Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed “trained immunity.” An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to “bend the pandemic curve,” averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.     

Successful stenting in ductal disruption favorably impacts treatment outcomes in patients undergoing transmural drainage of peripancreatic fluid collections

Background and Aim: The role of pancreatic duct (PD) stenting in patients undergoing endoscopic transmural drainage of peripancreatic fluid collection (PFC) remains unclear. The objective of this study is to evaluate the effect of PD stenting on treatment success in patients undergoing endoscopic transmural drainage of PFC. Methods: This is a retrospective follow‐up study of all patients who underwent endoscopic and endoscopic ultrasonography‐guided transmural drainage of PFC during a 5‐year period. Double‐pigtail stents were deployed in all patients; in addition, nasocystic catheters were deployed in those with abscess/necrosis. An endoscopic retrograde cholangiopancreatogram was attempted whenever feasible in all patients, and pancreatic stents were placed when the duct disruption could be bridged. Success was defined as an improvement in symptoms and resolution of PFC upon follow‐up computed tomography at 8 weeks. Results: Of the 110 patients who underwent PFC drainage, 40 (36%) underwent simultaneous PD stenting. Treatment was successful in 95 of the 110 patients (86%). The PFC types were: pseudocyst (62%), necrosis (20%), and abscess (18%). The median duration of follow up was 9.9 months. Those who underwent PD stenting were significantly more likely to have treatment success than those who did not undergo PD stenting (97.5% vs 80%; risk ratio [RR]_crude = 1.48, P = 0.01). In the multivariable analysis, this association remained significant (RR_adjusted = 1.14, 95% confidence interval: 1.01–1.29, P = 0.036), even after adjusting for the etiology of pancreatitis, type and location of PFC, luminal compression at endoscopy, enteral nutrition, white blood cell count, and number of endoscopic interventions. Conclusions: Transpapillary PD stenting improves treatment outcomes in patients undergoing endoscopic transmural drainage of PFC.     

Mycophenolic acid concentrations in long-term heart transplant patients: relationship with calcineurin antagonists and acute rejection

BACKGROUND: When used in conjunction with steroids and cyclosporin, mycophenolate mofetil (MMF) has been shown to significantly reduce mortality and incidence of rejection in the first year after heart transplantation. It also appears that in this early post-transplantation period, the monitoring of immunosuppressive therapies may be warranted. The current study was undertaken to determine if such monitoring is still useful more than 1 yr after heart transplantation. METHODS: Twenty-six patients who had survived the first year after orthotopic heart transplantation and had been on MMF therapy for more than 3 months were prospectively followed. At the time of their routine endomyocardial biopsy blood samples were taken to monitor immunosuppressive therapy. Most patients had two samples taken, on average 109 d apart. RESULTS: There were 22 episodes of asymptomatic rejection documented on a total of 48 biopsies. Of these, only two were of ISHLT (International Society for Heart and Lung Transplantation) grade 3A the remainder being of ISHLT grades 1 or 2. There was no relation between immunosuppressive regimen (tacrolimus and MMF or cyclosporin and MMF) and rejection. There was no relation between monitored immunosuppressive levels and rejection. Patients with the combination of MMF and tacrolimus had significantly higher plasma mycophenolic acid levels despite significantly lower daily MMF dose. CONCLUSION: There does not appear to be a benefit in continued monitoring of plasma mycophenolic acid levels beyond the first year of heart transplantation. There were significant differences in plasma mycophenolic acid levels depending on the type of calcineurin inhibitor concomitantly used.     

Evaluation of intermittent pneumatic compression systems

The operational characteristics of eight intermittent pneumatic compression systems were evaluated. Considerable differences between the pressure/time curves were found when different pumps were compared. The pressure attained in the garments varied from 6 to 124 mmHg and the rate of inflation from less than 1 to 9 mmHg per second.