Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders.

Despite optimal suppression of HIV replication, restoration of CD4(+) T cells is not always achieved in antiretroviral therapy-treated individuals. Defective CD4 recovery in immunologic nonresponders is possibly associated with TLR-mediated immune activation driven by alterations of gut permeability. Hydroxychloroquine (HCQ) reduces endosomal TLR signaling; thus, we verified whether HCQ could dampen immune activation and be associated with an increase in CD4(+) T cells. To this end, we enrolled in a prospective study 20 HIV-infected immunologic nonresponders (CD4 count < 200 cells/mL or CD4 increase < 5% in the last 12 months) who received 400 mg/day HCQ for 6 months. HCQ had a notable impact on immune activation as shown by significant modifications of the following parameters: (1) reduced plasma lipopolysaccharide; (2) decreased TLR4-expressing CD14(+) cells, TLR4-mediated signal transduction, and mRNA synthesis; (3) reduced percentages of activated CD4(+) (CD4(+)/Ki67(+)) and CD14(+) (CD14(+)/CD69(+)) cells; (4) increased T-regulatory cells (Tregs), naive Tregs, and TLR4-expressing Tregs; (5) augmented plasmacytoid dendritic cells and reduced IFNα-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNFα production. HCQ-induced immune modulation was associated with increased percentages of circulating CD4(+) T cells and was mostly retained 2 months after therapy interruption. HCQ reduces lipopolysaccharide/TLR-mediated immune activation; this compound could be a useful immunomodulant in HIV-infected patients. This study is registered at EutraCT as 2009-012499-28 with study number HLS01/2009-1-16-03-2009.

Disseminated Cryptococcosis in a Patient With Metastatic Prostate Cancer Who Died in the Coronavirus Disease 2019 (COVID-19) Outbreak.

We report the case of a 61-year-old patient with a history of prostate cancer affected by bone metastasis. He presented to our attention for ulcerous and necrotic cutaneous lesions unresponsive to antibiotics. The spread of cutaneous lesions and the onset of neurological symptoms suggested a cryptococcal disease, which was confirmed by lumbar puncture and cutaneous biopsy. We present the diagnostic and therapeutic approach to this case.

Can Drainage Using a Negative-Pressure Wound Therapy Device Replace Traditional Sample Collection Methods?

BACKGROUND: In 2015 a new device for the collection of mediastinal fluid from patients with deep sternal wound infection (DSWI) in the presence of negative-pressure wound therapy (NPWT) became available. The present study was designed to evaluate whether changing sample collection devices increased micro-organism detection in patients undergoing NPWT. METHODS: During 2013-2014, 207 samples were collected and cultured from NPWT patients (n = 23) to demonstrate the presence of DSWI using reticulated polyurethane sponge culture, a swab, and blood culture. In 2015, a new collection device was introduced for specimen collection. A total of 357 samples (n = 17) were collected using the ESwab(™) (Copan, Murrieta, CA) for deep and superficial wound sample collection. In addition, blood culture devices were used for collecting mediastinal fluid aspirated directly from the wound and biologic fluid obtained from the NPWT device. Fisher exact test was performed to test the rate of independence rate of micro-organism identification using the NPWT sponge device and taking blood culture results as a reference for micro-organism identification. RESULTS: After the introduction of the new collection device in our hospital, an overall increase in the detection of micro-organisms (46.7%) was reported. During 2013-2014 our traditional microbiologic collection method did not detect a pathogen in 30.4% of patients. During 2015, the new sample collection approach, direct from the NPWT device, improved micro-organism detection by 10.4% and reduced DSWIs with undetected pathogens to 17.6% (p < 0.01). CONCLUSIONS: As a result of proficiency gained in the last year, the most representative specimen in wound infection was represented by mediastinal fluid collected directly from the wound and the NPWT device. Given the correlation between the blood culture of micro-organisms detected using the ESwab device from the wound, mediastinal drainage, and drainage from the NPWT device, we can assume that the NPWT device may replace the other biologic sampling devices.