Comorbidity and multimorbidity in patients with cirrhosis, hospitalised in an internal medicine ward: a monocentric, cross-sectional study.

OBJECTIVES: There are no data regarding the prevalence of comorbidity (ie, additional conditions in reference to an index disease) and multimorbidity (ie, co-occurrence of multiple diseases in which no one holds priority) in patients with liver cirrhosis. We sought to determine the rate and differences between comorbidity and multimorbidity depending on the aetiology of cirrhosis. DESIGN: This is a subanalysis of the San MAtteo Complexity (SMAC) study. We have analysed demographic, clinical characteristics and rate of comorbidity/multimorbidity of patients with liver cirrhosis depending on the aetiology-alcoholic, infectious and non-alcoholic fatty liver disease (NAFLD). A multivariable analysis for factors associated with multimorbidity was fitted. SETTING: Single-centre, cross-sectional study conducted in a tertiary referral, academic, internal medicine ward in northern Italy (November 2017-November 2019). PARTICIPANTS: Data from 1433 patients previously enrolled in the SMAC study were assessed; only those with liver cirrhosis were eventually included. RESULTS: Of the 1433 patients, 172 (median age 79 years, IQR 67-84; 83 females) had liver cirrhosis. Patients with cirrhosis displayed higher median Cumulative Illness Rating Scale (CIRS) comorbidity (4, IQR 3-5; p=0.01) and severity (1.85, IQR 16.-2.0; p<0.001) indexes and lower educational level (103, 59.9%; p=0.003). Patients with alcohol cirrhosis were significantly younger (median 65 years, IQR 56-79) than patients with cirrhosis of other aetiologies (p<0.001) and more commonly males (25, 75.8%). Comorbidity was more prevalent in patients with alcohol cirrhosis (13, 39.4%) and multimorbidity was more prevalent in viral (64, 81.0%) and NAFLD (52, 86.7%) cirrhosis (p=0.015). In a multivariable model for factors associated with multimorbidity, a CIRS comorbidity index >3 (OR 2.81, 95% CI 1.14 to 6.93, p=0.024) and admission related to cirrhosis (OR 0.19, 95% CI 0.07 to 0.54, p=0.002) were the only significant associations. CONCLUSIONS: Comorbidity is more common in alcohol cirrhosis compared with other aetiologies in a hospital, internal medicine setting.

Rate and risk factors of in-hospital and early post-discharge mortality in patients admitted to an internal medicine ward.

BACKGROUND: We sought to quantify in-hospital and early post-discharge mortality rates in hospitalised patients. METHODS: Consecutive adult patients admitted to an internal medicine ward were prospectively enrolled. The rates of in-hospital and 4-month post-discharge mortality and their possible associated sociodemographic and clinical factors (eg Cumulative Illness Rating Scale [CIRS], body mass index [BMI], polypharmacy, Barthel Index) were assessed. RESULTS: 1,451 patients (median age 80 years, IQR 69-86; 53% female) were included. Of these, 93 (6.4%) died in hospital, while 4-month post-discharge mortality was 15.9% (191/1,200). Age and high dependency were associated (p<0.01) with a higher risk of in-hospital (OR 1.04 and 2.15) and 4-month (HR 1.04 and 1.65) mortality, while malnutrition and length of stay were associated (p<0.01) with a higher risk of 4-month mortality (HR 2.13 and 1.59). CONCLUSIONS: Several negative prognostic factors for early mortality were found. Interventions addressing dependency and malnutrition could potentially decrease early post-discharge mortality.

Resilience is associated with frailty and older age in hospitalised patients.

BACKGROUND: Little is known about resilience in an internal medicine setting. We aimed to assess the relationship between resilience and frailty and other clinical and sociodemographic characteristics in a cohort of prospectively enrolled hospitalised patients. METHODS: In 2017-2019, we consecutively enrolled patients in our internal medicine wards. We selected all patients who filled in the 25-item Connor-Davidson resilience scale (CD-RISC). Mean resilience was evaluated according to baseline demographic (i.e., age, sex, marital and socioeconomic status) and clinical (i.e., Cumulative Illness Rating Scale [CIRS], Edmonton Frail Scale [EFS], Barthel index, Short Blessed test, length of stay [LOS]) data. A multivariable analysis for assessing factors affecting resilience was fitted. RESULTS: Overall, 143 patients (median age 69 years, interquartile range 52-79, 74 females) were included. Resilience was significantly lower in frail (p = 0.010), elderly (p = 0.021), dependent (p = 0.032), and more clinically (p = 0.028) and cognitively compromised patients (p = 0.028), and in those with a low educational status (p = 0.032). No relation between resilience and LOS was noticed (p = 0.597). Frail patients were significantly older (p < 0.001), had a greater disease burden as measured by CIRS comorbidity (p < 0.001) and severity indexes (p < 0.001), were more dependent (p < 0.001), more cognitively impaired (p < 0.001), and displayed a lower educational level (p = 0.011) compared to non-frail patients. At multivariable analysis, frailty (p = 0.022) and dependency (p = 0.031; according to the Barthel index) were associated with lower resilience in the age groups 18-64 and ≥ 65 years, respectively. CONCLUSIONS: Low resilience was associated with frailty and dependency with an age-dependent fashion. Studies assessing the impact of this finding on important health outcomes are needed. TRIAL REGISTRATION: Clinical Complexity in Internal Medicine Wards. San MAtteo Complexity Study (SMAC); NCT03439410 . Registered 01/11/2017.

Aging underlies heterogeneity between comorbidity and multimorbidity frameworks.

Studies exploring differences between comorbidity (i.e., the co-existence of additional diseases with reference to an index condition) and multimorbidity (i.e., the presence of multiple diseases in which no one holds priority) are lacking. In this single-center, observational study conducted in an academic, internal medicine ward, we aimed to evaluate the prevalence of patients with two or more multiple chronic conditions (MCC), comorbidity, or multimorbidity, correlating them with other patients' characteristics. The three categories were compared to the Cumulative Illness Rating Scale (CIRS) comorbidity index, age, gender, polytherapy, 30-day readmission, in-hospital and 30-day mortalities. Overall, 1394 consecutive patients (median age 80 years, IQR 69-86; F:M ratio 1.16:1) were included. Of these, 1341 (96.2%; median age 78 years, IQR 65-84; F:M ratio 1.17:1) had MCC. Fifty-three patients (3.8%) had no MCC, 286 (20.5%) had comorbidity, and 1055 (75.7%) had multimorbidity, showing a statistically significant (p < 0.001) increasing age trend (median age 38 years vs 71 vs 82, respectively) and increasing mean CIRS comorbidity index (1.53 ± 0.95 vs 2.97 ± 1.43 vs 4.09 ± 1.70, respectively). The CIRS comorbidity index was always higher in multimorbid patients, but only in the subgroups 75-84 years and ≥ 85 years was a significant (p < 0.001) difference (1.24 and 1.36, respectively) noticed. At multivariable analysis, age was always independently associated with in-hospital mortality (p = 0.002), 30-day mortality (p < 0.001), and 30-day readmission (p = 0.037), while comorbidity and multimorbidity were not. We conclude that age determines the most important differences between comorbid and multimorbid patients, as well as major outcomes, in a hospital setting.

A New Lung Ultrasound Protocol Able to Predict Worsening in Patients Affected by Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate severe pneumonia associated with high mortality. A bedside lung ultrasound (LUS) examination has been shown to have a potential role in this setting. The purpose of this study was to evaluate the potential prognostic value of a new LUS protocol (evaluation of 14 anatomic landmarks, with graded scores of 0-3) in patients with SARS-CoV-2 pneumonia and the association of LUS patterns with clinical or laboratory findings. METHODS: A cohort of 52 consecutive patients with laboratory-confirmed SARS-CoV-2 underwent LUS examinations on admission in an internal medicine ward and before their discharge. A total LUS score as the sum of the scores at each explored area was computed. We investigated the association between the LUS score and clinical worsening, defined as a combination of high-flow oxygen support, intensive care unit admission, or 30-day mortality as the primary end point. RESULTS: Twenty (39%) patients showed a worse outcome during the observation period; the mean LUS scores ± SDs were 20.4 ± 8.5 and 29.2 ± 7.3 in patients without and with worsening, respectively (P < .001). In a multivariable analysis, adjusted for comorbidities (>2), age (>65 years), sex (male), and body mass index (≥25 kg/m2 ), the association between the LUS score and worsening (odds ratio, 1.17; 95% confidence interval, 1.05 to 1.29; P = .003) was confirmed, with good discrimination of the model (area under the receiver operating characteristic curve, 0.82). A median LUS score higher than 24 was associated with an almost 6-fold increase in the odds of worsening (odds ratio, 5.67; 95% confidence interval, 1.29 to 24.8; P = .021). CONCLUSIONS: Lung ultrasound can represent an effective tool for monitoring and stratifying the prognosis of patients with SARS-CoV-2 pulmonary involvement.

Clinical complexity and hospital admissions in the December holiday period.

BACKGROUND: Christmas and New Year's holidays are risk factors for hospitalization, but the causes of this "holiday effect" are uncertain. In particular, clinical complexity (CC) has never been assessed in this setting. We therefore sought to determine whether patients admitted to the hospital during the December holiday period had greater CC compared to those admitted during a contiguous non-holiday period. METHODS: This is a prospective, longitudinal study conducted in an academic ward of internal medicine in 2017-2019. Overall, 227 consecutive adult patients were enrolled, including 106 cases (mean age 79.4±12.8 years, 55 females; 15 December-15 January) and 121 controls (mean age 74.3±16.6 years, 56 females; 16 January-16 February). Demographic characteristics, CC, length of stay, and early mortality rate were assessed. Logistic regression analyses for the evaluation of independent correlates of being a holiday case were computed. RESULTS: Cases displayed greater CC (17.7±5.5 vs 15.2±5.9; p = 0.001), with greater impact of socioeconomic (3.51±1.7 vs 2.9±1.7; p = 0.012) and behavioral (2.36±1.6 vs 1.9±1.8; p = 0.01) CC components. Cases were also significantly frailer according to the Edmonton Frail Scale (8.0±2.8 vs 6.4±3.1; p<0.001), whilst having similar disease burden, as measured by the CIRS comorbidity index. Age (OR 1.02; p = 0.039), low income (OR 1.97, 95% CI 1.10-3.55; p = 0.023), and total CC (OR 1.06; p = 0.014) independently correlated with the cases. Also, cases showed a longer length of stay (median 15.5 vs 11 days; p = 0.0016) and higher in-hospital (12 vs 4 events; p = 0.021) and 30-day (14 vs 6 events; p = 0.035) mortality. CONCLUSIONS: Patients hospitalized during the December holiday period had worse health outcomes, and this could be attributable to the grater CC, especially related to socioeconomic (social deprivation, low income) and behavioral factors (inappropriate diet). The evaluation of all CC components could potentially represent a useful tool for a more rational resource allocation over this time of the year.

Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes.

Chronic heart failure (CHF) is characterized by an ongoing nonresolving inflammatory status, where T lymphocytes seem critical. It has been recently recognized that transition from acute to chronic inflammation could be caused by defects in resolving inflammation, the resolution of which is mediated by a novel family of ω-3-derived specialized proresolving lipid mediators such as resolvins. We analyzed 27 elderly patients with CHF and 23 healthy age-matched control subjects, and we reported significantly lower levels of D-series resolvin (RvD)1 in plasma of patients with CHF that were associated with a reduced ability of their leukocytes to produce this lipid via its biosynthetic enzyme 15-lipoxygenase and that correlated with gas exchange dysfunction. Furthermore, when pretreating ex vivo peripheral blood mononuclear cells of patients with CHF with RvD1 or RvD2, we found that neither of them was able to modulate the immune response of CD8+ and CD4+ T cells in terms of proinflammatory cytokine production, namely TNF-α, IFN-γ, IL-17, and IL-2. Such impaired T-cell responsiveness in patients with CHF was associated with a significant reduction in mRNA and protein expression of RvD1 receptor GPR32, suggesting a defective signaling in the proresolving pathway. We conclude that patients with CHF show alterations in producing proresolving mediator RvD1 and a failure of adaptive immune cells in responding to the anti-inflammatory actions of RvDs that may contribute to the progression of chronic inflammation. Thus, the proresolution pathway might be a potential candidate to design better treatments for CHF aimed at reducing T cell-mediated chronic inflammation.-Chiurchiù, V., Leuti, A., Saracini, S., Fontana, D., Finamore, P., Giua, R., Padovini, L., Incalzi, R. A., Maccarrone, M. Resolution of inflammation is altered in chronic heart failure and entails a dysfunctional responsiveness of T lymphocytes.