Dual combined antiviral treatment with remdesivir and nirmatrelvir/ritonavir in patients with impaired humoral immunity and persistent SARS-CoV-2 infection.

Despite global vaccination efforts, immunocompromized patients remain at high risk for COVID-19-associated morbidity. In particular, patients with impaired humoral immunity have shown a high risk of persistent infection. We report a case series of adult patients with B cell malignancies and/or undergoing B cell targeting therapies with persisting SARS-CoV-2 infection and treated with a combination antiviral therapy of remdesivir and nirmatrelvir/ritonavir, in three Italian tertiary academic hospitals. A total of 14 patients with impaired adaptive humoral immunity and prolonged SARS-CoV-2 infection were treated with the dual antiviral therapy. The median age was 60 (IQR 56-68) years, and 11 were male. Twelve patients had B cell lymphoma, one patient had chronic lymphocytic leukemia and one patient had multiple sclerosis. Thirteen out of 14 patients had received prior B cell-targeting therapies, consisting of anti-CD20 monoclonal antibodies in 11 patients, and chimeric antigen receptor T therapy in 2 patients. The median time between diagnosis and therapy start was 42.0 (IQR 35-46) days. Seven patients had mild, 6 moderate and one severe disease. Nine patients had signs of interstitial pneumonitis on chest computed tomography scans before treatment. The median duration of nirmatrelvir/ritonavir and remdesivir combination therapy was 10 days. All patients showed resolution of COVID-19-related symptoms after a median of 6 (IQR 4-11) days and viral clearance after 9 (IQR 5-11) days. Combination therapy with remdesivir and nirmatrelvir/ritonavir is a promising treatment option for persistent COVID-19 in immunocompromized patients with humoral immunity impairment, worthy of prospective comparative trials.

Are Parapoxvirus zoonotic diseases doomed to remain neglected?

Parapoxvirus (PPV) infections are considered neglected zoonoses because their incidence is often unknown or greatly underestimated despite being endemic globally. Here, we report the comprehensive diagnostic workflow that led to the identification of two cases of persistent PPV infections. The results obtained underline the importance of adopting a "One Health" approach and cross-sectoral collaboration between human and veterinary medicine for precise aetiological diagnosis and correct management of patients affected by zoonotic diseases.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

Background: The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods: A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results: Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion: Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

A singular case of cavernous internal carotid artery aneurysm in patient with cavernous sinus syndrome and bacterial meningitis.

We report the uncommon case of an acute cavernous sinus syndrome in a patient who was consequently discovered to have both a cavernous internal carotid artery aneurysm and bacterial meningitis. Which came first, the chicken or the egg? Which of the two, the aneurysm or the meningitis, gave rise to the patient's symptoms? We briefly reviewed the literature of similar cases and tried to analyze the possible pathophysiological relationship between these findings. Moreover, this case highlights the importance of a multidisciplinary management of these patients to better decide between a medical and a surgical and/or endovascular treatment.

[Respiratory and uro-genital infection with bacillus of Calmette-Guerin following administration as a local adjuvant therapy of bladder carcinoma]. / Infezione respiratoria e genito-urinaria da bacillo di Calmette-Guérin dopo instillazione endovescicale come terapia adiuvante locale di un carcinoma vescicale.

An exemplary case report of dual-site, respiratory and genito-urinary granulomatous infection caused by bacillus of Calmette-Guerin (BCG) in a patient with prior pulmonary tuberculosis and with chronic obstructive pulmonary disease (COPD), treated for several weeks with local, intravesical adjuvant BCG therapy for a relapsing transitional bladder carcinoma, is presented and discussed in the context of the cumbersome diagnostic and differential diagnostic process, as well as recent findings in the literature. Only four cases of respiratory BCG-itis (tuberculosis-like forms) have been reported until now to the best of our knowledge (two of them following bladder instillation of BCG), but our case is the only one which showed a dual, concurrent granulomatous localization of BCG-itis, also involving the genito-urinary tract.

Tubercular disease caused by Bacillus of Calmette-Guérin as a local adjuvant treatment of relapsing bladder carcinoma.

Two (2) exemplary case reports of respiratory granulomatous infection caused by Bacillus of Calmette-Guérin (BCG), in patients who were repeatedly treated with local, intravesical adjuvant BCG therapy for a relapsing transitional bladder carcinoma, are outlined and discussed on the grounds of the cumbersome diagnostic and differential diagnostic process (especially when a prior tuberculosis and a concurrent chronic obstructive pulmonary disease are of concern), along with an updated literature revision. Only 4 cases of respiratory BCG-itis (pulmonary tuberculosis-like forms) have been reported, to date, to the best of our knowledge (2 of them following the bladder instillation of BCG). One (1) episode of ours represents the first described case with a dual, concomitant granulomatous localization of BCG-itis, also involving the genitourinary tract.

Tubercular disease caused by bacillus of Calmette-Guerin administered as a local adjuvant treatment of relapsing bladder carcinoma: Pathogenetic, diagnostic and therapeutic issues, and literature review

Two exemplary case reports of respiratory granulomatous infection caused by bacillus of Calmette-Guérin (BCG) in patients who were repeatedly treated with local, intravesical adjuvant BCG therapy for a relapsing transitional bladder carcinoma, are outlined and discussed, on the ground of the cumbersome diagnostic and differential diagnostic process (especially when a prior tuberculosis and a concurrent chronic obstructive pulmonary disease are of concern), and an updated literature revision. Only four cases of respiratory BCG-itis (pulmonary tuberculosis-like forms), have been reported until now to the best of our knowledge (two of them following bladder instillation of BCG). One episode of ours represents the first described case with a dual, concomitant granulomatous localization of BCG-itis, also involving the genitourinary tract

[Therapeutic use of interferons and their toxicity. Focus on peripheral neuropathy]. / Impiego terapeutico degli interferoni e tossicità correlata. Focus sulle neuropatie periferiche.

When evaluating the tolerability profile of interferons, the authors focus their attention on peripheral neuropathy, by assessing the epidemiological, pathogenetic, clinical, and outcome aspects, in relation with the administration of these drugs and the concurrent increase of risk factors associated with underlying diseases (including chronic viral hepatitis, solid organ malignancies, hematological disorders, autoimmune diseases, HIV infection). Even though it is often impossible to exclude a direct or indirect interferon-associated pathogenetic pathways in the occurrence of peripheral neuropathies, predominatly through immune-mediated mechanisms, the episodes reported by the international literature are steadily on the rise, paralleling the enlargement of therapeutic indications, and the availability of novel interferon formulations for clinical use. The increased indications of interferons in a broadening spectrum of clinical disorders, and especially their use in chronic hepatitis, recommend a strict monitoring of all possible adverse events, in order to reach a better epidemiological, pathogenetic, and clinical awareness of clinical events which are still infrequent, but potentially severe, such as those involving the peripheral nervous system.

Disseminated, lethal prostate cancer during human immunodeficiency virus infection presenting with non-specific features. Open questions for urologists, oncologists, and infectious disease specialists.

INTRODUCTION: Prostate cancer is a very infrequent occurrence in persons aged 55 years or less, and it has been rarely reported in HIV-infected patients (10 overall cases so far); therefore, an increased incidence compared with the general population has not been established, although a younger age seems more frequent among population with HIV disease. CASE REPORT: We report a case of metastatic prostate cancer occurred in a 53-year-old HIV-infected man, admitted due to non-specific signs, and symptoms: impaired general conditions, fever, weight loss, fatigue, and exertional dyspnea. A remarkable anemia and an aortic systolic murmur were the prominent initial findings, while AIDS-related conditions were not suspected due to a sustained CD4+ count and a contained viremia, which never required antiretroviral therapy. Repeated red blood cell transfusions and an empiric, combined antimicrobial therapy were promptly carried out, under the suspicion of infectious endocarditis, but no appreciable improvement of clinical conditions was achieved. Subsequently, our patient complained not only of an increasingly severe pain at the root of his left thigh, together with overcoming dysuria and urgency, but also urinary tract infection that was rapidly ruled out. During the diagnostic workup for an HIV-associated fever of undetermined origin, a bone marrow biopsy disclosed a metastatic prostatic cancer, with elevated prostate specific antigen (PSA) and acid phosphate levels. An abdominal-pelvic ultrasonography and computerized tomographic scan allowed to detect a dyshomogeneous endopelvic expansive mass with extrinsic compression of the urinary bladder, and involvement of the last lumbar vertebra, large portions of pelvis, and the proximal epiphysis of the right femur. A skeleton scintigraphy pointed out multiple hypercaptation (areas of concentrated traces of radioactivity) areas with involvement of cranial, cervical, dorsal, lumbar, and sacral vertebrae, as well as the pelvis and upper portions of both femurs. Despite therapeutic attempts, our patient deceased after seven weeks due to an overwhelming disseminated intravascular coagulation (DIC). CONCLUSIONS: The non-specific clinical presentation of our case (mimicking other generalized or focal illnesses), and the final, lethal complication (DIC) pose striking problems related to the differential diagnosis during HIV disease, while the rapid evolution into an advanced, complicated, and widely metastatic disease with extensive bone marrow invasion which preceded the appearance of local signs-symptoms, and the lethal overwhelming DIC, deserves attention by specialists who care for HIV-infected subjects.

Severe pneumococcal meningitis heralding a deep hypogammaglobulinaemia related to common variable immunodeficiency, at the age of 27 years.

Common variable immunodeficiency with an associated broad immunoglobulin (0.7%) deficit affecting all subclasses, was revealed in a 27-y-old previously healthy female, upon development of a severe pneumococcal meningitis. We report the third case of purulent meningitis complicating this primary immunodeficiency, and the second due to Streptococcus pneumoniae. Clinicians should maintain an elevated suspicion for congenital immunodeficiency, especially when observing adult patients with a negligible prior history.

Hodgkin's disease in the setting of human immunodeficiency virus infection.

The incidence of Hodgkin's disease appears to progressively increase in human immunodeficiency virus (HIV)-infected patients, with the relative risk of developing this malignancy rising from the early phase to the advanced stage of HIV disease. Clinical and pathological features of Hodgkin's lymphoma in HIV-positive subjects differ from those of the general population, showing a higher frequency of unfavourable histological subtypes, advanced stage with frequent extranodal involvement at initial diagnosis, and a poor therapeutic outcome. The optimal therapeutic strategy is still controversial, and median overall survival is short, ranging from 12 to 18 months. In this report cases of Hodgkin's disease are described among over 1,000 HIV-infected patients referring to a tertiary care centre during a 6 y study period.

[Myocardial infarction in hiv patients treated with protease inhibitors: report of two cases]. / Considerazioni su due casi di infarto miocardico in pazienti HIV positivi trattati con inibitori delle proteasi.

The Authors describe two cases of HIV patients treated with Protease Inhibitors that have gone on to suffer from lipodystrophy, metabolic disorder, diabetes and myocardial infarction (fatal in one of them). The surviving patient underwent a Percutaneous Transluminal Coronary Angioplasty (PTCA) with improvement of the acute coronary syndrome. In the light of the review of literature and our observations, we propose some considerations about prevention, diagnostic and therapeutic management of HIV patients treated with IP and cardiovascular risk.