Abdominal Lymphadenopathies: Lymphoma, Brucellosis or Tuberculosis? Multidisciplinary Approach-Case Report and Review of the Literature.

Abdominal pain represents a frequent symptom for referral to emergency departments and/or internal medicine outpatient setting. Similarly, fever, fatigue and weight loss are non-specific manifestations of disease. The present case describes the diagnostic process in a patient with abdominal pain and a palpable abdominal mass. Abdominal ultrasonography confirmed the presence of a mass in the mesogastrium. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans oriented toward calcific lymphadenopathies with increased metabolism in the positron emission tomography-computed tomography (PET-CT) scan. Laboratory examinations were inconclusive, although serology for Brucella and the Quantiferon test were positive. After multidisciplinary discussion, the patient underwent surgical excision of the abdominal mass. Histological examination excluded malignancies and oriented toward brucellosis in a patient with latent tuberculosis. The patient was treated with rifampin 600 mg qd and doxycycline 100 mg bid for 6 weeks with resolution of the symptoms. In addition, rifampin was continued for a total of 6 months in order to treat latent tuberculosis. This case underlines the need for a multidisciplinary approach in the diagnostic approach to abdominal lymphadenopathies.

Low eGFR Is a Strong Predictor of Worse Outcome in Hospitalized COVID-19 Patients.

BACKGROUND: The clinical course of COVID-19 is more severe in elderly patients with cardio-metabolic co-morbidities. Chronic kidney disease is considered an independent cardiovascular risk factor. We aimed to evaluate the impact of reduced eGFR on the composite outcome of admission to ICU and death in a sample of consecutive COVID-19 hospitalized patients. METHODS: We retrospectively evaluated clinical records of a consecutive sample of hospitalized COVID-19 patients. A total of 231 patients were considered for statistical analysis. The whole sample was divided in two groups on the basis of eGFR value, e.g., ≥ or <60 mL/min/1.73 m2. Patients with low eGFR were further divided among those with a history of chronic kidney disease (CKD) and those without (AKI, acute kidney injury). The primary outcome was a composite of admission to ICU or death, whichever occurred first. The single components were secondary outcomes. RESULTS: Seventy-nine (34.2%) patients reached the composite outcome. A total of 64 patients (27.7%) died during hospitalization, and 41 (17.7%) were admitted to the ICU. A significantly higher number of events was present among patients with low eGFR (p < 0.0001). Age (p < 0.001), SpO2 (p < 0.001), previous anti-platelet treatment (p = 0.006), Charlson's Comorbidities Index (p < 0.001), serum creatinine (p < 0.001), eGFR (p = 0.003), low eGFR (p < 0.001), blood glucose levels (p < 0.001), and LDH (p = 0.003) were significantly associated with the main outcome in univariate analysis. Low eGFR (HR 1.64, 95% CI 1.02-2.63, p = 0.040) and age (HR per 5 years 1.22, 95% CI 1.10-1.36, p < 0.001) were significantly and independently associated with the main outcome in the multivariate model. Patients with AKI showed an increased hazard ratio to reach the combined outcome (p = 0.059), while those patients with both CKD had a significantly higher probability of developing the combined outcome (p < 0.001). CONCLUSIONS: Patients with reduced eGFR at admission should be considered at high risk for clinical deterioration and death, requiring the best supportive treatment in order to prevent the worst outcome.

A "Galactic" Chest X-ray.

Clinical manifestations accompanying respiratory failure with insidious and rapidly progressive onset are often non-specific. Symptoms such as a cough, dyspnea, and fever are common to a large number of inflammatory, infectious, or neoplastic diseases. During the COVID-19 pandemic it is essential to limit the use of hospital services and inappropriate diagnostic techniques. A particular radiological pattern can orient the clinical and laboratory scenario and guide the diagnostic workup. A 58-year-old woman was admitted to our COVID-19 unit for suspected coronavirus infection. She was complaining of worsening dyspnea, tachycardia, and low grade fever. A chest X-ray showed diffuse, alveolar, and interstitial lung involvement with micronodules tending to coalescence. This radiographic pattern known as "galaxy sign", consistent with diffuse, coalescing nodular miliary pulmonary involvement, simulating a non-specific alveolar opacification of the lungs is typical of a few pneumological differential diagnoses, represented by sarcoidosis, tuberculosis, pneumoconiosis, and metastatic lesions, and virtually excludes an interstitial viral pneumonitis. The use of endoscopic techniques can, in such cases, confirm the clinical suspicion for initiating appropriate targeted therapies.

Diagnosis of COVID-19 in Patients with Negative Nasopharyngeal Swabs: Reliability of Radiological and Clinical Diagnosis and Accuracy Versus Serology.

BACKGROUND: The diagnosis of Coronavirus disease 2019 (COVID-19) relies on the positivity of nasopharyngeal swab. However, a significant percentage of symptomatic patients may test negative. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs. METHODS: Admission chest CT-scans and clinical records of swab-negative patients, treated according to the COVID-19 protocol or deceased during hospitalization, were retrospectively evaluated by two radiologists and two clinicians, respectively. RESULTS: Of 254 patients, 169 swab-confirmed cases and one patient without chest CT-scan were excluded. A total of 84 patients were eligible for the reliability study. Of these, 21 patients died during hospitalization; the remaining 63 underwent serological testing and were eligible for the accuracy evaluation. Of the 63, 26 patients showed anti-Sars-Cov-2 antibodies, while 37 did not. The inter-rater agreement was "substantial" (kappa 0.683) between radiologists, "moderate" (kappa 0.454) between clinicians, and only "fair" (kappa 0.341) between radiologists and clinicians. Both radiologic and clinical evaluations showed good accuracy compared to serology. CONCLUSIONS: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up.

Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease.

Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium.

Carotid intima-media thickness is not associated with vitamin D and PTH levels in patients admitted to an Internal Medicine Department.

Vitamin D (25OHD) and/or parathyroid hormone (PTH) levels have been associated with common carotid intima-media thickness (IMT). We investigated such associations in inpatients consecutively admitted to an Internal Medicine Department. In 168 consecutive patients admitted to our department, 25 hydroxyvitamin D (25OHD) was measured by means of RIA and PTH by means of ICMA, whereas IMT by means of ultrasonography. The main cardiovascular risk factors were also explored. In patients with either diabetes, or hypertension, or both, 25OHD values were not significantly lower than in other patients. No difference was found among the IMT values across tertiles of 25OHD level, as like as in the 25OHD, PTH, PTH/25OHD ratio values of patients either grouped by tertiles of IMT, or categorized according to IMT of <0.9, 0.9-1.5, and >1.5 mm. IMT did not significantly associate with 25OHD, PTH, and PTH/25OHD ratio, whereas it positively associated with age (r = 0.281; p < 0.001) and BMI (r = 0.138; p = 0.074), and negatively with eGFR (r = -154; p = 0.046). Multiple regression models showed that IMT was significantly associated to age and BMI, while 25OHD, PTH, or PTH/25OHD ratio did not increase the significance of the models. IMT assessment does not seem to be associated with 25OHD and PTH levels in unselected inpatients.

Endothelial dysfunction associated with mild cognitive impairment in elderly population.

BACKGROUND AND AIMS: According to the original Petersen criteria, we investigated the association between endothelial dysfunction and mild cognitive impairment (MCI) by flow-mediated dilation (FMD). We aimed to verify if endothelial dysfunction occurs in MCI and whether vascular factors are implicated in the MCI pathogenesis. METHODS: This is a cross-sectional study performed on 34 subjects with clinical diagnosis of MCI and 37 controls, older than 60 years. Patients were enrolled from a geriatric outpatient clinic. All the recognized cardiovascular risk factors and an objective state of cognitive impairment were used as exclusion criteria. Cognitive function was evaluated using a scientific-validated neuropsychological battery, whereas MCI was recognized according to the Petersen criteria. Endothelial function was evaluated according to FMD from the brachial artery. The association between FMD and MCI was evaluated both by using a multivariate analysis and a correlation test. Finally, using the ANOVA analysis of variance, we tested the differences in flow-mediated dilation among MCI subgroups. RESULTS: Brachial FMD was significantly associated with MCI (p < 0.01). The multivariate analysis showed that age, years of education and MMSE independently predicted the FMD variation (r (2)  = 0.73; p < 0.0001). In addition, MCI patients with prevalent amnestic multiple domain impairment showed the worst brachial FMD. CONCLUSIONS: This finding suggests that vascular dysfunction may play a role in the pathogenesis of cognitive impairment and underlines the lack of therapeutic strategies targeted to such dysfunctions.

Influence of the Gly1057Asp variant of the insulin receptor substrate 2 (IRS2) on insulin resistance and relationship with epicardial fat thickness in the elderly.

Insulin receptor substrate 2 (IRS2) plays a crucial role in the regulation of insulin signaling. Several polymorphisms of the gene encoding IRS2 have been identified. The variant causing Gly1057Asp substitution is relatively frequent in humans and its impact on insulin sensitivity seems to be dependent on age and body weight. The aim of our study was to evaluate the relationships between Gly1057Asp variant and insulin sensitivity assessed by HOMA, and adiposity evaluated by measurement of epicardial fat (EpiF) thickness in the elderly. We studied 87 subjects, 42 men and 45 women, mean age±SD: 74.23±7.24years. In the subjects carrying the Gly1057Asp variant of the IRS2 gene we found higher HOMA index values (3.40±1.14 vs. 2.21±1.25, p<0.001) and increased epicardial adipose tissue (11.77±1.65 vs. 10.43±1.93mm, p<0.001) compared to wild type subjects. Univariate linear regression analyses evidenced that HOMA index was correlated with BMI (beta=0.152, p<0.001), fasting plasma glucose (beta=0.018, p=0.002), LDL cholesterol (beta=0.008, p=0.024), total cholesterol (beta=0.007, p=0.039), weight (beta=0.054, p<0.001), presence of Gly1057Asp variant (beta=1.185, p<0.001) and EpiF thickness (beta=0.540, p<0.001). In multivariate analysis HOMA index was still associated with the presence of the Gly1057Asp variant of the IRS-2 gene (beta=0.568, p=0.002) and with EpiF thickness (beta=0.414, p<0.001). Furthermore, a statistically significant positive correlation between EpiF thickness and HOMA was found (r=0.773, p<0.001) and this was not different between wild type control subjects and carriers of Gly1057Asp variant of the IRS2 gene (p=0.718). Similar results were obtained in comparing subjects with normal fasting glucose levels. In conclusion, in our elderly subjects the presence of the allelic variant Gly1057Asp of IRS2 gene was associated to the degree of insulin resistance assessed by HOMA index and with EpiF thickness, independently from the extent of obesity, suggesting its contribution to global cardiometabolic risk.

Oxidative stress and aging.

The fountain of youth has always been a myth for mankind. Aging is a physiologic state in which a progressive decline of organ functions is accompanied with the development of age-related diseases. The causes of aging remain unknown, probably being related to a multifactorial process. To date, the free radical and mitochondrial theories seem to be the 2 most prominent theories on aging and have survived the test of time. Such theories claim that oxidative stress within mitochondria can lead to a vicious cycle in which damaged mitochondria produce increased amounts of reactive oxygen species, leading in turn to progressive augmentation in damage. If aging results from oxidative stress, it may be corrected by environmental, nutritional and pharmacological strategies. This review summarizes the role of free radicals and oxidative stress in developing aging in kidney and human pathologies.

Endothelial dysfunction evaluated by flow mediated dilation is strongly associated to metabolic syndrome in the elderly.

This study was carried out to assess whether endothelial dysfunction, evaluated by flow-mediated dilation (FMD), is related to the occurrence of the Metabolic Syndrome (MetS) in old age. Eighty patients (25 men and 55 women), mean age 74.1±7.4 years (range 65-99 yrs) were studied. Information on all subjects, medical history and regular medications was obtained. Subjects underwent a clinical examination and laboratory tests. The presence of MetS was evaluated according to the revised NCEP-ATP III criteria. An ultrasound vascular examination (US) of the carotid and brachial arteries was performed in all patients. Intima-media thickness (IMT), presence of plaques (PL), endothelium-dependent (EDV) and -independent vasodilation (EIDV) were also evaluated. Patients were divided into two groups according to the presence/absence of MetS. Significant differences were found between MetS and non MetS patients in: EDV (p<0.01), EIDV (p<0.05) and Homeostatic model assessment index (HOMA) (p<0.02), but not in IMT or PL. MetS was significantly associated with FMD reduction (R 0.4, p<0.005) independently of all possible confounding factors other than EIDV, IMT and PL.