Early prone positioning does not improve the outcome of patients with mild pneumonia due to SARS-CoV-2: results from an open-label randomised controlled trial - the EPCoT study.

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.

Isavuconazole-induced Acute Liver Failure in a Pediatric Patient With Invasive Aspergillosis.

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.

Combination Antifungal Therapy for Invasive Mold Infections Among Pediatric Patients with Hematological Malignancies: Data from A Real-Life Case-Series.

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.

Primary Whipple disease of the Central Nervous System presenting with rhombencephalitis.

Primary Whipple disease of the Central Nervous System is a rare entity whose outcome might be fatal if not promptly diagnosed and treated. Few cases are reported in the literature with heterogeneous clinical and radiological presentations which often make the diagnosis extremely challenging. We report a case of primary Whipple disease of the Central Nervous System presenting with rhombencephalitis in a female patient in immunosuppressive treatment for rheumatoid arthritis. We describe the management of our patient and discuss the features of this rare clinical entity.

The hidden hypothesis: A disseminated tuberculosis case.

CASE PRESENTATION: 77-year-old former smoker admitted because of fatigue and abdominal distention. Past medical history positive for two previous hospitalizations for pericardial and pleural effusions (no diagnosis achieved). At admission erythrocyte sedimentation rate was 122mm per hour. Baseline investigations revealed ascitic, pleural and pericardial effusion. Effusions were tapped: neoplastic cells and acid-fast bacilli (AFB) were not identified, aerobic and mycobacterial culture resulted negative. QuantiFERON TB-Gold test was negative. Total body PET-CT and autoimmunity panel were negative. A neoplastic process was considered the most likely explanation. Before signing off the patient to comfort care, a reassessment was performed and an exposure to tuberculosis during childhood was documented. Because of constrictive pericarditis, pericardiectomy was performed: histologic examination showed chronic pericardial inflammation without granulomas, but Ziehl-Neelsen stain identified AFB and PCR was positive for Mycobacterium tuberculosis complex. Patient was started on anti-TB therapy with resolution of the effusions in the following months. Genes associated with defects in innate immunity were sequences and dentritic cells were studied, but no alterations were identified. DISCUSSION: A Bayesian approach to clinical decision making should be recommended. Interpretation of diagnostic tests should take into account the imperfect diagnostic performance of the majority of these tests. Further studies to investigate genetic susceptibility to tuberculosis are needed.

Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report.

BACKGROUND: Cytomegalovirus is responsible for an opportunistic infection that can be life threatening in immunocompromised patients, while it is usually mild or completely asymptomatic in immunocompetent subjects. In the recent years, however, some cases of severe cytomegalovirus infection in immunocompetent patients have been reported, showing this to be a less rare occurrence than previously reported. CASE PRESENTATION: We report the case of an 83-year-old man, admitted to our hospital for gastroenteritis, complicated by dehydration and severe prothrombin time prolongation due to oral anticoagulant therapy accumulation, who developed hospital-acquired pneumonia; neither of these illnesses responded to several lines of antibiotic therapy. All microbiologic tests were negative, except cytomegalovirus DNA test in blood, which showed high viral load. Antiviral therapy with ganciclovir was then started and a quick favourable response followed. A state of immunodeficiency was excluded, based on normal CD4 count and patient's clinical history. CONCLUSION: Different risk factors for severe cytomegalovirus disease in immunocompetent patients may exist, besides the ones already known, which could be responsible for severe cytomegalovirus disease in immunocompetent patients; thus, these patients should be tested for cytomegalovirus infection, if the clinical picture is compatible, to avoid delay in diagnosis and allow prompt start of specific therapy.

Acute Human Immunodeficiency Virus (HIV) Infection Presenting With Bilateral Interstitial Pneumonia: Case Report and Discussion of Potential HIV-Induced Interstitial Pneumonia.

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.

Tigecycline Lock Therapy for Catheter-Related Bloodstream Infection Caused by KPC-Producing Klebsiella pneumoniae in Two Pediatric Hematological Patients.

Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection.

Combination versus sequential monotherapy in chronic HBV infection: a mathematical approach.

Sequential monotherapy is the most widely used therapeutic approach in the treatment of hepatitis B virus (HBV) chronic infection. Unfortunately, under therapy, in some patients the hepatitis virus mutates and gives rise to variants which are drug resistant. We wonder whether those patients would have benefited from the choice of combination therapy instead of sequential monotherapy. To study the action of these two therapeutic approaches and to explain the emergence of drug resistance, we propose a stochastic model for the infection within a patient who is treated with two drugs, either sequentially or contemporaneously, and who, under the first kind of therapy develops a strain of the virus which is resistant to both drugs. Our stochastic model has a deterministic approximation which is a slight modification of a classic three-strain model. We discuss why stochastic simulations are more suitable than the study of the deterministic approximation, when modelling the rise of mutations (this is mainly due to the amplitude of the stochastic fluctuations). We run stochastic simulations with suitable parameters and compare the time when, under the two therapeutic approaches, the resistant strain first reaches detectability in the serum viral load. Our results show that the best choice is to start an early combination therapy, which allows one to stay drug resistance free for a longer time and in many cases leads to viral eradication.

Highly active antiretroviral therapy reduces the age-associated risk of dementia in a cohort of older HIV-1-infected patients.

Historically, older patients have shown a higher risk of HIV-1-associated dementia (HIVD). The objective of this study was to evaluate the association of aging with HIVD and minor cognitive motor disorders (MCMDs) during the late-highly active antiretroviral therapy (HAART) era and to analyze characteristics, predictive factors, and survival of older HIV-1-infected individuals affected by these disorders. A nested longitudinal study was designed for a cohort of HIV-1-infected individuals with neurological diseases. Multiple logistic regression and Cox regression for survival were employed. From 2000 to 2003, 195 patients with HIVD (53%) or MCMD (47%) were enrolled. The cumulative prevalence of these two disorders was 21%, with an increasing rate for calendar year (p < 0.001). Previous antiretroviral exposure occurred in 46% of patients. Mean CD4(+) cell count and plasma HIV-1 RNA were 144 cells/microl and 4.5 log10 copies/ml, respectively. The mean age was 44 years (SD, 9.9), with 35% of patients aged 20-39 years (I), 45% aged 40-49 years (II), and 20% aged >/=50 years (III). Among drug-naive patients, the prevalence of HIVD progressively increased in older subjects: 7.2% (I), 15.3% (II), and 27.3% (III) (p < 0.001), whereas no significant increase in HIVD with older age was observed in drug-treated subjects. Older age was independently associated with an increased risk of HIVD (odds ratio, 6.44; 95% confidence interval, 2.82-14.69) in naive but not in experienced individuals, but had no significant effect on survival. No significant effect of age was observed for MCMD. We conclude that in our cohort, HAART seems to alter the relationship between aging and HIVD, conferring a neuroprotective effect to older patients. These results may have significant implications for the clinical management of the older HIV population.