Disseminated nocardiosis and anti-GM-CSF antibodies.

Infections that are unusually severe or caused by opportunistic pathogens are a hallmark of primary immunodeficiency (PID). Anti-cytokine autoantibodies (ACA) are an emerging cause of acquired immunodeficiency mimicking PID. Nocardia spp. are Gram-positive bacteria generally inducing disseminated infections in immunocompromised patients, but seldom also occurring in apparently immunocompetent hosts. Anti-GM-CSF autoantibodies are associated with autoimmune pulmonary alveolar proteinosis (PAP). In those patients, an increased incidence of disseminated nocardiosis and cryptococcosis has been observed. It is unclear whether the PAP or the autoantibodies predispose to the infection. We report an apparently immunocompetent woman presenting with disseminated nocardiosis without any evidence of PAP. Clinical data and radiological images were retrospectively collected. Lymphocyte populations were analyzed by flow cytometry. Anti-GM-CSF autoantibodies were measured by ELISA. A 55-year-old otherwise healthy woman presented with cerebral and pulmonary abscesses. Personal and familial history of infections or autoimmunity were negative. After extensive examinations, a final diagnosis of disseminated nocardiosis was made. Immunologic investigations including neutrophilic function and IFN-γ/IL-12 circuitry failed to identify a PID. Whole-exome sequencing did not find pathogenic variants associated with immunodeficiency. Serum anti-GM-CSF autoantibodies were positive. There were no clinical or instrumental signs of PAP. Trimethoprim-sulfamethoxazole and imipenem were administered, with progressive improvement and recovery of the infectious complication. We identified anti-GM-CSF autoantibodies as the cause of disseminated nocardiosis in a previously healthy and apparently immunocompetent adult. This case emphasizes the importance of including ACA in the differential diagnosis of PID, especially in previously healthy adults. Importantly, anti-GM-CSF autoantibodies can present with disseminated nocardiosis without PAP.

SSRIs in the course of COVID-19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study.

INTRODUCTION: Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels. METHODS: The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed. RESULTS: The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison. CONCLUSIONS: Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

Preoperative echocardiography in patients with hip fracture: a prospective cohort study.

Introduction: Although clinical guidelines suggest echocardiography before surgery in patients with hip fracture, no prospective studies exist in the literature. The aim of the present investigation was to assess whether preoperative echocardiography affects time to surgery, length of hospital stay (LOS), and in hospital mortality in high-risk patients who need surgery for a hip fracture. Material and methods: In the study entered 255 consecutive patients with hip fracture referred to a multidisciplinary hip fracture unit. Seven hundred seventeen patients referred before the implementation of routine echocardiographic examination were considered as control group. Echocardiography was performed in patients with systolic murmurs, unstable clinical conditions, recent decompensation of heart failure or hospital admission for coronary disease. Time to surgery, LOS, and in hospital mortality in patients who underwent preoperative echocardiography (high-risk group) were compared with patients who did not undergo echo (low-risk group) and with the control group. Results: 122/255 patients underwent echocardiography. The two groups did not differ for age, sex, type or fracture, and notably time to surgery and LOS. Coronary heart disease, atrial fibrillation, and two or more comorbidities were more frequent in the echo group. Overall clinical characteristics were not different from group of patients referred before the implementation of the echocardiographic protocol but in these last patients time to surgery and LOS were significantly longer. As well in hospital mortality was not significantly different in the two groups (1.9 in echo vs. 1.7% in nonecho) but lower than in the control group (4.1% ). Conclusions: An echocardiographic guide may be useful in a high-risk group with a hip fracture to choose the proper anesthetic setting, referral for intensive care observation after surgery and, optimal medical treatment, including fluid management without delay in time to surgery.

Effects of Atrial Fibrillation Radiofrequency Ablation in Patients Aged > 75 Years Undergoing Mitral Valve Surgery.

BACKGROUND: Few data exist about the efficacy of radiofrequency (RF) maze procedures in elderly patients with atrial fibrillation (AF) undergoing surgery for mitral valve disease. The aim of the present investigation was to evaluate the effects of AF ablation associated with mitral valve surgery on the recovery and long-term maintenance of sinus rhythm in elderly patients aged > 75 years. Moreover, we evaluated the effects on survival. METHODS AND RESULTS: This study included 96 consecutive patients with AF (42 men and 56 women) aged > 75 years (mean age 78 ± 3) who underwent RF ablation associated with mitral valve surgery (group I). This group was compared to 209 younger patients (mean age 65 ± 8 years) treated in the same period (group II). Baseline clinical and echocardiographic characteristics were similar in the two groups. Four patients died during hospitalization, one aged > 75 years. In surviving patients at the end of the follow-up period, sinus rhythm was present respectively in 64% of the elderly and 74% of younger patients (p = 0.778). The rate of persistence of sinus rhythm without AF recurrences (38% vs. 41%, p = 0.705) was similar in the two groups. After surgery, sinus rhythm was frequently never regained in aged patients (27% vs. 20%, p = 0.231). Elderly patients more frequently needed permanent pacing and had more hospitalizations and a higher number of non-AF atrial tachyarrhythmias. At eight-year follow-up, survival was lower in older patients (48% aged > 75 vs. 79% aged < 75 years). CONCLUSION: Elderly patients had a similar long-term rate of stable sinus rhythm maintenance in comparison to younger patients after AF radiofrequency ablation associated with mitral valve surgery. However, they needed more frequent permanent pacing and had higher rates of hospitalizations and post-procedural atrial tachyarrhythmias. The effects of survival are difficult to evaluate due to the different life expectancies of the two groups.

Leukostasis retinopathy with leukemic infiltrates as onset manifestation of chronic myeloid leukemia: a case report.

PURPOSE: To describe a case of retinopathy as onset manifestation of chronic myeloid leukemia (CML), successfully treated with leukapheresis and medical therapy. METHODS: A 28-year-old male patient presented complaining painless acute visual impairment in his right eye (RE). He reported moderate asthenia and episodes of night sweats during the previous month. His past medical history was unremarkable. BCVA at presentation was 20/80 in RE and 20/32 in left eye (LE). Fundus examination revealed venous congestion, diffuse Roth spots, and whitish macular infiltrates in both eyes. OCT showed hyperreflective foveal infiltrates, in both eyes. Blood test showed markedly elevated white blood cells (WBCs) count (430 × 103/mm3). Clinical-instrumental examination revealed hepatosplenomegaly. These features were consistent with CML. The patient was treated with leukapheresis and nilotinib. RESULTS: After 2 weeks of treatment, the WBCs count dropped (71 × 103/mm3), and the patient reported subjective improvement of symptoms. At 1-month follow-up, BCVA and retinopathy signs were improved in both eyes. OCT showed the almost complete resolution of foveal infiltrates with ellipsoid zone focal defects. At 4-months follow-up, we observed complete resolution of retinopathy. BCVA was 20/32 in RE and 20/25 in LE. OCT showed the persistence of ellipsoid zone focal defects in RE and complete anatomical restoration in LE. At 6-months follow-up, the patient was clinically well and his WBCs count was normal. CONCLUSION: In our case, the CML-related retinopathy represented the onset sign of the underlying systemic pathology, leading to proper management and treatment, with hematological normalization and resolution of the retinopathy.

Acute heart failure in the elderly: setting related differences in clinical features and management.

BACKGROUND: Administrative data show that acute heart failure (HF) patients are older than those enrolled in clinical registries and frequently admitted to non-cardiological settings of care. The purpose of this study was to describe clinical characteristics of old patients hospitalised for acute HF in Cardiology, Internal Medicine or Geriatrics wards. METHODS: Data came from ATHENA (AcuTe Heart failurE in advaNced Age) registry which included elderly patients (≥ 65 years) admitted to the above mentioned settings of care from December 1, 2014 to December 1, 2015. RESULTS: We enrolled 396 patients, 15.4% assigned to Cardiology, 69.7% to Internal Medicine, and 14.9% to a Geriatrics ward. Mean age was 83.5 ± 7.6 years (51.8% of patients ≥ 85 years) and was higher in patients admitted to Geriatrics (P < 0.001); more than half were females. Medical treatments did not differ significantly among settings of care (in a context of a low prescription rate of renin-angiotensin-aldosterone system inhibitors) whereas significant differences were observed in comorbidity patterns and management guidelines recommendation adherence for decongestion evaluation with comparison of weight and N-terminal pro-B-type natriuretic peptide levels on admission and at discharge (both P = 0.035 and P < 0.001), echocardiographic evaluation ( P < 0.001) and follow-up visits planning ( P < 0.001), all higher in Cardiology. Mean in-hospital length of stay was 9 ± 5.9 days, significantly higher in Geriatrics (13.7 ± 6.5 days) and Cardiology (9.9 ± 6.7 days) compared to Internal Medicine (8 ± 5.2 days), P < 0.001. In-hospital mortality was 9.3%, resulting higher in Geriatrics (18.6%) and Cardiology (16.4%) than Internal Medicine (5.8%), P = 0.001. CONCLUSIONS: In elderly patients hospitalised for acute HF, clinical characteristics and management differ significantly according to the setting of admission.

Use of the FebriDx point-of-care test for the exclusion of SARS-CoV-2 diagnosis in a population with acute respiratory infection during the second (COVID-19) wave in Italy.

OBJECTIVE: Evaluate the real-world accuracy of Myxovirus resistance protein A (MxA) detected by the rapid, point-of-care FebriDx test during the second-wave pandemic in Italy in patients with acute respiratory infection (ARI) and a clinical suspicion of COVID-19. DESIGN AND METHODS: Prospective, observational, diagnostic accuracy study whereby hospitalized patients with ARI were consecutively enrolled in a single tertiary care center in Italy from August 1, 2020 to January 31, 2021. RESULTS: COVID-19 was diagnosed in 136/200 (68.0%) patients and Non-COVID-19 was diagnosed in 64/200 (32.0%) patients. COVID-19 patients were younger and had a lower Charlson comorbidity index compared to Non-COVID-19 patients (p < 0.001). Concordance between FebriDx, MxA and rt-PCR for SARS-CoV-2 (gold standard) was good (k 0.93, 95% CI 0.87-0.99). Overall sensitivity and specificity were 97.8% [95% CI 93.7-99.5] and 95.3% [95% CI 86.9%-99.0%], respectively. FebriDx demonstrated a negative predictive value of 95.3% (95% CI 86.9-99.0) for an observed disease prevalence of 68%. CONCLUSIONS: FebriDx MxA showed high diagnostic accuracy to identify COVID-19 and could be considered as a real-time triage tool to streamline the management of suspected COVID-19 patients. FebriDx also detected bacterial etiology in Non-COVID-19 patients suggesting good performance to distinguish bacterial from viral respiratory infection.

Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: a randomized controlled trial.

AIMS: Although acute decompensated heart failure (ADHF) is a common cause of dyspnoea, its diagnosis still represents a challenge. Lung ultrasound (LUS) is an emerging point-of-care diagnostic tool, but its diagnostic performance for ADHF has not been evaluated in randomized studies. We evaluated, in patients with acute dyspnoea, accuracy and clinical usefulness of combining LUS with clinical assessment compared to the use of chest radiography (CXR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in conjunction with clinical evaluation. METHODS AND RESULTS: This was a randomized trial conducted in two emergency departments. After initial clinical evaluation, patients with acute dyspnoea were classified by the treating physician according to presumptive aetiology (ADHF or non-ADHF). Patients were subsequently randomized to continue with either LUS or CXR/NT-proBNP. A new diagnosis, integrating the results of both initial assessment and the newly obtained findings, was then recorded. Diagnostic accuracy and clinical usefulness of LUS and CXR/NT-proBNP approaches were calculated. A total of 518 patients were randomized. Addition of LUS had higher accuracy [area under the receiver operating characteristic curve (AUC) 0.95] than clinical evaluation alone (AUC 0.88) in identifying ADHF (P < 0.01). In contrast, use of CXR/NT-proBNP did not significantly increase the accuracy of clinical evaluation alone (AUC 0.87 and 0.85, respectively; P > 0.05). The diagnostic accuracy of the LUS-integrated approach was higher then that of the CXR/Nt-proBNP-integrated approach (AUC 0.95 vs. 0.87, p < 0.01). Combining LUS with the clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to 2.42 cases/100 patients in the CXR/Nt-proBNP group. CONCLUSION: Integration of LUS with clinical assessment for the diagnosis of ADHF in the emergency department seems to be more accurate than the current diagnostic approach based on CXR and NT-proBNP.

Accuracy of abdominal ultrasound for the diagnosis of pneumoperitoneum in patients with acute abdominal pain: a pilot study.

BACKGROUND: Pneumoperitoneum is a rare cause of abdominal pain characterized by a high mortality. Ultrasonography (US) can detect free intraperitoneal air; however, its accuracy remains unclear. The aims of this pilot study were to define the diagnostic performance and the reliability of abdominal US for the diagnosis of pneumoperitoneum. METHODS: This was a prospective observational study. Four senior and two junior physicians were shown, in an unpaired randomized order, abdominal US videos from 11 patients with and 11 patients without pneumoperitoneum. Abdominal US videos were obtained from consecutive patients presenting to ED complaining abdominal pain with the diagnosis of pneumoperitoneum established by CT. Abdominal US was performed according to a standardized protocol that included the following scans: epigastrium, right and left hypochondrium, umbilical area and right hypochondrium with the patient lying on the left flank. We evaluated accuracy, intra- and inter-observer agreement of abdominal US when reviewed by senior physicians. Furthermore, we compared the accuracy of a "2 scan-fast exam" (epigastrium and right hypochondrium) vs the full US examination and the accuracy of physicians expert in US vs nonexpert ones. Finally, accuracy of US was compared with abdominal radiography in patients with available images. RESULTS: Considering senior revision, accuracy of abdominal US was 88.6 % (95 % CI 79.4-92.4 %) with a sensitivity of 95.5 % (95 % CI 86.3-99.2 %) and a specificity of 81.8 % (95 % CI 72.6-85.5 %). Inter- and intra-observer agreement (k) were 0.64 and 0.95, respectively. Accuracy of a "2 scan-fast exam" (87.5 %, 95 % CI 77.9-92.4 %) was similar to global exam. Sensitivity of abdominal radiography (72.2 %, 95 % CI 54.8-85.7 %) was lower than that of abdominal US, while specificity (92.5 %, 95 % CI 79.5-98.3 %) was higher. Accuracy (68.2 %, 95 % CI 51.4-80.9 %) of junior reviewers evaluating US was lower than senior reviewers. CONCLUSIONS: Senior physicians can recognize US signs of pneumoperitoneum with a good accuracy and reliability; sensitivity of US could be superior to abdominal radiography and a 2 fast-scan exam seems as accurate as full abdominal examination. US could be a useful bedside screening test for pneumoperitoneum. Trial registry ClinicalTrials.gov; No.: NCT02004925; URL: http://www.clinicaltrials.gov.

Diagnostic performance of emergency transthoracic focus cardiac ultrasound in suspected acute type A aortic dissection.

Type A aortic dissection (AD) is a deadly disease. Rapid identification of patients requiring immediate advanced aortic imaging or transfer to specialized centers is needed to improve outcomes. We evaluated the diagnostic performance of transthoracic focus cardiac ultrasound (FOCUS) performed by emergency physicians, alone and in combination with the aortic dissection detection (ADD) risk score in suspected type A AD. This was a prospective study performed on patients with suspected type A AD. FOCUS evaluated the presence of intimal flap/intramural hematoma (direct signs of AD), ascending aorta dilatation, aortic valve insufficiency or pericardial effusion/tamponade (indirect signs of AD). The ADD risk score of each patient was calculated according to guidelines. The final diagnosis was established after review of complete clinical data. 50 (18%) patients of 281 had a final diagnosis of type A AD. Detection of any FOCUS sign (direct or indirect) of AD had a sensitivity of 88% (95% CI 76-95%) for the diagnosis of type A AD. Presence of ADD risk score > 0 or detection of any FOCUS sign increased diagnostic sensitivity to 96% (95% CI 86-99%). Detection of direct FOCUS signs had a specificity of 94% (95% CI 90-97%), while combination of ADD risk score > 1 with detection of direct FOCUS signs had a specificity of 98% (95% CI 96-99%). FOCUS demonstrated acceptable accuracy as a triage tool to rapidly identify patients with suspected type A AD needing advanced aortic imaging or transfer, but it cannot be used as a stand-alone test even if combined with ADD risk score classification.

Point-of-care testing of cholesterol and triglycerides for epidemiologic studies: evaluation of the multicare-in system.

Cardiovascular disease is the leading cause of death in the world with 80% of cardiovascular events that occur in low- and middle-income countries. Reliable data on the prevalence of risk factors in developing countries can be obtained in door-to-door epidemiologic studies with the use of automatic instruments. This study was performed to assess the sensitivity and specificity of a low-cost and manageable point-of-care testing (POCT) instrument (HPS MultiCare-in, Italy) for cholesterol and triglyceride assays. Plasma blood samples were obtained from consecutive subjects referred to our clinic for diagnostic evaluation. The analyzer currently used in our central laboratory (ADVIA 2400; Siemens, Deerfield, Ill) was used as comparison method. The inter-assay imprecision (expressed as variation coefficient) of the MultiCare POCT system was 4.51% (range, 2.38%-8.54%) and was 3.29% (range, 1.06%-7.45%) for cholesterol and triglycerides systems, respectively. The mean percent bias for capillary samples was 3.5 +/- 4.3% for total cholesterol and -2.4 +/- 4.9% for triglycerides. The difference in results obtained by nonprofessionals compared with professionals (practicability testing) was 0.28 +/- 7.61% and 1.26 +/- 9.86%, respectively (P value was nonsignificant for both). Sensitivity and specificity measurements were 95.7% and 61.9% (threshold value of cholesterol 190 mg/dL) and 98% and 93.5% (threshold value of triglycerides 170 mg/dL), respectively. POCT instruments are essential to perform epidemiologic studies while avoiding transportation and storage of biologic material. The characteristics of sensitivity and specificity as well as diagnostic accuracy make the POCT instrument useful for obtaining an accurate stratification of a study population.