Citations

Abstract Climate change, exemplified by higher average global temperatures resulting in more frequent extreme weather events, has the potential to significantly impact human migration patterns and health. The consequences of environmental catastrophes further destabilize regions with pre‐existing states of conflict due to social, political, and/or economic unrest. Migrants may carry diseases from their place of origin to their destinations and once there may be susceptible to diseases in which they had not been previously exposed to. Skin diseases are among the most commonly observed health conditions observed in migrant populations. To improve awareness among dermatologists of the burden of skin diseases among migrants, the group searched the English language scientific literature to identify articles linking climate change, migration, and skin disease. Skin diseases associated with human migration fall into three major categories: (i) communicable diseases, (ii) noncommunicable diseases, and (iii) environmentally mediated diseases. Adopting comprehensive global strategies to improve the health of migrants requires urgent attention.

Abstract Background Capnocytopha ga is a gram-negative, facultative anaerobe. Human infection is rare but can lead to devastating outcomes. Capnocytophaga canimorsus can cause sepsis following an animal bite, whereas human-oral–associated Capnocytophaga infections were reported in immunocompromised patients. Current data on these infections are not robust. Our goal is to provide a contemporary description of a unique characteristic of Capnocytophaga infections. Methods We performed a retrospective review of all patients with Capnocytophaga infection from January 2010 to August 2020 at 3 main hospitals of Mayo Clinic in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. We collected baseline demographic data, clinical characteristics, microbiological data, and outcomes of C. canimorsus and human-oral–associated Capnocytophaga infection. Results Among 82 patients with Capnocytophaga infection, 46 patients (56.0%) had bacteremia. The most common species identified in this group was C. sputigena (57.9%), followed by C. canimorsus (34.8%). Patients with human-oral–associated Capnocytophaga bacteremia were often immunocompromised, presented with neutropenic fever, and had worse 6-month all-cause mortality compared to C. canimorsus bacteremia (36.4% vs 6.2%, P = .03). They also had a higher β-lactamase production rate (36.4% vs 0.0%, P = .02). Among patients without bacteremia, the main clinical syndrome was polymicrobial head and neck infections (47.2%). Conclusions Human-oral–associated Capnocytophaga bacteremia occurs primarily in immunocompromised patients, particularly those with hematologic malignancy. In contrast, C. canimorsus bacteremia is more likely to present with community-onset infection related to zoonotic exposure. Human-oral–associated Capnocytophaga infection without bacteremia is frequently isolated in polymicrobial infection; this phenomenon’s significance is yet to be fully understood.

Introduction Approximately 15-20% of treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL) have CD20-low tumors, while CD19 is homogeneously expressed in >90% of cases of DLBCL. CD20-low DLBCL is associated with poor response to rituximab-based regimens (Johnson NA, et al. 2009). CD19 functions as a positive regulator of B-cell receptor signaling and is important for B-cell activation and proliferation and is therefore an attractive therapeutic target in addition to CD20. Tafasitamab (MOR208) is a humanized, Fc-enhanced, anti-CD19 monoclonal antibody with improved antibody-dependent cellular cytotoxicity and phagocytosis. Monotherapy with tafasitamab has shown clinical activity in relapsed/refractory (R/R) non-Hodgkin's lymphoma (Jurczak W, et al. 2018). In the Phase II, single-arm L-MIND study (NCT02399085) in patients with R/R DLBCL, combined treatment of tafasitamab with lenalidomide resulted in a high proportion of patients having a complete response (Salles GA, et al. 2020). First-MIND (NCT04134936) is a Phase Ib, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed DLBCL. Here, we report data from the safety run-in phase. Study design and methods Patients must be aged ≥18 years, treatment naïve, with histologically confirmed DLBCL not otherwise specified and have intermediate- to high-risk disease (International Prognostic Index [IPI] 2-5) and an ECOG performance status of 0-2. Known double- or triple-hit lymphoma and transformed lymphoma are excluded. Treatment consists of six 21-day cycles of tafasitamab (12 mg/kg intravenously [IV], on Day [D] 1, 8 and 15) in addition to R-CHOP (Arm A) or tafasitamab (12 mg/kg IV, on D1, 8 and 15) + lenalidomide (25 mg orally, on D1-10) in addition to R-CHOP (Arm B). Granulocyte-colony stimulating factor prophylaxis was mandatory in all patients. The study includes a safety run-in phase and a main phase. In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include ORR, PET-CR rate at end of treatment, PFS, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab. Exploratory objectives include the assessment of circulating cell-free tumor DNA. Approximately 60 patients will be recruited in 9 countries across Europe and the US. Results Recruitment is ongoing. Thirty-six patients were randomized; 18 in each arm. The data presented for the safety run-in phase consist of 24 patients: 13 patients in Arm A and 11 patients in Arm B. All completed the first treatment cycle; 88% of patients entered into Cycle 2 and 50% of patients entered into Cycle 3 of treatment. At baseline, their median age was 67 years (range: 47-76; Arm A) and 65 years (range: 40-74; Arm B). Overall, 33% of patients were male and 67% female; IPI scores were: IPI 2, 33%; IPI 3, 42%; IPI 4, 25%. Most patients had advanced stages III/IV (92%) and approximately 50% had bulky disease. Cell of origin was determined to be germinal center B-cell (GCB) DLBCL in 13%, non-GCB DLBCL in 42% and not yet classified in 46% of cases. A total of 248 treatment-emergent adverse events (AEs) by system organ class were documented: 111 in Arm A and 137 in Arm B. Grade ≥3 neutropenia was observed in 54% (Arm A) and 46% (Arm B) of patients. Thrombocytopenia Grade ≥3 was observed in 8% (Arm A) and 18% (Arm B) of patients. Diarrhea, fatigue and vomiting were comparable between the two arms. Febrile neutropenia was uncommon in both arms, with one event each (Figure 1). To date, 23 serious AEs were observed: 11 in Arm A (Grade 2, 1; Grade 3, 6; Grade 4, 4) and 12 in Arm B (Grade 2, 3; Grade 3, 7; Grade 4, 2). One suspected unexpected serious adverse reaction was reported in Arm B - pneumocystis jirovecii pneumonia. No treatment-associated deaths occurred. Conclusions R-CHOP can be safely combined with tafasitamab or tafasitamab + lenalidomide in patients with treatment-naïve DLBCL. Toxicities appear to be similar to what is expected with R-CHOP alone or in combination with lenalidomide. Enrollment is ongoing and updated safety and early efficacy data will be presented at the meeting. Disclosures Belada: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nowakowski:NanoString: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; MorphoSys: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Kite: Consultancy; Kymera: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees. André:Takeda: Consultancy; Karyopharm: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Research Funding; Seattle Genetics: Consultancy; Abbvie: Consultancy; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; Celgene: Other, Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Stevens:Amgen, MorphoSys: Consultancy. Trněný:Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria, Other: Travel Expenses; Gilead: Consultancy, Honoraria, Other: Travel Expenses. Pérez Persona:Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Jannsen: Consultancy, Speakers Bureau; Amgen: Consultancy; Abbvie: Consultancy, Speakers Bureau; Takeda: Consultancy. Klöpfer:MorphoSys AG: Current Employment. Brackertz:MorphoSys AG: Current Employment. Lohrmann:MorphoSys AG: Current Employment. Lahiry:MorphoSys AG: Current Employment. Shah:MorphoSys AG: Current Employment. Fingerle-Rowson:MorphoSys AG: Current Employment. Brugger:MorphoSys AG: Current Employment. Burke:Epizyme: Consultancy; Roche: Consultancy; Bristol Myers Squibb: Consultancy; Kura: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Gilead: Consultancy; Seattle Genetics: Speakers Bureau; AbbVie: Consultancy; Verastem: Consultancy; Bayer: Consultancy; Astra Zeneca: Consultancy; Adaptive: Consultancy; Morphosys: Consultancy.

Abstract Background Vaccine-preventable diseases account for significant morbidity and mortality in the kidney transplant (KT) patient population. AST Guidelines support review and documentation of pneumococcal vaccines in KT candidate infectious disease (ID) evaluations. The objective of this study is to determine the number of KT candidates screened for prior pneumococcal immunizations and the frequency of vaccines ordered by providers when indicated at Mayo Clinic Florida’s (MCF) Transplant Center. Methods This study was an institution-based retrospective analysis of all KT candidates evaluated at MCF from December 2, 2019 – January 14, 2020. Data collection was obtained by electronic health record review. Outcomes included known history and documentation rates of prior pneumococcal vaccinations (both Prevnar 13 and Pneumovax 23) by infectious disease (ID) providers, as well as pneumococcal vaccine order frequency during ID pre-transplant evaluation when indicated. Data analysis was done using simple descriptive statistics. Results Sixty-one patients underwent KT evaluation during the study period. Among the 61 patients, 20 (32.8%) and 20 (32.8%) had a known prior history of receiving Prevnar 13 and Pneumovax 23 vaccinations, respectively. Vaccine history was unknown for Prevnar 13 and Pneumovax 23 in 39 (63.9%) patients. Vaccine status was not documented by ID providers in 2 (3.3%) patients. When appropriate, ID providers ordered Prevnar 13 and Pneumovax 23 in 38 (92.7%) and 41 (100%) patients, respectively. Orders included both electronic and written documentation to account for patients planning immunization elsewhere. Of the 38 patients advised to receive the Prevnar 13 vaccine, 17 (41.5%) patients were documented completing immunization. Pneumovax 23 order completion rates were not recorded since the study period only lasted six weeks due to closure by COVID-19. Table 1. Pneumococcal Vaccine History Documentation Rates Obtained by Patient Recall or Records Table 2. Pneumococcal Vaccine Order Rates at Pre-Kidney Transplant Consultations Table 3. Prevnar 13 Order Completion Rate by Documentation Conclusion The data reflect a high number of patients who either do not recall or have documentation of prior pneumococcal vaccination available at time of KT ID evaluation. Providers documented history of pneumococcal vaccinations extremely well, ordering immunizations when necessary. This study highlights lack of portability of immunization histories in a given patient population and opportunity for improved care. Disclosures Claudia R. Libertin, MD, Pfizer, Inc. (Grant/Research Support, Research Grant or Support)

AbstractBackground:Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (<50 years) patients with esophageal adenocarcinoma. We aimed to assess time trends in the incidence and outcomes of “young-onset” esophageal adenocarcinoma using a population-based database.Methods:We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: <50, 50 to 69, and ≥70 years. Staging was stratified as localized, regional, and distant. Trends in incidence, disease stage, and survival were assessed in three periods (1975–89, 1990–99, and 2000–2015). Univariate and multivariate models were created to identify predictors of mortality.Results:Esophageal adenocarcinoma incidence has increased in patients <50 years of age, with an annual percentage change of 2.9% (95% confidence interval, 1.4%–4.4%) from 1975 to 2015. Young-onset esophageal adenocarcinoma presented at more advanced stages (regional + distant) compared with older patients (84.9% vs. 67.3%; P < 0.01), with increasing proportion of advanced stages over the study period. These patients also experienced poorer 5-year esophageal adenocarcinoma–free survival compared with older patients (22.9%% vs. 29.6%; P < 0.01), although this finding was attenuated on stage-stratified analysis.Conclusions:Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma–free survival.Impact:Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma–specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.