Pre-Endoscopy real-time PCR testing for SARS-CoV2 does not reduce health care workers infection and is associated with a higher reduction of endoscopic activity in an outpatient setting.

Objective: The role of pre-procedure SARS-CoV2 testing in digestive endoscopy is still debated. AGA guidelines recommend against pre-procedure testing considering low prevalence of SARS- CoV2 infection in the general population and low incidence of infection among endoscopy units Health Care Workers (HCWs). However, no studies have compared pre-procedure testing associated to symptom screening vs. symptom screening alone in reducing the risk of infection for HCWs. Main aim of the present study is to compare the risk of infection for HCWs in different Endoscopy Units adopting different pre-endoscopy screening and operating in two nearby hospital of the same region in Northern Italy in pre-vaccination period. For outpatients in the Endoscopy Unit of Trento (Unit 1) only pre-procedure symptom screening was performed, while in the Endoscopy Unit of Bolzano (Unit 2) pre-procedure symptom screening and negative pre-procedure real-time PCR were requested. Secondary aims were to assess the impact of pre-procedure real-time PCR testing on endoscopic activity and diagnostic delay. Design: Retrospective data collection on a prospectively maintained database was performed, including outpatient endoscopy procedures performed between June 1st 2020 and February 28th 2021 in Unit 1 and Unit 2. Results: No differences in terms of infection rate in HCWs have been identified in Unit 1 and Unit 2 (9.0 vs. 19.3% P=0.2) over a nine-month period. Moreover, in the unit performing pre- procedure real-time PCR before endoscopy a significantly higher reduction in endoscopic activity has been recorded (61.9% vs. 53.4%; P<0.01). In patients with positive real-time PCR, endoscopy was performed with a mean delay of 61.7 days (range 9-294) and 22.5% of them were lost at follow-up and did not undergo any endoscopic procedure in the following 12 months. Conclusions: This study supports the AGA recommendation suggesting that pre-endoscopy real-time PCR is an expensive and time-consuming procedure without proven benefits in an outpatient setting.

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Impact of the SARS-CoV2 pandemic dissemination on the management of neuroendocrine neoplasia in Italy: a report from the Italian Association for Neuroendocrine Tumors (Itanet).

INTRODUCTION: The organization of the healthcare system has significantly changed after the recent COVID-19 outbreak, with a negative impact on the management of oncological patients. The present survey reports data collected by the Italian Association for Neuroendocrine Tumors on the management of patients with neuroendocrine neoplasia (NEN) during the pandemic dissemination. METHODS: A survey with 57 questions was sent to NEN-dedicated Italian centers regarding the management of patients in the period March 9, 2020, to May 9, 2020 RESULTS: The main modification in the centers' activity consisted of decreases in newly diagnosed NEN patients (- 76.8%), decreases in performed surgical procedures (- 58%), delays to starting peptide receptor radionuclide therapy (45.5%), postponed/canceled follow-up examinations (26%), and canceled multidisciplinary teams' activity (20.8%). A low proportion of centers (< 10%) reported having to withdraw systemic anti-tumor medical treatment due to concerns about the pandemic situation, whereas PRRT was withdrawn from no patients. CONCLUSION: Although the COVID-19 outbreak induced the centers to reduce some important activities in the management of NEN patients, the Italian network was able to provide continuity in care without withdrawing anti-tumor treatment for the majority of patients.

Prevalence of gastrointestinal symptoms in coronavirus disease 2019: a meta-analysis.

BACKGROUND AND STUDY AIMS: The coronavirus disease 2019 (COVID-19) is a pandemic infection spreading worldwide at an unprecedented rate. Our aim was to assess the frequency of gastrointestinal (GI) involvement in COVID-19. PATIENTS AND METHODS: We performed a systematic review and meta-analysis of all studies reporting clinical data about COVID-19 patients, published until 25th March 2020. The primary endpoint was the pooled prevalence of COVID-19 patients complaining of GI symptoms. Secondary endpoints were the pooled prevalence of cases with COVID-19 positive stool samples, and of asymptomatic COVID-19 patients. We used random-effects model for meta-analysis. RESULTS: Thirty-three studies were included in the meta-analysis. Out of 4434 COVID-19 patients, the pooled prevalence of GI manifestations was 11.51% (95% CI : 8.16 to 15.35). The most frequent GI symptom was diarrhea (7.78% of cases ; 95% CI : 5.05 to 11.04), followed by nausea/vomiting (3.57% ; 95% CI : 1.87 to 5.80), poor appetite (2.39% ; 95%CI : 0.55 ; 5.46) and abdominal pain (0.78% ; 95% CI : 0.26 to 1.57). Positivity for COVID-19 in stool samples was observed in 41.50% (95% CI : 17.70 to 67.65) of cases. 11.85% (95% CI : 3.53 to 24.17) of COVID-19 patients remained asymptomatic. CONCLUSIONS: The present meta-analysis shows that a significant proportion of COVID-19 patients suffer from GI manifestations, as well as COVID-19 positivity in stool samples. Asymptomatic patients need to be considered a further potential route of viral transmission.

Prevalence of liver injury in patients with coronavirus disease 2019 (COVID-19) : a systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: The coronavirus disease 2019 (COVID-19) represents a public health emergency of international concern, causing thousands of deaths worldwide. We performed a systematic review with meta-analysis in order to investigate the prevalence of COVID-19-induced liver injury. PATIENTS AND METHODS: We searched MEDLINE, Scopus, Web of Science and the Cochrane Library, for studies reporting laboratory data about COVID-19 patients, with last update on 25th March 2020. The primary outcome was the pooled prevalence of COVID- 19-induced liver damage, mainly represented by increase in serum transaminases and bilirubin. The secondary outcome was the description of abnormalities in serum albumin and prothrombin time (PT). We focused on laboratory data only on hospital admission, and adopted random-effects model for meta-analysis. RESULTS: Eleven studies were eligible for meta-analysis. Out of 793 included patients, the pooled prevalence of COVID-19-related liver damage was 22.17% (95% CI 17.64 to 27.07), mostly indicated by hypertransaminasemia. Serum bilirubin was increased in 5.53% (95% CI 3.60 to 7.85) of cases. Abnormal serum albumin was observed in 78.92% (95% CI 39.82 to 99.56), and increased PT value in 19.98% (95% CI 2.49 to 78.23), but these results derived from significantly heterogeneous studies. CONCLUSIONS: COVID-19-induced liver injury must not be ignored, as it is observed in one fifth of infected patients. Prospective studies evaluating liver function during the course of COVID-19 are needed to provide a complete overview of hepatic involvement during this viral infection.

Portosystemic encephalopathy in an 86-year-old patient : a clinical challenge.

Abernethy malformations are rare vascular abnormalities, classified into two types : type 1 if the portal vein is absent, type 2 when the portal blood is diverted into vena cava through a hypoplastic portal vein. These conditions present symptoms related to portosystemic shunting, and usually become clinically evident in children or young adults. Here we report the first case of Abernethy malformation diagnosed in an 86-year-old female patient affected by portosystemicencephalopaty.

Inhibition of endosomal acidification in normal cells mimics the derangements of cellular insulin and insulin-receptor metabolism observed in non-insulin-dependent diabetes mellitus.

Dissociation of the insulin-insulin receptor complex plays a crucial role in the processing of both insulin and the insulin receptor, and the acidification of endocytic vesicles may be the mechanism by which internalized insulin is dissociated from its receptor and properly sorted and processed. Internalized insulin-insulin receptor complexes are abnormally processed in cells from patients with non-insulin-dependent diabetes mellitus (NIDDM). Accordingly, to further investigate the mechanisms of the derangements observed in NIDDM cells, we examined the effects of the ionophore monensin, which inhibits endosomal acidification, on the cellular processing of insulin and insulin receptor in monocytes from control subjects (n = 12) and NIDDM patients (n = 14). This study confirms that monocytes from NIDDM patients, compared with cells from normal controls, had reduced binding (P < .01), internalization (P < .01), and degradation (P < .01) of insulin. In addition, the release of intracellular radioactivity was slower (P < .01), and recycling of the insulin receptor was inhibited (P < .01). Moreover, these defects were associated with a significant (P < .01) decrease of dissociation of the internalized insulin-insulin receptor complex. In cells from normal controls, incubation with monensin decreased insulin binding (P < .01), but not insulin internalization. High-performance liquid chromatography (HPLC) analysis of intracellular radioactivity showed that after monensin intracellular intact insulin significantly increased (P < .01), thus suggesting a decrease of intracellular insulin degradation. Moreover, insulin receptor recycling was completely disrupted. All of these derangements were associated with a significant decrease (P < .01) of dissociation of insulin-insulin receptor complexes. On the contrary, in diabetic monocytes, monensin had no significant additional effect on NIDDM-linked alterations. Comparison of the results obtained in cells from NIDDM patients to those found in monensin-treated normal cells demonstrates that NIDDM and monensin gave rise to a superimposable impairment of dissociation of the intracellular insulin-insulin receptor complex, associated with similar abnormal sorting and processing of insulin and its receptor. The only defect present in NIDDM cells but not in monensin-treated cells is the decrease of insulin internalization, which thus seems independent of the action of monensin on the processing of internalized insulin-insulin receptor complex. These results suggest that the impairment of dissociation of the insulin-insulin receptor complex may play a crucial role in the subsequent altered processing of insulin and insulin receptor. Moreover, they raise the question as to a possible similar alteration of the same intracellular mechanism by NIDDM and monensin, and point out that the derangements found in cells from NIDDM patients could be localized within the endosomal apparatus and consist mainly of a defective acidification of its interior.

[Occupational hypersensitivity to spiramycin. Report of a case]. / Hipersensibilidad ocupacional a espiramicina. A propósito de un caso.

A case report of occupational hypersensitivity to Spiramycin. Rhinoconjunctivitis and spasmodic cough are reported in a 34 year-old female handling spiramycin powder in a pharmaceutical factory. The symptoms appeared within the first few hours of coming into contact with the drug and continued for several hours after leaving her place of work. The patient had no personal case history of atopy. Results for prick-test with extracts using a concentration of 1/100 (w/v) were positive, as were results por intradermical tests with a solution using a concentration of 1/10.000 (w/v). The diagnostic was confirmed with the application of a nasal provocation test. Our criteria to determine positivity to this test was according to Bachman (1) and the European Committee of Rhinomanometry. On our suggestion the patient was transferred to another section of the pharmaceutical company whereupon all symptoms disappeared immediately and no further allergic reactions to drugs were registered. This case suggest that reactions to a chemical product may involve immunological mechanisms.

Inhibitory effect of peak 2-4 of uremic middle molecules on platelet aggregation.

It is well-known that uremic patients present prolonged bleeding times as a common complication. Factors responsible for this disorder have been extensively investigated. In order to elucidate the possible role of uremic middle molecules as responsible for the bleeding tendency observed in uremia, we have studied the effect on platelet aggregation of middle molecules obtained from uremic plasma by Sephadex and ion-exchange chromatography. Our results show that some purified middle molecular fractions have a specific inhibitory activity on platelet aggregation and suggest an important role for these compounds in the pathogenesis of uremic bleeding.