Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term.

BACKGROUND: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). METHODS: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. RESULTS: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25-48) weeks after COVID-19 onset, and they had higher carotid Young's elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P=0.04). Moreover, aPWV (path coefficient: -0.186; P=0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (-9%; P=0.01), incremental Young's elastic modulus (-17%; P=0.03), baroreflex sensitivity (+28%; P=0.049), heart rate variability triangular index (+15%; P=0.01), and subendocardial viability ratio (+12%; P=0.01×10-4) were significantly improved. There was a trend toward improvement in brachial PWV (-6%; P=0.14) and carotid distensibility (+18%; P=0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P=0.04) remained significantly higher in patients with COVID-19 than in control subjects. CONCLUSIONS: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

Progression and prognosis of interstitial pneumonia with autoimmune features: a longitudinal, prospective, multi-centre study.

OBJECTIVES: To evaluate the rate of progression towards specific autoimmune diseases (SADs) of a prospective, multi-centre cohort of patients classifiable as interstitial pneumonia with autoimmune features (IPAF). METHODS: IPAF patients were enrolled based on specific research criteria, and jointly followed by rheumatologists and pulmonologists for at least one year with clinical check-ups, serological exams including autoimmunity, capillaroscopy and high-resolution computed tomography (HRCT). Diagnostic assessment was repeated at least once a year, or earlier when deemed useful. RESULTS: We enrolled 191 IPAF patients through 95 different combinations of IPAF criteria. Of these, 24.1% progressed towards SAD, mainly in connective tissue diseases but also in microscopic polyangiitis. The IPAF patients who progressed were younger than stable IPAF patients (63±10 years vs. 68±9 years, p=0.002) and had a longer follow-up (36.9±18.7 vs. 29.3±15.7 months, p=0.007), but similar severity. No parameters were associated with overall progression, but some parameters were associated with the development of specific diagnoses: Sjögren's syndrome with positivity for SSA (p=0.007, χ2 7.4); idiopathic inflammatory myopathy with mechanic's hands (p=<0.0001, χ2 12.6), organizing pneumonia pattern (p=0.01, χ2 6.1), positivity for anti-Pm/scl (p=0.04 χ2 4.1) and anti-MDA5 (p=0.04, χ2 4.2); systemic sclerosis with palmar telangiectasias (p=<0.0001 2 18.3), positivity for anti-Scl70 (p=<0.0001 χ2 12.5) and anti-PM/Scl (p=0.001 χ2 10.1). CONCLUSIONS: IPAF patients had a rate of progression towards SAD similar to that reported in previous studies on undifferentiated connective tissue diseases, thus including some patients in which lung involvement could represent the first or even the sole clinical manifestation of a SAD.

Clinical Presentation of Connective Tissue Disease Patients with and without Interstitial Lung Disease: A Retrospective Study.

BACKGROUND: Connective tissue diseases (CTDs) are responsible for about 20% of interstitial lung disease (ILD) cases, but their diagnosis in a pulmonary unit (PU) is not always straightforward due to a heterogeneous clinical picture. OBJECTIVES: The aim of this study was to evaluate the clinical presentation of rheumatoid arthritis (RA) and CTD-ILD cases diagnosed in PU, compared to RA and CTD patients diagnosed in a rheumatologic unit (RU). METHODS: Patients with RA, systemic sclerosis (SSc), primary SjÓ§gren's syndrome (pSS), and idiopathic inflammatory myopathy were retrospectively enrolled from an RU and a PU designated to manage ILD during a period from January 2017 to October 2022. The classification of CTD-PU was carried out in a multidisciplinary setting, including the same rheumatologists that diagnosed CTD in the RU. RESULTS: ILD-CTD-PU patients were prevalently male and older. Progression from undifferentiated CTD to a specific condition was more common in ILD-CTD-PU, and those patients generally obtained a lower score on specific classification criteria. RA-PU patients resembled polymyalgia rheumatica in 47.6% of cases, also showing a greater proportion of typical joint deformities (p = 0.02). SSc-PU patients showed a usual interstitial pneumonia pattern in 76% of cases and, compared with SSc-RU, were more commonly seronegative (p = 0.03) and generally lacked fingertip lesions (p = 0.02). The majority of the diagnoses of pSS-PU were in patients with previously diagnosed ILD, in which seropositivity and sicca syndrome developed during follow-up. CONCLUSIONS: CTD-ILD patients diagnosed in the PU show severe lung involvement and a nuanced autoimmune clinical picture.

Associations between Host Genetic Variants and Subgingival Microbiota in Patients with the Metabolic Syndrome.

Host genetic variants may affect oral biofilms, playing a role in the periodontitis-systemic disease axis. This is the first study to assess the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed, assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis testing) and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed and stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics with no genome-wide associations detected for periodontitis severity or Mets components at p < 10-7. Severe periodontitis was associated with pathogenic genera and species. Some SNPs correlated with specific bacterial genera as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and the microbiome.

Quantitative chest tomography indexes are related to disease activity in systemic sclerosis: results from a cross-sectional study.

OBJECTIVES: The aim of this study is to verify if there are correlations between quantitative chest tomography (QCT) indexes and disease activity (DA) in a cohort of patients with systemic sclerosis (SSc). METHODS: SSc patients were assessed for DA and underwent high resolution chest tomography (CT). CT images were analysed with an operator-independent algorithm extracting the QCT indexes. DA assessment was conducted according to the EUSTAR index, where a score ≥2.5 indicates high DA (hDA). Correlations between clinical data and QCT indexes were investigated with the Spearman's test. The Mann-Whitney test assessed the distribution of the QCT indexes among the groups. Receiver operating characteristics (ROC) curve and linear regression analysis were conducted in order to identify the best cut-off value and contribution for each QCT index in assessing hDA in SSc patients. RESULTS: Sixty patients (52 females, mean age 53.2 years, mean disease duration 5.3 years) were enrolled. A significant difference was found in QCT indexes distribution between patients with hDA and those with low DA. A mild strength correlation between QCT indexes and DA was observed. Once performed ROC curves and linear regression, Skewness on parenchymal lung <1.85 gave a significant contribution to the model in identifying subjects with hDA (p<0.001), showing sensitivity 79.5%, specificity 68.7%, and accuracy 76.6%. CONCLUSIONS: QCT indexes correlate with SSc DA. These data introduce new possibilities for QCT application in clinical practice, especially in patient's follow-up. Moreover, QCT could be implemented in a new SSc DA score based on operator-independent parameters.

Reduction of carotid baroreceptor sensitivity in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by diffuse vasculopathy and fibrosis of skin and visceral organs. Moreover, autonomic dysfunction is also suggested as an important step during the multifactorial SSc pathogenesis. Baroreceptors are responsible for maintaining blood pressure by means of autonomic system modulation. Considering that autonomic dysfunction and arteriosclerosis can both reduce baroreceptor sensitivity (BRS), in this cross-sectional study we investigated BRS in SSc patients. METHODS: Twenty-one SSc patients (mean age 55±10 years, 18 females) and 147 age/sex-matched healthy controls were recruited for the study. BRS (ms/mmHg) was measured by a Finapres® Midi device (Finapres Medical Systems, Amsterdam, The Netherlands). Other parameters were measured: blood pressure, heart rate, heart rate variability triangular index (HRVI), intima-media thickness (IMT), carotid distensibility and pulse wave velocity (PWV). RESULTS: BRS was significantly lower in SSc patients compared to controls (6.3±3.3 vs. 10.7±6.8 ms/mmHg; p=0.004). IMT was comparable between SSc and controls, whereas carotid distensibility was lower in SSc (20.1±7.6 vs. 26.6±13.3 KPa-1·10-3; p=0.02) and PWV higher in SSc (8.4±1.3 vs. 7.1±1.1 m/sec; p=0.01). Furthermore, HRVI was lower in SSc (4.5±2.1 vs. 7.5±2.8; p<0.001). BRS impairment was independent from age and carotid distensibility in SSc patients, suggesting that BRS dysfunction could be only partially a consequence of SSc vasculopathy. CONCLUSIONS: BRS was reduced in SSc patients compared with healthy controls. This finding could represent a SSc-related alteration involving the autonomic system, besides being the mere consequence of sclerodermic vasculopathy.

"Usual" interstitial pneumonia with autoimmune features: a prospective study on a cohort of idiopathic pulmonary fibrosis patients.

OBJECTIVES: The classification interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease (ILD) associated with autoimmune characteristics insufficient to reach classification criteria for a specific autoimmune disease (SAD). These criteria are divided into three domains: clinical, serological and morphological. The latter domain does not include the usual interstitial pneumonia (UIP) pattern, which is deemed not to be significantly associated with SAD. Therefore, the enrolment of these patients is more difficult, requiring at least one item from both of the other domains. The objective of this study is to evaluate the rate of progression towards SAD of a cohort of UIP patients satisfying only one IPAF domain (we called this group "UIPAF") compared with classic idiopathic pulmonary fibrosis (IPF). METHODS: We prospectively enrolled IPF patients with radiologic and/or histologic UIP pattern, followed jointly by rheumatologists and pulmonologists from January 2017 to January 2021, with a minimum follow-up of 12 months. RESULTS: We enrolled 190 IPF patients, 38 (20%) of whom were classified as UIPAF. IPF and UIPAF patients were similar for general characteristics, severity and prognosis, at presentation and at annual check-up. However, 28.9% of UIPAF patients progressed towards SAD, compared with 2% of IPF patients (χ2=30.4, p≤0.0001). CONCLUSIONS: The association between a single clinical or serological domain of IPAF and UIP pattern is predictive for the development of a SAD if compared with isolated UIP. ILD can be the first manifestation of SAD, even with a UIP pattern, therefore, the morphological domain of IPAF criteria could be removed.

Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases.

Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity.

Heart Valve Abnormalities in Systemic Sclerosis Patients: A Multicenter Cohort Study and Review of the Literature.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease that is characterized by vasculopathy and fibrosis of the skin and visceral organs. Heart valve diseases are poorly described and generally not considered typical of SSc. We aimed to describe valvular abnormalities in a multicenter cohort of SSc patients and to investigate their correlation with SSc features. METHODS: We recruited 118 consecutive SSc patients (male/female, 14/104; mean age, 55.2 ± 12.1 years) in 3 rheumatology centers in Sicily, Italy, from January to October 2019. RESULTS: Mitral and tricuspid valve insufficiency was found in 85% and 91% of patients, respectively; regurgitations were generally mild and never severe. Mitral stenosis was rare (2%), and tricuspid stenosis was not observed. Sclerosis and calcification were present in 30% of mitral valves and in only 4% of tricuspid valves. The aortic valve was affected in 25% of cases, and it generally presented as regurgitation or sclerosis, whereas stenosis was rare (3%). Finally, 11% of SSc patients showed regurgitation of the pulmonary valve. No specific associations between SSc features and valve alterations were found. CONCLUSIONS: Valvular diseases are frequently observed in SSc patients, with a predominant pattern of valvular regurgitations. Therefore, echocardiography should be routinely performed during SSc patient follow-up, considering the potential influence of additional cardiac involvement in the prognosis of these patients.

Amiodarone in ventricular arrhythmias: still a valuable resource?

Ventricular arrhythmias still represent an important cause of morbidity and mortality, especially in patients with heart failure and reduced left ventricular ejection fraction. Amiodarone is a Class III Vaughan-Williams anti-arrhythmic drug widely used in ventricular arrhythmias for its efficacy and low pro-arrhythmogenic effect. On the other hand, a significant limitation in its use is represented by toxicity. In this review, the pharmacology of the drug is discussed to provide the mechanistic basis for its clinical use. Moreover, all the latest evidence on its role in different clinical settings is provided, including the prevention of sudden cardiac death, implanted cardioverter defibrillators, ischemic and non-ischemic cardiomyopathies. A special focus is placed on everyday clinical practice learning points, such as dosage, indications, and contraindications from the latest guidelines.

Adherence to abiraterone or enzalutamide in elderly metastatic castration-resistant prostate cancer.

PURPOSE: To evaluate adherence to abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS: In an observational prospective cohort study, we monitored patients with mCRPC for their adherence to abiraterone or enzalutamide in the pre- or post-chemotherapy setting. RESULTS: Fifty-eight patients with median age of 76 years (range 56-94), age-adjusted Charlson comorbidity score of 10 (range, 4-15), and geriatric G8 score of 14 (range, 6-17) were enrolled. Twenty-two (38%) patients were treated with abiraterone and 36 (62%) with enzalutamide, while forty-two (72%) were in the pre-chemotherapy setting. Forty-seven patients (81%) had a caregiver. Based on the pill counting, a non-adherence rate of 4.8% and 6.2% was observed for the whole period and the first 3 months, respectively, without a statistically significant difference between abiraterone and enzalutamide cohorts. A lower non-adherence rate (1.3%) was reported by patients during the whole period, mainly due to a misperception (77%) and forgetfulness (19%). Non-adherence rate to the fulfilling of the clinical diary was 38% for the whole period. Non-adherence in the whole period was related to the radiological response (p = 0.03) and geriatric G8 score (p = 0.005). By the receiver operating characteristic (ROC) curve based on the radiological response, non-adherence cut-off was 1.87% (p = 0.04). By this non-adherence cut-off, the G8 cut-off was 14.75 (p = 0.0003). CONCLUSION: Non-adherence to abiraterone or enzalutamide for mCRPC may have an impact on disease response and be related to patients' frailty, suggesting their geriatric assessment and clinical interventions to monitor and increase their adherence.

Arterial Stiffness in the Heart Disease of CKD.

CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.

Circulating MiRNA-195-5p and -451a in Diabetic Patients with Transient and Acute Ischemic Stroke in the Emergency Department.

(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.

Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2-5 years after diagnosis. Therefore, IPF patient identification represents an important and challenging clinical issue. Current research is still searching for novel reliable non-invasive biomarkers. Therefore, we explored the potential use of long non-coding RNAs (lncRNAs) and mRNAs as biomarkers for IPF. METHODS: We first performed a whole transcriptome analysis using microarray (n = 14: 7 Control, 7 IPF), followed by the validation of selected transcripts through qPCRs in an independent cohort of 95 subjects (n = 95: 45 Control, 50 IPF). Diagnostic performance and transcript correlation with functional/clinical data were also analyzed. RESULTS: 1059 differentially expressed transcripts were identified. We confirmed the downregulation of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) lncRNA, hsa_circ_0001924 circularRNA, utrophin (UTRN) and Y-box binding protein 3 (YBX3) mRNAs. The two analyzed non-coding RNAs correlated with Forced Vital Capacity (FVC)% and Diffusing Capacity of the Lung for carbon monoxide (DLCO)% functional data, while coding RNAs correlated with smock exposure. All analyzed transcripts showed excellent performance in IPF identification with Area Under the Curve values above 0.87; the most outstanding one was YBX3: AUROC 0.944, CI 95% = 0.895-0.992, sensitivity = 90%, specificity = 88.9%, p-value = 1.02 × 10-13. CONCLUSIONS: This study has identified specific transcript signatures in IPF suggesting that validated transcripts and microarray data could be useful for the potential future identification of RNA molecules as non-invasive biomarkers for IPF.

Upregulated microRNAs in membranous glomerulonephropathy are associated with significant downregulation of IL6 and MYC mRNAs.

Membranous glomerulonephropathy (MGN) is a glomerulopathy characterized by subepithelial deposits of immune complexes on the extracapillary side of the glomerular basement membrane. Insertion of C5b-9 (complement membrane-attack complex) into the membrane leads to functional impairment of the glomerular capillary wall. Knowledge of the molecular pathogenesis of MGN is actually scanty. MicroRNA (miRNA) profiling in MGN and unaffected tissues was performed by TaqMan Low-Density Arrays. Expression of miRNAs and miRNA targets was evaluated in Real-Time polymerase chain reaction (PCR). In vitro transient silencing of miRNAs was achieved through transfection with miRNA inhibitors. Ten miRNAs (let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, miR-107, miR-129-3p, miR-423-5p, miR-516-3p, miR-532-3p, and miR-1275) were differentially expressed (DE) in MGN biopsies compared to unaffected controls. Interleukin 6 (IL6) and MYC messenger RNAs (mRNAs; targets of DE miRNAs) were significantly downregulated in biopsies from MGN patients, and upregulated in A498 cells following let-7a-5p or let-7c-5p transient silencing. Gene ontology analysis showed that DE miRNAs regulate pathways associated with MGN pathogenesis, including cell cycle, proliferation, and apoptosis. A significant correlation between DE miRNAs and mRNAs and clinical parameters (i.e., antiphospholipid antibodies, serum creatinine, estimated glomerular filtration, proteinuria, and serum cholesterol) has been detected. Based on our data, we propose that DE miRNAs and their downstream network may be involved in MGN pathogenesis and could be considered as potential diagnostic biomarkers of MGN.

Left ventricular geometry and periodontitis in patients with the metabolic syndrome.

OBJECTIVE: The presence of periodontal disease (PD) in subjects affected by the metabolic syndrome (MetS) may affect their risk of developing cardiovascular disease. The aim of this cross-sectional study was to investigate the systemic impact of PD in MetS, by assessing measures of sub-clinical atherosclerosis and left ventricular mass and geometry. MATERIALS AND METHODS: A total of 103 patients undergoing treatment for MetS were examined for confirmation of diagnosis, blood sampling, and measures of pulse wave velocity (PWV), carotid intima-media thickness (c-IMT), left ventricular mass index (LVM), and relative wall thickness (RWT). All subjects underwent a detailed dental assessment, including measurements of DMFT (decayed-missing-filled teeth) and periodontal parameters. RESULTS: Ten patients (10%) were diagnosed with healthy-mild periodontitis, 38 patients (37%) were diagnosed in the moderate periodontitis group, and 55 (53%) had severe periodontitis. A total of 37% of subjects were affected by dental caries. Linear regression analysis revealed that patients with severe PD had increased average ventricular RWT (adjusted p = 0.032). Average full mouth probing pocket depth (PPD) was also associated with RWT (adjusted p = 0.006). No associations between PD and c-IMT, PWV, and LVM were detected after adjusted analyses. CONCLUSION: This study suggests that periodontitis may be associated with concentric left ventricular remodeling, a predictive index of cardiovascular events. CLINICAL RELEVANCE: The presence of periodontitis in patients with MetS might have an effect on left ventricular geometry. These findings stress the importance of prevention, diagnosis, and management of periodontitis in patients with MetS. TRAIL REGISTRATION: NCT03297749.

Outcomes of non-invasive ventilation in 'very old' patients with acute respiratory failure: a retrospective study.

BACKGROUND: Non-invasive ventilation (NIV) is increasingly used to support very old (aged ≥85 years) patients with acute respiratory failure (ARF). This retrospective observational study evaluated the impact of NIV on the prognosis of very old patients who have been admitted to the intermediate care unit (IMC) of the Emergency Department of the University Hospital Policlinico-Vittorio Emanuele of Catania for ARF. METHODS: All patients admitted to the IMC between January and December 2015 who received NIV as the treatment for respiratory failure were included in this study. Outcomes of patients aged ≥85 years were compared with lower ages. The expected intrahospital mortality was calculated through the Simplified Acute Physiology Score (SAPS) II and compared with the observed mortality. RESULTS: The mean age was 87.9±2.9 years; the M:F ratio was approximately 1:3. The average SAPS II was 50.1±13.7. The NIV failure rate was 21.7%. The mortality in the very old group was not statistically different from the younger group (20% vs 25.6%; d=5.6%; 95% CI -8% to 19%; p=0.404). The observed mortality was significantly lower than the expected mortality in both the group ≥85 (20.0% vs 43.4%, difference=23.4%; 95% CI 5.6% to 41.1%, p=0.006) and the younger group (25.6% vs 38.5%, difference=12.9%; 95% CI -0.03% to 25.8%, p=0.046). In both age groups, patients treated with NIV for chronic obstructive pulmonary disease had lower mortalities than those treated for other illnesses, although this was statistically significant only in the younger group. CONCLUSION: In very old patients, when used with correct indications, NIV was associated with mortality similar to younger patients. Patients receiving NIV had lower than expected mortality in all age groups.

Endocrine disorders associated with hepatitis C virus chronic infection.

The term "HCV syndrome" encompasses several organ- and systemic pathophysiological states, which often recognize autoimmunity or neoplastic evolution in their pathophysiology, as well as chronic HCV infection as trigger. The clinical features of HCV patients are heterogenous, and may include endocrine or metabolic disorders, namely autoimmune thyroiditis, type 2 diabetes mellitus, and erectile/sexual dysfunctions. In this review, we summarize current knowledge on the endocrine/metabolic diseases associated with chronic HCV infection, focusing on the main concepts emerged in the recent literature in this field. The application of this knowledge in everyday clinical practice may be relevant, in order to reinforce a holistic vision of the patient with chronic HCV infection, stimulating in turn a multi-disciplinary approach, thus increasing the probability of early diagnosis, more effective treatments, and a better prognostic outcome.

Management of hypertension in the elderly: Looking for a trade-off between cardiovascular prevention and serious adverse events.

Despite the effectiveness of anti-hypertensive therapy is well recognized, the most adequate target to achieve in the management of hypertension in the elderly is still under debate. Indeed, looking at the balance between benefits and risks, accumulating evidence has recently specifically addressed this issue, focusing on controversies. Evidence surrounding a more aggressive treatment may lead to a turnaround in the clinical care of older adult hypertensives, but a balanced trade-off between benefits and risks needs to be programmed and achieved, particularly in this clinical setting. We argue whether and how the results from recent trials could influence the management of hypertension in older people.

Serum sodium correction rate and the outcome in severe hyponatremia.

STUDY OBJECTIVE: We investigated the serum sodium correction rate on length of hospitalization and survival rate, in severe chronic hyponatremic patients at the Emergency Department (ED). DESIGN: An observational study using clinical chart review. SETTING: The ED of the University Hospital of Marcianise, Caserta, Italy with approximately 30,000 patients visits a year. TYPE OF PARTICIPANTS: We reviewed sixty-seven patients with severe hyponatremia subdivided in 2 subgroups: group A consisting of 35 patients with serum sodium correction rate<0.3mmol/h and group B consisting of 32 patients with serum sodium correction rate between <0.5 and ≥0.3mmol/h. INTERVENTION: Emergency patients were evaluated for serum sodium correction rate for hyponatremia by clinical chart review. MEASUREMENTS AND MAIN RESULTS: Severe hyponatremia was defined as a serum sodium level<120mmol/l. Mean serum sodium correction rate of hyponatremia was of 0.17±0.09% in group A and 0.41±0.05% in group B (p<0.001 vs group A). The length of hospital stay was 10.7±3.7days for group A, and it was significantly decreased to 3.8±0.4days for group B (p<0.005 vs group A). In addition we observed that correction rate of hyponatremia in group A was associated with a significantly lower survival rate (25%) in comparison to group B (60%) (p<0.001 vs group A). CONCLUSION: We observed that serum sodium correction rate ≥0.3 and <0.5mmol/h was associated with a shorter length of hospital stay and a major survival rate.