Spotlight on NKG2C and the human NK‐cell response to CMV infection

Immune responses to cytomegalovirus (CMV) infection in the mouse and human involve the expansion of specific subsets of natural killer (NK) cells with specific phenotypic characteristics and a heightened ability to produce interferon (IFN)‐gamma. In humans, these NK‐cell responses are largely driven by the activating receptor NKG2C, which recognize human leukocyte antigen (HLA)‐E in complex with leader sequence peptides. In this issue of the European Journal of Immunology, Noyola et al. [Eur. J. Immunol. 2012, 42: 3256‐3266] examine NK‐cell responses in a unique cohort of young children with asymptomatic and symptomatic congenital CMV infection. They also address NK‐cell responses to CMV in relation to NKG2C gene copy number. Children with a symptomatic congenital infection exhibited a marked expansion of NKG2C⁺ NK cells. However, despite having slightly lower frequencies of NKG2C⁺ NK cells, children with a heterozygous deletion of the NKG2C gene seemed to control the virus as efficiently as those with two copies of the NKG2C gene. The present studies shed new light on the role of NKG2C copy number variation on the human NK‐cell response to CMV infection.     

Antibody prevalence and titer to norovirus (genogroup II) correlate with secretor (FUT2) but not with ABO phenotype or Lewis (FUT3) genotype

BACKGROUND: Histo-blood group antigens and secretor status have been associated with susceptibility to Norovirus infections, which suggests that antibody prevalence and titer might correlate with these phenotypes. METHODS: Plasma samples (n = 105) from Swedish blood donors that had been genotyped for secretor (FUT2) and Lewis (Le; FUT3) genotypes and phenotyped for ABO and Le blood groups were analyzed for immunoglobulin G antibody prevalence and titers to norovirus genogroup (GG) II.4. RESULTS: The results showed that nonsecretors (se4128se428) and Lea+b- individuals not only had significantly lower antibody titers than did secretors (P < .0001) and Lea-b+ individuals (P < .0002) but were also significantly more often antibody negative (P < .05). Antibody titers in secretors were not significantly different between individuals of different Le (FUT3) genotypes or different ABO phenotypes. CONCLUSIONS: Nonsecretors and Lea+b- individuals are significantly less prone to be infected with GGII noroviruses. This new information extends previous knowledge and supports the hypothesis that nonsecretors are relatively but not absolutely resistant to norovirus infections.     

Distribution and origin of the peripheral innervation of rat cervical esophagus

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C₂–C₇, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored NPY. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.     

Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR)

Background

Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance.

Methods

Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009–2018) were retrospectively analyzed.

Results

Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively.

Conclusion

Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.     

Life of patients 10 years after a successful pediatric intestinal transplantation in Europe

A multicenter Europe‐wide single‐point study in intestinal transplantation (ITx) centers was conducted to identify and describe patients surviving for more than 10 years after ITx in childhood. The health and nutritional status, care requirements and psychosocial status were recorded. Among 120 transplanted before 2005, 38 patients with a functioning graft were included. Thirty (79%) had an exclusive oral diet, seven (18%) complimentary enteral nutrition for eating disorders, and one a combination of parenteral and enteral nutrition. They received a median of five drugs daily and five had a stoma. We did not observe any catch‐up growth during the 10 years of follow‐up. In the previous five years, 22 patients needed unplanned hospitalization with a median in‐patient stay of six days. Eleven needed ongoing psychiatric follow‐ups, and nine needed other specialist follow‐ups. An increasing independency from parents was seen after the age of 18, with three having a stable employment and 31 pursuing education. Despite a good graft function, growth may not catch up. The burden of medical care remains high in the long term. This has to be closely followed in a multidisciplinary setting to improve long‐term quality of life in these patients.     

Measurement error of the Mini-Mental State Examination among individuals with dementia that reside in nursing homes

Few studies have investigated the measurement error of the Mini-Mental State Examination (MMSE) in the same unit of measurement, also known as absolute reliability. This measurement can help determine whether an observed score change for an individual is likely to represent true change. The aim of this study was to investigate the absolute reliability of the MMSE among individuals with dementia that reside in nursing homes. Among 88 participants, 19 (21.6%) were men, 35 (39.8%) had Alzheimer’s disease, 35 (39.8%) had vascular dementia, and the mean age was 84.0 years (range 65–98). The participants were tested and retested with the MMSE within 1–6 days. Both tests were administered by the same assessor at the same time of day. The mean MMSE score was 13.7 (range 0–28). The absolute difference between MMSE scores varied from 0 to 6 points, and the differences did not correlate with the corresponding score means (p = 0.874). The smallest detectable change (SDC) between two measurements was 4.00. The SDC was independent of depression, impaired vision and hearing, delirium within the last week, dementia type and age. However, the SDC was 5.56 among men and 3.50 among women (p = 0.003). In conclusion, for individuals with dementia that reside in nursing homes, it seems like their MMSE score needs to change by four or more points between two measurements in order for their score change to be reliably higher than the measurement error.Electronic supplementary materialThe online version of this article (10.1007/s10433-020-00572-9) contains supplementary material, which is available to authorized users.