Delphine Maucort-Boulch

A 2-Year Prospective Study of Human Papillomavirus Persistence among Women with a Cytological Diagnosis of Atypical Squamous Cells of Undetermined Significance or Low-Grade Squamous Intraepithelial Lesion

BACKGROUND Cervical cancer is caused by persistent infection with human papillomavirus (HPV). Most infections and associated lesions clear spontaneously. It is important to define the determinants and timing of clearance, so that viral persistence can be recognized and managed. METHODS We investigated HPV natural history among 4504 subjects from ALTS (Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study). A discrete-time Markov model was used to simultaneously describe the prevalence, incidence, and persistence of type-specific HPV infection over 24 months in women with equivocal or mildly abnormal cytological results. Interactions between multiple HPV types infecting the same woman were examined for incidence of new infection (after an HPV-16 infection) and persistence of a current infection within groups defined by phylogenetic relatedness or by carcinogenicity. RESULTS Ninety-one percent (95% credible interval [CI], 90%-92%) of prevalent HPV infections at enrollment cleared within 24 months. The probability that an infection would persist for a further 6 months increased with the duration of infection, from 37% (95% CI, 35%-39%) for a newly observed infection to 65% (95% CI, 61%-70%) for an infection that had already persisted for > or =18 months. No consistent evidence of interactions was found between multiple HPV types regarding the incidence of new infection after an HPV-16 infection or regarding persistence of current HPV infection. CONCLUSION Although virtually all HPV infections clear within 2 years, the remaining infections have a high potential for persistence and, by implication, progression to precancer and cancer. Once biological and behavioral determinants are controlled for, HPV infections with different types seem to be independent of each other.

Long-term outcomes of chronic minimally conscious and vegetative states.

Objective: The present retrospective cohort study compares the long-term functional outcome, improvement or deterioration, of patients considered in a vegetative state (VS) or a minimally conscious state (MCS) 1 year after coma onset, then yearly for up to 5 years. Methods: We reviewed the clinical courses of 12 patients in VS and 39 in MCS. The outcomes were assessed at 2, 3, 4, and 5 years after injury using the 5 categories of the Glasgow Outcome Scale plus an additional category for patients in MCS. A logistic regression analysis investigated the relationships between each outcome and 10 predictor variables. Four of these variables were auditory evoked potentials recorded at the early stage of coma. Results: None of the patients in VS improved during the follow-up period: 1 was lost to follow-up, 9 died, and 2 remained in VS. Among patients in MCS, 3 were lost to follow-up, 14 died, 9 remained in MCS, and 13 emerged from MCS with severe disabilities. VS, age >39 years, and bilateral absence of cortical components of middle-latency auditory evoked potentials were significantly associated with deterioration. Conclusions: In contrast to patients in VS, a third of patients in MCS improved more than 1 year after coma onset. This emphasizes the need to define reliable boundaries between VS and MCS using repeated clinical evaluations and all imaging and neurophysiologic tools available today.

World‐wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC). In order to assess the relative contribution of HBV and HCV to HCC worldwide, and identify changes over time, we conducted a systematic review of case series published up to the year 2014. Eligible studies had to report seroprevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti‐HCV), alone and in combination, for at least 20 adult HCC cases. Studies using a first‐generation enzyme‐linked immunosorbent assay test for HCV were excluded. A total of 119,000 HCC cases in 260 studies were included from 50 countries. Most European and American countries show a preponderance of HCV over HBV and a substantial fraction of viral marker–negative cases. Asian and African countries generally show a predominance of HBV. The fraction of HCV‐positive HCC cases is substantial in Taiwan, Mongolia, Japan, and Pakistan as well as in Western‐Central Asia and Northern Africa. No eligible studies were available in Oceania, large parts of Africa, Eastern Europe, and Central Asia. The United States, Brazil, and Germany show evidence of higher prevalence of HCV in HCC since the year 2000. Conversely, Japan and Italy show a decline in the proportion of HCV‐positive HCC. Conclusion: HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of HCC cases in several countries attributable to HCV. (Hepatology 2015;62:1190‐1200)

High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial

The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte–monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients.

AbstractWe conducted a retrospective observational study to describe a cohort and identify the prognostic factors in adult-onset Still disease (AOSD). Patients enrolled in this retrospective chart review fulfilled either Yamaguchi or Fautrel criteria. Candidate variables were analyzed with logistic unadjusted and adjusted regression models.Fifty-seven patients were seen in the internal medicine (75%) and rheumatology (25%) departments over a mean period of 8.4 years. The median time to diagnosis was 4 months. The course of AOSD was monocyclic in 17 patients, polycyclic in 25, and chronic in 15. The assessment of glycosylated ferritin (GF) in 37 patients was correlated with early diagnosis. Nine 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) scans identified the lymph nodes and glands as the main sites of hypermetabolism. Complications were frequent (n = 19), including reactive hemophagocytic syndrome (n = 8). None of the 3 deaths could be attributed to AOSD. Corticosteroid dependence, as predicted by a low GF level, occurred in 23 patients (45%). A quarter of the patients received tumor necrosis factor-&agr; blockers or anakinra with good tolerance. Fever >39.5°C was predictive of monocyclic AOSD, while arthritis and thrombocytopenia were associated with chronic and complicated AOSD, respectively. The youngest patients had the highest risks of resistance to first-line treatments.AOSD remains difficult to diagnose. Mortality is low despite frequent complications. GF and 18FDG-PET scans were of value in the diagnostic approach. The condition in highly symptomatic patients evolved to systemic AOSD, whereas more progressive patterns with arthritis predicted chronic AOSD.

Predictors of human papillomavirus persistence among women with equivocal or mildly abnormal cytology.

We investigated short‐term persistence of human papillomavirus (HPV) infection among 2,408 women with low‐grade or equivocal cytological abnormalities followed for 24 months. Odds ratios (ORs) for persistence to the next 6‐month visit were estimated by a discrete time survival model. Prevalent HPV infections persisted longer in older women, but no association with age was found for incident HPV infections. Increased likelihood of persistence was found among current smokers of >20 cigarettes per day compared with smokers of ≤10 cigarettes per day (OR=1.43; 95% confidence interval [CI]: 1.02–2.01) and among current injectable contraceptive users (OR=1.15; 95% CI: 1.01–1.32). Persistence was more likely among infections with higher viral load (OR=2.05; 95% CI: 1.65–2.53) or with concurrent cytological abnormalities (OR=1.19; 95% CI: 1.03–1.39 and 1.29; 95% CI: 0.99–1.70 for ASCUS/LSIL and ASC‐H/HSIL, respectively). We conclude that new HPV infections in older women are not riskier by the metric of viral persistence than those in younger women. Other risk factors such as oral contraceptive use and multiparity that have been associated with cervical cancer or cervical intraepithelial neoplasia grade 3 were not associated with short‐term HPV persistence.

International Correlation between Human Papillomavirus Prevalence and Cervical Cancer Incidence

Data from population-based human papillomavirus (HPV) surveys in regions of low, intermediate, and high cervical cancer incidence were used to study the ecologic correlation between high-risk HPV prevalence and cervical cancer incidence. All the surveys were conducted by the IARC according to a standardized protocol for the collection of female population samples and detection of HPV DNA using PCR assay in a central laboratory. Cervical cancer incidence data were extracted, when available, from a cancer registry covering the surrounding or nearby area of the prevalence survey. Thirteen areas were included in this analysis. The relation between high-risk HPV prevalence and cervical cancer incidence was investigated within 10-year age groups from age 25 to 65 years. A Poisson regression model was used to predict cervical cancer incidence from HPV prevalence, and the strength of the correlation was assessed using Spearman’s rank correlation coefficient. The rank correlation was weakest in women ages 25 to 34 years and strongest in women ages 55 to 64 years. In addition, the prevalence of high-risk HPV was not able to predict cervical cancer incidence accurately in every country. Nevertheless, our data raise a concern about the cervical cancer burden in areas where reliable cervical cancer statistics do not exist but where the prevalence of high-risk HPV in women over age 45 is high. (Cancer Epidemiol Biomarkers Prev 2008;17(3):717–20)

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients

Background Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. Patients and methods Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as ‘unfavourable neurological outcome’. Results Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. Conclusion Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

Very Low Cerebral Blood Volume Predicts Parenchymal Hematoma in Acute Ischemic Stroke

Background and Purpose— Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization. Methods— The volume of cerebral tissue with CBV ⩽2.5th percentile of the normal hemisphere was calculated within the acute diffusion-weighted imaging lesion. Hemorrhagic transformation was assessed on day 2 MRI according to the European Cooperative Acute Stroke Study II criteria. Recanalization and reperfusion were assessed on 3-hour follow-up MRI. Results— Of the 110 patients, hemorrhagic transformation occurred in 59 patients, including 7 PH. In univariate analysis, the acute National Institutes of Health Stroke Scale score (P=0.002), acute diffusion-weighted imaging lesion volume (P=0.02), and thrombolysis (P=0.03), but not very low CBV (P=0.52), were associated with hemorrhagic transformation. The volume of very low CBV was the only predictor of PH (P=0.007). Early reperfusion and recanalization had no influence on either hemorrhagic transformation or PH. Conclusion— Very low CBV was the only independent predictor of PH in patients with acute stroke.

Extremely low birthweight infants: how neonatal intensive care unit teams can reduce postnatal malnutrition and prevent growth retardation

To evaluate the impact of an improved nutritional policy for extremely low birthweight (ELBW) infants on nutritional deficits and postnatal growth.