Climate change, human migration and health nexus: what do we know about public health implications on a global scale?

OBJECTIVE: to address the nexus among climate change, migration, and health at global and Italian levels. DESIGN: narrative review. SETTING AND PARTICIPANTS: comprehensive, critical, and objective analysis of the current knowledge on the topic by searching online databases. MAIN OUTCOME MEASURES: evidence from the literature examining health issues associated with migration in the context of climate change. RESULTS: anthropogenic climate change has recently influenced the scale and patterns of human mobility, not only as a driver of migration, but also by interacting with and amplifying the effects of migration determinants, including health determinants. Despite research focusing on the distinct relationship between climate change and migration, as well as climate change and health, little attention has been paid to the nexus among climate change, migration, and health. Evidence available examining various health issues associated with migration in the context of climate change include changing patterns of infectious diseases and their risks, rising cases of malnutrition, trauma and injuries, changing patterns of noncommunicable diseases, impact on mental health. Inadequacy of access to health services due to the weakening and overstretching health systems also plays an important role. In a country like Italy, even if the immediate threats posed by climate change differ from one area to another, these threats are already exacerbating the country's existing infrastructure deficiencies, industrial pollution, and hydrogeological and seismic vulnerability. In addition, Italy has historically been a destination country of immigrant afflux through different migration routes. It is possible that the consequences of climate change in Sub-Saharan Africa will drive a growing number of people to cross the sea to reach Europe, specifically Italy. Conclusions: climate change, human migration, and health should be considered as an interconnected and complex issue. A shift to climate resilient health systems' is a useful precautionary measure as it aims to strengthen multiple aspects of national and sub-national health systems, regardless of the extent to which climate-related migration might occur.

Health needs and perception of health care quality among Asylum Seekers and Refugees in an Italian local health authority: A qualitative study.

Background: Migrants, Asylum Seekers and Refugees (ASRs) represent a vulnerable diversified population with increased risks of developing health problems, and in the hosting countries several barriers often hamper their access to the health services. Gathering information about ASRs' experiences and perceptions of host country health care systems may contribute to improve the quality of health care provided. The aim of this study was to explore the health needs in their bio-psycho-social meaning, and the quality of health care as perceived from the ASRs' perspective. Methods: The qualitative descriptive study was conducted as part of the Project "G-START - testing a governance model of receiving and taking care of the Asylum Seekers and Refugees." Through purposeful and snowball sampling, four Focus Groups conducted in English, Italian and French were carried out between July and August 2019, involving 50 ASRs hosted by four reception centers located on the territory pertaining to an Italian Local Health Authority covering a general population of 500.000 people. The analysis of data was categorical, and was performed using N-Vivo software. Results: The macro-categories emerged were the ASRs' bio-psycho-social health needs, including mental health, sexual and reproductive health, food and nutrition, knowledge of the health care system, need for inclusion; healthcare services access, including barriers before and after the access and the ability of the local health system to respond to existing and evolving demands; strengths of the healthcare and reception systems, and suggestions for improving them in the future. Discussion and conclusions: ASRs present vulnerabilities and specific health needs, and the health care system is not always able to guarantee access or to respond to these needs. Several obstacles have been highlighted, such as linguistic barriers and lack of cultural mediation, bureaucratic and administrative barriers, lack of knowledge of the Italian health care system. An effective reorganization of services driven by a more detailed output analysis of the target population needs, together with the use of cultural mediation, peer to peer education and support, and the training of health professionals are recommended to ensure a more accessible, equitable and effective health care system at local level.

Clusterin exerts a cytoprotective and antioxidant effect in human osteoarthritic cartilage.

Osteoarthritis (OA) is the most common joint disease characterized by destruction of articular cartilage. OA-induced cartilage degeneration causes inflammation, oxidative stress and the hypertrophic shift of quiescent chondrocytes. Clusterin (CLU) is a ubiquitous glycoprotein implicated in many cellular processes and its upregulation has been recently reported in OA cartilage. However, the specific role of CLU in OA cartilage injury has not been investigated yet. We analyzed CLU expression in human articular cartilage in vivo and in cartilage-derived chondrocytes in vitro. CLU knockdown in OA chondrocytes was also performed and its effect on proliferation, hypertrophic phenotype, apoptosis, inflammation and oxidative stress was investigated. CLU expression was upregulated in human OA cartilage and in cultured OA cartilage-derived chondrocytes compared with control group. CLU knockdown reduced cell proliferation and increased hypertrophic phenotype as well as apoptotic death. CLU-silenced OA chondrocytes showed higher MMP13 and COL10A1 as well as greater TNF-α, Nox4 and ROS levels. Our results indicate a possible cytoprotective role of CLU in OA chondrocytes promoting cell survival by its anti-apoptotic, anti-inflammatory and antioxidant properties and counteracting the hypertrophic phenotypic shift. Further studies are needed to deepen the role of CLU in order to identify a new potential therapeutic target for OA.

Ultrasound-guided Interfascial Plane Blocks for Non-anesthesiologists in Breast Cancer Surgery: Functional Outcomes and Benefits.

AIM: Acute post-operative pain following modified radical mastectomy (MRM) in patients with breast cancer is challenging for anesthesiologists. This study aimed to prospectively compare the quality outcome of interfascial plane blocks performed with ultrasound guidance, and evaluate the consequences of sharing tasks with the breast surgeon. PATIENTS AND METHODS: The study involved 255 patients scheduled for unilateral MRM, who were divided into two groups: Pecs group: General anesthesia plus ultrasound-guided modified pectoral nerves blocks type I and II, including serratus and parasternal infiltration according to surgical requirements; and Control group: general anesthesia only. Quality was evaluated based on perioperative opioid consumption, reported pain intensity, rescue analgesic requirement, side-effects and length of hospital stay. Moreover, a breast surgeon with expertise in ultrasound-guided breast biopsy was trained to perform the blocks. The patient benefits from regional anesthesia delivered by a non-anesthesiologist were assessed. RESULTS: Significant reductions were noted in all of the following: Intraoperative opioid consumption (p<0.001), Numerating Rating Scale pain scores taken 0 and 24 h after surgery (p<0.001), post-operative analgesic administration (p<0.001), nausea and vomiting at 0, 6, and 12-h intervals (p<0.05), and hospital stay (p<0.001) were observed in the Pecs group compared with the control group. Furthermore, data obtained from patients receiving the block from the surgeon showed comparable benefits with no complications. CONCLUSION: Interfascial plane blocks may be an important alternative protocol in MRM, enhancing patient safety and cost benefits. Improvements in cross-disciplinary expertise through flexibility in the training of professionals with other backgrounds may provide effective analgesia and favorable outcomes.

Access to health care, nutrition and dietary habits among school-age children living in socio-economic inequality contexts: results from the "ForGood: Sport is Well-Being" programme.

Social frailty is a warring phenomenon in Europe, negatively impacting children's health and nutrition. We present the results of a social programme facilitating access to physical activities for vulnerable children in Italy. 311 school-age children enrolled in the programme between 2015 and 2017 were assessed for health and lifestyle, anthropometric and nutritional status. Data were compared by origin (Italians vs. immigrants) and then immigrants were split into sub-groups: first- and second-generation. Poor socio-economic status exposed children to a lack of access to health services, and drove imbalanced eating behaviour. 20.8% of children were not registered with the National Health Services (immigrants p < .0001); 22% were not fully vaccinated (no differences between groups). A double burden of malnutrition coexisted: overweight was higher for Italians, underweight and poor linear growth for immigrants. Nearly 40% of children had a poor Mediterranean Diet adequacy (KIDMED index). Our findings show that when social programmes, besides their main scope of inclusion and integration, holistically approach their beneficiaries, they can play an important role in monitoring lifestyle conditions and facilitating access to primary health care.

Heterogeneous risk profiles among B3 breast lesions of uncertain malignant potential.

BACKGROUND: Most cases of breast lesions of uncertain malignant potential (B3) undergo surgical intervention. We aimed to analyze the outcome of B3 lesion subtypes in a large series of screen-detected cases. METHODS: We screened 2,986 core needle biopsies to classify B3 lesions. Positive predictive values (PPVs) for malignancy were calculated for a comprehensive risk characterization according to clinicopathologic and morphologic variables. RESULTS: B3 lesions comprised 35% atypical ductal hyperplasia (PPV = 20%), 16.7% flat epithelial atypia (PPV = 12%), 22.7% lobular neoplasia (PPV = 16.2%), 9% papillary lesion (PPV = 18.5%), 8.6% phyllodes tumor (PPV = 3.8%), and 8% radial scars (PPV = 4.1%) based on histopathologic diagnosis. Upgrade rates were 15.9% for calcifications, 13.7% for mass lesions, and 16.7% for architectural deformities, with 8.3% of malignant lesions classified as ductal carcinoma in situ and 6.7% as invasive cancers (PPV = 15%). CONCLUSION: B3 lesions entail a heterogeneous risk of malignancy, and careful radiologic-pathologic correlation is required for optimal treatment.

Outpatient surgery is the solution at hand for reducing costs and hospital stays for pediatric surgery too: a hospital trial.

BACKGROUND: Outpatient management has proven to be the most useful method of treatment for various minimally complex surgical specialties compared to day-hospital management or ordinary inpatient processes, a fact confirmed by numerous technical documents and works in the literature. METHODS: We analyzed 27,713 surgical interventions carried out in our hospital between 2005 and 2017. This analysis included all interventions for which the indication of the level of care has moved, over the years, to an outpatient setting. We evaluated the direct costs of these services, comparing them by year and by treatment setting. RESULTS: From the analysis of costs in general, for the same number of services, a reduction of 56.6% can be seen in the comparison between 2005 and 2017. In addition, the analysis of the length of stay shows an average reduction in the number of days of hospitalization from 2.9 to 1.2 between 2005 and 2017. On the basis of a large quantity of data, our study confirms that outpatient surgery can have a significant impact in reducing costs and days of hospitalization, even in a pediatric setting, demonstrating that it is the best choice in terms of saving resources and, above all, clinical and organizational appropriateness. CONCLUSIONS: Outpatient surgery is in fact a valuable solution that provides an advantage for both the patient and his/her family, especially in the pediatric field, for the hospital and more generally for the health system as a whole.

Evaluation of the Usefulness of FDG-PET/CT for Nodal Staging of Breast Cancer.

BACKGROUND/AIM: Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has recently been used to investigate lymph node (LN) metastases and several predictive features in patients with breast cancer (BC). The aim of this study was to assess the value of this non-invasive imaging procedure for axillary staging. PATIENTS AND METHODS: Fifty patients with early primary unilateral, locally advanced, or recurrent invasive operable BC were enrolled. All patients underwent preoperative 18F-FDG PET/CT, and the results were compared with the histopathology of dissected axillary LNs and their biological and immunohistochemical characteristics. The diagnostic performance of 18F-FDG PET/CT in detecting LN metastases from primary or recurrent BC was analyzed. The mean values of the initial PET/CT parameters, including the primary tumour (SUV T) and ipsilateral axillary LNs (SUV LN), were compared with the clinicopathological features of patients to determine their usefulness for predicting clinical interactions. RESULTS: The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT for axillary LN staging were 87%, 90%, 88%, 93%, and 82%, respectively. Bivariate analyses showed strong interactions of nuclear grade (p=0.05), progesterone receptor expression (p=0.001), Ki-67 index (0.027), and local relapse with the SUV T. A high SUV LN value was significantly correlated with a higher nuclear grade score (p=0.05), oestrogen receptor negativity (p=0.001), progesterone receptor negativity (p=0.014), a high Ki-67 index (>20%; p=0.048), LN metastasis (p<0.001), a basal tumour (p=0.04), and locoregional recurrence (p<0.001). CONCLUSION: PET/CT is a reproducible, non-invasive imaging modality that is useful for evaluating a primary BC mass and its relationship with metastatic axillary LNs, thereby predicting tumour behaviour and guiding clinical practice.

Additional Nodal Disease Prediction in Breast Cancer with Sentinel Lymph Node Metastasis Based on Clinicopathological Features.

AIM: The standard-of-care in breast cancer (BC) with positive sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND); however, almost half of such cases have no further tumor burden. This study aimed to assess the clinicopathological factors that predict non-SLN metastasis to define subgroups of SLN-positive patients in whom the axilla may be staged by SLN biopsy alone, while avoiding unnecessary overtreatment. PATIENTS AND METHODS: The records of 191 patients with histologically-proven primary BC who underwent a positive (SLN) biopsy between 2005 and 2017 were reviewed. Patients with at least one tumor-involved SLN who underwent completion ALND were enrolled. Demographic and clinicopathological characteristics, including age, primary tumor size and histological grade, lymphovascular invasion, ratio of positive SLNs to the harvested SLNs, SLN metastasis size, and molecular subtype classification according to immunohistochemical biomarker status [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], were evaluated. Data were collected retrospectively and analyzed using the Mann-Whitney and Chi-square tests (statistical significance: p<0.05). RESULTS: The incidence of non-SLN metastasis associated with positive SLN was 48.6% (93/191). The risk of additional nodal spread correlated with high sentinel nodal ratio >0.67 [odds ratio (OR)=2.55, p=0.032], luminal BC subtype (OR=2.67, p=0.06), HER2 overexpression (OR=0.4, p=0.016), and ER+PR-HER2- profile (OR=2.95, p=0.027). There was a tendency (statistically insignificant; p>0.05) toward higher incidence of non SLN metastasis with increasing age and histological grade, which could be attributed to the small sample size. CONCLUSION: According to this study, sentinel nodal ratio and BC subtypes as per ER, PR, and HER2 status significantly predicted the likelihood of additional lymphatic involvement. Validation of these parameters in prospective studies is indicated, and may help individualize treatment modalities.

New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes.

Despite advances in treatment, up to 30% of patients with early breast cancer (BC) experience distant disease relapse. However, a comprehensive understanding of tumor spread and site-specific recurrence patterns remains lacking. This retrospective case-control study included 103 consecutive patients with metastatic BC admitted to our institution (2000-2013). Cases were matched according to age, tumor biology, and clinicopathological features to 221 patients with non-metastatic BC (control group). The median follow-up period among the 324 eligible patients was 7.3 years. While relatively low values for sensitivity (71%) and specificity (56%) were found for axillary lymph node (ALN) involvement as an indicator of risk and pattern of distant relapse, nodal status remained the most powerful predictor of metastases (OR: 3.294; CL: 1.9-5.5). Rates of dissemination and metastatic efficiency differed according to molecular subtype. HER2-positive subtypes showed a stronger association with systemic spread (OR: 2.127; CL: 1.2-3.8) than other subgroups. Classification as Luminal or Non-Luminal showed an increased risk of lung and distant nodal recurrence, and a decreased risk in bone metastases in the Non-Luminal group (OR: 2.9, 3.345, and 0.2, respectively). Tumors with HER2 overexpression had a significantly high risk for distant relapse (OR: 2.127) compared with HER2-negative tumors and also showed higher central nervous system (CNS) and lung metastatic potential (OR: 5.6 and 2.65, respectively) and low risk of bone disease progression (OR: 0.294). Furthermore, we found significant associations between biological profiles and sites of recurrence. A new process of clinical/diagnostic staging, including molecular subtypes, could better predict the likelihood of distant relapses and their anatomical location. Recognition and appreciation of clinically distinct molecular subtypes may assist in evaluation of the probability of distant relapses and their sites. Our analysis provides new insights into management of metastatic disease behavior, to lead to an optimal disease-tailored approach and appropriate follow-up.

Frequent Use of Emergency Departments by the Elderly Population When Continuing Care Is Not Well Established.

INTRODUCTION: The elderly, who suffer from multiple chronic diseases, represent a substantial proportion of Emergency Department (ED) frequent users, thus contributing to ED overcrowding, although they could benefit from other health care facilities, if those were available. The aim of this study was to evaluate and characterize hospital visits of older patients (age 65 or greater) to the ED of a university teaching hospital in Rome from the 1st of January to the 31st of December 2014, in order to identify clinical and social characteristics potentially associated with "elderly frequent users". MATERIAL AND METHODS: A retrospective study was performed during the calendar year 2014 (1st January 2014 - 31st December 2014) analyzing all ED admissions to the University Hospital of Rome Tor Vergata. Variables collected included age, triage code, arrival data, discharge diagnosis, and visit outcome. We performed a risk analysis using univariate binary logistic regression models. RESULTS: A total number of 38,016 patients accessed the ED, generating 46,820 accesses during the study period, with an average of 1.23 accesses for patient. The elderly population represented a quarter of the total ED population and had an increased risk of frequent use (OR 1.5: CI 1.4-1.7) and hospitalization (OR 3.8: CI 3.7-4). Moreover, they showed a greater diagnostic complexity, as demonstrated by the higher incidence of yellow and red priority codes compared to other ED populations (OR 3.1: CI 2.9-3.2). DISCUSSION: Older patients presented clinical and social characteristics related to the definition of "elderly frail frequent users". The fact that a larger number of hospitalizations occurred in such patients is indirect evidence of frailty in this specific population, suggesting that hospital admissions may be an inappropriate response to frailty, especially when continued care is not established. CONCLUSION: Enhancement of continuity of care, establishment of a tracking system for those who are at greater risk of visiting the ED and evaluating fragile individuals should be the highest priority in addressing ED frequent usage by the elderly.

[eHealth: necessity and challenges]. / eHealth: tra necessità e criticità

In times of economic crisis and a national healthcare system that absorbs more than 7% of the gross domestic product, there is a need to "rethink" healthcare practice. EHealth is part of this process of improving accessibility to services, use of available resources and coordination of program choices, and is an indispensable tool for implementing this cultural and management revolution. How realistic is it, today, to think of implementing a digitalized healthcare practice network? To settle this question is essential for today's national healthcare system.

[Communicating the benefits and risks of vaccination: a focus on the PFCC (Patient and Family Centered Care) approach]. / I segreti della comunicazione in ambito vaccinale.

In recent years an important reduction in the access to vaccination was noticed in Italy. Health care workers involved in health promotion must necessarily find new strategies to overcome the mistrust of the population. The application of some instruments of counselling in the vaccination field can improve the therapeutic alliance, making users to take the best decisions for their own wellness. The approach called Patient- and Family-Centered Care includes the relational processes within the skills of the health care worker.

New Insights into the CD133 (Prominin-1) Expression in Mouse and Human Colon Cancer Cells.

Following its discovery as a cancer stem cell marker, CD133 has been widely studied for its role in colorectal tumorigenesis. Indeed, colon cancer remains one of the major causes of cancer-related disease and death worldwide, and there is a strong need for an improvement of current diagnostic, prognostic, and therapeutic strategies. Thus, efforts have been devoted to try to understand whether CD133 might play a role in human colorectal tumorigenesis and might contribute to a better management of colon cancer patients. This chapter reviews the current knowledge on CD133 expression in normal and cancer colon tissues, both in humans and mice, discussing apparently conflicting data reported in the two species. Moreover, a great attention is devoted to the available information regarding the functional role of CD133 in colon cancer cells. Finally, the proposed clinical applications of CD133, as a prognostic and/or predictive marker as well as a target for novel antineoplastic strategies in colorectal cancer, are discussed. Overall, the available data support a potential important role of CD133 as cancer stem cell marker in colon cancer cells and warrant future studies to verify its potential use in the routine clinical management of colon cancer patients.

Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients.

BACKGROUND: Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers. METHODS: Expression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. RESULTS: Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0-80). A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002) and overall (p = 0.008) survival.Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002) and death (RR = 2.3; p = 0.003). CONCLUSIONS: Loss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.

Increased expression of CD133 is a strong predictor of poor outcome in stage I colorectal cancer patients.

OBJECTIVE: Stage I colorectal carcinomas display a highly variable behavior which is not accurately predicted by the available prognostic markers. CD133 is considered a useful marker to identify the so-called cancer stem cells in colorectal cancers (CRCs) and its expression has been shown to have prognostic significance in CRC patients. This study aimed to verify whether immunohistochemical evaluation of CD133 might correlate with the progression risk of stage I CRC patients. MATERIAL AND METHODS: Expression levels of the CD133 molecule were analyzed and compared in two series of stage I surgically resected CRC patients showing disease progression and death for the disease and patients with no evidence of disease progression after at least 6 years after surgery. RESULTS: A positive staining for CD133 was detected in 52% of the cases with poor prognosis and only in 9% of the group with good prognosis, and this difference was highly significant (p < 0.001). A significant correlation was detected between CD133 expression and histological parameters, such as tumor budding, vascular invasion, and presence of lymph node micrometastases but not tumor grading, gender, and age. Disease-free survival and cancer-specific survival of CD133 negative tumors were significantly longer compared to positive cases. In multivariate analyses, CD133 staining confirmed to be a predictor of shorter survival independent from vascular invasion but not from lymph nodes micrometastases. CONCLUSIONS: These findings demonstrate that CD133 immunostaining is a useful predictor of high risk progression in stage I CRC patients and might help to identify patients eligible for adjuvant chemotherapy.

Rhodium and iridium salts inhibit proliferation and induce DNA damage in rat fibroblasts in vitro.

Environmental concentration of the platinum group elements is increased in the last years due to their use in automobile catalytic converters. Limited data are available on the effects of such elements at a cellular level and on their toxicity, especially for rhodium and iridium which have been more recently introduced in use. The toxic effects of rhodium and iridium salts were analyzed on a normal diploid rat fibroblast cell line in vitro. Both salts halted cell growth in a dose- and time-dependent fashion by inhibiting cell cycle progression, inducing apoptosis and modulating the expression of cell cycle regulatory proteins. In fact, they both caused an accumulation of cells in the G2/M phase of the cell cycle and affected the expression levels of pRb, cyclins D1 and E, p21(Waf1) and p27(Kip1). DNA strand breaks, as assessed by comet test, and an increase in the intracellular levels of reactive oxygen species also occurred in exposed cell cultures. These findings suggest a potential toxicity of both iridium and rhodium salts and emphasize the need for further studies to understand their effects at a cellular level to enable a better assessment of their toxic effects and to identify ways for their modulation and/or prevention.

Differential CD133 expression pattern during mouse colon tumorigenesis.

BACKGROUND/AIM: The cancer stem cell model suggests that only a rare subpopulation, known as cancer stem cells (CSC) are responsible for tumor initiation. CSC from several human carcinomas are characterized by specific cell surface markers, such as CD133. The CD133 role in colon tumorigenesis remains controversial. MATERIALS AND METHODS: CD133 was evaluated by immunohistochemistry in a mouse model of colitis-related colon tumorigenesis induced by a combined treatment with azoxymethane (AOM) and dextran sodium sulphate (DSS). RESULTS: In normal tissue rare scattered positive cells were detectable at the bottom of the crypts. The percentage of positive cells significantly increased in dysplastic lesions and appeared to progressively decrease in the passage from dysplasia to adenoma and then to cancer, although always remaining greater in number than in the normal tissue. CONCLUSION: An increased CD133 expression occurs at early stages of colon tumorigenesis in the mouse. CD133-expressing cells might play an important role from the earlier phase and throughout the entire process of colon cancer development.