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Patricia D Jones,1,2 Andrew R Scheinberg,3 Valery Muenyi,3 Joselin Gonzalez-Diaz,1 Paul M Martin,1,2 Erin Kobetz2,4 1Department of Medicine, Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, Florida, USA; 2Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA; 3Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA; 4Department of Medicine, Division of Computational Medicine and Population Health, University of Miami Miller School of Medicine, Miami, Florida, USACorrespondence: Patricia D JonesDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 NW 14 th Street, Miami, FL 33136, USATel +1 305 243-0779Email pdjones@med.miami.eduBackground: Disparities in hepatocellular carcinoma (HCC) have been partly attributed to low socioeconomic status among minorities. We investigated associations between race, socioeconomic characteristics, geographic characteristics and survival in HCC patients in Florida.Methods: Using the Florida Cancer Data System (FCDS), we analyzed HCC cases diagnosed between 1/1/2004 and 12/31/2013. To ascertain population-level socioeconomic characteristics, we linked FCDS to the 2010–2014 US Census American Community Survey and the 2013 Florida Behavioral Risk Factor Surveillance System. We also estimated patient distance to liver transplant and academic cancer centers. Using Cox proportional hazards, we modeled the association between race and survival.Results: Of 10,852 patients, 13.1% were Black, 67.1% White, 15.7% Hispanic, and 3.2% Asian. At diagnosis, Blacks were younger with more extensive disease, p

The impact of preserved museum specimens is transforming and increasing by three-dimensional (3D) imaging that creates high-fidelity online digital specimens. Through examples from the openVertebrate (oVert) Thematic Collections Network, we describe how we created a digitization community dedicated to the shared vision of making 3D data of specimens available and the impact of these data on a broad audience of scientists, students, teachers, artists, and more. High-fidelity digital 3D models allow people from multiple communities to simultaneously access and use scientific specimens. Based on our multiyear, multi-institution project, we identify significant technological and social hurdles that remain for fully realizing the potential impact of digital 3D specimens.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKƴ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 dose (RP2D) for phase 2 expansion. Phase 2 patients (n = 30) received RP2D (nanatinostat 20 mg daily, 4 days per week with valganciclovir 900 mg orally daily) for 28-day cycles. The primary end points were safety, RP2D determination (phase 1b), and overall response rate (ORR; phase 2). Overall, 55 patients were enrolled (B-non-Hodgkin lymphoma [B-NHL], [n = 10]; angioimmunoblastic T-cell lymphoma-NHL, [n = 21]; classical Hodgkin lymphoma, [n = 11]; and immunodeficiency-associated lymphoproliferative disorders, [n = 13]). The ORR was 40% in 43 evaluable patients (complete response rate [CRR], 19% [n = 8]) with a median duration of response of 10.4 months. For angioimmunoblastic T-cell lymphoma-NHL (n = 15; all refractory to the last prior therapy), the ORR/CRR ratio was 60%/27%. The most common adverse events were nausea (38% any grade) and cytopenia (grade 3/4 neutropenia [29%], thrombocytopenia [20%], and anemia [20%]). This novel oral regimen provided encouraging efficacy across several EBV+ lymphoma subtypes and warrants further evaluation; a confirmatory phase 2 study (NCT05011058) is underway. This phase 1b/2 study is registered at www.clinicaltrials.gov as #NCT03397706.

Based on results collected through a comprehensive needs assessment of farmers market (FM) vendors in Pennsylvania, the purpose of this study was to develop and pilot-test a customized, food safety training program for FM vendors. A customized 3-hour, in-person, training program was developed and pilot tested. Using pre- and post-test assessment tests through piloted training, the results found participants scores on knowledge questions increased significantly by [approximately]20%.

Introdução: A Doença do enxerto contra hospedeiro (DECH) hiperaguda é uma complicação rara no transplante de células tronco hematopoiéticas (TCTH). É caracterizada pela presença de febre com rash cutâneo e/ou alteração hepática e/ou diarreia que precede a enxertia neutrofílica e ocorre uma semana após a infusão das células. Relatamos um caso de DECH hiperaguda confirmada com biópsia cutânea que necessitou de uso de corticoterapia em dose imunossupressora associada a terapia de segunda linha com alcance de resposta completa. Relato de caso: Paciente de 48 anos, branco, masculino, com diagnóstico de Leucemia Linfoblástica Aguda com presença de cromossomo Filadélfia (Ph+), submetido a TCTH alogênico não aparentado HLA 10 × 10 com doadora do gênero feminino, 56 anos e 8 gestações prévias. O regime de condicionamento foi mieloablativo com Fludarabina 30 mg/m2 por 4 dias associado a irradiação corporal total (TBI) na dose 800cGy, e a profilaxia de DECH foi com timoglobulina na dose total de 4,5 mg/kg, Metotrexate 5 mg/m2 nos D+1, D+3, D+5, D+11 e Tacrolimus. Foram infundidas 7.31 × 106 de células CD34+/kg. No sexto dia após a infusão das células progenitoras hematopoiéticas (CPH), o paciente evoluiu com rash maculopapular difuso em 90% de superfície corpórea associado a febre e diarreia. Realizada investigação de diagnósticos diferenciais evidenciando: rotavírus, clostridium e adenovírus em fezes, além de HHV-6 e CMV séricos negativos. Realizada biópsia de lesão cutânea em região abdominal e iniciada metiprednisolona 2 mg/kg/dia endovenosa associado a corticoterapia tópica devido a suspeita de DECH hiperaguda extensa, MAGIC II, IBMTR C. A biópsia de pele evidenciou dermatite de interface de padrão vacuolar corroborando a hipótese de doença do enxerto contra hospedeiro hiperaguda, grau I-II histológico. Em seguimento de corticoterapia em dose imunossupressora paciente apresentou resposta inicial completa e no desmame evoluiu com reaparecimento das lesões, evidenciando corticodependência. Assim, optado por indicação de terapia de segunda linha com ruxolitinibe e fototerapia com UVB-NB (20 sessões), além de manutenção de inibidor de calcineurina e desmame gradual de corticoterapia, atingindo resposta completa. Atualmente, paciente em D+87 em remissão completa do quadro de DECH hiperaguda, em retirada gradual dos imunossupressores. Discussão: A DECH hiperaguda é uma complicação rara do transplante de medula óssea, no entanto apresenta como fatores de risco relacionados a realização de transplante com doador não aparentado, regime de condicionamento mieloablativo e mismatch de gênero (no caso de um doador feminino para receptor masculino). Este tipo de DECH apresenta taxa de resposta completas inferiores quando comparado ao DECH agudo, e, em geral, necessita de terapias adicionais complementares, estando associada a maior mortalidade não relacionada a recaída.

Context: High dose intravenous melphalan followed by Autologous Hematopoietic Stem Cell Transplant (ASCT) has been as essential part of light chain (AL) amyloidosis since 1990s. Patients who achieve complete hematologic response following ASCT have better Overall Survival (OS). However Transplant-Related Mortality (TRM) and clinical complications during ASCT continue to be a challenge and a major concern. Objective/Methods: We retrospectively reviewed AL patients who underwent ASCT between 2016 and 2024 at Beneficência Portuguesa de São Paulo (BP) to assess the procedure's safety and long-term outcomes. We analyzed patient baseline characteristics, Progression-Free Survival (PFS), ICU admission rates and Overall Survival (OS). Results: Twenty seven patients met criteria for this retrospective study. The median age was 60 y/o (95% CI 38‒70), 17 (63%) had an ECOG score 0, 11 (40%) had a mayo score of 1, 11 of which had cardiac involment and 23 renal invovement. Amog them, 81% (95% CI 61%‒92%) received ASCT as part of a first line therapy, five (18%) patients received no therapy prior to ASCT. Twelve (44%) received CyBorDex and nine (33%) Dara-based quadruplet regimens. The most commoly used conditioning regimen was Melphalan 200 mg/m2 (55.6%) with the remainder of patients received 140 mg/m2. During hospitalization, 11 patients experienced congestive heart failure de-compensation (4 profile ‘B’, 7 profile ‘C’), no patients were on dialysis at baseline, but 4 required hemodialysis during hospital follow-up. There were no in-hospital deaths in this cohort, however 33% of patients were admitted to the ICU within 30 days of follow-up (95% CI 16‒510). The OS and progression free survival rates, as estimated at 2 years by Kaplan Meier, were 88% (95% CI 73‒100) and 89% (95% CI 76‒100) respectively, without any mortality within 100 days from ASCT. Conclusion: In the present experience ASCT was safe and resulted in favorable outcomes, without TRM demonstrated.

Introduction: Matched-Sibling Donor (MSD) is considered the gold standard in Hematopoietic Cell Transplantation (HCT). However, for patients lacking an MSD, alternative options include a Matched-Unrelated (MUD) or Haploidentical (HAPLO) donor. Although MUD is an established procedure in Brazil, with the third-largest unrelated donor registry (REDOME), HAPLO with Posttransplant Cyclophosphamide (PTCy) is a novel procedure that has become extremely popular worldwide since the original report in 2008. Objectives: To compare outcomes of HCT using MSD, MUD, and HAPLO in Brazil. Methods: This is a registry-based multicenter prospective study including patients who underwent HCT with MSD, MUD, or HAPLO (with PTCy) donor for Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), or Myelodysplasia (MDS) between 2018 and 2021. The data were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR), which curated the database before providing it to us. Studied outcomes were Overall Survival (OS) and Graft-versus-host disease-, Relapse-Free Survival (GRFS). Survival curves were estimated with the Kaplan-Meier method and compared with the logrank test. Multivariable analysis was performed with Cox models. Multivariable models were selected based on the lowest AIC. This study was approved by the CIBMTR and by local Ethics Committees. Disclaimer: The CIBMTR has not yet reviewed or endorsed the results. Results: We included 513, 262, and 480 patients in the MSD, MUD, and HAPLO groups, respectively, with median follow-up times of 25-, 33-, and 24-months. MSD patients were generally older, and MUD patients had a longer time to transplant. Almost all MUD patients received ATG. Other variables were roughly balanced. Two-year OS was 58% for MSD, 61% for MUD, and HAPLO 54% (p = 0.03). In OS multivariable analysis, HAPLO was associated with inferior OS (HR = 1.30, p = 0.009) compared with MSD, while MUD was not significantly different (HR = 0.93, p = 0.58). Additionally, HAPLO was associated with lower OS compared with MUD (HR = 1.39, p = 0.007). Of note, results were poorer in older patients, those receiving peripheral blood (PBSC, HR = 1.21, p = 0.05), and higher DRI groups. Two-year GRFS was 27% for MSD, 37% for MUD, and 28% HAPLO (p = 0.05). In GRFS multivariable analysis, HAPLO led to inferior GRFS (HR = 1.19, p = 0.03) compared with MSD, with MUD showing no significant difference (HR = 0.95, p = 0.59). HAPLO also had a lower GRFS compared to MUD (HR = 1.26, p = 0.02). Discussion: Our results show that HAPLO's outcomes are slightly poorer compared to MSD or MUD. Some international reports have reached the same result, especially when MUD receives PTCy. Many factors may have influenced the results, two of the most obvious being the high prevalence of CMV in our population and the high genetic miscegenation in Brazil. Moreover, time-to-transplant was longer in MUD, indicating that there could be some kind of survival bias. Our series represents one of the largest in the world in a study conducted with the support of the CIBMTR. Conclusion: MUD transplants should not be systematically replaced by HAPLO in Brazil. However, in situations where the expected time to transplant with MUD donors is long, HAPLO can offer acceptable results, given the small magnitude of the effect and the possibility of survival bias in the MUD group.

Introdução: O anticorpo anti-antígeno plaquetário humano 1a (anti-HPA-1a) está classicamente associado à púrpura aloimune neonatal. Sua descrição no Transplante de Medula Óssea (TMO) alogênico é rara. Apresentamos um caso em que o anticorpo anti-HPA-1a foi identificado em uma paciente com refratariedade plaquetária no período pós TMO alogênico. Relato de caso: Paciente, gênero feminino, 63 anos, caucasiana, foi submetida a TMO alogênico devido ao diagnóstico de mielofibrose primária. Possuía histórico de duas gestações, ambas há mais de vinte anos e sem intercorrências. Havia recebido um total de seis concentrados de hemácias filtrados e irradiados durante o tratamento e nunca necessitou de transfusão de plaquetas pré TMO. A coleta de células progenitoras para o TMO foi realizada via sangue periférico, proveniente de doador não aparentado, gênero masculino, 19 anos, com compatibilidade HLA 12/12. Foi realizada infusão de 7.900.000 de células CD34+/Kg com viabilidade de 82%. O regime de condicionamento foi mieloablativo com fludarabina 30 mg/m2 e bussulfano 130 mg/m2 (com cálculo de AUC 4500) por 4 dias além de timoglobulina dose total 4,5 mg/kg. A profilaxia de doença do enxerto contra o hospedeiro foi realizada com tacrolimus e metotrexato 5 mg/m2 em D+1, D+3, D+6 e D+11. A paciente apresentou plaquetopenia grave a partir do D+5, evoluindo com bolhas hemorrágicas em cavidade oral e epistaxe de repetição. Recebeu neste período um total de sete transfusões de plaquetas não tipadas, sem rendimento transfusional em nenhuma ocasião após realização de cálculo de incremento plaquetário. Foi realizado o ensaio MAIPA no D+8, com detecção de anticorpos anti-HPA-1a. A partir do D+11, recebeu transfusão de plaquetas tipadas HPA-1a negativas, com bom rendimento transfusional, atingindo em torno de 25 mil plaquetas. Foi realizado genotipagem de doador e receptor, que evidenciou receptora HPA-1b/1b e doador HPA-1a/1a. Foi analisada amostra de soro da receptora antes da infusão de células precursoras, já contendo anticorpos anti-HPA-1a, em títulos superiores aos apresentados no D+8. Até o momento deste relato, a paciente encontra-se em D+22 do TMO, ainda apresentando necessidade transfusional de plaquetas HPA-1a compatíveis aproximadamente duas vezes por semana, sem sinais de enxertia plaquetária, apesar de enxertia neutrofílica confirmada no D+14. Discussão: A compatibilidade HPA independe da compatibilidade HLA. Desta forma, apesar de rara, a trombocitopenia aloimune por anticorpo HPA após TMO pode ocorrer em doadores HLA compatíveis. Encontram-se em literatura relatos de casos de plaquetopenia prolongada após TMO devido a anticorpos derivados do doador, tanto em regimes mieloablativos como não mieloablativos, com dependência transfusional de hemocomponentes tipados perdurando por meses. Relatamos um caso de plaquetopenia por anticorpo HPA-1a derivado da receptora, que se manteve mesmo após o regime de condicionamento mieloablativo contendo timoglobulina. A investigação de anticorpos anti-HPA ou a compatibilidade HPA de doador e no pré-TMO não são realizados de rotina. Todavia, a presença de anticorpos anti-HPA-1a pode levar não apenas a refratariedade plaquetária, mas também a plaquetopenia prolongada, podendo gerar morbidade e custos não esperados após TMO alogênico.

Objetivo: Implantação de uma ferramenta digital para manejar os sintomas de pacientes com diagnóstico de Mieloma Múltiplo (MM) assistido por uma enfermeira navegadora, compreendendo os benefícios e os desafios ao paciente e atuação do enfermeiro. Material e métodos: Foram selecionados 284 pacientes a partir do levantamento dos pacientes com diagnóstico de MM cadastrados na base de dados do serviço de arquivo médico e estatística através do CID-10. Foram excluídos pacientes encaminhados para realizar transplante de medula óssea autólogo e participantes em estudos de pesquisa clínica não foram selecionados. Do total, 108 foram elegíveis para o estudo. A abordagem dos participantes foi feita pela enfermeira navegadora que explicou as funcionalidades do aplicativo e a atuação junto a equipe de saúde. Os pacientes que concordaram em participar, assinaram o termo de consentimento e receberam um código para acesso ao aplicativo, do qual possibilita a navegação em um ambiente virtual individualizado sob acompanhamento da enfermeira. Para triagem dos sintomas o aplicativo utiliza a escala do Common Terminology Criteria for Adverse Events (CTCAE) com graduações medidas através de uma régua e com frases que descrevem os sintomas percebidos pelos pacientes. Casos com grau moderado disparam um alerta imediato para a equipe de saúde. Resultados: No período entre maio de 2021 a maio de 2023, todos os 108 pacientes foram abordados, 50 se cadastraram no aplicativo (adesão de 46%). Dos pacientes cadastrados: 26 são do sexo masculino (52 %) e 24 do sexo feminino (48 %). A média de idade foi de 63 anos (34-87; DP 12.). Em relação a linha de tratamento: 46% (23) estavam em primeira; 24% (12) em segunda; 24% (12) em terceira, 4% (2) em quinta linha e 2% (1) paciente sem tratamento iniciado. No aplicativo, 312 reports foram acusados, sendo que 146 estavam relacionados a sintomas; 49 sobre gratidão; 43 sobre sono; 40 registros de peso e 34 de atividade física. 26 pacientes reportaram sintomas dos quais os principais foram: fadiga (20%); dor (18%); constipação intestinal (11%) e diarreia (8%). Questões como problemas com cateter (3%) e casos como neutropenia periférica convulsão (2%) também apareceram. Em relação a gravidade: 32% (46) leve, 39% (57) moderado; 25% (37) grave e 4% (6) muito grave. Sobre as tratativas dos reports: 83% (122) foram resolvidas através da orientação de enfermagem, 8% (12) correspondem a sintomas do paciente reportando durante a instalação do aplicativo e os pacientes foram orientados e esclarecidos pela enfermeira, 4% (6) receberam orientação de enfermagem e compartilhado com a equipe médica para ciência; 2% (3) foram encaminhados para equipes de especialistas; 2% (3) encaminhamento direto o pronto atendimento; e 1% (1) foi encaminhado ao pronto atendimento por conduta médica. Discussão: O uso do aplicativo monitorado por uma enfermeira navegadora, possibilitou compreender e mapear os principais sintomas dos pacientes em tratamento, comunicar a equipe de maneira assertiva, definir condutas médicas e direcionar ao serviço de emergência de maneira mais rápida e coerente. O uso de tecnologias aplicadas a gestão de saúde estão cada vez mais presentes no dia-a-dia dos pacientes e instituições hospitalares. O movimento de pensar e repensar sobre novas formas de prestar assistência através de canais seguros e formais de comunicação com os pacientes, fomenta ações futuras para facilitar a jornada dos pacientes e manejo dos sintomas.

Introduction/Purpose: Bunionette deformity affects 23% of the population and has numerous surgical options, including a minimally invasive approach (MIA) to decrease complications. Percutaneous surgery is favored by patients as it decreases pain, inflammation, and noticeable incision sites. Three possible osteotomy sites have been identified: proximal, diaphyseal, and distal. The study investigates the anatomic structures at risk during distal osteotomy of bunionette deformity using a Shannon burr. The distal osteotomy site was on average greater than 8mm from the extensor digitorum longus and adductor digiti minimi while it was 1.64mm from the lateral dorsal cutaneous nerve. The study highlighted the challenges posed by minimally invasive approaches to treating bunionette deformity and the need for cautious consideration when utilizing percutaneous methods. Methods: Eleven fresh frozen below-knee amputated foot and ankle cadavers were used for this study. Cadavers were allowed to thaw for 12 hours at room temperature before performing any tissue handling. All cadavers were visually inspected for evidence of gross pathology. Fluoroscopic radiographs were used to inspect for evidence of preexisting pathology of the fifth metatarsal. All cadavers with gross pathology or radiographic fifth metatarsal pathology were excluded from the study. All procedures were performed by a fellowship trained orthopaedic foot and ankle surgeon. Results: All eleven cadavers met the inclusion criteria for this study. The average age of the patients was 66.6 +/- 20.1 years. There were five female feet and six male feet. There were seven right feet and four left feet. Distance from the percutaneous access site was measured to structures at potential risk. The closest structure at risk was the lateral dorsal cutaneous nerve (LDCN) (1.64 mm), which was contacted 2/11 times and transected both times. The extensor digitorum longus (EDL) and abductor digiti minimi (ADM) had no instances of contact during the procedure. Dissection allowed for the identification of structures at risk and the assessment of osteotomy. All procedures resulted in a complete osteotomy. Conclusion: Overall, distal percutaneous bunionette osteotomy is largely safe. Structures pertinent to the surgery were identified with ease and were intact after osteotomy with a Shannon burr. Anatomic variations of LDCN can present challenges to the procedure. Meticulous dissection and judicious use of fluoroscopy can help prevent further damage. Surgeons should be aware of anatomic variations in order to proceed safely.