Risk of SARS-CoV-2 transmission in the close contacts in a small rural area in the Veneto Region (NE-Italy): past evidence for future scenarios.

Background: During the first pandemic phase of COVID-19, an epidemiological study, named First survey, was conducted on the population of a small rural area in northern Italy. In spring 2020, the results showed how a prolonged lockdown slowed down the spread of the virus. Methods: After contacting positive First Survey subjects and their families, those who decided to join voluntarily underwent a blood test to assess the presence of qualitative lgG about 2 months after the previous one. This was to determine if IgG persisted in individuals who tested positive in the First Survey as well as to assess the antibody status of their close family members, to determine if they were unintentionally infected. Results: Based on serological analysis, 35.1% of the samples contained blood IgG. In subjects who tested positive during the First Survey, 62.5% remained IgG positive more than 2 months later. Among family members who were exposed to a positive relative, 23.7% were infected. Linear regression analysis showed that the presence of an infected person within a household resulted in the infection spreading to the others, but not excessively. Induced isolation extinguished the infection regardless of the extent of the contagion (intra-family or extra-family). Micro-outbreaks of SARS-Cov-2 infection which arose in the same household from extra-familial infections played a decisive role on the statistical significance of IgG-positive subjects (p < 0.001). Discussion: The study reveal 52.6% of the IgG-positive subjects in the Second Survey came from the First Survey and 47.4% were family members previously in contact with positive subjects. Data suggest that there have been undiagnosed patients feeding the spread of the virus since the beginning of the pandemic. In conclusion, for future pandemics, it will be necessary: i) to ensure the rapid isolation of symptomatic patients and the early identification of their close contacts, ii) to carry out the maximum number of tests in the shortest possible time, both on symptomatic and asymptomatic subjects, and iii) to implement information campaigns to make people aware of their risks, and implement clear, non-conflicting communication.

Pesticides monitoring in biological fluids: Mapping the gaps in analytical strategies.

Pesticides play a key-role in the development of the agrifood sector allowing controlling pest growth and, thus, improving the production rates. Pesticides chemical stability is responsible of their persistency in environmental matrices leading to bioaccumulation in animal tissues and hazardous several effects on living organisms. The studies regarding long-term effects of pesticides exposure and their toxicity are still limited to few studies focusing on over-exposed populations, but no extensive dataset is currently available. Pesticides biomonitoring relies mainly on chromatographic techniques coupled with mass spectrometry, whose large-scale application is often limited by feasibility constraints (costs, time, etc.). On the contrary, chemical sensors allow rapid, in-situ screening. Several sensors were designed for the detection of pesticides in environmental matrices, but their application in biological fluids needs to be further explored. Aiming at contributing to the implementation of pesticides biomonitoring methods, we mapped the main gaps between screening and chromatographic methods. Our overview focuses on the recent advances (2016-2021) in analytical methods for the determination of commercial pesticides in human biological fluids and provides guidelines for their application.

Epidemiological study in a small rural area of Veneto (Italian region) during Sars-Cov-2 Pandemia.

The emergence of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) and its complications have demonstrated the devastating impact of a new infectious pathogen. The organisational change promulgated by the isolation of affected communities is of extreme importance to achieve effective containment of the contagion and good patient care. The epidemiological study of the population of a small rural community in the North East of Italy revealed how much the virus had circulated during Spring, 2020, and how contagion has evolved after a prolonged lockdown. In the 1st phase, NAAT (Nucleic Acid Amplification Testing) was performed in cases with more or less severe symptoms and a study was performed to trace the infection of family members. Only 0.2% of the population tested positive on NAAT, via nasopharyngeal swab during this 1st phase. In the 2nd phase a random sample of the general population were tested for circulating anti-Sars-Cov-2 immunoglobulins. This showed that approximately 97.9% of the population were negative, while 2.1% (with positive IgG at a distance) of the population had contracted the virus in a mildly symptomatic or asymptomatic form. The main symptom in subjects who developed immunity was fever. Antibodies were found in subjects with forced coexistence with quarantined or infected subjects. The mutual spatial distance by categories has shown higher relative prevalence of IgG positive and IgM negative cases in close proximity but also far from the infected, with respect to an intermediate distance. This suggests that subjects living in thinly populated areas could come in contact with the virus more likely due to intentional/relational proximity, while those living nearby could also be infected through random proximity.

Syngeneic living-donor liver transplantation for hemangioendothelioma: a clinical model for studying liver regeneration.

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Multimodal therapy before liver transplantation for hepatocellular carcinoma.

BACKGROUND: : The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study. METHODS: : Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy). RESULTS: : Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3-16 months). On histological examination, 42% of the group did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%). CONCLUSIONS: : The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence.

Isoniazid-related fulminant hepatic failure in a child: assessment of the native liver's early regeneration after auxiliary partial orthotopic liver transplantation.

We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF.

Role of blood AFP mRNA and tumor grade in the preoperative prognostic evaluation of patients with hepatocellular carcinoma.

AIM: To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria. METHODS: Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies. RESULTS: At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables. CONCLUSION: The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.

Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma.

BACKGROUND: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical-pathological parameters remains controversial, however. METHODS: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time. RESULTS: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p<0.01), nodule size (p=0.03), vascular invasion (p=0.006) and moderately or poorly differentiated HCC (p<0.0001). Moreover, survival analysis showed a significant impact of AFPmRNA detection on overall (p=0.04) and recurrence-free survival (p=0.0007) after a median follow-up of 17 months. CONCLUSIONS: Although AFPmRNA is frequently detected in the blood, even in benign liver diseases or gastroenteric tumors, in HCC patients without clinical evidence of extrahepatic metastases it seemed to identify the biologically more aggressive tumors.

Growth hormone/insulin-like growth factor 1 axis recovery after liver transplantation: a preliminary prospective study.

Many studies on cirrhotic patients have shown that insulin-like growth factor 1 (IGF-1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF-1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF-1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age-matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF-1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group-IPF). GH and IGF-1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF-1 levels in Group-IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF-1 levels were higher in Group-IPF than in the group with normal graft function. In conclusion, the severe GH/IGF-1 axis impairment found in patients with end-stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF-1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post-OLT liver function recovery.

Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma.

OBJECTIVE: To determine the long-term results of liver transplantation for well- or moderately differentiated hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: HCC patient selection for liver transplantation remains controversial, and deciding exclusively on the strength of criteria such as number and size of nodules appears prognostically inaccurate. METHODS: Since 1991, preoperative tumor grading has been used at our center to establish whether a patient with HCC is fit for transplantation. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. Thirty-three patients with moderately or well-differentiated HCC were prospectively studied after liver transplantation. A group of 15 patients with incidental HCC transplanted during the same period were also evaluated and compared with the 33 patients with preoperatively diagnosed HCC. RESULTS: On histologic examination, 38% of the entire group of 48 patients did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 44 months. The 5-year actuarial survival rate was 75% and recurrence-free survival was 92%. HCC recurred in only 3 patients (6%). The only histomorphologic variable differing significantly between incidental and nonincidental HCC was nodule size. The timing of diagnosis (incidental vs. nonincidental HCC), the Milan criteria, and the TNM stage revealed no statistically significant impact on overall and recurrence-free survival rates. CONCLUSIONS: The routine pre-orthotopic liver transplantation tumor grading may represent a valid tool in the selection of unresectable HCC patients for transplantation.

The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?

BACKGROUND/AIMS: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). METHODS: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. RESULTS: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.

Multimodal approach and its impact on survival for patients with hepatocellular carcinoma.

BACKGROUND: There are few studies evaluating the prognostic impact on survival of treatment strategy in patients with hepatocellular carcinoma (HCC). The aim of this study was to analyse whether a multimodal approach, that represents a synergic association of different therapeutic procedures, may improve survival of patients with HCC. PATIENTS AND METHODS: Two hundred and fourteen patients with HCC were enrolled in the study. The multimodal approach was chosen for 27 out of 106 (25%) non surgical patients, 42 out of 81 (52%) patients who underwent liver resection and 19 out of 27 (70%) patients who underwent liver transplantation. RESULTS: The long-term survival of patients who underwent the multimodal approach improved significantly with respect to patients treated by both resection and other therapies alone. The 5-year survival rates were 52% vs. 11% (p < 0.05) in the non surgical group and 40% vs. 24% (p < 0.05) in the resection group when a multimodal approach was used for the treatment of recurrences. In patients with advanced HCC undergoing liver transplantation, multimodal treatment resulted in long-term survival comparable to that of patients with early HCC. CONCLUSION: A multimodal approach should be suggested in all patients with HCC, since a careful integration of surgical and non surgical treatments may improve long-term survival in such patients.

Thermal homeostasis and liver transplantation.

Thermal homeostasis represents the major issue during liver transplantation (OLT) since severe hypothermia may have a deleterious effect on both liver recipient organism and postoperative graft functioning. Because of the known negative influence of hypothermia on intraoperative cardiovascular activity and coagulation system, numerous methods have been suggested to reduce intraoperative heat loss and promote active warming (continuous temperature monitoring, external heat sources, improvement in surgical technique and technologies). A good intraoperative OLT course has an obvious influence on post OLT graft function recovery, but thermal homeostasis has also an essential direct effect on the graft as a constitutive component of conventional cold preservation methods. Hypothermia, however, contributes directly to the graft ischemia-reperfusion injury particularly in marginal and partial organs by several angiogenic mechanisms. For these reasons, on the light of the development of new strategies to increase the donor pool, clinical research is focusing on new preservation methods such as extracorporeal circuits with normothermic oxygenated perfusion.