Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.     

Differences in patient perceptions of integrated care among black,hispanic, and white Medicare beneficiaries

ObjectiveThis study sought to identify potential disparities among racial/ethnic groups in patient perceptions of integrated care (PPIC) and to explore how methodological differences may influence measured disparities.Data SourceData from Medicare beneficiaries who completed the 2015 Medicare Current Beneficiary Survey (MCBS) and were enrolled in Part A benefits for an entire year.Study DesignWe used 4‐point measures of eight dimensions of PPIC and assessed differences in dimensions among racial/ethnic groups. To estimate differences, we applied a “rank and replace” method using multiple regression models in three steps, balancing differences in health status among racial groups and adjusting for differences in socioeconomic status. We reran all analyses with additional SES controls and using standard multiple variable regression.Data Collection/Extraction MethodsNot applicable.Principal FindingsWe found several significant differences in perceived integrated care between Black versus White (three of eight measures) and Hispanic versus White (one of eight) Medicare beneficiaries. On average, Black beneficiaries perceived more integrated support for self‐care than did White beneficiaries (mean difference = 0.14, SE = 0.06, P =.02). Black beneficiaries perceived more integrated specialists’ knowledge of past medical history than did White beneficiaries (mean difference = 0.12, SE = 0.06, P =.01). Black and Hispanic beneficiaries also each reported, on average, 0.18 more integrated medication and home health management than did White beneficiaries (P <.01 and P <.01). These findings were robust to sensitivity analyses and model specifications.ConclusionsThere exist some aspects of care for which Black and Hispanic beneficiaries may perceive greater integrated care than non‐Hispanic White beneficiaries. Further studies should test theories explaining why racial/ethnic groups perceive differences in integrated care.     

"Diaphragm-like" strictures of the small bowel in patients treated with non-steroidal anti-inflammatory drugs

The radiological findings are described in four patients who developed strictures of the small bowel, and who had received non-steroidal, anti-inflammatory drugs (NSAIDs) for 1.5-15 years. Clinical presentation was that of subacute small bowel obstruction. Small bowel barium studies showed multiple discrete strictures. Some strictures were indistinguishable from those of regional enteritis. Others however were narrow "diaphragm-like" septae encroaching on and markedly narrowing the ileal lumen, and shown histologically to be due to submucosal fibrosis. It is suggested that these strictures are likely to be consequent on NSAIDs administration and that radiologists and surgeons need to be aware of these "diaphragms" which can be very difficult to detect on barium examination, either small bowel follow-through or enteroclysis, and at laparotomy.     

Modulatory effects of phosphatidylserine on the binding of muscarinic cholinergic receptor ligands

The modulation of the binding of muscarinic cholinergic receptor ligands by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was examined in vitro and in vivo. The enrichment of bovine cerebral cortical synaptosomal membranes with BC-PS, using a fusion technique, produced a concentration-dependent decrease in the affinity (increase in K _d ) of [³H]quinuclidinyl benzylate (³H-QNB) specific binding to muscarinic acetylcholine receptors (mAChR), without changes in their maximal number (Bmax). Similar results were observed when [³H]oxotremorine (³H-OXO) was used to label a high affinity subpopulation of mAChR. On the other hand, preincubation of BC-PS liposomes with synaptosomal membranes in a nonoptimum fusion condition (at pH 7.4) did not alter the binding properties of both radioligands. Fusion experiments using a pure phosphatidylserine preparation from spinal cord revealed a similar decrement in the affinity of³H-QNB specific binding. Five day’s intraperitoneal (i.p.) administration of 15 mg/kg of BC-PS liposomes in rats increased the maximal number of cerebral cortical binding sites for³H-OXO. Scatchard analysis revealed no changes in the apparent dissociation constant. This modification is selective in relation to the neural structure studied. Thus, BC-PS treatment did not modify³H-OXO binding in the hippocampal formation and cerebellum. In contrast, parallel experiments using the muscarinic antagonist³H-QNB showed no alteration in the binding properties of mAChR. Five day’s i.p. administration of 15 mg/kg/d of phosphatidylcholine from bovine cerebral cortex (BC-PC) liposomes produced quite similar results to those obtained with BC-PS. These results indicate that mAChR are under the modulatory action of phosphatidylserine (PS) and phosphatidylcholine (PC), and suggest that this endogenous phospholipids may play a regulatory role on the mAChR. The possible implications of these findings on the effects of PC or PS treatment in neurological disorders involving a decrease in central cholinergic functions are discussed.     

Emergency shelters in Vancouver,Canada

The shelter experiences, employment history, income and social service needs utilization were examined among 124 emergency shelter users in Vancouver, British Columbia. Thirty-six (30.5%) reported this as their first experience with living in a shelter; the length of stay in the present shelter ranged from one to 90 days. Reasons for shelter use included: eviction from last place of residence, loss of job, or suffering from health problems rendering one unable to work. The highest unmet service needs were finding affordable housing and finding a job. This combination of scarcity of low-cost housing, health problems, and difficulty in finding employment have led to a situation where emergency shelters have become extended places of residence, a home to many.Sonia Acorn, RN, PhD is an Associate Professor at the School of Nursing, University of British Columbia, Vancouver, Canada.This research was funded by the Mr. and Mrs. P.A. Woodward's Foundation and the Vancouver Foundation.     

The intrauterine ponderal index in relation to birth weight discordance in twin gestations

Objective: To establish the relationship between the fetal ponderal index and birth weight discordance in twins. Method: The fetal ponderal index (estimated fetal weight ÷ femur length³) was calculated in 86 pairs of twins delivered within 2 weeks of the last sonography and analyzed in relation to birth weight discordance. Results: A weak but significant correlation between fetal ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (<15% birth weight difference) had a significantly higher fetal ponderal index compared with members of mildly (15–25%) discordant pairs (P < 0.02), but not as compared with members of severely discordant (>25%) pairs. Conclusion: The characteristics of the fetal ponderal index in twins are similar to those in singletons. Fetal size seems to be diminished in severe but not in mild discordants. However, in its present form, the fetal ponderal index is a poor predictor of discordant growth and therefore should be employed cautiously in twin gestations.     

Pregnancies in an 18-Year Follow-up after Biliopancreatic Diversion

Background: 239 pregnancies occurred in 1136 women who had undergone biliopancreatic diversion (BPD). Methods: There were 73 abortions, and 14 pregnancies are presently in their course. The 152 term pregnancies (six twins) occurred in 129 women 2-173 months (mean 42.7) after BPD. Mean age and current excess weight were 31.4 years (20-42) and 29.1% (-6.9-78.2), and mean excess weight loss was 72.9% (30.4-110.5). Results: Mean weight gain during pregnancy was 6.2 kg (-21-25). In 32 patients (21%), parenteral nutritional support was needed. In all the other patients (79%), the usual supplementations were given. Of the newborns, 122 were delivered at term (84.7%) with a mean weight of 2842.4 g (1760-4600 g) and a mean length of 48.5 cm (43-59 cm), while the 22 preterm babies (15.3%) weighed 2151.1 g (1400-3850 g) and had a length of 44.6 cm (33-56 cm). Forty infants (27.8%) were small for gestational age but 17 of them weighed more than 2500 g. Eleven twins (one abortion at 26th week) were also delivered, with a mean weight of 2088.6 g (1200-3100 g) and a mean length of 45.6 cm (35-50 cm). Delivery was spontaneous in 85 instances (56%), while vacuum extractor was used in one, and 66 cesarean sections were performed. There were two birth malformations, one infant died after surgery for meconium obstruction and two died from unknown causes. Of the 129 women, 35 had been infertile before BPD. Conclusions: Disappearance of infertility and decrease of pregnancy risk are to be considered among the beneficial effects of weight reduction following BPD.     

Physical examination--the significance of Homan's sign]

Homans's sign is often used in the diagnosis of deep venous thrombosis of the leg. A positive Homans's sign (calf pain at dorsiflexion of the foot) is thought to be associated with the presence of thrombosis. However, Homans's sign has a very poor predictive value for the presence or absence of deep vein thrombosis, like any other symptom or clinical sign of this disease.