transmitted drug resistance mutations and trends of hiv 1 subtypes in treatment naive patients a single centre experience

Abstract Background Transmitted drug resistances (TDRs) and HIV-1 diversity could affect treatment efficacy and clinical outcomes. Here we describe the circulating viral subtypes and estimate the prevalence of resistance among drug naive patients attending Sapienza University Hospital in Rome from 2006-2017. Methods Genotypic resistance test (GRT) was performed on 668 ART-naive patients. GRT were conducted in integrase (n = 52), protease and reverse transcriptase (n = 668) sequences. Results Twenty-one different subtypes and Circulating Recombinant Forms (CRFs) were identified. Subtype B was the most common (67%), followed by CRF02_AG (8.3%), subtypes C and F (6%). We found a significantly increased overtime in the proportion of non-B strains and in the rates of non-Italian patients (p  Minor or accessory INSTI mutations were detected in 17.3% of patients. No significant decrease of TDR prevalence was documented overtime. Conclusion The significant increase of non-B subtypes suggests that the molecular epidemiology of HIV-1 is changing. The detection of a major INSTI mutation in two naive patients highlights the importance of performing GRT before commencing treatment. This finding and the lack of a significant reduction of TDR underline the importance of a continuous surveillance of resistance mutations

SARS-CoV-2 pandemic. Implications in the management of patients with colorectal cancer

The SARS-CoV-2 pandemic has already reached 3,207,248 patients with more than 225,000 deaths all over the world. Colorectal cancer is the third most diagnosed cancer worldwide, and the healthcare system is struggling to manage daily activities for elective cancer surgery. This review integrates clinical, microbiological, architectural and surgical aspects to develop indications on strategies to manage colorectal cancer patients and ensure safety during the pandemic. Telephone or virtual clinics must be encouraged and phone follow-up should be implemented. Indications for surgery must be rigorous, balancing the advantage of early surgical treatment and risks of treatment delay. To decrease the occupancy rate of intensive care unit beds, elective surgical treatment should be delayed until local endemic control, according to stage of disease. Patients with SARS-CoV-2 infection should be treated only after clinical recovery, two consecutive negative oropharyngeal swabs and, if available, a negative stool sample. Before any elective oncologic procedure, a multidisciplinary oncologic team including an anaesthesiologist and an infectious disease specialist must assess every patient to evaluate the risk of infection and its impact on perioperative morbidity, mortality and oncologic prognosis. The hospital should organise to manage all elective oncologic patients in an "infection-free" area or refer them to a non-SARS-CoV-2 hospital

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Detection of SARS-CoV-2 RNA and antibodies in breast milk of infected mothers

The SARS-CoV-2 outbreak in December 2019 brought many challenges to be addressed. One concerns the possible transmission of the virus and protective antibodies against SARS-CoV-2 to newborns through breastfeeding. The aim of this study was the detection of SARS-CoV-2 RNA and antibodies in the milk of SARS-CoV-2 positive mothers. Milk and blood samples were collected from twelve women with SARS-CoV-2 positive nasopharyngeal swabs. Viral RNA was investigated by RT-PCR, and the presence of IgA, IgM, and IgG anti-SARS-CoV-2 was evaluated in both breast milk and maternal blood. All milk samples showed negative results for SARS-CoV-2 RNA. Eight women (66%) had a detectable level of anti -SARS-CoV-2 IgA in their milk. Of this group, only one sample presented simultaneously serum antiviral IgM and IgG while other three samples showed only anti-SARS-CoV-2 IgG. The remaining four mothers with anti-SARS-CoV-2 IgA in their breast milk had no serum antibodies against SARS-CoV-2. Finally, four mothers (34%) did not have any anti-SARS-CoV-2 antibodies in breast milk and serum, except one mother who had antiviral IgG and IgA in serum. Our results suggest that breastfeeding of SARS-CoV-2 infected mothers is safe and should be encouraged as breast milk transmits maternal antiviral antibodies which protect the infant while its immune system is immature

CARATTERIZZAZIONE CLINICA E VIROLOGICA DEI GENOTIPI NA1 E ON1 DEL VIRUS RESPIRATORIO SINCIZIALE A (RSV-A) E DEL VIRUS RESPIRATORIO SINCIZIALE B (RSV-B) IN BAMBINI AFFETTI DA BRONCHIOLITE

INTRODUZIONE Il virus respiratorio sinciziale umano (RSV), principale agente eziologico della bronchiolite, è il maggior responsabile di ospedalizzazione infantile. Esistono due tipi, RSV-A e –B e numerosi genotipi. Durante le varie stagioni epidemiche possono circolare diversi genotipi di RSV-A e di RSV-B con un andamento non regolare. Numerosi studi dimostrano che l’RSV-A causa un quadro più severo di bronchiolite mentre altri studi dimostrano che non ci sono differenze cliniche significative. La circolazione dei diversi genotipi durante le varie epidemie stagionali potrebbe almeno in parte giustificare tale incongruenza. Scopo di questo studio è caratterizzare i differenti genotipi di RSV circolanti in undici epidemie stagionali e di valutare il loro impatto clinico e di severità della malattia nei bambini ricoverati per bronchiolite. METODI Bambini assistiti presso il Dipartimento di Emergenza pediatrica del Policlinico Umberto I e successivamente ricoverati con diagnosi clinica di bronchiolite sono stati arruolati durante undici stagioni epidemiche consecutive, 2005/06 – 2015/16. Al momento del ricovero è stato determinato un punteggio di severità dell’infezione (da 0 a 8) calcolato in base alla frequenza di respirazione, alla saturazione di ossigeno, rientramenti e all’abilità di alimentazione orale. I lavaggi nasali ottenuti da questi pazienti sono stati esaminati per 14 virus respiratori e i campioni risultati positivi all’RSV sono stati sequenziati e analizzati filogeneticamente. Sono stati poi analizzati i dati clinici, familiari e demografici. RISULTATI Su 300 casi di RSV positivi, 272 casi sono stati sequenziati: 133 sono risultati positivi all’RSV-A genotipo NA1 mentre 80 sono risultati positivi all’ RSV-A genotipo ON1. 59 casi sono risultati positivi all’RSV-B genotipo BA. Durante le prime stagioni epidemiche il ceppo RSV-A circolante è risultato il genotipo NA1. Nel 2011/12 il ceppo emergente ON1 è stato rilevato in circa il 20% dei casi mentre dal 2012/13 in poi ON1 è stato il ceppo predominante. Tutti i casi di RSVB appartenevano al genotipo BA. Tutti i bambini in cui è stato isolato l’NA1 avevano un grado maggiore di severità dell’infezione (relativamente alla frequenza di respirazione e alla saturazione di ossigeno). I bambini con l’RSV-B avevano una età più alta, presentavano febbre con più frequenza e una storia familiare con asma e fumo passivo. CONCLUSIONI I risultati ottenuti suggeriscono che la severità clinica dell’infezione è influenzata dal genotipo di RSV e da fattori di rischio familiare. I dati ottenuti potrebbero essere utili per capire la patogenesi delle bronchioliti e di sviluppare un vaccino e una sorveglianza più efficace contro le infezioni da RSV

Effects of short sleep duration on energy metabolism and energy balance in subjects with overweight and obesity

Introduction: The chronic reduction of sleep duration is associated to an increased risk of weight gain, but mechanistic aspects remain to be fully elucidated. The aim of our study was to examine the relationship between short sleep duration and energy metabolism, fuel selection and energy balance in overweight and obesity. Methods: Inclusion criteria were: age 18–65 years, BMI ≥25 kg/m2. Use of any CNS medications, any psychiatric disorders and night shift work were considered as exclusion criteria. Body composition was evaluated by DXA. All participants underwent indirect calorimetry. The respiratory quotient (RQ) was calculated from gas exchanges. The equations by Weir and by Frayn were used to calculate the resting energy expenditure (REE), and carbohydrate and fat oxidation, respectively. Sleep duration, total daily energy expenditure (TDEE) and the level of physical activity (METs/day) were objectively assessed (Sensewear Armband). A 3-day dietary record was administered. Participants were divided into two groups, “regular sleep” (RS): >300 min/day or “short sleep”(SS): ≤300 min/day. Results: 88 women and 30 men were included (age:49.6±12.1 years), of whom 30.5% exhibited a short sleep duration. BMI (39.7±7.1 vs. 36.2±5.0 kg/m2, P=0.03) and truncal body fat (18.7±6.2 vs. 16.1±4.6 kg, P=0.04) were higher in the SS group than the RS group. Subjects with short sleep had a lower RQ (0.71±0.12 vs. 0.76±0.12, P=0.004) and oxidized more fat (113±55 vs. 95±56 g/min, P=0.006) than regular sleepers. The METs/day were higher in the SS group compared to the RS group (1.56±0.55 vs. 1.35±1.24, P=0.04). RQ was positively associated to sleep duration (P=0.04, adj. for age, sex, and body fat). No difference emerged in TDEE or energy intake (SS group: 23±10 vs. RS group: 25±6 kcal/kg/day, P>0.05). Conclusion: Short sleep affects energy substrate metabolism and adiposity distribution in overweight and obese subjects

TREATED HIV-1 PATIENTS WITH DIFFERENT LEVELS OF VIRAL SUPPRESSION: CHANGES IN MICRORNA EXPRESSION PROFILES

Background: Antiretroviral therapy (ART) can suppress the HIV-1 replication but is not able to eradicate the virus due to the existence of viral reservoirs. Optimal virological suppression remains often an ideal goal since some patients may show persistent plasma residual viremia (RV). To date, it is unclear if RV may be regarded as an indication of the potency and tolerability of the regimen, adherence, drug resistance, and pharmacokinetics. Recent studies have shown that other factors, closely related to host, could improve optimal viral suppression. It has been demonstrated that cellular miRNAs like miR-150, miR-33a-5p, miR-223, miR-382 could affect HIV-1 latency in resting CD4+ T cells and miR-324-5p interfere with HIV-1 replication. Moreover, other investigators have suggested the role of miR-34a and miR-132 as enhancer of viral replication. The aim of the study was to investigate if different miRNAs profile could be associated to residual replication in treated HIV-1 positive patients with different levels of viral suppression. Methods: To evaluate cellular expression of miR-33a-5p, miR-34a, miR-132, miR-150, miR-223 miR-324 -5p and miR-382 RT-Taqman assay was performed. Levels of miRNA were measured in peripheral blood mononuclear cells (PBMC) from 56 antiretroviral therapy (ART) treated patients grouped according viremia in group I (28 patients with a sustained undetectable viremia for at least 3 years) and group II (28 patients with at least 3 values of low level viremia (LLV) between 37 -200 copies /ml). Twenty-three cellular samples from healthy donor (HD) were used as a control group. Results: PBMCs levels of miR-33a-5p, miR-34a, miR-150, and miR-324-5p were significantly higher in HIV infected patients compared to HD (tab1). When we stratified levels of miRNA according to group I and II, miR-33a-5p, miR-34a, miR-150 were confirmed significantly higher in either groups compared to HD. On the contrary, the expression levels of miR-324-5p were similar to HD (tab1). A positive correlation between miR-150 and time of HIV diagnosis was found (r=0.47 p=0.012). There was not significant correlation between CD4+ T cell count and miRNA levels. Conclusions: The expression pattern of some miRNA is altered in HIV infected population but no differences between patients with maximal viral suppression and patients with LLV was detected

Analysis of viral nucleic acids in duodenal biopsies from adult patients with celiac disease

Objective: The purpose of this study was to investigate the presence of Adenovirus, Epstein-Barr virus (EBV), HHV-6 and cytomegalovirus (CMV) nucleic acids in the gastrointestinal biopsies from active CD patients. Methods: Gastrointestinal biopsies of 40 active CD patients and 40 non-CD patients were collected during the endoscopic investigation of gastrointestinal symptoms. Results: HHV-6B was found in 62.5% of CD patients and in 65% of non-CD individuals, whereas the prevalence of EBV-positive samples was 20 and 10%, respectively. Nucleic acids from HHV-6A, CMV and adenovirus were not detected in any group. Conclusion: These data suggest that these viruses may not play a role in the pathogenesis of acute CD, but they do not exclude the possibility that viruses can act as a trigger for the onset of celiac disease

HIV-1 DIVERSITY AND ANTIRETROVIRAL RESISTANCE MUTATIONS AMONG TREATMENT NAÏVE PATIENTS FROM 2005-2017: A SINGLE CENTER EXPERIENCE

Background: Transmitted drug resistance (TDR) in antiretroviral (ART)-naïve patients remains a serious concern since it can reduce the efficacy of treatment and may affect clinical outcomes. The aim of this retrospective study is to describe circulating viral subtypes and evaluate the prevalence of TDR in drug naïve patients from Sapienza University Hospital. Materials/methods: Genotypic resistance tests (GRT) of 668 ART-naïve patients attending Sapienza University Hospital, Rome, between 2005 and 2017 were analyzed. GRT were conducted in integrase (n= 52), protease and reverse transcriptase (RT) (n=668) sequences (Trugene® HIV-1 Genotyping Kit, Siemens; ViroSeq™ HIV-1 Genotyping System, Abbott). Results: Most of patients were male (76.1%), of Italian origin (70.9%), with a median age of 38 years (IQR 31- 48 years); the median viral load was 4.7 log10 copies/mL (IQR 4.1-5.3) and the mean baseline CD4 cell count was 352 cells/mm3 (IQR 148-570). Phylogenetic analysis revealed the presence of 21 different subtypes and Circulating Recombinant Forms (CRFs). Subtype B was most common (67.1%), followed by CRF02_AG (8.4%), subtypes C and F (6%). A significantly increased overtime in the proportion of non-B strains (p<0.001) and in the rates of nonItalians patients (p<0.001) was found. Most individuals (92.7%) had no TDR mutations and were susceptible to all drugs. The overall prevalence of TDR was 9.4% [nucleoside reverse transcriptase inhibitors (NRTIs)= 4.2%, non-nucleoside reverse transcriptase inhibitors (NNRTIs)= 5.8%, protease inhibitors (PIs)= 1.0%] and was higher in subtype B strains. The most common resistant mutations were K103N (1.9%) and T215D/S (1.5%) in RT region and M46I (0.4%) in protease. Among integrase resistance mutations,7 individuals had a minor or accessory mutation and 2 showed major mutations. Among the minor mutations, T97A and G140S were detected in 3 and 2 patients respectively; E138K occurred in 1 individual. Interestingly, 2 patients harbored the major Q148H and the minor G140S mutation and share also the reverse transcriptase mutations (E138G, T215S, H221Y, M230L). These individuals were a couple, both active drug users and in acute phase of infection. Phylogenetic analysis confirmed that these patients harboring the same virus. No significant decrease of TDR was documented overtime. Conclusions: TDR rate observed in our population is in agreement with the average rate in Europe. The lack of a significant reduction of TDR underlines the importance of a continuous surveillance of resistance mutations. These data on INSTI mutations reinforce the recommendations to perform INSTI GRT before commencing treatment, especially in those presenting resistance to other classes of drugs and in difficult population like active drug users. Moreover, the significant increase of non-B viruses suggests the importance to monitor dynamics of HIV transmission, since this may have important clinical and diagnostic implication