Multidrug-Resistant Bacterial Colonization and Infections in Large Retrospective Cohort of Mechanically Ventilated COVID-19 Patients1.

Few data are available on incidence of multidrug-resistant organism (MDRO) colonization and infections in mechanically ventilated patients, particularly during the COVID-19 pandemic. We retrospectively evaluated all patients admitted to the COVID-19 intensive care unit (ICU) of Hub Hospital in Milan, Italy, during October 2020‒May 2021. Microbiologic surveillance was standardized with active screening at admission and weekly during ICU stay. Of 435 patients, 88 (20.2%) had MDROs isolated ≤48 h after admission. Of the remaining patients, MDRO colonization was diagnosed in 173 (51.2%), MDRO infections in 95 (28.1%), and non-MDRO infections in 212 (62.7%). Non-MDRO infections occurred earlier than MDRO infections (6 days vs. 10 days; p<0.001). Previous exposure to antimicrobial drugs within the ICU was higher in MDRO patients than in non-MDRO patients (116/197 [58.9%] vs. 18/140 [12.9%]; p<0.001). Our findings might serve as warnings for future respiratory viral pandemics and call for increased measures of antimicrobial stewardship and infection control.

Incidence, microbiological and immunological characteristics of ventilator-associated pneumonia assessed by bronchoalveolar lavage and endotracheal aspirate in a prospective cohort of COVID-19 patients: CoV-AP study.

BACKGROUND: No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients. METHODS: Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BALFAPPP) as well as immunological markers (immune cells and inflammatory cytokines) was analysed. RESULTS: Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5-9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1-44.0) and 20.1 (95% CI 12.5-27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BALFAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8-97.7) sensitivity and 50.0% (95% CI 28.2-71.8) specificity (Cohen's Kappa 0.40, 95% CI 0.16-0.65). BALFAPPP showed 95.0% (95% CI 75.1-99.9) sensitivity and 69% (95% CI 49.2-84.7) specificity (Cohen's Kappa 0.60, 95% CI 0.39-0.81). BAL IL-1ß differed significantly between VAP (135 (IQR 11-450) pg/ml) and no-VAP (10 (IQR 2.9-105) pg/ml) patients (P = 0.03). CONCLUSIONS: In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BALFAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1ß showed potential in discriminating microbiologically confirmed VAP. CLINICAL TRIAL REGISTRATION: NCT04766983, registered on February 23, 2021.

Who Smokes in Europe? Data From 12 European Countries in the TackSHS Survey (2017-2018).

BACKGROUND: Population data on tobacco use and its determinants require continuous monitoring and careful inter-country comparison. We aimed to provide the most up-to-date estimates on tobacco smoking from a large cross-sectional survey, conducted in selected European countries. METHODS: Within the TackSHS Project, a face-to-face survey on smoking was conducted in 2017-2018 in 12 countries: Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania, and Spain, representing around 80% of the 432 million European Union (EU) adult population. In each country, a representative sample of around 1,000 subjects aged 15 years and older was interviewed, for a total of 11,902 participants. RESULTS: Overall, 25.9% of participants were current smokers (31.0% of men and 21.2% of women, P < 0.001), while 16.5% were former smokers. Smoking prevalence ranged from 18.9% in Italy to 37.0% in Bulgaria. It decreased with increasing age (compared to <45, multivariable odds ratio [OR] for ≥65 year, 0.31; 95% confidence interval [CI], 0.27-0.36), level of education (OR for low vs high, 1.32; 95% CI, 1.17-1.48) and self-rated household economic level (OR for low vs high, 2.05; 95% CI, 1.74-2.42). The same patterns were found in both sexes. CONCLUSIONS: These smoking prevalence estimates represent the most up-to-date evidence in Europe. From them, it can be derived that there are more than 112 million current smokers in the EU-28. Lower socio-economic status is a major determinant of smoking habit in both sexes.

Markers of microbial exposure lower the incidence of atopic dermatitis.

BACKGROUND: The hygiene hypothesis proposes that reduced exposure to infectious agents in early life would explain the increase of allergic and autoimmune diseases observed over the past decades in high-income countries. METHODS: We conducted a matched case-control study on incident atopic dermatitis (AD). Cases were 426 outpatient children with a first diagnosis of incident AD. Controls were 426 children attending a pediatric/dermatological visit for nonatopic disorders matched to cases (1:1). Particular attention was paid to the time elapsed between the markers of microbial exposure and disease onset, and we considered for controls the same time window of exposures from birth as his/her matched case. Odds ratios (ORs) were computed using multivariable conditional logistic regression models, according to center, sex, age, and period of enrollment, and including as potential confounders a family history of any allergy in parents, type of delivery, having siblings, keeping pets, age at weaning, and having had ≥4 infections. RESULTS: The OR of AD first occurrence was 0.35 (P-value = .039) for children who had experienced ≥4 infections compared with those with no infections. A decreasing trend in risk was observed with increasing number of siblings (P-value = .023), the protective effect reaching about 40% for children with 2 or more siblings (OR = 0.62; P-value = .048). Pet keeping, in particular daily contact with dogs, was inversely associated with AD risk (OR = 0.40; P-value = .004). CONCLUSIONS: These results support the hygiene hypothesis in its broad sense. Early-life environmental exposures, including pathogens and commensals, act as "microbes contact carriers" influencing immune system balance early in life.

Psoriasis Incidence and Lifetime Prevalence: Suggestion for a Higher Mortality Rate in Older Age-classes among Psoriatic Patients Compared to the General Population in Italy.

Data on the psoriasis incidence and prevalence in the Italian population are limited, and a timely and accurate understanding of the disease epidemiology is needed. This ad hoc study investigated psoriasis incidence and lifetime prevalence in a representative sample (n = 14,705) of the Italian population. Information on lifetime history of skin disorders with details about their onset, duration, and treatment was collected. Psoriasis incidence showed a bimodal distribution pattern, with peaks in age classes characteristic of early-onset (35-44 years) and late-onset (65-74 years) psoriasis. Late-onset psoriasis showed some variations according to the sex, with females being diagnosed earlier than males. Lifetime prevalence of psoriasis was 2.7% (95% confidence interval: 2.5-3.0): it increased to 3.5% at age 60-64 years, then decreased steadily after age 64, to 1.7% at age > 74 years. This decrease, despite a peak in incidence rates, after age 64, may suggest a higher mortality rate among psoriasis patients in older age classes, compared to the general population.

Laryngeal cancer mortality trends in European countries.

After a steady increase between the 1950s and the 1970s, laryngeal cancer mortality has been levelling off since the early 1980s in men from most western and southern European countries and since the early 1990s in central and eastern Europe. To update trends in laryngeal cancer mortality, we analyzed data provided by the World Health Organization over the last two decades for 34 European countries and the European Union (EU) as a whole. For major European countries, we also identified significant changes in trends between 1980 and 2012 using joinpoint regression analysis. Male mortality in the EU was approximately constant between 1980 and 1991 (annual percent change, APC=-0.5%) and declined by 3.3% per year in 1991-2012. EU age-standardized (world population) rates were 4.7/100,000 in 1990-91 and 2.5/100,000 in 2010-2011. Rates declined in most European countries, particularly over the last two decades. In 2010-11, the highest male rates were in Hungary, the Republic of Moldova, and Romania (over 6/100,000), and the lowest ones in Finland, Norway, Sweden, and Switzerland (below 1/100,000). In EU women, mortality was stable around 0.29/100,000 between 1980 and 1994 and slightly decreased thereafter (APC=-1.3%; 0.23/100,000 in 2000-01). We also considered male incidence trends for nine European countries or cancer registration areas. In most of them, declines were observed over recent decades. Laryngeal cancer mortality thus showed favourable trends over the last few decades in most Europe, following favourable changes in tobacco and, mostly for Mediterranean countries, alcohol consumption.

Perinatal factors and the risk of atopic dermatitis: a cohort study.

OBJECTIVE: To analyze the effects of pregnancy and early events in the newborn on the risk of subsequent atopic dermatitis (AD) during the first year of life. PATIENTS AND METHODS: This is a prospective multicenter cohort study of newborns during the first year of life. Newborns identified on random days in three obstetrics departments in the area of Bergamo, Lombardy, Northern Italy, were eligible. At baseline, the mothers were interviewed by medical staff during their stay in hospital after delivery. At 6 and 12 months after delivery, a postal questionnaire was sent to the parents. Relative risks were calculated with and without adjustment by multiple regression analysis. RESULTS: A total of 1081 newborns entered the study: 796 (74%) parents answered the 12-month questionnaire. Hundred and thirty-eight (17%) reported a diagnosis of AD at 6 months and 222 (28%) at 12 months. Parental history of AD and/or asthma was associated with an increased risk of AD (RR 1.5, 95%CI 1.1-2.0). Birth weight was slightly associated with an increased risk of AD: RR 1.04, 95%CI 1.001-1.08 (continuous variable, increment of 100 grams). No association emerged between breast feeding, smoking, and risk of AD. CONCLUSIONS: This study in an Italian offspring cohort points to family history of atopic diseases and body weight at birth as relevant risk factors. The study was unable to document associations with other perinatal factors particularly breast feeding and parental smoking in the perinatal period.

Pet exposure and risk of atopic dermatitis at the pediatric age: a meta-analysis of birth cohort studies.

BACKGROUND: Findings on pet exposure and the risk of atopic dermatitis (AD) in children are inconsistent. OBJECTIVE: With the aim to summarize the results of exposure to different pets on AD, we undertook a meta-analysis of epidemiologic studies on this issue. METHODS: In August 2012, we conducted a systematic literature search in Medline and Embase. We included analytic studies considering exposure to dogs, cats, other pets, or pets overall during pregnancy, infancy, and/or childhood, with AD assessment performed during infancy or childhood. We calculated summary relative risks and 95% CIs using both fixed- and random-effects models. We computed summary estimates across selected subgroups. RESULTS: Twenty-six publications from 21 birth cohort studies were used in the meta-analyses. The pooled relative risks of AD for exposure versus no exposure were 0.72 (95% CI, 0.61-0.85; I(2) = 46%; results based on 15 studies) for exposure to dogs, 0.94 (95% CI, 0.76-1.16; I(2) = 54%; results based on 13 studies) for exposure to cats, and 0.75 (95% CI, 0.67-0.85; I(2) = 54%; results based on 11 studies) for exposure to pets overall. No heterogeneity emerged across the subgroups examined, except for geographic area. CONCLUSION: This meta-analysis reported a favorable effect of exposure to dogs and pets on the risk of AD in infants or children, whereas no association emerged with exposure to cats.

Parents' age and total fertility rate in selected high-income countries from Europe and North America, 1990-2020.

OBJECTIVE: To provide a comprehensive picture of trends in parents' age and total fertility rate in selected most populous high-income countries from Europe and North America. STUDY DESIGN: Data were retrieved from official statistics published by the United Nations, the World Bank, the European Union (EU), and by national health statistics offices. RESULTS: Mean maternal age at birth showed increasing trends in all considered countries; in 2020, the highest mean age was observed in Italy (32.2) and Spain (32.3), and the lowest one in the USA (28.8). Mean maternal age at first birth also showed upward trends. In the 1990s, mean age at first birth ranged from 25.5 to 26.9 years, except for the USA where it was below 25 years. The countries with the highest average maternal age at first birth were Italy and Spain, reaching 31 years over the most recent years. Data on mean paternal age at birth were scant. In Germany (2019) it was 34.6 and in the USA (2014) 27.9 years. In Italy, mean paternal age increased from 34.2 in 2000 to 35.5 in 2018, in the UK from 30.7 in 1990 to 33.4 in 2017, and in Canada, a decrease was observed from 29.1 in 2006 to 28.3 in 2011. Finally, Sweden and the USA had the highest fertility rates, around two children in some years, while Italy and Spain had the lowest ones, with less than 1.5 children over the whole period. CONCLUSIONS: Monitoring of trends in reproductive factors is crucial to gain insight into society from a cultural and sociological point of view and to analyze the impact of these changes on reproductive health and related conditions.

Trends in mortality from leukemia in Europe: an update to 2009 and a projection to 2012.

We considered trends in mortality from leukemia in Europe over the period 1970-2009 using data from the World Health Organization. We computed age-standardized (world population) mortality rates, at all ages and in selected age groups, in 11 selected European countries, the European Union (EU) and, for comparative purposes, in the USA and Japan. For the EU, we also provided projections of the mortality to 2012. Over the period considered, mortality from leukemia steadily declined in most European countries in children and young adults, as well as in western and southern Europe at middle-age (45-69 years); in central/eastern Europe, reductions at ages 45-69 started since the mid-late 1990s. In the EU, annual percent changes were -3.7% in males and -3.8% in females at age 0-14, -2% in both sexes at age 15-44, and -0.6% in males and -1% in females at middle-age and overall. No decline was observed at age 70 or more. Between 1997 and 2007, overall EU rates decreased from 5.4 to 4.8/100,000 males and from 3.4 to 2.9/100,000 females. Declines were from 6.2 to 5.5/100,000 males and from 3.7 to 3.2/100,000 females in the USA and from 3.9 to 3.5/100,000 males and from 2.5 to 2.0/100,000 females in Japan. Projected overall rates in the EU at 2012 are 4.3/100,000 males (-11% compared to 2007) and 2.6/100,000 females (-12%).

Hodgkin's lymphoma mortality in the Americas, 1997-2008: achievements and persistent inadequacies.

Although therapeutic advancements have made Hodgkin's lymphoma (HL) a largely curable disease, trends in HL mortality have been variable across countries. To provide updated information on HL mortality in the Americas, overall and 20-44 years age-standardized (world population) mortality rates from HL were derived for the 12 Latin American countries providing valid data to the World Health Organization database and with more than two million of inhabitants. For comparative purpose, data for the United States and Canada were also presented. Trends in mortality over the 1997 to 2008 period are based on joinpoint regression analysis. Declines in HL mortality were registered in all Latin American countries except in Venezuela. In most recent years, HL mortality had fallen to about 0.3/100,000 men and 0.2/100,000 women in Argentina, Brazil, Chile, Colombia, Ecuador and Guatemala, that is, to values similar to North America. Despite some declines, rates remained high in Cuba (1/100,000 men and 0.7/100,000 women), Costa Rica and Mexico as well as in Venezuela (between 0.5 and 0.6/100,000 men and between 0.3 and 0.5/100,000 women). In young adults, trends were more favorable in all Latin American countries except Cuba, whose rates remained exceedingly high (0.8/100,000 men and 0.6/100,000 women). Thus, appreciable declines in HL mortality were observed in most Latin America over the last decade, and several major countries reached values comparable to North America. Substantial excess mortality was still observed in Cuba, Costa Rica, Mexico and Venezuela, calling for urgent interventions to improve HL management in these countries.

Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (CRAB) in Mechanically Ventilated COVID-19 Patients and Impact of Infection Control Measures on Reducing CRAB Circulation during the Second Wave of the SARS-CoV-2 Pandemic in Milan, Italy.

COVID-19 has significantly affected hospital infection prevention and control (IPC) practices, especially in intensive care units (ICUs). This frequently caused dissemination of multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB). Here, we report the management of a CRAB outbreak in a large ICU COVID-19 hub Hospital in Italy, together with retrospective genotypic analysis by whole-genome sequencing (WGS). Bacterial strains obtained from severe COVID-19 mechanically ventilated patients diagnosed with CRAB infection or colonization between October 2020 and May 2021 were analyzed by WGS to assess antimicrobial resistance and virulence genes, along with mobile genetic elements. Phylogenetic analysis in combination with epidemiological data was used to identify putative transmission chains. CRAB infections and colonization were diagnosed in 14/40 (35%) and 26/40 (65%) cases, respectively, with isolation within 48 h from admission in 7 cases (17.5%). All CRAB strains belonged to Pasteur sequence type 2 (ST2) and 5 different Oxford STs and presented blaOXA-23 gene-carrying Tn2006 transposons. Phylogenetic analysis revealed the existence of four transmission chains inside and among ICUs, circulating mainly between November and January 2021. A tailored IPC strategy was composed of a 5-point bundle, including ICU modules' temporary conversion to CRAB-ICUs and dynamic reopening, with limited impact on ICU admission rate. After its implementation, no CRAB transmission chains were detected. Our study underlies the potentiality of integrating classical epidemiological studies with genomic investigation to identify transmission routes during outbreaks, which could represent a valuable tool to ensure IPC strategies and prevent the spread of MDROs. IMPORTANCE Infection prevention and control (IPC) practices are of paramount importance for preventing the spread of multidrug-resistant organisms (MDROs) in hospitals, especially in the intensive care unit (ICU). Whole-genome sequencing (WGS) is seen as a promising tool for IPC, but its employment is currently still limited. COVID-19 pandemics have posed dramatic challenges in IPC practices, causing worldwide several outbreaks of MDROs, including carbapenem-resistant Acinetobacter baumannii (CRAB). We present the management of a CRAB outbreak in a large ICU COVID-19 hub hospital in Italy using a tailored IPC strategy that allowed us to contain CRAB transmission while preventing ICU closure during a critical pandemic period. The analysis of clinical and epidemiological data coupled with retrospective genotypic analysis by WGS identified different putative transmission chains and confirmed the effectiveness of the IPC strategy implemented. This could be a promising approach for future IPC strategies.

Changes in upper airways microbiota in ventilator-associated pneumonia.

BACKGROUND: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. METHODS: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). RESULTS: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. CONCLUSIONS: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP.

Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis.

BACKGROUND: The study of probiotics to prevent allergic conditions has yielded conflicting results in children. We undertook a meta-analysis of randomized controlled trials to investigate whether probiotic use during pregnancy and early life decreases the incidence of atopic dermatitis and immunoglobulin E (IgE)-associated atopic dermatitis in infants and young children. METHODS: We performed a systematic literature search in Medline, Embase, and Cochrane Library, updated to October 2011. The intervention was diet supplementation with probiotics versus placebo. Primary outcomes were incidence of atopic dermatitis and IgE-associated atopic dermatitis. We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs), using both fixed- and random-effects models. We computed summary estimates across several strata, including study period, type of patient, dose, and duration of intervention, and we assessed the risk of bias within and across trials. RESULTS: We identified 18 publications based on 14 studies. Meta-analysis demonstrated that probiotic use decreased the incidence of atopic dermatitis (RR = 0.79 [95% CI = 0.71-0.88]). Studies were fairly homogeneous (I = 24.0%). The corresponding RR of IgE-associated atopic dermatitis was 0.80 (95% CI = 0.66-0.96). No appreciable difference emerged across strata, nor was there evidence of publication bias. CONCLUSIONS: This meta-analysis provided evidence in support of a moderate role of probiotics in the prevention of atopic dermatitis and IgE-associated atopic dermatitis in infants. The favorable effect was similar regardless of the time of probiotic use (pregnancy or early life) or the subject(s) receiving probiotics (mother, child, or both).

Rationale and design of a multicenter prospective cohort study for the eVALuation and monitoring of HPV infections and relATEd cervical diseases in high-risk women (VALHIDATE study).

BACKGROUND: Pap screening, an effective method for cervical cancer prevention, is now supported by molecular human papillomavirus (HPV) testing. Recently commercialised preventive vaccines also provide new tools for the primary prevention of cervical cancer. To determine appropriate prevention strategies, the Health General Direction, Lombardy Region, funded a project that aims to characterize and monitor HPV infections and related cervical diseases in high-risk women. METHODS/DESIGN: VALHIDATE is a 5-year multicentre open prospective cohort study. It will recruit 7000 consenting women aged 13-65 years to provide information about the local biomolecular epidemiology of HPV infection and cervical diseases in high-risk women recruited from nine clinical centres and one faith-based organisation. The study will estimate the overall and type-specific prevalence of HPV infection and cervical abnormalities. It also aims to compare standard Pap screening with biomolecular screening, and to assist in the design of targeted regional prevention programs directed specifically at high-risk groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26-65 years), 1000 recent migrant women (aged 26-65 years) and 3000 young women (aged 13-26 years) and 1 control group: 2000 women (aged 26-45 years) attending a spontaneous screening program, will be recruited. Sample sizes will be revised after the first year. Adult participants will undergo conventional cervical cytology, HPV DNA screening and genotyping. Paediatric participants will undergo HPV DNA testing and genotyping of urine samples. HPV DNA, cytological abnormalities and HPV types will be analysed according to demographic, epidemiological, behavioural, and clinical data collected in an electronic case report form. Overall and stratified prevalences will be estimated to analyse the associations between HPV infection and selected characteristics. Logistic regression models will be used to estimate crude and adjusted odds ratios. Cox proportional hazard models will be used to estimate hazard ratios over time and between groups. DISCUSSION/MAIN EXPECTED RESULTS: This study will provide substantial insight into HPV infections and related cervical diseases in high-risk groups and will help determine appropriate regional cervical cancer prevention strategies.

Pregnancy Outcomes in Women With Mechanical Valve Prostheses Using Vitamin K Antagonist Therapy: The Experience of the Salam Centre for Cardiac Surgery in Sudan.

Pregnancy and childbirth on anticoagulants after mechanical heart valve replacement present a high risk of complications for both mother and baby. On top of pregnancy worsening the mother's cardiac function, anticoagulant therapy itself is a crucial problem. A safe and effective anticoagulation regimen for both mother and fetus is not possible. The most effective drugs for preventing valve thrombosis are VKAs, whose dosage needs to be adjusted with frequent INR checks. Moreover, VKAs can have embryopathic and teratogenic action. Patients in follow-up and anticoagulant treatment at the Salam Centre for Cardiac Surgery in Sudan live spread out over a large area where transport to the Center is generally difficult; pregnancy treatment has, therefore, been adapted to the limitations of reality. Pregnancy is discouraged and contraception and therapeutic abortion are recommended, but this guidance frequently goes unheeded. Here we describe maternal and fetal outcomes in 307 consecutive pregnancies recorded by staff at the oral anticoagulant clinic (OAC) from April 2017 to November 2021. Out of 307 pregnancies, there were 15 maternal deaths (4.9%), 24 thrombotic events (7.8%) and 22 major bleedings (7.2%). Fifty pregnancies (16.3%) were terminated by therapeutic abortion. Only 47.6% of pregnancies had good maternal and neonatal outcomes. Data clearly show that, due to the complexity of pregnancy in women with mechanical heart valves and the scarcity of tertiary healthcare services in the area where patients live, maternal mortality is at an unacceptable level and requires a structured, multi-disciplinary intervention.

Simple open-heart surgery protocol for sickle-cell disease patients: a retrospective cohort study comparing patients undergoing mitral valve surgery.

OBJECTIVES: Sickle-cell disease (SCD) patients are considered to be at high risk from open-heart surgery. This study assessed the role of a simple sickling-prevention protocol. METHODS: Perioperative non-specific and SCD-specific morbidity and 30-day mortality are investigated in a retrospective cohort study on patients undergoing isolated mitral valve surgery. Patients with and without SCD were compared. In the SCD cohort, a bundle of interventions was applied to limit the risk of sickling: 'on-demand' transfusions to keep haemoglobin levels of around 7-8 g/dl, cardiopulmonary bypass (CPB) with higher blood flow and perfusion temperature, close monitoring of acid-base balance and oxygenation. RESULTS: Twenty patients with and 40 patients without SCD were included. At baseline, only preoperative haemoglobin levels differed between cohorts (8.1 vs 11.8 g/dl, P < 0.001). Solely SCD patients received preoperative transfusions (45.0%). Intraoperative transfusions were significantly larger in SCD patients during CPB (priming: 300 vs 200 ml; entire length: 600 vs 300 ml and 20 vs 10 ml/kg). SCD patients had higher perfusion temperatures during CPB (34.7 vs 33.0°C, P = 0.01) with consequently higher pharyngeal temperature, both during cooling (34.1 vs 32.3°C, P = 0.02) and rewarming (36.5 vs 36.2°C, P = 0.02). No mortality occurred, and non-SCD-specific complications were comparable between groups, but one SCD patient suffered from perioperative cerebrovascular accident with seizures, and another had evident haemolysis. CONCLUSIONS: SCD patients may undergo open-heart surgery for mitral valve procedures with an acceptable risk profile. Simple but thoughtful perioperative management, embracing 'on-demand' transfusions and less-aggressive CPB cooling is feasible and probably efficacious.

Prognostic Value of Mid-Region Proadrenomedullin and In Vitro Interferon Gamma Production for In-Hospital Mortality in Patients with COVID-19 Pneumonia and Respiratory Failure: An Observational Prospective Study.

Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFNγ) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFNγ production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1−Q3 54.5−75) years, and 58% had ≥1 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157−309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12−1.77) nmol/L vs. 0.79 (0.63−1.03) nmol/L, p < 0.001) and T1 (1.67 (1.08−1.96) nmol/L vs. 0.66 (0.53−0.95) nmol/L, p < 0.001). In vitro IFNγ production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79−0.94), with the best cut-off point at 1.04 nmol/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFNγ production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression.

Coronary heart disease and cerebrovascular disease mortality in young adults: recent trends in Europe.

BACKGROUND: Over the last two decades, mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) declined by about 30% in the European Union (EU). DESIGN: We analyzed trends in CHD (X ICD codes: I20-I25) and CVD (X ICD codes: I60-I69) mortality in young adults (age 35-44 years) in the EU as a whole and in 12 selected European countries, over the period 1980-2007. METHODS: Data were derived from the World Health Organization mortality database. With joinpoint regression analysis, we identified significant changes in trends and estimated average annual percent changes (AAPC). RESULTS: CHD mortality rates at ages 35-44 years have decreased in both sexes since the 1980s for most countries, except for Russia (130/100,000 men and 24/100,000 women, in 2005-7). The lowest rates (around 9/100,000 men, 2/100,000 women) were in France, Italy and Sweden. In men, the steepest declines in mortality were in the Czech Republic (AAPC = -6.1%), the Netherlands (-5.2%), Poland (-4.5%), and England and Wales (-4.5%). Patterns were similar in women, though with appreciably lower rates. The AAPC in the EU was -3.3% for men (rate = 16.6/100,000 in 2005-7) and -2.1% for women (rate = 3.5/100,000). For CVD, Russian rates in 2005-7 were 40/100,000 men and 16/100,000 women, 5 to 10-fold higher than in most western European countries. The steepest declines were in the Czech Republic and Italy for men, in Sweden and the Czech Republic for women. The AAPC in the EU was -2.5% in both sexes, with steeper declines after the mid-late 1990s (rates = 6.4/100,000 men and 4.3/100,000 women in 2005-7). CONCLUSIONS: CHD and CVD mortality steadily declined in Europe, except in Russia, whose rates were 10 to 15-fold higher than those of France, Italy or Sweden. Hungary and Poland, and also Scotland, where CHD trends were less favourable than in other western European countries, also emerge as priorities for preventive interventions.