COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge.

B cell-targeting strategies such as rituximab are widely used in B cell hematologic malignancies, rheumatologic and musculoskeletal diseases and a variety of autoimmune disorders. The purpose of this paper is to illustrate how exposure to anti-CD20 treatment profoundly affects B cell functions involved in anti-SARS-CoV-2 immunity and significantly impacts on the clinical and serological course of SARS-CoV-2 infection, long term immunity and vaccine responses. The data presented here suggest that the effects of B cell-depleting agents on adaptive immunity should be taken into account for the proper selection and interpretation of SARS-CoV-2 diagnostics and to guide appropriate therapeutic approaches and protective measures. Combination therapeutic strategies including immunotherapy in association with prolonged antiviral treatment may play a decisive role in the setting of B cell immune deficiencies.

Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19.

Importance: An altered sense of smell and taste has been reported to be associated with coronavirus disease 2019 (COVID-19). To understand the evolution of these symptoms during the course of the disease is important to identify patients with persistent loss of smell or taste and estimate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the burden of olfactory and gustative dysfunctions. Objective: To evaluate the evolution of the loss of sense of smell and taste in a case series of mildly symptomatic patients with SARS-CoV-2 infection. Design, Setting, and Participants: This cross-sectional survey-based study included 202 mildly symptomatic adults (≥18 years) consecutively assessed at Treviso Regional Hospital, Italy, between March 19 and March 22, 2020, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction on nasopharyngeal and throat swabs. Main Outcomes and Measures: Prevalence of altered sense of smell and taste at follow-up and their variation from baseline. Results: Of 202 patients completing the survey at baseline, 187 (92.6%) also completed the follow-up survey (103 [55.1%] women; median age, 56 years). The evaluation of the evolution of altered sense of smell or taste in the 113 patients reporting sudden onset of these symptoms at baseline showed that 55 patients (48.7%; 95% CI, 39.2-58.3) reported complete resolution of smell or taste impairment, 46 (40.7%; 95% CI, 31.6-50.4) reported an improvement in the severity, and only 12 (10.6%; 95% CI, 5.6-17.8) reported the symptom was unchanged or worse. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection. Conclusions and Relevance: At 4 weeks from the onset, 89% of the SARS-CoV-2-positive mildly symptomatic patients who had had a sudden onset of altered sense of smell or taste experienced a complete resolution or improvement of these symptoms. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection.

New onset of loss of smell or taste in household contacts of home-isolated SARS-CoV-2-positive subjects.

PURPOSE: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. METHODS: Cross-sectional study based on ad hoc questions. RESULTS: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p < 0.001). CONCLUSION: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection.

Association between hepatitis C and B viruses and head and neck squamous cell carcinoma.

BACKGROUND: Hepatitis B and C viruses are known to be carcinogenic and have been associated with the development of non-Hodgkin's lymphoma as well as hepatocellular carcinoma. The incidence of head and neck cancer is increasing worldwide, and early diagnosis is vital in order to achieve good oncological outcomes. OBJECTIVES: To investigate the association between chronic hepatitis B and C infection, and head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: We performed a retrospective case control study with 774 head and neck squamous cell carcinoma (HNSCC) patients undergoing treatment, and 1518 cancer-free controls undergoing hernia surgery. Hepatitis B and C serologies were tested prior to treatment, and cases and controls were age- and sex-matched before analysing rates of infection. RESULTS: HNSCC patients were more likely than controls to have evidence of chronic hepatitis B (OR = 2.76; CI 95 %, 1.64-4.64) and hepatitis C (OR = 2.59; 95 % CI, 1.46-4.60) infection. No substantial association was found between hepatitis B and C infection and other known risk factors for head and neck cancer. CONCLUSIONS: These findings suggest a positive association between both hepatitis B and hepatitis C chronic infection, and HNSCC. More work is needed to establish a causal role, however an awareness of the possibility of increased risk of HNSCC may lead to earlier diagnosis and better outcomes in patients with hepatitis B and C.

Mycobacterium chimaera infections following cardiac surgery in Treviso Hospital, Italy, from 2016 to 2019: Cases report.

BACKGROUND: An epidemic of Mycobacterium chimaera (M. chimaera) infections following cardiac surgery is ongoing worldwide. The outbreak was first discovered in 2011, and it has been traced to a point source contamination of the LivaNova 3T heater-cooler unit, which is used also in Italy. International data are advocated to clarify the spectrum of clinical features of the disease as well as treatment options and outcome. We report a series of M. chimaera infections diagnosed in Treviso Hospital, including the first cases notified in Italy in 2016. CASE SUMMARY: Since June 2016, we diagnosed a M. chimaera infection in nine patient who had undergone cardiac valve surgery between February 2011 and November 2016. The time between cardiac surgery and developing symptoms ranged from 6 to 97 mo. Unexplained fever, psychophysical decay, weight loss, and neurological symptoms were common complaints. The median duration of symptoms was 32 wk, and the longest was almost two years. A new cardiac murmur, splenomegaly, choroidoretinitis, anaemia or lymphopenia, abnormal liver function tests and hyponatremia were common findings. All the patients presented a prosthetic valve endocarditis, frequently associated to an ascending aortic pseudoneurysm or spondylodiscitis. M. chimaera was cultured from blood, bioprosthetic tissue, pericardial abscess, vertebral tissue, and bone marrow. Mortality is high in our series, reflecting the poor outcome observed in other reports. Three patients have undergone repeat cardiac surgery. Five patients are being treated with a targeted multidrug antimycobacterial regimen. CONCLUSION: Patients who have undergone cardiac surgery in Italy and presenting with signs and symptoms of endocarditis must be tested for M. chimaera.

Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010-2013).

INTRODUCTION: Pseudomonas aeruginosa is the predominant pathogen responsible of chronic colonization of the airways in cystic fibrosis (CF) patients. There are few European data about antibiotic susceptibility evolution of P aeruginosa in CF patients. OBJECTIVES: The aim of this study is to evaluate the evolution of antibiotic resistance in the period 2010-2013 in CF patients chronically colonized by P aeruginosa and to highlight the characteristics of this evolution in patients younger than 20 years. METHODS: Clinical and microbiological data were extracted from two electronic databases and analyzed. Antibiotic resistance was defined according to European Committee of Antimicrobial Susceptibility Testing for levofloxacin, ciprofloxacin, meropenem, amikacin and ceftazidime. The between-group comparison was drawn with the Chi-square test for proportions, with the T-test for unpaired samples for normally distributed data and with Mann-Whitney test for non-normally distributed data. Significancy was defined by P < .05. RESULTS: Fifty-seven CF patients, including thirteen subjects aged less than 20 years, were enrolled. P.. aeruginosa antibiotic sensitivity decreased significantly for fluoroquinolones, mainly in patients aged <20 years, while it increased for amikacin and colistin. The analysis of minimum inhibitory concentration confirmed these trends. In pediatric patients treated with more than three antibiotic cycles per year, greater resistance was found, except for amikacin and colistin. CONCLUSION: An evolution in P aeruginosa antibiotic resistances is observed in the 4-year period studied. Responsible and informed use of antibiotics is mandatory in CF.

Management of patients with infective endocarditis by a multidisciplinary team approach: an operative protocol.

Even in the modern era of advanced diagnostic imaging, improved antibiotic therapy and potentially curative surgery, infective endocarditis remains a serious disease with high rates of morbidity and mortality. Reasons for such a persistently poor outcome may be represented by the changing epidemiology and microbiology, with new groups of patients at risk and new and more aggressive microorganisms. However, the inadequate use of both diagnostic (blood cultures and echocardiography) and therapeutic (antibiotics and surgery) means can influence the generally delayed diagnosis and poor prognosis seen in patients with infective endocarditis. We tried to identify the critical points in the management of patients with infective endocarditis and to elaborate a formal multidisciplinary approach based on the strict collaboration of specialists in infectious diseases, microbiology, cardiology and cardiac surgery. We hypothesized that this approach could increase the adherence to the published guidelines, and could represent a means to improve the outcome of patients with infective endocarditis.

Management strategies and outcome for prosthetic valve endocarditis.

The aim of this study was to assess the impact of an operative protocol with a multidisciplinary approach on the outcome of patients with prosthetic valve endocarditis (PVE). A formal policy for the care of PVE was introduced at our hospital in 2003 in which patients were referred to and managed by a preexisting team involving a cardiologist, a specialist in infectious diseases, and a cardiac surgeon. All patients underwent transesophageal echocardiography as soon as clinical suspicion of PVE arose. If high-risk conditions such as heart failure, ring abscess, conditions associated with impending malfunctioning of the prosthesis, or vegetations at high risk for systemic embolization were found during the initial multidisciplinary evaluation (performed within 12 hours of admission), patients were operated on within 48 hours. Stable patients were evaluated weekly by the multidisciplinary team, and on-treatment surgery was performed whenever high-risk conditions developed or when there was persistent fever/bacteremia after 1 week of adequate antibiotic therapy. Comparing the period 2003 through 2009 with 1996 through 2002 (when a multidisciplinary policy was not followed), patients with PVE were more numerous (61 vs 38), older (mean age 68.3 vs 63.1, p = 0.01), and had more co-morbidities (mean Charlson index 3.15 vs 2.42, p = 0.03). The most frequent causative organisms were Staphylococci in both periods. In the second period, fewer patients had delayed diagnosis (39% vs 71%, p = 0.03), heart failure (20% vs 45%, p = 0.01), abscess (20% vs 39%, p = 0.04), culture-negative infective endocarditis (11% vs 29%, p = 0.03), and worsened renal function (21% vs 42%, p = 0.04). A significant reduction in in-hospital mortality (53% to 23%, p = 0.04) and 3-year mortality (60% to 28%, p = 0.001) was observed, driven by the increased number of patients successfully treated with medical therapy alone (44% vs 16%, p = 0.04). In conclusion, formalized, collaborative management led to significant improvement in PVE-related mortality.

Impact of a multidisciplinary management strategy on the outcome of patients with native valve infective endocarditis.

Strategies to improve management of patients with native valve endocarditis (NVE) are needed because of persistently high morbidity and mortality. We sought to assess the impact of an operative protocol of multidisciplinary approach on the outcome of patients with NVE. A formal policy for the care of infective endocarditis was introduced at our hospital in 2003 in which patients were referred to and managed by a preexisting team involving a cardiologist, a specialist in infectious diseases, and a cardiac surgeon. The initial multidisciplinary evaluation was performed within 12 hours of admission. Whenever conditions associated with impending hemodynamic impairment, high-risk for systemic embolization, or unsuccessful medical therapy were found, patients were operated on within 48 hours. Stable patients were evaluated weekly by the multidisciplinary team, and on-treatment surgery was performed whenever the above high-risk conditions had developed. Comparing the period 2003 through 2009 with 1996 through 2002 (when a multidisciplinary policy was not followed), patients were more numerous (190 vs 102), older (mean age 59.1 vs 54.2, p = 0.01), and had more co-morbidities (mean Charlson index 3.01 vs 2.31, p = 0.02). The pattern of infection did not change in terms of valve infected or paravalvular complications. In the second period, fewer patients had culture-negative NVE (8% vs 21%, p = 0.01) and worsened renal function (37% vs 58%, p = 0.001). A significant reduction in overall in-hospital mortality (28% to 13%, p = 0.02), mortality for surgery during the active phase (47% to 13%, p ≤0.001), and 3-year mortality (34% vs 16%, p = 0.0007) was observed. In conclusion, formalized, collaborative management led to significant improvement in NVE-related mortality, notwithstanding the less favorable patients' baseline characteristics.

Heterogeneity of West Nile virus genotype 1a in Italy, 2011.

West Nile virus (WNV) is currently circulating in several European countries and, over recent decades, concomitantly with enhanced surveillance studies and improved diagnostic capabilities, an increase in the geographical distribution and in the number of cases in Europe has been documented. In Italy in 2011, 14 human cases of WNV neuroinvasive infections due to lineage 1 strains were registered in several Italian regions. Here we report WNV partial sequences obtained from serum samples of two patients living in different regions of Italy (Veneto and Sardinia). Phylogenetic analysis, performed on a fragment (566 nt) of the envelope gene, showed that WNV strains circulating in Italy in 2011 belong to lineage 1a, but are different from lineage 1a strains isolated in 2008-2009.The data reported here are consistent with the hypothesis of multiple recent introductions of WNV lineage 1a strains into Italy.