Gastrointestinal endoscopy can be safely performed during pandemic SARS-CoV-2 infection in Central Italy.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious; gastrointestinal endoscopies are considered risky procedures for the endoscopy staff. Data on the SARS-CoV-2-exposure/infection rate of gastrointestinal endoscopy staff is scarce. This study aimed to assess the SARS-CoV-2-exposure/infection rate among gastrointestinal endoscopists/nurses performing gastrointestinal endoscopies before and after the adoption of specific prevention measures. PATIENTS AND METHODS: Cross-sectional study in a teaching hospital (Rome, Central Italy) on retrospective data (9 March-15 April 2020) of consecutive gastrointestinal endoscopies, characteristics of procedures, patients and endoscopy staff, SARS-CoV-2-exposure/positivity of patients and staff before and after adoption of prevention measures. Exposed staff tested for SARS-CoV-2 by nasopharyngeal swabs(RNA-PCR) and serology. RESULTS: A total of 130 gastrointestinal endoscopies were performed in 130 patients (age 66 ± 14 years, 51% women, 51% inpatients, 56.9% lower). A total of 12 (9.2%) patients were SARS-CoV-2-positive and 14(10.8%) had a high risk of potential infection. Of the endoscopy staff (n = 16, 5 endoscopists, 8 nurses and 3 residents), 14 (87.5%) were exposed to SARS-CoV-2-infected and 16 (100%) to potentially infected patients. 3/5 and 5/5 endoscopists were exposed to actual and potential, 1/3 and 3/3 residents to actual and potential and 8/8 nurses to actual and potential infection, respectively. None of the staff was found to be infected with SARS-CoV-2. None experienced fever or any other suspicious symptoms of coronavirus disease 2019. Before the adoption of prevention measures, more endoscopists/nurses were in the endoscopy room than after (3.5 ± 0.6 vs. 2.1 ± 0.3, P < 0.0001). CONCLUSIONS: Despite supposed high infection risk, gastrointestinal endoscopies may be safe for the endoscopy staff during the SARS-CoV-2 pandemic.

Patterns of Presentation of SARS-CoV-2 Infection in Children. Experience at the Italian Epicentre of the Pandemic.

Background: COVID-19, a disease caused by the new coronavirus SARS-CoV-2, spread worldwide, and Bergamo was one of the most affected areas in Europe. Following the first outbreak, more than half of the population of the Bergamo province had been infected. We aimed to describe the patients admitted to our unit shortly after the first outbreak. Methods: we retrospectively reviewed the notes of all pediatric patients diagnosed with COVID-19. We enrolled patients with positive swabs or serology and classified them based on the pattern and the timing of presentation after the first outbreak. This setting was considered a reliable reflection of the consequences of unmitigated SARS-CoV-2 circulation. Results: We diagnosed 35 patients over a 3-month period and we identified six patterns presenting in two temporal phases: Early phase, Group 1 (median of 20 days from epidemic start, IQR: 15-27): neonatal sepsis (n.7), pneumonia (n.5), flu-like symptoms (n.2). Late phase, Group 2 (59:51-66 days, p < 0.001): MIS-C (n.18), neurological manifestations (n.3). Group 1 differed from Group 2 for younger age (1 vs. 8 years, p = 0.02), lower C-reactive protein (0.9 vs. 16.6 mg/dl, p = 0.008), procalcitonin (0.16 vs. 7.9 ng/ml, p = 0.008) and neutrophil count (3,765 vs. 6,780/µl, p = 0.006), higher rate of positive swabs (14/14 vs. 9/21, p < 0.001), higher lymphocyte count (3,000 vs. 930/µl, p = 0.006) and platelet count (323,000 vs. 210,000/µl, p = 0.009). Conclusions: Following an outbreak of unmitigated SARS-CoV-2 diffusion, infected children may present with clinical patterns suggesting two temporal clusters, the first characterized by markers of direct viral injury, the second suggesting an immune-mediated disease.

Erratum: Improving assessment and management of large non-pedunculated colorectal lesions in a Western center over 10 years: lessons learned and clinical impact.

[This corrects the article DOI: 10.1055/a-1220-6261.].

Improving assessment and management of large non-pedunculated colorectal lesions in a Western center over 10 years: lessons learned and clinical impact.

Background and study aims Outcomes of endoscopic assessment and management of large colorectal (CR) non-pedunculated lesions (LNPLs) are still under evaluation, especially in Western settings. We analyzed the clinical impact of changes in LNPL management over the last decade in a European center. Patients and methods All consecutive LNPLs ≥ 20 mm endoscopically assessed (2008-2019) were retrospectively included. Lesion, patient, and resection characteristics were compared among clinically relevant subgroups. Multivariate logistic regression (for predictors of submucosal invasion [SMI] and recurrence), Kaplan-Meier curves and ROC curves (for temporal cut-offs in trends analyses) were used. Results A total of 395 LNPLs were included (30 mm [range 20-40]; SMI = 9.6 %; primary endoscopic resection [ER] = 88.4 %). Pseudo-depression and JNET classification independently predicted SMI beyond single morphologies/location. After complete ER, involvement of ileocecal valve/dentate line, piece-meal resection and high-grade dysplasia independently predicted recurrence. Rates of 5-year recurrence-free, surgery-free and cancer-free survival were 77.5 %, 98.6 % and 100 %, respectively, with 93.8 % recurrences endoscopically managed and no death attributable to ER or CR cancer (versus 3.4 % primary surgery mortality). ROC curves identified the period ≥ 2015 (following Endoscopic Submucosal Dissection [ESD] introduction and education on pre-resective lesion assessment) as associated with improved lesions' characterization, increased en-bloc resection of SMI lesions (87.5 % vs 37.5 %; p = 0.0455), reduced primary surgery (7.5 % vs 16.7 %; p = 0.0072), surgical referral of benign lesions (5.1 % vs 14.8 %; p = 0.0019), and recurrences. Conclusions ESD introduction and educational interventions allowed ER of more complex lesions, offset by increased complementary surgery for complications or intrinsic histological risk. Nevertheless, overall, they have reduced surgery demand and increased appropriateness and safety of LNPL management in our center.

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.

BACKGROUND: The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population. In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic. METHODS: All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic. Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications. Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria. Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively. FINDINGS: Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020. Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both. The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01). INTERPRETATION: In the past month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic. FUNDING: None.

Occurrence of Acute Oesophageal Necrosis (Black Oesophagus) in a Single Tertiary Centre.

Acute oesophageal necrosis (AON) is a rare condition characterised by the endoscopic finding of diffuse, circumferential, black mucosal pigmentation of the oesophagus, which typically stops at the gastro-oesophageal junction. This observational study aimed to assess the occurrence, clinical characteristics and outcomes of AON in a consecutive endoscopic cohort in a single tertiary university centre. A retrospective analysis of endoscopic data of upper gastrointestinal endoscopy (UGE) was carried out from 2008 to 2018. Out of 25,970 UGE, 16 patients (0.06%) had AON; 75.0% were men with a median age of 75 years. Almost all patients underwent diagnosis during emergency UGE performed for gastrointestinal bleeding, but one patient was diagnosed during elective UGE for persistent vomiting and diarrhoea. All patients reported one or more pre-existing comorbidities and concomitant acute events. Two patients had AON as the first presentation of Zollinger-Ellison syndrome (ZES). One patient developed an oesophageal stenosis, and another patient presented a relapse of AON. Mortality was 50%, but no patient died as a direct consequence of AON. AON is a rare cause of gastrointestinal bleeding diagnosed mainly during emergency UGE. Our study showed that ZES might manifest with this critical presentation, and endoscopists must be aware of this evidence.

Clinical management of endoscopically resected pT1 colorectal cancer.

Background Implementation of colorectal cancer (CRC) screening programs increases endoscopic resection of polyps with early invasive CRC (pT1). Risk of lymph node metastasis often leads to additional surgery, but despite guidelines, correct management remains unclear. Our aim was to assess the factors affecting the decision-making process in endoscopically resected pT1-CRCs in an academic center. Methods We retrospectively reviewed patients undergoing endoscopic resection of pT1 CRC from 2006 to 2016. Clinical, endoscopic, surgical treatment, and follow-up data were collected and analyzed. Lesions were categorized according to endoscopic/histological risk-factors into low and high risk groups. Comorbidities were classified according to the Charlson comorbidity index (CCI). Surgical referral for each group was computed, and dissociation from current European CRC screening guidelines recorded. Multivariate analysis for factors affecting the post-endoscopic surgery referral was performed. Results Seventy-two patients with endoscopically resected pT1-CRC were included. Overall, 20 (27.7 %) and 52 (72.3 %) were classified as low and high risk, respectively. In the low risk group, 11 (55 %) were referred to surgery, representing over-treatment compared with current guidelines. In the high risk group, nonsurgical endoscopic surveillance was performed in 20 (38.5 %) cases, representing potential under-treatment. After a median follow-up of 30 (6 - 130) months, no patients developed tumor recurrence. At multivariate analysis, age (OR 1.21, 95 %CI 1.02 - 1.42; P  = 0.02) and CCI (OR 1.67, 95 %CI 1.12 - 3.14; P  = 0.04) were independent predictors for subsequent surgery. Conclusions A substantial rate of inappropriate post-endoscopic treatment of pT1-CRC was observed when compared with current guidelines. This was apparently related to an overestimation of patient-related factors rather than endoscopically or histologically related factors.

Congenital Chagas disease in a non-endemic area: Results from a control programme in Bergamo province, Northern Italy.

INTRODUCTION: In non-endemic countries, one of the most important routes of transmission of Trypanosoma cruzi is vertical transmission. The objective of this work is to report the results of the screening activities for the control of congenital Chagas Disease (CD) implemented in Bergamo province between January 2014 and December 2016. METHODS: The programme addressed Bolivian pregnant women settled in Bergamo province. All the eight hospitals offering antenatal and delivery care in that area were involved. We retrospectively calculated the coverage rate of the screening programme, the prevalence of CD in this population, as well as transmission rate to their offspring. RESULTS: During the study period, 376 Bolivian women accounted for 387 deliveries. The coverage rate of serologic screening was 85.6%. Confirmed seropositive women were 28, accounting for a prevalence of CD of 8.7% (95% IC 5.9-11.5). Among 29 children born to positive mothers, one infected child was detected (transmission rate of 4.3%, 95% IC 0-12.6) and treated accordingly. Other 13 children previously born from the same mothers were retrieved and tested for CD: no additional congenital cases were diagnosed. DISCUSSION: Our screening programme presented a high coverage, although widely variable in the different birthing facilities. National guidelines recommending CD testing in pregnant women would help to increase case detection countrywide.

Congenital Chagas disease in a Bolivian newborn in Bergamo (Italy).

Chagas disease (CD) is an uncommon disease in Europe. Its epidemiology has changed because of mass migration from Latin America to Europe. Herein we describe a congenital case of CD in a Bolivian newborn in Bergamo, the main city of residence for the Bolivian community in Italy. At delivery, serological analyses evidenced IgG antibodies against Trypanosoma cruzi both in the child and mother, as expected. Hemoscopic analyses on peripheral blood were repeatedly negative during the first months of life. Eventually, thanks to T. cruzi Real Time polymerase chain reaction (RT-PCR) positivity on peripheral blood and development of progressive anemia in the following weeks, congenital Chagas disease was diagnosed and benznidazole-based therapy started. A progressive antibodies' index decrease was observed till negativity (306 days apart). RT-PCR was negative at the end of treatment. Our case is instructive and management of congenital CD is discussed from the perspective of a non-endemic country.

Rapid Diagnosis of Mycobacterium genavense Disseminated Infection by the Microseq 500: A Case Report in A Two Year Old HIV-Negative Child.

This paper evaluates the capability of MicroSeq 500 instrument to improve the diagnosis of Mycobacterium genavense The strain was isolated from a two year old child admitted to our hospital for hepatosplenomegaly and massive abdominal lymphadenopathies. DNA was extracted from a lymph node and examined by amplifying 500 bp at the 5' end of 16S rRNA gene using MicroSeq 500 16S rDNA Bacterial Identification PCR kit. Sequencing reactions were performed with MicroSeq 500 16S rDNA Bacterial Identification Sequencing kit (Applied Biosystems, USA). Afterwards, sequences were analyzed by GenBank database and identified as Mycobacterium genavense, a slow-growing nontuberculous mycobacterium. The use of 16S rRNA gene sequencing for the identification of bacteria allows the recognition of new clinically relevant agents, eliminating the culture result waiting times.

Outcome and risk of recurrence for endoscopic resection of colonic superficial neoplastic lesions over 2 cm in diameter.

BACKGROUND: Large colorectal superficial neoplastic lesions are challenging to remove. This study aimed to assess the outcomes of routine endoscopic resection of large (≥2 cm and <3 cm) and giant (≥3 cm) lesions. METHODS: From 4587 endoscopic resections, 265 (5.7%) large and giant lesions were removed in 249 patients. We retrospectively analyzed 125 patients (141 endoscopic mucosal resection, 73 large and 68 giant lesions) with a follow-up of 6-12 months. Rate of en bloc and piecemeal resection, recurrence and risk factors were analyzed. RESULTS: En bloc was performed in 92 cases (65.2%) and piecemeal resection in 49 (34.8%). A complete endoscopic resection was achieved in 139 cases (98.5%) with radical resection in 84/139 cases (60.4%). Argon plasma coagulation was applied in 18/141 lesions (12.8%). A recurrence occurred in 16/139 lesions (11.5%). The risk of recurrence at one year was significantly higher for giant than large lesions (p=0.03). The recurrence risk was higher in treated than in non-argon plasma coagulation treated lesions (p=0.01). CONCLUSIONS: endoscopic mucosal resection is a safe and effective routine treatment for large superficial neoplastic lesions. The risk factors for recurrence include giant size, non-protruding morphology, piecemeal technique and argon plasma coagulation.

Potential role of raltegravir-based therapy to induce rapid viral decay in highly viraemic HIV-infected neonates.

We report safety and tolerability of raltegravir (RAL) as a forth HIV agent in two highly viraemic newborns. Raltegravir (6 mg/kg) was given orally twice daily. The other antiretrovirals were assumed according to standard dose for newborns. The first baby was born at week 36. An antiretroviral therapy consisting of zidovudine, lamivudine, and lopinavir/ritonavir was started 96 hour after delivery. Raltegravir was added at hour 120, being plasma HIV-1 RNA above 10×10(6) copies/ml. HIV RNA declined to 5·000 copies/ml at day 30. The second baby was born at week 40. He was started on zidovudine, lamivudine, and nevirapine at day 0, while RAL was added at day 3. Plasma HIV-1 RNA declined from 6·6×10(6) at birth to 52 copies/ml at day 28. RAL tolerability was good in both patients, one with gamma-glutamyltransferase increase, which normalized after RAL discontinuation. Raltegravir-based four drug regimen may be effective and well tolerated in highly viraemic HIV neonates up to 4 weeks.

Chromobacterium violaceum lymphadenitis successfully treated in a Northern Italian hospital.

Lymphadenitis can be caused by different gram positive and gram negative bacteria and non-tuberculous mycobacteria. Cervical lymphadenitis in children is thought to result from ingestion of or contact with environmental microrganisms. Chromobacterium violaceum is a common inhabitant of soil and water in tropical and sub tropical countries. In these parts of the world Chromobacterium violaceum is able to cause skin infection with diffuse pustular lesions and also multiple liver abscess with often fatal evolution in sepsis. We describe a case of cervical lymphadenitis caused by Chromobacterium violaceum in a 14-year-old boy, born in Guinea and resident in Italy for 7 years in a fair condition with general measurable swelling in the right lateral cervical region and with blood tests that showed increased inflammatory indices. The patient was subjected to surgical incision. Antibiotic therapy with ceftriaxone was continued for 10 days, then replaced successfully with oral ciprofloxacin on the basis of purulent material culture positive for Chromobacterium violaceum sensitive to fluoroquinolones.

Is the interruption of antiretroviral treatment during pregnancy an additional major risk factor for mother-to-child transmission of HIV type 1?

BACKGROUND: There is currently an experts' agreement discouraging interruption of antiretroviral treatment (ART) during the first trimester of pregnancy in women infected with human immunodeficiency virus type 1 (HIV-1). However, this recommendation is poorly supported by data. We evaluated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission. METHODS: Logistic regression models were performed in a prospective cohort of 937 children who were perinatally exposed to HIV-1 to estimate adjusted odds ratios for confounding factors on mother-to-child transmission, including maternal interruption of ART. RESULTS: Among 937 pregnant women infected with HIV-1, ART was interrupted in 81 (8.6%) in the first trimester and in 11 (1.2%) in the third trimester. In the first trimester, the median time at suspension of ART was 6 weeks (interquartile range [IQR], 5-6 weeks) and the time without treatment was 8 weeks (IQR, 7-11 weeks). In the third trimester, the median time at suspension of ART was 32 weeks (IQR, 23-36 weeks) and the time without treatment was 6 weeks (IQR, 2-9 weeks). The plasma viral load was similar in women who had treatment interrupted in the first trimester and in those who did not have treatment interrupted. Overall, the rate of mother-to-child transmission in the whole cohort was 1.3% (95% confidence interval [CI], 0.7%-2.3%), whereas it was 4.9% (95% CI, 1.9%-13.2%) when ART was interrupted in the first trimester and 18.2% (95% CI, 4.5%-72.7%) when ART was interrupted in the third trimester. In the multiple logistic regression models, only interruption of ART during either the first or the third trimester, maternal mono- or double therapy, delivery by a mode other than elective cesarean delivery, and a viral load at delivery >4.78 log(10) copies/mL were independently associated with an increased rate of mother-to-child transmission. CONCLUSIONS: Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester. This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health.

Evaluation of the MicroSeq 500 16S rDNA-based gene sequencing for the diagnosis of culture-negative bacterial meningitis.

Gene amplification using 16S rDNA primers has been proposed as a strategy for the diagnosis of bacterial meningitis. The aim of this study was to evaluate the performance of the MicroSeq 500 16S ribosomal DNA test (Applied Biosystems) from patients with suspected bacterial meningitis and CSF negative-culture in comparison to traditional methods. Twelve purulent culture-negative CSF samples were collected between January 2005 and January 2007. For DNA extraction, 500 microl of CSF samples were treated using the QIAamp mini kit (QIAGEN). The extracted DNA was examined amplifying 500 bp at the 5' end of 16S rRNA gene using MicroSeq500 16S rDNA Bacterial Identification PCR kit and the sequencing reactions were performed with the MicroSeq500 16S rDNA Bacterial Identification Sequencing kit (Applied Biosystems). The sequences were compared with those available in GenBank. For the culture-negative CSF samples the MicroSeq 500 16S rDNA yielded a positive result in 9 cases (75.0%): three samples were identified as Streptococcus. pneumoniae, three as Neisseria meningitidis, and the remaining 3 as Haemophilus influenzae, Abiotrophia defectiva and Porphyromonas gingivalis. The MicroSeq 500 16S ribosomal DNA test may improve the microbiological diagnosis of bacterial meningitis, especially when spinal fluid samples are obtained after the administration of antimicrobial therapy.

Atazanavir plus low-dose ritonavir in pregnancy: pharmacokinetics and placental transfer.

BACKGROUND: Adequate antiretroviral exposure during pregnancy is critical to prevent the vertical transmission of HIV and for maternal health. Pregnancy can alter drug kinetics. We assessed the pharmacokinetics of atazanavir/ritonavir (300/100 mg a day) during pregnancy. METHODS: An intensive steady-state 24-h pharmacokinetic profile of atazanavir was performed in the third trimester of pregnancy and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured atazanavir by reverse-phase high-performance liquid chromatography. RESULTS: Seventeen women completed the study. Antepartum, the atazanavir geometric mean area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 28 510 ng.h/l, the maximum observed plasma concentration (Cmax) was 2 591 ng/ml and the 24-h postdose concentration (Ctrough) was 486 ng/ml. The same postpartum parameters were 30 465 ng.h/l, 2 878 ng/ml and 514 ng/ml, respectively. The antepartum to postpartum ratio for AUC0-24 was 0.94 and for Ctrough was 0.96, indicating equivalence, whereas Cmax values were slightly although not significantly lower. The ratio of cord blood/maternal atazanavir concentration in 14 paired samples was 0.13. CONCLUSION: Atazanavir exposure during the third trimester of pregnancy is similar to that observed in the non-pregnant period. Over the whole dosing interval, therapeutic drug concentrations well above the wild-type HIV 90% inhibitory concentration are maintained. Atazanavir crosses the placenta, potentially providing further protection for the newborn. As pregnancy does not appear to alter atazanavir exposure, no dose adjustment is required in pregnant women. Results suggest that atazanavir is a reasonable component of HAART during pregnancy.