Non-Invasive Ventilation Support during Hospitalization for SARS-CoV-2 and the Risk of Venous Thromboembolism.

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.

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia.

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).

The association of serum procalcitonin and high-sensitivity C-reactive protein with pneumonia in elderly multimorbid patients with respiratory symptoms: retrospective cohort study.

BACKGROUND: Serum procalcitonin and high-sensitivity 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.

Family history influences clinical course of idiopathic calcium nephrolithiasis: case-control study of a large cohort of Italian patients.

AIM: To evaluate the contribution of family history of stones (FHS), up to second-degree relatives, on clinical course (age of first renal colic, bilateral disease, retained calculi, recurrences, urological procedures) of idiopathic calcium nephrolithiasis (ICN) and urinary parameters of lithogenic risk, a case-control study was carried out. METHOD: Clinical records of 2080 patients with ICN were evaluated and categorized according to FHS. Data about clinical course of disease and urinary parameters of lithogenic risk were collected. Student's t, Chi square tests and binary logistic regression were applied to discriminate groups with vs. without FHS. RESULTS: FHS was associated with an earlier onset of stone disease (age at first episode 32 ± 13 vs. 37 ± 15 years, p <0.001), particularly in females. After adjustment for multiple covariates, FHS was significantly associated to a higher risk of recurrence [odds ratio (OR) 1.2, 95 % confidence interval (1.1-1.4), p = 0.04], retained stones [OR 1.3, CI (1.1-1.5), p = 0.004], bilateral stones [OR 1.2, 95 % CI (1.1-1.5), p = 0.022] and urological procedures [OR 1.2, 95 % CI (1.1-1.5), p = 0.034]. FHS did not influence urinary parameters of lithogenic risk, except for calcium excretion in females. CONCLUSION: A positive family history influences the clinical course of ICN with some significant gender-related differences, substantially irrespective of urinary parameters of lithogenic risk.

An investigation of multimorbidity measures as risk factors for pneumonia in elderly frail patients admitted to hospital.

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.

Multimorbidity in elderly hospitalised patients and risk of Clostridium difficile infection: a retrospective study with the Cumulative Illness Rating Scale (CIRS).

OBJECTIVES: To identify the role of chronic comorbidities, considered together in a literature-validated index (Cumulative Illness Rating Scale, CIRS), and antibiotic or proton-pump inhibitor (PPI) treatments as risk factors for hospital-acquired Clostridium difficile infection (CDI) in elderly multimorbid hospitalised patients. DESIGN: Retrospective cohort study. SETTING: Subacute hospital geriatric care ward in Italy. PARTICIPANTS: 505 (238 male (M), 268 female (F)) elderly (age≥65) multimorbid patients. MAIN OUTCOME MEASURES: The relationship between CDI and CIRS Comorbidity Score, number of comorbidities, antibiotic, antifungal and PPI treatments, and length of hospital stay was assessed through age-adjusted and sex-adjusted and multivariate logistic regression models. The CIRS Comorbidity Score was handled after categorisation in quartiles. RESULTS: Mean age was 80.7±11.3 years. 43 patients (22 M, 21 F) developed CDI. The prevalence of CDI increased among quartiles of CIRS Comorbidity Score (3.9% first quartile vs 11.1% fourth quartile, age-adjusted and sex-adjusted p=0.03). In the multivariate logistic regression analysis, patients in the highest quartile of CIRS Comorbidity Score (≥17) carried a significantly higher risk of CDI (OR 5.07, 95% CI 1.28 to 20.14, p=0.02) than patients in the lowest quartile (<9). The only other variable significantly associated with CDI was antibiotic therapy (OR 2.62, 95% CI 1.21 to 5.66, p=0.01). PPI treatment was not associated with CDI. CONCLUSIONS: Multimorbidity, measured through CIRS Comorbidity Score, is independently associated with the risk of CDI in a population of elderly patients with prolonged hospital stay.

Comorbidities and disease severity as risk factors for carbapenem-resistant Klebsiella pneumoniae colonization: report of an experience in an internal medicine unit.

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.

Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?

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.

Exacerbations of severe asthma: a focus on steroid therapy.

Bronchial asthma remains one of the most common chronic diseases in the world; approximately 10% of patients shows exacerbations severe enough to be judged life-threatening, whereas around 2-20% of patients are admitted to the Intensive Care Unit (ICU). Acute severe asthma is a dangerous condition where the deterioration of the asthmatic exacerbation usually progresses over days or weeks, although in a few patients over hours or even minutes. Morbidity and mortality are mainly related to the underestimation of the severity of the exacerbation, delay in referring to hospital and inadequate emergency treatment. The cornerstone measures of therapy for acute severe asthma are oxygen supplementation, as to achieve arterial saturation >90%, and repetitive or continuous administration of bronchodilators (short-acting inhaled ß2-agonists and ipratropium bromide) and corticosteroids. Despite extensive clinical experience in treatment of chronic asthma with steroids, there is considerable uncertainty about the accurate use of these agents for treatment of acute severe asthma in emergency settings.

Transient global amnesia.

Transient Global Amnesia (TGA) is a clinical syndrome characterized by temporary inability to form new memories described as anterograde amnesia. It is associated with retrograde amnesia and repetitive questioning. During the attack patients remain conscious and communicative and personal identity is preserved. Focal neurological symptoms and epileptic features are absent and general conditions appear intact. The ability to store new memories gradually recovers and subjects return to normal conditions except for a substantial amnestic gap for the duration of the attack. TGA has an incidence of 3-8 per 100 000 people per year. It usually affects patients between the ages of 50 and 70 years, at an average age of 61 years; occurrence in patients younger than 40 years of age is rare. The rate of recurrence is between 6% and 10% per years. No gender prevalence has been recorded. The patients with definite TGA have a very good prognosis; their rate of subsequent major vascular events is less than 1% per year.

Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker for the early diagnosis of acute kidney injury (AKI).

Acute kidney injury (AKI) is a common complication that occurs in a broad spectrum of clinical settings. Cardiac surgery-associated AKI continues to be a well-recognized complication of cardiac surgery with high morbidity and mortality. The lack of early biomarkers has for long prevented timely interventions to mitigate the effects of AKI. Serum creatinine is not a timely marker of AKI, so that it cannot be used to set potentially effective therapies to treat AKI in patients during phases when the injury is still potentially reversible. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a promising biomarker for early detection of AKI. Several studies have shown that NGAL levels significantly increase in AKI patients 24 to 48 hours before a detectable increase of serum creatinine. Recent studies also suggest that measurements of urinary NGAL levels in patients at risk for cardiac surgery-associated AKI may facilitate its early diagnosis and allow clinicians to implement therapeutic adjustments that have the potential to reverse renal cellular damage and minimize further kidney injury.

Fad diets and their effect on urinary stone formation.

The influence of unhealthy dietary habits on urinary stone formation has been widely recognized in literature. Dietary advice is indeed the cornerstone prescription for prevention of nephrolithiasis as well. However, only a small amount of medical literature has addressed the influence of popular or fad diets, often self-prescribed for the management of obesity and overweight or for cultural beliefs, on the risk of kidney stones. Thereby in this paper we analyze the current knowledge on the effects of some popular diets on overall lithogenic risk. High-protein diets, like Dukan diet, raise some concerns, since animal proteins are able to increase urinary calcium and to decrease urinary citrate excretion, thus leading to a high overall lithogenic risk. Low-carbohydrate diets, like Atkins diet or zone diet, may have a protective role against kidney stone formation, but there are also evidences stating that this dietary approach may rise calciuria and decrease citraturia, since it is generally associated to a relatively high intake of animal proteins. Vegan diet can be harmful for urinary stone disease, especially for the risk of hyperuricemia and micronutrient deficiencies, even if only few studies have addressed this specific matter. On the other side, the benefits of a lacto-ovo-vegetarian diet on kidney stone prevention have been largely emphasized, provided that the intake of calcium and oxalate is balanced. Traditional Mediterranean diet should exert a protective effect on nephrolithiasis as well, even if specific studies have not been carried out yet. High phytate and antioxidant content of this diet have however demonstrated to be beneficial in preventing the formation of new or recurrent calculi. Anyway, at the current state of knowledge, the most effective dietary approach to prevent kidney stone disease is a mild animal protein restriction, a balanced intake of carbohydrates and fats and a high intake of fruit and vegetables. Other fundamental aspects, which are often neglected in fad diets, are a normal intake of milk and dairy products and salt restriction. All these nutritional aspects should be greatly taken into account when patients who are willing to undergo fad or commercial diets ask for dietary advice.