In the Era of mRNA Vaccines,Is There Any Hope for HIV Functional Cure?

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.     

Five Year Trends in the Utilization of Robotic Bariatric Surgery Procedures,United States 2015–2019

Purpose

Robotic approaches have been steadily replacing laparoscopic approaches in metabolic and bariatric surgeries (MBS); however, their superiority has not been rigorously evaluated. The main goal of the study was to evaluate the 5-year utilization trends of robotic MBS and to compare to laparoscopic outcomes.

Methods

Retrospective analysis of 2015–2019 MBSAQIP data. Kruskal-Wallis test/Wilcoxon and Fisher’s exact/chi-square were used to compare continuous and categorical variables, respectively. Generalized linear models were used to compare surgery outcomes.

Results

The use of robotic MBS increased from 6.2% in 2015 to 13.5% in 2019 (N= 775,258). Robotic MBS patients had significantly higher age, BMI, and likelihood of 12 diseases compared to laparoscopic patients. After adjustment, robotic MBS patients showed higher 30-day interventions and 30-day readmissions alongside longer surgery time (26–38 min).

Conclusion

Robotic MBS shows higher intervention and readmission even after controlling for cofounding variables.

Graphical Abstract

     

Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.     

REM sleep behavior disorder and vocal cord paralysis in Machado-Joseph disease.

We evaluated the occurrence of REM sleep behaviour disorder (RBD) and vocal cord abductor paralysis (VCAP) in a group of 9 Machado-Joseph disease (MJD) patients. RBD was diagnosed by clinical history plus audiovisual polysomnography in 4 men and 1 woman (55%). While dreaming, 4 fell out of the bed and the other injured his arms. Laryngoscopy detected bilateral VCAP in 1 patient with stridor who required emergency tracheotomy, and partial vocal cord abductor restriction in 2. RBD and VCAP are two potentially injurious conditions that should be considered part of the clinical spectrum of MJD.     

Drug-Induced Lung Diseases: Most Common Reaction Patterns and Corresponding High-Resolution CT Manifestations

Drug-induced lung disease is an increasingly common cause of morbidity and mortality. The diagnosis is based on clinical history and consistent radiologic findings. Lung biopsy is performed in a small percentage of cases. High-resolution CT may demonstrate parenchymal abnormalities in patients with normal radiographs and provides a better depiction of the pattern and distribution of findings. Knowledge of the most common high-resolution CT manifestations and the corresponding histologic patterns is important for early recognition and proper management of drug-induced lung disease.