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1.
ERJ Open Res ; 9(4)2023 Jul.
Article in English | MEDLINE | ID: mdl-37389899

ABSTRACT

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio (PaO2/FIO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and PaO2/FIO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a PaO2/FIO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted. Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.

2.
IJID Reg ; 6: 167-170, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36910842

ABSTRACT

Objectives: Healthcare-associated bacteraemia is defined as bacteraemia diagnosed ≤48 h after hospital admission in patients recently exposed to healthcare procedures or settings. It differs from hospital-acquired bacteraemia, which is diagnosed >48 h after hospital admission. Healthcare-associated bacteraemia is reported increasingly, often due to resistant pathogens including extended-spectrum beta-lactamase (ESBL) producers, representing a challenge to empirical treatment. This study aimed to assess the appropriateness of empirical treatment for ESBL bacteraemia at the authors' centre, to perform a descriptive analysis according to the mode of infection acquisition (community-acquired, healthcare-associated, hospital-acquired), and to assess the risk factors for mortality. Methods: A retrospective study on patients with ESBL bacteraemia was undertaken. Results: In total, 129 consecutive cases of bacteraemia due to ESBL producers were included in this study. Compared with community- and hospital-acquired bacteraemia, healthcare-associated bacteraemia affected older patients (P=0.001) and patients with higher Charlson Comorbidity Index scores (P=0.007), and was more frequently associated with piperacillin-tazobactam resistance (P=0.025) and multi-drug resistance (P=0.026). Overall, ineffective empirical treatment was common (42%). Factors associated with 30-day mortality were septic shock [odds ratio (OR) 7.096, 95% confidence interval (CI) 2.58-24.58], high Pitt score (OR 6.636, 95% CI 1.71-23.62) and unknown source of bacteraemia (OR 19.28, 95% CI 2.80-30.70). Conclusions: Antimicrobial stewardship interventions focusing on both in-hospital and community settings are advocated to better manage healthcare-associated infections due to ESBL producers.

3.
Pediatr Transplant ; 27(5): e14503, 2023 08.
Article in English | MEDLINE | ID: mdl-36915258

ABSTRACT

BACKGROUND: In Fanconi anemia bone marrow failure is the major cause of morbidity and mortality and hematopoietic stem cell transplantation represents the only curative treatment. Liver disease, in terms of elevated liver function tests, as well as benign and malignant liver tumors, occurs especially in case of androgen treatment. We report a unique case of a child with Fanconi anemia with FANCD2 mutation who developed neonatal cryptogenic liver cirrhosis and bone marrow failure. The child successfully underwent sequential liver transplantation and hematopoietic stem cell transplantation in the first 2 years of life. Nineteen months after hematopoietic stem cell transplantation and 30 months after liver transplantation, the patient is clinically well with normal hematopoietic function and excellent liver function. CONCLUSION: This is the first FA patient who successfully received sequential LT and HSCT highlighting that successful sequential transplantation is feasible in Fanconi anemia patients.


Subject(s)
Fanconi Anemia , Hematopoietic Stem Cell Transplantation , Liver Transplantation , Pancytopenia , Child , Infant, Newborn , Humans , Fanconi Anemia/complications , Fanconi Anemia/therapy , Bone Marrow Failure Disorders , Liver
4.
Open Forum Infect Dis ; 7(11): ofaa481, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33204761

ABSTRACT

BACKGROUND: Remdesivir has been associated with accelerated recovery of severe coronavirus disease 2019 (COVID-19). However, whether it is also beneficial in patients requiring mechanical ventilation is uncertain. METHODS: All consecutive intensive care unit (ICU) patients requiring mechanical ventilation due to COVID-19 were enrolled. Univariate and multivariable Cox models were used to explore the possible association between in-hospital death or hospital discharge, considered competing-risk events, and baseline or treatment-related factors, including the use of remdesivir. The rate of extubation and the number of ventilator-free days were also calculated and compared between treatment groups. RESULTS: One hundred thirteen patients requiring mechanical ventilation were observed for a median of 31 days of follow-up; 32% died, 69% were extubated, and 66% were discharged alive from the hospital. Among 33 treated with remdesivir (RDV), lower mortality (15.2% vs 38.8%) and higher rates of extubation (88% vs 60%), ventilator-free days (median [interquartile range], 11 [0-16] vs 5 [0-14.5]), and hospital discharge (85% vs 59%) were observed. Using multivariable analysis, RDV was significantly associated with hospital discharge (hazard ratio [HR], 2.25; 95% CI, 1.27-3.97; P = .005) and with a nonsignificantly lower mortality (HR, 0.73; 95% CI, 0.26-2.1; P = .560). RDV was also independently associated with extubation (HR, 2.10; 95% CI, 1.19-3.73; P = .011), which was considered a competing risk to death in the ICU in an additional survival model. CONCLUSIONS: In our cohort of mechanically ventilated patients, RDV was not associated with a significant reduction of mortality, but it was consistently associated with shorter duration of mechanical ventilation and higher probability of hospital discharge, independent of other risk factors.

5.
AIDS ; 34(1): 53-61, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31567160

ABSTRACT

BACKGROUND: Efavirenz (EFV) association with neurocognitive impairment is debated. Whether switching away from EFV improves neurocognitive performances is still controversial. METHODS: In a randomized open-label controlled trial, patients under effective treatment with tenofovir disoproxil-fumarate (TDF), emtricitabine (FTC) and EFV, who had altered neurocognitive assessment (z-transformed score below -1 in at least one cognitive domain), depression, anxiety or low sleep-quality, were randomized 1 : 1 to immediate or delayed (24-weeks) switch to TDF/FTC/rilpivirine (RPV). Treatment efficacy, neurocognitive function, symptoms and quality of life were evaluated 12, 24 and 48 weeks after randomization. FINDINGS: Seventy-four patients were randomized to immediate (36 patients) or delayed switch (38 patients). At baseline, 63 and 25% of patients had z-scores below -1 in at least one or two neurocognitive domains, 31.1, 17.6 and 44.6% had significant depression or anxiety symptoms or low sleep quality. At week 24 (primary end-point), overall neurocognitive improvement was observed, with no statistically significant differences between arms, neither considering the global z score (between arms difference +0.1; P = 0.458), nor domain-specific z scores. Patients switching away from EFV had significant greater improvement of sleep quality index (between-arm difference -1.5; P = 0.011), self-reported cognitive failures (-6.2; P = 0.001) and CNS symptoms score (-5; P = 0.002), but not of anxiety or depression. No protocol defined virological failure, grade at least 3 lab abnormalities or drug-related serious adverse events were reported. CONCLUSION: Our results do not support the hypothesis that switching to RPV improves cognitive function in patient under stable treatment with EFV. Nonetheless, improvements in neuropsychiatric symptoms, sleep quality and self-perceived cognition were observed.


Subject(s)
Alkynes/therapeutic use , Anti-HIV Agents/therapeutic use , Benzoxazines/therapeutic use , Cognition/drug effects , Cyclopropanes/therapeutic use , Drug Substitution , HIV Infections/drug therapy , Rilpivirine/therapeutic use , Sleep/drug effects , Adult , Alkynes/adverse effects , Anti-HIV Agents/adverse effects , Benzoxazines/adverse effects , Cyclopropanes/adverse effects , Emtricitabine , Female , HIV Infections/psychology , Humans , Male , Middle Aged , Quality of Life , RNA, Viral , Rilpivirine/adverse effects , Tenofovir , Viral Load
6.
Can J Cardiol ; 36(1): 127-134, 2020 01.
Article in English | MEDLINE | ID: mdl-31813674

ABSTRACT

The introduction of combination of antiretroviral therapy and advancement in care of HIV have dramatically changed the natural history of patients living with HIV. Today, HIV+ patients have a life expectancy not significantly different from HIV uninfected people. However, concerns remain about all the comorbidities associated with aging and the effects of chronic therapies in such high-risk patients. HIV+ subjects exhibited accelerated atherosclerosis and have a 1.5- to 2-fold increased risk of having coronary artery disease (CAD), usually presenting early and aggressively with acute coronary events. Furthermore, HIV+ patients with CAD often complain recurrent acute coronary events, and they are plagued by major adverse cardiac outcomes. This review will focus on the current understanding of the CAD phenotype in HIV+ patients highlighting the topic of acute coronary event recurrence and underscoring the role of percutaneous management strategies in the light of information derived from invasive coronary imaging.


Subject(s)
Coronary Artery Disease/epidemiology , HIV Infections/complications , HIV , Risk Assessment/methods , Chronic Disease , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnosis , Global Health , Humans , Incidence , Recurrence , Risk Factors
7.
Pediatr Infect Dis J ; 38(10): 1035-1037, 2019 10.
Article in English | MEDLINE | ID: mdl-31568141

ABSTRACT

Isavuconazole is a new azole approved for adults with invasive aspergillosis and mucormycosis, with a favorable hepatic tolerability reported in Phase III trials. Here, we report on a case of drug-induced liver failure related to isavuconazole in a pediatric patient treated for invasive aspergillosis after bone marrow transplant.


Subject(s)
Antifungal Agents/adverse effects , Invasive Pulmonary Aspergillosis/complications , Invasive Pulmonary Aspergillosis/drug therapy , Liver Failure, Acute/chemically induced , Liver Failure, Acute/pathology , Nitriles/adverse effects , Pyridines/adverse effects , Triazoles/adverse effects , Adolescent , Antifungal Agents/administration & dosage , Bone Marrow Transplantation/adverse effects , Humans , Male , Nitriles/administration & dosage , Pyridines/administration & dosage , Triazoles/administration & dosage
8.
Pathog Immun ; 4(2): 180-194, 2019.
Article in English | MEDLINE | ID: mdl-31538132

ABSTRACT

BACKGROUND: Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. METHODS: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients' characteristics. RESULTS: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. CONCLUSIONS: In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.

10.
Open Forum Infect Dis ; 4(4): ofx256, 2017.
Article in English | MEDLINE | ID: mdl-29308407

ABSTRACT

A 50-year-old man was admitted to intensive care unit because of acute respiratory failure due interstitial pneumonia; after admission, a diagnosis of acute human immunodeficiency virus (HIV)-1 infection was made. Clinical and radiological improvement was observed only after introduction of antiretroviral treatment. We discuss the hypothesis of interstitial pneumonia induced by the acute HIV-1 infection.

11.
Pathog Immun ; 1(2): 352-370, 2016.
Article in English | MEDLINE | ID: mdl-30993245

ABSTRACT

BACKGROUND: During the last decade, the spread of Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) has increased dramatically worldwide. In this scenario, growing interest has been addressed to genotyping of KPC-Kp strains, which emerged as an important tool for a better understanding of the epidemiological and clinical characteristics of the outbreaks. METHODS: We performed a retrospective cohort study on patients infected with KPC-Kp during a 28-month outbreak period (January 2010-April 2012) at San Gerardo Hospital (Monza, Italy), investigating KPC-Kp genotypes by means of repetitive element sequence-based polymerase chain reaction (Rep-PCR). RESULTS: We enrolled 97 patients infected with KPC-Kp. Rep-PCR analysis identified 5 distinct clone types, with different distribution over time. During the first 12 months of the outbreak period, only 1 clone was detected (clone A, in 47 patients), while the 4 other clones were identified over the remaining 16 months (clones C, E, and F/L in 23, 24, and 3 patients respectively). Mechanical ventilation was less frequent in patients infected with clones C/E/F/L (OR = 0.14; 95% CI: 0.05-0.37) compared to clone A, and the Charlson comorbidity index (CI) was more likely to have a score >5 in patients infected with clones C/E/F/L (OR = 7.21; 95% CI: 2.24-23.14) compared to clone A.Overall mortality was higher in patients infected with clones C/E/F/L (13/20 patients, 65%) compared to those infected with clone A (7/20, 35%). Mortality in patients infected with clones C/E/F/L remained significantly higher even after adjusting for the potential confounding effect of comorbidities (ie, CI), with a hazard ratio (HR) of 4.65 (95% CI: 1.83-11.89). CONCLUSIONS: Our results suggested a close relationship between strain genotype and clinical outcome.

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