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Background A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. Conclusions CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug’s seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Background: Hepatitis C virus (HCV) chronic infection has been associated with increased risk of non-Hodgkin lymphoma (NHL) in people living with human immunodeficiency virus (HIV) as well as with a trend of inferior overall survival (OS) in HIV-associated NHL in the modern antiretroviral therapy (ART) era (Besson 2020). The recent introduction of interferon (IFN)-free direct-acting antivirals (DAAs) led to the achievement of sustained virologic response (SVR) in nearly all treated patients (pts) with negligible toxicity in all settings, including HIV/HCV coinfected pts, in which, however, careful attention to interactions with ART is required. We recently showed that DAAs' administration after immuno-chemotherapy (I-CT) may improve long-term outcome in HIV-negative HCV-associated diffuse large B-cell lymphomas (DLBCL) pts (Merli 2019), however, only scant data have been reported so far about the use of DAAs in HIV/HCV coinfected NHL pts. METHODS: We retrospectively collected clinical and virological features, treatments and outcome data of all consecutive pts with NHL and HIV/HCV co-infection, diagnosed and treated at 13 Italian centers between 2005 and 2021, with a special focus on pts affected by DLBCL and treated with DAAs. Only pts who received ART were included. The primary endpoints were SVR rate after DAAs and 2-year OS in HIV/HCV-positive NHL pts. RESULTS: Overall, we collected data of 74 HIV/HCV coinfected pts with NHL (69 males, 93%), including 52 DLBCL, 13 Burkitt lymphoma (BL), 5 plasmablastic lymphoma (PL), 1 anaplastic large-cell ALK negative, 1 T lymphoblastic, 1 gastric MALT and 1 lymphoplasmacytic lymphoma (Table 1). Median age was 51 years (22-57). Previous AIDS defining event was recorded in 16 cases (22%). The main HIV transmission group was represented by intravenous drug users (69%). Stage was III-IV in 63 pts (85%) and aaIPI was ≥2 in 57 pts (77%). At NHL diagnosis 38% of pts had CD4+ DAAs use was associated with improved OS in all pts (p=0.01) and in DLBCL (p=0.04) and with better PFS (p=0.01) in all pts. Similarly, the achievement of SVR after either DAAs or IFN predicted a better OS (Fig.2) and PFS in all pts (p=0.005 and p=0.008, respectively) and in DLBCL (p=0.018 and p=0.047, respectively). The impact of DAAs and SVR on OS remained significant also if considering only pts who achieved CR or PR after I-CT (p At univariate analysis, age >60 years (p=0.02), ARL-IPI (p=0.013), PS ECOG ≥2 (p=0.018) were associated with inferior OS. By applying multivariate Cox regression analysis, age >60 years (HR 67.9, 95% CI 7.2- 643.3, p CONCLUSIONS: In this very high risk series of HIV/HCV coinfected pts with NHL, mainly represented by DLBCL, the administration of DAAs after I-CT resulted feasible and effective (SVR 95%), and displayed an independent favourable influence on OS. These results strongly support DAAs' use in this hard to treat population. Figure 1 Figure 1. Disclosures Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Passamonti: AbbVie: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau.

BackgroundMesothelioma is a lung cancer that kills thousands of people worldwide annually, especially those with exposure to asbestos. Diagnosis of mesothelioma in patients often requires time-consuming imaging techniques and biopsies. Machine learning can provide for a more effective, cheaper, and faster patient diagnosis and feature selection from clinical data in patient records.Methods and findingsWe analyzed a dataset of health records of 324 patients having mesothelioma symptoms from Turkey. The patients had prior asbestos exposure and displayed symptoms consistent with mesothelioma. We compared probabilistic neural network, perceptron-based neural network, random forest, one rule, and decision tree classifiers to predict diagnosis of the patient records. We measured classifiers' performance through standard confusion matrix scores such as Matthews correlation coefficient (MCC). Random forest outperformed all models tried, obtaining MCC = +0.37 on the complete imbalanced dataset and MCC = +0.64 on the under-sampled balanced dataset. We then employed random forest feature selection to identify the two most relevant dataset traits associated with mesothelioma: lung side and platelet count. These two risk factors resulted so predictive, that decision tree focusing on them achieved the second top accuracy on the complete dataset diagnosis prediction (MCC = +0.28), outperforming all other methods and even decision tree itself applied to all features.ConclusionsOur results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity, in few minutes. Additionally, random forest can efficiently select the most important features of this clinical dataset (lung side and platelet count) in few seconds. The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms. Moreover, doctors can exploit our machinery to predict patient diagnosis when only lung side and platelet data are available.

Phaeohyphomycosis is a diverse group of uncommon mycotic infections caused by dematiaceous fungi which appears to be increasing in incidence, particularly in transplant recipients. Alternaria is the most frequent isolated genus. Subcutaneous, pulmonary and disseminated disease are the most common sites of Alternaria infection in solid organ transplant recipients. We report the first case, to our knowledge, of a kidney transplant recipient with Alternaria alternata subcutaneous infection who was successfully treated with isavuconazole.

Background Multi-targeted treatment strategies including maraviroc (MVC) during Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of this CCR5-inhibitor. Objectives We conducted a proof-of-concept clinical trial aimed at assessing whether maraviroc in addition of a combination antiretroviral therapy (cART) initiated during PHI would improve immunological and virological parameters. Study design The MAIN (Maraviroc in HIV Acute INfection) study was a randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which enrolled 29 patients with PHI. Subjects were randomly assigned to receive cART-only (cART), cART + 8 weeks of MVC (ST-MVC) or cART + 48 weeks of MVC (LT-MVC), regardless of predicted co-receptor usage. After 48 weeks patients in ST-MVC and LT-MVC groups discontinued MVC. Patients were evaluated at week 48 and at week 96 of follow-up to assess differences in CD4 T-cell gain and plasma HIV-RNA. Results Twenty-nine patients were enrolled. Seven patients (24%) had a predicted CXCR4 co-receptor usage. At week 48, 27 patients (93.1%) reached HIV-RNA

Most animal cells contain a structure called the centrosome, which plays a vital role in helping cells to divide for producing new cells. Early in the cell division process, cells make a copy of their centrosome. Each centrosome includes two cylindrical structures called centrioles encased in a complex web of other proteins. The centrioles must get longer for the duplication process to work correctly, but it is not clear which proteins help the centrioles to elongate. Previous work suggested that a protein called PPP1R35 might be a centrosome protein. To investigate its role, Sydor et al. performed experiments that reduced the amount of PPP1R35 in cells grown in the laboratory. Cells that contained fewer PPP1R35 proteins also contained fewer centrioles; these centrioles were also shorter and lacked some of the proteins that can elongate them. Super-resolution microscopy found PPP1R35 in the centre of the centrioles, in a region involved in the early stages of elongation. Sydor et al. also found that PPP1R35 interacts with a protein called RTTN, which is linked to centriole elongation. RTTN contributes to a condition called microcephaly, which prevents the brain from developing properly and results in individuals having a small head. Future work that builds on the findings presented by Sydor et al. could therefore help researchers to understand the causes of microcephaly in patients.

A 39-year-old Ethiopian HIV-positive man with peripheral T-cell lymphoma developed Strongyloides stercoralis hyperinfection. The patient was initially treated with oral ivermectin for three weeks without response, most likely due to malabsorption because of concomitant paralytic ileus. Given the persistence of larvae in the body fluids, the worsening respiratory status and clinical malabsorption, veterinary parenteral formulation of ivermectin was administered. The very high plasma concentration of ivermectin achieved in the patient after parenteral administration led to a rapid improvement in his clinical condition and rapid disappearance of the parasite from biological samples, without any adverse reaction.

Objectives: The aim of the study was to determine the prevalence of abnormal cytological findings, high risk (HR)-HPV genotypes and to identify factors associated with an abnormal cytological findings in a cohort of HIV-infected males. Patients and methods: Retrospective observational study on HIV-infected male patients who performed screening in the absence of clinical symptoms. Cytological abnormalities were classified as atypical squamous cells of undetermined significance (ASC-US), low-grade(LSIL) or high high-grade squamous intraepithelial lesion (HSIL). Logistic regression models were used to identify predictors of having LSIL/HSIL. Results: Among 875 pts, abnormal cytology findings were observed in 254 (29%, 95% CI: 26.1%-32.1%) subjects: 142 (16%) had LSIL and 49 (6%) HSIL. Overall, 581 (66%, 95%CI: 63.2%-69.5%) subjects had ≥1 HR-HPV type and 269 (31%) had ≥2 HR HPV types. Multivariate logistic regression showed that subjects with multiple HR-HPV genotypes (OR = 1.351, 95%CI: 1.005–2.111) and with HPV-16 type (OR = 2.032, 95%CI: 1.313–3.146) were more likely to have LSIL/HSIL in addition to a lower CD4+/CD8+ ratio, a previous diagnosis of syphilis and a positive viral load. In another multivariate model, the presence of multiple HPV types in subjects with HPV-16 type was associated with the highest adjusted OR of having a LSIL/HSIL (OR = 2.598, 95%CI: 1.460–4.624). Conclusions: In HIV-infected men, the prevalence of abnormal cytological findings was of 29% and of HR-HPV was 66%. The concomitant presence of HPV-16 and multiple HR genotypes was associated with an increased risk of abnormal cytological findings. These data highlight the importance of screening multiple HPV genotypes in HIV-infected patients.