Risk of SARS-CoV-2 infection and severe COVID-19 in hematological patients who received or not pre-exposure prophylaxis with tixagevimab/cilgavimab: a target trial emulation.

We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who received prophylaxis (cases) were compared to those who did not (controls). The main outcome was SARS-CoV-2 infection in the subsequent 6 months. Inverse probability weighting (IPW) was used to adjust for confounders. A multivariable analysis was performed to identify variables associated with SARS-CoV-2 infection. We recruited 462 patients: 228 received prophylaxis, 234 were controls. COVID-19 was lower in cases compared to controls (16.7% vs 24.8%, p = 0.03, after IPW 14.3% vs 24.6%, p = 0.01). On multivariable analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, p = 0.037) were associated with increased risk of COVID-19, while tixagevimab/cilgavimab prophylaxis (HR 0.45, 95%CI 0.27-0.73, p = 0.001) and previous SARS-CoV-2 infection (HR 0.27, 95%CI 0.14-0.51, p < 0.001) were protective. In conclusion, prophylaxis with monoclonal antibodies may reduce the risk of COVID-19 in hematological patients.

Uncommon Haemorrhagic Cystitis of Infectious Origin: A Narrative Review for Urologists.

Purpose: Haemorrhagic cystitis may be due to different etiologies with infectious diseases representing an insidious cause to diagnose. The aim of this narrative review is to provide a comprehensive overview of less common but difficult-to-diagnose causes of infectious haemorrhagic cystitis of bacterial, mycobacterial, and parasitic origin, Moreover, we highlight possible diagnostic tools and currently available treatment options in order to give an updated tool for urologists to use in daily practice. Patients and Methods: The search engine PubMed was used to select peer-reviewed articles published from 1/Jan/2010 to 31/Aug/2022. Results: Bacteria, fungal, TB and schistosomiasis are uncommon causes of haemorrhagic cystitis burdened by high morbidity, especially if not promptly diagnosed. Conclusion: Because haemorrhagic cystitis ranges in severity from mild dysuria associated with pelvic discomfort to severe life-threatening haemorrhage, punctual diagnosis, and immediate treatment are essential to avoid further complications.

Treatment of latent tuberculosis infection in incarcerated people: a systematic review.

BACKGROUND: The estimated number of people deprived of liberty is increasing, with 11.55 million incarcerated globally in 2021. Transmission of Mycobacterium tuberculosis strains is facilitated in over-crowded, poorly ventilated settings, such as jails and penitentiaries. Moreover, inmates may show individual risk factors for the development of tuberculosis disease. Treatment regimens for latent tuberculosis infection (LTBI) may require up to 9 months of drug exposure and are characterized by adverse events (AE) and low completion rates. OBJECTIVES: To describe current scientific evidence on feasibility, acceptability, and completion rate of LTBI treatment in prison or correctional institutes. DATA SOURCES: Articles were retrieved from MEDLINE/PubMed, no time restriction was applied. STUDY ELIGIBILITY CRITERIA: Human retrospective and prospective studies published on LTBI treatment in incarcerated populations were included. ASSESSMENT OF RISK OF BIAS: Bias assessment plots and Egger weighted regression test were used to determine the risk of bias. METHODS OF DATA SYNTHESIS: Absolute and relative frequencies were assessed for qualitative data. Pooled proportion of included study groups and 95% confidence interval estimates, weighted for sample sizes, were illustrated in forest plots. I2 indicator association were used for true variability and overall variation. Fixed and random-effects models were chosen depending on the estimated between-study heterogeneity. RESULTS: Of the 11 selected studies, only 1 was conducted in a high tuberculosis incidence country. Overall, completion rates ranged from 26% to 100% across the included studies. Reason for the discontinuation of treatment were transfer to other facilities, release, or loss to follow-up (range, 0-74%), incidence of AEs (range, 0-18%), and refusal or withdrawal from treatment (range, 0-16%). CONCLUSIONS: Implementation of short-course regimens in prisons should be considered given the low incidence of AEs observed; however, inmates consistently refused to complete LTBI treatment, thus underlining the need for improvement in retention in care.

Efficacy and Safety of Nirmatrelvir/Ritonavir, Molnupiravir, and Remdesivir in a Real-World Cohort of Outpatients with COVID-19 at High Risk of Progression: The PISA Outpatient Clinic Experience.

INTRODUCTION: Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression. METHODS: This prospective observational study conducted in the University Hospital of Pisa (January 2022-July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization. RESULTS: Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one. CONCLUSION: Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs.

Pretomanid for tuberculosis treatment: an update for clinical purposes.

Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.

Infectious Diseases in Internationally Adopted Children and Intercountry Discrepancies Among Screening Protocols, A Narrative Review.

Internationally adopted children (IAC) require thorough health assessments at time of arrival in the host country. As these children are at higher risk for infectious diseases, such as gastrointestinal parasites, tuberculosis, hepatitis, syphilis, and human immunodeficiency virus, early diagnosis of infectious diseases is fundamental for the optimal management of the child and, also, to reduce the risk of transmission to the adopting community. Comparative analysis of the screening protocols adopted in Europe, the United States, and Canada revealed different approaches to the adopted children. A homogeneous and internationally shared standard of care in the management of IAC should be provided.

Use of Second-line Medications and Treatment Outcomes in Children With Tuberculosis in a Single Center From 2007 to 2018.

BACKGROUND: The incidence of drug-resistant forms of tuberculosis (DR-TB) and the number of children treated with second-line drugs (SLDs) are increasing. However, limited amount of information is available regarding the use of SLDs in this population. METHODS: To describe the treatment of pediatric TB with SLDs and factors associated with use of SLDs in children with and without documented DR-TB, records of pediatric TB patients referred to a center in Italy from 2007 to 2018 were reviewed retrospectively. RESULTS: Of 204 children diagnosed with active TB during the study period, 42 were treated with SLDs because of confirmed or probable drug resistance (42.8%), adverse reactions to first-line drugs (7.1%), central nervous system involvement (11.9%) or unconfirmed possible drug resistance (38.1%). There were no deaths or adverse reactions to SLDs reported. Treatment was successful in 85.2% children treated with first-line drugs and 92.9% children treated with SLDs. After adjusting for calendar period, the only factor associated with DR-TB was <2 years old [odds ratio (OR): 5.24 for <2 years vs. 5-18 years; P = 0.008]. Factors associated with treatment with SLDs were TB at 2 or more sites (OR: 11.30; P < 0.001), extrapulmonary TB (OR: 8.48; P < 0.001) or adverse reactions to first-line drugs (OR: 7.48; P = 0.002). No differences were noted in age or region of origin. CONCLUSIONS: A substantial proportion of TB children were treated with SLDs. The main reason for using SLDs was failure of a first-line drug regimen, suggesting possible DR-TB and underestimation of DR-TB in children. The use of SLD regimens was associated with a high success rate and good tolerability profile.

Treating children with tuberculosis: new weapons for an old enemy.

Tuberculosis has risen to worldwide attention due to its widespread diffusion and overall impact on health and life expectancy. Despite being historically neglected, children require a different approach and management from adults. From the treatment of drug-susceptible pulmonary tuberculosis to extensively drug-resistant strains, and extrapulmonary disease, therapies in children require revision and a more children-oriented approach. We therefore exposed the main critical points and differences between treatment in adults and children and the possible consequences on outcome, safety and tolerability.

Combined capillary-venous-lymphatic malformations without overgrowth in patients with Klippel-Trénaunay syndrome.

OBJECTIVE: Klippel-Trénaunay syndrome (KTS) is described in the literature as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with limb overgrowth. In the first description by Maurice Klippel and Paul Trénaunay, tridimensional bone hypertrophy was believed to be the cause of limb enlargement. The purpose of this study was primarily to assess the presence of real bone hypertrophy as a cause of enlargement of the limb and to underline the rare presence of undergrowth of the affected limb in patients with KTS. METHODS: A two-center retrospective review including 17 KTS patients with various combinations of capillary, venous, and lymphatic malformation affecting the lower limb was performed. Differences in limb dimension were evaluated clinically. Width and length discrepancy of the affected limb was measured with radiologic imaging. RESULTS: We found an increase of length in the affected limb in 80% of the patients. The leg length discrepancy varied from 0.2 to 2.6 cm. The median leg length discrepancy was found to be 1.4 cm. Three patients had a reduced length of the affected limb. Girth enlargement of the affected extremity was noticed in 60% of the patients, and 2 of 17 patients had hypotrophy of the involved limb. Hypertrophy (an increase in both length and width) of the bone was found in none of our cases, and the circumferential enlargement of the affected extremity was related only to soft tissue enlargement. CONCLUSIONS: In the literature, KTS is considered the prototype of overgrowth syndromes associated with complex vascular malformations. The majority of our patients showed limb length increase associated with soft tissue enlargement without an increase of bone width; there were also two patients with limb undergrowth. A real bone overgrowth (an increase in both length and width) was not present in our patients. Therefore, we could consider the absence of real bone hypertrophy as probably a new aspect of such confusing and controversial definitions of KTS. In addition, it would be more accurate to classify KTS patients on the basis of their phenotypic features (type of vascular malformation, types of overgrown tissue) rather than by use of an outdated eponym.