Evaluation of Vascular Neurology Fellowship Websites in the U.S.

Objectives: Due to the limitations of the Coronavirus disease pandemic, medical applicants have relied on remote means of information, such as a program's website, to decide where to apply. However, studies have shown that many residency and fellowship websites lack information. Vascular neurology fellowship websites have not yet been studied. This study evaluates the availability and accessibility of information on vascular neurology fellowship websites. Methods: From 2021 to 2022, a total of 109 U.S. vascular neurology fellowship programs from the Fellowship and Residency Electronic Interactive Database were investigated to determine whether they had websites. Each website was evaluated on the immediate availability of 34 different criteria, which were deemed important by past studies. These criteria were reviewed under four categories: program overview, application information, fellow life, and curriculum. The comprehensiveness of the information among these different categories were analyzed. Programs were grouped by geographic region and electronic residency application service (ERAS)-participation status and comparisons were made within these groups. Results: There were 107 programs with websites (98%). ERAS-participating programs fulfilled more criteria on average than non-participating programs (P = 0.004). All websites provided information on general descriptions of their programs, but information on board exam pass rates, fellow testimonials, history of the fellowship program, responsibility progression, family and social events, parking availability, and application deadline were provided by less than 25% of websites. Conclusion: This study found that there was a large lack of information on vascular neurology fellowship websites, which could be improved to attract more applicants.

Relationship between serum Betatrophin, GPIHBP1, and LDL subfractions in patients with gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) leads to changes in the lipid metabolism. In this study, we aimed to compare serum levels of LDL subfractions, betatrophin, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) between patients with GDM and healthy pregnant women. DESIGN AND METHODS: We designed a prospective case-control study with 41 pregnant women. Subjects were divided into two groups: GDM and control. Betatrophin and GPIHBP1 levels were measured by ELISA method. Lipoprint LDL subfraction kit was used to perform LDL subfraction analysis electrophoretically. RESULTS: Serum levels of LDL6 subfraction, betatrophin, and GPIHBP1 were found to be higher in GDM group compared to the controls (p < 0.001). The mean LDL size were also found larger in GDM group. A positive correlation was found between betatrophin and GPIHBP1 levels (rho = 0.96, p < 0.001). CONCLUSIONS: Our findings suggest that betatrophin, and GPIHBP1 levels were found to be increased in GDM. This maybe the result of adaptive mechanisms in response to insulin resistance, but also this relationship should be evaluated for their effects on impaired lipid metabolism and lipoprotein lipase metabolism. There is a need for further prospective studies with larger samples to fully elucidate the mechanisms of this relationship both in pregnant patients and the other patient groups.

Comparison of orexin-A and neurofilament light chain levels in patients with relapsing-remitting multiple sclerosis: a pilot study.

Background and purpose: Multiple sclerosis is an autoimmune disease of the central nervous system, with myelin degeneration and Relapsing-Remitting Multiple Sclerosis (RRMS) as the most common type. The aim of this study was to determine the levels of Neurofilament Light Chain (NFL) and Orexin-A (OXA) in patients with RRMS and compare it with healthy control subjects' data. Methods: In this case-control study of 61 subjects, serum and cerebrospinal fluid samples were collected from 23 RRMS patients and 38 healthy control subjects. NFL and OXA levels were determined in cerebrospinal fluid and serum samples using enzyme-linked immunosorbent assay kits. Self-reported questionnaires were also administered to evaluate fatigue severity and impact. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value of NFL and OXA. Results: The NFL and OXA concentrations in cerebro-spinal fluid of RRMS patients were significantly higher than those of the control group (p < 0.001), but no sig-nificant difference was found in the serum concentrations (p = 0.842, p = 0.597, respectively). The cut-off values were found to be 1.194 ng/ml for NFL and 77.81 pg/ml for OXA in cerebrospinal fluid. A positive correlation was found between the Expanded Disability Status Scale and Epworth Sleepiness Scale in RRMS patients (ρ = 0.49, p = 0.045). Conclusion: These results suggest that increased levels of both NFL and OXA in cerebrospinal fluid reflect neuronal destruction in RRMS. Further research of neurodegeneration should focus on neuropeptides to determine the possible roles in RRMS pathogenesis.

The role of Wnt pathway antagonists in early-stage lung adenocarcinoma.

PURPOSE: We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors. MATERIALS AND METHODS: The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis. RESULTS: The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039). CONCLUSION: In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.

Investigation of the protective effect of nesfatin-1 on testicular ischaemia-reperfusion damage: An experimental study.

This study aimed to determine oxidative stress in the tissue after testicular torsion biochemically and histopathologically and to examine the effects of Nesfatin-1 treatment on this injury. Thirty-two rats were randomly divided into four groups: sham, torsion + detorsion (4 hr torsion followed by 1 hr detorsion), ischaemia/reperfusion + saline (I/R + S) and I/R + nesfatin-1. I/R + S group a single-dose saline treatment was administered intraperitoneally at the two-hundred-tenth minute of torsion (ischaemia; 10 cc/kg). Similarly, I/R + nesfatin-1 group a single dose of nesfatin-1 treatment was administered intraperitoneally at the two-hundred-tenth minute of ischaemia (10 µg/kg). Myeloperoxidase, total oxidant status and oxidative stress index values were significantly increased in the I/R and I/R + S group compared to the sham group. Superoxide dismutase was significantly decreased in the I/R + S group compared to the sham group. No significant difference was found between the I/R + nesfatin-1 group and the other I/R groups (I/R and I/R + S) in terms of biochemical parameters. The mean diameter of the seminiferous tubule decreased in the I/R groups. However, the mean diameter of the seminiferous tubules was not significantly different between the I/R + S group and the I/R + nesfatin-1 group. Thus, the administration of nesfatin-1 after ischaemia did not reduce testicular-oxidative stress.

Assessment of COL1A1 and MMP9 expression in patients with dermatochalasis.

PURPOSE: Dermatochalasis is a clinical condition characterized by loss of elasticity of eyelid skin and soft tissue, which typically affects the elderly population. The aim of this study is to investigate the mRNA expression levels of collagen type 1 alpha 1 (COL1A1) and matrix metalloproteinase-9 (MMP9) genes in dermatochalasis tissue. METHODS: The study group consisted of 15 patients who underwent upper eyelid blepharoplasty and were above 40 years old. The patients in our control group were divided into two subgroups according to their ages. Fourteen patients who were under 40 years old and had anterior blepharoptosis surgery for blepharoptosis were designed as the young control group. Sixteen patients who were older than 40 years old and had anterior blepharoptosis surgery for blepharoptosis were designed as the old control group. The patients in the dermatochalasis group were also evaluated according to their smoking status. Surgical tissue specimens were analyzed for COL1A1 and MMP9 mRNA gene expression levels by using real-time polymerase chain reaction. RESULTS: COL1A1 and MMP9 mRNA gene expression levels were not statistically different between the groups (p = 0.247; p = 0.052, respectively). When compared in means of the smoking habit, smokers in the dermatochalasis group exhibited higher COL1A1 mRNA expression levels when compared to nonsmokers (p = 0.008). MMP9 gene expression levels of smokers exhibited almost statistically higher levels but at the limit when compared to nonsmokers (p = 0.05). CONCLUSIONS: This study represents a preliminary study to detect the tissue changes at a molecular level in dermatochalasis, which is known to be related to connective tissue pathology. Collagen and MMPs are essential components of the extracellular matrix, and smoking might affect their gene expression. Further prospective studies on these regulatory genes and encoded protein levels with a larger group of patients may provide particular contribution to explaining the pathophysiology of dermatochalasis.

The association of low levels of nesfatin-1 and glucagon-like peptide-1 with oxidative stress in Parkinson's disease.

AIM: In Parkinson's disease (PD), oxidative stress plays a substantial role in degeneration of dopaminergic neurons at the substantia nigra. Recent reports describe nesfatin-1 and glucagon-like peptide-1 (GLP-1) as molecules with neuroprotective property that relieve oxidative stress. In this study, we aimed to determine the blood levels of nesfatin-1, GLP-1 and oxidative stress status in patients with PD. MATERIAL AND METHOD: Forty patients with PD, followed-up at the Department of Neurology of Mugla Sitki Kocman University Training and Research Hospital, were enrolled, as well as 40 age- and sex-matched participants as a control group. We determined and compared nesfatin-1, GLP-1, total antioxidant status (TAS), and total oxidant status (TOS) levels in patients with PD and control group. RESULTS: The mean GLP-1 and nesfatin-1 values of patients with PD were lower than those of the control group, whereas their mean TOS value was higher. The mean TAS values, on the other hand, did not reveal any significant difference between the patient and the control groups. CONCLUSION: The lower nesfatin-1 and GLP-1 levels, in addition to higher TOS levels, in patients with PD compared to those of control group suggest that the neuroprotective effects of these molecules might be related to the oxidative processes. Further studies are required to search for the impact of abovenamed molecules on the treatment option and the likelihood that they may slow down disease progression.

The methylation status of NKCC1 and KCC2 in the patients with refractory temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Methylation is a key epigenetic modification of DNA and regarding its impact on epilepsy, it is argued that "DNA methylation may play an important role in seizure susceptibility and maintenance of the disorder". DNA methylation status of KCC2 (SCL12A5) and NKCC1 (SCL12A2) associated with refractory temporal lobe epilepsy was investigated in our study. METHODS: Thirty-eight patients with temporal lobe epilepsy (TLE) who were diagnosed by video EEG monitoring and 32 healthy control subjects were included in the study. Twenty-three patients in TLE group were men and the remaining 15 were women. Among them, 27 had unilateral temporal focus (9 with right; 18 with left) and 11 patients had bilateral TLE. We analyzed promoter region methylation status of the KCC2 (SCL12A5) and NKCC1 (SCL12A2) genes in the case and control groups. Gene regions of interest were amplified through PCR and sequencing was accomplished with pyro-sequencing. RESULTS: We found a significant relationship between TLE and methylation on the NKCC1. However, there was no association between TLE and methylation on the KCC2 gene. Also, we found no association between right or left and unilateral or bilateral foci of TLE. There was no relationship between TLE and methylation on the NKCC1and KCC2 genes in terms of mesial temporal sclerosis in cranial MRI, head trauma or febrile convulsions. CONCLUSION: The methylation of NKCC1 can be a mecha-nism of refractory temporal lobe epilepsy. There are limited findings about DNA methylation in TLE. Therefore, further studies with large sample sizes are necessary.

Diagnostic Value of MiR-125b as a Potential Biomarker for Stage I Lung Adenocarcinoma.

BACKGROUND: We aimed at exploring biological functions of differentially expressed miRNAs during carcinogenesis, to identify miRNAs dysegulations involved in DNA repair mechanisms, and to evaluate potential of miRNAs as prognostic and diagnostic biomarkers for early lung adenocarcinomas (LAC). METHODS: We obtained 21 LAC and paired adjacent normal formalin-fixed, paraffinembedded lung tissues from patients who underwent curative resection for stage I LAC. We compared expression levels of eight miRNAs involved in the DNA repair mechanism between LAC and adjacent tissues. RESULTS: Expressions of Hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-125a-3p, hsa-miR- 125b-5p, hsa-miR-155-5p, and hsa-let-7a-5p were significantly up-regulated in stage I LAC tissues compared with those in the adjacent tissues. In addition, expressions of hsa-mir-9-5p, hsa-mir-24-3p, hsa-mir-125a-3p, hsa-mir-125b-5p, and hsa-mir-155-5p were significantly up-regulated in stage Ia LAC tissues, whereas expressions of hsa-mir- 125a-3p and hsa-mir-125b-5p were significantly up-regulated in stage Ib LAC tissues. Receiver operating characteristic (ROC) analysis revealed that AUROC of hsa-mir-125b- 5p was 0.875 (P < 0.001). CONCLUSION: Expression of hsa-mir-125b-5p could be used to distinguish LAC from adjacent tissues. Our result suggests that hsa-mir125b-5p can be a prognostic and diagnostic biomarker for LAC.

Methylation of cation-chloride cotransporters NKCC1 and KCC2 in patients with juvenile myoclonic epilepsy.

The etiology of juvenile myoclonic epilepsy (JME) is still unknown and the process of elaboration of multiple genetic mechanisms is ongoing. The aim of this study was to investigate the potential role of NKCC1 (SCL12A2) and KCC2 (SCL12A5) in JME by comparing their DNA methylation status in patients with JME versus healthy controls. Forty-nine patients with JME and 39 healthy individuals were compared for DNA methylation at the 5CpG islands. A total of 71 (81%) samples were found to have methylation in the NKCC1 gene, 36 (73%) from patients and 35 (90%) from healthy individuals. Out of the KCC2 samples, 50 (57%) were found to have methylation, 33 (67%) from patients and 17 (44%) from healthy individuals. In patients with JME, methylation of NKCC1 (73%) was lower than its methylation in the controls (90%) (p = 0.047). On the other hand, methylation of KCC2 in patients with JME (67%) was greater than the methylation in the controls (44%) (p = 0.022). Twenty-eight patients were treated with VPA and ongoing medications were not found to be associated with methylation (p > 0.05). In the present study, we determined significantly lower NKCC1 DNA methylation and significantly higher KCC2 DNA methylation levels in patients with JME compared with the healthy controls. This implies that NKCC1 expression can be higher and KCC2 expression can be reduced in affected people. Further studies that investigate the potential effect of DNA methylation mechanisms regulating gene expression on seizure activity and how they change JME network activity will be helpful.

The effect on outcomes of the application of circumferential cerclage cable following intramedullary nailing in reverse intertrochanteric femoral fractures.

INTRODUCTION: The aim of this study was to evaluate the effect on union results of the application of cerclage cable around the lateral femoral wall (LFW) in postoperative fracture displacement. PATIENTS AND METHODS: A retrospective evaluation was made of all the cases of reverse intertrochanteric fractures over a 7-year period in a trauma center. The study included 69 fractures treated with intramedullary nailing. The age of the patients, postoperative reduction quality and complications such as mechanical failure and non-union (1.4%) were obtained from the medical records. Changes in the neck-shaft angle, the amount of LFW displacement and telescoping of proximal femoral nail antirotation blades and lag screws were measured on anteroposterior and lateral radiographs. The functional evaluation of the Harris Hip Score was recorded at the final follow-up examination. RESULTS: The mean age of the patients was 56.31 years (range 18-93 years). Closed reduction was applied in 37 (53.7%) cases, open reduction in 10 (14.5%) and with cerclage cable in 22 (31.8%). Mechanical failure developed in 8 (11.5%) cases where cerclage cable was not used. In 2 of these 8 cases, open reduction was successful. In the patients where cerclage cable was applied, no mechanical failure developed and no case underwent revision surgery. In the cases where cerclage cable was not used, a significantly higher rate of telescoping was found. (p = 0.001). The application of cerclage cable was seen to significantly reduce the amount of LFW displacement (2.23 mm vs 8.86 mm) and shorten the time to partial weight bearing (p = 0.000). CONCLUSION: In reverse intertrochanteric fractures, the application of circumferential cerclage cable with cephalomedullary nailing contributes to primary stability and accelerates mobilization. Therefore, it can be considered a good option. It reduces the risk of failure internal fixation for intertrochanteric fracture.

Association between obstructive sleep apnea syndrome and waist-to-height ratio.

PURPOSE: Obesity is among the known risk factors for obstructive sleep apnea syndrome (OSAS). In this study, our aim was to investigate the correlation of waist-to-height ratio, an indicator of central obesity, with presence and severity of OSAS; to compare the use of this ratio with the use of waist circumference and body mass index (BMI); and to determine OSAS-related cutoff values. METHODS: The patient records were retrospectively analyzed for whom a polysomnography was conducted at our sleep. Sex, age, Apnea-Hypopnea Index (AHI), waist circumference, height, and BMI values of those patients were recorded. AHI scores were used to classify severity of OSAS. RESULTS: The study included 437 OSAS patients and 72 control cases. Out of the patient group, OSAS was severe in 208 (47%) patients, moderate in 124 (28%), and mild in 105 (24%) of them. In the group of OSAS patients, waist-to-height ratio, waist circumference, and BMI were higher compared to the control group with a further difference of all three parameters among severe, moderate, mild OSAS, and controls both in males and females. Cutoff values for OSAS of females were 95.5 cm for waist circumference, 0.595 for waist-to-height ratio, and 27.75 for BMI whereas the cutoff values of males were 100.5 cm, 0.575, and 27.75, respectively. CONCLUSIONS: A high value of waist circumference, waist-to-height ratio, and BMI is associated with the presence and severity of OSAS. We have determined the cutoff values of the studied anthropometric measurements in both sexes for OSAS and severe OSAS.

Correlation of Prognostic Gleason Grade Grouping and Histopathological Parameters: Can the "New System" Reflect the Pathological Perspective for Prognosis?

BACKGROUND: Gleason score is one of the strongest prognostic predictors of prostate cancer;however, a change was published which is a 5 step grouping system of prostatic adenocarcinomas according to their Gleason scores. The aim of this study is to determine the relationship between histopathological findings and prognosis of tumors subgrouped according to the new Gleason grade grouping system. METHODS: A total of 163 radical prostatectomies subgrouped into 5 prognostic groups were investigated for prognostic features such as pathological stage, extraprostatic extension, surgical margin status, involvement of seminal vesicles, perineural invasion, necrosis, vascular invasion, ganglionic involvement, concomitant high grade prostatic intraepithelial neoplasia (HPIN) in addition to other microscopic features of tumors such as the presence of mucin and foamy cytoplasmic change between groups. RESULTS: The mean age of patients was 65.72 ± 6.67 (min = 46, max = 82). Among 131 patients who completed the study, the mean prostate specific antigen (PSA) value was 11.29 ± 10.88. The statistically significant factors were significantly related to both the original Gleason and the prognostic grade groups.The recurrence rate of grade group 4 patients (57%) was significantly higher than grade group 3 patients (8%) (P = 0.038). But no significant difference was found between grade group 4 and 5 (P = 0.25). CONCLUSION: Grade grouping systems reflect prognostic differences but adapting this new system into routine evaluation of patients may confuse the clinicians; however, pathology reports stating both the traditional Gleason score and the new prognostic group may soften the transition.

A comparison of the InterTan nail and proximal femoral fail antirotation in the treatment of reverse intertrochanteric femoral fractures.

The aim of this study was to compare the clinical and radiological results of InterTan nail and proximal femoral nail antirotation (PFNA) in the treatment of reverse intertrochanteric fractures (AO/OTA 31-A3). The study included a total of consecutive patients who presented at trauma centre with a reverse intertrochanteric fracture between in the last 7 years. Treatment was applied with PFNA in 33 patients and with InterTan nail in 36. Evaluation was made from the radiographs taken on postoperative day 1 and at the final follow-up examination of changes in the femoral neck and shaft angulation, measurement of telescoping of blade and lag screws and reduction quality. The mean telescoping was measured as 7.21±7.13mm in the PFNA group and 4.18±4.32 mm in the InterTan group (p = 0.039). Mechanical failure was seen in 8 (24.2%) cases in the PFNA group and in one case of the InterTan group. Cut-out was observed in 4 cases of the PFNA group and in none of the InterTan group. No statistically significant difference was determined between the groups in respect of time to union and functional scores (p = 0.573 and p = 0.294). The use of InterTan nailing in the fixation of reverse intertrochanteric fractures provided better clinical and radiological results compared to PFNA in terms of less telescoping, less change in the neck shaft angle and lower complication rates.

Evaluation of Erythroid Disturbance and Thiol-Disulphide Homeostasis in Patients with Psoriasis.

This study aims to assess how mean corpuscular volume (MCV), red cell distribution width (RDW), and thiol-disulphide homeostasis are altered in psoriasis patients. This is a cross-sectional review of 76 healthy volunteers and 87 psoriasis patients who were consecutively admitted to the department of dermatology. Psoriasis patients and healthy controls were statistically similar with respect to age, sex, body mass index, blood pressures, and disease duration (p > 0.05 for all). When compared to healthy controls, psoriasis patients had significantly higher MCV, RDW, C-reactive protein (CRP), disulphide, disulphide/native thiol, and disulphide/total thiol (p < 0.001 for all). However, psoriasis patients had significantly lower native thiol and native thiol/total thiol (p = 0.009 and p < 0.001, respectively). When compared to healthy controls, the patients with Psoriasis Area Severity Index (PASI) ≤ 10 and patients with PASI > 10 had significantly higher MCV, disulphide, disulphide/native thiol, and disulphide/total thiol (p < 0.001 for all). The patients with PASI ≤ 10 and patients with PASI > 10 had significantly lower native thiol/native thiol than healthy controls (p < 0.001 for all). The psoriasis patients with PASI > 10 had significantly higher RDW and CRP than healthy controls and patients with PASI ≤ 10 (p < 0.001 for all). Disulphide, disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol correlate significantly with both PASI scores and disease duration. Thiol-disulphide homeostasis is enhanced in psoriasis patients. Ongoing inflammation and increased oxidative stress in psoriasis patients also trigger the formation of prooxidants which are neutralized by antioxidants such as thiols. That is why plasma thiol levels are decreased in psoriasis patients.

Agreement between the Turkey Guidelines and the Fracture Risk Assessment Tool®-based Intervention Threshold.

BACKGROUND: The aim of this study was to evaluate the agreement between the fracture-risk assessment tool (FRAX®)-based intervention strategy in Turkey and the recommendations published in the Healthcare Practices Statement (HPS). METHODS: This descriptive cross-sectional study included individuals aged 40 to 90 years who were previously diagnosed as having osteoporosis but had not received any treatment. The intervention thresholds recommended by the National Osteoporosis Foundation for treatment were used. The criteria necessary for the start of administration of pharmacological agents in osteoporosis treatment were evaluated on the basis of the HPS guidelines. RESULTS: Of the 1,255 patients evaluated, 161 (12.8%) were male and 1,094 (87.2%) were female. In the evaluation, according to HPS, treatment was recommended for 783 patients (62.4%; HPS+) and not recommended for 472 (37.6%; HPS-). Of the 783 HPS+ patients, 391 (49.9%) were FRAX+, and of the 472 HPS- patients, 449 (95.1%) were FRAX-. A statistically significant difference was observed between the treatment recommendations of HPS and FRAX® (P<0.001). In the age group of 75 to 90 years, excellent agreement was found between the two strategies (Gwet's agreement coefficient 1=0.94). As age increased, the agreement between the two treatment strategies also increased. CONCLUSIONS: The FRAX® model has different treatment recommendation rates from the HPS. The agreement between the two is at a minimal level. However, as age increased, so did the agreement between the FRAX® and the HPS treatment recommendations. In the recommendation to start pharmacological treatment primarily based on age, non-medical interventions that preserve bone density should be evaluated.

Evaluation of inter- and intra-observer reliability of current classification systems for subtrochanteric femoral fractures.

INTRODUCTION: To evaluate the inter- and intra-observer reliability of the Russell Taylor, Seinsheimer and AO classification systems, and to investigate whether or not the experience of the surgeon had any effect on the classification. PATIENTS AND METHODS: All the radiographs of 35 patients with subtrochanteric femur fracture were classified by 16 observers using the Russell Taylor, Seinsheimer and 31-AO classifications. Two groups of observers were formed of eight orthopedic surgeons, each with at least five-year experience and eight orthopedic assistants, from six different hospitals, who were invited to participate in the study. All the observers reviewed all the X-rays at this first evaluation. At 6 weeks after the first evaluation, the same radiographs were presented to each observer again in a random order and all the observers were requested to classify the fractures again. To evaluate the inter- and intra-observer reliability, the Fleiss kappa and Cohen's kappa values were used. RESULTS: In the inter-observer reliability, the mean values of the two evaluations for the Russell Taylor classification were determined to be κ:0.724 (substantial) for the specialists and κ:0.722 (substantial) for the assistants. Using the Seinsheimer classification, the mean values were κ:0.691 (substantial) for the specialists and κ:0.629 (substantial) for the assistants, and for the AO classification, the mean values were κ:0.279 (fair) for the specialists and κ:0.291 (fair) for the assistants. In the intra-observer reliability, the median values for the Russell Taylor classification were determined to be κ:0.955 (almost perfect) for the specialists and κ:0.855 (almost perfect) for the assistants. Using the Seinsheimer classification, the median values were κ:0.915 (almost perfect) for the specialists and κ:0.900 (almost perfect) for the assistants, and for the AO classification, the median values were κ:0.665 (substantial) for the specialists and κ:0.695 (substantial) for the assistants. CONCLUSIONS: As both the Russell Taylor and Seinsheimer classifications were found to be more reliable and reproducible than the AO classification for subtrochanteric femoral fractures, they can be considered to be more valuable in clinical practice and communication. The experience of the surgeons was not found to have any significance in the evaluation of these three classification systems in these types of fractures.

Impact and interactions between smoking and traditional prognostic factors in lung cancer progression.

BACKGROUND: Cigarette smoking is a well-known risk factor of lung carcinogenesis. The clinical impact of smoking on lung cancer metastases and survival remains unclear. We sought to investigate the effect of smoking intensity on lung cancer treatment failure (represented by overall survival), and the interactions between smoking and clinicopathological factors in lung cancer progression. METHODS: Clinical information was obtained from four non-small cell lung cancer patient cohorts (n=347). Twenty patients were excluded from the analysis because their smoking history was not available. The distribution of smoking intensity on patient age (> or =60 years or <60 years), gender, tumor differentiation (poor, moderate and well differentiated), and clinical stage (1, 2, or 3) was assessed with Kruskal-Wallis rank sum tests. The effect of smoking on cause-specific lung cancer mortality was estimated by using Cox proportional hazard models and Kaplan-Meier analysis. The interactions between clinicopathological factors and smoking intensity with regard to lung cancer overall survival were evaluated with analysis of variance (ANOVA) for Cox modeling. RESULTS: Greater smoking intensity at diagnosis was found in older patients (> or =60 years; p=0.022), male (p=1.35e-7), poorly differentiated tumors (p=8.51e-5), patients with tumor stage 2 (p=0.031), and squamous cell lung cancer patients (p=2.2e-16). Patients who smoked more than 61 packs/year had an increased risk for lung cancer recurrence (hazard ratio=1.41, 95% CI: [1.03, 1.94], log-rank p=0.032) and shorter overall survival period (log-rank p=0.033, Kaplan-Meier analysis) than those who smoked less than 61 packs/year. ANOVA analysis showed that smoking intensity (p=0.03) and tumor stage (p=1.2e-6) are the only significant prognostic factors of lung cancer, whereas patient age, gender, and tumor differentiation were not significant in lung cancer prognostication. There were significant interactions between smoking and clinical stage (p=0.02) as well as patient age and tumor differentiation (p=0.03) in lung cancer progression. CONCLUSION: Smoking intensity at diagnosis is an independent, significant prognostic factor of non-small cell lung cancer. This factor could be used in patient selection for chemoprevention of tumor metastases and relapse. Additionally, the information may be used for clinically relevant tobacco prevention and intervention messages.

An integrative genomic and proteomic approach to chemosensitivity prediction.

New computational approaches are needed to integrate both protein expression and gene expression profiles, extending beyond the correlation analyses of gene and protein expression profiles in the current practices. Here, we developed an algorithm to classify cell line chemosensitivity based on integrated transcriptional and proteomic profiles. We sought to determine whether a combination of gene and protein expression profiles of untreated cells was able to enhance the performance of chemosensitivity prediction. An integrative feature selection scheme was employed to identify chemosensitivity determinants from genome-wide transcriptional profiles and 52 protein expression levels in 60 human cancer cell lines (the NCI-60). A set of 118 anti-cancer drugs whose mechanisms of action were putatively understood was evaluated. Classifiers of the complete range of drug response (sensitive, intermediate, or resistant) were generated for the evaluated anti-cancer drugs, one for each agent. The classifiers were designed to be independent of the cells' tissue origins. The classification accuracy of all the evaluated 118 agents was remarkably better (P<0.001) than that would be achieved by chance. Furthermore, 76 out of the 118 classifiers identified from integrated genomic and protein profiles significantly (P<0.05) improved the accuracy of protein expression-based classifiers identified previously. These results demonstrate that our integrated genomic and proteomic approach enhances the performance of chemosensitivity prediction. This study presents a new analytical framework to identify integrated gene and protein expression signatures for predicting cellular behavior and clinical outcome in general.