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Liver transplant (LT) for undocumented immigrants presents numerous challenges. Although the United Network for Organ Sharing has implemented multiple policy changes to lessen the disparities in LT throughout the years, undocumented immigrants remain especially marginalized and disadvantaged when compared with other populations. Since 2013, the Mount Sinai Hospital’s Recanati Miller Transplant Institute has transplanted 16 undocumented immigrants with successful outcomes. Here, we will share our experience of evaluating, caring for, and transplanting these patients and also highlight our team’s mission to ensure that this population has equitable access to lifesaving medical treatment.

Early liver transplantation (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT, but prediction of harmful alcohol use post-LT remains limited. Among 10 ACCELERATE-AH centers, we examined psychosocial evaluations from consecutive LT recipients for AH from 2006 to 2017. A multidisciplinary panel used content analysis to develop a maximal list of psychosocial variables. We developed an artificial intelligence model to predict post-LT harmful alcohol use. The cohort included training (N= 91 among 8 centers) and external validation (N= 25 among 2 centers) sets, with median follow-up of 4.4 (IQR 3.0–6.0) years post-LT. In the training set, AUC was 0.930 (95%CI 0.862–0.998) with positive predictive value of 0.891 (95%CI 0.620–1.000), internally validated through fivefold cross-validation. In the external validation set, AUC was 0.692 (95%CI 0.666–0.718) with positive predictive value of 0.82 (95%CI 0.625–1.000). The model identified specific variables related to social support and substance use as highly important to predict post-LT harmful alcohol use. We retrospectively developed and validated a model that identified psychosocial profiles at LT predicting harmful alcohol use post-LT for AH. This preliminary model may inform selection and post-LT management for AH and warrants prospective evaluation in larger studies among all alcohol-associated liver disease being considered for early LT.

Among children at a community testing site, a widely available SARS-CoV-2 antigen test was highly specific. Although it had lower sensitivity relative to real-time reverse transcription-polymerase chain reaction, antigen testing identified children with live SARS-CoV-2 virus.

Gastroenteritis caused from infections with Salmonella enterica(salmonellosis) causes significant morbidity in Australia. In addition to acute gastroenteritis, approximately 8.8% of people develop irritable bowel syndrome (IBS) and 8.5% of people develop reactive arthritis (ReA). We estimated the economic cost of salmonellosis and associated sequel illnesses in Australia in a typical year circa 2015. We estimated incidence, hospitalizations, other health care usage, absenteeism, and premature mortality for four age groups using a variety of complementary data sets. We calculated direct costs (health care) and indirect costs (lost productivity and premature mortality) by using Monte Carlo simulation to estimate 90% credible intervals (CrI) around our point estimates. We estimated that 90,833 cases, 4,312 hospitalizations, and 19 deaths occurred from salmonellosis in Australia circa 2015 at a direct cost of AUD 23.8 million (90% CrI, 19.3 to 28.9 million) and a total cost of AUD 124.4 million (90% CrI, 107.4 to 143.1 million). When IBS and ReA were included, the estimated direct cost was 35.7 million (90% CrI, 29.9 to 42.7 million) and the total cost was AUD 146.8 million (90% CrI, 127.8 to 167.9 million). Foodborne infections were responsible for AUD 88.9 million (90% CrI, 63.9 to 112.4 million) from acute salmonellosis and AUD 104.8 million (90% CrI, 75.5 to 132.3 million) when IBS and ReA were included. Targeted interventions to prevent illness could considerably reduce costs and societal impact from Salmonellainfections and sequel illnesses in Australia.

Autologous ex vivohematopoietic stem cell gene therapy is particularly relevant in lysosomal storage diseases (LSD) as it offers the prospect of both a safe transplant, as observed in immune deficiency and hematologic illness, and an effective transplant, since it delivers greater enzyme levels to host tissues than is possible in allogeneic transplant. We report early data from such an approach in an allogeneic transplant refractory LSD, Mucopolysaccharidosis type IIIA (MPSIIIA, Sanfilippo syndrome).

Mouse innate-like B cells are a heterogeneous collection of multifunctional cells that control infection, play housekeeping roles, contribute to adaptive immunity, and suppress inflammation. We show that, among leukocytes, chemokine internalization by the D6 receptor is a unique and universal feature of all known innate-like B-cell populations and, to our knowledge, the most effective unifying marker of these cells. Moreover, we identify novel D6activeB1-cell subsets, including those we term B1d, which lack CD5 and CD11b but exhibit typical B1-cell properties, including spontaneous ex vivo production of IgM, IL-10, and anti-phosphorylcholine antibody. The unprecedented opportunity to examine D6 on primary cells has allowed us to clarify its ligand specificity and show that, consistent with a scavenging role, D6 internalizes chemokines but cannot induce Ca2+fluxes or chemotaxis. Unexpectedly, however, D6 can also suppress the function of CXCR5, a critical chemokine receptor in innate-like B-cell biology. This is associated with a reduction in B1 cells and circulating class-switched anti-phosphorylcholine antibody in D6-deficient mice. Therefore, in the present study, we identify a unifying marker of innate-like B cells, describe novel B1-cell subsets, reveal a dual role for D6, and provide the first evidence of defects in resting D6-deficient mice.

To define the role of the α2β1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and α2-null mice. Our findings reveal that the α2β1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F10 melanoma cells, mice lacking α2β1 integrin ex-pression exhibit increased tumor angiogenesis associated with up-regulated VEGFR1 expression. In contrast, there was no α2β1 integrin-dependent difference in the angiogenic response to Lewis lung carcinoma (LLC) cells. Interestingly, whereas B16F10 cells secrete high levels of placental growth factor (PLGF), LLC cells produce high levels of VEGF, but low levels of PLGF. The α2β1 integrin-dependent difference in angiogenesis was restored to LLC cells by expression of PLGF, strongly suggesting that the angiogenic phenotype and tumor growth in the α2-null host is dependent on specific interactions between the tumor cell and the genetically defined integrin repertoire of the host microenvironment. Thus integrin α2-null mice represent an example of genetic alterations of “the soil” determining response to the “seed.”

Griffiths: Affymetrix: Research Funding.

There is no single technology capable of detecting the various genetic and genomic aberrations observed in patients with neoplasia. Patients with myelodysplastic syndrome (MDS) may present with chromosomal copy number changes (duplication, deletion, and amplification), balanced chromosome rearrangements, copy neutral loss of heterozygosity (CN-LOH) and/or gene mutations. Currently only microscopic chromosomal changes, as dictated by the international prognostic scoring system (IPSS-R), are used to determine the genetic risk in MDS. However, different genetic aberrations, particularly gene mutations are anticipated to be incorporated into the IPSS-R in the near future. The Affymetrix CytoScan® HD Array is a high definition array with over 2.6 million markers (both copy number and SNP) allowing resolution capabilities way beyond that of metaphase chromosome analysis.

The α2β1 integrin, a receptor for collagen, laminin, and other matrix and non-matrix ligands, is expressed on some subsets of hematopoietic stem cells (HSC). Previous studies of mobilized HSC suggested that α2β1 integrin expression may distinguish long-term (LT-HSC) from short-term (ST-HSC) HSC. We sought to address the role of the integrin in normal hematopoiesis and following bone marrow transplant. Evaluation of mice in which the α2β1 integrin was genetically deleted demonstrated that peripheral blood counts, bone marrow cellularity, and bone marrow morphology were identical in α2-null mice and their wild type littermate controls, suggesting that α2β1 integrin is not required for hematopoiesis. To further explore the role of the α2β1 integrin in HSC homing and engraftment, we undertook a competitive repopulation assay using a 1:1 mix of α2β1−/− (Ly5.2) and α2β1+/+ (Ly5.1) cells transplanted into lethally irradiated Ly5.1/Ly5.2 mice. Analysis of peripheral blood, bone marrow, spleen, and lymph nodes post-transplant by FACS for the detection of lineage markers (CD3, B220, CD11b, F4/80, Gr-1, NK1.1) and for expression of either CD45.1 (Ly5.1) or CD45.2 (Ly5.2), demonstrated significantly greater reconstitution with α2β1−/− marrow than α2β1+/+ wild type marrow for lymphoid, myeloid, and monocytic lineages. The ratios ranged from 2:1(CD3, p=0.0024) − 5.6:1 (F4/80, p=0.0021). Secondary transplants of bone marrow harvested from primarily reconstituted mice showed similar findings with α2β1−/− (Ly5.2) to α2β1+/+ (Ly5.1) ratios ranging from 3.2:1 (CD3, p=0.0001) to 6.5:1 (F4/80, p<0.0001). The ratio was also altered within the HSC population (Lin−ThyloSca+c-kit+ (LTSK)) after transplant with an α2β1−/− (Ly5.2) to α2β1+/+ (Ly5.1) ratio of 4.63:1 (p=0.0136). To evaluate the molecular mechanisms that resulted in dramatic engraftment advantage, quantitative analysis of resting HSC in α2-null and wild-type bone marrow and spleen by FACS was performed. However, no quantitative difference in the LTSK population, and no difference in LT-HSC (LSK CD34−Flk-2−), ST-HSC (LSK CD34+Flk-2−), or multipotent progenitors (LSK CD34+ Flk-2+) was identified. FACS analysis of α4β1 expression showed no increase in α4β1 expression in a2-null HSC compared to wild-type, indicating that α2-null HSC do not compensate with upregulation of α4β1 expression. Homing assays using CFSE labeled α2-null or wild-type bone marrow transplanted into lethally irradiated α2-null or wild type recipients showed no difference in homing, regardless of the donor or recipient genotype. Although HSC numbers were the same, methylcellulose cultures for hematopoietic progenitors showed significantly greater numbers of CFU-C for α2-null bone marrow compared to wild-type (p=0.0067), suggesting either a proliferative advantage or heightened sensitivity to growth factors present in the media. Immunohistochemical analysis of bone marrow from α2-null and wild-type mice for Ki-67 showed significantly greater proliferation in the wild-type compared to α2-null bone marrow. These studies suggest that although α2β1 integrin is not required for normal hematopoiesis, the integrin may play important roles in regulation of HSC proliferation as well as maintenance of the HSC niche.