A long-term nationwide study on chronic kidney disease-related mortality in Italy: trends and associated comorbidity.

BACKGROUND: Chronic kidney diseases (CKDs) represent a major public health concern worldwide with increasing incidence and prevalence. However, the epidemiological dimension of CKD in Italy is still under evaluation. By analyzing all the conditions reported on death certificates (multiple causes of death), we aimed to investigate the real burden of CKD mortality in Italy over 15 years and identify the main conditions contributing to death in association with CKD. METHODS: Death certificates of all deaths occurring in Italy from 2003 to 2017 were analyzed. Certificates reporting CKD were identified as CKD-related deaths. CKD-related mortality was investigated through age-standardized mortality rates, by sex and age. Conditions associated with CKD were identified through an indicator (age-standardized proportion ratio) measuring the excess proportion (value > 1) of having such conditions mentioned in the death certificate with and without CKD. RESULTS: From 2003 to 2017, multiple-cause-based CKD mortality rates increased by 60% in males and by 54% in females. The overall increase was mostly attributable to people aged 80 years or more. Several conditions were associated with CKD, the most relevant being diabetes (age-standardized proportion ratio = 2.2), obesity (2.1), systemic connective tissue disorders (2.3), anemia (2.7), and genitourinary system diseases (2.6). CONCLUSIONS: Multiple-cause-of-death data revealed a significant increase in CKD-related mortality in recent years, providing a measure of the burden of CKD on overall mortality in Italy. Moreover, multiple cause analysis allowed to identify the main conditions contributing to death in association with CKD, which should be aggressively targeted by clinicians to prevent CKD adverse outcomes.

Gut Microbiota and Autoimmune Diseases: A Charming Real World Together with Probiotics.

BACKGROUND: The role of gut microbiota in human disease is fascinating for hundreds of researchers worldwide. Many works have highlighted that gut microbiota modulates the immune system and that its disruption can trigger autoimmune and inflammatory immune-mediated diseases. Probiotics are able to positively modify microbiota composition. OBJECTIVE: The aim of this review is to report the most important findings regarding the effects of probiotics administration in the most common autoimmune disease and inflammatory immune-mediated diseases. METHODS: Literature research was performed in PubMed, Google Scholar, and Medline, as well as in specific journal websites using the keywords: "autoimmunity", "microbiota", and "probiotics". The article selection has been made independently by three authors, and controversies have been solved by a fourth researcher. Only English-language articles were included and preference was given to clinical trials, meta-analysis, and case series. After the review process, 68 articles have been considered. RESULTS: Relying on this evidence, many studies have investigated the potential of probiotics in restoring gut eubiosis, thus affecting pathogenesis, clinical manifestations, and course of these pathologies. Even in the light of few and sometimes contradictory studies, physicians should start to consider these preliminary findings when approaching patients suffering from autoimmune disease. After an accurate case-by-case evaluation of potential candidates, probiotics might be introduced besides the standard therapeutic plan as supportive measures.

Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates.

Background: In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death. Methods: Death certificates of persons who died and tested positive for SARS-CoV-2, provided by the National Surveillance system, were coded according to ICD rev10. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death. Results: The percentage of COVID-19 deaths varied over time. It decreased in the downward phase of the epidemic curve (76.6 vs. 88.7%). In February-April 2020, hypertensive heart disease was mentioned as a comorbidity in 18.5% of death certificates, followed by diabetes (15.9% of cases), ischemic heart disease (13.1%), and neoplasms (12.1%). In May-September, the most frequent comorbidity was neoplasms (17.3% of cases), followed by hypertensive heart disease (14.9%), diabetes (14.8%), and dementia/Alzheimer's disease (11.9%). The most mentioned complications in both periods were pneumonia and respiratory failure with a frequency far higher than any other condition (78.4% in February-April 2020 and 63.7% in May-September 2020). Discussion: The age of patients dying from COVID-19 and their disease burden increased in the May-September 2020 period. A more serious disease burden was observed in this period, with a significantly higher frequency of chronic pathologies. Our study suggests better control of the virus' lethality in the second phase of the epidemic, when the health system was less burdened. Moreover, COVID-19 care protocols had been created in hospitals, and knowledge about the diagnosis and treatment of COVID-19 had improved, potentially leading to more accurate diagnosis and better treatment. All these factors may have improved survival in patients with COVID-19 and led to a shift in mortality to older, more vulnerable, and complex patients.

The Role of COVID-19 in the Death of SARS-CoV-2-Positive Patients: A Study Based on Death Certificates.

Background: Death certificates are considered the most reliable source of information to compare cause-specific mortality across countries. The aim of the present study was to examine death certificates of persons who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to (a) quantify the number of deaths directly caused by coronavirus 2019 (COVID-19); (b) estimate the most common complications leading to death; and (c) identify the most common comorbidities. Methods: Death certificates of persons who tested positive for SARS-CoV-2 provided to the National Surveillance system were coded according to the 10th edition of the International Classification of Diseases. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death. Complications were defined as those conditions reported as originating from COVID-19, and comorbidities were conditions independent of COVID-19. Results: A total of 5311 death certificates of persons dying in March through May 2020 were analysed (16.7% of total deaths). COVID-19 was the underlying cause of death in 88% of cases. Pneumonia and respiratory failure were the most common complications, being identified in 78% and 54% of certificates, respectively. Other complications, including shock, respiratory distress and pulmonary oedema, and heart complications demonstrated a low prevalence, but they were more commonly observed in the 30-59 years age group. Comorbidities were reported in 72% of certificates, with little variation by age and gender. The most common comorbidities were hypertensive heart disease, diabetes, ischaemic heart disease, and neoplasms. Neoplasms and obesity were the main comorbidities among younger people. Discussion: In most persons dying after testing positive for SARS-CoV-2, COVID-19 was the cause directly leading to death. In a large proportion of death certificates, no comorbidities were reported, suggesting that this condition can be fatal in healthy persons. Respiratory complications were common, but non-respiratory complications were also observed.

Indications for Non-Invasive Ventilation in Respiratory Failure.

BACKGROUND: Non-invasive ventilation (NIV) is increasingly being used to treat episodes of acute respiratory failure not only in critical care and respiratory wards, but also in emergency departments. AIM: Aim of this review is to summarize the current indications for the management of NIV for respiratory failure. METHODS: Current literature about the topic was reviewed and critically reported to describe the rationale and physiologic advantages of NIV in various situations of respiratory failure. RESULTS: Early NIV use is commonly associated with the significant decrease in endotracheal intubation rate, the incidence of infective complications (especially ventilatory associated pneumonia), Intensive Care Units and the length of hospital stay and, in selected conditions, also in mortality rates. Severe acute exacerbation of chronic obstructive pulmonary disease (pH<7.35 and relative hypercarbia) and acute cardiogenic pulmonary oedema are the most common NIV indications; in these conditions NIV advantages are clearly documented. Not so evident are the NIV benefits in hypoxaemic respiratory failure occurring without prior chronic respiratory disease (De novo respiratory failure). One recent randomized control trial reported in hypoxaemic respiratory failure a survival benefit of high-flow nasal cannulae over standard oxygen therapy and bilevel NIV. Evidence suggests the advantages of NIV also in respiratory failure in immunocompromised patients or chest trauma patients. Use during a pandemic event has been assessed in several observational studies but remains controversial; there also is not sufficient evidence to support the use of NIV treatment in acute asthma exacerbation. CONCLUSION: NIV eliminates morbidity related to the endotracheal tube (loss of airway defense mechanism with increased risk of pneumonia) and in selected conditions (COPD exacerbation, acute cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates and hypoxia) is clearly associated with a better outcome in comparison to conventional invasive ventilation. However, NIV is associated with complications, especially minor complications related to interface. Major complications like aspiration pneumonia, barotrauma and hypotension are infrequent.

Geographic Inequalities in Breast Cancer in Italy: Trend Analysis of Mortality and Risk Factors.

We calculated time trends of standardised mortality rates and risk factors for breast cancer (BC) from 1990 to 2016 for all women resident in Italy. The age-standardised mortality rate in Italy decreased from 4.2 in 1990 to 3.2 (×100,000) in 2016. While participation in organised screening programmes and age-standardised fertility rates decreased in Italy, screening invitation coverage and mammography uptake, the prevalence of women who breastfed and mean age at birth increased. Although southern regions had favourable prevalence of protective risk factors in the 1990s, fertility rates decreased in southern regions and increased in northern regions, which in 2016 had a higher rate (1.28 vs. 1.32 child per woman) and a smaller increase in women who breastfed (+4% vs. +30%). In 2000, mammography screening uptake was lower in southern than in northern and central regions (28% vs. 52%). However, the increase in mammography uptake was higher in southern (203%) than in northern and central Italy (80%), reducing the gap. Participation in mammographic screening programmes decreased in southern Italy (-10%) but increased in the North (6.6%). Geographic differences in mortality and risk factor prevalence is diminishing, with the South losing all of its historical advantage in breast cancer mortality.

[Impact of the implementation of ICD-10 2016 version and Iris software on mortality statistics in Italy]. / Impatto dell'implementazione della versione 2016 dell'ICD-10 e del software Iris sulle statistiche di mortalità in Italia.

OBJECTIVES: to assess the impact of coding causes of death with the ICD-10 2016 version and the software Iris on Italian official statistics on mortality. DESIGN: coding of a sample of death certificates with two different coding systems (bridge coding). SETTING AND PARTICIPANTS: a sample of 63,525 deaths occurred throughout 2015 among people aged over one year, already coded using the ICD-10 2009 version and the Mortality Medical Data System (MMDS) software, was re-coded through the ICD-10 2016 version and the Iris software. MAIN OUTCOME MEASURES: the transition matrix between the two coding systems was realized and the agreement percentages between the two coding systems, the comparability ratios, and the relative 95% confidence intervals were calculated. Comparability ratios have been calculated for both the underlying cause of death and the multiple causes. RESULTS: overall, 79% of deaths showed exactly the same underlying cause of death (ICD-10 code, 4 digits) in the two coding systems. On the three-digit level, the agreement was 89%; on ICD-10 chapter level, the agreement was 95%. At the chapter level, the most important changes were observed for: • certain infectious and parasitic diseases (-18% in ICD-10 2016/Iris); • diseases of the genitourinary system (-17%); • diseases of the respiratory system (+7%); • diseases of the nervous system and sense organs (+5%); • external causes of morbidity and mortality (+5%). Analyzing the multiple causes, the most important changes were observed for: • certain infectious and parasitic diseases (-19% in ICD-10 2016/Iris); • external causes of morbidity and mortality (+28%); • symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified (+7%). CONCLUSION: the results are very useful to explain any change in the Italian statistics on mortality comparing 2015 with the following years.

Identity and ranking of colonic mesenchymal stromal cells.

Although ongoing clinical trials utilize systemic administration of bone-marrow mesenchymal stromal cells (BM-MSCs) in Crohn's disease (CD), nothing is known about the presence and the function of mesenchymal stromal cells (MSCs) in the normal human bowel. MSCs are bone marrow (BM) multipotent cells supporting hematopoiesis with the potential to differentiate into multiple skeletal phenotypes. A recently identified new marker, CD146, allowing to prospectively isolate MSCs from BM, renders also possible their identification in different tissues. In order to elucidate the presence and functional role of MSCs in human bowel we analyzed normal adult colon sections and isolated MSCs from them. In colon (C) sections, resident MSCs form a net enveloping crypts in lamina propria, coinciding with structural myofibroblasts or interstitial stromal cells. Nine sub-clonal CD146(+) MSC lines were derived and characterized from colon biopsies, in addition to MSC lines from five other human tissues. In spite of a phenotype qualitative identity between the BM- and C-MSC populations, they were discriminated and categorized. Similarities between C-MSC and BM-MSCs are represented by: Osteogenic differentiation, hematopoietic supporting activity, immune-modulation, and surface-antigen qualitative expression. The differences between these populations are: C-MSCs mean intensity expression is lower for CD13, CD29, and CD49c surface-antigens, proliferative rate faster, life-span shorter, chondrogenic differentiation rare, and adipogenic differentiation completely blocked. Briefly, BM-MSCs, deserve the rank of progenitors, whereas C-MSCs belong to the restricted precursor hierarchy. The presence and functional role of MSCs in human colon provide a rationale for BM-MSC replacement therapy in CD, where resident bowel MSCs might be exhausted or diverted from their physiological functions.