The growth of new therapeutic options and practices increases the risk of hepatitis B virus (HBV) reactivation in patients with haematologic malignancies and/or patients undergoing haematologic stem ...cell transplantation (HSCT).
To provide a systematic review supporting recommendations for prevention, monitoring, prophylaxis and therapy of HBV reactivation in patients with haematologic malignancies and HSCT.
The systematic review was based on a strategy using PubMed and the Cochrane Library searching literature published from 1991 to December 31, 2016. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed.
Randomized control trials, prospective and retrospective cohort studies.
Cochrane Risk of Bias Tool and Newcastle Ottawa Quality Assessment Scale.
Forty-two studies of fair or good quality were included in this systematic review. The following main results were obtained: haematologic patients should be screened for HBV before chemotherapy; HBV DNA levels should be monthly monitored in all HBV-positive patients not receiving prophylaxis; hepatitis B surface antigen (HBsAg)-positive haematologic patients and patients undergoing HSCT should receive prophylaxis and third-generation HBV drugs should be provided; and anti–hepatitis B core protein–positive lymphoma patients and patients who underwent HSCT should receive antiviral prophylaxis.
A higher quality of evidence is needed. However, the level of evidence was sufficient to support the recommendations published in this issue of the journal.
Objective
To assess the magnitude of COVID-19 spread and the associated risk factors among health care workers (HCWs), we conducted an in-hospital survey in a central Italian COVID Hospital.
Methods
...Participants underwent nasopharyngeal swab and/or serum collection for SARS-CoV-2 IgG examination. We divided participants according to working status, into rotating-night shift workers (r-NSW) and day-workers.
Results
We found 30 cases of COVID-19 infection in a total of 1180 HCWs (2.5%). Most COVID-19-positive hospital employees were r-NSWs with significantly higher BMI than that of individuals who tested negative. After adjustment for covariates, night work and BMI > 30 were associated with a markedly greater risk of COVID-19 diagnosis (OR 3.049 95%CI 1.260–7.380 and OR 7.15 95%CI 2.91–17.51, respectively).
Conclusions
Our results describe a low prevalence of COVID-19 infection among HCWs at a central Italian COVID Hospital. COVID-19 infection risk appears to be associated with obesity and night shift work, thus supporting the need for careful health surveillance among frontline HCWs exposed to COVID-19.
Abstract
Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This ...study explored patients’ coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.
Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). ...However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above.
These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality.
These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted?
Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future.
Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex ...hormones total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D 25(OH)D and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19.
We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020.
Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality.
Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.
Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options.
The aim of this article ...was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease.
Two databases (PubMed and ClinicalTrial.gov) were reviewed.
Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort.
Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the ‘off label’ use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study.
There is a concern regarding the use of iodinated contrast agents (ICA) for chest and neck computed tomography (CT) to localize metastatases in patients with differentiated thyroid cancer (DTC). This ...is because the iodine in ICA can compete with (131)I and interfere with subsequent whole scans or radioactive iodine treatment. The required period for patients to eliminate the excess iodine is not clear. Therefore, knowing the period for iodine levels to return to baseline after the injection of ICA would permit a more reliable indication of CT for DTC patients. The most widely used marker to assess the plasmatic iodine pool is the urinary iodine (UI) concentration, which can be collected over a period of 24 hours (24U) or as a single-spot urinary sample (sU). As 24U collections are more difficult to perform, sU samples are preferable. It has not been established, however, if the measurement of iodine in sU is accurate for situations of excess iodine.
We evaluated 25 patients with DTC who received ICA to perform chest or neck CT. They collected 24U and sU urinary samples before the CT scan and 1 week and 1, 2, and 3 months after the test. UI was quantified by a semiautomated colorimetric method.
Baseline median UI levels were 21.8 μg/dL for 24U and 26 μg/dL for sU. One week after ICA, UI median levels were very high for all patients, 800 μg/dL. One month after ICA, however, UI median levels returned to baseline in all patients, 19.0 μg/dL for 24U and 20 μg/dL for sU. Although the values of median UI obtained from sU and 24U samples were signicantly different, we observed a significant correlation between samples collected in 24U and sU in all evaluated periods.
One month is required for UI to return to its baseline value after the use of ICA and for patients (after total thyroidectomy and radioiodine therapy) to eliminate the excess of iodine. In addition, sU samples, although not statistically similar to 24U values, can be used as a good marker to evaluate patients suspected of contamination with iodine.
•In the last decade, resistance in HIV-DNA was 35% in Italy.•Resistance in HIV-DNA was stable over the period 2010-2021.•Complex treatment history was associated with resistance in HIV-DNA.•APOBEC ...editing was found in around one quarter of HIV-DNA sequences.
We aimed at evaluating the temporal trend of drug-resistance and APOBEC editing from HIV-DNA genotypic resistance tests (GRT) in virologically suppressed individuals.
Major resistance mutations (MRM), genotypic susceptibility score (GSS) for the current regimen and APOBEC-related mutations (APO-M) were evaluated. Potential changes in trends of MRM and APO-M over-time were assessed and predictors of MRM detection or sub-optimal GSS (GSS<2) at HIV-DNA-GRT were estimated through logistic regression analyses.
Among the 1126 individuals included, 396 (35.2%) harboured at least one MRM (23.4% to NRTI, 18.8% to NNRTI, 7.7% to PI and 1.4% to INSTI N=724); 132 (12.3%) individuals showed a GSS <2. APO-M and stop codons were found in 229 (20.3%) and 105 (9.3%) individuals, respectively. APO-DRMs were found in 16.8% of individuals and were more likely observed in those individuals with stop codons (40.0%) compared to those without (14.4%, P<0.001). From 2010 to 2021 no significant changes of resistance or APO-M were found. Positive predictors of MRM detection at HIV-DNA GRT were drug abuse, subtype B infection, and a prolonged and complex treatment history. Perinatal infection and having at least 2 stop codons were associated with a current suboptimal regimen.
In virologically suppressed individuals, resistance in HIV-DNA and the extent of APOBEC editing were generally stable in the last decade. A careful evaluation of APOBEC editing might be helpful to improve the reliability of HIV-DNA GRT. Further investigations are required to understand how to apply the estimation of APOBEC editing in refining genotypic evaluation.
Abstract
Objectives
To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.
Methods
...Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).
Results
Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance.
Conclusions
A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
The transition from pediatric to adult health care is a vulnerable time for patients with chronic conditions. We need to better understand the factors affecting the health of kidney transplant ...recipients during this transition.
To determine the age at which renal transplant recipients are at greatest risk for graft loss.
We performed a retrospective analysis of 168,809 first kidney-only transplant events from October 1987 through October 2010, in recipients up to age 55 years as reported by the Organ Procurement Transplantation Network Standard Transplant Analysis and Research Database. Recipient age at transplant was the primary predictor studied. Confounder and effect modifier covariates were identified and studied using Cox proportional hazard models.
Kidney-only transplant.
Patient and renal graft survival, along with death-censored and non–death-censored information.
A total of 168,809 renal transplant events met the inclusion criteria. Recipients who received their first kidney transplant at age 14 to 16 years were at the highest risk of graft loss, with inferior outcomes starting at 1 and amplifying at 3, 5, and 10 years after transplant. Black adolescents were at disproportionately high risk of graft failure. The variables that had significant interaction with recipient age were donor type (deceased vs living) and insurance type (government vs private). Among 14-year-old recipients, the risk of death was 175% greater in the deceased donor–government insurance group vs the living donor–private insurance group (hazard ratio, 0.92 95% CI, 0.90-0.94 vs 0.34 95% CI, 0.33-0.36), whereas patient survival rates in the living donor–government insurance and deceased donor–private insurance groups were nearly identical (hazard ratio, 0.61 95% CI, 0.58-0.63 vs 0.54 95% CI, 0.51-0.56).
Recipients aged 14 to 16 years have the greatest risk of kidney allograft failure. Black adolescents and those with government insurance are at even higher risk. Private insurance reduces risk of death across all ages. Comprehensive programs are needed for adolescents, especially for those at greater risk, to reduce graft loss during the transition from adolescence to adulthood.
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