Publications by authors named "J S Palmer"

4,221 Publications

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Posttransplant cyclophosphamide as GVHD prophylaxis for peripheral blood stem cell HLA-mismatched unrelated donor transplant.

Blood Adv 2021 Jun;5(12):2650-2659

Department of Hematology and HCT.

Efficacy of PTCy after mismatched unrelated donor (MMUD) HCT is unknown. In this pilot clinical trial, we enrolled 38 patients with hematologic malignancies scheduled to undergo MMUD-HCT (≥6/8 HLA-matched donors) onto 1 of 2 conditioning strata: myeloablative using fludarabine and fractionated total body irradiation (n = 19) or reduced intensity with fludarabine/melphalan (n = 19). Graft source was peripheral blood stem cells (PBSCs), and GVHD prophylaxis was PTCy, tacrolimus, and mycophenolate mofetil. Patients' median age was 53 years (range, 21-72 years). Median number of HLA mismatches was 2 (range, 1-4) of 12 loci. Twenty-three patients (61%) were considered racial (n = 12) or ethnic (n = 11) minorities. Median time to neutrophil engraftment was 16 days (range, 13-35 days). With a median follow-up of 18.3 months (range, 4.3-25.0 months) for surviving patients, 1-year overall survival (OS) and GVHD-free/relapse-free survival (GRFS) were 87% (95% confidence interval [CI]: 71-94) and 68% (95% CI: 51-81), respectively. Cumulative incidence of nonrelapse mortality at 100 days and 1 year were 0% and 11% (95% CI: 4-27), respectively, whereas relapse/progression was 11% (95% CI: 4-27). Cumulative incidence of 100-day acute GVHD grades 2-4 and 3-4 and 1-year chronic GVHD were 50% (95% CI: 36-69), 18% (95% CI: 9-36), and 48% (95% CI: 34-68), respectively. The rate of moderate/severe chronic GVHD was 3% in the entire cohort. We showed highly promising OS/GRFS rates with an acceptable risk profile after PBSC-MMUD-HCT with PTCy. This trial was registered at www.clinicaltrials.gov as #NCT03128359.
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http://dx.doi.org/10.1182/bloodadvances.2021004192DOI Listing
June 2021

Association of Convalescent Plasma Therapy With Survival in Patients With Hematologic Cancers and COVID-19.

JAMA Oncol 2021 Jun 17. Epub 2021 Jun 17.

Departments of Medicine and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: COVID-19 is a life-threatening illness for many patients. Prior studies have established hematologic cancers as a risk factor associated with particularly poor outcomes from COVID-19. To our knowledge, no studies have established a beneficial role for anti-COVID-19 interventions in this at-risk population. Convalescent plasma therapy may benefit immunocompromised individuals with COVID-19, including those with hematologic cancers.

Objective: To evaluate the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic cancers and COVID-19 from a multi-institutional cohort.

Design, Setting, And Participants: This retrospective cohort study using data from the COVID-19 and Cancer Consortium registry with propensity score matching evaluated patients with hematologic cancers who were hospitalized for COVID-19. Data were collected between March 17, 2020, and January 21, 2021.

Exposures: Convalescent plasma treatment at any time during hospitalization.

Main Outcomes And Measures: The main outcome was 30-day all-cause mortality. Cox proportional hazards regression analysis with adjustment for potential confounders was performed. Hazard ratios (HRs) are reported with 95% CIs. Secondary subgroup analyses were conducted on patients with severe COVID-19 who required mechanical ventilatory support and/or intensive care unit admission.

Results: A total of 966 individuals (mean [SD] age, 65 [15] years; 539 [55.8%] male) were evaluated in this study; 143 convalescent plasma recipients were compared with 823 untreated control patients. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (HR, 0.60; 95% CI, 0.37-0.97). This association remained significant after propensity score matching (HR, 0.52; 95% CI, 0.29-0.92). Among the 338 patients admitted to the intensive care unit, mortality was significantly lower in convalescent plasma recipients compared with nonrecipients (HR for propensity score-matched comparison, 0.40; 95% CI, 0.20-0.80). Among the 227 patients who required mechanical ventilatory support, mortality was significantly lower in convalescent plasma recipients compared with nonrecipients (HR for propensity score-matched comparison, 0.32; 95% CI, 0.14-0.72).

Conclusions And Relevance: The findings of this cohort study suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic cancers and COVID-19.
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http://dx.doi.org/10.1001/jamaoncol.2021.1799DOI Listing
June 2021

Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study.

Diabetes Care 2021 Jun 16. Epub 2021 Jun 16.

Kaiser Permanente Southern California, Pasadena, CA.

Objective: To compare effects of medications and laparoscopic gastric band surgery (LB) on α-cell function in dysglycemic youth and adults in the Restoring Insulin Secretion (RISE) Study protocols.

Research Design And Methods: Glucagon was measured in three randomized, parallel, clinical studies: ) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; ) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and ) 88 adults studied at baseline and after 12 and 24 months of LB or MET. Fasting glucagon, glucagon suppression by glucose, and acute glucagon response (AGR) to arginine were assessed during hyperglycemic clamps. Glucagon suppression was also measured during oral glucose tolerance tests (OGTTs).

Results: No change in fasting glucagon, steady-state glucagon, or AGR was seen at 12 months following treatment with MET or G/M (in youth and adults) or PLAC (in adults). In contrast, L+M reduced these measures at 12 months (all ≤ 0.005), which was maintained 3 months after treatment withdrawal (all < 0.01). LB in adults also reduced fasting glucagon, steady-state glucagon, and AGR at 12 and 24 months ( < 0.05 for all, except AGR at 12 months [ = 0.098]). Similarly, glucagon suppression during OGTTs was greater with L+M and LB. Linear models demonstrated that treatment effects on glucagon with L+M and LB were largely associated with weight loss.

Conclusions: Glucagon concentrations were reduced by L+M and LB in adults with dysglycemia, an effect principally attributable to weight loss in both interventions.
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http://dx.doi.org/10.2337/dc21-0461DOI Listing
June 2021

The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis.

Hepatology 2021 Jun 15. Epub 2021 Jun 15.

Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK.

Background And Aims: Stratified therapy has entered clinical practice in primary biliary cholangitis (PBC), with routine use of second-line therapy in non-responders to first-line therapy with ursodeoxycholic acid (UDCA). The mechanism for non-response to UDCA remains, however, unclear and we lack mechanistic serum markers. The UK-PBC study was established to explore the biological basis of UDCA non-response in PBC and to identify markers to enhance treatment.

Approach And Results: Discovery serum proteomics (O-link) with targeted multiplex validation were carried out in 526 subjects from the UK-PBC cohort and 97 healthy controls. In the discovery phase, untreated PBC patients (n=68) exhibited an inflammatory proteome that is typically reduced in scale, but not resolved, with UDCA therapy (n=416 treated patients). 19 proteins remained at a significant expression level (defined using stringent criteria) in UDCA treated patients, 6 of them representing a tightly-linked profile of chemokines (including CCL20, known to be released by biliary epithelial cells (BEC) undergoing senescence in PBC). All showed significant differential expression between UDCA responders and non-responders in both the discovery and validation cohorts. A linear discriminant analysis using serum levels of CXCL11 and CCL20 as markers of responder status indicated a high level of discrimination with an area under the curve of 0.91 (CI 0.83-0.91).

Conclusions: UDCA under-response in PBC is characterised by elevation of serum chemokines potentially related to cellular senescence and previously shown to be released by biliary epithelial cells in PBC, suggesting a potential role in the pathogenesis of high-risk disease. These also have potential for development as biomarkers for identification of high-risk disease and their clinical utility as biomarkers should be evaluated further in prospective studies.
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http://dx.doi.org/10.1002/hep.32011DOI Listing
June 2021

Microscopic Detection, Hematological Evaluation and Molecular Characterization of Piroplasms from Naturally Infected Dogs in Rio de Janeiro, Brazil.

Acta Parasitol 2021 Jun 15. Epub 2021 Jun 15.

Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Rua Professor Hernani Mello, São Domingos, Niterói, Rio de Janeiro, 24210-130, Brasil.

Purpose: This study aimed to analyze the frequency of piroplasmids in the blood of dogs in Rio de Janeiro, compare the performance of microscopic techniques, assess the risk factors associated with infections and also molecularly and morphologically characterize the piroplasmids identified.

Methods: In all, 407 blood samples were collected from dogs between 2018 and 2019. These were subjected to microscopic parasitological techniques for thin and thick smears, stained with Giemsa and using a rapid staining kit. The slides were read under an optical microscope and the protozoa were characterized morphometrically. In addition, the blood samples were subjected to molecular characterization for diagnosing piroplasmid species using primers that amplified the gene 18S rRNA.

Results: Piroplasmids were detected in 38 (9.3%) samples. Of these, 33 samples presented nucleotide sequences compatible with Babesia vogeli. Most of the positive samples were young, male, defined breeds dogs that had been attended in clinics in São Gonçalo city. Thrombocytopenia and leukopenia were the hematological alterations more observed in positive samples, but positive samples without alterations were also detected. The sex was the only variable that showed statistical differences. Males dogs being more often infected than females (p < 0.05). The microscope slides mostly showed piriform and oval merozoites measuring greater than 2.5 µm in length, which were compatible with B. vogeli. However, smaller forms were also identified, thus demonstrating the polymorphic nature of this parasite.

Conclusion: Babesia vogeli was detected in blood samples from dogs in the metropolitan cities of Rio de Janeiro by molecular techniques in different parasite morphotypes.
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http://dx.doi.org/10.1007/s11686-021-00426-zDOI Listing
June 2021