Summary Background & aims Old persons are more likely to suffer from malnutrition, which may result in higher dependency in activities of daily living. We aimed to provide a quantitative synthesis of ...prevalence data on malnutrition and its risk as assessed by the Mini Nutritional Assessment across different healthcare settings. The association between nutritional status and setting-related level of dependence was also investigated. Methods Non-interventional studies published as full-text articles in English up to 31th December 2014 were searched for in PubMed and by reviewing references of eligible articles. Meta-analysis and meta-regression of potential sources of heterogeneity were conducted. Results A total of 240 studies/795 citations – providing 258 setting-specific prevalence estimates (113,967 subjects) - fulfilled inclusion criteria for meta-analysis. Prevalence of malnutrition differed significantly across the healthcare settings considered: community, 3.1% (95%CI, 2.3–3.8); outpatients, 6.0% (95%CI, 4.6–7.5); home-care services, 8.7% (95%CI, 5.8–11.7); hospital, 22.0% (95%CI, 18.9–22.5); nursing homes, 17.5% (95%CI, 14.3–20.6); long-term care, 28.7% (95%CI, 21.4–36.0); rehabilitation/sub-acute care, 29.4% (95%CI, 21.7–36.9). For every setting significant heterogeneity in individual study results was observed ( I 2 ≥80%, P < 0.001) and meta-regression showed that study quality was the most important determinant. Finally, meta-regression of all the studies included showed that both malnutrition and its risk were directly associated with the setting-related level of dependence (P < 0.001). However, despite multiple adjustments, residual heterogeneity remained high. Conclusion We provided updated estimates of malnutrition and its risk in different healthcare settings. Although the level of dependence appears to be an important determinant, heterogeneity in individual study results remained substantially unexplained. The cause–effect relationship between nutritional status and level of dependence deserves further investigation.
Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to ...pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%.
We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis.
A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%).
In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).
Unique immunological profile in patients with COVID-19 Varchetta, Stefania; Mele, Dalila; Oliviero, Barbara ...
Cellular & Molecular Immunology/Cellular & molecular immunology,
03/2021, Letnik:
18, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients ...with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8
T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56
and an expansion of mature CD57
FcεRIγ
adaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8
T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.
Objectives The purpose of this study was to assess the effect of remote patient monitoring (RPM) on the outcome of chronic heart failure (HF) patients. Background RPM via regularly scheduled ...structured telephone contact between patients and health care providers or electronic transfer of physiological data using remote access technology via remote external, wearable, or implantable electronic devices is a growing modality to manage patients with chronic HF. Methods After a review of the literature published between January 2000 and October 2008 on a multidisciplinary heart failure approach by either usual care (in-person visit) or RPM, 96 full-text articles were retrieved: 20 articles reporting randomized controlled trials (RCTs) and 12 reporting cohort studies qualified for a meta-analysis. Results Respectively, 6,258 patients and 2,354 patients were included in RCTs and cohort studies. Median follow-up duration was 6 months for RCTs and 12 months for cohort studies. Both RCTs and cohort studies showed that RPM was associated with a significantly lower number of deaths (RCTs: relative risk RR: 0.83, 95% confidence interval CI: 0.73 to 0.95, p = 0.006; cohort studies: RR: 0.53, 95% CI: 0.29 to 0.96, p < 0.001) and hospitalizations (RCTs: RR: 0.93, 95% CI: 0.87 to 0.99, p = 0.030; cohort studies: RR: 0.52, 95% CI: 0.28 to 0.96, p < 0.001). The decrease in events was greater in cohort studies than in RCTs. Conclusions RPM confers a significant protective clinical effect in patients with chronic HF compared with usual care.
To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population.
We gathered for ...analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed.
There was a strong correlation between the extent of reduction of amyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs dFLC < 40 mg/L), partial response (dFLC decrease > 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation.
This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials.
Objectives This study evaluated the safety, efficacy, and effect of MitraClip treatment on symptoms and left ventricular (LV) remodeling in nonresponders to cardiac resynchronization therapy (CRT). ...Background Moderate to severe functional mitral regurgitation (FMR) frequently persists after CRT, contributing to reduced or no response to CRT. Percutaneous repair with the MitraClip has been proposed as an additional therapeutic option in select patients with significant FMR. Methods Fifty-one severely symptomatic CRT nonresponders with significant FMR (grade ≥2, 100%) underwent MitraClip treatment. Changes in New York Heart Association functional class, degree of FMR, LV ejection fraction (EF), and LV end-diastolic/end-systolic volumes (EDV/ESV) before and after (3, 6, and 12 months) MitraClip implantation were recorded. Mortality data, including cause of death, were collected. Results MC treatment was feasible in all patients (49% 1 clip, 46% 2 clips). There were 2 periprocedural deaths. Median follow-up was 14 months (25th to 75th percentile: 8 to 17 months). New York Heart Association functional class improved acutely at discharge (73%) and continued to improve progressively during follow-up (regression model, p < 0.001). The proportion of patients with significant residual FMR (grade ≥2) progressively decreased during follow-up (regression model, p < 0.001). Reverse LV remodeling and improved LVEF were detected at 6 months, with further improvement at 12 months (regression model, p = 0.001, p = 0.008, and p = 0.031 for ESV, EDV, and LVEF, respectively). Overall 30-day mortality was 4.2%. Overall mortality during follow-up was 19.9 per 100 person-years (95% confidence interval: 10.3 to 38.3). Nonsurvivors had more compromised clinical baseline conditions, longer QRS duration, and a more dilated heart. Conclusions FMR treatment with the MitraClip in CRT nonresponders was feasible, safe, and demonstrated improved functional class, increased LVEF, and reduced ventricular volumes in about 70% of these study patients.
Objectives Chronic thromboembolic pulmonary hypertension can be cured by pulmonary endarterectomy. Operability assessment remains a major concern, because there are no well-defined criteria to ...discriminate proximal from distal obstructions, and surgical candidacy depends mostly on the surgeon's experience. The intraoperative classification of chronic thromboembolic pulmonary hypertension describes 4 types of lesions, based on anatomy and location. We describe our recent experience with the more distal (type 3) disease. Methods More than 500 pulmonary endarterectomies were performed at Foundation I.R.C.C.S. Policlinico San Matteo (Pavia, Italy). Because of recent changes in the patient population, 331 endarterectomies performed from January 2008 to December 2013 were analyzed. Two groups of patients were identified according to the intraoperative classification: proximal (type 1 and type 2 lesions, 221 patients) and distal (type 3 lesions, 110 patients). Results The number of endarterectomies for distal chronic thromboembolic pulmonary hypertension increased significantly over time (currently ∼37%). Deep venous thrombosis was confirmed as a risk factor for proximal disease, whereas patients with distal obstruction had a higher prevalence of indwelling intravascular devices. Overall hospital mortality was 6.9%, with no difference in the 2 groups. Postoperative survival was excellent. In all patients, surgery was followed by a significant and sustained improvement in hemodynamic, echocardiographic, and functional parameters, with no difference between proximal and distal cases. Conclusions Although distal chronic thromboembolic pulmonary hypertension represents the most challenging situation, the postoperative outcomes of both proximal and distal cases are excellent. The diagnosis of inoperable chronic thromboembolic pulmonary hypertension should be achieved only in experienced centers, because many patients who have been deemed inoperable might benefit from favorable surgical outcomes.
Accurate diagnosis of systemic amyloidosis is necessary both for assessing the prognosis and for delineating the appropriate treatment. It is based on histologic evidence of amyloid deposits and ...characterization of the amyloidogenic protein. We prospectively evaluated the diagnostic performance of immunoelectron microscopy (IEM) of abdominal fat aspirates from 745 consecutive patients with suspected systemic amyloidoses. All cases were extensively investigated with clinical and laboratory data, with a follow-up of at least 18 months. The 423 (56.8%) cases with confirmed systemic forms were used to estimate the diagnostic performance of IEM. Compared with Congo-red–based light microscopy, IEM was equally sensitive (75% to 80%) but significantly more specific (100% vs 80%; P < .001). In amyloid light-chain (AL) amyloidosis, κ cases were more difficult to diagnose (sensitivity 71%), whereas the analysis of abdominal aspirate was informative in only 40% of patients with transthyretin amyloidosis. We found a high prevalence (20%) of a monoclonal component in patients with non-AL amyloidosis, highlighting the risk of misdiagnosis and the need for unequivocal amyloid typing. Notably, IEM identified correctly the specific form of amyloidosis in >99% of the cases. IEM of abdominal fat aspirates is an effective tool in the routine diagnosis of systemic amyloidoses.
•The first wide, prospective report on the role of IEM in the differential diagnosis of systemic amyloidosis.•IEM allows for the correct characterization of the amyloid protein in virtually all cases and represents a viable alternative to mass spectrometry.
Summary Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both ...regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of many publications detailing management. This Review represents the views from an international conference, for which 15 expert working groups prepared evidence-based assessments addressing specific questions, and from which an independent jury derived final recommendations. The aim of the conference was to review the existing approaches to neuroendocrine liver metastases, assess the evidence on which management decisions were based, develop internationally acceptable recommendations for clinical practice (when evidence was available), and make recommendations for clinical and research endeavours. This report represents the final clinical statements and proposals for future research.
PDF
