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Background/Objectives: Although SARS-CoV-2 infection is a significant risk factor for venous thromboembolism (VTE), data on the impact of the use of non-invasive ventilation support (NIVS) to mitigate the risk of VTE during hospitalization are scarce. Methods: Data for 1471 SARS-CoV-2 patients, hospitalized in a single hub during the first pandemic wave, were collected from clinical records, including symptom duration and type, information on lung abnormalities on chest computed tomography (CT), laboratory parameters and the use of NIVS. Determining VTE occurrence during hospital stays was the main endpoint. Results: Patients with VTE (1.8%) had an increased prevalence of obesity (26% vs. 11%), diabetes (41% vs. 21%), higher CHA2DS2VASC score (4, IQR 2–5 vs. 3, IQR 1–4, age- and sex-adjusted, p = 0.021) and cough (65% vs. 44%) and experienced significantly higher rates of NIVS (44% vs. 8%). Using a stepwise multivariate logistic regression model, the prevalence of electrocardiogram abnormalities (odds ratio (OR) 2.722, 95% confidence interval (CI) 1.039–7.133, p = 0.042), cough (OR 3.019, 95% CI 1.265–7.202, p = 0.013), CHA2DS2-VASC score > 3 (OR 3.404, 95% CI 1.362–8.513, p = 0.009) and the use of NIVS (OR 15.530, 95% CI 6.244–38.627, p < 0.001) were independently associated with a risk of VTE during hospitalization. NIVS remained an independent risk factor for VTE even after adjustment for the period of admission within the pandemic wave. Conclusions: Our study suggests that NIVS is a risk factor for VTE during hospitalization in SARS-CoV-2 patients. Future studies should assess the optimal prophylactic strategy against VTE in patients with a SARS-CoV-2 infection candidate to non-invasive ventilatory support. [ABSTRACT FROM AUTHOR]

Background/Objectives: Older patients are subject to a high number of Emergency Department (ED) visits and hospitalizations. Innovative strategies to manage geriatric urgencies in the community are thus needed. Methods: In this prospective observational study, we examined the case mix of a hospital-based domiciliary urgent care service tailored to older patients, called Multidisciplinary Mobile Unit (MMU), from January to September 2023. The service, activated by general practitioners or territorial specialists during workdays, provided domiciliary geriatric assessment, point-of-care diagnostics, including multi-site ultrasound and lab tests, and therapeutical measures, including intravenous treatment and insertion of invasive devices, with the goal of reaching on-site stabilization and avoiding ED referral. We collected data regarding multimorbidity, polypharmacy, and frailty according to the Clinical Frailty Scale (CFS), reasons for MMU activation, and diagnostic and therapeutical services provided. The assessed outcomes were immediate hospitalization after a visit, 30-day admission, and 30-day mortality. Results: Participants (n = 205, 102 M) were mostly aged (median age 83 years old), with multimorbidity and frailty (CFS median 6). The most frequent reasons for MMU activation were dyspnea (49%), cough (34%), and musculoskeletal pain (17%), while the commonest diagnostic test provided was thoracic ultrasound (81%). Only five patients (2.4%) were hospitalized immediately after MMU visit. The 30-day rate of hospitalization was 10.2%, with age, cancer, and abdominal pain as independent predictors on a stepwise binary logistic regression model. 30-day mortality was 4.9%. Conclusions: The MMU model is a feasible strategy to manage geriatric urgencies, especially involving the cardiorespiratory system, is associated with good outcomes and may prevent ED visits. [ABSTRACT FROM AUTHOR]

The aims of this study were to describe the characteristics of patients hospitalized with delta SARS-CoV-2 breakthrough infection, and to identify factors associated with pneumonia on chest Computed Tomography (CT) and mortality. The clinical records of 229 patients (105 F), with a median age of 81 (interquartile range, IQR, 73–88) years old, hospitalized between June and December 2021 after completion of the primary vaccination cycle, were retrospectively analyzed, retrieving data on comorbidities, Clinical Frailty Scale (CFS), clinical presentation and outcomes. Multimorbidity (91.7% with ≥2 chronic illnesses) and frailty (61.6% with CFS ≥ 5) were highly prevalent. CFS (OR 0.678, 95% CI 0.573–0.803, p < 0.001) and hypertension were independently associated with interstitial pneumonia. Mortality was 25.1% and unrelated with age. PaO2/FiO2 on blood gas analysis performed upon admission (OR 0.986, 95% CI 0.977–0.996, p = 0.005), and CFS (OR 1.723, 95% CI 1.152–2.576, p = 0.008) were independently associated with mortality only in subjects < 85 years old. Conversely, serum PCT levels were associated with mortality in subjects ≥ 85 years old (OR 3.088, 95% CI 1.389–6.8628, p = 0.006). In conclusion, hospitalization for COVID-19 breakthrough infection mainly involved geriatric patients, with those aged ≥ 85 more characterized by decompensation of baseline comorbidities rather than typical COVID-19 respiratory symptoms. [ABSTRACT FROM AUTHOR]

Animal studies increasingly indicate that the gut microbiota composition and function can be involved in the pathophysiology and progression of Alzheimer's disease (AD) at multiple levels. However, few studies have investigated this putative gut-brain axis in human beings, and none of them considered diet as a determinant of intestinal microbiota composition. Epidemiological studies highlight that a high intake of fruit and vegetables, such as that typical of the Mediterranean diet, can modulate AD progression. Thus, nutritional interventions are being increasingly studied as a possible non-pharmacological strategy to slow down the progression of AD. In particular, polyphenols and fibers represent the nutritional compounds with the higher potential of counterbalancing the pathophysiological mechanisms of dementia due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. These actions are mediated by the gut microbiota, that can transform polyphenols and fibers into biologically active compounds including, among others, phenyl-γ-valerolactones, urolithins, butyrate, and other short-chain fatty acids. In this review, the complex mechanisms linking nutrition, gut microbiota composition, and pathophysiology of cognitive decline in AD are discussed, with a particular focus on the role of polyphenols and fibers. The gaps between pre-clinical and clinical studies are particularly emphasized, as well as the urgent need for studies comprehensively evaluating the link between nutrition, microbiome, and clinical aspects of AD. [ABSTRACT FROM AUTHOR]

Background: Older patients evaluated in Emergency Departments (ED) for suspect Myocardial Infarction (MI) frequently exhibit unspecific elevations of serum high‐sensitivity troponin I (hs‐TnI), making interpretation particularly challenging for emergency physicians. The aim of this longitudinal study was to identify the interaction of multimorbidity and frailty with hs‐TnI levels in older patients seeking emergency care. Methods: A group of patients aged≥75 with suspected MI was enrolled in our acute geriatric ward immediately after ED visit. Multimorbidity and frailty were measured with Cumulative Illness Rating Scale (CIRS) and Clinical Frailty Scale (CFS), respectively. The association of hs‐TnI with MI (main endpoint) was assessed by calculation of the Area Under the Receiver‐Operating Characteristic Curve (AUROC), deriving population‐specific cut‐offs with Youden test. The factors associated with hs‐TnI categories, including MI, CFS and CIRS, were determined with stepwise multinomial logistic regression. The association of hs‐TnI with 3‐month mortality (secondary endpoint) was also investigated with stepwise logistic regression. Results: Among 268 participants (147 F, median age 85, IQR 80–89), hs‐TnI elevation was found in 191 cases (71%, median 23 ng/L, IQR 11–65), but MI was present in only 12 cases (4.5%). hs‐TnI was significantly associated with MI (AUROC 0.751, 95% CI 0.580–0.922, p = 0.003), with an optimal cut‐off of 141 ng/L. hs‐TnI levels ≥141 ng/L were significantly associated with CFS (OR 1.58, 95% CI 1.15–2.18, p = 0.005), while levels <141 ng/L were associated with the cardiac subscore of CIRS (OR 1.36, 95% CI 1.07–1.71, p = 0.011). CFS, but not hs‐TnI levels, predicted 3‐month mortality. Conclusions: In geriatric patients with suspected MI, frailty and cardiovascular multimorbidity should be carefully considered when interpreting emergency hs‐TnI testing. [ABSTRACT FROM AUTHOR]

Objectives: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization.Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality.Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality.Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality.• Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media.• PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients.• PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.Methods: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization.Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality.Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality.Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality.• Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media.• PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients.• PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.Results: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization.Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality.Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality.Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality.• Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media.• PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients.• PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.Conclusion: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization.Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality.Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality.Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality.• Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media.• PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients.• PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.Clinical relevance statement: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization.Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality.Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality.Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality.• Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media.• PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients.• PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies.Key Points: The main factors associated with coronavirus disease-19 (COVID-19) mortality are age, comorbidities, pattern of inflammatory response, and SARS-CoV-2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri-coronary adipose tissue attenuation (PCAT), available from high-resolution chest computed tomography (HRCT) in COVID-19 patients with severe disease requiring hospitalization.Two distinct groups of patients were admitted to Parma University Hospital in Italy with COVID-19 in March 2020 and March 2021 (first- and third-wave peaks of the COVID-19 pandemic in Italy, with the prevalence of wild-type and B.1.1.7 SARS-CoV-2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in-hospital mortality. Demographic, clinical, laboratory, HRCT data, and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to show which variables were associated with mortality.Among the 769 patients enrolled, 555 (72%) were discharged alive, and 214 (28%) died. In multivariable logistic regression analysis age (p < 0.001), number of chronic illnesses (p < 0.001), smoking habit (p = 0.006), P/F ratio (p = 0.001), platelet count (p = 0.002), blood creatinine (p < 0.001), non-invasive mechanical ventilation (p < 0.001), HRCT visual score (p < 0.001), and PCAT (p < 0.001), but not the calcium score, were independently associated with in-hospital mortality.Coronary inflammation, measured with PCAT on non-triggered HRCT, appeared to be independently associated with higher mortality in patients with severe COVID-19, while the pre-existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.The current study demonstrates that a relatively simple measurement, peri-coronary adipose tissue attenuation (PCAT), available ex-post from standard high-resolution computed tomography, is strongly and independently associated with in-hospital mortality.• Coronary inflammation can be measured by the attenuation of peri-coronary adipose tissue (PCAT) on high-resolution CT (HRCT) without contrast media.• PCAT is strongly and independently associated with in-hospital mortality in SARS-CoV-2 patients.• PCAT might be considered an independent prognostic marker in COVID-19 patients if confirmed in other studies. [ABSTRACT FROM AUTHOR]

Aim. To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients (age > 75 years). Methods. The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. Results. With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend (P < 0.0001) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001), but not in subjects aged 75 or younger. Conclusions. In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects (age > 75). [ABSTRACT FROM AUTHOR]

Bedside chest ultrasonography, when integrated with clinical data, is an accurate tool for improving the diagnostic process of many respiratory diseases. This study aims to evaluate the feasibility of a chest ultrasonographic screening program in nursing homes for detecting coronavirus disease-19 (COVID-19)–related pneumonia and improving the appropriateness of hospital referral of residents. Pragmatic, descriptive, feasibility study from April 2 to April 9, 2020. A total of 83 older residents (age 85 ± 8) presenting mild to moderate respiratory symptoms and not previously tested for COVID-19, residing in 5 nursing homes in Northern Italy. Chest ultrasonography was performed at the bedside by a team of hospital specialists with certified expertise in thoracic ultrasonography, following a systematic approach exploring 4 different areas for each hemithorax, from the anterior and posterior side. Presence of ultrasonographic signs of interstitial pneumonia, including comet-tail artifacts (B-lines) with focal or diffuse distribution, subpleural consolidations, and pleural line indentation, was detected. The specialist team integrated ultrasonography data with clinical and anamnestic information, and gave personalized therapeutic advice for each patient, including hospital referral when needed. The most frequent reasons for ultrasonographic evaluation were fever (63% of participants) and mild dyspnea (40%). Fifty-six patients (67%) had abnormal ultrasonographic findings. The most common patterns were presence of multiple subpleural consolidations (32 patients) and diffuse B-lines (24 patients), with bilateral involvement. A diagnosis of suspect COVID-19 pneumonia was made in 44 patients, and 6 of them required hospitalization. Twelve patients had ultrasonographic patterns suggesting other respiratory diseases, and 2 patients with normal ultrasonographic findings were diagnosed with COPD exacerbation. In nursing home residents, screening of COVID-19 pneumonia with bedside chest ultrasonography is feasible and may represent a valid diagnostic aid for an early detection of COVID-19 outbreaks and adequate patient management. [ABSTRACT FROM AUTHOR]

Pure calcium oxalate is the most frequent type of idiopathic kidney stone composition. Fourier transform infrared spectroscopy (FT-IR) allows to detect the ratio of calcium oxalate dihydrate (COD) and monohydrate (COM) crystals in stones, but the clinical significance of this parameter remains uncertain. The objective of this observational study was to verify the association of clinical and laboratory parameters of kidney stone disease with COD/COM ratio in a group of 465 (322 M, age 46 ± 14) patients suffering from idiopathic calcium nephrolithiasis with pure calcium oxalate stones (≥ 97%). Each participant underwent a complete clinical examination, serum chemistry, 24-h urine collection for the determination of the profile of lithogenic risk, and had stones analyzed by FT-IR. Most (62%) of the stones had a COD/COM ratio ≤ 0.25, and the urine chemistry of the corresponding patients showed a low prevalence of urinary metabolic abnormalities. With increasing COD/COM ratio intervals (0–0.25, 0.26–0.50, 0.51–0.75, 0.76–1), a significant association was observed for the number of urological procedures, serum calcium, 24-h urinary calcium excretion, prevalence of hypercalciuria and relative calcium oxalate supersaturation, and a negative trend was detected for the age of the first stone episode (all p values < 0.05). A linear regression model showed that the only parameters significantly associated with COD/COM ratio were 24-h urinary calcium excretion (standardized β = 0.464, p < 0.001) and urine pH (standardized β = 0.103, p = 0.013). In pure calcium oxalate idiopathic stones, COD/COM ratio may reflect the presence of urinary metabolic risk factors, and represent a guide for the prescription of urinary analyses. [ABSTRACT FROM AUTHOR]

Gut microbiota composition and functionality are involved in the pathophysiology of several intestinal and extraintestinal diseases, and are increasingly considered a modulator of local and systemic inflammation. However, the involvement of gut microbiota in diverticulosis and in diverticular disease is still poorly investigated. In this review, we critically analyze the existing evidence on the fecal and mucosa-associated microbiota composition and functionality across different stages of diverticular disease. We also explore the influence of risk factors for diverticulosis on gut microbiota composition, and speculate on the possible relevance of these associations for the pathogenesis of diverticula. We overview the current treatments of diverticular disease targeting the intestinal microbiome, highlighting the current areas of uncertainty and the need for future studies. Although no conclusive remarks on the relationship between microbiota and diverticular disease can be made, preliminary data suggest that abdominal symptoms are associated with reduced representation of taxa with a possible anti-inflammatory effect, such as Clostridium cluster IV, and overgrowth of Enterobacteriaceae, Bifidobacteria and Akkermansia. The role of the microbiota in the early stages of the disease is still very uncertain. Future studies should help to disentangle the role of the microbiome in the pathogenesis of diverticular disease and its progression towards more severe forms. [ABSTRACT FROM AUTHOR]

In older patients with acute illness, a condition of "hospital-dependence" may arise: patients get adapted to the hospital care and, once discharged, may experience health status decline, requiring repeated readmissions despite appropriate treatments. The objective of this case-series study was to describe the characteristics of 118 patients (72 F) aged ≥75 (mean 83.7 ± 4.9) who were urgently admitted to our institution at least 4 times in 2015. For each patient and admission, data on multimorbidity (Cumulative Illness Rating Scale Comorbidity Score and Severity Index), frailty (Rockwood Clinical Frailty Scale), functional dependence, functional status, polypharmacy, length of stay and interval between admissions were extrapolated from clinical records. Mortality during the years 2015 and 2016 was assessed on the institutional database. At the first admission, patients had a high burden of polypharmacy (median number of drugs 8.5, IQR 6–11) and multimorbidity (Comorbidity Score 15.8 ± 4.1, Severity Index 2.9 ± 1.1). However, most (55.5%) were fit or pre-frail according to Clinical Frailty Scale (score 1–4). At multivariate models, Severity Index was significantly correlated with the length of stay (β ± SE 2.23 ± 0.89, p =.01) and readmission interval (β ± SE -22.49 ± 9.27, p =.02). Significantly increasing trends of multimorbidity and disability occurred across admissions. By the end of 2016, 66% of patients had died. Frailty (RR 2.005, 95%CI 1.054–3.814, p =.007) and cancer were the only predictors of mortality. Hospital-dependent patients had severe multimorbidity, but exhibited an unexpectedly low prevalence of frailty/disability at baseline, though increasing across admissions. Trends of frailty and multimorbidity are paramount for profiling the hospital-dependence risk. • Hospital-dependence in older patients is associated with severe multimorbidity. • Hospital-dependence may arise also in subjects with a good functional status. • Frailty and cancer, but not multimorbidity, predict adverse outcomes in these patients. • The severity of multimorbidity is associated with length of stay and early readmissions. • Hospital-dependence implies a rapid decline of functional performance. [ABSTRACT FROM AUTHOR]

The role of the strength of family history of stones (FHS), i.e., degree of relatives with the disease, on the course of calcium urolithiasis (CU) is not fully understood, particularly in young patients where genetic background has the greatest influence on disease expression. Thus, with a retrospective cross-sectional design, we examined baseline clinical parameters and urinary chemistries of 369 subjects (196 M) with CU and 96 controls (41 M) aged between 15 and 25 at the time of the first visit at our stone clinic. Subjects with metabolic syndrome traits, known causes of CU or CU onset before the age of 15 were excluded. Clinical and metabolic parameters were compared among stone formers (SF) and controls, stratified by gender, the presence and type of FHS determined through the kinship coefficient of relatives with stones. No significant differences in clinical course were found between SF with and without FHS, except for the presence of bilateral stones (OR 2.01, 95% CI 1.20-3.39, p < 0.01). A significant age-, sex- and disease duration-adjusted trend for a higher number of colics ( p for trend = 0.001), number of stones ( p for trend = 0.002), stone rate ( p for trend = 0.003) and the presence of retained stones (OR 1.60, 95% CI 1.14-2.21, p = 0.006) was detected with increasing FHS strength. Urinary chemistries were unaffected by FHS in both SF and controls, except for a higher calcium excretion in females with FHS ( p < 0.05). The type of FHS, thus, significantly influences the clinical course of CU in young SF, mainly irrespective of urinary factors. [ABSTRACT FROM AUTHOR]

The worldwide burden of dementia is immense, and set to increase to unprecedented levels in the coming decades, due to population aging. In the absence of disease-modifying treatment, there is therefore a strong rationale to support the assumption that acting on modifiable risk factors, especially in midlife, is a good strategy for reducing the burden of dementia. Among these risk factors, nutrition is key, as it is fundamental to healthy aging, and has interrelated benefits on a number of organ systems, metabolic processes and health states that can all contribute to modifying the risk of dementia. In this paper, we review the methodological challenges of comparing studies of dietary interventions. We then discuss the effect of genetics and the environment on brain health, and review in particular the literature data on the effect of nutrition on cognition. We summarize the body of data reporting the largely beneficial effects of the Mediterranean diet on brain health, and the possible mechanisms that mediate these effects. Finally, we discuss future perspectives for further research in the field, notably the "gut-brain axis", thought to be a key mediator of the effect of nutrition on brain health. • The burden of dementia is huge and will affect 130 million persons by 2050. • Acting on modifiable risk factors, e.g. diet, is key to delaying or preventing AD. • Consistent evidence shows that the Mediterranean-type diet benefits brain health. • The "gut-brain axis" may mediate the effect of nutrition on brain health. [ABSTRACT FROM AUTHOR]

Adequate hydration, as to maintain urinary volume over 2 L/day, has long been considered as the cornerstone medical prescription for preventing nephrolithiasis. However, scientific evidence about what kind of water stone formers should drink and about the effects of other beverages on urinary stone risk factors is sometimes unclear. Moreover, the recommendation that water therapy prevents kidney stone recurrence relies on only one randomized controlled trial, even if more epidemiologic and basic science studies seem to support this assumption. Therefore, in this review we analyze current evidence that support water therapy in nephrolithiasis and we highlight the possible effects of different types of water and other beverages on lithogenic risk, giving some practical recommendations for what stone formers should be advised to prevent recurrence. [ABSTRACT FROM PUBLISHER]

Introduction A precise quantitative measurement of skeletal muscle mass is fundamental for diagnosing sarcopenia in older individuals. The current techniques of assessment, including dual-energy x-ray absorptiometry (DXA), bioimpedance analysis (BIA), and magnetic resonance imaging (MRI) are either difficult to perform in everyday clinical practice or biased by concurrent clinical confounders. B-mode muscle ultrasound can be helpful in assessing muscle mass and architecture, and thus possibly useful for diagnosing or screening sarcopenia. Methods A literature search of published articles on muscle ultrasound and sarcopenia in older individuals as of July 31, 2016, was made on PubMed and Scopus. Manual search and cross-referencing from reviews and original articles was also performed. Results Most of the existing studies were carried out on healthy well-fit subjects, with a low prevalence of sarcopenia. The main parameters that can be assessed through muscle ultrasound are muscle thickness, cross-sectional area, echo intensity, and, for pennate muscles, fascicle length and pennation angle. In older subjects, all these parameters show some degree of alteration compared to young adults, particularly in lower limb muscles with antigravitary function, such as the quadriceps femoris and gastrocnemius medialis. Each of these parameters may be theoretically useful for detecting the loss of muscle mass and functionality in geriatric patients. They are also poorly influenced by the presence of acute and chronic diseases and fluid balance, unlike DXA and BIA, but a high degree of standardization in ultrasound protocols is necessary. Frontier applications of ultrasound in the assessment of sarcopenia may include contrast-enhanced and diaphragm ultrasound. Conclusions The current literature does not allow to make conclusive recommendations about the use of muscle ultrasound in geriatric practice. However, this technique is very promising, and further studies should validate its applications in the context of sarcopenia assessment. [ABSTRACT FROM AUTHOR]

The role of serum uric acid (SUA), an inflammatory agent and potential mediator of cardiovascular diseases, in endothelial function (EF) has been tested only in middle-aged subjects affected by specific diseases. Our aim was to assess the relationship between SUA and measures of EF in a cohort of elderly community-dwellers. This study involved 424 males and 426 females aged 70 years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), having complete data on SUA and EF assessed by flow-mediated vasodilation (FMD) and by intra-arterial infusion of acetylcholine (endothelium-dependent vasodilation, EDV) and sodium nitroprusside (endothelium-independent vasodilation, EIDV). Univariate and multivariate regression models obtained by backward selection from initial fully-adjusted models were built to assess the relationship between SUA and measures of EF in both genders. Cardiovascular risk factors, serum hormonal and metabolic mediators, and body composition were considered as potential confounders. In the univariate model, SUA was inversely associated in both genders with log(EDV) (β ± SE males − 0.39 ± 0.17, p = 0.03; females − 0.57 ± 0.19, p = 0.003) and log(EIDV) (males − 0.23 ± 0.12, p = 0.05; females − 0.49 ± 0.15, p = 0.002), but not with log(FMD). After adjustment for BMI, only the association between SUA and log(EIDV) in females persisted, though attenuated (− 0.32 ± 0.16, p = 0.049), and was no longer significant in the fully-adjusted multivariate model including waist/hip ratio. In conclusion, in older subjects, especially women, SUA is associated with EF not independently of a list of confounders including BMI and trunk fat mass, suggesting a role as surrogate metabolic marker rather than an active player in EF. [ABSTRACT FROM AUTHOR]

The physiology of inflammatory response is modified by the aging process and is substantially affected by multimorbidity and disability. Infection is the most frequent cause of acute inflammation in both adult and older subjects. C-reactive protein (CRP) is the most used biomarker of inflammation, and a substantial amount of literature has demonstrated its importance and clinical usefulness in adult subjects. However, the clinical significance of serum CRP determination has not been completely clarified in older subjects with acute infection, especially in the light of the age-related rearrangements in immunity and cytokine production. Thus, in the present review, we focus on the existing knowledge about serum CRP level interpretation in geriatric patients hospitalized with acute infection. Our aims were to determine the significance of CRP measurement at hospital admission for establishing a diagnosis of infection and/or a prognosis and to evaluate whether it is indicated to repeat hs-CRP measurements during hospital stay for monitoring disease course and, possibly, guiding the discharge timing. We concluded that CRP dosage at hospital admission is helpful to detect acute infection, and particularly sepsis, in geriatric patients, and that CRP elevation may provide valuable short-term prognostic information. At the current state of art, serial CRP measurements are instead not indicated to monitor disease course and plan hospital discharge in this setting. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association of different chronic comorbidities, considered singularly and together in Cumulative Illness Rating Scale (CIRS) indexes, with pneumonia diagnosis in a group of elderly frail hospitalized patients. Design and methods With a retrospective cohort design, all clinical records of frail (Rockwood ≥ 5) nonterminal patients ≥ 65 years old acutely admitted over a 8-month span in an internal medicine ward were evaluated. Pneumonia status and its categorization (community-acquired, CAP, vs healthcare-associated, HCAP) were defined according to chest radiology findings and validated criteria. Chronic comorbidities, CIRS Comorbidity Score and CIRS Severity Index were collected for each participant through a standardized methodology. Multivariate logistic regression models were applied to assess the association of each comorbid condition or scores with pneumonia. Results 1199 patients (546 M, median age 81.9, IQR 72.8–87.9 years), of whom 239 with pneumonia (180 CAP, 59 HCAP) were evaluated. CIRS Comorbidity Score was significantly associated with pneumonia, both at an age- and sex-adjusted model and at a multivariate model (OR for each unitary increase 1.03, 95% CI 1.001–1.062, p = 0.04), together with provenience from nursing home (OR 1.96, 95% CI 1.41–2.73, p < 0.001). Among single comorbidities, only COPD (OR 2.7, 95% CI 1.9–3.6, p < 0.001) and dementia (OR 2.3, 95% CI 1.7–3.3, p < 0.001) were associated with pneumonia, while stroke, cancer, cardiovascular, chronic liver and kidney disease were not. Conclusions In a small cohort of elderly frail hospitalized patients, measures of multimorbidity, like CIRS, are significantly associated with the risk of pneumonia. COPD and dementia are the main conditions concurring to define this risk. [ABSTRACT FROM AUTHOR]

Dietary sodium chloride intake is nowadays globally known as one of the major threats for cardiovascular health. However, there is also important evidence that it may influence idiopathic calcium nephrolithiasis onset and recurrence. Higher salt intake has been associated with hypercalciuria and hypocitraturia, which are major risk factors for calcium stone formation. Dietary salt restriction can be an effective means for secondary prevention of nephrolithiasis as well. Thus in this paper, we review the complex relationship between salt and nephrolithiasis, pointing out the difference between dietary sodiumand salt intake and the best methods to assess them, highlighting the main findings of epidemiologic, laboratory and intervention studies and focusing on open issues such as the role of dietary salt in secondary causes of nephrolithiasis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between vitamin D deficiency (25-hydroxyvitamin D <20 ng/mL) and idiopathic calcium nephrolithiasis (ICN).Methods: A total of 884 patients with ICN (363 males, mean age of 51 ± 14) and 967 controls (162 males, mean age of 59 ± 15) from an area with no food fortification policy were considered following a case-control study design. Patients were enrolled at a third-level outpatient stone clinic. Controls were selected from a laboratory database after exclusion of those with nephrolithiasis, bone, endocrine, liver, and kidney diseases. Serum 25-hydroxyvitamin-D (25-OH-D), date of test, presence/history of diabetes, and cardiovascular disease including hypertension were recorded for all subjects. Serum parathormone, calcium, phosphorus, and urinary factors of lithogenic risk were available in stone formers (SF). After univariate statistical analysis, propensity score matching with conditional logistic regression was used to control for the possible effects of covariates.Results: The prevalence of 25-OH-D <20 ng/mL was 56% in SF and 44% in controls (P <.001), with median levels of 18 ng/mL [interquartile range (IQR) of 12-24)] versus 23 ng/mL (IQR of 14-30) (age and sex adjusted P <.001). After a fully adjusted conditional logistic regression analysis, performed on propensity-matched cohorts (442 SF, 442 controls), there was a statistically significant association between vitamin D deficiency and odds of nephrolithiasis (estimated odds ratio of 2.29, confidence interval 95% 1.74-3.02, P <.001). 25-OH-D levels were not different in hypercalciuric and normocalciuric SF (median and IQR of 18 ng/mL and 13-23 vs 19 ng/mL and 13-26, respectively, P = .2).Conclusions: SF have lower serum 25-OH-D levels than controls. The role of hypovitaminosis D in the onset of ICN should be better reconsidered. [ABSTRACT FROM AUTHOR]

Carbapenemase-producing Klebsiella pneumoniae (CPKP) is rapidly emerging as a leading nosocomial infection in many countries, especially in Italy where it is considered endemic. In this paper we briefly summarize the main characteristics of this outbreak, focusing on its recent spread to elderly frail patients admitted to internal medicine and geriatric wards. Severity of disease, clinical complexity and a large number of comorbidities seem to be major risk factors in clinical practice, although scientific evidence is still lacking, since until now studies have been carried out mainly in intensive care settings. We also discuss the possible role of gut microbiota in CPKP colonization onset and the possible role of pre-probiotics in promoting eradication. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging multidrug-resistant nosocomial pathogen, spreading to hospitalized elderly patients. Risk factors in this setting are unclear. Our aims were to explore the contribution of multi-morbidity and disease severity in the onset of CRKP colonization/infection, and to describe changes in epidemiology after the institution of quarantine-ward managed by staff-cohorting. Methods and Findings: With a case-control design, we evaluated 133 CRKP-positive patients (75 M, 58 F; mean age 79±10 years) and a control group of 400 CRKP-negative subjects (179 M, 221 F; mean age 79±12 years) admitted to Internal Medicine and Critical Subacute Care Unit of Parma University Hospital, Italy, during a 10-month period. Information about comorbidity type and severity, expressed through Cumulative Illness Rating Scale-CIRS, was collected in each patient. During an overall 5-month period, CRKP-positive patients were managed in an isolation ward with staff cohorting. A contact-bed isolation approach was established in the other 5 months. The effects of these strategies were evaluated with a cross-sectional study design. CRKP-positive subjects had higher CIRS comorbidity index (12.0±3.6 vs 9.1±3.5, p<0.0001) and CIRS severity index (3.2±0.4 vs 2.9±0.5, p<0.0001), along with higher cardiovascular, respiratory, renal and neurological disease burden than control group. CIRS severity index was associated with a higher risk for CRKP-colonization (OR 13.3, 95%CI6.88–25.93), independent of comorbidities. Isolation ward activation was associated with decreased monthly incidence of CRKP-positivity (from 16.9% to 1.2% of all admissions) and infection (from 36.6% to 22.5% of all positive cases; p = 0.04 derived by Wilcoxon signed-rank test). Mortality rate did not differ between cases and controls (21.8% vs 15.2%, p = 0.08). The main limitations of this study are observational design and lack of data about prior antibiotic exposure. Conclusions: Comorbidities and disease severity are relevant risk factors for CRKP-colonization/infection in elderly frail patients. Sanitary measures may have contributed to limit epidemic spread and rate of infection also in internal medicine setting. [ABSTRACT FROM AUTHOR]

Idiopathic calcium nephrolithiasis (ICN) is a disease whose prevalence is rising. Our aim was to assess whether lifestyle indicators and habits of calcium stone formers in Italy have changed over the last 25 years, trying to establish a connection with the diffusion of Internet access. Therefore we examined the database of the Stone Clinic of Parma University Hospital and extracted 1952 (1192 M, 760 F) patients with ICN who underwent a full clinical and laboratory evaluation from 1986 to 2010. Laboratory evaluation included data on urinary 24-h volume, pH, sodium, potassium, chloride, calcium, phosphate, uric acid, magnesium, oxalate, and citrate. Patients were split in three groups on a chronological basis, according to official EUROSTAT-ISTAT data of Internet connection among families in Italy: Group 1, pre-Internet era (1986-1998, 853 patients); Group 2, narrow-band era (1999-2004, 467 patients); Group 3, broad-band era (2005-2010, 632 patients). Over the time we found a significant increase in water intake (1.37 vs. 1.78 L in men and 1.21 vs. 1.55 L in women, Group 1 vs. Group 3, p-trend<0.001) and a decrease in urinary sodium and chloride for both genders and calcium and magnesium only for males, while females experienced a slight increase in oxalate excretion. Supersaturation indexes for calcium and uric acid stones dramatically fell for both genders. The percentage of stone formers performing physical activity significantly rise (41% Group 3 vs. 8% Group 1, p<0.001) and we also found a trend of reduction in mean blood pressure. Therefore, the lifestyle of Italian idiopathic calcium stone formers has changed over the last 25 years, and the rising Internet access may have played a great role in driving this change. [ABSTRACT FROM AUTHOR]

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Older multimorbid frail subjects have been severely involved in the coronavirus disease-19 (COVID-19) pandemic. The aim of this retrospective study is to compare the clinical features and outcomes of patients admitted in different phases of the outbreak in a COVID-19 hospital hub, with a particular focus on age, multimorbidity, and functional dependency. The clinical records of 1264 patients with clinical and radiological features compatible with COVID-19 pneumonia admitted in February–June, 2020, were analyzed, retrieving demographical, clinical, laboratory data, and outcomes. All variables were compared after stratification by the period of admission (first phase: rising slope of pandemic wave; second phase: plateau and falling slope), age, results of the first reverse transcriptase-polymerase chain reaction (RT-PCR) test for detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), multimorbidity (≥2 chronic diseases), and presence of disability. Factors independently associated with hospital mortality were determined by multivariate forward-selection logistic regression. Patients admitted during the second phase were older, more frequently multimorbid, disabled, and of female gender. However, on admission they exhibited milder respiratory impairment (PaO2/FiO2 268, IQR 174–361, vs. 238, IQR 126–327 mmHg, p < 0.001) and lower mortality (22% vs. 27%, p < 0.001). Age, respiratory exchanges, positive RT-PCR test, number of chronic diseases (odds ratio (OR) 1.166, 95% confidence interval (CI) 1.036–1.313, p = 0.011), and disability (OR 1.927, 95% CI 1.027–3.618, p = 0.022) were positively associated with mortality, while admission during the second phase exhibited an inverse association (OR 0.427, 95% CI 0.260–0.700, p = 0.001). In conclusion, older multimorbid patients were mainly hospitalized during the second phase of the pandemic wave. The prognosis was strongly influenced by the COVID-19 phenotype and period of admission, not just by age, multimorbidity, and disability. [ABSTRACT FROM AUTHOR]

To investigate the current evidence on the use of point-of-care chest ultrasonography in older patients and geriatric settings and present the current state of the art of chest ultrasound applications. Special article based on a literature review with narrative analyses and expert clinical knowledge. All studies performed in a geriatric setting were included. Observational and intervention studies and meta-analyses including participants aged ≥70 years were also considered, even if not specifically focused on a geriatric setting. Data on participant characteristics, diagnostic accuracy of chest ultrasonography, and outcomes were collected for each considered study. Data were analyzed and discussed with a particular focus on the possible applications and advantages of chest ultrasonography in geriatric medicine, underlining the possible areas of future research. We found only 5 studies on the diagnostic accuracy and prognostic relevance of chest ultrasonography in geriatrics. However, several studies performed in emergency departments, intensive care units, and internal medicine wards included a large number of participants ≥70 years old; they suggest that chest ultrasonography may represent a valid aid to the diagnostics of acute dyspnea, pneumonia, acute heart failure, pneumothorax, and pleural diseases, with an accuracy in some cases superior to standard x-rays, especially when mobility limitation is present. Diaphragm ultrasonography may also represent a valid tool to guide mechanical ventilation weaning in older patients with acute respiratory failure. Chest ultrasonography may represent a valid bedside diagnostic aid to the management of acute respiratory diseases in older patients. However, specific evidence is lacking for geriatric patients. Future research will need to focus on defining the reference standards and the diagnostic accuracy for older patients with frailty and multimorbidity, cost-efficacy and cost-effectiveness of the technique, its impact for clinical outcomes, and role for follow-up in the post-acute care. [ABSTRACT FROM AUTHOR]

The prognostic value of quick Sepsis-related Organ Failure Assessment (qSOFA) score in geriatric patients is uncertain. We aimed to compare qSOFA vs. Systemic Inflammatory Response Syndrome (SIRS) criteria for mortality prediction in older multimorbid subjects, admitted for suspected sepsis in a geriatric ward. We prospectively enrolled 272 patients (aged 83.7 ± 7.4). At admission, qSOFA and SIRS scores were calculated. Mortality was assessed during hospital stay and three months after discharge. The predictive capacity of qSOFA and SIRS was assessed by calculating the Area Under the Receiver Operating Characteristic Curve (AUROC), through pairwise AUROC comparison, and multivariable logistic regression analysis. Both qSOFA and SIRS exhibited a poor prognostic performance (AUROCs 0.676, 95% CI 0.609–0.738, and 0.626, 95% CI 0.558–0.691 for in-hospital mortality; 0.684, 95% CI 0.614–0.748, and 0.596, 95% CI 0.558–0.691 for pooled three-month mortality, respectively). The predictive capacity of qSOFA showed no difference to that of SIRS for in-hospital mortality (difference between AUROCs 0.05, 95% CI −0.05 to 0.14, p = 0.31), but was superior for pooled three-month mortality (difference between AUROCs 0.09, 95% CI 0.01–0.17, p = 0.029). Multivariable logistic regression analysis, accounting for possible confounders, including frailty, showed that both scores were not associated with in-hospital mortality, although qSOFA, unlike SIRS, was associated with pooled three-month mortality. In conclusion, neither qSOFA nor SIRS at admission were strong predictors of mortality in a geriatric acute-care setting. Traditional geriatric measures of frailty may be more useful for predicting adverse outcomes in this setting. [ABSTRACT FROM AUTHOR]

Background: Serum procalcitonin and highsensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients =65 years old admitted to hospital with acute respiratory symptoms. Methods: With a retrospective cohort study design, all multimorbid patients =65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney's U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker's association with pneumonia diagnosis. Results: Four hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5-179.0, vs 22.5 mg/dl, IQR 6.9-84.4, p < 0.0001), while procalcitonin median levels were not (0.22 ng/ml IQR 0.12- 0.87, vs 0.15 ng/ml, IQR 0.10-0.35, p = 0.08). The ROC analysis showed that, unlike procalcitonin, hs- CRP values were predictive of pneumonia (AUC 0.76, 95% CI 0.72-0.79, p < 0.0001, cut-off value 61 mg/L), even after adjustment for possible confounders including nursing home residence and dementia. Serum hs-CRP levels >61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95% CI 2.35-5.48, p < 0.0001). Conclusion: In elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting. [ABSTRACT FROM AUTHOR]

Previous observational studies using old qualitative methods have not clarified the role of amyloid positron emission tomography (PET) in the assessment of dementia. Given the moderately positive predictive value, the presence of amyloid deposition does not necessarily imply the diagnosis of dementia. Conversely, the absence of amyloid PET deposition has been shown to be useful in excluding the neurodegenerative pathology, irrespective of the aging process. We describe the clinical application of new innovative software recently developed to increase the sensitivity of this technique and to discriminate pathological deposition of cerebral amyloid from the age-related changes, reporting preliminary findings from a case-series study. In three different clinical profiles, we underline the need of integrating neuropsychological assessment and findings with this new PET scan and software that provide quantitative information of the cerebral amyloid and may increase the probability of rapid and accurate assessment of Alzheimer's disease. Although this amyloid quantification is promising, these preliminary results should be confirmed in future prospective studies with adequate sample size. [ABSTRACT FROM AUTHOR]

Background: The role of body composition (lean mass and fat mass) on urine chemistries and bone quality is still debated. Our aim was therefore to determine the effect of lean mass and fat mass on urine composition and bone mineral density (BMD) in a cohort of healthy females.Materials and Methods: 78 female volunteers (mean age 46 ± 6 years) were enrolled at the Stone Clinic of Parma University Hospital and subdued to 24-hour urine collection for lithogenic risk profile, DEXA, and 3-day dietary diary. We defined two mathematical indexes derived from body composition measurement (index of lean mass-ILM, and index of fat mass-IFM) and the cohort was split using the median value of each index, obtaining groups differing only for lean or fat mass. We then analyzed differences in urine composition, dietary intakes and BMD.Results: The women with high values of ILM had significantly higher excretion of creatinine (991 ± 194 vs 1138 ± 191 mg/day, p = 0.001), potassium (47 ± 13 vs 60 ± 18 mEq/day, p < 0.001), phosphorus (520 ± 174 vs 665 ± 186 mg/day, p < 0.001), magnesium (66 ± 20 vs 85 ± 26 mg/day, p < 0.001), citrate (620 ± 178 vs 807 ± 323 mg/day, p = 0.002) and oxalate (21 ± 7 vs 27 ± 11 mg/day, p = 0.015) and a significantly better BMD values in limbs than other women with low values of ILM. The women with high values of IFM had similar urine composition to other women with low values of IFM, but significantly better BMD in axial sites. No differences in dietary habits were found in both analyses.Conclusions: Lean mass seems to significantly influence urine composition both in terms of lithogenesis promoters and inhibitors, while fat mass does not. Lean mass influences bone quality only in limb skeleton, while fat mass influences bone quality only in axial sites. [ABSTRACT FROM AUTHOR]

Recent pandemic infection caused by SARS‐CoV‐2 (COVID‐19) led the scientific community to investigate the possible causes contributing to the physiopathology of this disease. In this context, analyses of the intestinal microbiota highlighted possible correlation between host‐associated bacterial communities and development of the COVID‐19. Nevertheless, a detailed investigation of the role of the human microbiota in the severity of the symptoms of this disease is still lacking. This study performed a comprehensive meta‐analysis of 323 faecal samples from public and novel Italian data sets based on the shotgun metagenomic approach. In detail, the comparative analyses revealed possible differences in the microbial biodiversity related to the individual health status, highlighting a species richness decrease in COVID‐19 patients with a severe prognosis. Moreover, healthy subjects resulted characterized by a higher abundance of protective and health‐supporting bacterial species, while patients affected by COVID‐19 disease displayed a significant increase of opportunistic pathogen bacteria involved in developing putrefactive dysbiosis. Furthermore, prediction of the microbiome functional capabilities suggested that individuals affected by COVID‐19 subsist in an unbalanced metabolism characterized by an overrepresentation of enzymes involved in the protein metabolism at the expense of carbohydrates oriented pathways, which can impact on disease severity and in excessive systemic inflammation. [ABSTRACT FROM AUTHOR]

The recent COVID-19 pandemic prompted a rapid-growing interest in the investigation of the human microbiota of the upper airways. In fact, the resident microbial community of this body district may have an influence on the onset of SARS-CoV-2 infection and its clinical course in terms of presence, symptom severity, and outcomes. However, several microbiological methodologies are available to study the human microbiota, reflecting the extensive fragmentation of methodological approaches. We investigate the impact of two critical steps that can induce biases in the downstream analyses, i.e. sampling method and microbial DNA extraction kit employed. We observed major discrepancies regarding the total amount of prokaryotic DNA that could be retrieved from a biological sample and the proportion between bacterial DNA and human host DNA. Moreover, shotgun DNA sequencing and taxonomic profile reconstruction also revealed correlations between sampling methods and the procedures applied for microbial DNA extraction. Based on all the data collected in this study, we formulate indications regarding the most efficient and reliable methodological procedures for the metagenomic analyses of the upper airways' microbiota to maximize accuracy and reproducibility. [ABSTRACT FROM AUTHOR]

Background: Transthoracic strain elastosonography (TSE) is being increasingly studied for estimating lung-pleura interface stiffness in pulmonary fibrosis. To date, no data exist on its application in chronic obstructive pulmonary disease (COPD). Objectives: The aim of this article was to describe the TSE pattern in patients with COPD and healthy subjects, either smokers or nonsmokers, and evaluate the feasibility of this technique for early detection of COPD in smokers. Methods: Nineteen patients with COPD, twenty-one healthy smokers, and twenty healthy nonsmokers underwent spirometry and TSE. Elastosonography was performed by one ultrasound-certified operator on 12 different scans for each participant, on right and left sides, anteriorly and posteriorly, on upper and lower lobes. For each scan, lung-pleura interface stiffness index (SI) was calculated, and the average SI on all 12 scans (SI-12) and on posterior basal scans (SI-PB) was calculated and used for comparisons among groups of participants and correlations with spirometric parameters. Results: Patients with lung injury (i.e., with COPD or healthy smokers) exhibited significantly increased lung-pleura interface stiffness on TSE, measured by SI-12 and SI-PB, than healthy nonsmokers (p < 0.05). Unlike SI-12, SI-PB was able to discriminate between subjects with lung injury and healthy nonsmokers on receiver operating characteristics analysis (area under the curve 0.846, 95% confidence interval 0.730–0.926, p < 0.001) and correlated with forced expiratory volume in the first second (r = −0.31, p = 0.018). Conclusion: The measurement of lung-pleura interface stiffness by TSE in posterior basal scans was able to discriminate patients with lung injury from healthy nonsmokers. The role of TSE for detecting early lung damage in COPD should be further investigated. [ABSTRACT FROM AUTHOR]

Background: Manual measurement of 4-meter gait speed by a stopwatch is the gold standard test for functional assessment in older adults. However, the accuracy of this technique may be biased by several factors, including intra- and inter-operator variability. Instrumental techniques of measurement using accelerometers may have a higher accuracy. Studies addressing the concordance between these two techniques are missing. The aim of the present community-based observational study was to compare manual and instrumental measurements of 4-meter gait speed in older individuals and to assess their relationship with other indicators of physical performance. Methods: One-hundred seventy-two (69 men, 103 women) non-disabled community-dwellers aged ≥65 years were enrolled. They underwent a comprehensive geriatric assessment including physical function by Short Physical Performance Battery (SPPB), hand grip strength, and 6-minute walking test (6MWT). Timed usual walking speed on a 4-meter course was assessed by using both a stopwatch (4-meter manual measurement, 4-MM) and a tri-axial accelerometer (4-meter automatic measurement, 4-MA). Correlations between these performance measures were evaluated separately in men and women by partial correlation coefficients. Results: In both genders, 4-MA was associated with 4-MM (men r = 0.62, p<0.001; women r = 0.73, p<0.001), handgrip strength (men r = 0.40, p = 0.005; women r = 0.29, p = 0.001) and 6MWT (men r = 0.50, p = 0.0004; women r = 0.22, p = 0.048). 4-MM was associated with handgrip strength and 6MWT in both men and women. Considering gait speed <0.6 m/s as diagnostic of dismobility syndrome, the two methods of assessment disagreed, with a different categorization of subjects, in 19% of men and 23% of women. The use of accelerometer resulted in 29 (13 M, 16 F) additional diagnoses of dismobility, compared with the 4-MM. Conclusions: In an older population, the concordance of gait speeds manually or instrumentally assessed is not optimal. The results suggest that manual measures might lead to misclassification of a substantial number of subjects. However, longitudinal studies using standardized and validated procedures aimed at the comparison of different techniques are needed before recommending the use of accelerometers in comprehensive geriatric assessment. [ABSTRACT FROM AUTHOR]

The recent COVID-19 pandemic prompted a rapid-growing interest in the investigation of the human microbiota of the upper airways. In fact, the resident microbial community of this body district may have an influence on the onset of SARS-CoV-2 infection and its clinical course in terms of presence, symptom severity, and outcomes. However, several microbiological methodologies are available to study the human microbiota, reflecting the extensive fragmentation of methodological approaches. We investigate the impact of two critical steps that can induce biases in the downstream analyses, i.e. sampling method and microbial DNA extraction kit employed. We observed major discrepancies regarding the total amount of prokaryotic DNA that could be retrieved from a biological sample and the proportion between bacterial DNA and human host DNA. Moreover, shotgun DNA sequencing and taxonomic profile reconstruction also revealed correlations between sampling methods and the procedures applied for microbial DNA extraction. Based on all the data collected in this study, we formulate indications regarding the most efficient and reliable methodological procedures for the metagenomic analyses of the upper airways' microbiota to maximize accuracy and reproducibility. [ABSTRACT FROM AUTHOR]

Objectives: Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. Methods: This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. Results: Amongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients. Conclusion: In this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasound (LUS) is an accurate, safe, and cheap tool assisting in the diagnosis of several acute respiratory diseases. The diagnostic value of LUS in the workup of coronavirus disease-19 (COVID-19) in the hospital setting is still uncertain. Objectives: The aim of this observational study was to explore correlations of the LUS appearance of COVID-19-related pneumonia with CT findings. Methods: Twenty-six patients (14 males, age 64 ± 16 years) urgently hospitalized for COVID-19 pneumonia, who underwent chest CT and bedside LUS on the day of admission, were enrolled in this observational study. CT images were reviewed by expert chest radiologists, who calculated a visual CT score based on extension and distribution of ground-glass opacities and consolidations. LUS was performed by clinicians with certified competency in thoracic ultrasonography, blind to CT findings, following a systematic approach recommended by ultrasound guidelines. LUS score was calculated according to presence, distribution, and severity of abnormalities. Results: All participants had CT findings suggestive of bilateral COVID-19 pneumonia, with an average visual scoring of 43 ± 24%. LUS identified 4 different possible -abnormalities, with bilateral distribution (average LUS score 15 ± 5): focal areas of nonconfluent B lines, diffuse confluent B lines, small subpleural microconsolidations with pleural line irregularities, and large parenchymal consolidations with air bronchograms. LUS score was significantly correlated with CT visual scoring (r = 0.65, p < 0.001) and oxygen saturation in room air (r = –0.66, p < 0.001). Conclusion: When integrated with clinical data, LUS could represent a valid diagnostic aid in patients with suspect COVID-19 pneumonia, which reflects CT findings. [ABSTRACT FROM AUTHOR]

Reorganization of a large academic hospital to face COVID-19 outbreak: The model of Parma, Emilia-Romagna region, Italy Keywords: care algorithm; hospital organization; pneumonia; SARS-CoV-2 EN care algorithm hospital organization pneumonia SARS-CoV-2 1 3 3 06/04/20 20200601 NES 200601 Since 21 February 2020, Italy has developed an outbreak of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with 159 516 confirmed cases until 13 April, mostly concentrated in the Northern part of the country.[1] This situation represents a massive stress for the Italian healthcare system, forcing health authorities to take urgent measures to limit disease spread and potentiate territorial Emergency systems to intercept novel cases.[[2]] Public hospitals are subjected to overflow of SARS-CoV-2-infected patients rapidly saturating the bed capacity of Infectious Disease units and ICUs.[[2], [4]] To face this challenge, Parma University Hospital, a 1200-bed facility with a catchment area of >400 000 inhabitants around the city of Parma, Emilia-Romagna region, has implemented an algorithm, based on the current disease knowledge,[3] to manage the flow of suspected COVID-19 cases that are triaged at the Emergency Department (ED) (Figure 1). COVID-19-dedicated wards have been obtained by reconversion of internal medicine, geriatric and rehabilitation wards, whose patients have been transferred to community hospitals or territorial facilities. [Extracted from the article]

Venous thromboembolism (VTE) is a common and potentially life-threatening condition which includes both deep-vein thrombosis (DVT) and pulmonary embolism (PE). VTE has a significant clinical and epidemiological impact in the elderly, and its incidence increases to more than 1% per year in older patients, suggesting the presence of specific age-related risk factors in this population. Immobilization seems to predominate as the main cause in patients admitted for medical acute illness in medicine wards, and there is evidence of a high risk in older patients with immobilization resulting from advanced forms of Parkinson’s disease (PD), regardless of the presence of an acute medical condition. In this review, we would to discuss the recent evidence on clinical, molecular and epidemiological features of VTE in older frail subjects focusing on patients with PD and parkinsonism. We also discuss some therapeutic issues about the risk prevention and we suggest a thorough comprehensive geriatric assessment that can represent an optimal strategy to identify and prevent the VTE risk in these patients. [ABSTRACT FROM AUTHOR]

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals. [ABSTRACT FROM AUTHOR]

This work aimed to underline the prospects of hippuric acid, a product of the metabolism of polyphenols, as a new biomarker of fruits and vegetables intake associated with lithogenic risk. Biochemical parameters of lithogenic risk and hippuric acid were measured in the 24 h urine collections of a cohort of 696 Italian kidney stone formers divided into two subgroups according to their different dietary habits. The link between lithogenic risk parameters and hippuric acid was assessed and this compound was revealed as a valuable biomarker of fruits and vegetables intake in kidney stone formers. A cut-off value of urinary excretion of hippuric acid, 300 mg/24 h, was set as the threshold of discrimination between low and high intake of fruits and vegetables for these patients. These results highlight the importance of monitoring of the excretion hippuric acid in urine to address proper dietary guidelines for the management of stone former patients. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice. [ABSTRACT FROM AUTHOR]

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly. [ABSTRACT FROM AUTHOR]

Background: Concern is growing about the negative consequences that response measures to the COVID-19 epidemic may have on the management of other medical conditions. Methods: A retrospective descriptive case-series study conducted at a large University-hospital in northern Italy, an area severely hit by the epidemic. Results: Between 23 February and 14 May 2020, 4160 (52%) COVID-19 and 3778 (48%) non-COVID-19 patients were hospitalized. COVID-19 admissions peaked in the second half of March, a period characterized by an extremely high mortality rate (27.4%). The number of admissions in 2020 was similar to 2019, but COVID-19 patients gradually occupied all available beds. Comparison between COVID-19 and non-COVID-19 admissions in 2020 revealed significant differences concerning all age classes and gender. Specifically, COVID-19 patients were older, predominantly male, and exhibited more comorbidities. Overall, admissions for non-communicable diseases (NCDs) in 2020 vs. 2019 dropped by approximately one third. Statistically significant reductions were observed for acute myocardial infarction (−78, −33.9%), cerebrovascular disease (−235, −41.5%), and cancer (−368, −31.9%). While the first two appeared equally distributed between COVID-19 and non-COVID-19 patients, chronic NCDs were statistically significantly more frequent in the former, except cancer, which was less frequent in COVID-19 patients. Conclusions: Prevention of collateral damage to patients with other diseases should be an integral part of epidemic response plans. Prospective cohort studies are needed to understand the long-term impact. [ABSTRACT FROM AUTHOR]