Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

A COPD Case-Finding Program in a Large Cohort of HIV-Infected Persons.

BACKGROUND: COPD screening guidelines in patients with HIV are lacking, and data about its under-diagnosis are still limited. This study aimed to determinate the feasibility of a case-finding program and the prevalence of COPD under-diagnosis in a large cohort of HIV-infected subjects. METHODS: All out-patients attending their routine visit for HIV monitoring at Spedali Civili General Hospital in Brescia, Italy, from February 2015 to January 2016, were enrolled. The case-finding program was structured in three steps: questionnaire administration, pre-bronchodilator spirometry testing measured with a portable spirometer, and post-bronchodilator diagnostic spirometry during a pulmonology appointment. RESULTS: A total of 1,463 subjects were included; the average age was 46.2 ± 10.3 y. Two hundred eighty-two subjects had a positive questionnaire; 190 completed portable spirometry, and approximately 34% (65 of 190 subjects) reported respiratory impairment; of these 65 subjects, 33 completed diagnostic spirometry, and 66.7% (22 of 33) showed evidence of COPD, including 2 subjects with severe airway obstruction (GOLD stage 3, according to the Global Initiative for Chronic Obstructive Lung Disease). High dropout rates were observed in our program. Individuals with COPD exacerbations showed lower CD4+ cell counts at screening compared to those without acute worsening of symptoms (534 cells/mm3 for subjects with GOLD 1 exacerbations and 495 cells/mm3 for subjects with GOLD 2 exacerbations vs 781 cells/mm3 for those without acute worsening of symptoms). The positive predictive value of the COPD screening questionnaire and portable spirometry was 33.8%. CONCLUSIONS: COPD may be under-diagnosed in HIV-infected people, and case-finding programs are an urgent issue to address as part of routine practice in these individuals.

Perinatally HIV-Infected Youths After Transition from Pediatric to Adult Care, a Single-Center Experience from Northern Italy.

With the development of combination antiretroviral therapy (cART), the first generation of perinatally HIV-infected children has reached young adulthood. A retrospective study was conducted on perinatally HIV-infected young adults after transition to adult care in Brescia (Northern Italy). Twenty-four patients were transferred to Infectious Disease outpatient Clinic from Pediatric Clinic between 2004 and 2016. Median age at transition was 18 years. 37.5% were male, and 75% were Italian. Median CD4+ T-cell count was 534 cell/µL, and 9/24 presented detectable HIV-RNA at the time of transition. At month 12 after transition, median CD4+ T-cell count was 626 cell/µL, and HIV-RNA was still detectable in 25% of patients. Nineteen patients were still in care at the end of follow-up (median of 52 months); 100% on cART, with undetectable HIV-RNA and a median CD4+ T-cell count of 716 cell/µL. After transition, cART regimen was modified in 14/19 patients (in 13 of them it was modified at least twice). Resistance testing is available for 13 patients showing resistance-associated mutations to at least one class of drugs in 9 patients. Transition to adult care is a critical point and youths present lower rates of viral suppression compared to adults. We observed 80% of viral suppression (5 young patients were lost to follow-up and considered as failures), notwithstanding social problems and resistance mutations. With the availability of more potent and better-tolerated drugs, optimization of cART is possible also in this previously difficult-to-treat group of patients. Novel tools to address adherence to cART in young adults and teenagers will also be needed.

Comparison between the gold standard DXA with calcaneal quantitative ultrasound based-strategy (QUS) to detect osteoporosis in an HIV infected cohort

ABSTRACT Introduction: Osteoporosis represents one of the most frequent comorbidity among HIV patients. The current standard method for osteoporosis diagnosis is dual-energy X-ray absorptiometry. Calcaneal quantitative ultrasound can provide information about bone quality. The aims of this study are to compare these two methods and to evaluate their ability to screen for vertebral fracture. Methods: This cross-sectional study was conducted in HIV patients attending the Clinic of Infectious and Tropical Diseases of Brescia during 2014 and who underwent lumbar/femoral dual-energy X-ray absorptiometry, vertebral fracture assessment and calcaneal quantitative ultrasound. The assessment of osteoporosis diagnostic accuracy was performed for calcaneal quantitative ultrasound and for vertebral fracture comparing them with dual-energy X-ray absorptiometry. Results: We enrolled 73 patients and almost 48% of them had osteoporosis with at least one of the method used. Vertebral fracture were present in 27.4%. Among patients with normal bone measurements, we found vertebral fracture in proportion between 10% and 30%. If we used calcaneal quantitative ultrasound method and/or X-ray as screening, the percentages of possible savable dual-energy X-ray absorptiometry ranged from 12% to 89% and misclassification rates ranged from 0 to 24.6%. A combined strategy, calcaneal quantitative ultrasound and X-Ray, identified 67% of patients with low risk of osteoporosis, but 16.4% of patients were misclassified. Conclusions: We observed that patients with osteoporosis determined by calcaneal quantitative ultrasound and/or dual-energy X-ray absorptiometry have higher probability to undergo vertebral fracture, but neither of them can be used for predicting vertebral fracture. Use of calcaneal quantitative ultrasound for screening is a reasonable alternative of dual-energy X-ray absorptiometry since our study confirm that none strategy is clearly superior, but both screen tools must be always completed with X-ray.

Comparison between the gold standard DXA with calcaneal quantitative ultrasound based-strategy (QUS) to detect osteoporosis in an HIV infected cohort.

INTRODUCTION: Osteoporosis represents one of the most frequent comorbidity among HIV patients. The current standard method for osteoporosis diagnosis is dual-energy X-ray absorptiometry. Calcaneal quantitative ultrasound can provide information about bone quality. The aims of this study are to compare these two methods and to evaluate their ability to screen for vertebral fracture. METHODS: This cross-sectional study was conducted in HIV patients attending the Clinic of Infectious and Tropical Diseases of Brescia during 2014 and who underwent lumbar/femoral dual-energy X-ray absorptiometry, vertebral fracture assessment and calcaneal quantitative ultrasound. The assessment of osteoporosis diagnostic accuracy was performed for calcaneal quantitative ultrasound and for vertebral fracture comparing them with dual-energy X-ray absorptiometry. RESULTS: We enrolled 73 patients and almost 48% of them had osteoporosis with at least one of the method used. Vertebral fracture were present in 27.4%. Among patients with normal bone measurements, we found vertebral fracture in proportion between 10% and 30%. If we used calcaneal quantitative ultrasound method and/or X-ray as screening, the percentages of possible savable dual-energy X-ray absorptiometry ranged from 12% to 89% and misclassification rates ranged from 0 to 24.6%. A combined strategy, calcaneal quantitative ultrasound and X-Ray, identified 67% of patients with low risk of osteoporosis, but 16.4% of patients were misclassified. CONCLUSIONS: We observed that patients with osteoporosis determined by calcaneal quantitative ultrasound and/or dual-energy X-ray absorptiometry have higher probability to undergo vertebral fracture, but neither of them can be used for predicting vertebral fracture. Use of calcaneal quantitative ultrasound for screening is a reasonable alternative of dual-energy X-ray absorptiometry since our study confirm that none strategy is clearly superior, but both screen tools must be always completed with X-ray.

Incidence of cardiovascular events in HIV-positive patients compared to general population over the last decade: a population-based study from 2000 to 2012.

Cardiovascular diseases are currently a main cause of death among people living with HIV. This population-based study aimed to investigate the incidence of cardiovascular events (CVEs) in HIV-positive people and factors associated with CVEs. We performed a retrospective cohort study of the HIV-infected patients residing in the Local Health Authority of Brescia, northern Italy, from 2000 to 2012. Incidence of CVEs events in HIV-positive patients was compared with that expected in general population living in the same area, computing standardized incidence ratios (SIRs). CVEs-associated risk factors were assessed using Cox regression analysis and competing risk model of death. About 3766 HIV-infected patients were included in the study. Over the 12-year-period, we recorded 134 CVEs: 83 (61.9%) acute myocardial infarctions (CVE type-1), and 51 (38.1%) strokes (CVE type-2). A twofold increased risk (SIR = 2.02) of CVEs was found in HIV-infected patients compared to the general population. Notably, within male patients: for CVE type-1, SIR = 1.89, for CVE type-2 SIR = 2.25; within female patients: for CVE type-1, SIR = 2.91, for CVE type-2 SIR = 2.07. Age >45 years, male gender, diabetes, and total blood cholesterol >200 mg/dl were significantly associated with CVEs incidence (for all, p < .05). These results were confirmed using the competing risk model. Our cohort study confirmed the higher incidence of CVEs in HIV-positive patients, and put emphasis on the importance of traditional cardiovascular risk factors. Overall CVE risk in HIV-positive patients was twice as high as CVE risk in general population. We found a peculiar gender distribution, with a relative risk for CVE type-1 higher in HIV-positive females, and a higher CVE type-2 risk in male patients. More studies are needed in order to support these findings and to further highlight possible gender differences in the risk of developing CVEs in HIV-positive patients.

Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy.

Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD--standard deviation--3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis.

Molecular epidemiology and phylogenetic analysis of Hepatitis B virus in a group of migrants in Italy.

BACKGROUND: Hepatitis B virus infection (HBV) is widespread and it is considered a major health problem worldwide. The global distribution of HBV varies significantly between countries and between regions of the world. Among the many factors contributing to the changing epidemiology of viral hepatitis, the movement of people within and between countries is a potentially important one. In Italy, the number of migrant individuals has been increasing during the past 25 years. HBV genotype D has been found throughout the world, although its highest prevalence is in the Mediterranean area, the Middle East and southern Asia. We describe the molecular epidemiology of HBV in a chronically infected population of migrants (living in Italy), by using the phylogenetic analysis. METHODS: HBV-DNA was amplified and sequenced from 43 HBV chronically infected patients. Phylogenetic and evolutionary analysis were performed using both maximum Likelihood and Bayesian methods. RESULTS AND CONCLUSION: Of the 43 HBV S gene isolates from migrants, 25 (58.1 %) were classified as D genotype. Maximum Likelihood analysis showed an intermixing between Moldavian and foreigners sequences mostly respect to Italian ones. Italian sequences clustered mostly together in a main clade separately from all others. The estimation of the time of the tree's root gave a mean value of 17 years ago, suggesting the origin of the tree back to 1992 year. The skyline plot showed that the number of infections softly increased until the early 2005s, after which reached a plateau. Comparing phylogenetic data to the migrants date of arrival in Italy, it should be possible that migrants arrived in Italy yet infected from their country of origin. In conclusion, this is the first paper where phylogenetic analysis and genetic evolution has been used to characterize HBV sub genotypes D1 circulation in a selected and homogenous group of migrants coming from a restricted area of Balkans and to approximately define the period of infection besides the migration date.

Point-of-care screening, prevalence, and risk factors for hepatitis B infection among 3,728 mainly undocumented migrants from non-EU countries in northern Italy.

BACKGROUND: Screening migrants from areas where hepatitis B virus (HBV) infection is endemic is important to implement preventive measures in Europe. The aim of our study was to assess (1) the feasibility of point-of-care screening in a primary care clinic and (2) hepatitis B surface antigen (HBsAg) prevalence, associated risk factors, and its clinical and epidemiological implications in undocumented migrants in Brescia, northern Italy. METHODS: A longitudinal prospective study was conducted from January 2006 to April 2010 to assess HBsAg reactivity and associated risk factors among consenting undocumented migrants who accessed the Service of International Medicine of Brescia's Local Health Authority. Genotyping assay was also performed in HBV DNA-positive patients. RESULTS: Screening was accepted by 3,728/4,078 (91.4%) subjects consecutively observed during the study period, 224 (6%) of whom were found to be HBsAg-positive. HBsAg reactivity was independently associated with the prevalence of HBsAg carriers in the geographical area of provenance (p < 0.001). On the contrary, current or past sexual risk behaviors (despite being common in our sample) were not associated with HBV infection. Half of the HBsAg patients (111/224) had either hepatitis B e-antigen (HBeAg)-positive or -negative chronic HBV infection with a possible indication for treatment. HBV genotypes were identified in 45 of 167 HBV-infected patients as follows: genotype D, 27 subjects; genotype A, 8; genotype B, 5; and genotype C, 5. The geographical distribution of genotypes reflected the geographic provenance. CONCLUSIONS: Our results suggest that point-of-care screening is feasible in undocumented migrants and should be targeted according to provenance. Case detection of HBV infection among migrants could potentially reduce HBV incidence in migrants' contacts and in the general population by prompting vaccination of susceptible individuals and care of eligible infected patients.

HIV infection among illegal migrants, Italy, 2004-2007.

To determine HIV prevalence and place of exposure for illegal migrants in Italy, we tested 3,003 illegal adult migrants for HIV; 29 (0.97%) were HIV positive. Antibody avidity index results (indicators of time of infection) were available for 27 of those persons and showed that 6 (22.2%) presumably acquired their infection after migration.

Dead blood under my skin.

The diagnostic attitude of western physicians toward migrants' complaints is often an unstable balance between the obstinate search for exotic tropical diseases and the overappreciation of the cultural dimensions of symptoms. Such attitude may divert attention from organic diseases. The careful assessment of all levels of possible misunderstandings (prelinguistic, linguistic, metalinguistic, cultural, and metacultural) may help the physician to discriminate between illness and disease. The long and difficult itinerary leading to the correct diagnosis of congenital myopathy in a migrant from Senegal is described, together with the barriers encountered by the caring staff.

Forty meals for a drop of blood ...

Increasing migration flow to Western countries poses formidable challenges from the epidemiological, clinical, and cultural standpoints. A case of Dhat syndrome is presented in a young Pakistani male migrant living in Italy, which required integrated medical and cultural approach to be solved after a through diagnostic workout that did not yield any result.

QuantiFERON-TB Gold test in the identification of latent tuberculosis infection in immigrants.

BACKGROUND: The identification and treatment of latent tuberculosis infection (LTBI) among immigrants are an effective strategy for TB control in developed countries. A new test for LTBI identification that uses more specific antigens of Mycobacterium tuberculosis is now commercially available under the brand name of QuantiFERON-TB Gold test. OBJECTIVE: To compare QuantiFERON-TB Gold test to tuberculin skin testing (TST) for the detection of LTBI among immigrants from high endemic TB areas. PATIENTS AND METHODS: Undocumented immigrants attending a district medical center were enrolled if they originated from high endemic TB areas, the time of arrival in Italy was < or = 5 years, had neither active TB disease nor known immunodeficiency status. The TST was applied according to standards and QuantiFERON-TB Gold test was performed following the manufacturer's instructions. RESULTS: Hundred subjects were included in the comparative analysis. TST was positive in 44% of subjects; 15% had a positive QuantiFERON-TB Gold test result. The total agreement between TST and QuantiFERON-TB Gold test was 71%, for a kappa statistics of 0.37; agreement was 100% for TST negative results, but only 34% for TST positive ones. In the multivariate logistic regression analysis, previous BCG vaccination was independently associated with a lower chance of disagreement between the tests. CONCLUSION: The prevalence of LTBI among immigrants was lower when determined by QuantiFERON-TB Gold; this may be a consequence of more specific MTB antigens used. Our results suggest that QuantiFERON-TB Gold may be used as confirmatory test for TST positive immigrants candidate to preventive therapy.