Preparedness and activities of the anti-SARS-CoV-2 convalescent plasma bank in the Veneto region (Italy): An organizational model for future emergencies.

BACKGROUND: Convalescent plasma (CP) has been used in the past in various pandemics, in particular in H1N1, SARS and MERS infections. In Spring 2020, when ongoing the SARS-CoV-2 pandemics, the Veneto Region (V-R) has proposed setting-up an anti-SARS-CoV-2 CP (CCP) Bank, with the aim of preparing a supply of CCP immediately available in case of subsequest epidemic waves. MATERIALS AND METHODS: Key-points to be developed for a quick set-up of the V-R CCP Bank have been recruitment of donors recovered from COVID-19 infection, laboratory analysis for the biological qualification of the CCP units, including titre of neutralizing antibodies and reduction of pathogens, according to National Blood Centre (CNS) Directives, adaptation of the V-R Information Technology systems and cost analysis. Some activities, including diagnostic and viral inactivation processes, have been centralized in 2 or 3 sites. Laboratory analysis upon preliminary admission of the donor included all tests required by the Italian laws and the CNS directives. RESULTS: From April to August 2020, 3,298 people have contacted the V-R Blood Transfusion Services: of these, 1,632 have been evaluated and examined as first time donors and those found to be suitable have carried out 955 donations, from which 2,626 therapeutic fractions have been obtained, at a cost around 215,00 Euro. Since October 2020, the number of COVID-19 inpatients has had a surge with a heavy hospital overload. Moreover, the high request of CCP therapy by clinicians has been just as unexpected, showing a wide therapeutic use. CONCLUSIONS: The organizational model here presented, which has allowed the rapid collection of a large amount of CCP, could be useful when facing new pandemic outbreaks, especially in low and middle income countries, with generally acceptable costs.

Initial Results of Peripheral-Blood Stem-Cell Mobilization, Collection, Cryopreservation, and Engraftment After Autologous Transplantation Confirm That the Capacity-Building Approach Offers Good Chances of Success in Critical Contexts: A Kurdish-Italian Cooperative Project at the Hiwa Cancer Hospital, Sulaymaniyah.

INTRODUCTION: At Hiwa Cancer Hospital (Sulaymaniyah, Iraqi Kurdistan) after the center was started by a cooperative project in June 2016, autologous transplantation was developed. PATIENTS AND METHODS: To develop the project, the capacity-building approach was adopted, with on-site training and coaching of personnel, educational meetings, lectures, on-the-job training, and the implementation of quality management planning. RESULTS: Here, we report initial results of peripheral-blood stem-cell mobilization and collection of the first 27 patients (age 12 to 61 years; 19 males and 8 females; multiple myeloma, n = 10; plasma cell leukemia, n = 1; Hodgkin lymphoma, n = 12; non-Hodgkin lymphoma, n = 3; and acute myeloid leukemia, n = 1). Only three (11.5%) of 26 patients experienced a failure of mobilization. A median of 6.1 × 106/kg CD34-positive cells per patient were collected (range, 2.4 to 20.8), with two apheretic runs. Twenty-four patients underwent autologous transplantation. All but one transplantation engrafted fully and steadily, with 0.5 and 1.0 × 109/L polymorphonucleates on day 10.5 (range, 8 to 12) and day 11 (range, 9 to 15), respectively, and with 20 and 50 × 109/L platelets on day 13 (range, 10 to 17) and day 17 (range, 2 to 44), respectively. More than 95% of patients are projected to survive 1 year after autograft. CONCLUSION: These data are the result of an Italian effort to establish in Iraqi Kurdistan a leading center for hemopoietic stem-cell transplantation. The capacity building approach was used, with on-site training and coaching as instruments for the development of provider ability and problem solving. With future limitations for immigration, this method will be helpful, especially in the field of high-technology medicine.

The Start-Up of the first Hematopoietic Stem Cell Transplantation Center in the Iraqi Kurdistan: a Capacity-Building Cooperative Project by the Hiwa Cancer Hospital, Sulaymaniyah, and the Italian Agency for Development Cooperation: an Innovative Approach.

We describe the entire process leading to the start-up of a hematopoietic stem cell transplantation center at the Hiwa Cancer Hospital, in the city of Sulaymaniyah, Kurdistan Iraqi Region. This capacity building project was funded by the Italian Development Cooperation Agency and implemented with the support of the volunteer work of Italian professionals, either physicians, nurses, biologists and technicians. The intervention started in April 2016, was based exclusively on training and coaching on site, that represent a significant innovative approach, and led to a first autologous transplant in June 2016 and to the first allogeneic transplant in October. At the time of reporting, 9 months from the initiation of the project, 18 patients have been transplanted, 15 with an autologous and 3 with an allogeneic graft. The center at the HCH represents the first transplantation center in Kurdistan and the second in wide Iraq. We conclude that international development cooperation may play an important role also in the field of high-technology medicine, and contribute to improved local centers capabilities through country to country scientific exchanges. The methodology to realize this project is innovative, since HSCT experts are brought as volunteers to the center(s) to be started, while traditionally it is the opposite, i.e. the local professionals to be trained are brought to the specialized center(s).

The SIRT1 promoter polymorphic site rs12778366 increases IL-6 related human mortality in the prospective study "Treviso Longeva (TRELONG)".

Studies on sirtuins (SIRT), a family of proteins with deacetylase activity, have provided convergent evidence of the key role of these enzymes in aging-linked physiological functions. The link between SIRT1 and longevity has emerged in model organism but few data are available in humans, in particular relying on longitudinal studies. Here, we assessed whether a genetic variant within SIRT1 gene promoter (rs12778366) was associated to human longevity. We analyzed 586 genomic DNA (gDNA) collected in the study "Treviso Longeva" (TRELONG), including elderly over 70 years of age from the municipality of Treviso, a town in the Northeast of Italy, with a 11-year follow-up. We genotyped SIRT1 rs12778366 by real-time polymerase chain reaction (RT-PCR) allelic discrimination assay. A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association between rs12778366 and longevity. When we performed a longitudinal analysis considering mortality as dependent variable, we did not observe an association of rs12778366 with longevity in the whole population (corrected P-value = 0.33). However, when we stratified the TRELONG subjects according to circulating level of interleukin-6 (IL-6), a predictor of disability and mortality, we found that rs12778366 (TC+CC) carriers were at increased risk of mortality in comparison to the TT reference group (corrected P-value = 0.03, HR 1.47). Our data do not support a major role of rs12778366 in human longevity, but the stratified analysis on IL-6 suggests that this variant may be involved in the detrimental effect of high circulating IL-6 in the elderly.

Melatonin and the Charlson Comorbidity Index (CCI): the Treviso Longeva (Trelong) study.

INTRODUCTION: It has been reported that elderly subjects have a compromised ability to produce melatonin nightly, and that reduced melatonin levels may be a risk factor for cancer. The purpose of this study was to evaluate the relationship between melatonin levels and chronic diseases in a cohort of elderly subjects using the Charlson comorbidity index (CCI). DESIGN: We performed a secondary data analysis of a longitudinal study of a representative, age-stratified, sample population. SETTING: The Treviso Longeva (Trelong) study, in Treviso, Italy. PARTICIPANTS: A total of 114 men and 146 women, aged 77 years and older, still alive after 7 years of follow-up. MEASUREMENTS: As an estimation of serum melatonin secretion levels, urinary 6-sulfatoxymelatonin (aMT6s) was assayed in the urine of 260 elderly subjects using an enzyme-linked immunosorbent assay (ELISA) kit (product 01-EK-M6S, ALPCO Immunoassays, Windham, NH). All aMT6s levels were creatinine standardized ([aMT6s]/[creatinine]), and the CCI was calculated. RESULTS: The melatonin levels decreased with aging despite not reaching statistical significance, and the decrease was more evident in males than in females (40.5 ng vs 47.0 ng aMT6s/mg creatinine, ns). Melatonin levels were significantly lower in patients reporting insomnia (p=0.05). The CCI score was inversely correlated with the levels of melatonin (p=0.03). Melatonin levels of subjects affected by CCI pathologies were significantly lower than those of healthy subjects (p=0.03) and of subjects suffering from diseases not included in the CCI and, therefore, less severe (p=0.03). CONCLUSION: Melatonin appears to be a marker of disease state and severity, as well as of sleep disorders, in the elderly. These early findings would confirm the protective role of melatonin against several chronic diseases. The benefits of this agent as a possible medication should be more thoroughly clinically tested.

Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study "Treviso Longeva (TRELONG)".

Human sirtuins are seven proteins with deacetylase activity that are emerging as key modulators of basic physiological functions. Some evidence links SIRT3 to longevity in mammals. This study aimed to investigate whether variants within SIRT3 gene were associated to human longevity. We analyzed 549 genomic DNA collected during the prospective study "Treviso Longeva," including elderly over 70 years of age from the municipality of Treviso, a small city in the northeast of Italy. We genotyped SIRT3 rs3825075, rs4980329, and rs11555236 single nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction allelic discrimination assay. A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association among the SIRT3 SNPs and longevity. However, when we performed a longitudinal analysis considering mortality as a dependent variable, we observed an association of SIRT3 rs11555236 and rs4980329 with longevity in the whole population (p values corrected for potential confounders = 0.04 and 0.03, respectively). After stratification according to gender, the same SNPs were associated to female longevity only (p values corrected for potential confounders = 0.03 and 0.02, respectively). Finally, as rs11555236 was reported to be in linkage disequilibrium with a putative functional enhancer within the SIRT3 gene, we assessed whether rs11555236 genotypes correlated with a different level of SIRT3 protein in peripheral blood mononuclear cells. We found an increased level of SIRT3 in subjects homozygous for the (T) allele. We suggest that SIRT3 genetic variability might be relevant for the modulation of human longevity in the Italian population.