Specificities of acute cholangitis in patients with cancer: a retrospective comparative study of 130 episodes.

Pancreatic and biliary duct cancers are increasing causes of acute cholangitis (AC). We retrospectively characterize 81 cancer-associated cholangitis (CAC) compared to 49 non-cancer-associated cholangitis (NCAC). Clinical and biological presentations were similar. However, in CAC, antibiotic resistance and inadequate empirical antibiotic therapy were more frequent; more patients required ≥ 2 biliary drainages; and mortality at day 28 was higher than in NCAC. Death was associated with initial severity and CAC in a multivariate analysis. Cholangitis associated with pancreatic or biliary duct cancers requires specific empirical antimicrobial therapy; early use of biliary drainage may improve outcomes.

Temocillin as an alternative treatment for acute bacterial cholangitis: a retrospective microbiology susceptibility-based study of 140 episodes.

With rising antibiotic resistance, alternatives to carbapenems are needed for acute cholangitis (AC). Temocillin reaches high biliary concentrations with limited impact on microbiota. We retrospectively included 140 AC episodes and assessed the efficacy of temocillin using microbiology susceptibility testing from blood cultures. Considering all bacteria collected by episode, resistance to temocillin, PIP/TAZ and 3GC occurred in 27/140 (26%), 32 (22.8%) and 31 (22%) episodes, respectively (p = 0.7). After documentation, temocillin could have spared PIP/TAZ or carbapenems in 14/26 and 4/11 episodes. Temocillin may constitute an alternative treatment after microbiological documentation by sparing carbapenems and/or PIP/TAZ, but not as an empirical therapeutic option.

Treatment and outcome of Unicentric Castleman Disease: a retrospective analysis of 71 cases.

We retrospectively analysed 71 cases of Unicentric Castleman disease, a rare, usually asymptomatic, benign lymphoproliferative disorder presenting as a unique nodal mass. Although surgery is considered as the gold standard therapy, only 38 patients (54%) underwent initial surgical resection and 95% were cured. An additional 9 patients had surgery after an attempt at medical reduction. Reduction therapy was used in 21 patients with a 55% response rate, but without evidence for an optimal regimen. Radiotherapy was limited to 8 patients because of associated toxicity. Watch and wait was considered in 13 asymptomatic patients and 11 of these remained stable for up to 17 years.

Prevalence and Risk Factors of Cytomegalovirus Among Men Having Sex With Men Enrolled in a Pre-Exposure Prophylaxis Study.

Risk factors for cytomegalovirus (CMV) acquisition in men having sex with men remain unclear. Seroprevalence, incidence, risk factors and shedding of CMV were analyzed among participants enrolled in the HIV pre-exposure prophylaxis IPERGAY-ANRS trial. Among the 417 participants tested, 382 were seropositive at baseline (prevalence of 91.6%; 95%CI[88.5-94.1]) and 10/35 seroconverted during the study (incidence of 17.1 per 100 person-years; 95%CI[8.2-31.3]). A high number of sexual partners was independently associated with CMV seroprevalence. Shedding among CMV-seroconverters was reported for 6/9 and 2/9 at the oral and anal levels, respectively. Our data supports transmission of CMV during sexual contacts. Study part of the ANRS-IPERGAY Clinical trial: ClinicalTrials.gov number, NCT01473472.

Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine.

OBJECTIVES: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as preexposure prophylaxis (PrEP), using ex-vivo rectal tissue infections and drug concentration measures in blood and rectal tissue. DESIGN/METHODS: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex-vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, 2 h after two pills or 7 days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection. RESULTS: Twelve and 11 men were analyzed in the 2 h-double dose and 7 days-single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144 pg/ml/mg (IQR[-259;-108]) for the 2 h-double dose group ( P  = 0.0005) and -179 pg/ml/mg (IQR [-253;-86]) for the 7 days-single dose group ( P  = 0.001), with no differences between groups ( P  = 0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at 7 days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose ( R  = -0.84; P  = 0.0001). CONCLUSION: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 h after a double dose or 7 days of a daily dose. At 2 h, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection.

Incidence of complications of herpes zoster in individuals on immunosuppressive therapy: A register-based population study.

OBJECTIVES: Herpes zoster (HZ) exposes to alterations of the quality-of-life. HZ is more frequent in immunocompromised individuals, but whether immunosuppression is associated with a higher rate of complications is not well documented. We aimed to assess association between drug-induced immunosuppression and HZ complications. METHODS: Data from a sample of the French healthcare claims from 01/01/2006 to 12/31/2018 were analyzed. Complicated zoster (CZ) was defined as a hospitalization with a code for HZ or the first-time dispensation of high-dose valacyclovir and specific neuralgia analgesics. Drug-induced immunosuppression was identified through medication dispensation. Risk ratios were calculated to compare incidences in exposed individuals (EI) and non-exposed to immunosuppressive therapy (NEI). RESULTS: We identified 227 and 2838 CZ, accounting for an incidence of 178 per 100,000 person-year (95%CI[154.9-201.1]) and 51.7 per 100,000 person-year (95%CI[49.8-53.6]), in EI and NEI, respectively (risk ratio: 3.44 (95%CI[3.01-3.94]). Mean age was 66 years in both groups. CZ occurred after a median of 11.7 months (IQR[5.3-49.9]) of immunosuppressive therapy. Post-herpetic neuralgia (PHN) lasted at least 3 months in 32.6% and 22.5% of cases in EI and NEI, respectively (p=.01). CONCLUSIONS: Drug-induced immunosuppression increases the risk of CZ and exposes to longer-lasting PHN. Figures provided in this study could help guide prophylaxis of HZ.

A Randomized, Open-Label, Crossover Phase 1 Safety and Pharmacokinetic Study of Oral Maraviroc and Maraviroc 1% Gel (the CHARM-03 Study).

The Combination HIV Antiretroviral Rectal Microbicide-3 (CHARM-03) study was a randomized, open-label, crossover Phase 1 safety and pharmacokinetic (PK) study of oral maraviroc (MVC) and MVC 1% gel. At a single site, healthy HIV-uninfected men and women were enrolled and randomized to an open label crossover sequence of eight consecutive daily exposures to MVC 300 mg dosed orally, MCV 1% gel dosed rectally, and MVC 1% gel dosed vaginally. Male participants received oral and rectal dosing and female participants received oral, rectal, and vaginal dosing. Assessments were undertaken at baseline and following each 8-day period and included collection of plasma, rectal/cervical tissue (CT), and rectal/endocervical/vaginal fluids. Eleven men and nine women were enrolled. Two participants withdrew from the study before receiving study product. There were 25 adverse events, of which 24 were Grade 1 (G1) and one was G2 (unrelated). After eight doses, MVC was quantifiable in all samples following oral, rectal, or vaginal product administration. The highest drug concentrations in plasma, rectal tissue (RT), and CT were associated with oral, rectal, and vaginal drug delivery, respectively. There were significant reductions in tissue drug concentrations when rectal and cervical biopsies were incubated in media before tissue processing for PK (p < .0001). Only oral MVC was associated with limited protection in the rectal explant HIV challenge model (p < .05). There were no immunological changes in RT, and all products were acceptable to participants. In conclusion, all products were found to be safe and acceptable and did not induce local inflammation. The lack of ex vivo efficacy demonstrated in study samples may be due to rapid disassociation of MVC from the explant tissue. ClinicalTrials.gov Identifier: NCT02346084.

Long-term impact of COVID-19 among maintenance haemodialysis patients.

BACKGROUND: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area. METHODS: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area. RESULTS: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed. CONCLUSIONS: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia.

Inflammatory Markers During Early Treatment of Seroconverters in a Randomized Placebo-Controlled Trial of PrEP (ANRS-IPERGAY).

HIV-related inflammation is associated with poor outcomes. We describe inflammatory biomarkers in 17 participants in a pre-exposure prophylaxis trial who seroconverted with very early initiation of antiretroviral therapy. Inflammation peaked at the time of HIV infection and returned to baseline within 6-12 months. Starting antiretroviral therapy very early could help mitigate long-lasting HIV-related inflammation.