Causes of Death and Survival in Alcoholic Cirrhosis Patients Undergoing Liver Transplantation: Influence of the Patient's Clinical Variables and Transplant Outcome Complications.

BACKGROUND: Clinical and molecular mechanisms involved in the cause and time of death of alcoholic cirrhosis (AC) patients undergoing liver transplantation (LT) are not entirely understood. In sudden death cases, judicial autopsy practice is mandatory for determining the cause and circumstances of death. The medico-legal autopsy data are essential for helping health authorities to guide future public health activities, assess the effectiveness of health systems, and adopt the necessary preventive measures to improve and adapt the treatments in order to increase these patients' survival. OBJECTIVE: Our study aimed to determine the different clinical and sociodemographic causes that influence the different causes of death and the short- and long-term survival of AC patients undergoing liver transplantation. METHODS: A total of 122 deceased AC patients undergoing LT were analyzed at different times post-transplantation. The main pre- and post-transplant complications were analyzed in relation to the cause of death and the patient's survival, as well as the causes and time at which the patient's death occurred. RESULTS: A total of 53.3% of non-sudden death was observed. A large number of the deaths of AC patients undergoing transplantation were due to non-sudden death, sepsis, and graft failure (GF), the main causes of death in the sample being similar in both sexes. In non-sudden deaths, there were no significant differences between the death rates either related or not related to the liver transplant. Sepsis was the main cause, with the highest percentage (21.3%) of mortality, followed by GF (18.9%) and multiorgan failure (15.6%) at ten years. Furthermore, our results showed how pre-transplant clinical complications, such as viral infections and encephalopathy, influence the age at which multiorgan failure occurs in the transplanted patient. CONCLUSION: Multiorgan failure is the leading cause of sudden death, with higher mortality during the first year after transplantation, followed by sepsis and GF. Our results show the vulnerability of AC patients, both in the hospital period after the transplant and outside.

Drug-facilitated sexual assault and other crimes: A systematic review by countries.

Drug-facilitated sexual assault (DFSA) and drug-facilitated crime (DFC) constitute a mode of violence that is generally unknown to the population and may go unnoticed by health professionals. The aim of this systematic review was to analyze the victims of DFC, compiling their sociodemographic characteristics, the toxic substances used and their biological matrices and modes of action, in order to identify the substances that are commonly put to criminal use. The aim would be to establish political and health strategies that inform and warn people about possible criminal social behaviors consequent danger to health. This systematic review was conducted following the PRISMA guidelines. Alcohol, benzodiazepines and cocaine were among the most commonly detected substances. In most of the hospitals, immunoassays, liquid chromatography (LC-MS), or gas chromatography-mass spectrometry (GC-MS) analyses were used to identify the substances, while the most frequently used biological matrices were blood and urine. From a judicial point of view, the instrumental protocols and techniques followed for the detection of toxics in different biological matrices must guarantee the reliability and validity of the results for use in a court of law. The recommendations of international organizations should be followed and must be called upon to strengthen their respective national laws against this chemical submission (CS) phenomenon.

Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Pretransplant CD28 Biomarker (Levels of Expression and Quantification of Molecules per Cell) in Peripheral CD4+ T Cells Predicts Acute Rejection Episodes in Liver and Kidney Recipients.

BACKGROUND: Acute rejection (AR) remains a significant cause of graft loss. Better approaches to predict AR are being investigated. Surface CD28 protein is essential for T-cell proliferation and survival as well as cytokine production. PATIENTS AND METHODS: Pretransplant CD4+CD28+ peripheral T cells were examined in 30 liver recipients (LRs) and 31 kidney recipients (KRs) by flow cytometry. RESULTS: Pretransplant CD4+CD28+ T cells in LRs were significantly lower in rejectors than nonrejectors (P = .002). Furthermore, the total number of CD28 molecules per cell in LRs (P = .02) as well as KRs (P = .047) was significantly lower in rejectors than nonrejectors. The healthy group did not display differences when compared with patients with end-stage liver disease or renal failure; however, stratification analysis displayed higher levels of CD4+CD28+ when compared with rejected LRs (P = .04) but not KRs. CD28 levels <41.94% were able to discriminate LRs at high risk of AR (P = .003). Similarly, a total number of CD28 molecules ≤8359 (P = .031) in LRs and ≤7669 (P = .046) in KRs correlated with high risk of AR. CONCLUSION: The preliminary results presented herein exhibit a fast and noninvasive method that assists clinicians to prevent AR by monitoring CD4+CD28+ peripheral T cells.

CD28 and KIR2D receptors as sensors of the immune status in heart and liver transplantation.

Viral infections and cellular acute rejection (AR) condition immunosuppressive therapy and compromise the evolution of allografts. Immune monitoring can be useful for ascertaining rejection and for differentiating allo-reaction from activation induced by infections. This work analyzes the usefulness of monitoring the expression of CD28 and KIR2D receptors in peripheral blood T lymphocytes by flow cytometry, to ascertain the immune response in heart and liver transplant recipients. In both types of transplant, the up-regulation of CD28 in CD4(+) lymphocytes in the periods of greatest AR frequency indicates an effective allo-response, whereas the post-transplantation emergence of circulating CD8(+)CD28(-) and CD8(+)CD28(-)KIR2D(+) T cells correlates with better early clinical results. Cytomegalovirus (CMV) infection, but not hepatitis C virus (HCV) or other infections, abrogated both CD28 up-regulation and CD8(+)CD28(-)KIR2D(+) T-cell expansion. Our results show that monitoring the expression of CD28 and KIR2D receptors on T lymphocytes might be considered as sensors of the immune status of heart and liver recipients.

Divergences in KIR2D+ natural killer and KIR2D+CD8+ T-cell reconstitution following liver transplantation.

Natural killer (NK) and CD8(+) T cells may be active elements in the allograft response, but little is known about their role in liver transplantation. Some of these cells express killer immunoglobulin-like receptors (KIRs), which after binding specific ligands may transmit inhibitory/activating signals. In this study, circulating NK and CD8(+) T cells expressing CD158a/h (KIR2DL1/S1) or CD158b/j (KIR2DL2/3/S(2)) receptors were analyzed in 142 liver recipients by flow cytometry. They were underrepresented in patients before transplantation, but following transplantation, whereas the KIR2D(+) NK subsets experienced a late recuperation (day 365) mainly in C2-homozygous patients developing early acute rejection, recovery of the 2 CD8(+)KIR2D(+) T cells started earlier, showing significant differences on day 365 between patients without acute rejection and those suffering from it (p = 0.004 and p < 0.0001, respectively). These differences were also evident when the human leukocute antigen-C genotypes of the recipient were considered. In conclusion, whereas the late recovery of KIR2D(+) NK cells in C2/C2 patients appears to be linked to acute rejection, the increase in early CD8(+)KIR2D(+) T cells in overall liver recipients correlates with a most successful early graft outcome. Therefore, monitoring of KIR2D(+) cells appears to be a useful tool for liver transplant follow-up.