Water in the terrestrial planet-forming zone of the PDS 70 disk.

Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks1. Water plays a key role in their formation2-4, although it is yet unclear whether water molecules are formed in situ or transported from the outer disk5,6. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks7, similar to PDS 70, the first system with direct confirmation of protoplanet presence8,9. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk10,11. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2 and/or OH, and survival through water self-shielding5. This is also supported by the presence of CO2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir12. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.

Endoscopic approach for orbital apex lesions: case series and review of the literature.

OBJECTIVE: The transnasal endoscopic approach may provide better visualisation and a safer approach to the orbital apex. This study presents a case series of orbital apex lesions managed by this approach. METHOD: This study was an eight-year retrospective analysis of seven patients who were operated on for orbital apex lesions in two tertiary medical centres. RESULTS: Complete tumour removal was performed in three patients and partial removal was performed in four patients. Visual acuity improved in three patients, remained stable in one patient and decreased in the other two patients. The visual field improved in four patients and did not change in two patients. Complications included worse vision and visual fields in 28.6 per cent of patients and late enophthalmos (of -1.25 ± 4.6 mm) in 2 patients. CONCLUSION: The transnasal approach to orbital apex lesions in selected cases may provide a rational alternative to transorbital surgery. Complete tumour removal should be weighed against the risk of damage to the optic nerve.

Endoscopic sinus surgery for dental implant displacement into the maxillary sinus-a retrospective clinical study.

The aims of this retrospective clinical study were to present our management protocol for the retrieval of impacted dental implants that have become displaced into the maxillary sinus cavity and to define the role of endoscopic sinus surgery in this setting. All 24 patients (25 implants) who underwent surgical retrieval of dental implants displaced into the maxillary sinus between 2012 and 2019 were included. Data on surgical interventions and complications were collected retrospectively. Eleven patients (46%) had chronic sinusitis associated with the migrated implant. All implants were successfully retrieved via transnasal endoscopic approach alone: 80% via a middle meatal antrostomy and 20% via a combined middle and inferior meatal antrostomy. Five patients required a concomitant transoral approach for oro-antral fistula repair. None required a transoral approach for displaced implant retrieval. All patients healed uneventfully without complications. Transnasal endoscopic sinus surgery via a middle meatal antrostomy or a combined middle and inferior antrostomy is recommended as the primary choice for dental implant retrieval from the maxillary sinus. A transoral approach should be performed simultaneously only for oro-antral fistula repair. This surgical protocol proved to be safe and efficient, and it obviated the need for osteotomies of the anterolateral maxillary wall.

[Tolerance of hypofractionated stereotactic radiotherapy for hepatic tumours]. / Tolérance de l'irradiation stéréotaxique hypofractionnée des tumeurs hépatiques.

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

[Extragenital endometriosis: Parietal, thoracic, diaphragmatic and nervous lesions. CNGOF-HAS Endometriosis Guidelines]. / Endométriose extra-génitale : atteinte pariétales, thoraciques, diaphragmatiques et nerveuses. RPC Endométriose CNGOF-HAS.

According to some studies, extragenital endometriosis represents 5% of the localisations. Its prevalence seems to be underestimated. The extra pelvic localisation can make the diagnosis more difficult. Nevertheless, the recurrent and catamenial symptomatology can evoke this pathology. Surgery seems to be the unique efficient treatment for parietal lesions. Pain linked to nervous lesions (peripheric and sacral roots) seems to be underestimated and difficult to diagnose because of various localisations. Neurolysis seems to have encouraging results. Diaphragmatic lesions are often discovered either incidentally during laparoscopy, or by pulmonary symptomatology as recurrent catamenial pneumothorax or cyclic thoracic pain. Surgical treatment seems as well to be efficient.

Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis.

Essentials The role of increased factor VIII in cirrhosis-induced hypercoagulability has never been demonstrated. Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin. Factor VIII elevation plays a significant role in cirrhosis-induced plasma hypercoagulability. Only protein C and factor VIII normalization led to thrombin generation similar to controls. SUMMARY: Background In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed. Objectives We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM. Methods Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child-Turcotte-Pugh [CTP]-A, n = 61; CTP-B, n = 19; and CTP-C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were normalized by adding an inhibitory anti-FVIII antibody and exogenous PC, respectively. Results The endogenous thrombin potential (ETP) in the presence of TM was higher in patients than in controls. After FVIII normalization, the ETP (median) decreased from 929 nm min to 621 nm min (CTP-A), 1122 nm min to 1082 nm min (CTP-B), and 1221 nm min to 1143 nm min (CTP-C); after PC normalization, it decreased from 776 nm min to 566 nm min (CTP-A), 1120 nm min to 790 nm min (CTP-B), and 995 nm min to 790 nm min (CTP-C). The ETP was reduced by 17% and 30%, respectively, but normal TG was not restored. When both FVIII and PC levels were normalized, the ETP decreased from 929 nm min to 340 nm min (CTP-A), 1122 nm min to 506 nm min (CTP-B), and 1226 nm min to 586 nm min (CTP-C), becoming similar to control levels. Conclusion Cirrhosis-induced plasma hypercoagulability, as demonstrated in these experimental conditions, can be partly explained by opposite changes in two factors: PC level (decrease) and FVIII level (increase).

Resistance characterization of ledipasvir and velpatasvir in hepatitis C virus genotype 4.

HCV genotype 4 (GT4) has often been overlooked in drug development, even though it infects ~20 million people worldwide. Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir were highly efficacious in GT4 HCV-infected patients from GS-US-337-1119 and GS-US-342-1138. Here, we characterize the resistance profile of ledipasvir (LDV) and velpatasvir (VEL) in patients with GT4 HCV infection. NS5A deep-sequencing was performed for 454 patients infected with HCV GT4 at baseline, including 44 patients enrolled in GS-US-337-1119 and 116 patients enrolled in GS-US-342-1138, and at relapse for patients with virologic failure. LDV and VEL susceptibilities of 56 patient isolates were determined. In GS-US-337-1119, SVR12 rates were 100% for all subtypes except 4b and 4r. Phenotypic assessment of 56 HCV NS5A patient isolates from various GT4 subtypes indicated that LDV had high potency for the common subtypes 4a/d, and subtypes 4c/f/k/l/m/n/o/p/r/t despite the presence of resistance-associated substitutions (RASs). For the rare GT4b, LDV median EC50 was higher, but with a broad range of individual values. Importantly, all GT4b isolates tested had 2-4 NS5A RASs, some including Y93H. Similarly, the 2 GT4r infected patients who had virologic relapse had rare triple RASs. Reversion of these substitutions to the consensus residue significantly increased LDV susceptibility. In GS-US-342-1138, all patients achieved SVR12, regardless of their subtype or presence of RASs. In vitro data confirmed that VEL is potent against all GT4 isolates tested. LDV and VEL are potent antiviral drugs, estimated to be effective against >95% and >99%, respectively, of GT4 HCV isolates.

Spatial distribution of FIR rotationally excited CH+ and OH emission lines in the Orion Bar PDR.

CONTEXT: The methylidyne cation (CH+) and hydroxyl (OH) are key molecules in the warm interstellar chemistry, but their formation and excitation mechanisms are not well understood. Their abundance and excitation are predicted to be enhanced by the presence of vibrationally excited H2 or hot gas (~500-1000 K) in photodissociation regions with high incident FUV radiation field. The excitation may also originate in dense gas (> 105 cm-3) followed by nonreactive collisions with H2, H, and electrons. Previous observations of the Orion Bar suggest that the rotationally excited CH+ and OH correlate with the excited CO, a tracer of dense and warm gas, and formation pumping contributes to CH+ excitation. AIMS: Our goal is to examine the spatial distribution of the rotationally excited CH+ and OH emission lines in the Orion Bar in order to establish their physical origin and main formation and excitation mechanisms. METHODS: We present spatially sampled maps of the CH+ J=3-2 transition at 119.8 µm and the OH Λ-doublet at 84 µm in the Orion Bar over an area of 110″×110″ with Herschel (PACS). We compare the spatial distribution of these molecules with those of their chemical precursors, C+, O and H2, and tracers of warm and dense gas (high-J CO). We assess the spatial variation of CH+ J=2-1 velocity-resolved line profile at 1669 GHz with Herschel HIFI spectrometer observations. RESULTS: The OH and especially CH+ lines correlate well with the high-J CO emission and delineate the warm and dense molecular region at the edge of the Bar. While notably similar, the differences in the CH+ and OH morphologies indicate that CH+ formation and excitation are strongly related to the observed vibrationally excited H2. This, together with the observed broad CH+ line widths, indicates that formation pumping contributes to the excitation of this reactive molecular ion. Interestingly, the peak of the rotationally excited OH 84 µm emission coincides with a bright young object, proplyd 244-440, which shows that OH can be an excellent tracer of UV-irradiated dense gas. CONCLUSIONS: The spatial distribution of CH+ and OH revealed in our maps is consistent with previous modeling studies. Both formation pumping and nonreactive collisions in a UV-irradiated dense gas are important CH+ J=3-2 excitation processes. The excitation of the OH Λ-doublet at 84 µm is mainly sensitive to the temperature and density.

Biliary stenting is not a prerequisite to endoscopic placement of duodenal covered self-expandable metal stents.

BACKGROUND: Duodenal covered self-expandable metal stent (cSEMS) can be used in malignant or benign gastroduodenal obstruction. The need for biliary stenting in patients with no concomitant biliary stricture, before duodenal cSEMS placement, remains unknown. The aim of this study was to determine whether cSEMS placement is responsible for biliary obstruction. METHODS: This is a single-center, retrospective, case-controlled study, including 106 patients with symptomatic gastric outlet obstruction or duodenal fistula who received a covered nitinol duodenal stent by using through-the-scope/over-the-wire placement procedure. The main outcome measurement was the occurrence comparison of jaundice and bilirubin level, between patients with previous or concomitant biliary stenting (cSEMS + BS group), and patients with no biliary stent (cSEMS group) during an observational period of 90 days. RESULTS: Hundred and six patients underwent cSEMS placement between June 2005 and March 2014: 53 in the cSEMS group (58% male, mean age 66.4 ± 13.3 years) and 53 in cSEMS + BS group (60% male, mean age 70.4 ± 11.6 years). The obstruction was due to cancer in 45% in cSEMS group and 87% in cSEMS + BS group. No case of jaundice was reported in the cSEMS group or in the cSEMS + BS group. In cSEMS group, the mean bilirubin level (µmol/L ± SD) was 8.0 ± 4 at baseline and 8.5 ± 4.6 at day 10, while in the cSEMS + BS group it was 91.4 ± 108 at baseline and 35.3 ± 39 at day 10 (p < 0.01). Patients from the two groups were matched on age, gender and bilirubin level at baseline. Evolution of bilirubinemia was +0.98 ± 2.76 µmol/L in experimental group and +0.39 ± 522 µmol/L in the control group (p = 0.34). No significant difference was observed between the two groups in term of technical success, clinical effectiveness, migration and other complications. CONCLUSIONS: Previous biliary stenting is not required before endoscopic covered duodenal stent placement in patients with no associated biliary obstruction. Prospective studies are needed.

Landscape and climatic characteristics associated with human alveolar echinococcosis in France, 1982 to 2007.

Human alveolar echinococcosis (AE) is a severe hepatic disease caused by Echinococcus multilocularis. In France, the definitive and intermediate hosts of E. multilocularis (foxes and rodents, respectively) have a broader geographical distribution than that of human AE. In this two-part study, we describe the link between AE incidence in France between 1982 and 2007 and climatic and landscape characteristics. National-level analysis demonstrated a dramatic increase in AE risk in areas with very cold winters and high annual rainfall levels. Notably, 52% (207/401) of cases resided in French communes (smallest French administrative level) with a mountain climate. The mountain climate communes displayed a 133-fold (95% CI: 95-191) increase in AE risk compared with communes in which the majority of the population resides. A case-control study performed in the most affected areas confirmed the link between AE risk and climatic factors. This arm of the study also revealed that populations residing in forest or pasture areas were at high risk of developing AE. We therefore hypothesised that snow-covered ground may facilitate predators to track their prey, thus increasing E. multilocularis biomass in foxes. Such climatic and landscape conditions could lead to an increased risk of developing AE among humans residing in nearby areas.

[Transvaginal hydrolaparoscopy for infertility investigation: a retrospective study, about 262 patients]. / Intérêt de la fertiloscopie dans la prise en charge de l'infertilité: étude rétrospective, à propos de 262 cas.

OBJECTIVES: To evaluate fertiloscopy's results and to redefine its place in the management of female infertility. PATIENTS AND METHODS: Retrospective study including 262 cases of fertiloscopy and 260 patients with primary or secondary idiopathic infertility. Analysis of infertility assessment's findings (hysterosalpingography), perioperative data (operating technique, laparoscopic conversion, failures and complications). Comparison of hysterosalpingography's findings and peroperative data; comparison of fertiloscopy and laparoscopy's findings. RESULTS: Access to peritoneal cavity was possible for 248 fertiloscopies (95%), and pelvic exploration was considered as complete for 226 cases (86%). Laparoscopic conversion was necessary in 54 cases (21%) and indicated by surgical pathology in more of one third of the cases (n=20). Our failure rate was only 5,3% (n=14), partially thanks to posterior colpotomie (70% of failures avoided). We deplored 8 complications (3.05%) which were not severe (no bowel injury), among which half were linked with the hysteroscopy (uterus perforation). In the cases of laparoscopic conversion, laparoscopic findings confirmed per-fertiloscopic data, considering adhesions and tubal patency. Hysterosalpingography had poor sensibility and positive predictive value. DISCUSSION AND CONCLUSION: Fertiloscopy is a safe, reproducible and not much invasive procedure. It can be substituted to laparoscopy in infertility assessment when there is no obvious surgical indication. Moreover, it could be considered as a first line way of investigation in female infertility management, instead of hysterosalpingography which has poor sensibility and positive predictive value.

A feature selection based framework for histology image classification using global and local heterogeneity quantification.

Biopsy remains the gold standard for the diagnosis of chronic liver diseases. However, the concordance between readers is subject to variability causing an increasing need of objective tissue description methods. A complete framework has been implemented to analyze histological images from any kind of tissue. Based on the feature selection approach, it computes the most relevant subset of descriptors in terms of classification from a wide initial list of local and global descriptors. In comparison with equivalent methods, this implementation is able to find lists of descriptors which are significantly shorter for an equivalent accuracy and furthermore it enables the classification of slides using combinations of global and local measurements. The results have pointed that it could reach an accuracy of 82.8% in a human liver fibrosis grading approach by selecting 6 descriptors from an initial set of 258 global and local descriptors.

Distribution of total DNA and cccDNA in serum and PBMCs may reflect the HBV immune status in HBsAg+ and HBsAg- patients coinfected or not with HIV or HCV.

BACKGROUND: The potential reservoir role of serum and peripheral blood mononuclear cells (PBMCs) for total HBV DNA (tDNA) and cccDNA still remains unknown. MATERIAL AND METHODS: We analyzed tDNA and cccDNA with a single sensitive and validated standardized real-time PCR method in serum and PBMCs in two populations of chronic HBV infection coinfected or not with HCV and/or HIV viruses: a retrospective cohort of 130 HBsAg-negative (HBsAg-) patients with "anti-HBc alone" or anti-HBc and anti-HBs antibodies (Ab) and a cohort of 70 HBsAg-positive patients, 16 of them being prospectively followed under treatment. RESULTS: Among HBsAg- patients, HBV DNA was detected in serum or PBMCs in about half of the cases with various distributions of tDNA and cccDNA: in HIV-negative patients with an "antiHBc alone" profile, tDNA was mostly detected in PBMCs suggesting a possible active role of PBMCs; although cccDNA was not detected in PBMCs in HIV-positive patients, tDNA and cccDNA were mostly observed in serum, suggesting a specific pattern of more "persistent" than "occult" infection in this population. Patients with anti-HBc and anti-HBs Ab harbored tDNA in serum or in PBMCs, regardless of their HIV or HCV status, raising the question of a viral reactivation risk during immunosupression in these patients. Among HBsAg+ patients, tDNA was detected in serum and PBMCs of 88.5% of the cases and cccDNA in 22%. Levels of tDNA in both compartments were highly correlated during treatment, suggesting a passive reservoir role for PBMCs. CONCLUSION: The respective distribution of tDNA and cccDNA in serum and PBMCs may reflect the different immune statuses of the host in HBsAg+ and HBsAg- patients. The frequency of HBV DNA in PBMCs from AgHBs- patients suggests a viral reactivation risk during immunodepression in those patients.

Hypersplenism due to portal hypertension: retrospective evaluation of 17 patients treated by splenic embolization.

PURPOSE: The objective of this retrospective study was to analyze the efficacy and morbidity associated with splenic artery embolization for hypersplenism due to portal hypertension (PHT), as a function of the volume of the splenic parenchyma embolized and the type of PHT (due to intrahepatic block or segmental PHT). PATIENTS AND METHODS: This study retrospectively included 17 patients with hypersplenism secondary to PHT (intrahepatic block, n=14; segmental, n=3) treated by splenic artery embolization. The splenic volume embolized was estimated by computed tomography (CT) one month after embolization. A clinical assessment and platelet count took place at 7 days, 1 month and 6 months after the embolization. RESULTS: In the group with PHT due to intrahepatic block, the mean volume of embolized splenic parenchyma was 63% of the initial volume (range: 30-95%). Six months later, the platelet level had increased by an average of 232%. All patients with fewer than 80,000 platelets/mL at 6 months had an embolization volume less than 50%. In the segmental PHT group, the mean volume of the embolized parenchyma was 62% of the initial volume (range: 20-95%), bleeding symptoms had disappeared in all patients, and the platelet level exceeded 80,000/mL. Six patients (6/17, 35%) had complications, two minor and four major: two splenic abscesses, one respiratory distress with ascites, and one pancreatitis with ascites. Five of the six complications were observed in patients with a volume of embolized splenic parenchyma more than 70%. CONCLUSION: Our results show that splenic embolization of more than 50% of the parenchyma is effective in the treatment of hypersplenism due to PHT, but that when the embolized volume exceeds 70%, the procedure is associated with considerable morbidity.

[The role of infection in preterm birth]. / Prématurité et infection : état des connaissances.

Intrauterine infection could be responsible for 25% up to 40% of preterm births. This relationship was initially demonstrated using animal models, inducing their abortion by injecting bacteria or endotoxins. In human research, examination of amniocentesis fluid showed the anteriority of infection over labor induction, and the existence of a subclinical latency phase between these two phenomena. The ascending route is preponderant, and four stages can be distinguished: cervical and vaginal infection, chorio-decidual infection, intra-amniotic infection, fetal infection. The intrauterine infection is very frequent in case of early preterm birth (<30 WG). It is associated with an increase of neurological and pulmonary morbidity. Most commonly found bacterial species are mycoplasma species, but also Escherichia coli, Gardnerella vaginalis and streptococcus B. Several markers of the infection have been studied: a maternal leukocytosis>15,000/mm(3) or a C-Reactive Protein (CRP)>20mg/l, an increase of fibronectin and/or IL-6 cervical, a short cervical length especially before 32 WG, a leukocytosis of the amniotic fluid, and/or high interleukin concentrations. The main marker used for the newborn is the CRP, but other markers can also be used for an early diagnosis of an infection, especially interleukin 6.