We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients.
One hundred and sixty-seven LT cases ...followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay).
In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection.
Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.
Hydatid cyst is a zoonotic disease caused by Echinococcus genera. Surgery is needed in most cases. We aimed to describe our center's experience in the surgical management of hepatic hydated cysts ...(HHC).
Data was retrospectively collected for patients who underwent operative management for HHC between the years 1994–2014.
Sixty-nine underwent surgical treatment for HHC. Group A included 34 treated with an unroofing procedure, group B included 24 patients who underwent hepatectomy and group C included 11 patients who underwent peri-cystectomy. The median ± (range) age for groups A, B and C were 39.5 (6.5–69), 40 (17–74) and 32 (20–62), respectively (P > 0.1). Post-operative complications occurred in 16, 11 and 5 patients in group A, B and C, respectively, as assessed by clavien-dindo classification (CDC). The average CDC was significantly higher in the hepatectomy group as compared to the unroofing group (2.3 vs.1.5, P = 0.04). Recurrence was significantly higher after the unroofing procedure as compared to the hepatectomy group (P = 0.05).
Surgery remains the mainstay of treatment for HHC, once surgery is pursued, the results are satisfactory.
The role of angioembolization in managing hemodynamically stable patients with liver injury has obviated the need for surgery. Although mortality and morbidity rates after the adoption of this ...technique have decreased, this procedure is not devoid of complications. This study assesses the impact of this procedure and its associated complications. We performed a case series analysis of patients with hepatic trauma in a level one trauma center over 10 years (2008–2017). Data were collected from hospital records of patients with liver injury and analyzed according to demographics, injury type, management strategy, procedure time, efficacy, complications of embolization, and outcome. We included all patients who underwent angioembolization. Patients who underwent surgery only or had incomplete records were excluded. Of 366 patients with liver trauma, eighteen were managed with angioembolization. Of which, thirteen had grade IV injury or higher, while five had grade II or III. Twelve patients had blunt liver trauma. Six patients were initially managed by laparotomy followed by angioembolization. The most common embolized artery was the right hepatic artery (eleven patients). Nine patients had at least one complication after the procedure. The liver collection was the most common complication (seven patients). There was one hepatic complication-related death. Morbidity was more common in patients who underwent exploratory laparotomy before angioembolization compared to angioembolization alone. Those who had a laparotomy before the angioembolization may have a higher complication rate.
Many obstacles may complicate renal transplant, the preferred treatment for end-stage renal disease. Anatomic anomalies are of special importance during surgery. Double inferior vena cava is a rare ...anomaly reported in 0.2% to 3% of the population and may complicate renal transplant in certain cases. We present a case of a 29-year-old man with end-stage renal disease who was scheduled for repeat kidney renal transplant from a living related donor. His transplant posed many challenges to the transplant team. These included (1) difficult access for dialysis, which required transhepatic insertion of a dialysis catheter, (2) anomalous inferior vena cava anatomy with a double inferior vena cava, (3) a blocked right inferior vena cava, and (4) a small blocked bridging vein connecting the right inferior vena cava to an additional left inferior vena cava. A stent was inserted into the bridging vein to allow venous drainage from the graft. During the transplant procedure, the donated kidney was transplanted into the left iliac fossa and anastomosed to the left external iliac vein. The surgery was successful, without major operative or postoperative complications. The patient was discharged with normal renal function and enjoys normal renal function 6 months after surgery. This case emphasizes the importance of pretransplant evaluation and preparation and the need for high index of suspicion for anatomic variants in donors and recipients.
Living donor kidney transplantation (LDKT) is one of the most effective treatment options for people with end-stage renal disease. Traditionally, LDKT can be either “directed” or “nondirected,” based ...on whether the recipient is specified by the donor. Recently, there has been an increase in conditional and semidirected live kidney donation among strangers, where the donor specifies the characteristics of the recipient whom they wish to donate to. This practice has both gained popularity and sparked controversy in the state of Israel through the nonprofit organization Matnat Chaim. We analyze the ethical implications of this practice by applying traditional principles of medical ethics to conditional LDKT. Although semidirected and conditional LDKT presents some ethical challenges, overall, its practice effectively aligns with core ethical principles. The donors' right to make stipulations respects the donor’s autonomy, the practice avoids harm and benefits both donor and recipient, and justice and utility are upheld as the practice specifically benefits marginalized patients and optimizes resource utilization. Finally, we present data from our institution demonstrating how conditional LDKT increased transplantation for all ethnic groups; Jewish recipients of LDKT increased by 151.32% (P = .034) Arab recipients of LDKT increased by 111.11% (P = .036).
DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes
. Current datasets ...typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells
. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.
The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the ...involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic factor found in the circulation of young mice is able to increase the proliferation rate of old pancreatic β-cells. Old mice parabiosed to young mice have increased β-cell replication compared with unjoined old mice or old mice parabiosed to old mice. In addition, we demonstrate that old β-cells transplanted into young recipients have increased replication rate compared with cells transplanted into old recipients; conversely, young β-cells transplanted into old mice decrease their replication rate compared with young cells transplanted into young recipients. The expression of p16/INK4A mRNA did not change in heterochronic parabiosis, suggesting the involvement of other pathways. We conclude that systemic factors contribute to the replicative decline of old pancreatic β-cells.
•Older liver transplantation recipient had good survival and graft-survival as younger.•Risk factors are male sex, COPD, IHD, DM, and concomitant kidney-liver transplantation.•Careful consideration ...of the pretransplantation risk factors leads to a better outcome.•The patient's age alone should not be used to deny access to transplantation.
Liver diseases epidemiology has changed with advances in perioperative care. Transplantation at large centers is favorable among older and younger recipients. Local limitations on transplantation for recipients older than 65 years were cancelled in 2014. This study evaluates the effects of age on the transplantation outcome of Israeli patients in the era after removal of the limitations on recipient age.
This retrospective analysis examined prospective data on patients older than 18 years who underwent liver or liver–kidney transplantation between 2014 and 2019 at 2 transplantation centers. Patients were divided into 4 age groups (group 1: ≤59 years; group 2: 60–64 years; group 3: 65-69 years; and group 4: ≥70 years). Each group's associations of pretransplantation factors with outcome and survival were examined.
Two hundred sixty-one recipients underwent 269 transplantations (mean age: 53 ± 12.61 y). There were 181 male (67.8%) and 88 female recipients (67.28%). Overall, 207 patients (79.6%) survived ≥12 months. One-year survival rates were 82.9%, 73.2%, 71.4%, and 93.8% for groups 1 to 4, respectively (not statistically significant; P = .11). One-year graft survival was similar between groups. More patients with chronic obstructive pulmonary disease, diabetes mellitus, or ischemic heart disease tended to survive <12 months. Cardiovascular complication was more common in older groups and affected survival.
Patient age alone should not be used to deny access to transplantation, which could benefit older nonfrail individuals. However, risk factors such as male sex, chronic obstructive pulmonary disease, ischemic heart disease, diabetes mellitus, and concomitant kidney-liver transplantation should be carefully considered.
γδT cells are a major component of epithelial tissues and play a role in tissue homeostasis and host defense. γδT cells also reside in the gingiva, an oral tissue covered with specialized epithelium ...that continuously monitors the challenging dental biofilm. Whereas most research on intraepithelial γδT cells focuses on the skin and intestine epithelia, our knowledge on these cells in the gingiva is still incomplete. In this study, we demonstrate that even though the gingiva develops after birth, the majority of gingival γδT cells are fetal thymus-derived Vγ6⁺ cells, and to a lesser extent Vγ1⁺ and Vγ4⁺ cells. Furthermore, we show that γδT cells are motile and locate preferentially in the epithelium adjacent to the biofilm. Vγ6⁺ cells represent the major source of IL-17–producing cells in the gingiva. Chimeric mice and parabiosis experiments indicated that the main fraction of gingival γδT cells is radioresistant and tissue-resident, persisting locally independent of circulating γδT cells. Notably, gingival γδT cell homeostasis is regulated by the microbiota as the ratio of Vγ6⁺ and Vγ4⁺ cells was reversed in germ-free mice, and their activation state was decreased. As a consequence, conditional ablation of γδT cells results in elevated gingival inflammation and subsequent alterations of oral microbial diversity. Taken together, these findings suggest that oral mucosal homeostasis is shaped by reciprocal interplays between γδT cells and local microbiota.
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