[High-intensity focused ultrasound for locally prostate cancer: An Afro-Caribbean single-center study]. / Ultrasons focalisés de haute intensité pour le traitement du cancer localisé de la prostate : étude mono-centrique caribéenne.

INTRODUCTION: High-intensity focused ultrasound (HIFU) has proved to be effective in the treatment of localized prostate cancer. The aim of this prospective study is to assess their first oncological and functional results in an Afro-Caribbean population. METHODS: From May 2018 to January 2020, 77 patients issued from French West Indies were included. Several treatments were carried out: whole-gland treatment hemi or focal ablation; in a primary setting (group I) or a salvage therapy (group II). PSA level was assessed at 2, 6, 9 and 12 months. MpMRI and post HIFU biopsy were performed between 6 and 9 months postoperatively. Continence, urinary end erectile functions were assessed by ICS, IPSS and IIEF scores. RESULTS: Groupe I included 71.2% patients, group II, 28.8%. The median age was 75.4 years [IQR 69.6-79.4]. The median follow-up was 8.3 months [IQR 3.5-12.25]. At inclusion, PSA was 7.7ng/ml [IQR 5.5-11.2] in group I, and 5.9ng/ml [IQR 4.4-7.9] in group II. In the whole population, there was 73.5% negative biopsies; 14.7% of the biopsies were positive in treated zone and 11.8% in non-treated zone. Regarding morbidities, urinary incontinence appeared in 7.5% and erectile dysfunction rate was 13.2%. CONCLUSION: Our study reveals the first experience of HIFU by Focal One® device in an Afro-Caribbean population. It seems to be a safe and reproducible treatment with acceptable oncological results and low genitourinary morbidity. Long term follow-up and a higher number of patients are necessary to validate these results.

Active surveillance in prostate cancer is possible for Afro-Caribbean population: Comparison of oncological outcomes with a Caucasian cohort.

BACKGROUND: Prostate cancer is supposedly more aggressive among Afro-Caribbean men. There is a lack of data in this population for active surveillance. Published series are retrospective or have small samples and results are discordant. The objective was to determinate whether actual active surveillance modalities can be applied for Afro-Caribbean men by comparing their oncological outcomes with Caucasian men. METHODS: A total of 449 consecutive patients who underwent active surveillance for favorable-risk prostate cancer in two French University-Medical-Centers between 2005 and 2018: 261 in Guadeloupe, French West Indies, and 188 in Bordeaux, metropolitan France. Median follow-up was 56 months, (95% CI [32-81]) and 52 months (95% CI [30-75]), respectively (P=0.07). Curative treatment was given in case of histological, biological, or imaging progression, or upon patient demand. Primary endpoints were treatment-free, overall and specific survival. Secondary outcomes were reasons of discontinuating active surveillance, histological poor prognosis factors after prostatectomy, CAPRA-S score, biochemical-recurrence-free after treatment and metastasis-free survival. Kaplan-Meier method was used. RESULTS: Median treatment free survival was 58.4 months (CI 95% [48.6-83.1]) for ACM and not reached at 120 months for CM (P=0.002). Overall survival (P=0.53), and specific survival (P=0.21) were similar in the two groups. CM were likely to have poor prognosis factor on prostatecomy piece (57 vs 30%, P=0.01). No difference for repartition of the CAPRA-S score (P=0.86), biochemical-recurrence-free (P=0.92) and metastasis-free (P=0.44) survival. CONCLUSIONS: Oncological outcomes for active surveillance of Afro-Caribbean and Caucasian men were similar in terms of mortality, recurrence and metastasis in our bicentric study, showing usability of current criteria for Afro-Caribbean. The higher rate of disease progression in the Afro-Caribbean population requires close monitoring. LEVEL OF EVIDENCE: 3.

[Pelvimetrics measures as predictives factors of positives surgical margins after robot-assisted laparoscopic prostatectomy]. / Mesures pelvimétriques prédictives de marges chirurgicales au décours d'une prostatectomie totale robot-assitée pour cancer prostatique.

INTRODUCTION: Anthropometric data report that pelvic bone of African subjects are narrower and the pelvic cavity is deeper. The aim of the study was to evaluate the influence of pelvic dimensions (PD) on Positive surgical margins (PSM) rate in Afro-Caribbean population after robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: Preoperative pelvic MRI of all patients who have had RALP at the University Hospital Center of Guadeloupe between January 2013 and December 2015 was retrospectively analyzed. PD, including the Height of the upper edge of the prostate (HP), the Apical Depth (AD) and Ischial Spines Distance (ISD), and indexes (prostate volumetric index [ISD/VP], apical depth index [ISD/AD] and prostate depth index [ISD/(AD/HP)]) were compared according to the presence or absence of PSM with uni and multivariate analysis. RESULTS: One hundred and seventy-eight patients were included in the study, of whom 60 (33.7%) presented PSM. In univariate analysis, significant differences between the presence or absence of PSM were observed on the AD (30.3±8.7mm versus 24.8±8.0mm, P<0.001), the HP (9.5±8.5mm versus 16.8±11.9mm, P<0.001) and the ISD (89.6±8.8mm versus 96.1±8.4mm) as well as the indexes of apical depth and prostatic depth. In multivariate logistic regression, the ISD (P<0.001) and HP (P=0.02) were associated with increased likelihood of PSM, but not AD or indexes. CONCLUSION: This study suggests that interspinous distance is the best predictor of PSM during RALP in Afro-Caribbean patients. This measure may be useful to define the therapeutic pattern of patients with prostate cancer. A prospective study with a larger population, comparing RALP in Afro-Caribbean and in caucasians patients, would be needed.

[Epidemiology of urolithiasis in French West Indies: A retrospective study]. / Épidémiologie de la lithiase urinaire aux Antilles françaises : étude rétrospective monocentrique.

INTRODUCTION: The incidence of urolithiasis is increasing with dietary changes especially in developed countries. Guadeloupe is a French department overseas where western diet meets traditional local food. The objective was to describe and analyze the epidemiology of urolithiasis in Guadeloupe. MATERIAL AND METHODS: We conducted a retrospective single-center study throughout the year 2015 on patients hospitalized for urolithiasis at University Hospital of Pointe-à-Pitre. Data of the patients, treatments performed and the types of stones were recorded. According to their mineral content, groups were composed. RESULTS: In total, 165 patients were included. The sex ratio was 1.61. The median body mass index (BMI) was 26.5kg/m2. The most common stone was oxalocalcic (64.7%). Mixed stones (24.7%) were in second place. There were only 3.5% of uric acid urolithiasis. Calcium oxalate stones were predominantly monohydrate. The oxalocalcic stones were significantly more frequent in men (80% versus 47.5%, P=0.01) and in the age group over 50 years old (72.2% versus 51.6%, P=0.04). There was no association between the type of stone and the BMI. CONCLUSION: Epidemiology of urolithiasis in our French Caribbean island is, therefore, similar to continental France. However, our population is distinguished by the proportion of women affected and by the different proportions among each type of stone. Other studies on larger samples are needed to study these specificities. LEVEL OF EVIDENCE: 4.

[Impact of Gleason score on biochemical recurrence free survival after radical prostatectomy with positive surgical margins]. / Impact du score de Gleason sur la survie sans récidive biologique après prostatectomie totale pour cancer avec marges chirurgicales positives.

PURPOSE: Research of predictive factors of biochemical recurrence to guide the establishment of an adjuvant treatment after radical prostatectomy for cancer with positive surgical margins. METHODOLOGY: A retrospective cohort of 1577 afro-caribbean patients undergoing radical prostatectomy operated between 1st January 2000 and 1st July 2013 was analyzed. In this cohort, 406 patients had positive surgical margin, we excluded 11 patients who received adjuvant therapy (radiotherapy, hormonotherapy, radio-hormonotherapy) and 2 patients for whom histological analysis of the surgical specimen was for a pT4 pathological stage. After a descriptive analysis, we used a Cox model to look for predictors of survival without biochemical recurrence then, depending on the significant variables, we separated our population into six groups: stage pT2 with Gleason score≤3+4 (group 1), stage pT2 with a score of Gleason≥4+3 (group 2), stage pT3a with a Gleason core≤3+4 (group 3), pT3a stage with a score of Gleason≥4+3 (group 4), stage pT3b with a Gleason score≤3+4 (group 5) and stage pT3b Gleason≥with a score of 4+3 (group 6) and compared survival without biochemical recurrence using a log rank test. After radical prostatectomy with surgical margins with an anatomopathological stage≤pT3b, a Gleason score≥4+3 had a pejorative survival without biochemical recurrence than pathological stage (P<0.001). RESULTS: In multivariate analysis, predictors of survival without biochemical recurrence after radical prostatectomy with positive surgical margins were the majority Gleason postoperative (P<0.0001), pathological stage (P=0.049) adjusted preoperative PSA (P=0.826), with the body mass index (BMI) (P=0.59) and tumor volume (P=0.95). CONCLUSION: A high postoperatively Gleason score (≥4+3) has a better predictive value of biochemical recurrence than pathological stage pT2 or pT3 at the patients having been treated for prostate cancer by radical prostatectomy with positive surgical margins. LEVEL OF EVIDENCE: 4.

Mechanisms of evolution in Rickettsia conorii and R. prowazekii.

Rickettsia conorii is an obligate intracellular bacterium that causes Mediterranean spotted fever in humans. We determined the 1,268,755-nucleotide complete genome sequence of R. conorii, containing 1374 open reading frames. This genome exhibits 804 of the 834 genes of the previously determined R. prowazekii genome plus 552 supplementary open reading frames and a 10-fold increase in the number of repetitive elements. Despite these differences, the two genomes exhibit a nearly perfect colinearity that allowed the clear identification of different stages of gene alterations with gene remnants and 37 genes split in 105 fragments, of which 59 are transcribed. A 38-kilobase sequence inversion was dated shortly after the divergence of the genus.

Real-time PCR strategy and detection of bacterial agents of lymphadenitis.

The aim of this study was to compare 16 S rRNA gene amplification and sequencing with a systematic real-time PCR assay screening strategy that includes all common known pathogens recovered from lymph node biopsy specimens. Lymph node biopsy samples sent to our laboratory from January 2007 to December 2008 were tested in the study. Lymph nodes were screened for the presence of any bacteria by PCR amplification and sequencing targeting the 16 S rRNA gene and also by a specific real-time PCR strategy that includes Bartonella henselae, mycobacteria, Francisella tularensis, and Tropheryma whipplei. By testing 491 lymph nodes, we found that the sensitivity of our specific real-time PCR assay strategy was significantly higher than 16 S rRNA PCR amplification and sequencing for the detection of Bartonella henselae (142 vs 98; p < 10(-4)), Francisella tularensis (16 vs 10, p < 10(-4)), and mycobacteria (8 versus 3, p < 10(-4)). None of the samples was positive for Tropheryma whipplei. Our study demonstrates the usefulness and specificity of a systematic real-time PCR strategy for molecular analysis of lymph node biopsy specimens and the higher sensitivity compared with standard 16 S rRNA gene amplification and sequencing.

Evaluation of the LightCycler SeptiFast test in the rapid etiologic diagnostic of infectious endocarditis.

The SeptiFast test (Roche Diagnostics) is a new commercial molecular technique that has emerged for the detection of bacteria in blood. We compared in this study the sensitivity of blood culture to a commercially available broad-range real-time polymerase chain reaction (PCR) assay for the detection in blood of 19 bacterial species and six fungal species (SeptiFast test, Roche Diagnostics) in 63 patients with infectious endocarditis (IE). The SeptiFast test is not more sensitive for organisms such as Streptococci, Enterococci, and Staphylococcus aureus (11/29 versus 12/29 for blood culture). It has detected less commonly coagulase-negative Staphylococci (0/15 versus 3/15, P = 0.2) and significantly fewer other microorganisms (0/6 versus 4/6, P = 0.03). However, bacteria were detected from three IE treated by antibiotics, with blood culture negative on admission. The SeptiFast test may be useful in cases of IE in patients treated with antibiotics before admission.

Arc-like magmas generated by mélange-peridotite interaction in the mantle wedge.

The mechanisms of transfer of crustal material from the subducting slab to the overlying mantle wedge are still debated. Mélange rocks, formed by mixing of sediments, oceanic crust, and ultramafics along the slab-mantle interface, are predicted to ascend as diapirs from the slab-top and transfer their compositional signatures to the source region of arc magmas. However, the compositions of melts that result from the interaction of mélanges with a peridotite wedge remain unknown. Here we present experimental evidence that melting of peridotite hybridized by mélanges produces melts that carry the major and trace element abundances observed in natural arc magmas. We propose that differences in nature and relative contributions of mélanges hybridizing the mantle produce a range of primary arc magmas, from tholeiitic to calc-alkaline. Thus, assimilation of mélanges into the wedge may play a key role in transferring subduction signatures from the slab to the source of arc magmas.

Influence of Thoracic Aortic Inflammation and Calcifications on Arterial Stiffness and Cardiac Function in Older Subjects.

BACKGROUND: Vascular aging is accompanied by gradual remodeling affecting both arterial and cardiac structure and mechanical properties. Hypertension is suggested to exert pro-inflammatory actions enhancing arterial stiffness. OBJECTIVE: To determine the influence of thoracic aortic inflammation and calcifications on arterial stiffness and cardiac function in hypertensive and normotensive older subjects. DESIGN: A prospective study. SETTING: An acute geriatrics ward of the University Hospital of Nancy in France. SUBJECTS: Thirty individuals ≥ 65 years were examined, including 15 hypertensive subjects and 15 controls well-matched for age and sex. MEASUREMENTS: Applanation tonometry was used to measure aortic pulse wave velocity (AoPWV) and carotid/brachial pulse pressure amplification (PPA). Left ventricular parameters were measured with magnetic resonance imaging. Local thoracic aortic inflammation and calcification were measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Biomarkers of low-grade inflammation were also quantified. RESULTS: AoPWV was higher in elderly hypertensive subjects comparatively to normotensive controls (15.5±5.3 vs. 11.9±2.5, p=0.046), and hypertensives had a higher calcification volume. In the overall population, calcifications of the thoracic descending aorta and inflammation of the ascending aorta accounted for respectively 18.1% (p=0.01) and 9.6% (p=0.07) of AoPWV variation. Individuals with high levels of calcifications and/or inflammation had higher AoPWV (p=0.003). Inflammation had a negative effect on PPA explaining 13.8% of its variation (p<0.05). CONCLUSION: This study highlights the importance of local ascending aortic inflammation as a potential major actor in the determination of PPA while calcifications and hypertension are more linked to AoPWV. Assessment of PPA in the very elderly could provide complementary information to improve diagnostic and therapeutic strategies targeting ascending aortic inflammation.

The 16S-23S rRNA intergenic spacer region of Bartonella (Rochalimaea) species is longer than usually described in other bacteria.

We amplified by polymerase chain reaction (PCR) and sequenced using an automated laser fluorescent DNA sequencer (Pharmacia) the intergenic spacer region (ITS) between the 16S and 23S rRNAs of the four species of Rochalimaea which were recently renamed Bartonella sp. We obtained DNA fragments of 1211, 1262, 1258 and 1529 bp for the reference species of B. quintana, B. henselae, B. vinsonii and B. elizabethae, respectively. The ITS of the four species are longer than previously reported in prokaryotes and contained the genes encoding isoleucine-tRNA (tRNA(Ile)) and alanine-tRNA (tRNA(Ala)). The sequences of the tRNA(Ala) genes are identical for the four Bartonella species, but the tRNA(Ile) gene sequence of B. quintana presents one mutation in comparison with the other species.

Suppression of in vitro maintenance of non-promyelocytic myeloid leukemia clonogenic cells by all-trans retinoic acid: modulating effects of dihydroxylated vitamin D3, alpha interferon and 'stem cell factor'.

In a liquid culture system, all-trans retinoic acid (ATRA), alone and in combination with dihydroxylated vitamin D3 (D3) or alpha interferon (alphaIFN) at concentrations achievable in vivo, could significantly suppress the maintenance of non-promyelocytic myeloid leukemia clonogenic cells (CFU-L) in 9/20, 9/18 and 7/11 cases, respectively. That suppression was counteracted only slightly by the addition of 'stem cell factor', a cytokine which promotes CFU-L expansion in vitro. Differentiated cells slightly increased in 5/17 cases only, suggesting the prevalence of anti-proliferative rather than differentiating mechanisms. The present results extend our previous ones and suggest the possible therapeutical value of ATRA+D3 or alphaIFN, even in cases of non-promyelocytic myeloid leukemia.

Phylogenetic analysis of the genus Rickettsia by 16S rDNA sequencing.

Rickettsiae are Gram-negative bacteria which multiply only inside host cells and need arthropods either as reservoirs or as vectors. Using the polymerase chain reaction and an automated laser fluorescent DNA sequencer, we amplified and sequenced the 16S rRNA (rDNA) of all available bacteria of the genus Rickettsia. R. tsutsugamushi remained close to the other bacteria of the genus Rickettsia using this technique, contrary to previous conclusions based on the study of the Sta-58 protein antigen. We found that R. canada was not included in the typhus group, as is currently recognized, but was grouped with the rickettsiae of the spotted fever group (SFG). All the SFG rickettsiae tested were grouped in the same cluster (R. conorii, Indian tick typhus rickettsia, Astrakhan fever rickettsia, Israeli tick typhus rickettsia, HA-91, R. sibirica, R. parkeri, "R. africae", "R. slovaca", R. rickettsii, Thai tick typhus rickettsia, R. japonica, R. massiliae, R. rhipicephali, R. montana, two recent isolates GS and Bar 29, R. australis, R. akari, R. bellii and R. helvetica). The recently described ELB bacterium, the agent of the Californian murine typhus, and AB bacterium, a bacterium associated with male killing in the ladybird beetle, were found in this cluster. The sequences of R. conorii Moroccan strain/Indian tick typhus rickettsia, R. massiliae/GS and R. sibirica/HA-91 were identical. All the rickettsiae had a unique ancestor with bacteria also isolated in arthropods (Ehrlichia, Cowdria, Anaplasma, Wolbachia pipientis), eventually pathogenic for mammals and implicated in parthenogenesis and cytoplasmic incompatibility. We conclude that a unique bacterium started a stable association with arthropod ancestors and generated the observed diversity of the currently isolated members of the Rickettsiales.

Isolation and identification of a rickettsial strain related to Rickettsia massiliae in Greek ticks.

Adult ticks were collected in a rural area of central Greece in order to isolate and identify rickettsiae. A hemolymph test using Gimenez staining was used for detection, while simultaneous isolation was performed using the shell-vial technique. Serologic, antigenic, and genomic characterization of the isolates was achieved by microimmunofluorescence, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and pulsed-field gel electrophoresis (PFGE), respectively. Although none of the 242 collected ticks was positive by the hemolymph test, one rickettsial isolate, designated GS, was obtained by the shell-vial technique. This isolate originated from a female Rhipicephalus sanguineus. Microimmunofluorescence serologic typing by the method of Philip and others demonstrated that GS belongs to the same serotype as the recently isolated Rickettsia massiliae (Mtu1). Protein analysis by SDS-PAGE and immunoblotting by Western blot revealed similar profiles between the two rickettsiae. Using Alu I, Rsa I, and Pst I restriction endonucleases in PCR-RFLP analysis, GS and R. massiliae were found to possess identical restriction sites. However, PFGE showed differences when the two genomes were digested with Bss HII and Sma I restriction endonucleases, in spite of their equal size. In conclusion, the first rickettsial isolation in Greece was found to be antigenically identical and genotypically close to the French isolate R. massiliae, despite small differences showed by PFGE.

Tick-borne rickettiosis in Guadeloupe, the French West Indies: isolation of Rickettsia africae from Amblyomma variegatum ticks and serosurvey in humans, cattle, and goats.

Twenty-seven rickettsiae were isolated and/or detected from 100 Amblyomma variegatum ticks collected on Guadeloupe in the French West Indies. In this study, the polymerase chain reaction procedure appeared to be more sensitive in detecting rickettsiae in ticks than the shell-vial technique. Sequencing a portion of the outer membrane protein A-encoding gene showed that these rickettsiae appeared to be identical to Rickettsia africae, a member of the spotted fever group rickettsiae recently described as an agent of African tick-bite fever occurring in sub-Sahelian Africa. A high seroprevalence of antibodies to R. africae was demonstrated among mammals, particularly humans, cattle, and goats. These results and a recently reported case of an infection due to R. africae on Guadeloupe demonstrate that R. africae is present on this island. Although this disease has been underdiagnosed there, it may be frequent and may exist on other Caribbean islands where A. variegatum has propagated dramatically over recent years.

Short report: isolation and identification of two spotted fever group rickettsial strains from patients in Catalonia, Spain.

Two rickettsial strains, 16B (previously isolated) and FB1, were isolated from blood from patients with Mediterranean spotted fever in Catalonia, Spain. These are the only 2 human rickettsial isolates of the spotted fever group obtained so far in Spain. These strains were identified by the polymerase chain reaction and sequence analysis of a fragment of the outer membrane protein A (ompA) gene. The partial ompA sequence was found to be 100% identical with that of Rickettsia conorii (Malish 7 strain) for both strains. These results confirm the presence of R. conorii in Catalonia, despite the fact that in a previous study, no R. conorii were isolated, but a new rickettsial strain of the spotted fever group (Bar29) was isolated from dog ticks (Rhipicephalus sanguineus) in Catalonia. Further studies are necessary to get a better knowledge of the epidemiology of rickettsiae in Catalonia.

Determination of the genome size of Ehrlichia spp., using pulsed field gel electrophoresis.

Ehrlichiae are obligatory intracellular, Gram-negative bacteria which belong to the alpha subclass of the phylum Proteobacteria and are responsible for infectious diseases of humans. Little is known about genetics and genomic organization of Ehrlichia spp. The genome sizes of four representatives of the genus Ehrlichia were determined for the first time by pulsed field gel electrophoresis. The sizes for E. sennetsu, E. risticii, E. chaffeensis (strain Arkansas and strain 91HE17), and the HGE agent were 878.5 kb, 880.3 kb, 1225.8 kb, 1262.3 kb and 1494 kb respectively.