Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Salivary biochemical variables in liver transplanted children and young adults.

PURPOSE: To investigate associations between levels of blood parameters used to monitor liver-transplanted children with their salivary levels, and compare the salivary parameters of transplant recipients with those of healthy controls. METHODS: Saliva and blood samples from 30 liver transplanted recipients, mean age 11.7 years and saliva from age and sex matched 27 healthy patients were analyzed using a standard complete blood count test. RESULTS: Uric acid and alkaline phosphatase levels correlated significantly between saliva and blood samples in the transplanted subjects. Median salivary sodium level was significantly lower and the median salivary potassium level significantly higher in transplant recipients compared with healthy subjects. No differences were found between the groups in salivary glucose, urea, chloride, total protein, albumin, calcium, phosphorus, uric acid, total bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), triglycerides, cholesterol, iron, transferrin, glutamic pyruvic transaminase (GPT) and gamma-glutamyltranspeptidase (GGT). CONCLUSION: Specific correlations of serum and salivary chemistry were found in liver transplant patients. Such information may lead to the development of noninvasive monitoring tools for this population.

Negative affect and self-agency's association with immunosuppressant adherence in organ transplant: A meta-analysis.

Objective: In organ transplant, prevalence estimates of negative affect (e.g., depressive symptoms) are higher than in the general population and self-agency is required for successful regimen self-management. Nonetheless, the roles of these psychological factors for immunosuppressant adherence in this population remain unclear. Method: Meta-analytic techniques were used to determine the associations between negative affect and self-agency with adherence and to identify moderators of these associational effect sizes (ES). Results: Across 50 studies and 46,106 adult organ recipients, there is a small negative association between negative affect and adherence (mean weighted ES: r = -.14, p < .001; 95% confidence interval, CI [-.175, -.096]) and a small positive association between self-agency and adherence (ES: r = .17, p < .001; 95% CI [.094, .251]). Studies conducted outside of Europe and North America, assessing illness-specific negative affect and utilizing questionnaire adherence measures, and studies of better quality were associated with a larger ES, explaining 54% of the heterogeneity in the negative affect and adherence association. For the association between self-agency and adherence, a higher percentage of females and medication-specific self-agency were associated with a larger ES, explaining 34% of the heterogeneity. Conclusions: By elucidating overlooked trends in the existing literature for the associations between negative affect and self-agency with adherence, the current meta-analyses clarify previously contradicting findings in organ transplant. The findings also shed light on factors contributing to the existing variability and highlight the importance of careful consideration of methodology in studies of adherence postorgan transplant. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Medication adherence in renal transplant recipients: A latent variable model of psychosocial and neurocognitive predictors.

OBJECTIVE: Estimates indicate that 20-70% of renal transplant recipients are medication non-adherent, significantly increasing the risk of organ rejection. Medication adherence is negatively impacted by lower everyday problem solving ability, and associations between depressive symptoms, self-efficacy, and adherence are reported in renal transplant recipients. Nonetheless, to date, these associations have not been examined concurrently. Given the relationship between non-adherence and organ rejection, it is critical to gain a better understanding of the predictors of adherence in renal transplant recipients. To this end, we modeled relationships among cognitive abilities, depressive symptoms, self-efficacy, and adherence in this group. METHODS: Participants (N = 211) underwent renal transplant at least one year prior to participation. Adherence was measured via self-report, medication possession ratio, and immunosuppressant blood-level. Traditionally-measured neurocognitive and everyday problem-solving abilities were assessed. Depressive symptoms were measured via self-report, as were general and medication adherence related self-efficacy. Structural equation modeling was used to assess the fit of the model to available data. RESULTS: Everyday problem solving and self-efficacy had direct positive associations with adherence. Depressive symptoms were negatively associated with self-efficacy, but not adherence. Traditionally-measured neurocognitive abilities were positively associated with self-efficacy, and negatively associated with depressive symptoms. CONCLUSIONS: We present a comprehensive investigation of relationships between cognitive and psychosocial factors and adherence in medically stable renal transplant recipients. Findings confirm the importance of everyday problem solving and self-efficacy in predicting adherence and suggest that influences of depressive symptoms and neurocognitive abilities are indirect. Findings have important implications for future development of interventions to improve medication adherence in renal transplant recipients.

Regression and Genomic Analyses on the Association Between Dose-Normalized Mycophenolic Acid Exposure and Absolute Neutrophil Count in Steroid-Free, De Novo Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant recipients who develop neutropenia have relatively higher dose-normalized MPA exposure than patients without neutropenia, and (ii) the observed neutropenia may be explained by polymorphisms in metabolism and/or transporter genes responsible for MPA disposition. METHODS: Adult kidney transplant recipients on steady-state tacrolimus and MPA, not receiving a corticosteroid, and with stable renal function were recruited for investigation at three periods post-transplant (1, 3, and 12 months; n = 21, 17, and 13, respectively). Clinical variables (age, weight, MPA daily dose, albumin, serum creatinine, absolute neutrophil count), tacrolimus and MPA concentrations (for exposure calculation), and genotypes (UGT2B7 G211T, UGT2B7 C802T, UGT1A9 T-275A, UGT1A9 T98C, MRP2 C-24T, MRP2 G1249A, OATP1B1 A388G, OATP1B1 C463A) were characterized. RESULTS: A significant inverse association between dose-normalized MPA exposure (a surrogate marker for apparent MPA clearance) and absolute neutrophil count in all three study periods (r2 ~ 0.3-0.7) was observed. No associations between characterized single nucleotide polymorphisms and MPA exposure or absolute neutrophil count were established. However, significant alterations in the minor allele frequencies of UGT2B7*2 C802T, UGT1A9 T275A, and MRP2 G1249A were evident. CONCLUSION: These findings support the clinical strategy for conducting MPA therapeutic drug monitoring in adult kidney transplant patients on steroid-free immunosuppressant therapy. The novel population genomic analysis data warrant further epidemiological investigations in a larger study sample.

Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney Transplantation in British Columbia: A Retrospective Cohort Analysis.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a major complication following kidney transplantation. OBJECTIVE: We undertook this study to characterize PTLD in kidney transplant patients in British Columbia with regard to incidence, patient and graft survival, histological subtypes, treatment modalities, and management of immunosuppression. DESIGN: Retrospective cohort analysis. SETTING: British Columbia. PATIENTS: All adult patients who underwent kidney transplantation in British Columbia between January 1, 1996, and December 31, 2012, were included. Patients less than 18 years of age at the time of first transplant and multiple organ transplant recipients were excluded from analysis. MEASUREMENTS: Patients with lymphoproliferative disorders that occurred subsequent to kidney transplantation were considered to have developed PTLD. METHODS: Cases of PTLD were identified by cross-referencing data abstracted from the provincial transplant agency's clinical database with the provincial cancer agency's lymphoma registry. Patients were followed up for the development of PTLD until December 31, 2012, and for outcomes of death and graft failure until December 31, 2014. Data collection was completed via an electronic chart review. RESULTS: Of 2217 kidney transplant recipients, 37 (1.7%) developed PTLD. Nine cases were early-onset PTLD, occurring within 1 year of transplant; of these cases, 6 were known/presumed Epstein-Barr virus mismatch, compared with only 2 of 28 late-onset cases. Patient survival for early-onset PTLD was 100% at 2 years post diagnosis. Late-onset PTLD had survival rates of 71.4% and 67.9% at 1 and 2 years, respectively. PTLD was associated with significantly decreased patient survival (P = .031) and graft survival (uncensored for death, P = .017), with median graft survival of PTLD and non-PTLD patients being 9.5 and 16 years, respectively. Immunosuppressant therapy was reduced in the majority of patients; additional therapies included rituximab monotherapy, CHOP-R, radiation, and surgery. LIMITATIONS: Limitations to this study include its retrospective nature and the unknown adherence of patients to prescribed immunosuppressant regimens. In addition, cumulative doses of immunosuppression received and the degree of immunosuppression reduction for PTLD management were not effectively captured. CONCLUSIONS: The incidence of PTLD in British Columbia following kidney transplantation was low and consistent with rates reported in the literature. The incidence of late-onset PTLD and its association with reduced patient and graft survival warrant further analysis of patients' long-term immunosuppression.

CONTEXTE: Le syndrome lymphoprolifératif post-greffe (SLPG) est une complication grave survenant à la suite d'une transplantation rénale. OBJECTIF DE L'ÉTUDE: Nous avons mené cette étude afin de caractériser le SLPG chez les receveurs d'une greffe rénale en Colombie-Britannique en ce qui a trait à son incidence, à la survie du patient et du greffon, aux sous-types histologiques, aux modalités de traitement et à la gestion de l'immunosuppression. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective effectuée en Colombie-Britannique. SUJETS: Ont été inclus dans l'étude tous les patients adultes ayant subi une transplantation rénale entre le 1er janvier 1996 et le 31 décembre 2012 en Colombie-Britannique. Les patients âgés de moins de 18 ans au moment de l'intervention et les patients receveurs de greffe de multiples organes ont été exclus. MESURES: Tout cas de SL apparu après une greffe rénale étaient considérés comme un SLPG. MÉTHODOLOGIE: Les cas de SLPG ont été répertoriés en recoupant les données extraites de la base de données cliniques de l'agence provinciale de transplantation avec les données du registre des lymphomes tenu par l'agence provinciale de lutte contre le cancer. Les participants ont été suivis jusqu'au 31 décembre 2012 pour l'apparition du SLPG et jusqu'au 31 décembre 2014 pour les issues défavorables telles que la mort du patient ou le rejet du greffon. L'examen du dossier électronique des patients a complété la collecte des données. RÉSULTATS: Des 2 217 receveurs d'une greffe rénale répertoriés, seuls 37 (1,7 %) ont développé un SLPG. L'apparition du SLPG s'est faite de façon précoce, soit dans la première année post-greffe, pour neuf de ces patients, dont six représentaient un cas connu ou présumé de non-concordance pour le virus d'Epstein Barr (EBV). En comparaison, seuls deux des 28 patients ayant expérimenté un développement tardif du SLPG étaient présumés non-concordants pour l'EBV. Deux ans après le diagnostic, 100 % des patients ayant eu une apparition précoce du SLPG avaient survécu. Dans les cas de développement tardif de la maladie, le taux de survie passait à 71,4 % après un an et à 67,9 % après deux ans pour les patients. Le développement du SLPG a été associé avec une réduction significative de la chance de survie du patient (p = 0,031) et du greffon (p = 0,017, cas de décès non censurés). La survie médiane du greffon était de 9,5 ans pour les patients ayant développé un SLPG alors qu'elle était de 16 ans pour les autres. L'intensité du traitement immunosuppresseur a pu être réduite pour la majorité des patients. Les traitements additionnels incluaient la monothérapie au rituximab, le R-CHOP, la radiation et la chirurgie. LIMITES DE L'ÉTUDE: La nature rétrospective de l'étude est un facteur limitant la portée de nos résultats, de même que l'absence de données sur l'adhérence des patients au traitement immunosuppressif. De plus, nous n'avons pu mesurer précisément les doses cumulatives d'immunosuppresseurs reçues, ni le degré de réduction de ces derniers dans la prise en charge du SLPG. CONCLUSION: En Colombie-Britannique, l'incidence du SL post-greffe rénale s'est avérée faible et cohérente avec les taux rapportés dans la littérature. L'incidence de l'apparition tardive du SLPG et son association à un taux et une durée de survie amoindris (à la fois pour le patient et pour le greffon) justifient une analyse plus poussée de l'immunosuppression à long terme dans la population en question.

Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

El uso de la presión positiva espiratoria final (PPEF) en el manejo de la insuficiencia respiratoria aguda / The use of final positive expiratory pressure (FPEP) in the management of acute respiratory failure / O uso da pressão positiva expiratória final (PEEP) no tratamento da insuficiência respiratória aguda

Resumen: Se analiza el efecto de la presión positiva espiratoria final (PPEF) en un grupo de pacientes con insuficiencia respiratoria aguda (IRA) de muy diversa etiología. Del mismo modo se analiza la evolución y otros aspectos del manejo ventilatorio de estos casos. La sola administración de la PPEF modificó en forma significativa y favorable varios de los parámetros respiratorios evaluados: aumento de la PaO2, disminución del índice FiO2/PaO2, disminución del Qs/Qt y del gradiente A-aDO2. No hubo alteración hemodinámica manifiesta a través de los parámetros clínicos: presión arterial, frecuencia cardiaca y diuresis, tampoco hubo alteraciones significativas del gradiente a-vDO2. Complicaciones atribuidas a la PPEF del tipo del «barotrauma¼ fueron encontrados en el 10.4% de los casos. El curso de la IRA fue hacia la mejoría en la mayoría de los pacientes al final de la evolución. La elevada tasa de mortalidad en este grupo de pacientes es atribuida a la presencia de sepsis no controlable y a la coexistencia de múltiples fallas orgánicas. En ninguno de los casos fue atribuida a hipoxemia aguda refractaria. La PPEF, una de las variedades de presión positiva continua, manejada en el concepto de «PPEF óptima¼, representa uno de los avances terapéuticos más importantes de la última década en el manejo de los pacientes con IRA.

Abstract: A group of 19 patients with acute respiratory failure (ARF) of diverse etiology received as a part of their treatment positive end expiratory pressure (PEEP). All of them were evaluated clinicaly and with several respiratory parameters. The response to treatment, complications and mortality rates are analyzed. The addition of PEEP in the management of this patients was accompanied by a significant increase of the PAO2 (p < 0.001) and a simultaneous decrease in the following parameters: FiO2/PaO2 index, Alveolo-arterial oxygen gradient (A-aDO2) and the pulmonary shunt (Qs/Qt). No hemodynamic deterioration was observed. None of the clinical parameters such as: blood pressure, heart rate and diuresis was significantly modified; neither a significant change in the arterious-venous oxygen gradient (a-vDO2) was detected. Pneumothorax as a complication of the use of PEEP was present in the 10.4% of the patients. The course of the ARF was toward the improvement in most of them at the end of the evolution. The high mortality rate in this study was considered to be secondary to uncontrolable sepsis and also to the presence of multiple organ failure. In none of the cases the poor outcome was secondary to refractory acute hypoxemia. PEEP which is one of the varieties of continuos positive pressure ventilation (CPPV) represents one of the most importants therapeutic advances in the last decade in the management of patients with acute respiratory failure.

Résumé: On analyse l'effet de la pression positive expiratoire finale (PPEF) dans un groupe de patients avec Insuf-misance respiratoire aiguë (IRA) d'une très diverse étiologie. De la même façon on analyse l'évolution et d'autres aspects du maniement ventriculaire de ces cas. La seule administration de la PPEF a modifié dans une forme significative et favorable plusieurs des paramètres respiratoires évalués: augmentation de la PaO2, diminution de I'ndice FiO2/PaO2, diminution du Qs/Qt et du gradient A-aDD2. Il n'y a pas eu d'altération hémodynamique manifeste à travers les paramètres cliniques: pression artérielle, fréquence cardiaque et diurèse, il n'y a pas eu non plus des altérations significatives du gradient a-vDO2. Des complications attribuées à la PPEF du type du «barotraume¼ ont été trouvées dans le 10.4% des cas. Le cours de l'IRA a tendu vers l'amélioration chez la plupart des patients à la fin de l'évolution. Le taux élevé de mortalité dans ce groupe de patients est attribué à la présense de sepsis non contrôlable et à la coexitance de multiples défauts organiques. Dans aucun des cas il a été attribué à hypoxémia aiguë réfractaire. La PPEF, une des variétés de pression positive continue, maniée dans le concept de «PPEF très bonne¼, représente l'un des avancements thérapeutiques les plus importants des dix dernières années dans le maniement des patients avec IRA.

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery.

BACKGROUND: During spinal anesthesia for cesarean delivery phenylephrine is the vasopressor of choice but can cause bradycardia. Norepinephrine has both ß- and α-adrenergic activity suitable for maintaining blood pressure with less bradycardia. We hypothesized that norepinephrine would be superior to phenylephrine, requiring fewer rescue bolus interventions to maintain blood pressure. METHODS: Eighty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to Group P (phenylephrine 0.1µg/kg/min) or Group N (norepinephrine 0.05µg/kg/min) fixed-rate infusions. Rescue bolus interventions of phenylephrine 100µg for hypotension, or ephedrine 5mg for bradycardia with hypotension, were given as required to maintain systolic blood pressure. Maternal hemodynamic variables were measured non-invasively. RESULTS: There was no difference between groups in the proportion of patients who required rescue vasopressor boluses (Group P: 65.8% [n=25] vs. Group N: 48.8% [n=21], P=0.12). The proportion of patients who received ⩾1 bolus of phenylephrine was similar between groups (Group P: 52.6% [n=20] vs. Group N: 46.5% [n=20], P=0.58). However, more patients received ⩾1 bolus of ephedrine in the phenylephrine group (Group P: 23.7% [n=9] vs. Group N: 2.3% [n=1], P<0.01). The incidence of emesis was greater in the phenylephrine group (Group P: 26.3% vs. Group P: 16.3%, P<0.001). Hemodynamic parameters including heart rate, the incidence of bradycardia, blood pressure, cardiac output, cardiac index, stroke volume, and systemic vascular resistance and neonatal outcome were similar between groups (all P<0.05). CONCLUSION: Norepinephrine fixed-rate infusion has efficacy for preventing hypotension and can be considered as an alternative to phenylephrine.

An observational study of health literacy and medication adherence in adult kidney transplant recipients.

BACKGROUND: There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. METHODS: Kidney recipients who were at least 6 months post-transplant and outpatients of Vancouver General Hospital in B.C., Canada were recruited through invitation letters. A total of 96 recipients completed the Health Literacy Questionnaire, which provides a multifactorial profile of self-reported health literacy and the Transplant Effects Questionnaire-Adherence subscale measuring self-reported immunosuppressant adherence. Hierarchical linear regression was used to analyze the association between health literacy and adherence after controlling for identified risk factors of non-adherence. RESULTS: Our sample was on average 53 years old, 56% male and 9 years post-transplant. Kidney recipients reported low levels of health literacy on scales measuring active health management and critical appraisal of information and 75% reported non-perfect adherence. Worse adherence was associated with poorer overall health literacy (ΔR2 = 0.08, P = 0.004) and lower scores on six of nine of the health literacy factors. CONCLUSIONS: Poorer health literacy is associated with lower immunosuppressant adherence in adult kidney transplant recipients suggesting the importance of considering a recipient's level of health literacy in research and clinical contexts. Medication adherence interventions can target the six factors of health literacy identified as being risk factors for lower medication adherence.

Belatacept Conversion in an HIV-Positive Kidney Transplant Recipient With Prolonged Delayed Graft Function.

We report an HIV-positive renal transplant recipient with delayed graft function who was converted from tacrolimus to belatacept in an attempt to improve renal function. The patient had kidney biopsies at 4 and 8 weeks posttransplant that revealed acute tubular necrosis and mild fibrosis. After 14 weeks of delayed function, belatacept was initiated and tacrolimus was weaned off. Shortly after discontinuing tacrolimus, renal function began to improve. The patient was able to discontinue dialysis 21 weeks posttransplant. HIV viral load was undetectable at last follow-up. To our knowledge, this is the first report of belatacept use in a patient with HIV.

Diagnosis and management of splenic injury following colonoscopy: algorithm and case series.

BACKGROUND: Splenic injury following colonoscopy is a rare yet life-threatening complication. These injuries are often associated with delayed diagnosis and may require invasive intervention. We sought to study the emergent presentation associated with splenic injury post-colonoscopy and to suggest a new treatment algorithm. METHODS: Six cases of splenic injury following colonoscopy were collected from three medical centers. Data regarding patient medical history, clinical presentation, laboratory and imaging findings and clinical management were recorded. A systematic PubMed/MEDLINE search was performed. Non-English-language publications and publications dating earlier than 2010 were excluded. An emergency department trauma-based management algorithm was designed according to the identified publications and review of the available trauma literature. RESULTS: The mean age was 65.3 years and the male-to-female ratio was 1:5. Five of the cases presented within 24 h of the colonoscopy complaining of severe abdominal pain. Hemodynamic instability was noted in four patients who presented with tachycardia (105-130), hypotension and/or a rapid drop in hemoglobin levels. All of the patients underwent initial resuscitation and a computerized abdominal tomography scan. Four of them required emergent splenectomy. No mortality or major morbidity was reported following the hospitalization. CONCLUSIONS: Although very rare, splenic injury during colonoscopy is an acute, severe and possible fatal complication. Patients may present with a rapid clinical deterioration and hemodynamic instability. Physicians should be familiar with the practical management of this surgical emergency and the treatment options available.

Should HLA mismatch acceptability for sensitized transplant candidates be determined at the high-resolution rather than the antigen level?

Defining HLA mismatch acceptability of organ transplant donors for sensitized recipients has traditionally been based on serologically defined HLA antigens. Now, however, it is well accepted that HLA antibodies specifically recognize a wide range of epitopes present on HLA antigens and that molecularly defined high resolution alleles corresponding to the same low resolution antigen can possess different epitope repertoires. Hence, determination of HLA compatibility at the allele level represents a more accurate approach to identify suitable donors for sensitized patients. This approach would offer opportunities for increased transplant rates and improved long term graft survivals.

Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK.

Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.

Hematite-coated microfossils: primary ecological fingerprint or taphonomic oddity of the Paleoproterozoic?

Microfossils belonging to the 1.88-billion-year-old 'Gunflint-biota' are preserved as carbonaceous and hematitic filaments and spheres that are believed to represent ancient chemolithoautotrophic Fe(II) oxidizing bacteria that grew above a chemocline where ferruginous seawater upwelled into shallow, oxygenated waters. This 'biological' model posits that hematite formed during burial from dewatering of the precursor ferric oxyhydroxides that encrusted Fe(II)-oxidizing bacteria. Here, we present an alternate 'taphonomic' model in which iron-rich groundwaters discharged into buried stromatolites; thus, the mineralization reactions are more informative of diagenetic processes than they are for primary marine conditions. We sampled centimeter-scale columnar stromatolites from both the lower and upper stromatolite horizons of the Biwabik and Gunflint formations, across a range of metamorphic gradients including unaltered to prehnite-pumpellyite taconite, supergene altered ore, and amphibolite-pyroxene grade contact-metamorphic zones. Fossils are rare to very rare and comprise curved filaments that exist in clusters with similar orientations. The filaments from throughout the Biwabik are similar to well-preserved carbonaceous Gunflintia from Ontario. Spheres of Huroniospora are also found in both formations. Microfossils from the least altered sections are preserved as carbon. Prehnite-pumpellyite samples are composed of either carbon or hematite (Fe2 O3 ). Within the contact aureole, filaments are densely coated by magnetite (Fe3 O4 ); the highest grade samples are secondarily oxidized to martite. The consistency in stromatolite microstructure and lithofacies throughout the metamorphic grades suggests they formed under similar environmental conditions. Post-depositional alteration led to replacement of the carbon by iron oxide. The facies association, filament distribution, and lack of branching and attached spherical cells argue against Gunflintia being a direct analogue to common marine, chemolithoautotrophic Fe(II)-oxidizing bacteria. Instead, we propose that the presence of hematite-coated microfossils is a reflection of taphonomic processes and does not necessarily reflect the byproduct of an original microbial ecosystem.

Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease.

Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality-of-life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion-centre administration, and the use of self- or health-professional-administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self-infusion regimens, however, require independence and self-reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self-administer or a lack of self-reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health-related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed.