Background.Campylobacter bacteremia is uncommon. The influence of underlying conditions and of the impact of antibiotics on infection outcome are not known. Methods.From January 2000 through December ...2004, 183 episodes of Campylobacter bacteremia were identified in 23 hospitals in the Paris, France, area. The medical records were reviewed. Characteristics of bacteremia due to Campylobacter fetus and to other Campylobacter species were compared. Logistic regression analysis was performed to identify risk factors for fatal outcome within 30 days. Results.Most affected patients were elderly or immunocompromised. C. fetus was the most commonly identified species (in 53% of patients). The main underlying conditions were liver disease (39%) and cancer (38%). The main clinical manifestations were diarrhea (33%) and skin infection (16%). Twenty-seven patients (15%) died within 30 days. Compared with patients with bacteremia due to other Campylobacter species, patients with C. fetus bacteremia were older (mean age, 69.5 years vs. 55.6 years; P<.001) and were more likely to have cellulitis (19% vs. 7%; P=.03), endovascular infection (13% vs. 1%; P=.007), or infection associated with a medical device (7% vs. 0%; P=.02). Independent risk factors for death were cancer (odds ratio OR, 5.1; 95% confidence interval CI, 1.2–20.8) and asymptomatic infection (OR, 6.7; 95% CI, 1.5–29.4) for C. fetus bacteremia, the absence of prescription of appropriate antibiotics (OR, 12.2; 95% CI, 0.9–157.5), and prescription of third-generation cephalosporins (OR, 10.2; 95% CI, 1.9–53.7) for bacteremia caused by other species. Conclusions.Campylobacter bacteremia occurs mainly in immunocompromised patients. Clinical features and risk factors of death differ by infection species.
Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral ...response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n = 81) or not (n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56-74.9) and 77.5% (95% CI = 68.5-87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31-80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.
The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir ...boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs.
We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed.
We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression.
Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.
Breast cancers expressing high levels of Ki67 are associated with poor outcomes. Oncotype DX test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by ...providing a Recurrent Score (RS). RS measures the expression of 21 specific genes from tumor tissue, including Ki67. The primary aim of this study was to assess the agreement between Ki67
obtained with Oncotype DX RS and Ki67
. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67
; and association between RS and Ki67
. Herein, we report a low agreement of 0.288 by Pearson correlation coefficient test between Ki67
and Ki67
in a cohort of 98 patients with early ER+/HER2- breast cancers. Moreover, Ki67
tumors were significantly associated with the occurrence of events (p = 0.03). On the other hand, we did not find any association between Ki67
and EFS (p = 0.26). We observed a low agreement between expression level of Ki67
and Ki67 protein labelling by IHC. Unlike Ki67
and independently of the RS, Ki67
could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67
measured by qRT-PCR. The Ki67
in medical routine could be a good support in countries where Oncotype DX is not accessible.
Metabolic syndrome (MetS) and nonalcoholic fatty liver disease have become a common finding in HIV-infected patients. However, the severity, risk factors and pathogenesis of liver fibrosis in this ...population have been poorly documented.
To assess the impact of MetS on liver fibrosis and analyze the association between MetS, liver fibrosis and markers of adipose tissue and macrophage activation.
In a matched cohort of HIV-1-monoinfected patients with and without MetS, after exclusion of other causes of liver disease, we assessed liver stiffness measurement and measured levels of serum adipokines, homeostasis model assessment index and soluble CD163 (sCD163) and CD14 as markers of fat, insulin resistance and macrophage/monocyte activation, respectively.
A total of 468 HIV-monoinfected individuals were enrolled; 405 (203 with MetS/202 without MetS) were analyzed. Patients with MetS were older and 49% had insulin resistance. The prevalence of significant liver fibrosis (≥F2) was higher in patients with MetS 25.1%, 95% confidence interval (19.3-31.2) compared with those without MetS 7.9%, (4.6-12.5), P < 0.0001. In multivariate analysis with adjustment on MetS, obesity odds ratio: 3.0 (1.1-8.4) and homeostasis model assessment 1.1 (1.007-1.2) were independent factors of advanced fibrosis (>= F3).. Serum levels of adipokines and sCD163 were significantly associated with the degree of liver fibrosis. When adjusted on MetS, leptin and sCD163 remained strongly associated with fibrosis/cirrhosis, whereas HIV parameters and antiretroviral therapy were not.
In HIV-monoinfected patients, MetS is an important risk factor of liver fibrosis. Adipose tissue and macrophage activation might be key players in the development of liver fibrosis but the exact mechanisms need to be elucidated.
We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence ...rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/μL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART.
A new approach for easy and fast modeling of EMI filter in aircraft application is proposed, in order to be used in an optimization process. A modular description in a user friendly environment ...allows describing the model and taking into account all the technological parameters of the system, i.e., the control strategy, the inverter model (semiconductors, layout, etc.), the filter, the cables, and the ac machine. The frequency model is automatically built from this description, as well as its gradients according to its inputs. In a second step, by using this model, an optimization of the filter values can be carried out, using various algorithms, to reach the smallest volume. This early design methodology can also be used to investigate the impact of some technological choices of the electrical drive (control strategy or cable characteristics for instance) on the filter volume.
ABSTRACT
The emergence of SARS‐CoV‐2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We ...report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID‐19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67–86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.
To investigate the extent to which drug resistance can be evaluated from proviral HIV-1 DNA genotype compared with RNA genotype at different timepoints.
In HIV-1-infected patients routinely seen at a ...university hospital, who needed to change their current ART, antiretroviral drug resistance was determined from DNA genotype and was compared with past RNA genotype (group 1) or same-day RNA genotype (group 2). A 'resistance sum' was defined as the sum of agents to which resistance was present and was calculated across NRTI, NNRTI and PI. We defined 'loss of information' as when a lower resistance sum was observed in DNA than in RNA samples.
Of the 74 and 26 patients included in groups 1 and 2, respectively, most had a long median duration of known HIV-1 infection (17.4 and 14.2 years) and ART (15.3 years and 13.5 years). For group 1, the median (range) resistance sums between DNA/RNA were 0 (0-6)/1 (0-6) for NRTIs, 0 (0-4)/0 (0-4) for NNRTIs and 0 (0-7)/0 (0-8) for PIs, which were comparable with group 2. Loss of information in DNA was substantial for group 1 (37.8%) and less so for group 2 (11.1%). In multivariable analysis, only longer ART duration was significantly associated with loss of information. Results were similar in patients harbouring resistance to one or more agents.
In a real-life setting, genotyping DNA from PBMC has some degree of concordance compared with RNA. Loss of information in DNA would appear to coincide with longer periods of ART.
To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS.
...Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres.
Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method.
Fifty-eight HIV-1-infected patients were diagnosed with RHS certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/microl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/microl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68).
In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era.