An odyssey from pre-Civil War Charleston to post-World
War II Minneapolis through Jewish immigrants' eyes
The histories of US immigrants do not always begin and end in
Ellis Island and northeastern ...cities. Many arrived earlier and some
migrated south and west, fanning out into their vast new country.
They sought a renewed life, fresh prospects, and a safe harbor,
despite a nation that was not always welcoming and not always
tolerant. How to Become an American begins with a widow's
abandoned diary-and from there author Daniel Wolff examines the
sweeping history of immigration into the United States through the
experiences of one unnamed, seemingly unremarkable Jewish family,
and, in the process, makes their lives remarkable. It is a deeply
human odyssey that journeys from pre-Civil War Charleston, South
Carolina, to post-World War II Minneapolis, Minnesota. In some
ways, the family's journey parallels that of the nation, as it
struggled to define itself through the Industrial Age. A persistent
strain of loneliness permeates this story, and Wolff holds up this
theme for contemplation. In a country that prides itself on being
"a nation of immigrants," where "all men are created equal," why do
we end up feeling alone in the land we love?
Disruptions of the intestinal microbiome are involved in the pathophysiology of acute gastrointestinal graft versus host disease in patients after allogeneic stem cell transplantation. Systemic ...broad-spectrum antibiotics display a major risk factor for the loss of protective commensal gut bacteria.
Abstract
Background
Maintaining gastrointestinal (GI) microbiome diversity plays a key role during allogeneic stem cell transplantation (ASCT), and loss of diversity correlates with acute GI graft versus host disease (GvHD) and poor outcomes.
Methods
In this retrospective analysis of 161 ASCT patients, we used serial analyses of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters within the first 10 days after ASCT to identify potential commensal microbiota–sparing antibiotics. Based on antibiotic activity, we formed 3 subgroups (Rifaximin without systemic antibiotics, Rifaximin with systemic antibiotics, and Ciprofloxacin/Metronidazole with/without systemic antibiotics).
Results
Mono-antibiosis with Rifaximin revealed higher 3-IS levels (P < .001), higher Clostridium cluster XIVa (CCXIVa) abundance (P = .004), and higher Shannon indices (P = .01) compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics. Rifaximin followed by systemic antibiotics maintained microbiome diversity compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics, as these patients showed still higher 3-IS levels (P = .04), higher CCXIVa copy numbers (P = .01), and higher Shannon indexes (P = .01). Even for this larger cohort of patients, the outcome was superior with regard to GI GvHD (P = .05) and lower transplant-related mortality (P < .001) for patients receiving Rifaximin plus systemic antibiotics compared to other types of systemic antibiotic treatment. Antibiosis with Ciprofloxacin/Metronidazole (n = 12, P = .01), Piperacillin/Tazobactam (n = 52, P = .01), Meropenem/Vancomycin (n = 16, P = .003), Ceftazidime (n = 10, P = .03), or multiple systemic antibiotics (n = 53, P = .001) showed significantly lower 3-IS levels compared to mono-antibiosis with Rifaximin (n = 14) or intravenous Vancomycin (n = 4, not statistically significant).
Conclusions
Different types of antibiotic treatments show different impacts on markers of microbiome diversity. The identification of antibiotics sparing commensal bacteria remains an ongoing challenge. However, Rifaximin allowed a higher intestinal microbiome diversity, even in the presence of systemic broad-spectrum antibiotics.
Chronic graft-versus-host disease (cGVHD) is one of the major causes of late mortality after allogenic hematopoietic stem cell transplantation. Moderate-to-severe cGVHD is associated with poor ...health-related quality of life and substantial disease burden. While corticosteroids with or without calcineurin inhibitors comprise the first-line treatment option, the prognosis for patients with steroid-refractory cGVHD (SR-cGVHD) remains poor. The mechanisms underlying steroid resistance are unclear, and there are no standard second-line treatment guidelines for patients with SR-cGVHD. In this review, we provide an overview on current treatment options of cGVHD and use a series of theoretical case studies to elucidate the rationale of choices of second- and third-line treatment options for patients with SR-cGVHD based on individual patient profiles.
Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease ...(PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promising treatment option. However, generation of antigen-specific T-cell populations has been difficult within a short time frame.
To improve availability in urgent clinical conditions, we developed a rapid protocol for isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) -specific T cells by using an interferon gamma (IFN-γ) capture technique.
We report on the use of adoptive transfer of EBNA-1-specific T cells in 10 pediatric and adult patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft-versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive T-cell transfer. In vivo expansion of transferred EBNA-1-specific T cells was observed in eight of 10 patients after a median of 16 days following adoptive transfer that was associated with clinical and virologic response in seven of them (70%). None of the responders had EBV-associated mortality. Within clinical responders, three patients were disease free by the day of last follow-up (2 to 36 months), three patients died of other infectious complications, and one patient died as a result of relapse of malignancy. EBV-related mortality was observed in two of 10 patients, and another patient had ongoing viremia without clinical symptoms at last follow-up.
Adoptive ex vivo transfer of EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option, representing a fast and efficient procedure to achieve reconstitution of antiviral T-cell immunity after SCT.
CAR-T cells are in standard clinical use to treat relapsed or refractory hematologic malignancies, such as non-Hodgkin's lymphoma, multiple myeloma and acute lymphoblastic leukemia. Owing to the ...rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between European centers in prevention, diagnosis and management of short- and long-term complications. To capture the current CAR-T cell management among EBMT centers and to determine the medical need and specific areas for future clinical research the EBMT Transplant Complications Working Party performed a survey among 227 EBMT CAR-T cell centers. We received complete servey answers from 106 centers (47%) addressing questions in the areas of product selection, CAR-T cell logistics, management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome as well as management in later phases including prolonged cytopenias. We identified common patterns in complication management, but also significant variety in clinical management of the centers in important aspects. Our results demonstrate a high medical need for treatment harmonization and future clinical research in the following areas: treatment of steroid-refractory and very severe CRS/neurotoxicity, treatment of cytopenia, early discharge and outpatient management, as well as immunoglobulin substitution.
Abstract
Background
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment option for many patients with hematological disorders but it includes a ...significant risk of mortality and long-term morbidity. Many patients and their support persons feel overwhelmed when being informed about alloHSCT and may benefit from improvements in consultation style and timing.
Aims
To explore, qualitatively, in a sample of hematological cancer patients and their support persons, their preferences for receiving one longer consultation or two shorter consultations when being informed about alloHSCT. Participants’ perceptions of when and how different consultation styles should be offered were also examined.
Methods
Semi-structured face-to-face and phone interviews were conducted. A purposeful sampling frame was used. Data were analysed using framework analysis.
Results
Twenty patients and 13 support persons were recruited (consent rate: 96%, response rate: 91%). Most patients (60%) and support persons (62%) preferred two shorter consultations over one longer consultation. This helped them digest and recall the information provided, remember questions they had, involve significant others and search for additional information. Patients would have liked to be offered paper and pen to take notes, take a break after 30 min and have their understanding checked at the end of the first consultation, e.g. using question prompt lists. Some patients and support persons preferred both consultations to happen on the same day to reduce waiting times as well as travel times and costs. Others preferred having a few days in-between both consultations to better help them prepare the second consultation. Participants reported varying preferences for different consultation styles depending on personal and disease-related characteristics, such as age, health literacy level and previous treatment.
Conclusion
To our knowledge, this is the first qualitative study to explore patients’ and their support persons’ preferences for having one longer consultation or two shorter consultations when being informed about alloHSCT. Receiving two shorter consultations may help patients process and recall the information provided and more actively involve their support persons. Clinicians should consider offering patients and their support persons to take a break after 30 min, provide paper and pen as well as question prompt lists.
Coordenação Bimanual ao Violão (CBV) é a ação conjunta das duas mãos do violonista na produção de notas, responsável pela qualidade individual de cada nota e pelo legato entre estas. Com vistas à ...análise quantitativa dessa questão, objetivamos investigar a CBV através de seus indícios em registros de áudio coletados. Para tal, procedemos à realização de estudos observacionais e um experimento com violonistas estudantes de graduação e pós-graduação de três instituições de ensino de diferentes regiões do Brasil. Neste trabalho, enfocamos o nosso segundo estudo piloto sobre a temática, realizado com quatro alunos do curso de Bacharelado em Música (Habilitação – Violão) da Faculdade de Música do Espírito Santo (FAMES). Em nossa revisão de literatura, abordamos a coordenação bimanual em diversos instrumentos e o comportamento motor das mãos. Após isso, apresentamos a elaboração, realização, resultados e discussão do nosso piloto observacional.
O presente texto aborda a versão para violão solo de Sérgio Abreu do Poco adagio, da Sonata per il flauto traverso solo senzabasso, Wq 152 (H 562), de Carl Philipp Emanuel Bach (1714-1788), ...comparando-o com o original e analisando suas características instrumentais. Busca-se esclarecer as modificações, os procedimentos e as soluções instrumentais encontradas pelo arranjador. Abreu acrescenta linhas de baixos e acompanhamentos, modifica notas da melodia, reordena notas da melodia, modifica ritmos, substitui pausas por notas, reescreve trechos com polifonias implícitas e adiciona ornamentos. São analisados também recursos mecânicos referentes à realização prática de uma possível versão ao violão, como as digitações de melodias em uma mesma corda, o uso de cordas soltas para mudanças de posição, a utilização de dedos guias, dedos pivôs, aberturas e sobreposições inversas. A partir deste debate é possível apresentar os aspectos musicais e instrumentais do arranjo e as características envolvidas nas escolhas do arranjador.
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in
can cause an immune dysregulation ...syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features. An increased frequency of malignancies in primary immunodeficiencies is known, but their incidence in CTLA-4 insufficiency is unknown.
Clinical manifestations and details of the clinical history were assessed in a worldwide cohort of 184
mutation carriers. Whenever a malignancy was reported, a malignancy-specific questionnaire was filled.
Among the 184
mutation carriers, 131 were considered affected, indicating a penetrance of 71.2%. We documented 17 malignancies, which amounts to a cancer prevalence of 12.9% in affected
mutation carriers. There were ten lymphomas, five gastric cancers, one multiple myeloma, and one metastatic melanoma. Seven lymphomas and three gastric cancers were EBV-associated.
Our findings demonstrate an elevated cancer risk for patients with CTLA-4 insufficiency. As more than half of the cancers were EBV-associated, the failure to control oncogenic viruses seems to be part of the CTLA-4-insufficient phenotype. Hence, lymphoproliferation and EBV viral load in blood should be carefully monitored, especially when immunosuppressing affected
mutation carriers.
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