Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis.

AIMS: For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF. METHODS AND RESULTS: We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61-0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53-0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70-1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78-1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49-0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74-1.30) (heterogeneity p = 0.07). CONCLUSION: In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.

Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status.

Background: Systemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients. Methods: Ninety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support. Results: Serum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 [PIIINP: 7.2 (5.4-9.5) vs. 7.1 (4.5-9.9), p = 0.782; TIMP-1: 298.1 (20.5-460) vs. 222.2 (28.5-452.8), p = 0.01; HA: 117.1 (55.4-193.7) vs. 75.1 (36.9-141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 [15.8 (9-44.5) vs. 9.3 (3.4-33.8), p = 0.039 and 373 (282-465) vs. 289 (218-383), p = 0.013, respectively]. Conclusion: In patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.

Enhanced liver fibrosis score as a noninvasive biomarker in hepatitis C virus patients after direct-acting antiviral agents.

Background: In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures. Objectives: In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs. Study design: We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples "Federico II" between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48. Results: One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (p = 0.086), 0.15 (p = 0.124), and 0.034 (p = 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (p < 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites. Conclusions: Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.

A Phase II Study on the Effect of Taurisolo® Administered via AEROsol in Hospitalized Patients with Mild to Moderate COVID-19 Pneumonia: The TAEROVID-19 Study.

BACKGROUND: Polyphenols are the largest class of bioactive compounds in plants, which are synthesized as secondary metabolites. In the last few years, interesting studies have demonstrated the efficacy of polyphenols against coronavirus infections. METHODS: we conducted a phase II multicentric clinical trial (TAEROVID-19) during the first wave of the COVID-19 pandemic in order to assess the safety and feasibility of Taurisolo® aerosol formulation in hospitalized patients suffering from SARS-CoV-2 pneumonia. RESULTS: we observed a rapid decline of symptoms and a low rate of intensive care in patients treated with Taurisolo®, with a faster decline of symptoms. CONCLUSIONS: This is the first trial assessing the safety and feasibility of Taurisolo® aerosol formulation. We could argue that this treatment could act as an add-on therapy in the treatment of COVID-19 patients, owing to both its anti-inflammatory and antioxidant effects. Further controlled trials are needed, which may be of interest to evaluate the compound's efficacy.

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

BACKGROUND: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). METHODS: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. RESULTS: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). CONCLUSIONS: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.

A Survey Among Italian Physicians During COVID-19 Outbreak. Could Bacillus Calmette-Guérin Vaccine Be Effective Against SARS-CoV2?

Background: Epidemiological studies show that BCG-vaccinated population seems to be more likely protected from COVID-19 infection, but WHO gave a stark warning on use of BCG vaccine without confirmed COVID-19 trials. The aim of the study is to evaluate whether TB vaccination, performed several years earlier, could confer protection against COVID-19. Methods: After the Ethical Committee authorization, professional orders were used to contact physicians with an online survey. Specialty, COVID-19 infection and previous BCG vaccination were recorded. Statistical data analysis was performed. Results: 1906 physicians answered the questionnaire, (M = 1068; F = 838; mean age 50.7 ± 13.3 years; range 24-87), more than half (1062; 55.7%) experienced BCG vaccination. Professional activity was recorded, and only 49 subjects (2.6%) of them were infected by SARS-CoV2. Among the group of infected people, asymptomatic form occurred in 12 subjects (24.5%); a pauci-symptomatic form in 24 subjects (49.0%); and a severe form (pneumonia and/or respiratory distress) in 13 (26.5%). Considering only the clinically relevant form of COVID-19, period prevalence was 2.2% (23/1062) in the vaccinated group and 1.7% (14/844) in the unvaccinated group (OR: 1.31, 95% C.I.: 0.68-2.63, p = 0.427). Conclusion: Our experience does not confirm the possible protective role of BCG vaccination, performed years earlier, against COVID-19. Although recent epidemiological studies point out in BCG-vaccinated population a lower prevalence of SARS-CoV2 infection, in our cohort of physicians no significant difference was found in terms of prevalence of COVID-19 infection. Our data underline the necessity to follow the WHO warning about the indiscriminate use of BCG vaccine, until clear evidence of protection by BCG vaccination against COVID-19 is fully demonstrated.

Systemic administration of glucocorticoids, cardiovascular complications and mortality in patients hospitalised with COVID-19, SARS, MERS or influenza: A systematic review and meta-analysis of randomised trials.

BACKGROUND: Administration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. OBJECTIVES: to investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. METHODS: We identified randomised trials published prior to July 28th, 2021. The Mantel-Haenszel random effects method and the Hartung and Knapp adjustment were used to obtain pooled estimates of treatment effect with 95% confidence intervals. RESULTS: No randomised trials of glucocorticoids for SARS, MERS or influenza reported relevant outcomes. We included eleven COVID-19 randomised trials (8109 patients). Overall, compared to placebo or standard care, glucocorticoids were not associated with a reduction of in-hospital mortality (p = 0.09). In a pre-specified sub-analysis, in-hospital mortality was reduced by 19% when follow-up was restricted to 14 days from randomisation (5/11 trials, 1329 patients, p = 0.02). With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57-1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 - 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Glucocorticoids reduced the risk of worsening renal function by 37% (4/11 trials); reported rate of other cardiovascular complications was low. CONCLUSIONS: Administration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not.

Comparing the COVID-19 pandemic in space and over time in Europe, using numbers of deaths, crude rates and adjusted mortality trend ratios.

Comparison of COVID-19 trends in space and over time is essential to monitor the pandemic and to indirectly evaluate non-pharmacological policies aimed at reducing the burden of disease. Given the specific age- and sex- distribution of COVID-19 mortality, the underlying sex- and age-distribution of populations need to be accounted for. The aim of this paper is to present a method for monitoring trends of COVID-19 using adjusted mortality trend ratios (AMTRs). Age- and sex-mortality distribution of a reference European population (N = 14,086) was used to calculate age- and sex-specific mortality rates. These were applied to each country to calculate the expected deaths. Adjusted Mortality Trend Ratios (AMTRs) with 95% confidence intervals (C.I.) were calculated for selected European countries on a daily basis from 17th March 2020 to 29th April 2021 by dividing observed cumulative mortality, by expected mortality, times the crude mortality of the reference population. These estimated the sex- and age-adjusted mortality for COVID-19 per million population in each country. United Kingdom experienced the highest number of COVID-19 related death in Europe. Crude mortality rates were highest Hungary, Czech Republic, and Luxembourg. Accounting for the age-and sex-distribution of the underlying populations with AMTRs for each European country, four different patterns were identified: countries which experienced a two-wave pandemic, countries with almost undetectable first wave, but with either a fast or a slow increase of mortality during the second wave; countries with consistently low rates throughout the period. AMTRs were highest in Eastern European countries (Hungary, Czech Republic, Slovakia, and Poland). Our methods allow a fair comparison of mortality in space and over time. These might be of use to indirectly estimating the efficacy of non-pharmacological health policies. The authors urge the World Health Organisation, given the absence of age and sex-specific mortality data for direct standardisation, to adopt this method to estimate the comparative mortality from COVID-19 pandemic worldwide.

An observational study of a cohort of citizens receiving the AZD1222 vaccine against SARS-CoV-2.

In this retrospective study, a cohort of 67 subjects vaccinated with AZD1222 was retrospectively observed. Consistently with published findings, no serious adverse event was reported, and all adverse events reported (fever, muscle ache and/or pain in the site of injection) had resolved by day 8. Of note, some citizens were prescribed low-dose aspirin and even heparin for thrombosis prevention. We also found variations in laboratory test results (full blood count and chemistry) on day 1 compared with day 8. Physicians should be aware that no prevention therapy for thrombosis is currently recommended, given the very low incidence of this side effect. Additional studies are warranted to interpret our findings.

Seroprevalence of SARS-CoV-2-specific antibodies in the town of Ariano Irpino (Avellino, Campania, Italy): a population-based study.

The Italian municipality of Ariano Irpino (Avellino, Campania, Italy) was locked down by the regional authorities from March until April 2020 after several citizens tested positive for SARS coronavirus 2 (SARS-CoV-2). A serological mass screening campaign targeting the Ariano Irpino population using the Roche Cobas Elecsys anti-SARS-CoV-2 assay was organized by the Zoo-Prophylactic Institute of Southern Italy (Portici, Italy) and conducted in cooperation with the Local Health Unit (Azienda Sanitaria Locale - ASL - Avellino, Avellino, Italy), the Department of Public Health of University Federico II (Naples, Italy) and Department of Health Services of Azienda Ospedaliera dei Colli-Cotugno and Monaldi Hospital (Naples, Italy) in May 2020. A total of 13,218 asymptomatic individuals were reviewed in this analysis. A total of 738 citizens tested positive for anti-SARS-CoV-2 antibodies (398 females, 340 males). The overall prevalence in the sample was 5.6% (95% CI: 5.2-6.0). Among seropositive citizens, 101 cases tested positive on RT-PCR (0.76% of the overall population). Among citizens aged 14-18, 18-65 and >65 years, the seroprevalence was equal to 6.1 (95% CI: 4.1-8.7), 5.6 (95% CI: 5.1-6.1) and 4% (95% CI: 3.3-4.8), respectively. In the pediatric cohort (<14 years old), seroprevalence was 13% (95% CI: 10.2-16.2). A serological-based screening strategy could be a cost-effective public health intervention to tackle the COVID-19 pandemic.

Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries.

BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.

Cytology in the time of coronavirus disease (COVID-19): an Italian perspective.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is changing the way we practice pathology, including fine needle aspiration (FNA) diagnostics. Although recommendations have been issued to prioritise patients at high oncological risk, postponing those with unsuspicious presentations, real world data have not been reported yet. METHODS: The percentages of the cytological sample types processed at the University of Naples Federico II, during the first 3 weeks of Italian national lockdown were compared with those of the same period in 2019. RESULTS: During the emergency, the percentage of cytology samples reported as malignant increased (p<0.001), reflecting higher percentages of breast (p=0.002) and lymph nodes FNAs (p=0.008), effusions (p<0.001) and urine (p=0.005). Conversely, thyroid FNAs (p<0.001) and Pap smears (p=0.003) were reduced. CONCLUSIONS: Even in times of COVID-19 outbreak, cytological examination may be safely carried out in patients at high oncological risk, without the need to be postponed.