Outcome of Pneumocystis pneumonia in transplant and non-transplant HIV-negative immunocompromised patients.

BACKGROUND: Previous studies showed HIV-negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV-negative immunocompromised patients. METHODS: In this retrospective cohort study at the University Health Network, we included all HIV-negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28-day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non-SOT patients. RESULTS: Of 160 non-HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21-87] years). PCP presentation in SOT recipients (n = 14) was more severe than non-SOT patients (n = 104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p = .037), shortness of breath (100% vs. 75/104 [74.3%], p = .037), median [range] O2 saturation (88% [75%, 99%] vs. 92%[70%, 99%], p = .040), and supplemental O2 requirement (12/14 [85.7%] vs. 59/104 [56.7%], p = .044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p = .176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p < .0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p = .0007) in SOT patients was different from non-SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non-SOT patients (aOR [CI95%]: 12.25 [3.08-48.62], p < .001). CONCLUSION: PCP presentation and outcomes in SOT recipients are more severe than in non-SOT patients. Further studies are required to explore the biological reasons for this difference.

Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies.

BACKGROUND: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. METHODS: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. RESULTS: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). CONCLUSIONS: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.

A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis.

Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/µL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

Problematic Social Media Use in Young Adults: A Mixed Serial-Parallel Mediation Model Involving Alexithymia, Defense Mechanisms, and Fear of Missing Out.

Problematic social media use (PSMU) can have profound and detrimental effects across various domains of life. As a result, scientific investigations into the risk factors associated with this phenomenon can hold substantial practical implications within the clinical and preventive realms. Consistently with this framework, this study aimed to examine the relationship between certain variables and PSMU, with a specific focus on alexithymia, defense mechanisms, and fear of missing out (FoMO). A sample of 340 young adults (Mage = 26.42 years; SD = 3.689) completed an online survey, including the Bergen Social Media Addiction Scale, FoMO scale, 40-Item Defense Style Questionnaire, and 20-Item Toronto Alexithymia Scale. Results showed a statistically significant mixed serial-parallel mediation model. A significant total effect in the association between alexithymia and FoMO emerged. Furthermore, defense mechanisms and FoMO significantly and totally mediated this relationship. These findings have the potential to provide valuable insights in the field of clinical research on PSMU, and can offer practical information for enhancing clinical practice.

Risk factors for COVID-19-associated pulmonary aspergillosis: a systematic review and meta-analysis.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been reported to be an emerging and potentially fatal complication of severe COVID-19. However, risk factors for CAPA have not been systematically addressed to date. METHODS: In this systematic review and meta-analysis to identify factors associated with CAPA, we comprehensively searched five medical databases: Ovid MEDLINE; Ovid Embase; the Cochrane Database of Systematic Reviews; the Cochrane Central Register of Controlled Trials; and the WHO COVID-19 Database. All case-control and cohort studies in adults (aged >18 years) that described at least six cases of CAPA and evaluated any risk factors for CAPA, published from Dec 1, 2019, to July 27, 2023, were screened and assessed for inclusion. Only studies with a control population of COVID-19-positive individuals without aspergillosis were included. Two reviewers independently screened search results and extracted outcome data as summary estimates from eligible studies. The primary outcome was to identify the factors associated with CAPA. Meta-analysis was done with random-effects models, with use of the Mantel-Haenszel method to assess dichotomous outcomes as potential risk factors, or the inverse variance method to assess continuous variables for potential association with CAPA. Publication bias was assessed with funnel plots for factors associated with CAPA. The study is registered with PROSPERO, CRD42022334405. FINDINGS: Of 3561 records identified, 27 articles were included in the meta-analysis. 6848 patients with COVID-19 were included, of whom 1324 (19·3%) were diagnosed with CAPA. Diagnosis rates of CAPA ranged from 2·5% (14 of 566 patients) to 47·2% (58 of 123). We identified eight risk factors for CAPA. These factors included pre-existing comorbidities of chronic liver disease (odds ratio [OR] 2·70 [95% CI 1·21-6·04], p=0·02; I2=53%), haematological malignancies (OR 2·47 [1·27-4·83], p=0·008; I2=50%), chronic obstructive pulmonary disease (OR 2·00 [1·42-2·83], p<0·0001; I2=26%), and cerebrovascular disease (OR 1·31 [1·01-1·71], p=0·05; I2=46%). Use of invasive mechanical ventilation (OR 2·83; 95% CI 1·88-4·24; p<0·0001; I2=69%), use of renal replacement therapy (OR 2·26 [1·76-2·90], p<0·0001; I2=14%), treatment of COVID-19 with interleukin-6 inhibitors (OR 2·88 [1·52-5·43], p=0·001; I2=89%), and treatment of COVID-19 with corticosteroids (OR 1·88 [1·28-2·77], p=0·001; I2=66%) were also associated with CAPA. Patients with CAPA were typically older than those without CAPA (mean age 66·6 years [SD 3·6] vs 63·5 years [5·3]; mean difference 2·90 [1·48-4·33], p<0·0001; I2=86%). The duration of mechanical ventilation in patients with CAPA was longer than in those without CAPA (n=7 studies; mean duration 19·3 days [8·9] vs 13·5 days [6·8]; mean difference 5·53 days [1·30-9·77], p=0·01; I2=88%). In post-hoc analysis, patients with CAPA had higher all-cause mortality than those without CAPA (n=20 studies; OR 2·65 [2·04-3·45], p<0·0001; I2=51%). INTERPRETATION: The identified risk factors for CAPA could eventually be addressed with targeted antifungal prophylaxis in patients with severe COVID-19. FUNDING: None.

First detection in Spain of NDM-1-producing Pseudomonas aeruginosa in two patients transferred from Ukraine to a university hospital.

OBJECTIVES: Carbapenemase-mediated carbapenem resistance in Pseudomonas aeruginosa is a relevant health problem. We detected for the first time in Spain two clinical NDM-producing P. aeruginosa (NDM-Pa) isolates in two Ukrainian patients admitted to our hospital between April and August 2022. METHODS: Antimicrobial susceptibility was studied by microdilution and MIC gradient strips (EUCAST-2022 criteria). Carbapenemase genes were detected by the Xpert Carba-R and immunochromatography assays. WGS (Illumina and Oxford-Nanopore) was also performed. RESULTS: In May 2022, we detected an NDM-Pa in a sternotomy wound in a patient. In June-2022, a second NDM-Pa along with an OXA-48-Klebsiella pneumoniae (OXA-48-Kp) isolate was detected in a mandibular abscess from an unrelated patient. Moreover, an NDM+OXA-48-K. pneumoniae (NDM+OXA-48-Kp) was also found in a rectal sample of this patient. Both patients had undergone surgery in Ukraine before their transfer to our hospital. NDM-Pa isolates were resistant to all tested antimicrobials with the exception of aztreonam (MIC = 8 mg/L), colistin (MIC =2 mg/L) and cefiderocol (MIC range = 0.75-2 mg/L). WGS confirmed that both P. aeruginosa isolates were NDM-1 producers, belonged to ST773 and shared an identical resistome. blaNDM-1 was located on a ∼117-Kb chromosomally integrated integrative conjugative element (ICE). OXA-48-Kp and NDM+OXA-48-Kp belonged to ST147 and contained blaOXA-48 on an identical ∼300-Kb IncHIB-plasmid. blaNDM-1 was located on a 51-Kb IncFIB-plasmid only found in NDM+OXA-48-Kp. CONCLUSIONS: This is the first description of NDM-Pa in Spain. We highlight the threat of further cross-border dissemination of NDM-1 through P. aeruginosa along with K. pneumoniae high-risk clones also carrying OXA-48, which draws a complex epidemiological scenario.

Alexithymia and Loneliness in Women with Endometriosis. Testing the Factorial Structure of the Italian Endometriosis Health Profile (EHP-30) and a Mediation Model.

Objective: Endometriosis is a pathological condition characterized by endometrial-like tissue outside the uterus, chronic inflammatory reaction, and pelvic pain that dramatically decrease women's health-related quality of life (HRQoL). Furthermore, this invisible and difficultly diagnosable disease might lead women to experience alexithymia, loneliness, and consequent impairment of perceived quality of life. Firstly, the present study aimed at validating the Italian EHP-30 version which is the most used specific questionnaire for HRQoL measurement. Secondly, the present study aimed at exploring the still understudied relationship between alexithymia and HRQoL in endometriosis conditions, evaluating the mediating role of perceived loneliness. Method: A total of 435 women with endometriosis (mean age=35.75 years) have been involved. All items were loaded on their own factors. Results: The measure showed good internal consistency (Cronbach's α ranged between 0.60-0.95 for core and 0.74-0.94 for modular parts). The Italian EHP-30 is a psychometrically valid measure of HRQoL with endometriosis. The tested mediation model provided adequate goodness-of-fit indices (χ2 (51) = 206.071; p < 0.001; RMSEA = 0.084; 90%CI: 0.072, 0.096, CFI = .933, SRMR= 0.058), showing that alexithymia only indirectly affected women's perceived HRQoL, via the mediating effect of feelings of loneliness. Conclusions: The current study highlighted the pivotal role of perceived loneliness in directly affecting women's quality of life and mediating the effect of the alexithymic experiences.