Functional outcome after inpatient rehabilitation in postintensive care unit COVID-19 patients: findings and clinical implications from a real-practice retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading worldwide, with survivors that suffer functional impairments with a consequent key role of rehabilitation in this context. To date, there is a lack of findings on the role of rehabilitation in postacute COVID-19 patients. AIM: Thus, we aimed at describing the role of a patient-tailored rehabilitation plan on functional outcome in hospitalized COVID-19 patients. DESIGN: Real-practice retrospective study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Postacute COVID-19 patients. METHODS: Medical records of patients referred to an Italian COVID-19 Rehabilitation Unit from March 10th, 2020 to April 30th, 2020 were collected. All patients underwent a rehabilitative (30 minutes/set, 2 times/day), aimed to improve gas exchanges, reducing dyspnoea, and improving muscle function. At the admission (T0) and at the discharge (T1), we evaluated as outcome measures: Barthel Index (BI), modified Medical Research Council Dyspnea Scale, 6-Minute Walking Test (6-MWT) and Borg Rating of Perceived Exertion (RPE) scale. We also assessed: type of respiratory supports needed, pulmonary function, coagulation and inflammation markers and length of stay (LOS) in Rehabilitation Unit. RESULTS: We included 41 postacute COVID-19 patients (25 male and 19 female), mean aged 72.15±11.07 years. Their mean LOS in the Rehabilitation Unit was 31.97±9.06 days, as 39 successfully completed the rehabilitation treatment and 2 deceased. We found statistically significant improvement in BI (84.87±15.56 vs. 43.37±26.00; P<0.0001), 6-MWT (303.37±112.18 vs. 240.0±81.31 meters; P=0.028), Borg RPE scale (12.23±2.51 vs. 16.03±2.28; P<0.0001). CONCLUSIONS: These findings suggest that postacute COVID-19 patients might beneficiate of a motor and respiratory rehabilitation treatment. However, further studies are advised to better understand long-term sequelae of the disease. CLINICAL REHABILITATION IMPACT: This study provides evidence on the role of rehabilitation COVID-19 postacute inpatients through a patient-tailored treatment.

Early rehabilitation in post-acute COVID-19 patients: data from an Italian COVID-19 Rehabilitation Unit and proposal of a treatment protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading, putting under heavy stress health systems worldwide and especially Intensive Care Units (ICU). Rehabilitation Units have a crucial role in reducing disability in order to reintroduce patients in the community. AIM: The aim of this study is to characterize pulmonary function and disability status and to propose an early rehabilitation protocol in a cohort of post-acute COVID-19 patients admitted to an Italian Rehabilitation Unit. DESIGN: Cross-sectional observational study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Post-acute COVID-19 patients. METHODS: Demographic, anamnestic and clinical characteristics, laboratory exams and medical imaging findings were collected for the entire cohort. Outcome measures evaluated at the admission in Rehabilitation Unit were: type of respiratory supports needed, fraction of inspired oxygen (FiO2), partial pressure of oxygen (PaO2), FiO2/PaO2, Barthel Index (BI), modified Medical Research Council (mMRC) Dyspnoea Scale, and 6-Minute Walking Test (6-MWT). Furthermore, we proposed an early rehabilitation protocol for COVID-19 patients based on baseline FiO2. RESULTS: We included 32 post-acute COVID-19 patients (22 male and 10 female), mean aged 72.6±10.9 years. BI was 45.2±27.6, with patients in need of higher FiO2 (≥40%) showing lower values: 39.6±25.7 vs. 53.3±29.3. All patients had grade 4 or 5 on the mMRC Dyspnea Scale. Only 14 COVID-19 patients were able to walk (43.7%). 6-MWT was feasible in 6 (18.8%) patients with a mean distance of 45.0±100.6 meters. CONCLUSIONS: Taken together, our findings suggest that post-acute COVID-19 patients suffered from dyspnea and shortness of breath even for minimal activities, with a resulting severe disability, and only a few of them were able to perform 6-MWT with poor results. An early rehabilitation protocol was proposed according to the baseline conditions of the patients. CLINICAL REHABILITATION IMPACT: This study could provide an accurate description of COVID-19 sub-acute patients admitted to a Rehabilitation Unit along with a proposal of treatment to help physicians to tailor the best possible rehabilitative treatment.

[Carcinogenicity of antineoplastic drugs: classification, protection and prevention, use and evidence]. / Cancerogenicità dei farmaci antiblastici, classificazioni, protezione e prevenzione, utilizzo ed evidenze.

Many antineoplastic agents have been shown to be mutagenic, teratogenic and carcinogenic in experimental studies and secondary malignant neoplasms are known to be associated with several specific therapeutic treatments. However, the occupational exposure to antineoplastic drugs in health care workers has different routes of exposure, dose and duration compared to patients undergoing treatment protocols. The aims of this review are to analyze and to update the National and International Classification, and deepening the topics of occupational exposure, current operating conditions, the technical and operational progress to reducing the exposure, the epidemiological evidence and exposure measurement data available. Finally, we illustrate the dispersion in the environment as a real risk for the general population.

Polychlorinated biphenyls in serum, liver and adipose tissue of subjects with hepatocellular carcinoma living in a highly polluted area.

Brescia (North Italy) is located in a highly industrialized area with diffuse environmental pollution by polychlorinated biphenyls (PCBs) and with a high incidence of hepatocellular carcinoma (HCC). We aimed to investigate the concentration of PCBs congeners in serum, liver and adipose tissue of patients with HCC living in this area. We enrolled prospectively 101 HCC incident cases. Lipid-adjusted PCBs concentration of single congeners and total PCBs concentration, computed as the sum of 24 PCBs congeners, were measured in the serum of all subjects and in the liver and abdominal fat of 59 HCC cases undergoing surgery. A high correlation was found between PCBs serum and liver (Spearman r=0.79), serum and fat (r=0.91), and liver and fat (r=0.75) concentrations. Serum PCBs concentration in HCC patients did not vary according to demographical, clinical or epidemiological variables, apart from age, as PCBs concentration increased linearly with the subject's age. This study confirms that serum lipid-adjusted PCBs concentration is a valid measure of PCBs body storage and is highly correlated with PCBs concentration detected in other biological samples.

Polychlorinated Biphenyls, Glycaemia and Diabetes in a Population Living in a Highly Polychlorinated Biphenyls-Polluted Area in Northern Italy: a Cross-sectional and Cohort Study.

UNLABELLED: CONFLICTS OF INTERESTS: the authors declare no potential conflict of interests. BACKGROUND: Polychlorinated biphenyls (PCBs) have been found to be associated with diabetes in some, but not all, studies performed so far. The aim of this study was to assess the association between PCB serum levels and glycaemia and diabetes in people living in Brescia, a highly industrialised PCB-polluted town in Northern Italy. DESIGN AND METHODS: 527 subjects were enrolled in a cross-sectional population-based study: they were interviewed face-to-face in 2003 and also provided a blood sample under fasting conditions. The concentration of 24 PCB congeners was determined using gas-chromatography (GC/MS). Subsequently, all subjects were included in a follow-up (cohort) study. According to the Local Health Authority health-care database, subjects were considered to be diabetic if they had diabetes at interview time (prevalent cases) or during a 7-year follow-up (incident cases). RESULTS: A total of 53 subjects (10.0%) were diabetics: 28 had diabetes at enrolment and other 25 developed the disease subsequently. Diabetes frequency increased according to the serum concentrations of total PCBs and single PCB congeners, but no association was found when estimates were adjusted for education, body mass index, age and gender by logistic regression analysis. Accordingly, glycaemia increased with PCB serum levels, but no association was observed when multiple regression analysis, including confounding factors, was performed. CONCLUSIONS: This study does not support the hypothesis that PCB environmental exposure is strictly associated with diabetes or glycaemia.

[Polychlorinated dibenzofurans and cancer]. / Policlorodibenzofurani e cancro.

The aim of the present report is to review the main scientific literature about polychlorinated dibenzofurans (PCDFs) and to focus the critical aspects of their identification and assessment of exposure. The 2,3,4,7,8- Pentachlorodibenzofuran (PeCDF) has been classified as carcinogenic to humans and included in Group 1 by IARC, as there is sufficient evidence of carcinogenicity in experimental animals and specific action mechanisms. Experimental studies demonstrated that PeCDF interacts through the binding with the aryl hydrocarbon receptor (AhR) as the 2,3,7,8-tetrachlorodibenzo-para dioxin (TCDD). The epidemiological studies on human exposure are limited to few cohort evaluations like the "Yusho" and "Yucheng" incidents, Swedish fishermen cohorts and workers employed in herbicide production. The PCDF as a group may be therefore classified at limited evidence of carcinogenicity. This paper concludes the cycle of review about other POPs, i.e. dioxins and PCBs.

Persistent organochlorine compounds in fetal and maternal tissues: evaluation of their potential influence on several indicators of fetal growth and health.

Some organochlorine compounds, such as polychlorinated biphenyls (PCBs), have a tendency to bioaccumulate in humans and predators at the top of the food chain. We have recently confirmed the transplacental transfer of these compounds and the present study has been designed on the same material with the aim of investigating their potential health effects on newborns from 70 pregnant women, resident in a Northern Italy industrial town. Organochlorine compounds [namely, p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and PCBs] have been analyzed both in cord and maternal serum, placenta, and maternal subcutaneous adipose tissue by GC-MSD. p,p'-DDT levels in the adipose tissue resulted significantly (p<0.05) related to birth length. Mothers of neonates born by preterm programmed caesarean delivery showed significantly (p<0.005 for both) higher serum p,p'-DDE serum concentrations and p,p'-DDT levels in the adipose tissue, as compared to mothers delivering at term.

[Classification as carcinogenic for 2,3,7,8-tetrachlorodibenzo-para-dioxin: an eventful journey]. / Classificazione della 2,3,7,8-tetraclorodibenzo-para-diossina come concerogena: un percorso accidentato.

Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8-TCDD) and some other dioxin congeners is long time discussed by epidemiological and experimental studies, often with conflicting findings. The inclusion of 2,3,7,8-TCDD in Group 1 by 1ARC in 1997 was based essentially on mechanistic evidence and experimental studies despite the limited evidence in humans. This procedure generated a lot of controversy. Some scientists agree with this classification and sometimes suggested increased cancer mortality risk with TCDD daily intake similar to those of the general population. Other authors re-analyzing data mainly from caselist previously investigated did not confirm the 2,3,7,8-TCDD carcinogenicity. In the review process of carcinogenic substances by IARC in 2010, the evidence for 2,3,7,8-TCDD carcinogenicity in humans upgraded from limited to sufficient, due to confirmed and integrated epidemiological evidences. It is also confirmed that these findings relate to all cancers combined, while for some "classic" cancers related to TCDD (as soft tissue sarcoma and non-Hodgkin lymphoma) the evidence remains limited. In this paper a literature review accompanied by comments is reported with the aim to provide information about the evaluation process and tools for its more critical and scrupulous interpretation.

[Environmental monitoring of volatile organic compounds and metallic elements in two analysis laboratories]. / Monitoraggio ambientale di composti organici volatili ed elementi metallici in due laboratori di analisi.

Environmental monitoring of volatile organic compounds (VOCs) in analytical chemistry laboratories is somewhat tricky because exposure levels are highly variable and the number of toxic compounds, often used in combination, may be very high. This study was designed to evaluate airborne levels of VOCs and metallic elements associated to inhalable dusts in two Italian labs. The airborne levels of VOCs and elements fell well below the occupational exposure limit values recorded in the Italian law (D.lgs. 81/2008, Allegato XXXVIII) and the TLV-TWA from the list of American Conference of Governmental Industrial Hygienists. The determination of measurable levels of toxic and potentially carcinogenic compounds in office rooms may be of interest for personnel not specifically engaged to handle chemicals.

Distribution of persistent organochlorine pollutants in maternal and foetal tissues: data from an Italian polluted urban area.

This study was designed to evaluate both levels and distributions of organochlorine pollutants in placenta and other maternal-foetal tissues, from women resident in an Italian highly industrialized urban area with demonstrated PCB pollution. To this end, 30 polychlorinated biphenyl congeners (PCBs), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB), were determined in placenta, both maternal and cord blood serum and adipose tissue of Caucasian pregnant women (n=70) undergoing to programmed caesarean delivery. Median placental concentrations of PCBs, p,p'-DDE and HCB (0.89 ng g(-1), 0.63 ng g(-1) and 0.19 ng g(-1) on wet tissue weight basis, respectively), were lower than previously published data. p,p'-DDT could be detected in most of adipose tissue samples, but very rarely in the other compartments. Distributions of investigated compounds in biological matrices showed significant relationships, confirming their transplacental transfer. It is worthy of note that HCB tended to be transferred more easily from maternal to foetal tissues. Maternal serum levels of these pollutants can allow a reliable estimation of organochlorine compound body burden, and can be useful markers of prenatal exposure, given their relationships with placental and umbilical cord serum levels.

Evaluation of different methods to determine total serum lipids for normalization of circulating organochlorine compounds.

OBJECTIVES: Serum levels of persistent organochlorine compounds may be predictive of their body burden, if adjusted by total serum lipids. Their value may be predicted by three different formulae, requiring only values of serum cholesterol and triglycerides. The study was aimed at: (i) evaluating the validity of these formulae; (ii) evaluating the influence of different estimates on serum levels of lipid adjusted persistent organochlorine compounds. METHODS: We determined the levels of cholesterol, triglycerides and phospholipids by enzymatic assays on serum samples from 121 subjects living in a polluted area of Northern Italy. On the same samples and on an additional set from 69 pregnant women of the same area, we determined also polychlorinated biphenyls, hexachlorobenzene and p,p'-dichlorodiphenyldichloroethylene. In women, analytes were determined also on adipose tissue samples. RESULTS: Formulae provided results comparable to those obtained as sum of cholesterol, triglycerides and phospholipids. In women, we found highly significant relationships among lipid adjusted pollutant levels in serum and adipose tissue, independently from the used formula. CONCLUSIONS: Formulae allow a valid adjustment of organochlorine compounds in serum. The algorithm proposed by Phillips et al. provides some slight advantage over the others, in terms of simplicity of use.

Polychlorinated biphenyls and thyroid hormone serum concentrations among people living in a highly polluted area: a cross-sectional population-based study.

BACKGROUND: Polychlorinated biphenyls (PCBs) may interact with several thyroid functions. Severe environmental pollution by PCBs has been observed in Brescia, Italy, due to the presence of a factory that produced these compounds until 1984. OBJECTIVES: We aimed to investigate the correlation between serum levels of total PCBs and PCB 153 and thyroid hormone serum levels in adults in a cross-sectional population-based study. METHODS: A total of 527 subjects were enrolled; they were face-to-face interviewed about their history of thyroid disease and provided a blood sample under fasting conditions. The serum levels of free and total triiodothyronine (FT3 and TT3), thyroxine (FT4 and TT4) and thyroid-stimulating hormone (TSH), anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TGA), and lipid-adjusted total PCBs and PCB 153 were determined. RESULTS: There was no statistically significant difference in total PCB and PCB 153 concentrations in subjects with and without thyroid disease. Inverse, weak, statistically significant correlations were found between total PCBs and FT3 (Spearman's r=-0.09) and between total PCBs and PCB 153 and TSH (Spearman's r=-0.16 and -0.12, respectively). However, multiple regression analysis with FT3 and TSH serum levels as dependent variables and total PCBs and PCB 153 serum levels as predictors, including age, gender and BMI, showed a positive, rather than negative, association of PCBs and PCB 153 with FT3 and no association with TSH. CONCLUSIONS: This study does not support the hypothesis that relatively high PCB environmental exposure can determine substantial alterations in thyroid function among adult people.

Exposure to polychlorinated biphenyls in residents near a chemical factory in Italy: the food chain as main source of contamination.

High levels of PCBs were recently found in soil, food and some farmers living close to a chemical factory which until the 1980s had produced polychlorinated biphenyls (PCBs) in Brescia, North Italy. We performed a survey on a random sample of subjects aged 20-79 years living in various areas of the town with different levels of soil pollution to investigate factors associated with increased levels of PCB in serum (24 congeners were tested). Total PCB values were closely related to age (Spearman r=0.68; p<0.0001). The 166 consumers of locally produced food had higher PCB levels than non-consumers (median=1143 versus 719; 95th centile=9301 versus 2635ng/g lipid) with the highest levels among consumers of food produced in the most contaminated area close to the factory (median=2551; 95th centile=33464ng/g lipid). A dose-effect relationship between consumption of food produced in this area and PCB blood levels was observed (Spearman r=0.52, p=0.0014). Consumers of only plant food produced in this area had higher levels of PCB than non-consumers (median=1100; 95th centile=10,800ng/g lipid). Three subjects who had worked at the factory in the past showed high PCB levels. Distribution of PCB congeners did not differ between consumers of locally produced food and non-consumers, apart from PCB 209 which was found at high levels in former factory workers and was more common among consumers of food produced in the polluted area. In conclusion, we found high serum PCB levels in humans living in a highly polluted area in an industrialized town in Italy, due mainly to consumption of food produced in polluted areas.

Assessment of reference values for polychlorinated biphenyl concentration in human blood.

A chemical factory which produced polychlorinated biphenyls (PCBs) operated in Brescia, North Italy, (about 200000 inhabitants) from the 1930s to the 1980s. High levels of PCBs were recently found in soil, food and people living in an area close to the factory. We performed a survey among the general population living in non-polluted areas of the town in order to define the reference values (RVs) of the non-exposed population. A random sample of subjects aged 20-79 years (50% males) was selected. Participants underwent PCB determination and were interviewed on their residential and occupational history and current diet. For RV determination, subjects who had resided in the polluted area or consumed any food produced in the area in their lifetime were excluded. Eight hundred and ninety-two subjects were contacted, 579 (65%) of whom agreed to participate; 311 of them were considered for RV determination (53% male, mean age=48.7 years). Total PCB serum levels, computed as the sum of the 24 congeners determined, were: mean=5.15ng/ml (SD=8.83), median=4.11ng/ml, range=0.4-34.12ng/ml, 95th centile=14.38ng/ml. Lipid-adjusted mean and median were 897 and 705ng/g lipid, respectively. PCB values showed positive correlations with age (Spearman's r=0.76) and with serum concentration of total cholesterol (r=0.40) and triglycerides (r=0.36). No association was found with gender, cigarette smoking, alcohol or diet. Seven PCB congeners, (PCB 180, 153, 138, 170, 194, 118, and 156), including those at higher chlorination, were present in more than 30% of the subjects and contributed 99% of the total PCB levels, with a modest role of dioxin-like congeners.

Exhaled breath condensate as a suitable matrix to assess lung dose and effects in workers exposed to cobalt and tungsten.

The aim of the present study was to investigate whether exhaled breath condensate (EBC), a fluid formed by cooling exhaled air, can be used as a suitable matrix to assess target tissue dose and effects of inhaled cobalt and tungsten, using EBC malondialdehyde (MDA) as a biomarker of pulmonary oxidative stress. Thirty-three workers exposed to Co and W in workshops producing either diamond tools or hard-metal mechanical parts participated in this study. Two EBC and urinary samples were collected: one before and one at the end of the work shift. Controls were selected among nonexposed workers. Co, W, and MDA in EBC were analyzed with analytical methods based on mass spectrometric reference techniques. In the EBC from controls, Co was detectable at ultratrace levels, whereas W was undetectable. In exposed workers, EBC Co ranged from a few to several hundred nanomoles per liter. Corresponding W levels ranged from undetectable to several tens of nanomoles per liter. A parallel trend was observed for much higher urinary levels. Both Co and W in biological media were higher at the end of the work shift in comparison with preexposure values. In EBC, MDA levels were increased depending on Co concentration and were enhanced by coexposure to W. Such a correlation between EBC MDA and both Co and W levels was not observed with urinary concentration of either element. These results suggest the potential usefulness of EBC to complete and integrate biomonitoring and health surveillance procedures among workers exposed to mixtures of transition elements and hard metals. Key words: cobalt, exhaled breath condensate, hard metals, lung, malondialdehyde, oxidative stress, tungsten.