Zinc deficiency enhances sensitivity to influenza A associated bacterial pneumonia in mice.

Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor to morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with supplemental zinc) for such a role in lower respiratory tract infection are somewhat ambiguous. In the current study, we provide the first preclinical evidence demonstrating that although diet-induced acute zinc deficiency (Zn-D: ~50% decrease) did not worsen infection induced by either influenza A (H1N1) or methicillin-resistant staph aureus (MRSA), Zn-D mice were sensitive to the injurious effects of superinfection of H1N1 with MRSA. Although the mechanism underlying the sensitivity of ZnD mice to combined H1N1/MRSA infection is unclear, it was noteworthy that this combination exacerbated lung injury as shown by lung epithelial injury markers (increased BAL protein) and decreased genes related to epithelial integrity in Zn-D mice (surfactant protein C and secretoglobins family 1A member 1). As bacterial pneumonia accounts for 25%-50% of morbidity and mortality from influenza A infection, zinc deficiency may be an important pathology component of respiratory tract infections.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Treatment Selection and Survival in Patients with Gray Zone Lymphoma: A Comprehensive Population-Based Analysis.

BACKGROUND AND OBJECTIVES: There are no treatment guidelines for gray-zone lymphoma (GZL), given the disease's rarity and being a relatively new entity. Our objective was to assess factors affecting treatment selection in GZL and its effect on survival, focusing on combined modality treatment (CMT) versus chemotherapy alone. PATIENTS AND METHODS: We identified 1047 patients with GZL treated with CMT or chemotherapy alone between 2004 and 2016 from the National Cancer Database (NCDB). We excluded patients without histologic confirmation of the diagnosis, those who did not receive chemotherapy, and those who started chemotherapy >120 days or radiation >365 days from diagnosis to account for immortal time bias. Factors affecting treatment selection were investigated using a logistic regression model. A propensity score-matched methodology was used to compare survival outcomes. RESULTS: Only 164 patients (15.7%) received CMT, while 883 (84.3%) received chemotherapy alone. Treatment selection was affected by clinical factors (age, odds ratio [OR] 0.99, 95% confidence interval [CI] 0.98-0.997, p-value 0.01 and advanced stage, OR for stage 4: 0.21, 95% CI 0.13-0.34, p-value < 0.001) but not socioeconomic factors. Higher median income was associated with better survival, while increased age, higher comorbidity score, and B symptoms were associated with worse survival. The use of CMT had a survival advantage over chemotherapy alone (hazard ratio [HR] 0.54, 95% CI 0.351-0.833, p-value 0.005). CONCLUSION: CMT is associated with survival advantage in our analysis. Careful selection of patients is essential to achieve the best outcomes with minimal toxicity. Socioeconomic factors affect treatment selection in patients with GZL that can alter outcomes. Future work should focus on strategies that access disparities without compromising survival.

Predictors and Long-Term Outcomes for Diffuse Large B-Cell Lymphoma (DLBCL) Patients Undergoing Surgery Prior to Systemic Therapy: A Nationwide Analysis.

BACKGROUND: A minority of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergo surgery before the initiation of systemic therapy. The aim of this study is to explore the characteristics of patients undergoing surgery prior to systemic therapy (surgfirst), the predictors for surgfirst, and the survival outcomes. METHODS: The National Cancer Database was queried for patients with DLBCL diagnosed between 2006 and 2015, and we performed a subgroup analysis of patients that received surgfirst. Time-to-initial therapy (TTI) was defined as the time in days (d) from diagnosis to systemic therapy. Overall survival was measured from the day of diagnosis in terms of months (m). RESULTS: Factors associated with lower likelihood of surgfirst were non-Hispanic Black race (p-value<0.005), rural location (p-value<0.005), treatment at academic center (p-value<0.005), Medicaid insurance (p-value=0.01), comorbidity score >=3 (p-value 0.007), year of diagnosis, advanced stages of disease, and presence of B-symptoms. The TTI of systemic therapy was delayed in the surgfirst group - 34 (IQR 22-52) days vs. 23 (IQR 13-38) days, p-value<0.005. The five-year overall survival was 62.7% (95% CI 62.1-63.2%) vs. 58.3% (95% CI 57.7-60.0%) - HR 0.87 (95% CI 0.85-0.89), p-value<0.005. The factors associated with higher mortality were advanced comorbidities, lower educational status, disease primarily located in the bone, brain, and spinal cord, advanced clinical stage, presence of B-symptoms, and advanced age. CONCLUSION: Despite the delay in systemic therapy, we could not identify a detrimental impact of surgfirst on survival. This needs to be confirmed in large-scale multicenter studies. We identified clinical and socioeconomic factors that affect treatment selection and survival.

The prognostic value of KRAS mutation in locally advanced rectal cancer.

BACKGROUND: The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). METHODS: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. RESULTS: Of the 784 eligible patients, 506 were KRAS-negative (KRAS -) and 278 were KRAS-positive (KRAS +). Median survival was 63.6 months and 76.3 months for KRAS + and KRAS - patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses. CONCLUSIONS: Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.

Novel Coronavirus Infection (COVID-19) Related Thrombotic and Bleeding Complications in Critically Ill Patients: Experience from an Academic Medical Center.

INTRODUCTION: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill. METHODS: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU. Secondary outcomes included mortality vis-a-vis the type of anticoagulation. RESULTS: The cohort included 144 consecutive COVID-19 patients with a median age of 64 years (IQR 54.5-75). The majority were male (85 (59.0%)) and Caucasian (90 (62.5%)) with a median BMI of 30.5 kg/m2 (IQR 25.7-36.1). The median APACHE score at admission to the ICU was 12.5 (IQR 9.5-22). The coagulation parameters at admission were a d-dimer level of 109.2 mg/mL, a platelet count of 217.5 k/mcl, and an INR of 1.4. The anticoagulation strategy at admission included prophylactic anticoagulation for 97 (67.4%) patients and therapeutic anticoagulation for 35 (24.3%) patients, while 12 (8.3%) patients received no anticoagulation. A total of 29 patients (20.1%) suffered from thrombotic or major bleeding complications. These included 17 thrombus events (11.8%)-8 while on prophylactic anticoagulation (7 regular dose and 1 intermediate dose) and 9 while on therapeutic anticoagulation (p-value = 0.02)-and 19 major bleeding events (13.2%) (4 on no anticoagulation, 7 on prophylactic (6 regular dose and 1 intermediate dose), and 8 on therapeutic anticoagulation (p-value = 0.02)). A higher thrombosis risk among patients who received remdesivir (18.8% vs. 5.3% (p-value = 0.01)) and convalescent serum (17.3% vs. 5.8% (p-value = 0.03%)) was noted, but no association with baseline characteristics (age, sex, race, comorbidity), coagulation parameters, or treatments (steroids, mechanical ventilation) could be identified. There were 10 pulmonary embolism cases (6.9%). A total of 99 (68.8%) patients were intubated, and 66 patients (45.8%) died. Mortality was higher, but not statistically significant, in patients with thrombotic or bleeding complications-58.6% vs. 42.6% (p-value = 0.12)-and higher in the bleeding (21.2%) vs. thrombus group (12.1%), p-value = 0.06. It did not significantly differ according to the type of anticoagulation used or the coagulation parameters. CONCLUSIONS: This study describes a high incidence of thrombotic and bleeding complications among critically ill COVID-19 patients. The findings of thrombotic events in patients on anticoagulation and major bleeding events in patients on no or prophylactic anticoagulation pose a challenging clinical dilemma in the issue of anticoagulation for COVID-19 patients. The questions raised by this study and previous literature on this subject demonstrate that the role of anticoagulation in COVID-19 patients is worthy of further investigation.

Characteristics and Outcomes of COVID-19 Patients Admitted to Intensive Care Units in a Large Health System in Western Pennsylvania.

Importance Despite growing literature, there is still limited understanding of factors that can predict outcomes in coronavirus disease 2019 (COVID-19) patients who require intensive care. Objective To evaluate the characteristics of COVID-19 patients admitted to the intensive care unit (ICU) and identify their associations with outcomes. Background There are limited data on the outcomes in COVID-19 patients in Pennsylvania. Design Retrospective study Setting Intensive care units in an academic health system in Western Pennsylvania. Participants Patients with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 admitted to ICUs as direct admission or transfers from regular floors between March 1, 2020, and April 30, 2020. Main outcome(s) and measure(s) The primary outcome was inpatient mortality. Secondary outcomes included complications during ICU stay, hospital length of stay, discharge disposition, and the need for oxygen at discharge. Categorical variables are described as frequencies and continuous variables as median with interquartile range (IQR). Regression modeling was used to identify the predictors of inpatient mortality in these patients. P-value <0.05 was considered statistically significant. Analysis was performed using Stata version 15.1 (StataCorp, College Station, Texas). Results The cohort included 58 consecutive patients, with a median age of 62 years (IQR 54-73), 63.8% of which were male. On presentation, constitutional symptoms were the most common (91.4%), followed by lower respiratory tract symptoms (87.9%). Tachypnea (65.5%) and hypoxia (67.2%) were the most common abnormal vital signs at presentation. Common comorbidities were cardiovascular disease (74.1%), obesity (53.5%), and diabetes (39.7%). The median Acute Physiology and Chronic Health Evaluation (APACHE) score on admission to ICU was 11 (IQR 8.5-17.5). The major complications included acute respiratory distress syndrome (ARDS) 50.0%, shock 41.4%, and acute kidney injury 41.4%. The proportion of patients who underwent mechanical ventilation, required vasopressors, or were on renal replacement therapy were 58.6%, 41.4%, and 10.3%, respectively. Overall mortality was 32.8%. Age, Charlson-comorbidity index, tachypnea, lymphopenia at presentation, high APACHE score, shock, ARDS, mechanical ventilation, and steroid use were significantly associated with mortality. Of the patients who survived their ICU stay, 63.2% were discharged home and 44.7% had a new oxygen requirement at discharge. Conclusion and relevance Our study reports high mortality in COVID-19 patients requiring ICU care in Western Pennsylvania. Identifying factors associated with poor prognosis could help risk-stratify these patients. Prospective studies are needed to assess whether early risk stratification and triaging result in improved outcomes.

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies.

PURPOSE: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls. METHODS AND MATERIALS: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate. RESULTS: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01). CONCLUSIONS: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae.

The use of adjuvant radiation therapy in male breast cancer and its impact on outcomes.

BACKGROUND: Male breast cancer (MBC) accounts for 1% of all breast cancers and there is a paucity of data on factors impacting the treatment strategies and outcomes. We sought to use a large national database to examine trends and predictors of the use of adjuvant radiation (Adj-RT), as well as any association with outcome. METHODS: We queried the National Cancer Database (NCDB) for patients with stages I-III MBC treated with surgery (breast conservation surgery-BCS or mastectomy-MS) within 180 days of diagnosis (years 2004-2015). Multivariable logistic regression identified predictors of adj-RT receipt. Multivariable Cox regression evaluated predictors of survival. Propensity matching for adj-RT was used to account for indication biases. RESULTS: We identified 6,217 patients meeting the eligibility criteria (1457 BCS vs. 4760 MS). The majority of patients were Caucasian (85%) and in an age range of 50-80 years (74%). Although adj-RT was omitted for 30% of BCS patients, the utilization was higher compared to MS (OR=26, p-value=0.001). The predictors of adj-RT use included African-American race, more advanced stage, higher grade, presence of lymphovascular invasion, and ER/Her-2 positivity for the entire cohort and increased age, urban location and higher income for BCS. Adj-RT was associated with lower mortality in the propensity matched model (overall HR for BCS=0.28, p-value<0.001; overall HR for MS=0.62, p-value=0.001). CONCLUSION: This study demonstrates that while adj-RT after BCS is associated with decreased mortality in MBC patients, adj-RT is omitted in up to a third of cases of MBC after BCS despite being standard of care.

Disparities in the enrollment to systemic therapy and survival for patients with multiple myeloma.

BACKGROUND: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for hematopoietic stem cell transplant in the first-line setting and how it varied over time. METHODS: We queried the National Cancer Database for patients diagnosed with MM between 2004 and 2016 and included only those who received systemic therapy as the first-line treatment. Enrollment rates for therapy were calculated as receipt of systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator) and used to calculate incident rate ratios that were further analyzed using Poisson regression analysis. A multivariate Cox proportional hazards model was constructed for survival analysis, and differences were reported as hazard ratios (HRs). RESULTS: We identified 56,102 patients for enrollment analysis and 50,543 patients for survival analysis. Therapy enrollment in a multivariate model was significantly impacted by race and sex (p < .005). Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were associated with poor survival (HR > 1), whereas female sex, non-Hispanic black race, higher income, and treatment at an academic center were associated with improved survival (HR < 1). CONCLUSION: Disparities in treatment of MM exist and are caused by a complex interplay of multiple factors, with socioeconomic factor playing a significant role. Studies exploring such determinants may help in equitable distribution of resources to overcome such differences.

Coincident remission of ankylosing spondylitis after autologous stem cell transplantation for multiple myeloma.

INTRODUCTION: Ankylosing spondylitis is an autoimmune disease with chronic inflammation of the spine and sacroiliac joints that is commonly treated with immunosuppressants including disease-modifying antirheumatic drugs and anti-tumor necrosis factor alpha therapy. CASE REPORT: A 75-year-old female with active ankylosing spondylitis on treatment with etanercept was referred to us for newly diagnosed IgG kappa free light chain multiple myeloma. After failing induction with revlimid, bortezomib, and dexamethasone, she was initiated on carfilzomib. Following the achievement of adequate response to induction, she underwent an autologous hematopoietic stem cell transplant selected for CD34+ cells with melphalan 200mg/m2 conditioning regimen. Given high-risk cytogenetics, i.e. monosomy 17 (17p) and hypodiploidy, she received two cycles of carfilzomib consolidation post-transplant. The patient tolerated the transplant well with successful engraftment and achieved complete remission of multiple myeloma with no detectable M spike, negative immunofixation study, and normalization of light chain ratio. While being off etanercept since the transplant, she noticed complete relief from joint pains related to her ankylosing spondylitis without a need to use the pain-relieving medications.Management and outcome: The patient has sustained remission of ankylosing spondylitis for two years post-transplant without flares or symptoms. She continues to remain off immunosuppressants. DISCUSSION: Although our patient had a coincident and unprecedented resolution of ankylosing spondylitis after receiving the hematopoietic stem cell transplant, this case consolidates the idea of transplant as a potential treatment option for ankylosing spondylitis and other rheumatological conditions.

Dichloroacetate-induced metabolic reprogramming improves lifespan in a Drosophila model of surviving sepsis.

Sepsis is the leading cause of death in hospitalized patients and beyond the hospital stay and these long-term sequelae are due in part to unresolved inflammation. Metabolic shift from oxidative phosphorylation to aerobic glycolysis links metabolism to inflammation and such a shift is commonly observed in sepsis under normoxic conditions. By shifting the metabolic state from aerobic glycolysis to oxidative phosphorylation, we hypothesized it would reverse unresolved inflammation and subsequently improve outcome. We propose a shift from aerobic glycolysis to oxidative phosphorylation as a sepsis therapy by targeting the pathways involved in the conversion of pyruvate into acetyl-CoA via pyruvate dehydrogenase (PDH). Chemical manipulation of PDH using dichloroacetic acid (DCA) will promote oxidative phosphorylation over glycolysis and decrease inflammation. We tested our hypothesis in a Drosophila melanogaster model of surviving sepsis infected with Staphylococcus aureus. Drosophila were divided into 3 groups: unmanipulated, sham and sepsis survivors, all treated with linezolid; each group was either treated or not with DCA for one week following sepsis. We followed lifespan, measured gene expression of Toll, defensin, cecropin A, and drosomycin, and levels of lactate, pyruvate, acetyl-CoA as well as TCA metabolites. In our model, metabolic effects of sepsis are modified by DCA with normalized lactate, TCA metabolites, and was associated with improved lifespan of sepsis survivors, yet had no lifespan effects on unmanipulated and sham flies. While Drosomycin and cecropin A expression increased in sepsis survivors, DCA treatment decreased both and selectively increased defensin.

Impact of the Affordable Care Act on Timeliness to Treatment for Patients With Multiple Myeloma.

BACKGROUND/AIM: To examine the impact of ACA and the association of socioeconomic factors on delay in initial treatment for multiple myeloma (MM). PATIENTS AND METHODS: Patients diagnosed with MM between 2004-2016 were identified in the National Cancer Database (NCDB). Time-to-initial treatment (TTI) was defined as the number of days from diagnosis to initial therapy. Patients were classified into quartiles and those belonging to the fourth quartile for TTI constituted the delayed treatment group. Study period was divided into pre-ACA and post-ACA using 2010 as the cut-off. RESULTS: A total of 65,723 patients met the eligibility criteria. Median TTI was 13 (IQR=5-27) days. Racial-ethnic minorities were associated with delayed-TTI. Delayed treatment was more likely for Hispanics pre-ACA but not post-ACA, while non-Hispanic Blacks (NHB) were more likely to have delayed treatment both, pre- and post-ACA. CONCLUSION: While ACA has been shown to help mitigate healthcare disparities in certain cancer diagnoses, the study suggests that the effect is still limited among MM patients.

Medicine and surgery residents' perspectives on the impact of COVID-19 on graduate medical education.

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents' professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or resident characteristics were related to stress during the pandemic. Our secondary goals were to examine which resident characteristics were related to survey responses. Data were analyzed with regression analyses. Ninety-six of 205 residents completed the survey (47% response rate). For our primary outcome, anxiety about PPE (P < 0.001), female gender (P = 0.03), and the interaction between female gender and anxiety about PPE (P = 0.04) were significantly related to increased stress during the COVID-19 pandemic. Secondary analyses suggested that medicine residents were more comfortable than surgical residents using telemedicine (P > 0.001). Additionally, compared to juniors, seniors believed that the pandemic was more disruptive, modified schedules were effective, and virtual meetings were less effective while virtual lectures were more effective (all P ≤ 0.05) Furthermore, the pandemic experience has allowed seniors in particular to feel more confident to lead in future health crises (P ≤ 0.05). Medicine and surgery residency programs should be cognizant of and closely monitor the effects of COVID-19 crisis-related factors on residents' stress and anxiety levels. Transparent communication, telemedicine, online lectures/meetings, procedure simulations, advocacy groups, and wellness resources may help to mitigate some of the challenges posed by the pandemic.

Impact of affordable care act on the treatment and outcomes for stage-IV colorectal cancer.

BACKGROUND: Patients with advanced cancers are among the most vulnerable group of patients. We sought to analyze the impact of Affordable Care Act (ACA) on the interaction of socioeconomic factors with treatment and survival in patients with metastatic colorectal cancers. METHODS: National Cancer Database (NCDB) was queried for patients with Stage-IV colon(CCa) and rectal cancers(R-Ca) diagnosed 2004-2015 and excluded those who did not receive any therapies within 6 months of diagnosis. Enrollment-rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy (denominator) and used to calculate incident-rate ratios that was analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, <1 indicating lower enrollment rate). Multivariate Cox-proportional hazard model was performed for survival analysis and reported as calculate Hazard Ratios (HR). RESULTS: For CCa, enrollment to primary therapies was significantly associated (p-value < 0.05) with gender, race, insurance status, educational status and treatment facility. The HR for non-Hispanic Blacks (NHB) vs. Whites (NHW) improved from 1.1(1.03-1.11),p-value<0.005 to no-significant difference post-ACA. For R-Ca, the enrollment rates were favorable for NHB vs. NHW and ER improved from 1.15(1.0-1.32),p-value = 0.054) to 1.29(1.06-1.58),p-value = 0.013 post-ACA. Despite this, the HR for mortality were unfavorable - 1.19(1.06-1.33),p-value = 0.003 that persisted through the post-ACA period. The HR was favorable for the insured group in both cancer groups (0.84 for R-Ca,0.86 for CCa) and for high-income vs. low-income group-0.90(0.87-0.94),p-value < 0.005 in CCa. CONCLUSION: The ACA appears to have had a positive impact overall but further research and ongoing interventions are warranted to mitigate disparities in this population.

Outcomes of Treatment for HIV-Infected Lymphoma Patients: A National Cancer Database (NCDB) Analysis.

BACKGROUND: Human immunodeficiency virus (HIV) infection may be a predictor of undertreatment of patients with lymphoma. We hypothesized treatment with systemic therapy (SysT) or hematopoietic stem cell transplantation (HCT) in the first-line setting leads to improved outcomes and sought to compare the predictors for treatment and outcomes with non-HIV (HIV-) patients. METHODS: Patients with lymphoma diagnosed between 2004 and 2015 were extracted from the National Cancer Database (NCDB). Patients were categorized as HIV+ and HIV-. First-line treatment was categorized as no systemic therapy reported (noSyst), SysT, or HCT. Multivariate analysis to predict treatment and survival was performed. RESULTS: We identified 552,513 lymphoma patients, of whom 11,160 HIV+ versus 349,607 HIV- patients were eligible for analysis. Among HIV+, the positive predictors for SysT were insurance and higher income, whereas female sex and minority racial status predicted lower likelihood for SysT. Forty HIV+ patients underwent HCT. Treatment of HIV+ lymphoma patients resulted in improved outcomes: 3-year overall survival 43.6% in noSyst versus 58.1% SysT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.52-0.61; P < .005) versus 62.2% HCT (HR 0.42; 95% CI, 0.14-1.3; P = .08). The outcomes were lower compared to non-HIV patients (3-yr overall survival 67.3% with SysT and 62.2% HCT). CONCLUSION: Patients with lymphoma with HIV benefit from SysT when feasible but outcomes are worse than non-HIV patients. HCT should be offered to HIV+ patients with lymphoma in the appropriate clinic setting. Individual characteristics of the patients and complications could not be evaluated in the present study but should be a focus for future research.

Free Clinic Patients' Perceptions and Barriers to Applying for Health Insurance After Implementation of the Affordable Care Act.

Despite implementation of the Affordable Care Act (ACA), many Americans remain uninsured and receive care in free clinics. It is unknown what free clinic attendees in Pennsylvania know about health insurance expansion or what they perceive as barriers in enrolling in health insurance. The objective of this study was to assess the perceptions and experiences of free clinic patients from southwestern Pennsylvania when applying for health insurance after implementation of the ACA. We designed and implemented a survey of patients at three free clinics within Allegheny County, Pennsylvania from September 2016 to February 2017. Our survey included 22-items, 7 sociodemographic questions and 15 questions regarding the patient's health status and their perspectives related to obtaining health insurance. Data was obtained from 203 patient surveys; 110 (55.3%) of the respondents were men and 99 (48.8%) were African American. There were 48 respondents (24.1%) who did not report any income at the time of the study, and of those that did report an income, 92 (46.2%) respondents reported an income below 133% of the federal poverty level. The main barriers patients faced when applying for health insurance were: (1) lack of knowledge about health insurance (n = 127, 58.1%), (2) cost of health coverage (n = 85, 41.9%), (3) lack of resources (n = 83, 40.4%), and (4) lack of enrollment documentation (n = 43, 23.8%). Significant work is needed to better educate patients about their eligibility and options for health insurance. Free clinics can play a key role in eliminating barriers to health insurance enrollment.

Risk factors for venous thromboembolism in hospitalized patients with hematological malignancy: an analysis of the National Inpatient Sample, 2011-2015.

Hospitalized patients with hematological malignancy (HM) suffer an increased incidence of venous thromboembolism (VTE). We sought to identify risk factors and rate of VTE in hospitalized patients with HM using National Inpatient Sample (NIS) for the years 2011 to 2015. We used ICD-9 codes to identify patients with HM as the primary diagnosis and VTE as a secondary diagnosis for hospitalization. The rate of VTE was highest in patients with acute myeloid leukemia (6.6%) followed by acute lymphocytic leukemia (6.1%) and non-Hodgkin's lymphoma (6.0%). The highest risk of VTE occurred among patients with HM receiving chemotherapy (OR 1.68; 95% CI 1.567-1.809) followed by infection such as pneumonia (OR 1.31; 95% CI 1.201-1.436) and sepsis (OR = 1.66; 95% CI = 1.524-1.621). Chemotherapy had the highest risk of developing VTE during hospitalization followed by sepsis and pneumonia. The identification of patients with HM most at risk for VTE could be used to design and test prophylactic strategy.

Retrospective review of total neoadjuvant therapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer. Using this approach, maChT administration can be delayed for several months, leading to concern for distant metastases. To counteract this, a novel treatment approach known as total neoadjuvant therapy (TNT) has gained popularity, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database to examine temporal trends in TNT usage, and any potential effect on survival. AIM: To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation. METHODS: We queried the National Cancer Database for patients with locally advanced rectal cancer, Stage II-III, from 2004-2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 d prior to nCRT initiation. Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival, with log-rank statistics to assess significance. Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias. RESULTS: We identified 9066 eligible patients, with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT, respectively. Nodal involvement, stage III disease, and treatment in recent years were predictive of TNT use. There was greater use of TNT with more advanced stage, specifically > 1 node involved (odds ratio [OR] = 2.88, 95% confidence interval [CI]: 2.11-3.93, P < 0.01) and stage III disease (OR = 2.88, 95%CI: 2.11-3.93, P < 0.01). From 2010 to 2012 the use of TNT increased (OR = 2.41, 95%CI: 1.27-4.56, P < 0.01) with a greater increase from 2013 to 2015 (OR = 6.62, 95%CI: 3.57-12.25, P < 0.01). Both the TNT and neoadjuvant chemoradiation arms had a similar 5-year survival at 76% and 78% respectively. Multivariable analysis with propensity score demonstrated that increased age, high comorbidity score, higher grade, African American race, and female gender had worse overall survival. CONCLUSION: Our data demonstrates a rising trend in TNT use, particularly in patients with worse disease. Patients treated with TNT and nCRT had similar survival. Randomized trials evaluating TNT are underway.