Advancing immunosuppression in liver transplantation: A narrative review.

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation (LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solid-organ transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

Impact of COVID-19 pandemic waves on changes in surgical urgency volumes and severity in the regional hospital network of Trento (Northern Italy): a descriptive epidemiological analysis.

OBJECTIVES: to analyse both direct and indirect impacts on surgical admissions, surgical rates, and clinical picture severity of the two COVID-19 pandemic waves in a hospital network covering an entire province (Trento, located in Trentino-Alto Adige Region, Northern Italy). DESIGN: retrospective epidemiological study. SETTING AND PARTICIPANTS: data regarding the patient load of the Surgical Urgencies/Emergencies flows (SUEs) of the Local Health Authority of the Autonomous Province of Trento derived from the Hospital Discharge Record (HDR) information flow. The population in study was that of patients hospitalized in the entire Province of Trento. This study compares the volume and characteristics of urgent/emergency surgery during the 2020 COVID-19 pandemic with the homologous period in 2019, subdividing the analysed pandemic period in 3 separated groups: • phase I (March-May 2020); • phase II (June-August 2020); • phase III (October-December 2020). The 3 groups represent, respectively: the 1st pandemic wave proclamation of national lockdown from 9 March to 18 May; the summer pandemic remission; the 2nd pandemic wave with partial restrictions on circulation and commercial activities. Clinical and surgical records of SUE population among these 3 periods (March-May; June-August; October-December) of both 2020 and 2019 were analyzed and compared. MAIN OUTCOME MEASURES: the overall number of admissions and surgical rates for SUEs in the study periods were chosen as primary outcomes. The same outcomes were analysed for the most represented diagnoses in the SUEs population: diverticulitis, intestinal obstruction, appendicitis, cholecystitis, gastrointestinal (GI) perforations, pancreatitis, traumas. To assess the degree of clinical picture severity, variables coming from the hospital discharging charts, commonly associated to worst outcomes in term of mortality and morbidity, such as age, length of hospital stay, DRG weight, and patients not discharged at home were extrapolated from the electronic database. A numerical weight was then assigned to each variable, obtaining a scoring system from 0 to 15 (severity index). RESULTS: the number of admissions for SUEs in the studied period showed a sinusoidal trend, with a dramatic decrease in phase I and III (-46.6% and -31.6%, respectively). This trend was also observed even by stratifying admissions for the most frequent pathologies, except for gastrointestinal perforations and pancreatitis. The surgical rate among hospitalised patients for SUEs was 35.2% in phase, significantly higher than that of 2019 (25.6%). Considering the most frequent diagnoses individually, some had a progressive increase in the surgical rate in phases I and II (diverticulitis, bowel obstructions, cholecystitis), others showed an initial decrease and then settled on values ​​not far from those of 2019 (GI perforations and appendicitis), others again had an initial significant increase and then gradually returned to values ​​similar to those of 2019 in phase III (traumas). The mean patients age was significantly higher in phase I than in 2019 (p-value <0.001) and in phase II (p-value <0.05). Consistently with the trend of the number of urgent admissions, even the severity index calculated on the SUEs population showed a sinusoidal trend with and evident increase during the two pandemic waves. CONCLUSIONS: the effect of the COVID-19 pandemic on SUEs was mainly indirect, manifesting itself with a significant reduction in surgical admissions, particularly in phases I and III. Conversely, in the same phases, the surgical rate showed a significant increase compared to 2019. The stratified analysis confirmed these findings for the most frequent diagnoses except for GI perforations and pancreatitis. The clinical pictures were more severe in the two pandemic waves than in the reference period of 2019. Although with a slight numerical attenuation, in general, the second pandemic wave confirmed the first one findings.

Changes in volumes and severity of surgical urgencies during the first two COVID-19 pandemic waves in a regional hospital network.

Background and aim This study analyses the impact of the first two pandemic waves on surgical urgencies/emergencies and their consequences on an entire provincial hospital network's surgical activities. Methods  Clinical and epidemiological data of urgent/emergent surgical admissions and interventions in the Autonomous Province of Trento's hospital network were collected from the internal common electronic database. The investigation periods were March-May 2019 (reference period), March-May 2020 (phase-I), June - August 2020 (phase-II), and October - December 2020 (phase-III). The same data were divided and grouped for the six most represented diagnoses. Results: The number of admissions for surgical emergencies in the studied periods showed a sinusoidal trend. In the reference period of 2019, 957 patients were admitted in urgency, while in the three pandemic phases, urgent admissions were 511, 888 and 633 respectively (-47% in phase I, - 8% in phase II, -34% in phase III). This trend was also observed by stratifying admissions for single disease, except for gastrointestinal perforations and pancreatitis, which showed a slight increasing trend in phase-I. Among the studied population, the surgical rate was 35.2% in phase-I and 34.3% in phase-III; these data were significantly higher than in 2019 (25.6%).  Conclusions The effect of the COVID pandemic on surgical emergencies and urgencies (SUEs) was mainly indirect, manifesting itself with a significant reduction in the number of surgical admissions, particularly in phases-I and-III. Conversely, in the same phases, the surgical rate showed a significant increase compared to 2019.