Prognostic Factor For Poor Outcome Research Articles

Prognostic value of corpus callosum injuries in severe head trauma.

This study was performed to investigate the relationship between corpus callosum (CC) injury and prognosis in traumatic axonal injury (TAI). We retrospectively reviewed 264 patients with severe head trauma who underwent a conventional MR imaging in the first 60days after injury. They were selected from a prospectively collected database of 1048 patients with severe head trauma admitted in our hospital. TAI lesions were defined as areas of increased signal intensity on T2 and FLAIR or areas of decreased signal on gradient-echo T2. We attempted to determine whether any MR imaging findings of TAI lesions at CC could be related to prognosis. Neurological impairment was assessed at 1 year after injury by means of GOS-E (good outcome being GOS-E 4/5 and bad outcome being GOS-E <4). We adjusted the multivariable analysis for the prognostic factors according to the IMPACT studies: the Core model (age, motor score at admission, and pupillary reactivity) and the Extended model (including CT information and second insults). We found 97 patients (37%) with TAI at CC and 167 patients (63%) without CC lesions at MR. A total of 62% of the patients with CC lesions had poor outcome, whereas 38% showed good prognosis. The presence of TAI lesions at the corpus callosum was associated with poor outcome 1year after brain trauma (p < 0.001, OR 3.8, 95% CI: 2.04-7.06). The volume of CC lesions measured on T2 and FLAIR sequences was negatively correlated with the GOS-E after adjustment for independent prognostic factors (p = 0.01, OR 2.23, 95% CI:1.17-4.26). Also the presence of lesions at splenium was statistically related to worse prognosis (p = 0.002, OR 8.1, 95% CI: 2.2-29.82). We did not find statistical significance in outcome between hemorrhagic and non-hemorrhagic CC lesions. The presence of CC is associated with a poor outcome. The total volume of the CC lesion is an independent prognostic factor for poor outcome in severe head trauma.

Reduced decorin expression in the tumor stroma correlates with tumor proliferation and predicts poor prognosis in patients with I-IIIA non-small cell lung cancer.

Decorin, chiefly synthesized by tumor stroma, is known as a tumor suppressor. However, the clinical and prognostic significance in lung cancer remained unclear. Here, decorin and Ki67 expression was detected by immunohistochemistry (IHC) in I-IIIA non-small cell lung cancer (NSCLC) tissues (n=264) in comparison to adjacent normal tissues (n=40). The relationship between the expression of decorin and clinical characteristics, as well as Ki67 index and prognosis, was analyzed. Decorin expression was decreased in both the stroma (P<0.001) and the tumor cells (P=0.038) in NSCLC specimens. There was the lowest stromal expression of decorin in patients with G3 adenocarcinoma and higher Ki67 index in the stromal decorin-negative group. The Kaplan-Meier survival analysis demonstrated that lack of decorin in the stroma was correlated with a shorter DFS and OS (P=0.005 and P=0.010, respectively), while there was no significant association between decorin expression in the tumor cells and outcome. Multivariate analysis showed that reduced expression of decorin in the stroma was an independent prognostic factor for poor outcome including DFS (HR=5.685, 95% CI 0.493-0.933; P=0.017) and OS (HR=6.579, 95% CI 0.484-0.908; P=0.010). Negative decorin in the stroma combined with high Ki67 index predicted poorer outcomes for I-IIIA NSCLC patients. Our results provide data on decorin expression in both the stroma and cancer cells in NSCLC and reveal that reduced expression of stromal decorin correlates with high Ki67 index and has prognostic significance for poor outcome in I-IIIA NSCLC. Our data suggest that evaluating stromal decorin expression might be useful in assessing the prognosis and malignant potential.

Prognostic factors for mortality in pediatric acute poststreptococcal glomerulonephritis

Background Acute post-streptococcal glomerulonephritis (APSGN) is one of the most common causes of glomerular disease in developing countries, including Indonesia. It can lead to end stage renal failure and higher mortality rates. To decrease morbidity and mortality, it is important to understand the prognostic factors affecting the disease.Objective To identify prognostic factors affecting outcomes in pediatric APSGN patients.Methods Study data were collected from medical records of patients with APSGN hospitalized in Wahidin Sudirohusodo Hospital, Makassar in 2009-2013. Possible prognotic factors analyzed were gender, age, nutritional status, level of consciousness, as well as proteinuria, hemoglobin, serum albumin, urea, and creatinine levels.Results Of 86 subjects, 82 (95.3%) survived and 4 (4.7%) died. Fifty-three (61.6%) patients were male and 33 (38.4%) were female. Subjects’ ages ranged from 3.42 to 14.67 years, with a mean age of 9.36 years. Multivariate analysis revealed serum creatinine level &gt;1.5 mg/dL to be an independent prognostic factor for mortality in children with APSGN (AOR 15.43; 95%CI 1.31 to 181.7; P=0.03).Conclusion High serum creatinine level is an independent prognostic factor for poor outcomes in children with APSGN. [Paediatr Indones. 2016;56:166-70.].

Poor Prognostic Outcome in Cerebral Venous Sinus Thrombosis Associated with Dyskinesia and Elevated Platelet Volume.

Although about 80% of patients with cerebral venous sinus thrombosis have a good prognosis, some patients develop severe complications and a small proportion do not survive. The study included patients who had been diagnosed with cerebral venous sinus thrombosis in our hospital from May 2008 to February 2014. Based on the modified Rankin Scale (mRS) scores at 3 months for outcome, the patients were divided into two groups: good prognosis (mRS score ≤ 2) and poor prognosis (mRS score > 2). Univariate and multivariate regression analysis were performed to identify significant prognostic factors for poor outcome. A total of 86 patients with cerebral venous sinus thrombosis, 54 males and 32 females, average age 41.3 years (range, 3-83 years), were enrolled. Of these 86 patients, 64 (74.4%) had a good prognosis and 22 (25.6%) a poor prognosis. Univariate analysis revealed that dyskinesia was a significant risk factor (factor with odds ratio >1) for poor prognosis. In multivariate analysis, the risk of poor prognosis in patients with dyskinesia was 23 times higher than for those without dyskinesia (p < 0.001). Thrombosis of the sinus transervus was found to reduce the risk of poor prognosis in both univariate and multivariate analysis. Most patients with cerebral venous sinus thrombosis have a good prognosis but patients with dyskinesia have a poorer prognosis.

High Ki67 Expression has Prognostic Value in Surgically-Resected T3 Gastric Adenocarcinoma.

Antigen KI-67 (Ki67) plays a critical role in regulation of cell proliferation and has prognostic value in several types of cancer; however, the relationship between Ki67 expression and prognosis in resected T3 gastric adenocarcinoma (GA) has not yet been investigated. Retrospective analysis of 693 patients with T3 GA who underwent surgical resection at a single institution between July 2003 and December 2009 was performed. Ki67 expression in tumor tissues was examined using immunohistochemistry (IHC); the associations between Ki67 and prognosis/survival outcomes were assessed using the Chi-square test, Kaplan-Meier survival analysis, log-rank test, and univariate and multivariate analysis. High Ki67 expression (IHC score > or = 3+) was observed in 335/693 (48.34%) of cases. Ki67 expression was significantly associated with distant metastasis, 5-year median recurrence-free survival time in months (MRFST), and 5-year median overall survival time in months (MOST). Median recurrence and overall survival were 20 and 28 months. High Ki67 expression was associated with shorter MRFST (13 vs. 27 months, p < 0.001) and MOST (21 vs. 35 months, p < 0.001 compared to low K67 expression). Multivariate analysis demonstrated that high K167 expression was an independent prognostic factor for an increased risk of recurrence (p = 0.001) and distant metastasis (p = 0.003) and poorer overall survival (p = 5.33 x 10(-5)). High Ki67 expression was frequently observed in resected T3 GA and was a significant prognostic factor for poor outcome with respect to recurrence, distant metastasis and overall survival. Ki67 may represent a useful prognostic biomarker for resected T3 GA.

Combination of galectin inhibitor GCS-100 and BH3 mimetics eliminates both p53 wild type and p53 null AML cells

Galectin 3 (LGALS3) expression is prognostic for poor survival in acute myeloid leukemia (AML) patients. GCS-100 is a novel galectin inhibitor that may prove useful for AML therapy. In this study, we found that GCS-100 induced apoptosis in AML cells. The agent reduced MCL-1 expression suggesting that GCS-100 could be more effective when combined with a BH3 mimetic. Indeed, potent synergistic cytotoxicity was achieved when GCS-100 was combined with ABT-737 or ABT-199. Furthermore, the GCS-100/ABT-199 combination was effective against primary AML blast cells from patients with FLT3 ITD mutations, which is another prognostic factor for poor outcome in AML. This activity may involve wild-type p53 as shRNA knockdown of LGALS3 or galectin 1 (LGALS1) sensitized wild-type p53 OCI-AML3 cells to GCS-100/ABT-737-induced apoptosis to a much greater extent than p53 null THP-1 cells. Suppression of LGALS3 by shRNA inhibited MCL-1 expression in OCI-AML3 cells, but not THP-1 cells, suggesting the induced sensitivity to ABT-737 may involve a MCL-1 mediated mechanism. OCI-AML3 cells with LGALS1 shRNA were also sensitized to ABT-737. However, these cells exhibited increased MCL-1 expression, so MCL-1 reduction is apparently not required in this process. A role for p53 appears important as GCS-100 induces p53 expression and shRNA knockdown of p53 protected OCI-AML3 cells from the cytotoxic effects of the GCS-100/ABT-737 treatment combination. Our results suggest that galectins regulate a survival axis in AML cells, which may be targeted via combined inhibition with drugs such as GCS-100 and ABT-199.

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis.

Background:The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because <i>NAB2-STAT6</i> gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs.Methods:This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically.Results:In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers.Conclusions:Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.

Characteristics and treatment outcomes of patients with multi-drug resistant tuberculosis at a tertiary care hospital in Peshawar, Pakistan.

Objectives:To determine characteristics and treatment outcomes of multidrugs resistant tuberculosis (MDR-TB) patients and risk factors for poor outcomes in MDR-TB patients in a tertiary care hospital in Peshawar, Pakistan.Methods:This retrospective study was conducted at the Programmatic Management of Drug Resistant TB Unit, Lady Reading Hospital Peshawar, Pakistan and included all MDR-TB patients registered between January 2012 and December 2012. A special proforma was used for data collection. Analysis was performed using SPSS version 16, after exporting data from the proforma. Differences in proportions were assessed using Pearson’s Chi square test whereas for predictors of poor outcomes, multivariate logistic regression analysis with Wald Statistical criteria using backward elimination method was performed.Results:The treatment success rate was 74.3%. In univariate analysis, poor outcomes were associated in patients with age ≥44 years (odds ratio [OR]=0.250; 95% confidence interval [CI]: 0.114-0.519, p=0.001), rural residence (OR=0.417; 95% CI: 0.18-0.937, p=0.03), lung cavitation (OR=0.22; 95% CI, 0.007-0.067, p=0.001), resistance to second line drugs (SLD) (OR=3.441; 95% CI: 1.579-7.497, p=0.001), and resistance to ofloxacin (OR=2.944; 95% CI: 1.361-6.365, p=0.005); whereas multivariate logistic regression analysis, poor outcomes were associated in patients with age ≥44 years (OR=0.249, 95% CI: 0.075-0.828, p=0.023), rural residence (OR=0.143, 95% CI: 0.052-0.774, p=0.032), and cavitatory lungs (OR=0.022, 95% CI: 0.007-0.072, p=0.000).Conclusion:The MDR-TB patient needs special attention for better treatment outcomes. The presence of older age, rural area residence, resistance to ofloxacin, SLD resistance, and cavitary disease are independent prognostic factors for poor outcome in patients with MDR-TB.

Prognostic factors of Streptococcus pneumoniae infection in adults

ObjectivesThe mortality of severe sepsis has markedly decreased since the implementation of the Surviving Sepsis Campaign guidelines. The next logical step is to examine the necessity of individualized management guidelines for targeted therapy against specific bacteria. Streptococcus pneumoniae is the leading cause of community-acquired severe sepsis; however, little is known regarding the prognostic factors in adult patients with S pneumoniae sepsis. We aimed to identify prognostic factors in patients with S pneumoniae sepsis and to explore a subgroup of patients at high risk for death with detailed Sequential Organ Failure Assessment (SOFA) score analysis. MethodsWe retrospectively reviewed the records of patients with S pneumoniae infection treated between 1st January 2006 and 31st July 2012. We identified prognostic factors for 28-day mortality using univariate and multivariate logistic regression models. ResultsOf 171 patients (median age, 72 years) with S pneumoniae infection who were included in this study, the 28-day mortality was 17% (29/171). The SOFA score (odds ratio, 2.25; 95% confidence interval, 1.60-3.18; P < .001) and bacteremia (odds ratio, 19.0; 95% confidence interval, 4.06-90.20; P < .001) were identified as prognostic factors for the 28-day mortality. In a subgroup analysis with a cutoff value of the SOFA score determined by receiver operating characteristic analysis, patients with bacteremia and a SOFA score of at least 7 had a significantly higher mortality than did patients without bacteremia and a SOFA score lower than 7 (84% vs 0%, respectively). ConclusionsBacteremia and a SOFA score at least 7 were independent prognostic factors of poor outcome in S pneumoniae sepsis.

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP. Of the 463 patients, 269 (58%) had survivin overexpression with a cutoff of >25%, associated with an International Prognostic Index score of >2 (P=0.015), disease in ≥2 extranodal sites (P=0.011), and a high Ki-67 index (P<0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivin-negative patients (P=0.033); multivariate analysis confirmed that in these patients, survivin overexpression was an independent prognostic factor for survival. Among patients with wild-type p53 overexpression, the overall survival and progression-free survival rates of the survivin-positive group were significantly lower than those of the survivin-negative group (P=0.035 and P=0.04 respectively). In STAT3-positive patients, survivin overexpression was associated with significantly better survival. Among patients with activated B cell-like disease, survivin-positive compared with survivin-negative groups had significantly different gene expression signatures, including genes involved in mitosis or tumor cell proliferation. Our results indicate that survivin is an independent prognostic factor for poor outcome in patients with activated B cell-like disease treated with the R-CHOP regimen, and patients with survivin-positive activated B cell-like diffuse large B-cell lymphoma seem to benefit less from this treatment and may require additional novel agents.

Chronic Lymphocytic Leukemia in the Elderly: Epidemiology and Proposed Patient-Related Approach.

Chronic lymphocytic leukemia (CLL) occurs primarily in the elderly, and the majority of deaths attributable to CLL occur in persons 65 years of age or older. The greater number of comorbidities and reduced functionality associated with aging have also made successful treatment of CLL in the elderly more difficult. The authors reviewed current epidemiology and guidelines for treatment of CLL, as well as recently approved therapies and studies of physiological aging. Determination of physiological age and performance of a thorough geriatric assessment play critical roles in the selection of optimal therapeutic approaches for older patients diagnosed with CLL. Older age, expressed via a frailty index, is a prognostic factor for poorer outcome in patients with CLL. However, several novel treatment options may result in reduced mortality and lessened treatment-related toxicity in older CLL patients.

Prognostic factors of poor outcome in patients with upper limb replantation surgery admitted to the icu

Methods Observational study of patients with ERS during a period of seven years (2008-2014). Computer research of electronic medical records in databases was conducted. We obtained a sample of 60 cases and classified them into two groups: good and poor outcome. We analyzed: epidemiological variables (age, smoking, diabetes, arteriopathy) variables related with injury mechanism (degloving, flattening, large bone lesion, neural lost and vascular affectation), surgery and postoperative care (amines, mechanical ventilation, transfusion, ICU stay). We compared the factors associated with poor outcome in both groups

Could an analysis of mean corpuscular volume help to improve risk stratification in non-anemic patients with acute myocardial infarction?

Nowadays, when the majority of patients with acute myocardial infarction (AMI) are treated with primary percutaneous coronary intervention and modern pharmacotherapy, risk stratification becomes a challenge. Simple and easily accessible parameters that would help in a better determination of prognosis are needed. The aim of the study was to estimate the prevalence of high mean corpuscular volume (MCV, defined as MCV > 92 fL) and to establish its prognostic value in non-anemic patients with AMI. We retrospectively analyzed the data of 248 consecutive non-anemic patients hospitalized due to AMI (median age: 65 [59-76] years, men: 63%, ST segment elevation myocardial infarction: 31%, and median left ventricular ejection fraction [LVEF]: 50%). The prevalence of high MCV was 39 ± 6% (± 95% confidence interval) in the entire AMI population. High MCV was more prevalent in males, patients with low body mass index, non-diabetics and cigarette smokers (all p < 0.05). During the 180-day follow-up, there were 38 (15%) events, defined as another AMI or death. In a multivariable Cox proportional hazard model, female gender (p < 0.01), low LVEF (p < 0.001), previous AMI (p < 0.05), arterial hypertension (p < 0.05), and high MCV (p < 0.001) were prognosticators of pre-defined events. In non-anemic patients with AMI, high MCV is an independent prognostic factor of poor outcome defined as another AMI or death.

Alternative lengthening of telomeres and loss of ATRX are frequent events in pleomorphic and dedifferentiated liposarcomas

Telomerase activation and alternative lengthening of telomeres are two major mechanisms of telomere length maintenance. Soft tissue sarcomas appear to use the alternative lengthening of telomeres more frequently. Loss of α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated protein 6 (DAXX) expression has been implicated in the pathogenesis of alternative telomere lengthening in pancreatic endocrine neoplasm and glioma. The mechanism leading to the alternative lengthening of telomeres in liposarcoma remains unknown. Whereas alternative telomere lengthening was determined to be an indicator of poor prognosis in liposarcomas as a whole, its prognostic power has not been verified in any subtype of liposarcoma. In this study, we characterized the status of alternative telomere lengthening and expression of ATRX and DAXX in 111 liposarcomas (28 well-differentiated, 52 dedifferentiated, 20 myxoid or round cell, and 11 pleomorphic liposarcomas) by telomere fluorescence in situ hybridization and immunohistochemistry, respectively. Alternative lengthening of telomere was observed in 0% (0/16) of well-differentiated, 30% (14/46) of dedifferentiated, 5% (1/19) of myxoid or round cell, and 80% (8/10) of pleomorphic liposarcomas. Eighteen (16%) and one (1%) tumors were negative for ATRX and DAXX immunostaining, respectively. Remarkably, all cases with loss of either ATRX or DAXX expression had alternative lengthening of telomeres, and 83% (19/23) of tumors that had alternative lengthening of telomeres showed loss of either protein. The correlation between loss of either ATRX or DAXX and alternative telomere lengthening was 100% in dedifferentiated liposarcoma. The presence of alternative telomere lengthening in dedifferentiated liposarcoma suggested poor overall survival (hazard ratio=1.954, P=0.077) and was the most significant indicator of short progression-free survival (hazard ratio=3.119, P=0.003). In conclusion, we found that ATRX loss was the most likely mechanism of alternative telomere lengthening in liposarcoma and alternative telomere lengthening was a prognostic factor of poor outcome in dedifferentiated liposarcoma.

Prognostic performance of inflammation-based prognostic indices in patients with resectable colorectal liver metastases.

A range of prognostic cellular indices of the systemic inflammatory response, namely the neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognostic nutritional index (PNI), have been developed and found to have prognostic utility across varied malignancies. The current study is the first to examine the prognostic value of these six inflammatory scores in patients with resectable colorectal liver metastases (CRLM). Data from 302 consecutive patients undergoing surgery for resectable CRLM were evaluated. The prognostic influence of clinicopathological variables and the inflammatory scores NLR, dNLR, PLR, LMR, COP-NLR and PNI upon overall survival (OS) and cancer-specific survival (CSS) were determined by log-rank analysis and univariate and multivariate Cox regression analyses. High preoperative NLR was the only inflammatory variable independently associated with shortened OS (HR 1.769, 95 % CI 1.302-2.403, P < 0.001) or CSS (HR 1.927, 95 % CI 1.398-2.655, P < 0.001) following metastasectomy. When NLR was replaced by dNLR in analyses, high dNLR was independently associated with shortened OS (HR 1.932, 95 % CI 1.356-2.754, P < 0.001) and CSS (HR 1.807, 95 % CI 1.209-2.702, P = 0.004). The inflammatory scores PLR, LMR, COP-NLR and PNI demonstrated no independent association with either overall or cancer-specific survival in the study population. Our findings support high preoperative NLR and dNLR as independent prognostic factors for poor outcome in patients undergoing CRLM resection, with prognostic value superior to other cellular-based systemic inflammatory scores.

Markers of inflammation and mortality in a cohort of patients with alcohol dependence.

Inflammation and intestinal permeability are believed to be paramount features in the development of alcohol-related liver damage. We aimed to assess the impact of 3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on mid-term mortality of patients with alcohol dependence.This longitudinal study included patients with alcohol dependence admitted for hospital detoxification between 2000 and 2010. Mortality was ascertained from clinical charts and the mortality register. Associations between markers of inflammation and all-cause mortality were analyzed with mortality rates and Cox proportional hazards regression models.We also performed a subgroup analysis of mortality rates in patients with anemia, based on their mean corpuscular volume (MCV).We included 909 consecutive patients with alcohol dependence. Patients were mostly male (80.3%), had a median age of 44 years (interquartile range [IQR]: 38–50), and upon admission, their median alcohol consumption was 192 g/day (IQR: 120–265). At admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels >4.5 mg/dL; and 365 (49.5%) had ferritin levels >200 ng/mL. At the end of follow-up (median 3.8 years [IQR: 1.8–6.5], and a total of 3861.07 person-years), 118 patients had died (12.9% of the study population). Cox regression models showed that the presence of anemia at baseline was associated with mortality (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11–2.52, P < 0.01); no associations were found between mortality and high fibrinogen or high ferritin levels.A subgroup of patients with anemia was analyzed and compared to a control group of patients without anemia and a normal MCV. The mortality ratios of patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41–7.26; P < 0.01) and 3.39 (95% CI: 1.86–6.43; P < 0.01), respectively.Patients with alcohol dependence admitted for detoxification had an increased risk of death when anemia was present at admission. More accurate markers of systemic inflammation are needed to serve as prognostic factors for poor outcomes in this subset of patients.

LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition.

LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.

Recent Treatment of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies.

Interstitial lung disease (ILD) is a prognostic factor for poor outcome in polymyositis (PM)/dermatomyositis (DM). The appropriate management of ILD is very important to improve the prognosis of patients with PM/DM. ILD activity and severity depend on the disease subtype. Therefore, clinicians should determine therapeutic strategies according to the disease subtype in each patient with PM/DM. Anti–melanoma differentiation-associated gene 5 antibody and hyperferritinemia predict the development and severity of rapidly progressive (RP) ILD, particularly in East Asian patients. Combination therapy with corticosteroids, intravenous cyclophosphamide pulse, and calcineurin inhibitors should be administered in RP-ILD. In contrast, patients with anti–aminoacyl-tRNA synthetase (ARS) show better responses to corticosteroids alone. However, ILDs with anti-ARS often display disease recurrence or become refractory to corticosteroid monotherapy. Recent studies have demonstrated that the administration of tacrolimus or rituximab in addition to corticosteroids may be considered in ILD patients with anti-ARS. Large-scale, multicenter randomized clinical trials should be conducted in the future to confirm that the aforementioned agents exhibit efficacy in ILD patients with PM/DM. The pathophysiology of ILD with PM/DM should also be elucidated in greater detail to develop effective therapeutic strategies for patients with ILD in PM/DM.

Prognostic value of anatomical dominance of coronary circulation in patients with surgical myocardial revascularization.

Introduction:This study evaluated the frequency of domination of the coronary arteries types in patients treated by surgical myocardial revascularization. The aim of the study was to determine whether the left coronary circulation dominance is a prognostic factor for poorer outcome in patients undergoing coronary artery bypass surgery.Material and methods:A total sample consisted of 100 patients with coronary artery disease that were treated with coronary artery bypass grafting at the Clinic for Cardiac Surgery, Clinical Center of the University of Sarajevo. To all patients on the basis of preoperative coronary angiography was determined the dominance of the coronary arteries. Patients included in the study were divided into two groups, with the left and right with coronary dominance.Results:Left coronary dominance in a sample of patients was present in 21/100 (21%), right in 69/100 (69%) and balanced in 10/100 (10%) cases. Female gender was significantly more frequent in patients with left coronary dominance and proved to be a stronger predictor of poorer outcome, especially in combination with left main stenosis of the left coronary artery and left coronary dominance. Inability of revascularization of the r. interventricularis posterior (RIVP) was statistically significantly higher in case of left dominance 9/21 (42.9%), compared to the right 16/79 (20.3%), p=0.033. Lethal outcome was more common in case of left dominance in relation to the right (9.4% vs 0.9%). The incidence of surgical complications, respiratory, neurological and renal complications was not significantly different between groups, while the length of hospital stay was significantly higher in the group of patients with left dominance, p = 0.003.Conclusion:Left coronary dominance is an important risk factor for patients undergoing surgical myocardial revascularization.

Is fourth-line chemotherapy routine practice in advanced non-small cell lung cancer?

Despite advances in palliative chemotherapy, patients with advanced non-small cell lung cancer (NSCLC) eventually experience disease progression during or after completion of first-line chemotherapy, which requires salvage therapy. Second- or third-line therapy in selected patients is recommended in the current guidelines. Although fourth-line therapy is often performed in daily practice in some countries, there are few reports about the clinical benefits of fourth-line therapy. A retrospective review was conducted on 383 patients who underwent at least first-line palliative chemotherapy for advanced NSCLC (stage IV or stage IIIB/recurrent disease unsuitable for definitive local therapy). Overall survival (OS) and clinicopathological characteristics were analyzed according to the lines of chemotherapy as well as for all study patients. The median OS for all patients after the initiation of first-line therapy was 11 months. The median OS for patients who received fourth- or further-line therapy (77 patients) was longer than that of patients who received third- or lesser-line therapy (27 versus 9 months, p<0.0001). In multivariate analysis, fourth- or further-line therapy was independently associated with favorable OS (hazard ratio: 0.44, 95% confidence interval: 0.34-0.57, p<0.0001) along with recurrent disease, female, age <70 years, and ECOG performance status (PS) 0 or 1. Median OS after the start of fourth-line therapy was 9 months. Good PS (ECOG PS 0, 1) at the initiation of fourth-line therapy (10 versus 2 months, p<0.0001) and disease control (10 versus 7 months, p=0.011) after first-line therapy were associated with favorable OS in univariate analysis, while poor PS (ECOG PS ≥2) was an independent prognostic factor for poor outcome (p<0.0001). The present study suggests that advanced NSCLC patients with good PS after progression from third-line therapy could be considered as reasonable candidates for fourth-line therapy in clinical practice.