Contribution of clinical severity and geriatric risk factors in predicting short-term mortality of older hospitalized pneumonia patients: the Pneumonia in Italian Acute Care for Elderly units (PIACE) study.

BACKGROUND: Clinical severity of pneumonia in older persons increases the risk for short-term mortality. Comprehensive geriatric assessment (CGA) may provide further insight in prognostic stratification. AIMS: To investigate whether CGA may improve prognostic stratification among older patients with pneumonia admitted to hospital. METHODS: Our series consisted of 318 consecutive patients hospitalized for pneumonia in a multicenter observational study. Disease severity was assessed by Sequential Organ Failure Assessment (SOFA) and Pneumonia Severity Index (PSI). CGA included the occurrence of delirium, Basic Activities of Daily Living (BADL) disability, cognitive impairment at Short Portable Mental Status Questionnaire (SPMSQ) and overall comorbidity assessed by Cumulative Illness Rating Scale (CIRS). The outcomes were in-hospital and post-discharge 3 month mortality. Statistical analysis was carried out by Cox regression, area under receiver operating curve (AUC) and net reclassification index (NRI). RESULTS: Overall, 53 patients died during hospitalization and 52 after discharge. Delirium, SOFA score and admission BADL disability were significant predictors of in-hospital mortality. SOFA score, CIRS, previous long-term oxygen therapy and discharge BADL dependency significantly predicted post-discharge mortality. The accuracy of SOFA in predicting in-hospital and post-discharge mortality was fair (AUC = 0.685, 95% CI = 0.610-0.761 and AUC = 0.663, 95% CI = 0.593-0.734, respectively). BADL dependency and delirium improved predictive accuracy for in-hospital mortality (ΔAUC = 0.144, 95% CI = 0.062-0.227, p < 0.001), while pre-admission oxygen therapy, CIRS and BADL dependency improved predictivity for 3 month mortality (ΔAUC = 0.177, 95% CI = 0.102-0.252, p < 0.001). DISCUSSION: Among older pneumonia patients, prognostic stratification obtained by clinical severity indexes is significantly improved by CGA risk factors. CONCLUSIONS: CGA provides important information for prognostic stratification and clinical management of older pneumonia patients.

The Respiratory "Overlap Syndrome": Efficacy and Usefulness of the Combined Double Bronchodilation.

The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome in a single patient is known as "overlap syndrome," and worsens the prognosis of the affected subjects. A marked bronchodilation may be useful for the treatment of this condition. In fact, as stated in the GOLD 2017 guidelines, the combination of indacaterol/glycopyrronium may exert positive synergistic effects on smooth muscle cell and airway resistance, with a more pronounced efficiency in reducing lung hyperinflation. Noteworthy, inhaled bronchodilators favorably alter the dynamically determined components of resting lung hyperinflation and help deflate the overinflated lungs. This is particularly important in order to improve dyspnea, exercise performance, and night saturation, especially when combined with continuous positive airway pressure ventilation, as reported in our case series. We report 3 cases of patients with COPD in a stable clinical condition, referred to the Department of Respiratory Pathophysiology at the "Mariano Santo" Hospital in Cosenza, due to possible symptoms suggestive of obstructive sleep apnea, and who were successfully treated with indacaterol/glycopyrronium at a fixed dose.

Clinical outcomes and phenotypes of respiratory failure in older subjects admitted to an acute care geriatric hospital ward.

Respiratory failure (RF) is frequent in hospitalized older patients, but was never systematically investigated in large populations of older hospitalized patients. We conducted a retrospective administrative study based on hospitalizations of a Geriatrics Unit regarding 2014, 2015, and 2016. Patients underwent daily screening for hypoxia. Hospital discharge records were coded through a standardized methodology. RF, defined as documented hypoxia on room air, was always coded, whenever present. We investigated how RF affected clinical outcomes, whether RF grouped into specific comorbidity phenotypes, and how phenotypes associated with the outcomes. RF was coded in 48.6% of the 1,810 hospitalizations. RF patients were older and more frequently had congestive heart failure (CHF: 49 vs 23%), chronic obstructive pulmonary disease (COPD: 27 vs 6%), pneumonia (14 vs 4%), sepsis (12 vs 7%), and pleural effusion (6 vs 3%), than non-RF patients. RF predicted longer length of stay (a-Beta 2.05, 95% CI 1.4-2.69; p < 0.001) and higher in-hospital death/intensive care units (ICU) need (aRR 7.12, 5-10.15; p < 0.001) after adjustment for confounders (linear and Poisson regression with robust error variance). Among RF patients, cerebrovascular disease, cancer, electrolyte disturbances, sepsis, and non-invasive ventilation predicted increased, while CHF and COPD predicted decreased in-hospital death/ICU need. The ONCO (cancer) and Mixed (cerebrovascular disease, dementia, pneumonia, sepsis, electrolyte disturbances, bedsores) phenotypes displayed higher in-hospital death/ICU need than CARDIO (CHF) and COPD phenotypes. In this study, RF predicted increased hospital death/ICU need and longer hospital stay, but also reflected diverse underlying conditions and clinical phenotypes that accounted for different clinical courses.

Association of age with emergency department visits and hospital admissions: A nationwide study.

AIM: Older adults are frequently stigmatized for improper emergency department (ED) visits and hospitalizations. In this study, we aimed to investigate the relationship between age and appropriateness of ED visits, and the mismatching between ED clinical severity and hospitalizations. METHODS: We carried out a nationwide assessment of Italian Informative System for the Emergency and Urgency data from 1 January 2015 to 31 December 2015 including patients admitted to all the Italian EDs for any reason. Appropriateness of ED visits was defined as a yellow/red/black color code (potentially life-threatening/dead patients), whereas clinical severity/hospitalization mismatching was defined as hospital admission after validated ED green/white codes. Analyses dedicated to people aged ≥75 years were carried out. RESULTS: There were 20 400 071 ED visits (3 444 091 aged ≥75 years), which increased with age, up to >650/1000 inhabitants aged ≥90 years. The appropriateness of ED visits increased with age, from 6.3% in the 5-9 years age group to 44.2% in the 95-99 years age group. Clinical severity/hospitalization mismatching decreased with age, from 62.9% in the 30-34 years age group to 27.7% in the 95-99 years age group. At ED presentation, 21.6% of patients aged ≥75 years complained of non-specific symptoms, and hospital discharge diagnoses frequently differed from the ED admission diagnoses; 11.4% died during hospitalization and 8.8% were discharged to long-term care facilities. CONCLUSIONS: The request for ED care and the admission to acute care ward are commonly appropriate for older patients. Clinical presentation at ED admission is frequently atypical. Health care systems should aim at improving outpatients' management to reduce the ED care need, but also at optimizing in-hospital strategies and pathways for older adults. Geriatr Gerontol Int 2022; 22: 917-923.

Erlotinib-induced hepatitis complicated by fatal lactic acidosis in an elderly man with lung cancer.

OBJECTIVE: To report a case of erlotinib-induced hepatitis complicated by fatal lactic acidosis in an elderly patient with lung adenocarcinoma and diabetes mellitus. CASE SUMMARY: A 77-year-old man with stage IIIB lung adenocarcinoma was treated with erlotinib 100 mg/day, an epidermal growth factor receptor inhibitor, after failure of chemotherapy and radiotherapy. The patient also had type 2 diabetes mellitus; metformin therapy had been initiated 5 years before presentation. Twelve days after the start of erlotinib therapy, he developed drug-related acute hepatitis complicated by renal deterioration (aspartate aminotransferase 1400 U/L, alanine aminotransferase 1299 U/L, creatinine 4.4 mg/dL, urea nitrogen 55 mg/dL). Viral causes of hepatitis were excluded and a recent computed tomography scan had ruled out liver metastases. According to the Roussel-Uclaf causality assessment method, the erlotinib-related hepatitis was classified as probable. The patient's condition was soon complicated by the onset of lactic acidosis, which caused death 2 hours after admission. DISCUSSION: In this patient, lactic acidosis was promoted by erlotinib-related hepatitis with initial liver failure (decreased lactate clearance), concomitant metformin treatment (increased lactate production), and acute renal deterioration (metformin accumulation). This is the second case of fatal erlotinib-induced liver toxicity in a patient with lung cancer. In the previous case, death occurred after about 11 days and was entirely due to fulminant hepatitis, whereas in our patient, the liver injury only initiated a drug-disease interaction that caused fatal lactic acidosis within a few hours. CONCLUSIONS: Liver function should be carefully monitored during erlotinib treatment, particularly in elderly and frail patients on multiple medications. Further studies are therefore needed for better testing the safety of erlotinib in such people, commonly encountered in the real world, but often excluded from participation in randomized trials of cancer treatment.

The association between metabolic syndrome and restrictive ventilatory dysfunction in older persons.

BACKGROUND: The restrictive, but not the obstructive respiratory dysfunction, is associated with an increased risk of developing type 2 diabetes mellitus. Our aim was to verify in an elderly nondiabetic population whether a restrictive respiratory pattern was associated with a higher prevalence of metabolic syndrome and increased insulin resistance than were obstructive and normal respiratory patterns. METHODS: We performed a cross-sectional study of 159 consecutive nondiabetic elderly persons attending two social centers. According to their spirometric pattern, volunteers were classified into the following categories: normal spirometry, obstructive (forced expiratory volume in 1 second/forced vital capacity<0.70), and restrictive pattern (forced vital capacity<80% predicted, forced expiratory volume in 1 second/forced vital capacity>or=0.70). Independent correlates of the metabolic syndrome were identified. RESULTS: The prevalence of metabolic syndrome was higher in restrictive (56%) than in both normal (21.4%, p=.001) and obstructive volunteers (12.9%, p=.001). Insulin resistance, as assessed by the log transformation of the HOmeostasis Model Assessment (HOMA), was higher in restrictive than in obstructive and normal volunteers (1+/-0.6 vs 0.3+/-0.6 and 0.5+/-0.5, p<.001). Restriction was an independent correlate of metabolic syndrome, also after adjustment for waist circumference and body mass index (odds ratio=3.23, 95% confidence interval, 1.23-8.48; p=.01). CONCLUSION: Restrictive, but not obstructive respiratory pattern, is associated with metabolic syndrome and insulin resistance, and does not only reflect a limitation of ventilation due to visceral obesity. Metabolic abnormalities likely mediate cardiovascular risk in patients with restrictive respiratory impairment.

The Severity of Acute Illness and Functional Trajectories in Hospitalized Older Medical Patients.

BACKGROUND: Acute diseases and hospitalization are associated with functional deterioration in older persons. Although most of the functional decline occurs before hospitalization in response to the acute diseases, the role played by comorbidity in the functional trajectories around hospitalization is unclear. METHODS: Observational prospective study of 696 elderly individuals hospitalized in two Italian general medicine wards. Functional status of the elderly patients at 2 weeks before hospitalization (baseline), at hospital admission, and at discharge was measured by the Barthel Index. Comorbidity was measured at admission by the Geriatric Index of Comorbidity (GIC), a tool mostly based on illness severity. The association of GIC with changes in functional status before hospitalization (between baseline and admission), during hospitalization (between admission and discharge), and in the overall period between baseline and discharge was assessed by logistic regression analyses. Hospitalization-associated disability (HAD) was defined as a functional decline between baseline and discharge. RESULTS: Illness severity (GIC 3-4 vs 1-2: odds ratio [OR] 2.2, 95% CI [confidence interval] 1.5-3.3, p < .0001) and older age significantly predicted prehospital functional decline (between baseline and admission). Illness severity (OR 1.9, 95% CI 1.2-3, p = .004) and older age were also predictive of HAD, even after adjustment for each coded primary discharge diagnosis. After adjustment for the occurrence of prehospital functional decline, however, illness severity and older age were not predictive of HAD anymore. CONCLUSIONS: The severity of illnesses was strongly associated with adverse functional outcomes around hospitalization, but frailty, intended as functional vulnerability to the acute disease before hospitalization, was a stronger predictor of HAD than illness severity and age.

Age, cancer and the risk of venous thromboembolism.

Cancer increases the risk for venous thromboembolism (VTE) and patients presenting with a seemingly idiopathic VTE often have an occult cancer. Aging also is a risk factor for VTE. Therefore, old patients with cancer are supposed to be at very high risk for VTE, but inherent data are sporadic and contrasting. We reviewed the literature about the relation between cancer and VTE, with particular attention to findings concerning elderly patients. While aging and postmenopausal status enhance the risk of chemotherapy-induced VTE in women with breast cancer, the rate of a cancer diagnosis in the first year after VTE seems to be even lower in elderly compared to young subjects. Thus, further studies are needed to understand whether or not aging and cancer have additive thrombogenic effects. Finally, we discuss prophylactic and therapeutic strategies.

The association between hyperhomocysteinemia and ischemic stroke in patients with non-valvular atrial fibrillation.

BACKGROUND AND OBJECTIVES: Atrial fibrillation is complicated by a high rate of ischemic stroke. Previous studies have shown that an increased level of circulating total plasma homocysteine (tHcy) is an independent predictor of stroke, but it is unclear whether it is also predictive of stroke in patients with atrial fibrillation. The objective of this study was to evaluate whether increased tHcy is an independent predictor of cardio-embolic stroke in patients with non-valvular atrial fibrillation. DESIGN AND METHODS: We studied 163 consecutive patients (77 males and 86 females; mean age 72.3+/-8.8 years) with permanent (n=118) or paroxysmal (n=45) atrial fibrillation of non-valvular origin hospitalized for cardiac reasons. Ischemic stroke, documented by nuclear magnetic resonance or computerized tomography imaging, had occurred at an average of 2 years before hospitalization in 40 patients (16 males and 24 females, mean age 74.8+/-8.8 years). Fasting tHcy levels were determined by high performance liquid chromatography. RESULTS: Multivariate analysis adjusting for traditional cardiovascular risk factors, thromboembolic risk factors and predictors of tHcy (glomerular filtration rate, uric acid, gender) and fibrinogen levels (age, alcohol intake) showed that total homocysteine (OR: 1.056; for each 1 micromol/L increase, 95% C.I.: 1.00-1.12; p=0.042) and fibrinogen (OR: 1.008 for each 1 mg/dL increase; 95% C.I.: 1.00-1.014; p=0.016) were independently associated with ischemic stroke. With respect to patients in the first quartile of the tHcy distribution (4.6-7.5 micromol/L), patients in the fourth quartile of the tHcy distribution (18.7-67.1 micromol/L) had a 2.73-fold increased probability of ischemic stroke INTERPRETATION AND CONCLUSIONS: In patients with non-valvular atrial fibrillation hospitalized for cardiac reasons, increased fasting tHcy levels are independently associated with a history of ischemic stroke.

Acute functional decline before hospitalization in older patients.

AIMS: Acute diseases and related hospitalization are crucial events in the disabling process of elderly individuals. Most of the functional decline occurs in the few days before hospitalization, as a result of acute diseases in vulnerable patients. The aim of the present study was to identify determinants of prehospital components of functional decline. METHODS: This was a prospective observational study carried out in three acute geriatric units and two general medicine units of three Italian hospitals. The participants were 1281 patients aged 65 years or older admitted to hospital for acute illnesses and discharged alive. Functional status 2 weeks before hospitalization (preadmission) and at hospital admission was measured by the Barthel Index to identify patients with prehospital decline. In this group of decliners, the percentage extent of prehospital decline (PEPD) was also calculated. RESULTS: Prehospital decline occurred in 541 (42.2%) patients, who were hospitalized mostly in geriatric wards (55.6%). Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.04-1.08) and dementia (OR 2.8, 95% CI 1.4-5.4) were significant predictors of prehospital decline, whereas a high preadmission function was protective (OR 0.992, 95% CI 0.987-0.997). Pulmonary disease as primary discharge diagnosis was also associated with prehospital decline (OR 1.8, 95% CI 1.3-2.5) after adjustment for age, diagnosis of dementia and preadmission function. Amongst decliners, a low preadmission function and the origin of patients (from emergency rooms or other hospital units) were associated with larger PEPD. CONCLUSIONS: Using a clinically meaningful change to define decline, disease-related prehospital disability is observed mainly in persons with low preadmission function, older age and dementia.

Lung function changes in older people with metabolic syndrome and diabetes.

AIM: Restrictive lung dysfunction (RLD; defined as reduced forced vital capacity [FVC] in the presence of normal forced expiratory volume in 1 s [FEV1]/FVC ratio) is highly prevalent in the elderly, and is associated with diabetes, metabolic syndrome (MetS) and abdominal obesity. The aim of this study was to assess the relative contribution of diabetes, MetS and abdominal obesity in characterizing RLD in the elderly. METHODS: This was cross-sectional analysis of 192 consecutive, community-dwelling persons (mean age 70.8 ± 8 years). The participants were grouped according to the number of MetS components (i.e. 0, 1, 2, 3 or 4) and the presence of diabetes. According to the Adult Treatment Panel-III criteria, participants with three or four components were considered to be affected by MetS. Independent correlates of RLD and obstructive lung dysfunction (OLD; FEV1/FVC < 0.70) were assessed by logistic regression models. RESULTS: The mean age of the sample population was 70.8 years. FVC expressed as percent of the predicted value declined for an increasing number of MetS components (P < 0.0001), but diabetes did not account for further ventilatory decline. Consistently, MetS (OR 3.03, 95% CI 1.16-7.89) and abdominal obesity (OR 4.89, 95% CI 1.17-20.3), but not diabetes, were independently associated with RLD. OLD did not worsen for an increasing number of MetS components and was only related to age (OR 1.07, 95% CI 1.01-1.13) and smoking (OR 1.04, 95% CI 1.01-1.06). CONCLUSIONS: MetS and abdominal obesity, two conditions of prediabetes, but not diabetes itself, are closely associated with RLD. These conditions might be implicated in the pathogenesis of the RLD, which is frequently observed in diabetic patients.

Functional recovery of elderly patients hospitalized in geriatric and general medicine units. The PROgetto DImissioni in GEriatria Study.

OBJECTIVES: To investigate the characteristics of patients who regain function during hospitalization and the differences in terms of functional outcomes between patients admitted to geriatric and general medicine units. DESIGN: Multicenter, prospective cohort study. SETTING: Acute care geriatric and medical wards of five Italian hospitals. PARTICIPANTS: One thousand forty-eight elderly patients hospitalized for acute medical diseases. MEASUREMENTS: Functional status 2 weeks before hospital admission (baseline), at admission, and at discharge, as measured using the Barthel Index (BI). RESULTS: Geriatric patients were older (P<.001) and had lower preadmission functional levels (P<.001) than medical patients. Between baseline and discharge, 43.2% of geriatric and 18.9% of medical patients declined in physical function. In the subpopulation of 464 patients who had declined before hospitalization (between baseline and admission), 59% improved during hospitalization (45% of geriatric and 75% of medical patients), whereas only approximately 1% declined further. High baseline function (odds ratio (OR)=1.03, 95% confidence interval (CI)=1.02-1.04, per point of BI) and greater functional decline before hospitalization (OR 0.95, 95% CI 0.94-0.97, per % point of BI decline) were significant predictors of in-hospital functional improvement; type of hospital ward and age were not. CONCLUSION: Although geriatric patients have overall worse functional outcomes, in-hospital functional recovery may be frequent even in geriatric units, particularly in patients with greater preadmission functional loss and high baseline level of function.

Why are people with "poor lung function" at increased atherothrombotic risk? A critical review with potential therapeutic indications.

Patients classified as having a "poor lung function" in large populations studies are at increased risk of atherothrombosis, but potential mechanisms are unclear. A large proportion of these people are affected by chronic obstructive pulmonary disease (COPD), a recognized risk factor for vascular events. Systemic inflammation is the main atherothrombotic abnormality in COPD, but hypoxia-related platelet activation, pro-coagulant status and oxidative stress may play a role. Systemic inflammation is presumably a leading mechanism of atherothrombosis also in people who have a "restrictive" spirometric dysfunction, rather than the classic obstructive pattern of COPD. Many persons with "poor lung function" are affected by diabetes and their cardiovascular risk is therefore linked to the diabetic status. Patients affected by diabetes tend to have a "restrictive" dysfunction, rather than COPD. Recent studies show that restriction at spirometry precedes the onset of diabetes, thereby representing a marker of mechanisms involved in the pre-diabetic, insulin-resistant state. This is also proved by the fact that most patients with metabolic syndrome, a pre-diabetic condition, have a restrictive ventilatory pattern at spirometry. A significant proportion of people with "poor lung function" have visceral obesity, a cardiovascular risk factor. By hampering lung expansion, visceral obesity causes a restrictive ventilatory pattern. In conclusion, the term "poor lung function" includes various chronic illnesses with different mechanisms of atherothrombosis. Research is needed for better understanding why persons with lung dysfunctions have higher cardiovascular risk, and for identifying adequate preventive strategies.

Portal vein thrombosis in liver cirrhosis.

Portal vein thrombosis (PVT) is observed in 10-20% of patients with liver cirrhosis, which is responsible for 20% of all PVT cases. The main pathogenic factor of PVT in cirrhosis is the obstacle to portal flow, but acquired and inherited clotting abnormalities may play a role. The formation of collateral veins allows many patients to remain asymptomatic and prevents the onset of clinical complications also in patients with totally occlusive PVT. Gastrointestinal bleeding, thrombosis of superior mesenteric vein and refractory ascites are typical manifestations of PVT. Instrumental diagnosis can be obtained by colour-doppler ultrasonography. Future studies should verify whether asymptomatic PVT worsens liver failure, or if its life-threatening complications reduce survival in patients with cirrhosis. Moreover, randomized controlled trials should clarify the potential effectiveness of anticoagulant therapy in the treatment of PVT.