2B4 co-stimulation: NK cells and their control of adaptive immune responses

NK cells have primarily been defined by their ability to kill infected cells, tumor cells and some normal cells expressing low levels of MHC class I molecules. NK cells have also been shown to affect adaptive immune responses by their production of both pro- and anti-inflammatory cytokines. Recently it has been shown that adaptive immune responses can be enhanced or maintained also through direct lymphocyte-lymphocyte interactions. One of these interactions was identified to occur between 2B4 and CD48, where 2B4 acted as a co-stimulatory ligand for both NK cells and T cells. In the current article, we discuss the role of 2B4 in the development of adaptive immune responses and the role of NK-T cell interactions in these responses.     

Prevalence and Associated Factors of Sarcopenia in Singaporean Adults—The Yishun Study

ObjectivesTo describe the normative values of sarcopenia among community-dwelling adults (≥21 years of age); compare the prevalence of sarcopenia using Asian Working Group for Sarcopenia criteria, 2014 (AWGS2014), Asian Working Group for Sarcopenia criteria, 2019 (AWGS2019), and European Working Group on Sarcopenia in Older People criteria, 2018 (EWGSOP2) guidelines; and identify factors associated with sarcopenia.DesignParticipants were recruited through random sampling. Sarcopenia assessments were performed using a dual-energy x-ray absorptiometry scan (muscle mass), handgrip test (muscle strength), and usual walking test (physical performance). Questionnaires were administered to evaluate lifestyle and cognition.Setting and ParticipantsIn total, 542 community-dwelling Singaporeans were recruited (21?90 years old, 57.9% women).MethodsWe assessed anthropometry, body composition, and questionnaire-based physical and cognitive factors, and estimated sarcopenia prevalence according to the AWGS2014, AWGS2019, and EWGSOP2 recommendations, and examined associations using logistic regression.ResultsAccording to AWGS2019, the Singapore population-adjusted sarcopenia prevalence was 13.6% (men 13.0%; women 14.2%) overall, and 32.2% (men 33.7%, women 30.9%) in those aged 60 years and above. The cut-offs derived from young adult reference group for low appendicular lean mass index were 5.28 kg/m2 for men and 3.69 kg/m2 for women (lower than AWGS recommended cut-off); for gait speed it was 0.82 m/s, (AWGS2019 recommended cut-off 1.0 m/s, AWGS2014 cut-off was 0.8 m/s); and for handgrip strength it was 27.9 kg/m2 for men and 16.7 kg/m2 for women (close to AWGS2019 recommendation). Age, sex, marital status, alcoholism, physical activity, body mass index, waist circumference, and global cognition were associated with sarcopenia (P < .05).Conclusions and ImplicationsThis is the first study to provide reference values of muscle mass, strength, and gait speed across the adult lifespan of Singaporeans. Using AWGS2019 criteria, sarcopenia is prominent in older age (32.2% in ≥60 years old), but it is already nontrivial (6.9%) among young and middle-age persons. Multidomain lifestyle modifications addressing muscle strength, cognition, and nutrition over the adult lifespan are important to delay the development of sarcopenia.     

Estimate of Burden and Direct Healthcare Cost of Infectious Waterborne Disease in the United States

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million–12.0 million), results in 601,000 ED visits (95% CrI 364,000–866,000), 118,000 hospitalizations (95% CrI 86,800–150,000), and 6,630 deaths (95% CrI 4,520–8,870) and incurring US $3.33 billion (95% CrI 1.37 billion–8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.     

Mitigating disparity in children with acute appendicitis: Impact of patient-driven protocols

PurposePrevious reports in the literature demonstrate racial and ethnic disparities for children diagnosed with acute appendicitis, with minorities experiencing worse outcomes. At our institution, we have developed an evidence based patient driven protocol for children following laparoscopic appendectomy. However, the influence of such protocol on mitigating racial and ethnic disparities in outcomes remains unknown. The purpose of our study is to assess the impact of our protocol by evaluating the influence of race and ethnicity on surgical outcomes among children treated for acute appendicitis.Material and methodsA retrospective review of prospectively collected data was conducted. Children undergoing a laparoscopic appendectomy at our freestanding children's hospital between December 2015 and July 2017 were included. Demographic data, post-operative length of stay, same day discharge rates and hospital readmission rates were abstracted from patient medical records. Patients were classified by their race and ethnic background. Comparative analysis was performed in STATA with a p value < .05 determined as significant.ResultsA total of 786 children were included, with the majority being either White (70%, n = 547), Black (8%, n = 62) or Hispanic (17%, n = 133); 569 patients (72%) were found to have non-perforated appendicitis. There was no statistically significant difference in the rates of same day discharge among White, Black or Hispanic children respectively (88% vs. 77% vs. 86%, p = .126). Of the 217 children with perforated appendicitis, Hispanic children had increased rates of perforation (41%, n = 55) compared to White and Black children respectively (23%, n = 128 and 29%, n = 18, p = .001). However, average post-operative length of stay were similar among White, Black and Hispanic children (96 h vs. 95 h vs. 98 h, p = .015). On multivariate analysis, the only significant risk factor for an elevated post-operative length of stay was the presence of a perforation.ConclusionOur evidence based patient driven protocol effectively mitigates racial and ethnic disparities found in children with acute appendicitis. Further prospective investigation into the role of such patient-driven protocols to mitigate healthcare disparities is warranted.Levels of EvidenceTherapeutic study; Level 3.     

Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign”

Most patients diagnosed with pancreatic cancer are classified as nonoperative candidates based on the contemporary guidelines of resectability. The advent of more potent control of systemic disease using neoadjuvant chemotherapy has enabled more aggressive operative interventions. In our multidisciplinary practice, patients with Stage III, locally advanced pancreatic cancer and superior mesenteric artery (SMA) encasement are now carefully triaged with high quality, preoperative imaging to determine if they can be considered candidates for operative resection with periadventitial dissection of the SMA. Patients displaying a “halo sign,” where the encased SMA remains fully patent and free from arterial invasion, are now candidates for SMA periadventitial dissection. This procedure involves the surgical stripping of the infiltrated neurolymphatic tissue off the SMA leaving behind a bare “skeletonized artery.” Alternatively, the “string sign” involving the SMA confers a more likely case of arterial invasion, where a complete oncologic resection cannot be achieved successfully. This method of patient selection in case of SMA involvement abandons the traditional metrics of circumferential degrees of the arterial encasement to guide surgical decisions. Our institutional approach has allowed us to meaningfully expand our operative methods of resection with the potential for improved longitudinal outcomes to pancreatic cancer patients who were deprived historically from the more effective and possibly curative treatment.     

The use of third-party packed red blood cells during ex situ normothermic machine perfusion of organs for transplantation: Underappreciated complexities?

Ex situ normothermic machine perfusion (NMP) is being used increasingly in the assessment of higher risk deceased donor organs and to facilitate prolonged organ storage. Third-party packed red blood cells (pRBCs) are often used as an oxygen carrier in the perfusate of ex situ NMP. Despite the increasing interest in NMP, comparatively little attention has been paid to the appropriate selection of pRBCs. This includes the choice of ABO blood group and Rhesus D status, the need for special requirements for selected recipients, and the necessity for traceability of blood components. Flushing organs with cold preservation solution after NMP removes the overwhelming majority of third-party allogeneic pRBCs, but residual pRBCs within the organ may have biologically relevant effects following implantation as they enter the recipient's circulation. This review considers these issues, and suggests that national transplant and blood transfusion agencies work together to develop a co-ordinated approach within each country. This is especially important given the possibility of organ re-allocation between centers after ex situ NMP, and the ongoing development of organ perfusion hubs.     

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7–14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.