Overall survival of patients with cHL who progress after autologous stem cell transplant: results in the novel agent era.

In the pre-novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time from posttransplant progression to death or last follow-up. Of 1158 patients who underwent ASCT, 367 had progressive disease. Median age was 34 years (range, 27-46) and 192 were male. Median PPS was 114.57 months (95% confidence interval [CI], 91-not achieved) or 9.5 years. In multivariate analysis, increasing age, progression within 6 months, and pre-ASCT positive positron emission tomography scan were associated with inferior PPS. When adjusted for these features, patients who received CPI, but not BV, as first treatment for post-ASCT progression had significantly higher PPS than the no CPI/no BV group (hazard ratio, 3.5; 95% CI, 1.6-7.8; P = .001). Receipt of allogeneic SCT (Allo-SCT) did not improve PPS. In the era of novel agents, progressive cHL after ASCT had long survival that compares favorably with previous reports. Patients who receive CPI as first treatment for progression had higher PPS. Receipt to Allo-SCT was not associated with PPS in this population.

Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States.

BACKGROUND: Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies. METHODS: A nationwide electronic health record (EHR)-derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC. Treatment trends over time were assessed by fitting a linear model to the percentage of patients receiving anti-EGFR therapy. A propensity score weighted Cox model was used to compare overall survival (OS) stratified by first-line targeted therapy received. RESULTS: A total of 1,607 patients with left-sided RAS/RAF WT mCRC received standard first-line chemotherapy. Of these, 965 (60%) received bevacizumab and 186 (12%) received an anti-EGFR agent. The percentage of patients receiving an anti-EGFR increased from 9% in 2013 to 16% in 2018. Median OS for patients treated with chemotherapy alone was 27.3 months (95% CI, 24.8-32.3), 27.5 months with bevacizumab (95% CI, 25.8-28.9; hazard ratio [HR], 0.88; P=.33), and 42.9 months with an anti-EGFR agent (95% CI, 36.0 to not reached; HR, 0.52; P=.005). CONCLUSIONS: This analysis suggests that chemotherapy with bevacizumab remained the most widely used first-line treatment strategy for patients with left-sided RAS/RAF WT mCRC in the United States in 2018. Despite this preference, treatment with an anti-EGFR agent was associated with improved OS.

Updates on adjuvant and neoadjuvant treatment strategies for surgically resectable and borderline resectable pancreatic ductal adenocarcinoma.

Pancreatic cancer is the third leading cause of cancer-related mortality in the US. Outcomes for patients with pancreatic cancer are poor as curative approaches are only available to the minority of patients who have localized tumors for which surgery may be an option. The past decade has established fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as the new standard of care following resection for fit patients with resectable pancreatic tumors. However, most patients will relapse and a large number of patients treated with upfront resection are unable to receive or complete adjuvant chemotherapy. There is therefore considerable interest in neoadjuvant treatment strategies for patients with resectable and borderline resectable pancreatic cancer as a way to provide early systemic treatment of micrometastatic disease, facilitate lymph node downstaging, and increase the likelihood of negative resection margins (R0). This review will focus on key aspects of completed trials evaluating adjuvant therapy in resectable pancreatic cancer and will provide an overview of emerging evidence supporting the use of neoadjuvant treatment strategies for both resectable and borderline resectable pancreatic cancer.

Racial/Ethnic Disparities in Prostate Cancer Incidence, Distant Stage Diagnosis, and Mortality by U.S. Census Region and Age Group, 2012-2015.

BACKGROUND: We sought to characterize recent prostate cancer incidence, distant stage diagnosis, and mortality rates by region, race/ethnicity, and age group. METHODS: In SEER*Stat, we examined age-specific and age-adjusted prostate cancer incidence, distant stage diagnosis, and mortality rates by race/ethnicity, census region, and age group. Incidence and mortality analyses included men diagnosed with (n = 723,269) and dying of (n = 112,116) prostate cancer between 2012 and 2015. RESULTS: Non-Hispanic black (NHB) and non-Hispanic Asian/Pacific Islander (NHAPI) men had the highest and lowest rates, respectively, for each indicator across regions and age groups. Hispanic men had lower incidence and mortality rates than non-Hispanic white (NHW) men in all regions except the Northeast where they had higher incidence [RR, 1.16; 95% confidence interval (CI), 1.14-1.19] and similar mortality. Hispanics had higher distant stage rates in the Northeast (RR, 1.18; 95% CI, 1.08-1.28) and South (RR, 1.22; 95% CI, 1.15-1.30), but similar rates in other regions. Non-Hispanic American Indian/Alaskan Native (NHAIAN) men had higher distant stage rates than NHWs in the West (RR, 1.38; 95% CI, 1.15-1.65). NHBs and Hispanics had higher distant stage rates than NHWs among those aged 55 to 69 years (RR, 2.91; 95% CI, 2.81-3.02 and 1.24; 95% CI, 1.18-1.31, respectively), despite lower overall incidence for Hispanics in this age group. CONCLUSIONS: For Hispanic and NHAIAN men, prostate cancer indicators varied by region, while NHB and NHAPI men consistently had the highest and lowest rates, respectively, across regions. IMPACT: Regional and age group differences in prostate cancer indicators between populations may improve understanding of prostate cancer risk and help inform screening decisions.

Baseline differences in characteristics and risk behaviors among people who inject drugs by syringe exchange program modality: an analysis of the Miami IDEA syringe exchange.

BACKGROUND: In March of 2016, Florida passed the Infection Disease Elimination Act (IDEA), legalizing the formation of the first syringe exchange program in Florida, which opened in December of 2016 at a fixed site in Overtown, Miami. Since that time, the exchange expanded in April of 2017 to include a mobile van unit that provides the same services at different locations throughout Miami-Dade County. METHODS: Trained interviewers conducted face-to-face interviews from all first-time participants at the IDEA Exchange, both at the fixed site and the mobile van unit. RESULTS: Among 718 first-time enrollees, 74.8% were male, 52.1% were non-Hispanic White, 85.9% completed high school, 59.8% were unemployed, 42.1% were homeless, 54.2% reported an annual income of less than $15,000, and the mean age was 38 years. Participants at the fixed site and mobile van unit reported differences in socioeconomic status, injection drug-related behaviors, and pre-existing hepatitis C virus (HCV) infection status. CONCLUSIONS: Taken together, these results suggest that the mobile unit is capturing a subset of PWID in Miami that the fixed site is not, and vice-versa. As the opioid crisis extends into all demographics, such multimodal efforts to target various populations of PWID should be kept in mind, especially when unveiling future syringe exchanges in Florida and other late-adopting states.

Discomfort discussing HIV/AIDS and lack of awareness are barriers to partner-to-partner pre-exposure prophylaxis education.

We suggest that people living with HIV (PLWH) may serve as pre-exposure prophylaxis (PrEP) educators for partners when informed about PrEP. Participants in this study were a convenience sample of PLWH at a public hospital in Miami. A cross-sectional survey assessed the frequency of serostatus disclosure, PrEP awareness, and willingness to recommend PrEP to intimate partners. To evaluate stigma surrounding human immunodeficiency virus (HIV), comfort discussing HIV with family, friends and intimate partners was interrogated. Surveys were completed by 137 participants; 39.5% had potentially sero-discordant sexual partners. Among respondents, 29.2% reported that they 'occasionally' or 'never' disclose HIV status to sexual partners. In all, 66.4% of patients reported that they had never heard of PrEP. After being educated about PrEP, 86.0% of respondents reported that they would encourage partners to use it. Participants were asked how often the subject of HIV comes up in conversations. Most indicated that 'rarely' or 'never' does it come up with friends and family; 46.1% indicated that 'never' or 'rarely' does it come up with partners. In bivariate analyses, participants with prior awareness of PrEP were more likely to indicate higher frequency of conversations regarding HIV with intimate partners. It is concluded that interventions which utilize partner education to increase PrEP uptake should address stigma and knowledge among other barriers.

Catatonia due to alprazolam withdrawal.

A 50-year-old man with multiple psychiatric comorbidities including major depressive disorder and general anxiety disorder presented to the emergency room (ER) with altered mental status, immobility and mutism. The patient was unresponsive to commands and unable to provide any history. In the ER he was given a provisional diagnosis of cerebrovascular accident (CVA). Vital signs on admission were stable. On physical examination, he exhibited grimacing, muscle rigidity and areflexia. Workup for CVA and infectious aetiology was unremarkable and the patient's urine toxicology screen was negative. History from the patient's family revealed that 4 days prior to presentation, the patient had discontinued his prescribed dose of alprazolam 1 mg four times per day. The patient was diagnosed with catatonia due to benzodiazepine withdrawal and had gradual return to baseline with administration of lorazepam 1 mg intravenous three times per day.

µ-Opioid receptors mediate the effects of chronic ethanol binge drinking on the hippocampal neurogenic niche.

Ethanol exposure and withdrawal alter the generation of new neurons in the adult hippocampus. The endogenous opioid system, particularly the µ-opioid receptor (MOR), can modulate neural progenitors and also plays a critical role in ethanol drinking and dependence. In the present study, we sought to determine whether MOR contributes to the effects of ethanol on the dentate gyrus (DG) neurogenic niche. MOR wild-type (WT), heterozygous (Het) and knockout (KO) littermates were subjected to voluntary ethanol drinking in repeated limited-access two-bottle choice (2BC) sessions. MOR deficiency did not alter progenitor proliferation, neuronal differentiation and maturation, apoptosis or microglia in ethanol-naïve mice. When exposed to five consecutive weeks of 2BC, MOR mutant mice exhibited a gene-dosage-dependent reduction of ethanol consumption compared with WT mice. Introducing a week of ethanol deprivation between each week of 2BC increased ethanol consumption in all genotypes and produced equivalent intakes in WT, Het and KO mice. Under the latter paradigm, ethanol drinking decreased progenitor proliferation and neuronal differentiation in the DG of WT mice. Interestingly, WT mice exhibited a strong negative correlation between ethanol intake and proliferation, which was disrupted in Het and KO mice. Moreover, MOR deficiency blocked the effect of ethanol on neuronal differentiation. MOR deficiency also protected against the neuroimmune response to ethanol drinking. Finally, chronic binge drinking induced a paradoxical decrease in apoptosis, which was independent of MOR. Altogether, our data suggest that MOR is implicated in some of the neuroplastic changes produced by chronic ethanol exposure in the DG.