < 0.001), parenteral nutrition (OR: 3.9, CI: 1.752-8.810, p = 0.001), previous antibacterial treatment (OR: 9.32, CI: 1.634-53.744, p = 0.012), newly developed renal failure after candidemia (OR: 2.7, CI: 1.079-6.761, p = 0.034), and newly developed thrombocytopenia after candidemia (OR: 2.6, CI: 1. 057-6.439, p = 0.038) were significantly associated with 30-day mortality. Central venous catheter removal was the only factor protective against mortality (OR: 0.34, CI:0.147-0.768, p = 0.010) in multivariable analysis. Candidemia mortality is high in patients with high SOFA scores, those receiving TPN therapy, and those who previously received antibacterial therapy. Renal failure and thrombocytopenia developing after candidemia should be followed carefully in patients. Antifungal therapy and removing the central venous catheter are essential in the management of candidemia.

Etiology, treatment options and prognosis of abdominal abscesses: A tertiary hospital experience.

INTRODUCTION: The principle of abdominal abscess treatment is drenage. However, whether this drainage is percutaneous or open surgery is the choice of the specialist or center. Recently, there have been reports indicating that percutaneous drainage is superior. In this study, patients followed up and treated in a ten-year period in our clinic were evaluated for both of the methods that we applied. METHODOLOGY: Cases of intra-abdominal abscess followed-up in a ten-year period were evaluated retrospectively. As well as some of the characteristics of the patients, the methods of drainage applied were recorded. The subjects who received percutaneous drainage and those undergoing open surgery were compared in terms of length of hospitalization, length of treatment and prognosis. RESULTS: The most common abscess site was intraperitoneal, and the origins of the abscesses were often hospital-based. The most commonly isolated organism, at a level of 33.8%, was Escherichia coli. Percutaneous drainage was applied at source control in 49 (43.8%) patients and open surgery drainage in 60 (53.6%). However, length of hospitalization, length of treatment and duration of drainage catheter use were statistically significantly higher in the percutaneous drainage group. No significant difference was observed between the groups in terms of prognosis. CONCLUSION: We attribute these results in disagreement with the literature to more patients being recommended for percutaneous drainage due to the fact that these patients were thought to be incapable of tolerating open surgery and to the higher probability of additional disease and complications.

The effect of placental elasticity on intraoperative bleeding in pregnant women with previous cesarean section.

Background We aimed to evaluate the efficiency of placental elasticity in predicting the amount of intraoperative bleeding via real-time tissue elastography technique. Methods Pregnant women in the third trimester of pregnancy who had planned delivery via cesarean section due to the recurrent cesareans were enrolled in the research (n = 78). Elastographic measurements of placental tissues of all cases were carried out by real-time elastographic ultrasonography. It is a tissue elastography software (Esaote MyLabSeven) that uses a 8-1-MHz multifrequency AC2541 Probe. Results A significant relationship was found between placental elasticity and intraoperative bleeding. There was a significant correlation between alterations in the preoperative and postoperative hemoglobin (Hb) and hematocrit (Hct) levels and placental strain ratio (SR) (P < 0.001, r: 0.831; P < 0.001, r: 0.733, respectively). Conclusion These findings may reflect an alteration at the tissue elasticity level. We hope that the use of real-time elastographic ultrasonography technique may give an idea about the amount of bleeding during the cesarean section.

Temporary Fixation of Reduction with Fabric Adhesive Bandage in the Surgical Treatment of Pediatric Supracondylar Humerus Fractures.

Background and objectives: Supracondylar humerus fractures are common in children andcan be surgically treated. However, the general surgical procedures involving reduction andfixation might lead to reduction loss, failure to direct the Kirschner (K)-wire toward the desiredposition, prolonged surgery, or chondral damage. This study aimed to show that temporaryfixation of closed reduction with a fabric adhesive bandage in pediatric supracondylar humerusfractures could maintain reduction so that surgical treatment can be easily performed by a singlephysician. Materials and Methods: Forty-six patients with Gartland type 3 supracondylar humerusfractures who underwent surgical treatment between May 2017 and June 2018 were retrospectivelyevaluated. Fluoroscopy-guided reduction and fixation were performed from the distal third of theforearm to the proximal third of the humerus using a fabric adhesive bandage. Two crossed pinswere applied on the fracture line by first inserting a lateral-entry K-wire and then inserting anotherK-wire close to the anterior aspect of the medial epicondyle and diverging from the ulnar nervetunnel. A tourniquet was not applied in any patient and no patients required open reduction.Results: The study included 32 boys (69.6%) and 14 girls (30.4%) (mean age, 7.1; range, 2-16 years).The mean hospital stay and follow-up duration were 4.3 ± 3.9 days and 48.1 ± 14.3 weeks,respectively. Heterotopic ossification was detected in one patient, and ulnar nerve neuropraxia wasdetected in another patient. Functional (according to Flynn criteria) and cosmetic outcomes wereexcellent in 95.6%, moderate in 2.2%, and poor in 2.2% of patients. The mean duration of fixation ofthe closed reduction with a fabric adhesive bandage was 8.1 ± 3.9 min, and the mean duration ofpinning was 7.9 ± 1.4 min. Conclusions: Temporary preoperative fixation of supracondylar humerusfractures that require surgical treatment with a fabric adhesive bandage may be significantlyconvenient in practice.

An investigation of the effectiveness against bacteriuria of silver-coated catheters in short-term urinary catheter applications: A randomized controlled study.

AIM: The aim of this study was to investigate the effectiveness of antimicrobial-coated catheters against bacteriuria and urinary tract infection in patients who have urinary catheterization. METHODS: Twenty eight and twenty six people similar in terms of demographic characteristics and primary and underlying diseases were randomly selected from patients undergoing short-time urinary catheterization in the intensive care unit. Silver-coated slicone foley catheters and normal slicone foley catheters were used for uninary catheterization in the first and second group of the patients respectively. Urine specimens were collected from patients at 2-day intervals and assessed in terms of bacteriuria. RESULTS: Bacteriuria was found in 12 (46.2%) of the patients using normal catheters and 13 (46.4%) of those using silver-coated catheters throughout the monitoring period. No significant relationship was determined between use of different catheter types and bacteriuria (p = 0.98). The most common microorganism was identified as E. coli in the normal catheter group while microorganism other than E. coli was identified in the silver-coated catheter group. The prevalence of bacteriuria was statistically significantly higher in patients with a history of hospitalization in the previous 3 months (p = 0.028). CONCLUSION: The use of silver-coated silicone catheters was not shown to have a protective effect against bacteriuria in this study. Further well-designed studies with larger case numbers are now needed to confirm whether history of hospitalization, which emerged as a statistically significant factor in this study, increases the prevalence of catheter-related bacteriuria.

The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML.

Bromodomain and extra-terminal (BET) protein inhibitors have been reported as treatment options for acute myeloid leukemia (AML) in preclinical models and are currently being evaluated in clinical trials. This work presents a novel potent and selective BET inhibitor (BI 894999), which has recently entered clinical trials (NCT02516553). In preclinical studies, this compound is highly active in AML cell lines, primary patient samples, and xenografts. HEXIM1 is described as an excellent pharmacodynamic biomarker for target engagement in tumors as well as in blood. Mechanistic studies show that BI 894999 targets super-enhancer-regulated oncogenes and other lineage-specific factors, which are involved in the maintenance of the disease state. BI 894999 is active as monotherapy in AML xenografts, and in addition leads to strongly enhanced antitumor effects in combination with CDK9 inhibitors. This treatment combination results in a marked decrease of global p-Ser2 RNA polymerase II levels and leads to rapid induction of apoptosis in vitro and in vivo. Together, these data provide a strong rationale for the clinical evaluation of BI 894999 in AML.

Acute Abdomen Caused by Brucellar Hepatic Abscess.

Brucellosis, a zoonosis that is common worldwide, is endemic in many countries, primarily those of the Mediterranean region (including Turkey). Human brucellosis is a systemic infection with a wide clinical spectrum. Although hepatic involvement is very common during the course of chronic brucellosis, hepatic abscess is a very rare complication of Brucella spp. infection. We present a case of hepatic abscess caused by Brucella melitensis, which resembled the clinical presentation of surgical acute abdomen.

Evaluation of patients with zygomycosis.

AIM: Zygomycosis is a severe angioinvasive infection caused by Zygomycetes. We retrospectively investigated 16 cases of zygomycosis. MATERIALS AND METHODS: The data of patients, who had been followed between 2004 and 2010 in 8 tertiary-care teaching hospitals, were reviewed. Demographic characteristics, underlying diseases, and clinical signs and symptoms of the patients, as well as diagnostic methods, data obtained by radiological imaging methods, and the therapies, were recorded. Therapeutic approaches, antifungal agents and duration of use, and the characteristics of the cases were identified. RESULTS: The study included 11 female and 5 male subjects. The most common symptoms and clinical signs were fever (n = 9) and retro- orbital pain (n = 7). Rhinocerebral zygomycosis was the most common form. The mean time elapsed for diagnosis was 14.26 + 13.96 (range: 2-52) days. Antifungal therapy was given to 15 patients (94%). In addition to antifungal therapy, 12 patients underwent surgical intervention 1 to 4 times. The mean duration of receiving antifungal therapy was 61.4 + 58.02 (range: 1-180) days. The median duration of treatment was 62.5 (range: 42-180) days in survivors. CONCLUSION: Zygomycosis is an infectious disease with high mortality despite antifungal therapy and surgical interventions.

Risk factors for bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli in a Turkish hospital.

INTRODUCTION: Bloodstream infection caused by extended-spectrum beta-lactamase (ESBL)-producing pathogens has become a serious concern worldwide. The purpose of this study was to identify risk factors for bacteremia due to ESBL-producing Escherichia coli in a Turkish hospital. METHODOLOGY: We retrospectively reviewed the medical records of patients with E. coli bacteremia in a tertiary care centre from January 2007 to October 2011. Data from patients such as demographic features, underlying conditions, and antibiotic exposure were analysed. RESULTS: A total of 113 patients with bacteremia due to E. coli were included and data from patients with ESBL-producing E. coli (case patients) were compared to those with non-ESBL-producing E. coli (control patients). The frequency of ESBL producers was 38.9% (44/113). Exposure to fluoroquinolones and cephalosporins, history of intra-abdominal surgery intervention, and presence of central venous catheteter and urinary catheteter were more frequently detected among case patients (P < 0.05). Independent risk factors for bacteremia due to ESBL-producing E. coli were exposure to fluoroquinolones (OR 13.39, 95% CI 1.28-140.03) and cephalosporins (OR 3.48, 95% CI 1.03-11.74). CONCLUSIONS: Previous use of fluoroquinolone and cephalosporin in patients with bacteremia caused by E. coli increased the risk for ESBL-producing strains.

Evaluation of endocervical canal in women with minimal cervical cytological abnormalities.

OBJECTIVE: This study aimed to examine the endocervical canal curettage (ECC) results of patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade intraepithelial lesion (LSIL) and secondarily to explore the features of patients who are at greatest risk for endocervical involvement. MATERIALS AND METHODS: This is a retrospective analysis of 846 women who underwent ECC with ASC-US or LSIL on cervical cytology between January 2003 and April 2011. Records of demographic data and colposcopic impression were evaluated. Histopathological results of biopsies and ECC were classified into 2 categories as less than cervical intraepithelial lesion 2 (CIN 2) and CIN 2+ lesions for comparison. Multivariate analysis was performed using binary logistic regression analysis to identify predictors of ECC results. RESULTS: CIN 1 lesions were detected in 8.9% of patients, and the rates of CIN 2 or 3 and invasive/microinvasive cancers in ECC were 3.8% and 0.7%, respectively. Cervical intraepithelial lesion 2 or worse lesions were detected in 1.6% (7/419) of the patients with normal colposcopic findings. There was no statistically significant difference in the rate of CIN 2+ lesion in endocervical canal between the patients with or without satisfactory colposcopic examination (4.4% vs 4.1% p = .69). A total of 1.7% of the patients who did not have cervical biopsy and also 1.1% of the patients who had less than CIN 2 biopsy results were diagnosed with CIN 2+ lesion by ECC despite the satisfactory colposcopy. Only a positive biopsy result for dysplasia was found to be an independent factor for the detection of a dysplastic lesion in endocervical canal (odds ratio = 0.06; 95% CI = 0.01-0.35; p = .02). CONCLUSIONS: Endocervical canal curettage had minimal diagnostic utility for the detection of CIN 2 or worse lesions in women with ASC-US or LSIL smear result and normal colposcopic findings. In addition to this, the presence or absence of CIN 2+ lesions diagnosed by means of endocervical curettage was independent of a satisfactory or unsatisfactory colposcopic examination.