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Outcome of the liver transplantation (LT) is worse in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients compared to patients infected with HCV alone. We report the world's first case of living donor domino liver transplantation (LDDLT) using a familial amyloid polyneuropathy (FAP) liver in a coinfected recipient with HCV-related liver cirrhosis.
The recipient was a 43-year-old male with a CD4 cell count of 52/μL and undetectable HIV-RNA at the time of LT. He received a domino liver graft from a 41-year-old female with FAP. No acute cellular rejection or infection occurred after LT. HCV recurrence was confirmed histologically on the posttransplant day 34. Peginterferon/ribavirin therapy resulted in non-response; however, the patient achieved a sustained viral response with sofosbuvir (SOF)/ledipasvir (LDV). Currently, HCV and HIV testing are negative, and symptomatic de novo amyloidosis has not occurred.
LDDLT allows successful LT in HCV/HIV-coinfected patients; posttransplant HCV recurrence can be successfully treated with anti-viral therapy.
LDDLT allows successful LT in HCV/HIV-coinfected patients; posttransplant HCV recurrence can be successfully treated with anti-viral therapy.The short residence time, corneal barrier functions, and other effective eye protective mechanisms limited the ocular availability after topical application. Ocular inserts are being developed as polymer films for insertion into the conjunctival sac with the goal of increasing ocular availability. Unfortunately, these devices are not convenient for patients and are associated with many problems. The use of in situ gel/film-forming systems may provide promising alternative with comparable efficacy but this requires verification. Therefore, the current study compared ocular inserts with in situ film-forming liquids containing the same polymer components for ocular delivery of pilocarpine nitrate. Solvent casting technique was employed to prepare the inserts using and polyvinyl alcohol (PVA) as film-forming polymer blended with sodium alginate, as bioadhesive polymer. The effect of addition of either carboxymethycellulose, carbopol, polyvinylpyrrolidone, or methylcellulose was investigated. Solid-state characterization of the inserts indicated compatibility of the drug with film component. All inserts were of acceptable bioadhesive parameters and folding endurance that depended on the film composition. In vitro release studies reflected matrix diffusion kinetics for the film and liquid formulations. This confirms the in situ gelation of liquids. The calculated in vivo miotic pharmacokinetics parameters, using albino rabbits, reflected a better rank for the film but the difference was not statistically different from the in situ gel/film-forming systems. Ocular safety, as reflected by tear volume test, indicated acceptable safety of both liquid and inserts to the eye. The study suggested comparable efficacy of film-forming liquids to that of ocular films. Graphical abstract.
To explore lymph node-related risk factors and investigate the benefit of different adjuvant therapy strategies in hypopharyngeal squamous-cell carcinoma (HPSCC) patients with nodal metastasis (N +).
We conducted a retrospective review covering 266 HPSCC patients with nodal metastasis. Kaplan-Meier curves and Cox proportional hazard models were utilized to evaluate recurrence-free survival (RFS) and independent risk factors.
pT3-T4, extranodal extension, lymphovascular invasion, and lower lymph node involvement were high-risk factors leading to poorer RFS in N + HPSCC patients. Patients were classified into three groups based on the recursive-partitioning analysis (RPA). Postoperative chemoradiation significantly improved RFS in patients in the high-risk group (p < 0.001). For patients in the low- and intermediate-risk groups, the application of adjuvant therapies showed no significant benefit on RFS (p = 0.74 and 0.53, respectively).
The novel risk stratification for N + HPSCC patients can predict the risk of postoperative recurrence effectively. Adjuvant chemoradiation is preferred for patients in the high-risk group as it lowers risk of recurrence. Conversely, for patients in the low- and intermediate-risk groups, regular observation and follow-up strategies are a valid form of treatment.
The novel risk stratification for N + HPSCC patients can predict the risk of postoperative recurrence effectively. Adjuvant chemoradiation is preferred for patients in the high-risk group as it lowers risk of recurrence. Conversely, for patients in the low- and intermediate-risk groups, regular observation and follow-up strategies are a valid form of treatment.The suite of phenotypic diversity across geographically distributed human populations is the outcome of genetic drift, gene flow, and natural selection throughout human evolution. Human genetic variation underlying local biological adaptations to selective pressures is incompletely characterized. With the emergence of population genetics modeling of large-scale genomic data derived from diverse populations, scientists are able to map signatures of natural selection in the genome in a process known as selection mapping. check details Inferred selection signals further can be used to identify candidate functional alleles that underlie putative adaptive phenotypes. Phenotypic association, fine mapping, and functional experiments facilitate the identification of candidate adaptive alleles. Functional investigation of candidate adaptive variation using novel techniques in molecular biology is slowly beginning to unravel how selection signals translate to changes in biology that underlie the phenotypic spectrum of our species. In addition to informing evolutionary hypotheses of adaptation, the discovery and functional annotation of adaptive alleles also may be of clinical significance. While selection mapping efforts in non-European populations are growing, there remains a stark under-representation of diverse human populations in current public genomic databases, of both clinical and non-clinical cohorts. This lack of inclusion limits the study of human biological variation. Identifying and functionally validating candidate adaptive alleles in more global populations is necessary for understanding basic human biology and human disease.
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