A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.

[Plastic surgery and fighting: Our experience during Nagorno-Karabakh war in 2020]. / Chirurgie plastique et conflit armé : notre expérience lors du conflit au Haut-Karabakh en 2020.

INTRODUCTION: This work relates the experience of three French surgical missions in the care of the war wounded during the armed conflict in Nagorno Karabakh which took place from September 27 to November 10, 2020. MATERIALS AND METHODS: Three surgical missions were carried out in Armenia between October 2020 and January 2021. Surgeons intervened in different hospitals, at different times of the conflict and on various war wounds. RESULTS: The presence of a plastic surgeon proved to be essential in the care of war wounded, especially in delayed emergency and secondary care. The ortho-plastic treatment offered during these missions has proven to be effective in the reconstruction of limbs. These missions made it possible to introduce the induced membrane technique of Masquelet AC in Armenia. During our visit to the Yerevan burn center, we mentioned the very probable use of white phosphorus as an etiology in several of the cases analyzed. CONCLUSION: We relate the particular experience of civilian surgeons in the context of a modern armed conflict. The presence of a plastic surgeon proved to be indispensable in the care of war wounded and especially in their secondary reconstructions.

Resistance profile and treatment outcomes in HIV-infected children at virological failure in Benin, West Africa.

Background: In Africa a high percentage of HIV-infected children continue to experience HIV treatment failure despite enormous progress. In Benin (West Africa), there are currently no data on HIV drug resistance at failure in paediatric populations. Objectives: To assess the frequency and patterns of HIV drug resistance among children with virological ART failures. Methods: Dried blood spots from 62 HIV-infected children with virological failure were collected at the paediatric clinic of the National Hospital Center in Cotonou for genotyping and plasma drug concentration determination. Results: Characteristics of the population show a median age of 10 years (IQR 6-13) and a median duration on ART of 5 years (IQR 3-7). Viruses from 53 children were successfully amplified. Of these, 76% of patients were on an NNRTI-based regimen and 24% on a boosted PI-based regimen. NRTI, NNRTI and dual-class resistance was present in 71%, 84% and 65% of cases, respectively. Only 4% of the children had major resistance mutations to PIs and none had major resistance mutations to integrase inhibitors. Among the participants, 25% had undetectable antiretroviral concentrations. Conclusions: Our results showed that the development of drug resistance could be one of the main consequences of high and continuous viral replication in HIV-infected children in Benin. Thus, inadequate attention to monitoring lifelong ART in children may prevent achievement of the goal of the United Nations Program on HIV and AIDS (UNAIDS) of 90% viral suppression among patients receiving ART.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Self-reported patient history to assess hepatitis B virus serological status during a large screening campaign.

When assessing hepatitis B virus (HBV) status in clinical settings, it is unclear whether self-reports on vaccination history and previous HBV-test results have any diagnostic capacity. Of 3997 participants in a multi-centre HBV-screening study in Paris, France, 1090 were asked questions on their last HBV-test result and vaccination history. Discordance between self-reported history compared with infection status (determined by serology) was calculated for participants claiming 'negative', 'effective vaccine', 'past infection', or 'chronic infection' HBV-status. Serological testing revealed that 320 (29.4%) were non-immunised, 576 (52.8%) were vaccinated, 173 (15.9%) had resolved the infection and 21 (1.9%) were hepatitis B surface antigen positive. In total 208/426 (48.8%) participants with a self-reported history of 'negative' infection had a discordant serological result, in whom 128 (61.5%) were vaccinated and 74 (35.6%) had resolved infections. A total of 153/599 (25.5%) participants self-reporting 'effective vaccine' had a discordant serological result, in whom 100 (65.4%) were non-immunised and 50 (32.7%) were resolved infections. Discordance for declaring 'past' or 'chronic infection' occurred in 9/55 (16.4%) and 3/10 (30.0%) individuals, respectively. In conclusion, self-reported HBV-status based on participant history is partially inadequate for determining serological HBV-status, especially between negative/vaccinated individuals. More adapted patient education about HBV-status might be helpful for certain key populations.

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression.

BACKGROUND: Individuals presenting for care with severe immunosuppression typically have high plasma HIV viral load (pVL) and may transmit HIV before and after initiation of combination antiretroviral therapies (cART). PATIENTS AND METHODS: Using risk equations and data collected in the IMEA 040 DATA trial on sexual behaviour and pVL level of 84 HIV-infected patients (23 women), we estimated monthly rates of HIV transmission for each virologically unsuppressed participant (pVL >50 copies/mL) who reported sex with HIV-negative or unknown serostatus (HNUS) partners at cART initiation, 24 weeks (W24) and W48 after; rates were considered negligible for other participants. RESULTS: At cART initiation, median pVL was 5.4 log10 copies/mL. The percentage of virologically unsuppressed patients decreased, from 100% at cART initiation to 27% (95% CI 16%-43%) for heterosexuals and 8% (95% CI 2%-22%) for MSM at W48 (P < 0.001). The percentage of patients reporting sex with HNUS partners increased between cART initiation and W48, from 23% (95% CI 10%-42%) to 42% (95% CI 25%-61%) for heterosexuals (P = 0.042) and from 41% (95% CI 21%-64%) to 73% (95% CI 52%-88%) for MSM (P = 0.004). Median monthly HIV transmission rates were 0.0540 (IQR 0.0339-0.0742) for MSM and 0.0018 (IQR 0.0014-0.0191) for heterosexuals at cART initiation, and were reduced by 95% (95% CI 87%-100%) for heterosexuals and 98% (95% CI 95%-100%) for MSM as early as W24. CONCLUSIONS: Risk of onward transmission for severely immunosuppressed individuals is high before and within the first weeks of cART, and persists, at a substantially reduced level, beyond 24 weeks of cART for some individuals. Earlier cART and protecting HIV-negative partners until full viral suppression is achieved could reduce HIV transmission.

Week 96 efficacy and safety of darunavir/ritonavir monotherapy vs. darunavir/ritonavir with two nucleoside reverse transcriptase inhibitors in the PROTEA trial.

OBJECTIVES: PROTEA is a randomized controlled trial to assess the efficacy and safety of darunavir/ritonavir (DRV/r) monotherapy as an alternative to triple therapy. METHODS: Patients fully suppressed on first-line antiretrovirals (viral load < 50 HIV-1 RNA copies/mL) were switched to DRV/r 800/100 mg once daily, either as monotherapy (n = 137) or with two nucleoside reverse transcriptase inhibitors (NRTIs) (n = 136). Treatment failure was HIV-1 RNA level ≥ 50 copies/mL at week 96 or discontinuation of study treatment [Food and Drug Administration (FDA) snapshot algorithm]. RESULTS: Patients were mainly male and white, with mean age 44 years. In the primary efficacy analysis, the percentage of patients with HIV-1 RNA < 50 copies/mL by week 96 [intent to treat (ITT)] was lower in the DRV/r monotherapy arm (103 of 137 patients; 75%) than in the triple therapy arm (116 of 136 patients; 85%) [difference -10.1%; 95% confidence interval (CI) -19.5, -0.7%]. In the switch-included analysis, monotherapy was noninferior to triple therapy. In a post hoc analysis, for patients with nadir CD4 count ≥ 200 cells/µL, rates of HIV-1 RNA suppression were 82 of 96 patients (85%) in the DRV/r monotherapy arm and 88 of 106 patients (83%) in the triple therapy arm. No treatment-emergent primary protease inhibitor mutations were detected in either arm. The frequency of adverse events was similar in the two arms; however, one patient in the monotherapy arm was hospitalized with HIV encephalitis and elevated cerebrospinal fluid HIV-1 RNA. CONCLUSIONS: In this study, in patients with HIV-1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy vs. triple therapy at week 96 in the primary ITT switch-equals-failure analysis, particularly in patients with CD4 counts < 200 cells/µL.

Usefulness of Dried Blood Spots (DBS) to perform hepatitis C virus genotyping in drug users in Senegal.

The aim of this pilot study was to analyze the Hepatitis C Virus (HCV) genotypes circulating in Senegal among Drug User (DUs), using Dried Blood Spots (DBS) as RNA source for molecular assays. Heroin and/or cocaine users (n = 506) were recruited in Dakar from April to July 2011, using a Respondent Driven Sampling (RDS) method. DBS preparation consisted of five drops of whole blood from finger applied to a Whatman paper card. HCV infection was screened by the detection of anti-HCV antibodies, using a rapid immune-chromatographic test. HCV RNA was quantified on anti-HCV positive DBS, using the Abbott RealTime HCV® Genotyping was performed on DBS with detectable viral load with Versant® HCV Genotype 2.0 Assay (LiPA) and Abbott RealTime HCV Genotype II assay®. Among the 506 participants, 120 were tested as positive for anti-HCV antibodies and their samples were analyzed for HCV RNA viral load and genotype. Out of the 120 DBS tested, HCV RNA was detected on 25 (20.8%). The median viral load was 15,058 IU/ml (ranging from 710 to 766,740 IU/ml). All positive DBS were suitable for the genotyping assay, that showed a predominance of genotype 1 (21/25) including 16 genotypes 1a and 5 genotypes 1b. HCV genotype 1 prevails in a DU population in Dakar. DBS could be useful for HCV RNA genotyping, but optimal storage conditions should required avoiding RNA impairment. Acknowledging this limitation, DBS could be a great interest for detecting and genotyping HCV viremic patients. J. Med. Virol. 89:484-488, 2017. © 2015 Wiley Periodicals, Inc.

Clinical and microbiological determinants of severe and fatal outcomes in patients infected with Enterobacteriaceae producing extended-spectrum ß-lactamase.

Although extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae have become a worldwide public health concern, little is known regarding the clinical course of colonized or infected individuals. Our objective was to characterize the determinants of fatal outcomes related to ESBL-producing microorganisms at a large hospital in Paris, France. In 2012-2013, all consecutive patients with clinical samples testing positive for ESBL-producing Enterobacteriaceae at Saint-Antoine Hospital were identified. Patient clinical data were obtained at hospital entry, while information on intensive care unit (ICU) admissions and death were prospectively collected. Risk-factors for fatal 1-year outcomes were assessed using logistic regression. In total, 643/4684 (13%) ESBL-positive samples were observed, corresponding to 516 episodes (n = 206, 40% treated) among 330 patients. Most episodes were nosocomial-related (n = 347/516, 67%) involving Escherichia coli (n = 232/516, 45%) or Klebsiella pneumoniae (n = 164/516, 32%). Empirical antibiotic therapy was adequate in 89/206 (43%) infections, while the median length of hospital stay was 30 days [interquartile range (IQR) = 11-55] and 39/201 (19%) were admitted to the ICU. Overall, 104/241 patients (43%) with available data died within 1 year. In the multivariable analysis, 1-year death was associated with age >80 years (p = 0.01), concomitant comorbidity (p = 0.001), nosocomial-acquired infection (p = 0.002), and being infected rather than colonized (p < 0.001). In this series of patients with identified samples of ESBL-producing Enterobacteriaceae, hospital burden was large and 1-year mortality rates high. Understanding which patients in this setting would benefit from broad-spectrum empirical antibiotic therapy should be further examined.

Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials.

OBJECTIVES: The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy. METHODS: A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (<50 HIV-1 RNA copies/mL). Rates of virological suppression were analysed using switch-equals-failure and intensification-included endpoints [intent-to-treat (ITT)]. The rate of treatment-emergent resistance mutations, neurocognitive function endpoints, and cerebrospinal fluid (CSF) HIV-1 RNA were also analysed by treatment arm. RESULTS: There were 2303 patients from 13 different randomized clinical trials of darunavir/r monotherapy (n = 784: MONET, MONOI, Monarch and PROTEA), lopinavir/r monotherapy (n = 829: OK pilot, OK-04, KalMo, KALESOLO, KRETA, MOST and DREAM), atazanavir/r monotherapy (n = 103: MODAT), or all three (n = 587: PIVOT). HIV-1 RNA plasma suppression was lower in the PI/r monotherapy arm compared with the triple therapy arm in the switch-equals-failure analysis [difference -8.3%; 95% confidence interval (CI) -11.9 to -4.8%], but not when intensification was included (difference 0.5%; 95% CI -2.5 to 3.6%). Rates of resistance mutations were similar between arms, as was overall neurocognitive function. CONCLUSIONS: PI/r monotherapy showed a higher risk of plasma HIV-1 RNA elevations. However, there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints did not differ, and HIV-1 RNA suppression rates after intensification were similar between PI/r monotherapy and triple therapy.

Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients.

In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10 IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10 IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.

Medial thighplasty: Current concepts and practices.

Medial thighplasty, also known as medial thigh lift, is a procedure that has been carried out for five decades. The original "Lewis" technique has undergone many changes, and thereby been rendered widely available to plastic surgeons. Given the increasingly high number of surgical reconstructions after massive weight loss, this technique is now an integral part of a surgeon's therapeutic arsenal as he strives to meet the evolving demands of patients. The objective of this article, which is based on a comprehensive review of the literature, is to summarize current knowledge on medial thighplasty and thereby allow plastic surgeons to adopt the operating technique best suited to the deformations presented by their patients and to the overall context. The different techniques, outcomes and complications are successively discussed.

[Study of parenteral iron use in a health facility and its impact in terms of hospital economics]. / Étude de l'usage du fer injectable en établissement de santé et de son impact en terme d'économie hospitalière.

INTRODUCTION: Administration of parenteral iron is a mainstay of iron deficiency treatment. Evaluation and control of this element is an issue for healthcare facilities. Study of parenteral iron use is thus to be evaluated in its impact in terms of hospital economics. MATERIALS AND METHODS: Parenteral iron administrations that took place on 2014 in our healthcare facility were retrospectively identified by pharmacists. Following data were extracted from Pharma™ and Crossway™ softwares: indication, diagnostic coding and total dose of iron received. They were then compared to the summary of product characteristics. RESULTS: Of 198 analyzed prescriptions, iron deficiency was known or suspected for 97% of patients. However, the total dose of iron administered was not in compliance for three quarters of prescriptions. Sixty-eight percent of patients appear under-dosed. Administration's traceability was found for two-thirds. Eighty-five hospital discharges did not have the right coding and 34 stays were charged like an external act instead sessions. Financial loss for the hospital is estimated at 49,300 euros. DISCUSSION AND CONCLUSION: As part of improving practice, close pharmaceutical monitoring of parenteral iron prescribed dosing regimen is essential. Effective communication with the medical information department and regular awareness raising of prescribers should also allow to give more value to this act. Hospital economics is a real tool to aid decision-making.

[Care pathway for high urinary tract infection: an update in an emergency department of a French military hospital]. / Parcours de prise en charge des infections urinaires hautes: état des lieux aux urgencies d'un établissement militaire français.

Objectives Assessing the impact of professional practices on a patient's course is an interesting way to optimize health care pathway. The aim of our study is to update and evaluate the compliance to the recommendations of the Societe de Pathologie Infectieuse de Langue Francaise with regards to professional practices and the route of patients admitted to the emergency department of a French military hospital for high urinary tract infection. Patients and methods A retrospective study was carried out on patients admitted to the emergency department and treated for high urinary tract infection from January 1st, 2015 to April 30th, 2015. Clinical and administrative data, medical exams, and antibiotic prescriptions were extracted from computerized patient medical files and from emergency medical files. Results Out of 91 medical cares, 57% were compliant with the recommendations. For 60% of the patients, blood cultures were not argued and in 70% of cases, imaging wasn't justified. Antibiotic prescriptions were not compliant in 31% of cases, mostly due to long prescription durations. Two third of patients received outpatient care. All hospitalizations were argued. Conclusions Drawing up a caring protocol, regularly raising awareness to the good use of antibiotics, as well as reinforcing a cross disciplinary approach will allow optimizing health care pathways for patients coming to the emergency department with high urinary tract infection.

Negative prognostic value of high levels of intracellular poly(ADP-ribose) in non-small cell lung cancer.

BACKGROUND: Cisplatin-resistant non-small cell lung cancer (NSCLC) cells are often characterized by alterations in vitamin B-related metabolic processes, including the overexpression and hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1) and the downregulation of pyridoxal kinase (PDXK), correlating with elevated apoptosis resistance. Low PDXK expression is an established negative prognostic factor in NSCLC. PATIENTS AND METHODS: We determined by immunohistochemistry the expression of PARP1 and the level of its product, poly(ADP-ribose) (PAR), in two independent cohorts of patients with resected NSCLC. RESULTS: Intratumoral high levels (above median) of PAR (but not PARP1 protein levels) had a negative prognostic impact in both the training (92 stage I subjects) and validation (133 stage I and II subjects) cohorts, as determined by univariate and multivariate analyses. The simultaneous assessment of PAR and PDXK protein levels improved risk stratification. CONCLUSION: NSCLC patients with high intratumoral PARP1 activity (i.e. elevated PAR levels above median) and low PDXK expression (below median) had a dismal prognosis, while patients with low PARP1 activity and high PDXK expression had a favorable outcome. Altogether, these results underscore the clinical potential and possible therapeutic relevance of these biomarkers.

Anti-A and anti-B haemagglutinin levels in intravenous immunoglobulins: are they on the rise? A comparison of four different analysis methods and six products.

Recent reports of severe haemolytic reactions upon high dose treatment with new generation intravenous immunoglobulins (IVIGs) prompted us to examine the anti-A and anti-B haemagglutinin content of these therapeutics. We compared four different test methods, namely the indirect and direct haemagglutination test as described in the European Pharmacopoiea (Ph. Eur.) and two commercial gelcard systems with the aim to define the most reliable method for a large-scale comparison of different IVIG products. Absolute titres varied when the same samples were analyzed by the four methods, while the relative ranking of six different IVIG preparations representing different manufacturing classes was identical. New generation IVIGs showed 1-2 titre steps higher anti-A titres than the older products. Haemagglutinin titres of all 48 IVIG batches analyzed were within the current Ph. Eur. specification of ≤1:64 when tested by the official pharmacopoeial method. Based on efficiency, reliability and lower costs, the direct gelcard method could be a valid alternative to the official Ph. Eur. method to serve as a limit test. However, due to the highest intermediate precision, the official Ph. Eur. method seems to be most suitable to compare haemagglutinin titres of different IVIG products.

Acquisition of carbapenemase-producing Enterobacteriaceae by healthy travellers to India, France, February 2012 to March 2013.

Healthy travellers to countries where carbapenemases-producing Enterobacteriaceae (CPE) are endemic might be at risk for their acquisition, even without contact with the local healthcare system. Here, we report the acquisition of CPE (two OXA-181, one New Delhi metallo-beta-lactamase 1 (NDM-1)) in three healthy travellers returning from India. The duration of CPE intestinal carriage was less than one month. The results indicate that healthy travellers recently returning from India might be considered as at risk for CPE carriage.

[Translation into French and republication of: "Central venous catheter associated upper extremity deep vein thrombosis in cancer patients: Diagnosis and therapeutic management"]. / Traduction et republication de : « Thrombose veineuse profonde du membre supérieur associée à un cathéter veineux central chez les patients cancéreux : diagnostic et prise en charge thérapeutique ¼.

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least 3 months, including at least 1 month after catheter removal following initiation of therapy.

[Translation into French and republication of: "Recurrent venous thromboembolism in anticoagulated cancer patients: diagnosis and treatment"]. / Traduction et republication de : « Maladie thromboembolique veineuse récidivante chez les patients cancéreux anticoagulés : diagnostic et traitement ¼.

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.

[Translation into French and republication of: "Treatment of cancer-associated venous thromboembolism in patients under palliative care"]. / Traduction et republication de : « Traitement de la maladie thromboembolique veineuse associée au cancer chez les patients en soins palliatifs ¼.

Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative care are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit/risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event.