Retrospective Analysis of the Efficacy and Tolerability of Gemcitabine-Based Chemotherapy in Relapsed/Refractory Lymphoma Patients Not Eligible for Stem Cell Transplant.

INTRODUCTION: Gemcitabine-based regimens are effective salvage therapy for RR lymphoma patients eligible for ASCT, but there is limited data in transplant-ineligible (TIE) patients. Here, we present a retrospective analysis on the outcome of TIE adult patients with RR lymphoma treated with gemcitabine, cisplatin or carboplatin and dexamethasone (GDP/GDCarboP) +/- rituximab regimen in our center. PATIENTS: We identified 33 patients: 54.5% diffuse large Bcell lymphoma (DLBCL), 6.1% double/triple hit lymphoma, 15% follicular lymphoma, 18% T-cell lymphoma, and 6% classical Hodgkin lymphoma. Majority of the patients had advanced-stage disease and raised LDH at relapse. The cohort's median age was 71 years. The median number of prior lines of treatment was 2, and 60.6% were refractory to their last line of treatment. RESULTS: The overall response rate was 33% (complete response 15%) for the entire cohort and 62.5% for DLBCL patients not refractory to prior line of treatment. At median follow-up of 25 months, the median duration of response and overall survival in the responders were not reached. Conversely, the median overall survival for the non-responders was dismal at 5 months. Fifty-five percent required treatment alteration (dose attenuation or omission and treatment delay for >1 week) due to adverse events, 73% needed transfusion, and 70% had at least 1 hospital admission during treatment. CONCLUSION: Our real-world data showed that GDP/GDCarboP provides meaningful efficacy and durability, especially among the responders. However, dose modification and inpatient support are frequently needed, indicating the need for good supportive care and close follow-up in this frailer population.

Analysis of transfusion therapy during the March 2019 mass shooting incident in Christchurch, New Zealand.

BACKGROUND AND OBJECTIVE: A mass casualty incident occurred in Christchurch in March 2019. Thirty-seven patients with gunshot wounds were admitted. We describe and analyse the transfusion management of these casualties. METHODS: Data on demographics, injury and laboratory characteristics, and transfusions are summarized using descriptive statistics. Relationships between variables are examined using Pearson's and Spearman's rank correlations. Univariate analysis of explanatory variables is performed to determine the best early predictors of transfusion requirements. The characteristics of massive transfusion and non-massive transfusion cases are compared using the t- and Mann-Whitney tests. RESULTS: Sixty-five per cent received transfusions. Initial Hb, platelet counts and clotting results were mostly normal. On average, each gunshot wound patient was transfused 4, 3·1, 1·2 and 0·4 units of RBC, FFP, cryoprecipitate and platelets, respectively, on the day. Base excess was the single best predictor of transfusion requirements. CONCLUSIONS: A greater proportion of those with gunshot wounds in this incident were transfused than in other such incidents. Transfusion requirements for patients varied but were generally modest. Blood component transfusion ratios were close to that recommended. The role of base excess as a predictor of transfusion requirements in patients with similar injuries needs more study.

Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study.

OBJECTIVE: We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. DESIGN: Population-based cohort study. STUDY SAMPLE: A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. RESULTS: Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. CONCLUSIONS: Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women.

Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study.

OBJECTIVE: to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people. DESIGN: population-based cohort study. PARTICIPANTS: the study population included 4,926 Icelandic individuals, aged ≥67 years, 43.4% male, who completed vision and hearing examinations between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) and were followed prospectively for mortality through 2009. METHODS: participants were classified as having 'moderate or greater' degree of impairment for vision only (VI), hearing only (HI), and both vision and hearing (dual sensory impairment, DSI). Cox proportional hazard regression, with age as the time scale, was used to calculate hazard ratios (HR) associated with impairment and mortality due to all-causes and specifically CVD after a median follow-up of 5.3 years. RESULTS: the prevalence of HI, VI and DSI were 25.4, 9.2 and 7.0%, respectively. After adjusting for age, significantly (P < 0.01) increased mortality from all causes, and CVD was observed for HI and DSI, especially among men. After further adjustment for established mortality risk factors, people with HI remained at higher risk for CVD mortality [HR: 1.70 (1.27-2.27)], whereas people with DSI remained at higher risk of all-cause mortality [HR: 1.43 (1.11-1.85)] and CVD mortality [HR: 1.78 (1.18-2.69)]. Mortality rates were significantly higher in men with HI and DSI and were elevated, although not significantly, among women with HI. CONCLUSIONS: older men with HI or DSI had a greater risk of dying from any cause and particularly cardiovascular causes within a median 5-year follow-up. Women with hearing impairment had a non-significantly elevated risk. Vision impairment alone was not associated with increased mortality.

Gliosis in neonatal SUDI cases.

AIM: To review sudden unexpected infant deaths (SUDI) in the first 28 days of life referred to a Coronial Perinatal Forensic Pathology Service over a 10-year period from 2000 to 2009. METHODS: Cases were collected from mortuary records, and a retrospective review of autopsy reports and other available infant records was undertaken. RESULTS: Twenty-four neonatal SUDI were reviewed. For eight infants, a diagnosis was made at autopsy. For the remaining 16 infants, 14 (87.5%) were bedsharing at the time of death. Maori infants and those living in deprived neighbourhoods were over-represented. Only two infants were preterm, and four were growth-restricted. At post-mortem, white matter gliosis was found in 10 of the 16 (62.5%) unexplained SUDI cases. CONCLUSION: Sudden unexpected infant deaths occur in the first month of life in association with bedsharing. Gliosis may be an important associated risk factor, and its presence indicates a previous insult of prenatal onset.

Characterization of morphine-glucose-6-phosphate dehydrogenase conjugates by mass spectrometry.

A key characteristic of the analyte-reporter enzyme conjugate used in the enzyme-multiplied immunoassay technique (EMIT) is the inhibition of the conjugate enzyme upon anti-analyte antibody binding. To improve our understanding of the antibody-induced inhibition mechanism, we characterized morphine-glucose-6-phosphate dehydrogenase (G6PDH) conjugates as model EMIT analyte-reporter enzyme conjugates. Morphine-G6PDH conjugates were prepared by acylating predominantly the primary amines on G6PDH with morphine 3-glucuronide NHS ester molecules. In this study, morphine-G6PDH conjugates were characterized using a combination of methods, including tryptic digestion, immunoprecipitation, matrix-assisted laser desorption ionization mass spectrometry, and electrospray ionization tandem mass spectrometry. Twenty-six conjugation sites were identified. The identified sites all were found to be primary amines. The degree of conjugation was determined to be less than the number of conjugation sites, suggesting heterogeneity within the morphine-G6PDH conjugate population. Two catalytically important residues in the active site (K22 and K183) were among the identified conjugation sites, explaining at least partially the cause of loss of activity due to the coupling reaction.

A convenient homogeneous enzyme immunoassay for estradiol detection.

A convenient homogeneous enzyme immunoassay for estradiol is described. Unlike heterogeneous immunoassays, which require time-consuming separation steps or expensive automated systems, homogeneous immunoassays, wherein all reagents are freely suspended in bulk solution, can be simple and fast without costly instrumentation. The key component of this assay system, an estradiol-reporter enzyme conjugate, was prepared by covalently binding ß-estradiol-6-(O-carboxymethyl)oxime to glucose-6-phosphate dehydrogenase (G6PDH) by an N-hydroxysuccinimide-enhanced, carbodiimide-mediated coupling reaction. The estradiol-G6PDH activity can be repressed up to 46% upon anti-estradiol antibody binding. The lower detection limit of the assay is 1 nM estradiol in aqueous solution, and the standard curve is linear on logit-log scale-up to 6.7 µM estradiol. A detection limit of 11.5 nM in estradiol-spiked human serum samples suggests the feasibility of applying this assay to monitor estradiol levels for the prediction and prevention of ovarian hyperstimulation syndrome.

An influenza hemagglutinin A peptide assay based on the enzyme-multiplied immunoassay technique.

A practical approach for constructing enzyme-multiplied immunoassay technique (EMIT)-based protein/peptide assays is described. Normally used in small-molecule drug testing, EMIT is a homogeneous assay method that is attractive for its simplicity, sensitivity, and rapidity. The EMIT-based peptide/protein assay was developed by conjugating a cysteine-modified HA peptide (from influenza hemagglutinin A) to the reporter enzyme, glucose-6-phosphate dehydrogenase. The 13-min assay gave a free HA limit of detection of 10 nM and proved effective for detection of a high-molecular-weight model protein tagged with HA. Similar EMIT-based assay approaches may be developed for applications in biotoxin and infectious disease detection.

Chemoselective catalytic hydrogenation of acrolein on Ag(111): effect of molecular orientation on reaction selectivity.

The adsorption and hydrogenation of acrolein on the Ag(111) surface has been investigated by high resolution synchrotron XPS, NEXAFS, and temperature programmed reaction. The molecule adsorbs intact at all coverages and its adsorption geometry is critically important in determining chemoselectivity toward the formation of allyl alcohol, the desired but thermodynamically disfavored product. In the absence of hydrogen adatoms (H(a)), acrolein lies almost parallel to the metal surface; high coverages force the C=C bond to tilt markedly, likely rendering it less vulnerable toward reaction with hydrogen adatoms. Reaction with coadsorbed H(a) yields allyl alcohol, propionaldehyde, and propanol, consistent with the behavior of practical dispersed Ag catalysts operated at atmospheric pressure: formation of all three hydrogenation products is surface reaction rate limited. Overall chemoselectivity is strongly influenced by secondary reactions of allyl alcohol. At low H(a) coverages, the C=C bond in the newly formed allyl alcohol molecule is strongly tilted with respect to the surface, rendering it immune to attack by H(a) and leading to desorption of the unsaturated alcohol. In contrast with this, at high H(a) coverages, the C=C bond in allyl alcohol lies almost parallel to the surface, undergoes hydrogenation by H(a), and the saturated alcohol (propanol) desorbs.

Sulfur, normally a poison, strongly promotes chemoselective catalytic hydrogenation: stereochemistry and reactivity of crotonaldehyde on clean and S-modified Cu(111).

Sulfur adatoms strongly activate the otherwise inert Cu(111) surface towards chemoselective hydrogenation of crotonaldehyde by electronically perturbing and strongly tilting the reactant.

Calcium and calcitriol prophylaxis attenuates posttransplant bone loss.

We performed a prospective, randomized, double-blind study to determine whether calcium and calcitriol prevents posttransplant bone loss. Thirty-eight nondiabetic and 26 diabetic patients without prior steroid exposure undergoing their first kidney or kidney-pancreas transplant were randomized to calcium, calcium plus calcitriol, or placebo. Lumbar spine (LS), femoral neck (FN), and distal radius (DR) bone mineral density scans (BMDs) were obtained at baseline, 6, and 12 months. At 1 year, patients treated with placebo experienced a 2% decline in BMD at the LS and DR and a 1.3% increase at the FN. In contrast, patients treated with calcium and vitamin D had a 0.1% decline at the LS and 2.9% and 4.8% increases at the DR and FN, respectively. Patients receiving cyclosporine had more bone loss than those receiving tacrolimus. Our results demonstrate a small therapeutic effect of calcium and calcitriol and suggest that tacrolimus is less osteotoxic than cyclosporine.