Current understanding and future implications of sepsis-induced thrombocytopenia.

Sepsis is a global health burden that needs intensive medical care. Thrombocytopenia in sepsis is well known to increase morbidity as well as mortality. Several studies have been performed both in animal models and in humans to understand the mechanism by which sepsis causes thrombocytopenia. Recent studies have shown that inhibiting thrombocytopenia improves outcomes in sepsis patients. Understanding these mechanisms to identify targets in use of newer treatment modalities besides using resuscitation measures, antibiotics and removal of thrombocytopenia inducing agent could potentially help us improve outcomes in sepsis.

Utilization of Surgery and Its Impact on Survival in Patients With Early Stage Small-cell Lung Cancer in the United States.

INTRODUCTION: For patients with T1 or T2 N0 M0 small-cell lung cancer (SCLC), lobectomy followed by chemotherapy is the standard of care. However, because of its tendency for early dissemination, patients are often treated with concurrent chemo-radiation without surgery. This study was conducted to evaluate the utilization of surgery and its impact on survival in patients with early stage SCLC. MATERIALS AND METHODS: The National Cancer Database was queried to identify patients with T1 or T2 N0 M0 SCLC diagnosed from 2004 to 2013. Multivariate logistic regression modeling was utilized to identify factors associated with receipt of surgery. Patients were stratified into 3 groups: chemo-radiation, surgery followed by chemotherapy, and surgery followed by chemotherapy and prophylactic cranial irradiation (PCI). Kaplan-Meier estimators and Cox proportional-hazards regression were used to compare overall survival. Patients were matched on the propensity score. RESULTS: A total of 3879 SCLC cases were identified. Of those cases, 80.7% received chemo-radiation. Surgery followed by chemotherapy with or without PCI was associated with better median overall survival (93.0 months [lower 95% confidence interval (CI), 72.5] and 61.7 months [95% CI, 51.8-76.5], respectively) compared with chemo-radiation (31.2 months [95% CI, 26.3-37.0]). PCI offered survival benefit in addition to surgery and chemotherapy (hazard ratio, 0.75). CONCLUSIONS: Our study showed a significant survival benefit with surgery (lobectomy or more), adjuvant chemotherapy, and PCI in patients with T1-T2 N0 M0 SCLC.

Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom.

Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5-11 years) and 10 adults (18-52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.

Cytoreductive Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma in the Targeted Therapy Era.

BACKGROUND/AIM: The role of cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) is not clearly understood after the approval of targeted therapies, particularly in the elderly population. The aim of this study was to compare survivals between patients who did and did not receive CN. PATIENTS AND METHODS: The SEER-18 database was utilized in order to identify elderly patients with mRCC to compare overall survival (OS) and cancer-specific survival (CSS) between patients who did or did not receive CN between February 2006 and 2012. Kaplan-Meier curve and log rank test were used to compare OS and CSS between these two arms. Cox proportional hazard model was used for multivariate analysis and statistical significance was defined as p≤0.05. RESULTS: There was a significant survival benefit for those who received CN compared to those who did not receive CN (median OS: 18 months vs. 4 months, p<0.001; median CSS: 21 months vs. 5 months, p<0.001). CONCLUSION: CN offered significant survival benefit, even in elderly patients with metastatic renal cell cancer.

The risk of second primary malignancy in patients with stage Ia non-small cell lung cancer: a U.S. population-based study.

BACKGROUND: Lung cancer is one of the most common cancers worldwide. Patients with early stage lung cancer have improved long-term survival. With the introduction of low-dose CT scan, more patients are going to be diagnosed at an early stage. However, there is limited data on the risk of second primary malignancies (SPMs) in these subsets of patients in the United States. METHODS: We utilized SEER-13 (Surveillance, Epidemiology and End Results) registry to obtain Multiple Primary- Standardized Incidence Ratio and an Absolute Excess Risk between January 2004 and December 2010 for patients with Stage Ia non-small cell lung cancer. RESULTS: The database comprised of 12,246 patients. A total of 1431 (11.68%) patients developed 1563 SPMs with an observed to expected (O/E) ratio of 2.07 (95% CI = 1.92-2.23, p < .001) in patients with adenocarcinoma and 2.05 (95% CI = 1.92-2.19, p < .001) in squamous cell carcinoma group. CONCLUSIONS: This study showed an excess risk of SPMs in patients with early stage non-small cell lung cancer. We recommend a close follow-up, paying attention to concerning symptoms or examination findings and judicious use of age-appropriate cancer screening.

Survival trends among patients with metastatic melanoma in the pretargeted and the post-targeted era: a US population-based study.

In 2011, ipilimumab was approved by the US Food and Drug Administration (FDA) for metastatic melanoma. Since its approval, numerous targeted therapies have been approved by the FDA. Population-based studies assessing the survival benefit from these agents are lacking. We therefore carried out this study to compare the 1-year, 2-year, and median overall survival (OS) among metastatic melanoma patients in pretargeted and post-targeted eras. This is a retrospective study that utilized the Surveillance, Epidemiology, and End Results (SEER-18) database, version 8.3.4 (22 March 2017). The patient groups were defined as the pretargeted era (2004-2010) and the post-targeted era (2011-2014) as ipilimumab was approved by the FDA in 2011. The database comprised of 5471 patients (3314 in the pretargeted era and 2157 in the post-targeted era). OS in the post-targeted era was found to be significantly better compared with the pretargeted era by Kaplan-Meier curve (1-year OS: 38.9 vs. 36.8%, 2-year OS: 28.3 vs. 23.5%, and median survival: 8 vs. 7 months, P=0.001 by the log-rank test). The survival was significantly better in the post-targeted era compared with the pretargeted era on multivariate analysis using a Cox proportional hazard model after adjusting for age, sex, race, and metasectomy status (adjusted hazard ratio of 0.889, 95% CI: of 0.832-0.951, P=0.001). There is significant survival benefit in metastatic melanoma patients since the introduction of immune checkpoint-blocking agents.

Unstaged Diffuse Large B-Cell Lymphoma in the United States: Predictors and Patient Outcomes.

BACKGROUND: Treatment and prognosis of diffuse large B-cell lymphoma (DLBCL) depends on the stage of lymphoma. We conducted this study to examine unstaged DLBCL in the United States. MATERIALS AND METHODS: We used Surveillance Epidemiology and End Result (SEER) 18 registries to select patients with DLBCL diagnosed during January 2000 to December 2012. Limited regional distant Summary stage 2000 was used to determine stage of the disease as localized, regional, distant or unstaged. We used logistic regression to investigate factors associated with unstaged DLBCL. Cox proportional hazards model was used to compare survival outcomes. RESULTS: Among 67,765 patients, disease in 3,194 (4.71%) was unstaged. Age (60+years), non-African American, not married marital status, metropolitan residence, median household income >$50,000, lymph node as the primary site and those with other primary malignancies before diagnosis of DLBCL were the factors associated with cases being unstaged. The 5-year relative survival rate for patients with unstaged DLBCL was inferior to that of those with localized and regional disease, and superior to that of those with distant disease (hazard ratios of 0.58, 0.66 and 1.24 for localized, regional and distant disease, respectively, when compared to unstaged cases). CONCLUSION: Several factors are associated with higher risk of unstaged DLBCL. Patients with unstaged DLBC had significantly inferior survival rates compared to patients with localized and regional stage.

Survival Trends in Elderly Patients with Glioblastoma in the United States: a Population-based Study.

BACKGROUND/AIM: Concomitant and adjuvant temozolomide along with radiotherapy following surgery (the Stupp regimen) is the preferred therapy for young patients with glioblastoma as well as for elderly (>70 years) ones with favorable risk factors. This study investigated the survival trend since the introduction of the use of the Stupp regimen in elderly patients in a population-based setting. MATERIALS AND METHODS: Surveillance, Epidemiology, and End Results 18 database was used to identify patients aged ≥70 years with glioblastoma as the first primary cancer diagnosed from 1999 to 2010. Chi-square test, Kaplan-Meier analysis with log-rank test and Cox proportional hazard method were used for analysis. RESULT: A total of 5,575 patients were included in the survival analysis. Survival in Stupp era (year of diagnosis ≥2005) was significantly better compared to the pre-Stupp era with p<0.001 by log-rank test, with 1-, 2- and 3-year overall survival of 18.8% vs. 12.9%, 6.5% vs. 2.1% and 3.1% vs. 0.9% respectively, and hazard ratio for death in 3 years in the Stupp era was 0.87 (95% confidence interval=0.82-0.92; p<0.001) when compared with the pre-Stupp era. Factors such as younger age (<85 years), female sex, married status, Caucasian race and total resection favored better survival compared to their counterparts. CONCLUSION: This study shows that the survival of elderly patients with glioblastoma has improved since the introduction of the Stupp regimen. However, there are significant differences in survival rates among various cohorts.

Disparities in Receipt of Radiotherapy and Survival by Age, Sex, and Ethnicity among Patient with Stage I Follicular Lymphoma.

BACKGROUND: Radiotherapy (RT) is a first-line treatment option for stage I follicular lymphoma (FL). We studied disparities in receipt of RT and survival among patients with stage I FL. METHODS: Adult patients (age ≥18 years) with stage I FL, as the first primary cancer, diagnosed between 1992 and 2007 were identified using Surveillance, Epidemiology, and End Results (SEER) 18 database. Study population was divided into various subgroups based on age, sex, race, and marital status. Factors associated with receipt of RT and survival, among patients receiving RT, was evaluated using regression analysis and Cox PH modeling, respectively. SEER*Stat was used to compute 1- and 5-year RS for various subgroups and compared using Z score. RESULTS: Of the total 7315 patients (median age: 64 years), 2671 (36.5%) received RT. African-Americans, older age group, and single and separated/divorced/widow marital status predicted omission of RT. The 1- and 5-year RS were significantly better in patients receiving RT. In multivariate analysis, male sex, age <60 years, Caucasian race, and married marital status were found to be independent predictor of better RS among patients receiving RT (P < 0.0001). CONCLUSION: This study showed that 36.5% patients with stage I FL received RT. Survival rates were significantly better for patients who received RT.

Disparities in receipt of radiotherapy and survival by age, sex and ethnicity among patients with stage I diffuse large B-cell lymphoma.

Disparities in cancer care have been documented. However, less is known about the disparities in diffuse large B-cell lymphoma (DLBCL). We reviewed the Surveillance, Epidemiology and End Results database to evaluate disparities in receipt of radiotherapy (RT) and relative survival among patients diagnosed with stage I DLBCL between 1998 and 2008 on the basis of age, sex and ethnicity. African Americans and other races were significantly less likely to receive RT compared to Caucasians (adjusted odds ratio [OR] of 0.743 and 0.81, respectively). Similarly, patients aged 60 + years and males were less likely to receive RT compared to their counterparts (p < 0.001). Caucasian race, younger age and female sex were associated with better survival among patients receiving RT. This study showed that 38.2% of patients with stage I DLBCL received radiotherapy. Survival rates were significantly higher for patients who received RT.

Survival in advanced diffuse large B-cell lymphoma in pre- and post-rituximab Eras in the United States.

BACKGROUND: Rituximab was approved by the United States Food and Drug Administration (FDA) as a first-line agent for treatment of advanced diffuse large B-cell lymphoma (DLBCL) in February 2006. We conducted this population-based study to determine if the results from the clinical trials have translated into survival benefit in the general population. PATIENTS AND METHODS: We selected patients with advanced diffuse large B-cell lymphoma from the Surveillance, Epidemiology, and End RESULTS (SEER) 18 database, and calculated relative survival rates for patients diagnosed from 2002-2005 (pre-rituximab) and 2006-2009 (post-rituximab). We used the Z-test in the SEER*Stat to compare relative survival rates of patients categorized by race (White, Black, or Others), gender (male, female), and age groups (<60, 60+ years). RESULTS: One-year relative survival in Whites and Others improved significantly in the post-rituximab era compared to the pre-rituximab era (64.80±0.6% vs. 61.3±0.6%; p=0.0002 and 64.5±1.9% vs. 54.9±2.2%; p=0.0011, respectively). The 3-year relative survival improved significantly in Whites and Others in the post-rituximab era compared to the pre-rituximab era (53.7±0.7% vs. 50.3±0.7%; p=0.0001 and 52.0±2.3% vs. 40.8±2.3%; p=0.0002, respectively). However, no significant improvements were observed in 1-year and 3-year relative survival in Blacks, and in young males during the post-rituximab era compared to the pre-rituximab era. CONCLUSION: The relative survival rates among young males and 'Black' patients with advanced diffuse large B-cell lymphoma have not improved during the post-rituximab era.

Implementing a systems-oriented morbidity and mortality conference in remote rural Nepal for quality improvement.

PROBLEM: In hospitals in rural, resource-limited settings, there is an acute need for simple, practical strategies to improve healthcare quality. SETTING: A district hospital in remote western Nepal. KEY MEASURES FOR IMPROVEMENT: To provide a mechanism for systems-level reflection so that staff can identify targets for quality improvement in healthcare delivery. Strategies for change To develop a morbidity and mortality conference (M&M) quality improvement initiative that aims to facilitate structured analysis of patient care and identify barriers to providing quality care, which can subsequently be improved. DESIGN: The authors designed an M&M involving clinical and non-clinical staff in conducting root-cause analyses of healthcare delivery at their hospital. Weekly conferences focus on seven domains of causal analysis: operations, supply chain, equipment, personnel, outreach, societal, and structural. Each conference focuses on assessing the care provided, and identifying ways in which services can be improved in the future. EFFECTS OF CHANGE: Staff reception of the M&Ms was positive. In these M&Ms, staff identified problem areas in healthcare delivery and steps for improvement. Subsequently, changes were made in hospital workflow, supply procurement, and on-site training. LESSONS LEARNT: While widely practiced throughout the world, M&Ms typically do not involve both clinical and non-clinical staff members and do not take a systems-level approach. The authors' experience suggests that the adapted M&M conference is a simple, feasible tool for quality improvement in resource-limited settings. Senior managerial commitment is crucial to ensure successful implementation of M&Ms, given the challenging logistics of implementing these programmes in resource-limited health facilities.