Socioeconomic factors and the probability of death by Covid-19 in Brazil.

BACKGROUND: To design better measures to contain the Covid-19 epidemics, it is relevant to know whether socioeconomic factors are associated with a higher risk of death by Covid-19. This work estimates the effects of individual socioeconomic characteristics on the risk of death by Covid-19. METHODS: Logistic models were estimated to assess the effect of socioeconomic characteristics (income, race/ethnicity, schooling, occupation and economic activity) on the risk of death from Covid-19. For this purpose, Covid-19 individual death records in Rio de Janeiro state, Brazil were combined with the Annual Register of Social Information, which contains socioeconomic information about formal workers. FINDINGS: Workers employed in establishments in the health and public safety sectors present a risk of dying 2.46 and 2.25 times higher than those employed in other activities. Non-white people, men, and those who work in the Metropolitan Region are also more likely to die from Covid-19. People with higher education are 44% less likely to die from the disease. CONCLUSIONS: Some population groups are more vulnerable to the Covid-19 pandemic and individual socioeconomic conditions play a relevant role in the probability of death by the disease. That should be considered in the design of prevention policies to be adopted.

Epidemiology and clinics of mushroom poisoning in Northern Italy: A 21-year retrospective analysis.

BACKGROUND: Limited information exists about epidemiology and management of mushroom poisoning. We analyzed and described epidemiology, clinical presentation, and clinical course of mushroom-poisoned patients admitted to emergency departments (EDs) of the Province of Parma, Italy. METHODS: Data from the database of mycological service were matched with clinical information retrieved from hospitals' database, from January 1, 1996 to December 31, 2016. RESULTS: Mycologist consultation was obtained in 379/443 identified mushroom poisonings. A remarkable seasonality was found, with significant peak in autumn. Thanks to the collaboration, the implicated species could be identified in 397 cases (89.6%); 108 cases (24.4%) were due to edible mushrooms, Boletus edulis being the most represented (63 cases). Overall, 408 (92%) cases presented with gastrointestinal toxicity. Twenty cases of amatoxin poisoning were recorded (11 Amanita phalloides and 9 Lepiota brunneoincarnata). One liver transplantation was needed. We observed 13 cases of cholinergic toxicity and 2 cases of hallucinogenic toxicity. Finally, 46 cases were due to "mixed" toxicities, and a total of 69 needed hospitalization. CONCLUSIONS: Early identification and management of potentially life-threatening cases is challenging in the ED, so that a mycologist service on call is highly advisable, especially during periods characterized by the highest incidence of poisoning.

Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy.

Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for FcγR polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab.

On the use of in vivo measured flow rates as boundary conditions for image-based hemodynamic models of the human aorta: implications for indicators of abnormal flow.

The purpose of this study is to investigate how the imposition of personalized, non-invasively measured blood flow rates as boundary conditions (BCs) influences image-based computational hemodynamic studies in the human aorta. We extracted from 4D phase-contrast MRI acquisitions of a healthy human (1) the geometry of the thoracic aorta with supra-aortic arteries and (2) flow rate waveforms at all boundaries. Flow simulations were carried out, and the implications that the imposition of different BC schemes based on the measured flow rates have on wall shear stress (WSS)-based indicators of abnormal flow were analyzed. Our results show that both the flow rate repartition among the multiple outlets of the aorta and the distribution and magnitude of the WSS-based indicators are strongly influenced by the adopted BC strategy. Keeping as reference hemodynamic model the one where the applied BC scheme allowed to obtain a satisfactory agreement between the computed and the measured flow rate waveforms, differences in WSS-based indicators up to 49% were observed when the other BC strategies were applied. In conclusion, we demonstrate that in subject-specific computational hemodynamics models of the human aorta the imposition of BC settings based on non-invasively measured flow rate waveforms influences indicators of abnormal flow to a large extent. Hence, a BCs set-up assuring realistic, subject-specific instantaneous flow rate distribution must be applied when BCs such as flow rates are prescribed.

Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies.

Left-ventricular hypertrophy (LVH) is a cardinal manifestation of hypertensive organ damage associated with an increased cardiovascular (CV) risk. We reviewed recent literature on the prevalence of LVH, as assessed by echocardiography, in order to offer an updated information on the magnitude of subclinical alterations in LV structure in contemporary human hypertension. A MEDLINE search using key words 'left ventricular hypertrophy', 'hypertension', 'echocardiography' and 'cardiac organ damage' was performed in order to identify relevant papers. Full articles published in English language in the last decade, (1 January 2000-1 December 2010), reporting studies in adult or elderly individuals, were considered. A total of 30 studies, including 37,700 untreated and treated patients (80.3% Caucasian, 52.4% men, 9.6% diabetics, 2.6% with CV disease) were considered. LVH was defined by 23 criteria; its prevalence ranged from 36% (conservative criteria) to 41% (less conservative criteria) in the pooled population. LVH prevalence was not different between women and men (range 37.9-46.2 versus 36.0-43.5%, respectively). Eccentric LVH was more frequent than concentric hypertrophy (range 20.3-23.0 versus 14.8-15.8, respectively, P<0.05); concentric phenotype was found in a consistent fraction (20%) of both genders. Despite the improved management of hypertension in the last two decades, LVH remains a highly frequent biomarker of cardiac damage in the hypertensive population. Our analysis calls for a more aggressive treatment of hypertension and related CV risk factors leading to LVH.

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma.

BACKGROUND: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. METHODS: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. RESULTS: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. CONCLUSION: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process.

Amazonia through time: Andean uplift, climate change, landscape evolution, and biodiversity.

The Amazonian rainforest is arguably the most species-rich terrestrial ecosystem in the world, yet the timing of the origin and evolutionary causes of this diversity are a matter of debate. We review the geologic and phylogenetic evidence from Amazonia and compare it with uplift records from the Andes. This uplift and its effect on regional climate fundamentally changed the Amazonian landscape by reconfiguring drainage patterns and creating a vast influx of sediments into the basin. On this "Andean" substrate, a region-wide edaphic mosaic developed that became extremely rich in species, particularly in Western Amazonia. We show that Andean uplift was crucial for the evolution of Amazonian landscapes and ecosystems, and that current biodiversity patterns are rooted deep in the pre-Quaternary.

Echocardiography in clinical practice: the burden of arterial hypertension. A multicenter Italian survey.

Little information is available about the burden of hypertension on echo-lab activity in current practice. The aim of the present nation-wide survey in outpatient echo-labs was to investigate the prevalence rates of (1) echo examinations performed for the evaluation of hypertensive cardiac damage; (2) reports providing quantitative data on left ventricular (LV) structure and geometry; (3) LV hypertrophy (LVH) in hypertensives referred to echo labs. The study was carried out in 14 outpatient echo-labs across Italy. Prescriptions written by general practitioners were used to identify the indications for the examinations. Estimates of LVH were derived from original echo reports or were calculated from LV primary measures, when available, with Devereux's formula in a post-analysis. Echo examination was performed in 2449 subjects (1245 men and 1204 women); hypertension was the indication for echo in 745 (30.4%) cases. In this subgroup, LV mass (LVM), LVM indexed to body surface area, LVM indexed to height(2.7) and relative wall thickness ratio were reported in 58, 59, 54 and 52%, respectively. LVH was present in 53% of untreated hypertensives and, among treated patients, in 45 and 65% of those with and without blood pressure control, respectively. Our findings show that (1) hypertension accounts for approximately one-third of echo examinations performed in clinical practice; (2) a large fraction of echo reports do not provide quantitative data on LVM and LV geometry, (3) LVH is highly prevalent in hypertensives referred to echo labs for assessment of cardiac damage.

PTEN status in advanced colorectal cancer treated with cetuximab.

BACKGROUND: Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with the epidermal growth factor receptor signal transduction pathway. METHODS: PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab. RESULTS: The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001). CONCLUSION: A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised.

Extracardiac organ damage in essential hypertensives with left ventricular concentric remodelling.

Clinical and prognostic values of left ventricular concentric remodelling (LVCR) are based on definition of this cardiac phenotype according to outdated guidelines indications. Thus, we analysed the association of extracardiac organ damage (OD) and LVCR (relative wall thickness >42) as defined by updated diagnostic criteria. Subclinical OD was searched in 1906 patients treated and untreated in essential hypertensives with normal echocardiographic LVMI as defined by two sets of gender-specific criteria based on LV mass (LVM) indexed to body surface area (125 g m(-2) in men and 110 g m(-2) in women) and height(2.7) (49 g m(-2.7) in men and 45 g m(-2.7) in women). Overall, 568 patients (29.8%), fulfilled the criteria for LVCR. Prevalence rates of carotid plaque, carotid intima-media (IM) thickening, grade II retinopathy and microalbuminuria (MA) were significantly higher in patients with LVCR compared with those with normal geometry (53, 24, 22, 10% versus 38, 15, 15, 7%, respectively, P<0.01, at least). Furthermore, an independent association between LVCR and continuous variables of OD such as carotid IM thickness (P<0.0001) and MA (P=0.004) was confirmed by a multivariate analysis. Our results indicate that LVCR identified by updated, less conservative, diagnostic criteria, is strongly associated with subclinical vascular and renal alterations of adverse prognostic significance. These findings support the view that LVCR should be searched for and regarded as a marker of target OD with an additional value for cardiovascular risk stratification in patients with normal LVM.

Indexation of left ventricular mass to body surface area and height to allometric power of 2.7: is the difference limited to obese hypertensives?

Whether left ventricular mass (LVM) should be normalized to different indexes in relation to body size is still debated. We sought to evaluate the prevalence of left ventricular hypertrophy (LVH) defined by different indexation criteria in a cohort of hypertensive subjects categorized according to body mass index (BMI). A total of 2213 essential hypertensive subjects included in the Evaluation of Target Organ Damage in Hypertension (ETODH) were divided in three groups according to BMI thresholds (<25, 25-29.9 and >or=30 kg m(-2)). All patients underwent extensive investigations including quantitative echocardiography. LVH was defined as an LVM index equal to or higher than (1) 125 g m(-2) in men and 110 g m(-2) in women, (2) 51 g m(-2.7) in men and 47 g m(-2.7) in women. Overall, 687 out of 2213 patients (31.0%) were found to have LVH when LVM was indexed to body surface area (BSA) and 1030 (46.5%) when indexed to height(2.7). A total of 845 patients (38.2%) had normal BMI, 954 patients (43.1%) were overweight and 414 (18.7%) were obese. Prevalence rates of LVH in the three groups were 25.1, 31.6, 41.2% by indexation to BSA and 29.9, 50.5, 71.8% by indexation to height(2.7), respectively. LVM indexed to BSA markedly underestimates LVH prevalence in obese as well as overweight hypertensive patients. To avoid a systematic misclassification of cardiovascular risk, LVM should be routinely indexed to height(2.7) in overweight and obese patients representing a large percentage of the hypertensive population.

Metabolic syndrome and biventricular hypertrophy in essential hypertension.

The metabolic syndrome (MS) is associated with structural and functional alterations of the left ventricle (LV); no evidence is available on the impact of the MS on the right ventricle (RV). To assess whether MS, as defined by the ATP III report, is associated with biventricular hypertrophy, a total of 286 hypertensive subjects (mean age 58.7+/-12.2 years) attending our outpatient clinic underwent the following procedures: (1) physical examination and standard clinic blood pressure (BP) measurement; (2) routine laboratory investigations; (3) M-mode, two-dimensional and Doppler echocardiography. LV hypertrophy (LVH) was defined by LM mass index>or=51/47 g m(-2.7) in men and women, respectively. Right-sided chambers were measured in parasternal long axis at the outflow tract and subcostal view; RV hypertrophy (RVH) was defined by anterior RV wall thickness>or=6.0/5.5 mm in men and women, respectively. Filling velocities of both ventricles were assessed by pulsed Doppler echocardiography. Structural cardiac alterations were more pronounced in hypertensive men and women with MS than in their non-MS counterparts and involved both ventricles as shown by the differences in continuous variables as well as in prevalence rates of LVH (58 and 48% vs 28 and 30%, respectively, P<0.01) and RVH (48 and 54% vs 25 and 35%, respectively, P<0.01). Both LV and RV filling in MS hypertensives were more dependent on the atrial systole. Our study shows that in human hypertension, structural and functional cardiac changes induced by MS are not limited to the LV but also involve the right one.

The role of cetuximab in pre-treated refractory patients with metastatic colorectal cancer: outcome study in clinical practice.

We carried out a multicentric retrospective study on cetuximab + chemotherapy in pre-treated refractory patients outside clinical protocols, by registering the main clinical and pathological parameters. We evaluated 144 pre-treated patients. Cetuximab was administered usually in combination with irinotecan (93.8%). A 45% disease control rate (complete plus partial responses plus stable disease) was obtained in 55 patients and was related to absence of weight loss (p<0.0001) and high grade (> or =2) skin toxicity (p<0.0001). Median time to progression (TTP) was 4 months (95%CI 2.7-5.3) and median overall survival (OS) was 11.8 months (95%CI 8.5-15.1). Performance status << or =1, no weight loss and high grade (>or =22) skin toxicity were related both to a longer TTP (p=0.035, p=0.035, p=0.0017) and OS (p<0.0001, p<0.0001, p=0.006). According to multivariate analysis, the absence of weight loss was related to longer TTP (HR 0.331, p=0.004) and OS (HR 0.176, p<0.0001), and EGFR over-expression (3+) to longer TTP (HR 0.402, p=0.020).

Prevalence and correlates of multiple organ damage in referred treated hypertensives: data from the ETODH study.

This study, carried out in a large cohort of treated essential hypertensives attending an out-patient hospital hypertension clinic, extends previous observations by showing that a clustering of two or three markers of organ damage (OD) has a higher prevalence than a single organ involvement. These findings call for a systematic evaluation of cardiac and extracardiac OD in treated hypertensive patients referred to a specialist setting.

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma.

The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 x 10(6) total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up.

Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy.

We analysed the expression of microsatellite instability, p53, p21, vascular endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy specimens from 57 locally advanced rectal cancers. The aim of the study was to correlate the expression of these markers with pathological response. Nineteen patients were treated with preoperative concomitant radiotherapy (RT) and fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone. Pathological complete remission (pCR) and microfoci residual tumour (micR) occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours (P=0.004). Among patients treated with RCT, high TS levels were associated with a higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT group. The other molecular factors were of no predictive value. Multivariate analysis confirmed a significant interaction between nodal status and the probability of achieving a pathological response (P=0.023) and between TS expression and treatment, indicating that a high TS level is predictive of a higher pathological response in the RCT subset (P=0.007). This study shows that lymph node status is the most important predictive factor of tumour response to preoperative treatment. Thymidylate synthase expression assessed immunohistochemically from pretreatment tumour biopsies may be a useful predictive marker of rectal tumour response to preoperative RCT.