Heel quantitative ultrasound in HIV-infected patients: a cross-sectional study.

PURPOSE: HIV infection has been associated with increased risk of osteoporosis and fragility fractures. Dual-energy X-ray absorptiometry (DXA) is the reference standard to assess bone mineral density (BMD); however, it is not easily accessible in several settings. Heel Quantitative ultrasound (QUS) is a radiation-free, easy-to-perform technique, which may help reducing the need for DXA. METHODS: In this cross-sectional study, we used heel QUS (Hologic Sahara(®)) to assess bone status in a cohort of HIV-infected patients. A QUS stiffness index (QUI) threshold >83 was used to identify patients with a low likelihood of osteoporosis. Moreover, we compared QUS results with those of 36 sex- and age-matched HIV-negative controls. RESULTS: 244 HIV-positive patients were enrolled. Median heel QUI value was 83 (73-96) vs. 93 (IQR 84-104) in the control group (p = 0.04). 110 patients (45 %) had a QUI value ≤83. Risk factors for low QUI values were age (OR 1.04 per year, 95 % CI 1.01-1.07, p = 0.004), current use of protease inhibitors (OR 1.85, CI 1.03-3.35, p = 0.039), current use of tenofovir (OR 2.28, CI 1.22-4.27, p = 0.009) and the number of risk factors for secondary osteoporosis (OR 1.46, CI 1.09-1.95, p = 0.01). Of note, QUI values were significantly correlated with FRAX score (r = -0.22, p = 0.004). According to EACS guidelines, 45 % of patients had risk factors for osteoporosis which make them eligible for DXA. By using QUS, we may avoid DXA in around half of them. CONCLUSIONS: As HIV-positive patients are living longer, the prevalence of osteoporosis is expected to increase over time. Appropriate screening, prevention and treatment are crucial to preserve bone health in this population. The use of screening techniques, such as heel QUS, may help reducing the need for DXA. Further studies are needed to define the diagnostic accuracy of this promising technique in the setting of HIV.

Mucorales/Fusarium Mixed Infection in Hematologic Patient with COVID-19 Complications: An Unfortunate Combination.

Hematological diseases, especially those causing severe neutropenia, represent the main factor in the development of invasive fungal infections (IFIs). Furthermore, COVID-19 has been considerably associated with IFIs due to immunological dysregulation, prolonged hospitalization in intensive care units, and immunomodulatory therapies. Opportunistic molds are correlated with elevated morbidity and mortality rates in these patients, due to immune impairment, diagnostic complexity, and therapeutic challenges. Among opportunistic fungal infections, the Mucorales and Fusarium species are considered particularly aggressive, especially during severe neutropenia. A mixed Mucorales/Fusarium infection has been rarely described in scientific literature. Herein, we report a case of Mucorales and Fusarium co-infection in a patient with acute leukemia whose clinical history was also complicated by COVID-19. Herein, we report a challenging case in order to encourage the clinical suspicion of combined fungal infections in immunosuppressed patients, performing a punctual microbiological diagnosis, and promptly administering the correct empiric and targeted antifungal therapy.

Long-Term Survivors in a Cohort of People Living with HIV Diagnosed between 1985 and 1994: Predictive Factors Associated with More Than 25 Years of Survival.

Although the mortality rate among individuals diagnosed during the pre-Highly Active Antiretroviral Treatment era has been substantial, a considerable number of them survived. Our study aimed to evaluate the prevalence of HIV long-term survivors in a cohort of People Living with HIV diagnosed between 1985 and 1994 and to speculate about potential predictive factors associated to long survival. This is a retrospective single-center study. Subjects surviving more than 300 months (25 years) from HIV diagnosis were defined as Long Term Survivors. Overall, 210 subjects were enrolled. More than 75.24% of the included people living with HIV were males, with a median age of 28 years (IQR 25-34). The prevalent risk factors for HIV infection were injection drug use (47.62%), followed by unprotected sex among heterosexual individuals (23.81%). Ninety-three individuals (44.29%) could be defined as LTS with a median (IQR) survival of 333 (312-377) months. A hazard ratio of 12.45 (95% CI 7.91-19.59) was found between individuals who were exposed to Highly Active AntiRetroviral Treatment (HAART) and individuals who were not, with the latter being at greater risk of death. The availability and accessibility of effective antiretroviral therapy for people living with HIV remain the cornerstone of survival.

Post-infectious ST elevation myocardial infarction following a COVID-19 infection: A case report.

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has been shown to increase the risk of thrombotic events due to a hypercoagulable state caused by several factors. The case of a 59-year-old woman affected by hypertension and metabolic disorders, treated for a COVID-19 infection who developed cardiac symptoms during the first days of hospitalization is reported. Electrocardiogram analysis and cardiac-ultrasound confirmed ST-segment elevation myocardial infarction (STEMI) diagnosis, thus the patient underwent percutaneous coronary intervention, which was successful. This case highlights a possible association between respiratory infection, particularly SARS-CoV-2 infection, and cardiovascular events, in particular Acute Coronary Syndrome. The association between these phenomena seems related to a range of factors, including a proinflammatory state and the hypoxemia. Moreover, the association amongst SARS-CoV-2 and cardiovascular diseases may be also linked to long-term sequelae. Thus, further studies are required to better understand the multifaceted and severe complications of this disease.

Intravenous Fosfomycin: A Potential Good Partner for Cefiderocol. Clinical Experience and Considerations.

Multidrug resistant Gram-negative bacteremia represents a therapeutic challenge clinicians have to deal with. This concern becomes more difficult when causing germs are represented by carbapenem resistant Acinetobacter baumannii or difficult-to-treat Pseudomonas aeruginosa. Few antibiotics are available against these cumbersome bacteria, although literature data are not conclusive, especially for Acinetobacter. Cefiderocol could represent a valid antibiotic choice, being a molecule with an innovative mechanism of action capable of overcoming common resistance pathways, whereas intravenous fosfomycin may be an appropriate partner either enhancing cefiderocol activity or avoiding resistance development. Here we report two patients with MDR Gram negative bacteremia who were successfully treated with a cefiderocol/fosfomycin combination.

Clinical characteristics and predictors of death among hospitalized patients infected with SARS-CoV-2 in Sicily, Italy: A retrospective observational study.

Since late December 2019, severe acute respiratory syndrome coronavirus 2 has spread across the world, which resulted in the World Health Organization declaring a global pandemic. Coronavirus disease 2019 (COVID-19) presents a highly variable spectrum with regard to the severity of illness. Most infected individuals exhibit a mild to moderate illness (81%); however, 14% have a serious disease and 5% develop severe acute respiratory distress syndrome (ARDS), requiring intensive care support. The mortality rate of COVID-19 continues to rise across the world. Data regarding predictors of mortality in patients with COVID 19 are still scarce but are being actively investigated. The present multicenter retrospective observational study provides a complete description of the demographic and clinical characteristics, comorbidities and laboratory abnormalities in a population of 421 hospitalized patients recruited across eight infectious disease units in Southern Italy (Sicily) with the aim of identifying the baseline characteristics predisposing COVID-19 patients to critical illness or death. In this study, older age, pre-existing comorbidities and certain changes in laboratory markers (such as neutrophilia, lymphocytopenia and increased C-reactive protein levels) at the time of admission were associated with a higher risk of mortality. Male sex, on the other hand, was not significantly associated with increased risk of mortality. Symptoms such as fatigue, older age, a number of co-pathologies and use of continuous positive airway pressure were the most significant contributors in the estimation of clinical prognosis. Further research is required to better characterize the epidemiological features of COVID-19, to understand the related predictors of death and to develop new effective therapeutic strategies.

Successful Extracorporeal Membrane Oxygenation Treatment in an Acquired Immune Deficiency Syndrome (AIDS) Patient with Acute Respiratory Distress Syndrome (ARDS) Complicating Pneumocystis jirovecii Pneumonia: A Challenging Case.

BACKGROUND Patients with HIV infection tend to have poor intensive care unit (ICU) outcomes; however, survival in the modern combination antiretroviral therapy (cART) era has markedly improved, but Pneumocystis jirovecii pneumonia (PJP) still remains a preeminent cause of respiratory failure in AIDS patients. Extracorporeal membrane oxygenation (ECMO) is an adapted cardiopulmonary bypass circuit for temporary life support for patients not responding to conventional treatment. CASE REPORT A 43-year-old male HIV "late presenter" was admitted to our hospital for fever and dyspnea. A chest CT scan revealed bilateral ground-glass opacities. Empiric antibiotic treatment and cART were started. The emergence of ARDS due to PJP dictated urgent veno-venous (VV) ECMO placement. One week later, radiologic findings and respiratory function had improved and the patient was started on a weaning trial from ECMO and removed 12 days after placement. CONCLUSIONS Acute respiratory distress syndrome (ARDS) is a potentially reversible clinical syndrome with a high mortality rate. ECMO is a rescue therapy allowing lung recovery during acute processes and should be considered an adequate treatment option in HIV+ patients with respiratory failure. ECMO should be considered a useful and adequate treatment option in AIDS patients who have a high risk of dying from respiratory failure.

Is it Safe and Cost Saving to Defer the CD4+ Cell Count Monitoring in Stable Patients on Art with More than 350 or 500 cells/µl?

BACKGROUND: CD4+ lymphocyte cell count represents the main immunological marker used to monitor HIV infection. However, frequent monitoring may be unnecessary, could cause anxiety to the patient as well as burdening healthcare with extra expenses. OBJECTIVES AND METHODS: A two-step retrospective (safety and cost-saving) analysis was performed to evaluate the probability of maintaining a safe number of more than 350 CD4+ cells/µl in HIV-positive subjects under treatment during a three-year follow up and secondarily to estimate in real life the cost of the CD4+ determinations in a 3 years period, speculating on possible cost-saving strategies. The safety analyses was conducted with Kaplan-Meyer method considering: 1) all patients independently from their viral load (VL); 2) patients with 500 > CD4+ ≥ 350 cells/µl versus (vs) CD4+ ≥ 500 cells/µl at baseline; 3) patients with VL < 20 copies/ml vs VL > 20 copies/ml. The cost-saving analysis measuring the costs of CD4+ determinations was calculated from April 1, 2013, to March 31, 2016. RESULTS: In the safety analysis, 253 subjects were enrolled. The median CD4+ count was 623 (489-805) cells/µl. Subjects maintaining ≥ 350 cells/µl in the first, second, and third year were respectively 238 (94.1%), 229 (90.5%), and 226 (89.3%), independently from VL. Within subjects with ≥ 350 CD4+/µl vs. ≥ 500 CD4+/µl at baseline, those who maintained ≥ 350 cells/µl until the third year were respectively 241 (95.3%) and 158 (98.1%). The probability of maintaining these values in the third year was 89.3% for those who had CD4+ ≥ 350/µl at baseline and 98.1% for those who had CD4+ ≥ 500/µl. This probability was around 90% vs. 99% for subjects with HIV-RNA above or below 20 copies/ml. In the real-life cost saving analysis, we evaluated subjects with a stable value or more than 500 CD4+ (respectively 343, 364 and 383 in the first, second and third period). We observed mean value of about two determinations patient/year (2.41 in 2013/2014; 2.32 in 2014/2015; 2.18 in 2015/2016), with a significant decrease between the first and the last period (p<0.001). The mean cost patient/year was €101.51 in the first year, €97.61 in the second, €92.00 in the third (p<0,001). Assuming to extend these procedures to all our patients with stable CD4+ cells/µl and monitoring CD4+ cell count once in a year, we were able to obtain an overall saving of €19,152/year. CONCLUSIONS: A very high percentage of subjects maintained a high and safe number of CD4+ cells (>350 cells/µl) during a three-year follow-up. It could be possible to save up to 66% of the costs by reducing the number of CD4+ count determinations in a year, to have other favorable consequences as well, releasing new resources for patient management.

High prevalence of parotideal abnormalities among HCV infected patients.

Several salivary diseases, such as Sjogren syndrome (SS), chronic lymphocytic sialadenitis and parotid non-Hodgkin's lymphoma, may occur in the setting of HCV infection. Our aim was to evaluate the prevalence of parotid abnormalities in a cohort of 310 patients with chronic hepatitis C (CHC) attending the Unit of Infectious Diseases of the Garibaldi Nesima Hospital of Catania. Our control group consisted of 188 patients with chronic HBV infection. We found that the prevalence of parotideal diseases was significantly higher among HCV-infected patients in comparison with HBV-infected (17% vs. 1%). Indeed, 53 CHC subjects had parotideal abnormalities: 24 patients (45.3%) had lymphoepithelial cysts of the salivary gland, six patients (11.3%) had a benign tumour, six patients (11.3%) had granulomatous lesions, 12 patients (22.7%) had Sjogren's syndrome and four patients (7.5%) were diagnosed as having chronic lymphocytic sialadenitis. Finally, one patient (1.9%) had parotid non-Hodgkin's lymphoma. In conclusion, parotideal abnormalities are common among HCV-infected individuals and targeted diagnostic protocols may help identify parotid involvement in this population of subjects.

Atypical Presentation of PKDL due to Leishmania infantum in an HIV-Infected Patient with Relapsing Visceral Leishmaniasis.

We describe the case of an Italian patient with HIV infection who developed an atypical rash resembling post-kala-azar dermal leishmaniasis (PKDL) when receiving liposomal Amphotericin B (L-AMB) for secondary prophylaxis of visceral leishmaniasis (VL). At the time of PKDL appearance, the patient was virologically suppressed but had failed to restore an adequate CD4+ T-cell count. Histology of skin lesions revealed the presence of a granulomatous infiltrate, with lymphocytes, plasma cells, and macrophages, most of which contained Leishmania amastigotes. Restriction fragment length polymorphism-polymerase chain reaction was positive for Leishmania infantum. Paradoxically, cutaneous lesions markedly improved when a new relapse of VL occurred. The patient received meglumine antimoniate, with a rapid clinical response and complete disappearance of cutaneous rash. Unfortunately, the patient had several relapses of VL over the following years, though the interval between them has become wider after restarting maintenance therapy with L-AMB 4 mg/kg/day once a month. Even if rare, PKDL due to Leishmania infantum may occur in Western countries and represents a diagnostic and therapeutic challenge for physicians. The therapeutic management of both PKDL and VL in HIV infection is challenging, because relapses are frequent and evidence is often limited to small case series and case reports.

Phylogenetic analysis of isolates from new cases of HBV infection in Southern Italy.

The level of endemicity of hepatitis B virus (HBV) infections in Italy is low and genotype D infections predominant. New HBV strains may however be introduced as a result of movements of people from regions of high endemicity. The aim of the present study was to determine whether strains from new cases of acute hepatitis B detected in southern Italy were due to endemic or new HBV strains. We studied 34 isolates from patients with acute hepatitis B infection, and 35 from chronic hepatitis B patients. A phylogenetic analysis of preS/S region was done by comparing the sequences from the acute and chronic cases with references sequences. The study showed that 44% of strain from acute hepatitis B patients were of genotype A, 53% of genotype D, and 3% of genotype E. The molecular analysis of isolates from acute hepatitis B patients from Sicily showed a change in the local epidemiology of this infection, with an increase in HBV/A infections and a clustering effect for HBV D2, possibly correlated to immigration. The introduction of new genotypes , could have an effect on HBV-correlated diseases due to the different association between genotype, liver disease and response to antiviral therapy.

[Clinical, virological and epidemiological aspects of acute B hepatitis in the Catania area (Italy)]. / Valutazione epidemiologica, virologica e clinica dell'epatite acuta B nella provincia di Catania.

Starting from January 1997 we prospectively evaluated all cases of acute hepatitis B admitted to two of the main Infectious Diseases Units in Catania (eastern Sicily). The survey was extended throughout a 10-year period up to December 2007. Between 1997 and 1999 we observed 21 cases of acute hepatitis B; between 2000 and 2002 18 cases; between 2003 and 2005 22 cases and, finally, 37 cases were reported in the period 2006-2007. We found an increase in acute hepatitis B cases among people aged 26 to 44 years (from 38% in 1997-99 to 70% in 2006-07). A progressive decrease in intravenous drug abuse as a risk factor for acute hepatitis B was also observed (from 61% to 14%) together with a parallel increase in cases due to sexual transmission (from 19% to 56%) and outpatient cosmetic surgical procedures. Mean time to serum HBsAg negativization was longer in the last period (2006-07), with 6 cases out of 37 showing HBsAg persistence beyond 12 months from the clinical onset. Furthermore, in 2006-07 there were 12 cases (42%) of acute hepatitis due to HBV genotypes A and F. In our area, a progressive drop of hepatitis B cases due to intravenous drug abuse occurred, whereas heterosexual and iatrogenic cases increased. Cases due to HBV non-D genotypes may well be related to migration from endemic areas towards Sicily.