Neutrophil-to-lymphocyte ratio (NLR) predicts mortality in hospitalized geriatric patients independent of the admission diagnosis: a multicenter prospective cohort study.

BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) is a marker of poor prognosis in hospitalized older patients with different diseases, but there is still no consensus on the optimal cut-off value to identify older patients at high-risk of in-hospital mortality. Therefore, in this study we aimed at both validating NLR as a predictor of death in older hospitalized patients and assess whether the presence of specific acute diseases can modify its predictive value. METHODS: This prospective cohort study included 5034 hospitalizations of older patients admitted to acute care units in the context of the ReportAge study. NLR measured at admission was considered as the exposure variable, while in-hospital mortality was the outcome of the study. ROC curves with Youden's method and restricted cubic splines were used to identify the optimal NLR cut-off of increased risk. Cox proportional hazard models, stratified analyses, and Kaplan-Meier survival curves were used to analyse the association between NLR and in-hospital mortality. RESULTS: Both continuous and categorical NLR value (cut-off ≥ 7.95) predicted mortality in bivariate and multivariate prognostic models with a good predictive accuracy. The magnitude of this association was even higher in patients without sepsis, congestive heart failure, and pneumonia, and those with higher eGFR, albumin, and hemoglobin (p < 0.001). A negative multiplicative interaction was found between NLR and eGFR < 45 (p = 0.001). CONCLUSIONS: NLR at admission is a readily available and cost-effective biomarker that could improve identification of geriatric patients at high risk of death during hospital stay independent of admitting diagnosis, kidney function and hemoglobin levels.

Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19.

Elevation of cardiac damage biomarkers is associated with adverse clinical outcomes and increased mortality in COVID-19 patients. This study assessed the association of admission serum levels of sST2 and H-FABP with in-hospital mortality in 191 geriatric patients (median age 86 yrs., IQR 82-91 yrs.) with COVID-19 and available measures of hs-cTnT and NT-proBNP at admission. Cox proportional hazards models were utilized to predict in-hospital mortality, considering clinical/biochemical confounders as covariates. A composite cardiac score was calculated to improve predictive accuracy. Patients deceased during their hospital stay (26%) exhibited higher levels of all biomarkers, which demonstrated good discrimination for in-hospital mortality. Addition of sST2 and H-FABP significantly improved the discriminatory power of hs-cTnT and NT-proBNP. The composite cardiac score (AUC=0.866) further enhanced the predictive accuracy. Crude and adjusted Cox regressions models revealed that both sST2 and H-FABP were independently associated with in-hospital mortality (HR for sST2 ≥129 ng/mL, 4.32 [1.48-12.59]; HR for H-FABP ≥18 ng/mL, 7.70 [2.12-28.01]). The composite cardiac score also independently correlated with in-hospital mortality (HR for 1-unit increase, 1.47 [1.14-1.90]). In older patients with COVID-19, sST2 and H-FABP demonstrated prognostic value, improving the predictive accuracy of the routinely assessed biomarkers hs-cTnT and NT-proBNP.

Clusters of Comorbidities in the Short-Term Prognosis of Acute Heart Failure among Elderly Patients: A Retrospective Cohort Study.

Background and Objectives: Elderly patients affected by acute heart failure (AHF) often show different patterns of comorbidities. In this paper, we aimed to evaluate how chronic comorbidities cluster and which pattern of comorbidities is more strongly related to in-hospital death in AHF. Materials and Methods: All patients admitted for AHF to an Internal Medicine Department (01/2015−01/2019) were retrospectively evaluated; the main outcome of this study was in-hospital death during an admission for AHF; age, sex, the Charlson comorbidity index (CCI), and 17 different chronic pathologies were investigated; the association between the comorbidities was studied with Pearson's bivariate test, considering a level of p ≤ 0.10 significant, and considering p < 0.05 strongly significant. Thus, we identified the clusters of comorbidities associated with the main outcome and tested the CCI and each cluster against in-hospital death with logistic regression analysis, assessing the accuracy of the prediction with ROC curve analysis. Results: A total of 459 consecutive patients (age: 83.9 ± 8.02 years; males: 56.6%). A total of 55 (12%) subjects reached the main outcome; the CCI and 16 clusters of comorbidities emerged as being associated with in-hospital death from AHF. Of these, CCI and six clusters showed an accurate prediction of in-hospital death. Conclusions: Both the CCI and specific clusters of comorbidities are associated with in-hospital death from AHF among elderly patients. Specific phenotypes show a greater association with a worse short-term prognosis than a more generic scale, such as the CCI.

Implementation of EHMRG Risk Model in an Italian Population of Elderly Patients with Acute Heart Failure.

Acute heart failure (AHF) is a cardiac emergency with an increasing incidence, especially among elderly patients. The Emergency Heart failure Mortality Risk Grade (EHMRG) has been validated to assess the 7-days AHF mortality risk, suggesting the management of patients admitted to an emergency department (ED). EHMRG has never been implemented in Italian ED nor among elderly patients. We aimed to assess EHMRG score accuracy in predicting in-hospital death in a retrospective cohort of elderly subjects admitted for AHF from the ED to an Internal Medicine Department. We enrolled, in a 24-months timeframe, all the patients admitted to an Internal Medicine Department from ED for AHF. We calculated the EHMRG score, subdividing patients into six categories, and assessing in-hospital mortality and length of stay. We evaluated EHMRG accuracy with ROC curve analysis and survival with Kaplan−Meier and Cox models. We collected 439 subjects, with 45 in-hospital deaths (10.3%), observing a significant increase of in-hospital death along with EHMRG class, from 0% (class 1) to 7.7% (class 5b; p < 0.0001). EHMRG was fairly accurate in the whole cohort (AUC: 0.75; 95%CI: 0.68−0.83; p < 0.0001), with the best cutoff observed at >103 (Se: 71.1%; Sp: 72.8%; LR+: 2.62; LR-: 0.40; PPV: 23.0%; NPV: 95.7%), but performed better considering the events in the first seven days of admission (AUC: 0.83; 95%; CI: 0.75−0.91; p < 0.0001). In light of our observations, EHMRG can be useful also for the Italian emergency system to predict the risk of short-term mortality for AHF among elderly patients. EHMRG performance was better in the first seven days but remained acceptable when considering the whole period of hospitalization.

Improving the EHMRG Prognostic Evaluation of Acute Heart Failure with TAPSE/PASp: A Sequential Approach.

The Emergency Heart Failure Mortality Risk Grade (EHMRG) can predict short-term mortality in patients admitted for acute heart failure (AHF) in the emergency department (ED). This paper aimed to evaluate if TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can improve in-hospital death prediction in patients at moderate-to-high risk, according to EHMRG score classification. From 1 January 2018 to 30 December 2019, we retrospectively enrolled all the consecutive subjects admitted to our Internal Medicine Department for AHF from the ED. We performed bedside echocardiography within the first 24 h of admission. We evaluated EHMRG and NYHA in the ED, days of admission in Internal Medicine, and in-hospital mortality. We assessed cutoffs with ROC curve analysis and survival with Kaplan-Meier and Cox regression. We obtained a cohort of 439 subjects; 10.3% underwent in-hospital death. Patients with normal TAPSE/PASp in EHMRG Classes 4, 5a, and 5b had higher survival rates (100%, 100%, and 94.3%, respectively), while subjects with pathologic TAPSE/PASp had lower survival rates (81.8%, 78.3%, and 43.4%, respectively) (p < 0.0001, log-rank test). TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can further stratify the risk of in-hospital death evaluated by EHMRG.

SOFA and qSOFA usefulness for in-hospital death prediction of elderly patients admitted for suspected infection in internal medicine.

PURPOSE: To reduce intensive care unit overcrowding and optimize resources, elderly patients affected by suspected infection with declining clinical conditions could be managed in internal medicine departments with stepdown beds. However, commonly used prognostic scores, as Sequential Organ Failure Assessment (SOFA) or quick SOFA (qSOFA) have never been studied in this specific setting. The aim of this study was to evaluate the role and the accuracy of SOFA and qSOFA as prognostic scores in a population of elderly patients with suspected infection admitted to stepdown beds of two internal medicine departments. METHODS: Elderly patients admitted from the emergency department in the stepdown beds of two different internal medicine departments for suspected infection were assessed with SOFA and qSOFA scores at the admission. All patients were treated according to current guidelines. Age, sex, comorbidities, Charlson comorbidity index, SOFA and qSOFA were assessed. In-hospital death and length of hospital admission were also recorded. RESULTS: 390 subjects were enrolled. In-hospital death occurred in 144 (36.9%) patients; we observed that both SOFA (HR 1.189; 95% CI 1.128-1.253; p < 0.0001) and qSOFA (HR 1.803; 95% CI 1.503-2.164; p < 0.0001) scores were independently associated with an increased risk of in-hospital death. However, the accuracy of both SOFA (AUC: 0.686; 95% CI 0.637-0.732; p < 0.0001) and qSOFA (AUC: 0.680; 95% CI 0.641-0.735; p < 0.0001) in predicting in-hospital death was low in this population. CONCLUSION: Elderly patients admitted to stepdown beds for suspected infection experience a high rate of in-hospital death; both SOFA and qSOFA scores can be useful to identify a group of patients who can benefit from admission to an intermediate care environment, however their accuracy is low.

Assessment of vulnerability measures and their effect on survival in a real-life population of multiple myeloma patients registered at Marche Region Multiple Myeloma Registry.

UNLABELLED: Multiple myeloma (MM) therapy should be tailored according to patient characteristics although we do not know which ones to use. By studying the characteristics of 266 real-life patients, we found performance status (PS) and Charlson Comorbidity Index (CCI) as factors affecting survival of MM patients regardless of their disease characteristics. This study might help to select patients for tailoring therapy in clinical practice. BACKGROUND: Multiple myeloma is a typical disease of the elderly but how many and which patients can be considered 'vulnerable' and how this may affect patient outcome remain unsolved issues. PATIENTS AND METHODS: Data from 266 symptomatic MM patients registered at Marche MM registry from 2007 to 2010 were evaluated retrospectively. Vulnerability was defined as age > 75 years, PS (World Health Organization) ≥ 2, renal insufficiency (RI), bone fracture, cytopenias, and CCI score ≥ 1. Kaplan-Meier method and Cox regression were used to assess survival and associated factors. A vulnerability score (VS) incorporating significant vulnerability features was pursued to predict survival. RESULTS: Thirty-eight percent of patients were older than 75 years, 39% had PS = 2-4, 35% had at least 2 cytopenias, 40% had bone fracture, 14% RI, and 51% had CCI score ≥ 1. Cox regression selected international staging system (ISS) = III (hazard ratio [HR] = 1.6; P = .033), PS = 2-4 (HR = 2.5; P = .007), and CCI = 1-3 (HR = 2.1; P = .028) as factors associated with a worse overall survival. A VS including PS and CCI predicted median survival of 27 months in the 63 patients having a VS = 2 (both PS = 2-4 and CCI = 1-3) versus not reached (NR) in the 203 patients with VS = 0-1 (HR = 4.0; P < .0001). In younger patients multivariate analysis selected ISS = III (HR = 5.2; P = .006) and VS = 2 (HR = 5.5; P = .024) as factors associated with shorter survival whereas only VS = 2 (HR = 3.5; P = .002) affected worse survival in elderly. CONCLUSION: Such VS proved to be a powerful prognostic factor for survival of MM patients and it might be useful to identify true vulnerable patients regardless of age.

ThaDD plus high dose therapy and autologous stem cell transplantation does not appear superior to ThaDD plus maintenance in elderly patients with de novo multiple myeloma.

OBJECTIVES: With the aim to address the issue whether high-dose therapy (HDT) is required after new drugs combinations to improve outcome of elderly newly diagnosed multiple myeloma (MM) patients, we compared the toxicity and the outcome of ThaDD plus maintenance to those of ThaDD plus HDT-autologous stem cell transplantation (ASCT). METHODS: Sixty-two patients not eligible for HDT receiving six courses of ThaDD regimen plus maintenance with thalidomide were compared to 26 patients eligible for HDT treated with four courses of ThaDD followed by melphalan 100-200 mg/m(2) and ASCT. The two groups were matched for the main characteristics except for age favouring the HDT group. RESULTS AND CONCLUSIONS: Complete remission (CR) obtained with ThaDD plus maintenance was 24% whereas it was 57% after ThaDD plus HDT-ASCT (P = 0.0232). However, after a median follow-up of 36 months, median time to progression (TTP) and progression free survival (PFS) of the group of patients undergone HDT were not significantly different to those of patients receiving ThaDD plus maintenance (32 vs. 31 months: P = 0.962; 32 vs. 29 months: P = 0.726, respectively). Five-year overall survival (OS) was 49% in the first group and 46% in the latter one (P = 0.404). As expected, a significantly higher incidence of grade 3-4 neutropenia, thrombocytopenia, infections, mucositis and alopecia were observed in the ThaDD plus HDT group. Our results suggest that in elderly MM patients ThaDD plus HDT, albeit significantly increases CR rate, seems to be equivalent to ThaDD plus maintenance in terms of TTP, PFS and OS. These results challenge the requirement for HDT consolidation in this subset of patients.

Thalidomide-dexamethasone versus interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study.

Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive alpha-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P = 0.024) and overall survival (84% vs. 68%; P = 0.030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm (P = 0.014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.

Serum C-reactive protein at diagnosis and response to therapy is the most powerful factor predicting outcome of multiple myeloma treated with thalidomide/ anthracycline-based therapy.

BACKGROUND: Few studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy. PATIENTS AND METHODS: Sixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (> or = very good partial remission [VGPR] vs. < VGPR], PFS, and OS. RESULTS: Overall, 45 patients (68%) showed response > or = VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment > or = VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy > or = VGPR (P = .019). CONCLUSION: Serum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide-based therapy.

Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma.

We present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria. Seventeen (34%) patients achieved CR, 7 (14%) nCR, 5 (10%) VGPR, 15 (30%) PR, and 5 (10%) MR, resulting in an ORR of 98%. Only 1 patient (2%) presented progressive disease. Time to progression (TTP), event-free survival (EFS), and overall survival (OS) projected at 3 years were 60%, 57%, and 74%, respectively, and these parameters were significantly higher in those patients achieving a response of at least VGPR versus those who did not. Grade 3 and 4 nonhematologic adverse events were constipation (10%), fatigue (6%), tremors (4%), mucositis (4%), and palmar-plantar erythrodysesthesia (2%). Grade 3 and 4 neutropenia occurred in 12% of patients. Grade 3 and 4 infections and thromboembolic accidents were observed in 22% and 14% of patients, respectively. In the treatment of elderly patients with newly diagnosed multiple myeloma, ThaDD is a very effective regimen with manageable toxicity.

Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter, phase II study.

The aim of this prospective, multicenter, phase II study was to investigate the combination of pegylated liposomal doxorubicin (Caelyx) 40 mg/m2 on day 1 every 28 days, dexamethasone 40 mg p.o. on days 1-4 and 9-12 and thalidomide 100 mg daily in 50 patients with advanced multiple myeloma. Twenty-six percent of patients achieved a complete response, 6% a near complete response, 6% a very good partial response, 38% a partial response, 16% a minor response and 8% progressed, for an overall response rate of 92%. The median event-free survival was 17 months and the median overall survival was not reached. Grade 3 non-hematologic toxicity occurred in 12% of patients, thromboembolic disease in 12% and severe infection in 16%. The combination of pegylated liposomal doxorubicin, dexamethasone an thalidomide is safe and very effective in advanced multiple myeloma.

[Electrical cardioversion for atrial fibrillation: advantages of the transthoracic biphasic method]. / Cardioversione elettrica della fibrillazione atriale: vantaggio della cardioversione transtoracica ad onda bifasica.

BACKGROUND: The purpose of this study was to evaluate efficacy and safety of biphasic shock for atrial fibrillation cardioversion to sinus rhythm. A second endpoint was to evaluate myocardial damage by means of cardiac troponin I dosage. METHODS: We studied 164 patients, with drug-resistant atrial fibrillation (208 episodes). Group A patients underwent biphasic shock normalized with respect to weight: 50 J (weight < 60 kg), 70 J (weight 61-84 kg) and 100 J (weight > 84 kg; the second and third shocks were 2 and 3 times higher than the first. Group B underwent sequential monophasic shock of 200, 300 and 360 J. Troponin I was evaluated at baseline, and 6, 12 and 24 hours after cardioversion. RESULTS: Total efficacy was 92% for biphasic shock and 89% for monophasic shock. First-shock efficacy with biphasic waveform (57.3%) was significantly greater than with first monophasic waveform (21.5%) (p = 0.000). Cardiac troponin I increased from 0.4 +/- 1.1 to 0.8 +/- 2.2 compared to a normal value of 2 ng/ml. CONCLUSIONS: For transthoracic cardioversion of atrial fibrillation, biphasic shock has a greater efficacy requiring less energy compared to monophasic shock. Normal mean values of cardiac troponin I proved the absence of myocardial damage.