Fasciola gigantica: Ultrastructural localisation of neoblast recruitment in somatic tissues during growth and development in the hepatic parenchyma of experimentally infected mice.

Application of 'omics' technology, and advances in in vitro methods for studying the growth of Fasciola hepatica, have highlighted the central role of migrating neoblasts in driving forward development and differentiation towards the adult-like form. Neoblast populations present molecular heterogeneity, morphological variation and changes associated with recruitment of these stem cells into their final tissue locations. However, terminal differentiation towards function, has received much less attention than has been the case for the free-living Platyhelminths. An actively replicating neoblast population, comprising cells with heterochromatic nuclei consistent with regulation of gene expression, has been identified in the parenchyma of juvenile Fasciola gigantica migrating in the liver of experimentally infected mice. In some of these cells, early cytoplasmic differentiation towards myocyte function was noted. Neoblasts have also been identified close to, and incorporated in, the subtegumental zone, the gastrodermis and the excretory ducts. In these locations, progressive morphological differentiation towards terminal function has been described. This includes the appearance of specific progenitors of type-1, type-2 and type-3 tegumental cells, the latter possibly contributing to tegumental spine development. 'Cryptic' surface molecular differentiation is postulated to account for recognition and 'docking' of migrating neoblasts with their final site for terminal differentiation.

Treatment of moderate-to-severe psoriasis in adults: An expert consensus statement using a Delphi method to produce a decision-making algorithm.

BACKGROUND: New highly effective drugs for moderate-to-severe cutaneous psoriasis are regularly marketed, and the hierarchy of treatments thus requires frequent review. OBJECTIVES: A Delphi method was used to enable a structured expert consensus on the use of systemic treatments and phototherapy among adults with moderate-to-severe psoriasis. METHODS: The Delphi method consists in achieving a convergence of opinions among a panel of experts using several rounds of questionnaires with controlled feedback between rounds. A two-part Delphi questionnaire was administered online to French psoriasis experts. In the first part, 180 items related to the prescription of systemic treatments and phototherapy for adult patients with moderate-to-severe psoriasis were grouped into 21 sections covering different lines of treatment and different forms of cutaneous psoriasis. The experts voted on each proposal using an ordinal 7-point Likert scale. The second part comprised 11 open-ended questions about special indications for each therapeutic class. These were converted into 101 questions for subsequent rounds. Consensus was deemed to have been reached if more than 80% of the experts agreed with a given proposal. RESULTS: Three rounds of questionnaires were sequentially sent to 35 participants between November 2021 and March 2022. Thirty-three (94%) completed all three rounds. For plaque psoriasis, only methotrexate was recommended by the experts as first-line systemic treatment (89% of votes). Cyclosporin was advocated in pustular and erythrodermic psoriasis, and acitretin was suggested for hyperkeratotic and palmoplantar psoriasis. In the event of failure of or intolerance to non-biological systemic treatments, guselkumab, risankizumab, ixekizumab or secukinumab were recommended by more than 80% of the experts. Tumor Necrosis Factor (TNF) inhibitors remain useful for patients with cardiovascular risk factors. Special indications were provided for each therapeutic class (methotrexate/narrowband ultraviolet B phototherapy, psoralen/ultraviolet A phototherapy, cyclosporin, acitretin, apremilast, TNF inhibitors, interleukin (IL)-12/23 inhibitors, IL-17(R)A inhibitors, and IL-23 inhibitors). CONCLUSIONS: This expert consensus statement indicate that newly available IL-17 and IL-23 inhibitors may be favored over TNF and IL-12/23 inhibitors as first-line biologics. The Centre of Evidence of the French Society of Dermatology has drawn up a decision-making algorithm to guide clinicians in the therapeutic management of moderate-to-severe psoriasis.

[Effet blouse blanche résiduel : un outil pertinent en soins premiers?] / Office white-coat effect tail: A useful tool in family practice?

BACKGROUND: White coat effect (WCE) and white coat hypertension (WCH) are hardly both compared in primary care. OBJECTIVE: To assess the usefulness of repeated measures of systolic blood pressure (SBP) to dissociate various forms of white-coat interactions. METHODS: An open cross-sectional study on consecutive patients treated or not for high blood pressure was made in family physicians' offices. SBP was measured 5 times by an electronic device. Measurements were performed before (SBP1) and after (SBP5) the office visit by a lay assistant and at the beginning (SBP2), middle (SBP3) and end (SBP4) of visit, by the family physician. Home BP (HBPM) was measured from 3 consecutive days by the patient. WCE and office WCE tail (OWCET) were defined, respectively, as a 10 mmHg SBP increase or decrease between SBP2-SBP1 or SBP4-SBP2. WCH was considered when HBPM was normal (SBP < 135 mmHg) at home and high during the SBP2 office visit. RESULTS: Two hundred five patients (134 women versus 71 men, ratio 1.9, aged 59.8±15.7 years) were recruited. In categorical terms, there were 51 patients (25%) who presented with WCE, OWCET was seen in 121 patients (62%) and 47 patients (23%) had WCH. Only 36 patients (18%) presented both OWCET and WCE and 32 (16%) had both OWCET and WCH. The receiver operating characteristic curves (ROCs) of OWCET in diagnosing WCE or WCH were respectively 0.67 (p<0.0001) and 0.53 (NS). CONCLUSION: Thus, OWCET was predictive of WCE and not of WCH and it is worthwhile to be measured in the family physician office.

Stochastic modelling of pesticide transport to drinking water sources via runoff and resulting human health risk assessment.

A modelling framework was developed to facilitate a probabilistic assessment of health risks posed by pesticide exposure via drinking water due to runoff, with the inclusion of influential site conditions and in-stream processes. A Monte-Carlo based approach was utilised to account for the inherent variability in pesticide and population properties, as well as site and climatic conditions. The framework presented in this study was developed with an ability to integrate different data sources and adapt the model for various scenarios and locations to meet the users' needs. The results from this model can be used by farm advisors and catchment managers to identify lower risk pesticides for use for given soil and site conditions and implement risk mitigation measures to protect water resources. Pesticide concentrations in surface water, and their risk of regulatory threshold exceedances, were simulated for fifteen pesticides in an Irish case study. The predicted concentrations in surface water were then used to quantify the level of health risk posed to Irish adults and children. The analysis indicated that herbicides triclopyr and MCPA occur in the greatest concentrations in surface water, while mecoprop was associated with the highest potential for health risks. The study found that the modelled pesticides posed little risk to human health under current application patterns and climatic conditions in Ireland using international acceptable intake values. A sensitivity study conducted examined the impact seasonal conditions, timing of application, and instream processes, have on the transport of pesticides to drinking water.

Impact of adjuvant radiotherapy and chemotherapy on thymoma.

PURPOSE: Thymoma is a rare tumour. The most common treatment for thymoma is surgical resection, while the use of radiotherapy and chemotherapy remains controversial. PATIENTS AND METHODS: We conducted a monocentric observational study of 31 patients diagnosed with thymoma from June 2004 to July 2020 at cancer centre in Strasbourg, France. We analysed the outcomes of the patients. RESULTS: The 2- and 5- year locoregional relapse-free survival rates were 96.3% (95% confidence interval [CI]: 76.5-99.5%) and 68.0% (95% CI: 43.8-83.5%), respectively. Radiotherapy and chemotherapy significantly improved local tumour control (P=0.0008 and 0.04, respectively), while a larger initial tumour size significantly worsened local control rates (P=0.04). The 5- and 10-year overall survival rates were 87.1% (95% CI: 69.2-95%) and 81.7% (95% CI: 60.3-92.2%), respectively. The median overall survival was not reached, and no favourable factor was retrieved. For relapsed patients, the median overall survival after relapse was 115 months. CONCLUSION: Despite the inherent limitations of retrospective studies with a limited patient sample size, we demonstrated that chemotherapy and radiotherapy in addition to surgery were effective in achieving local control and contributed to improving patient outcomes in thymoma. Notably, an aggressive treatment strategy at the time of relapse resulted in favourable outcomes for retreated patients.

[Splanchnic vein thrombosis]. / Thromboses veineuses splanchniques.

Splanchnic vein thrombosis includes Budd-Chiari syndrome and portal vein thrombosis. These diseases share common features: (i) they are rare diseases and (ii) they can lead to portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, the most common being myeloproliferative neoplasms. A rapid and comprehensive workup for thrombosis risk factors is necessary in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis, and is associated with a worse course of cirrhosis. Indications for anticoagulation in patients with cirrhosis are increasing. Transjugular intrahepatic portosystemic shunt is a second-line procedure in this setting. Because of the rarity of these diseases, high-level evidence studies are rare. However, collaborative studies have provided a better understanding of their natural history and allowed to improve the management of these patients. This review focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, patients with portal vein thrombosis without underlying liver disease, and patients with cirrhosis and portal vein thrombosis.

[Preoperative chemotherapy for patients with upper tract urothelial carcinoma: Impact on renal function]. / Chimiothérapie préopératoire des tumeurs des voies excrétrices supérieures : impact sur la fonction rénale.

PURPOSE: Upper tract urothelial carcinoma (UTUC) are rare tumors with a poor prognosis. The standard treatment for localized disease is based on total nephroureterectomy (NUT) followed by platinum-based adjuvant chemotherapy for eligible patients at risk of recurrence. However, many patients have renal failure after surgery preventing chemotherapy. Thus, the place of preoperative chemotherapy (POC) is questioned with little information available about renal toxicity and efficacity. METHODS: A single center retrospective study was performed on patients with UTUC who received POC. RESULTS: In all, 24 patients with localized UTUC were treated with POC between 2013 and 2022. Twenty-one (91%) had secondarily NUT. In this cohort, POC did not result in degradation of median renal function (pre-POC median GFR: 70mL/min, post-POC median GFR: 77mL/min, P=0.79), unlike NUT (post-NUT median GFR: 51.5mL/min, P<0.001). In addition, the rate of complete pathological response to pathological examination was 29%. After a median follow-up of 27.4 months, the overall survival rate was 74% and the recurrence-free survival rate was 46%. CONCLUSION: POC for UTUC shows a very reassuring renal toxicity profile and encouraging histological results. These data encourage prospective studies assessing its place for UTUC management.

Gender survival differences in hepatocellular carcinoma: Is it all due to adherence to surveillance? A study of 1716 patients over three decades.

Background and Aims: Hepatocellular carcinoma (HCC) is one of the commonest causes of cancer-related death worldwide. Whether gender is an independent factor for HCC survival is debatable. We studied the influence of gender on the clinical characteristics of HCC and on survival. Methods: The study cohort comprised patients with HCC seen in our department from 1988 to 2021. Clinical data were prospectively collected. We studied and compared demography, HCC characteristics, and survival between females and males. Survival analysis was censored on October 31, 2015. Results: There were 1716 HCC patients. 343 (20.0%) were females. Females were significantly older at diagnosis (median 69 vs 62 years, P < 0.001). More females were diagnosed via regular HCC surveillance (37.9% vs 29.6%, P = 0.003). Hence, as expected, females had less-advanced HCC at diagnosis with smaller median tumor diameter (30 vs 39.5 mm, P = 0.038), lower frequency of portal vein tumor thrombus (19.4% vs 33.4%, P < 0.001), less distant metastases (7.7% vs 11%, P = 0.043), and earlier Barcelona Clinic Liver Cancer (BCLC) stages (0/A, 39.7% vs 28.4%, P < 0.001). On multivariable analysis, HCC diagnosis via surveillance but not female gender was an independent predictor of improved HCC survival. Conclusions: In this large cohort of multi-ethnic Asian patients, females with HCC were significantly more adherent to surveillance and hence presented with less advanced HCC with correspondingly better overall survival than males. The gender difference in survival is likely due to females having better adherence to HCC surveillance. Surveillance to diagnose early-stage HCC remains crucial in improving outcomes.

Impact of historical legacy pesticides on achieving legislative goals in Europe.

Pesticides are widely used in agriculture to optimise food production. However, the movement of pesticides into water bodies negatively impacts aquatic environments. The European Union (EU) aims to make food systems fair, healthy and environmentally friendly through its current Farm to Fork strategy. As part of this strategy, the EU plans to reduce the overall use and risk of chemical pesticides by 50 % by 2030. The attainment of this target may be compromised by the prevalence of legacy pesticides arising from historical applications to land, which can persist in the environment for several decades. The current EU Farm to Fork policy overlooks the potential challenges of legacy pesticides and requirements for their remediation. In this review, the current knowledge regarding pesticide use in Europe, as well as pathways of pesticide movement to waterways, are investigated. The issues of legacy pesticides, including exceedances, are examined, and existing and emerging methods of pesticide remediation, particularly of legacy pesticides, are discussed. The fact that some legacy pesticides can be detected in water samples, more than twenty-five years after they were prohibited, highlights the need for improved EU strategies and policies aimed at targeting legacy pesticides in order to meet future targets.

[KINE PREOP pilot study: Prehabilitation in fast-track thoracic surgery protocol]. / KINE PREOP : réhabilitation préopératoire libérale et chirurgie thoracique pulmonaire.

INTRODUCTION: Prehabilitation preceding oncological thoracic surgery according to a fast-track enhanced recovery after surgery (ERAS) protocol is in full expansion. Many recent studies have demonstrated the benefits of preoperative pulmonary rehabilitation as a means of reducing postoperative pulmonary complications. Unfortunately, it is rarely carried out by independent physiotherapists, and questions arise: is it feasible in private practice? Can it yield results similar to those achieved in institutional settings? DESIGN: The study was non-interventional. The patients included had to be able to practice physical activities according to a standard ERAS approach. The endpoints were: postoperative pulmonary complications, physical condition (VO2max), and impact on the quality of life (SF-36 questionnaire). A statistical study was conducted to analyze the results with parametric and non-parametric tests. RESULTS: Between June 2018 and January 2019, nine patients were included. From two to fifteen pulmonary rehabilitation sessions were carried out by six volunteering independent physiotherapists. Only two minor postoperative complications ensued. VO2max post rehabilitation increased on average by 2.4mL.kg -1.min-1. The SF-36 physical score increased significantly (+17.9%). The physical functioning (PF) (+28.9), physical restrictions (PR) (+11.1) and vitality (VT) (+16.7) sub-scores likewise improved. CONCLUSION: Based on a literature review and on comparisons, our results seem promising. While further investigations are needed, it would seem that prehabilitation by independent physiotherapists leads to results similar to those achieved in inpatient prehabilitation.

[Pathological pelvic lymph node involvement in muscle-invasive bladder cancer patients treated with radical cystectomy: A narrative review]. / Envahissement ganglionnaire pelvien anatomopathologique après cystectomie totale pour le traitement des tumeurs de vessie infiltrant le muscle : une revue narrative de la littérature.

OBJECTIVE: To perform a narrative review of the contemporary literature on the diagnosis, prognosis and adjuvant management of muscle-invasive bladder cancer (MIBC) patients with pathological pelvic lymph node involvement (pN+) at radical cystectomy. METHOD: A narrative review of the contemporary literature available on Medline was conducted to report studies evaluating the diagnosis, prognosis and/or adjuvant treatments for MIBC patients with pN+ disease at radical cystectomy. RESULTS: Open or robotic extended pelvic lymph node dissection up to the crossing of the ureter with common iliac vessels can enhance the diagnosis of pN+ MIBC, especially using separate packages for the submission of a maximum number of lymph nodes. The main prognosis factors for pN+ patients are the number of positive and retrieved lymph nodes, lymph node density, extranodal extension as well as lymph node metastasis diameter. Adjuvant chemotherapy is likely to prolong overall survival in pN+ patients treated with radical cystectomy alone while adjuvant immunotherapy using nivolumab has been shown to decrease the risk of recurrence in all pN+ patients, especially those with ypN+ disease after neoadjuvant chemotherapy followed by radical cystectomy. However, few data are currently available on the role of adjuvant radiation therapy, which remains currently experimental for these patients. CONCLUSION: Multiple parameters have been reported to impact the diagnosis and prognosis of patients with pN+ MIBC at radical cystectomy. Adjuvant management is currently based on chemotherapy and immunotherapy with preliminary data on radiation therapy.

Microvascular density and tumor budding in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant head and neck tumor, excluding the nonmelanoma skin cancer. Despite recent advances in the diagnosis and treatment, the disease's mortality rate is nonetheless high. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, named tumor budding, is associated with a worse prognosis in OSCC. Angiogenesis has also been recognized as a determining factor in the progression of malignancies and in the development of metastases. Several studies have investigated the assessment of microvascular density (MVD) as a potential prognostic factor in OSCC. This study aimed to evaluate, in OSCC, differences in MVD between tumors with high-intensity tumor budding and tumors with low-intensity or no tumor budding. In samples with high-intensity tumor budding, differences in MVD between the budding area and the area outside the budding were also evaluated. Moreover, the study assessed differences in MVD concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size. MATERIAL AND METHODS: One hundred and fifty [150] samples of OSCC were subjected to immunohistochemistry to assess the intensity of tumor budding (by immunostaining for multi-cytokeratin) and MVD (by immunostaining for CD34 and CD105, independently). The data were treated using descriptive and analytical statistics. RESULTS: There were no differences in MVD, assessed by immunostaining for CD34 or CD105, concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size (p > 0.05). Tumors with high-intensity tumor budding did not show differences in MVD, assessed by immunostaining for CD34 or CD105, when compared to tumors with low-intensity or no tumor budding (p > 0.05). However, in samples with high-intensity tumor budding, the MVD assessed by immunostaining for CD34 was higher in the budding area than in the area outside the budding (p < 0.05). This difference was not observed when MVD was assessed by immunostaining for CD105 (p > 0.05). CONCLUSIONS: The higher MVD in the budding area may be an additional indication that this is a peculiar region of the tumor, associated with biological phenomena related to tumor progression.

Batch adsorption of herbicides from aqueous solution onto diverse reusable materials and granulated activated carbon.

This study reports the kinetics and isotherms of the adsorption of five herbicides, MCPA, mecoprop-P, 2,4-D, fluroxypyr and triclopyr, from aqueous solutions onto a range of raw and pyrolysed waste materials originating from an industrial setting. The raw waste materials investigated demonstrated little capability for any herbicide adsorption. Granulated activated carbon (GAC) was capable of the best removal of the herbicides, with >95% removal observed. A first order kinetic model fitted the data best for GAC adsorption of 2,4-D, while a pseudo-first order model fitted the data best for GAC adsorption of fluroxypyr and triclopyr, indicating that adsorption was via physisorption. A pseudo-second order kinetic model fitted the GAC adsorption of MCPA and mecoprop-P, which is indicative of chemisorption. The adsorption of the herbicides in all cases was best described by the Freundlich model, indicating that adsorption occurred onto heterogeneous surfaces.

[Virological diagnosis of anterior herpetic ocular disease on tear sample: A simple and non-invasive technique]. / Diagnostic virologique des atteintes oculaires herpétiques antérieures sur prélèvement lacrymal : une technique simple et non invasive.

INTRODUCTION: Virological diagnosis of anterior ocular herpetic disease (AOHD) is essential for the management of these often-chronic pathologies that may require long-term therapy. PCR has become the gold standard, but the type of sampling (tears, corneal scraping, aqueous tap) has not been standardized. In this study, we studied the technique of tear sampling for the diagnosis of AOHD. MATERIALS AND METHOD: We retrospectively analyzed the medical files of patients with a positive tear sample (Schirmer strip) for herpes simplex 1 virus (HSV-1) in the Department of Ophthalmology of Paris-Saclay Bicêtre Hospital between January 2018 and December 2020. We studied the clinical and virological characteristics (viral loads) of these cases of proven AOHD. RESULTS: Thirty-six samples (33 patients) were included: 12 epithelial keratitis, 9 stromal HSK with ulceration, 5 uveitis, 4 stromal HSK without ulceration, 3 blepharitis, 1 endothelial HSK, 1 neurotrophic keratitis, and 1 conjunctivitis. The mean viral load was 3.9×105 copies/mL. Viral load was higher in cases of corneal ulceration (5.2×105±9.4×105 versus 1.2×102±1.7×102 copies/mL, P<1×10-4). There was no significant difference between primary episodes and relapses. CONCLUSION: Tear sampling using Schirmer strips is a simple, non-invasive method that can be useful for the virological diagnosis of various clinical forms of AOHD.

Assessing the gender gap in musculoskeletal radiology authorship across three continents: are really the "ladies first"?

AIM: To assess gender-specific authorship trends in musculoskeletal (MSK) radiology in three major radiology journals, Skeletal Radiology (SR), Clinical Radiology (CR) and Indian Journal of Radiology and Imaging (IJRI). MATERIALS AND METHODS: Retrospective analysis of articles pertaining to MSK radiology was done for the years 2000, 2010, and 2020 for SR and CR and for the years 2010 and 2020 for IJRI. The number and positions of female authors was noted. RESULTS: Three hundred and twenty-five articles were reviewed after excluding the articles where the gender of one or more authors could not be conclusively determined. In SR, the percentage of female authors increased significantly from 4% in 2000 to 17% in 2010 (p<0.0001) and to 21.9% in 2020 (p<0.0001) with an increase in the percentage of first female authors from 0.8% in 2000 to 4.9% in 2010 and further to 5.4% in 2020. In CR, the percentage of female authors reduced from 13.8% in 2000 to 13.6% in 2010 (p=0.9798 and further reduced to 7% in 2020 (p=0.1592). In IJRI, the percentage of articles with no female authors went down from 36.4% (2010) to 26.7% (2020). CONCLUSION: There is an upward trend in female authorship in MSK radiology related articles in SR and IJRI with continued under-representation in CR. The first and middle order female authors have shown a significant increase, although the number of last female authors remains very low. Analysis of such trends in academic journals from other subspecialities in medicine needs to be undertaken to confirm or refute the findings of this study.

Management of gastro-intestinal emergencies in patients with ileal conduit ureteral diversion.

Radical cystectomy with urinary deviation is performed increasingly in France. Ileal conduit ureteral diversion (ICUD), described by Bricker and widely used after this type of radical resection, leads to substantial anatomic modifications that are potential danger zones during subsequent gastro-intestinal or urinary tract operations. Injury to the urinary diversion apparatus can lead to disastrous complications in these patients who are often elderly and frail. General surgeons are most often called upon to re-operate these patients, either for an ICUD-related gastro-intestinal complication, or for an unrelated abdominal emergency that arises later (bowel obstruction, infection, cancer). During such operations, certain anatomic structures are particularly exposed to injury that may be irreversible, particularly, the mesentery of the ileal conduit and the left ureter. Approaching the right lower quadrant, the dissection of the ileo-ileal anastomosis or of the left mesocolon are the procedures or maneuvers that pose the most risk. A number of simple but effective preventive measures are available and must be known, such as to operate the patient with an urologist or to insert ureteral stents before surgery. Preoperative contrast-enhanced computed tomography with late phase urinary imaging is essential to assess the anatomic modifications and anticipate the operative procedural steps. Finally, one should not hesitate to disinsert the stoma and proceed with retrograde dissection, thus facilitating the identification of the ileal conduit, the mesentery and the ureters.

A risk ranking of pesticides in Irish drinking water considering chronic health effects.

This paper presents a novel scoring system which facilitates a relative ranking of pesticide risk to human health arising from contaminated drinking water. This method was developed to identify risky pesticides to better inform monitoring programmes and risk assessments. Potential risk was assessed considering pesticide use, chronic human health effects and environmental fate. Site-specific soil conditions, such as soil erodibility, hydrologic group, soil depth, clay, sand, silt, and organic carbon content of soil, were incorporated to demonstrate how pesticide fate can be influenced by the areas in which they are used. The indices of quantity of use, consequence and likelihood of exposure, hazard score and quantity-weighted hazard score were used to describe the level of concern that should be attributed to a pesticide. Metabolite toxicity and persistence were also considered in a separate scoring to highlight the contribution metabolites make to overall pesticide risk. This study presents two sets of results for 63 pesticides in an Irish case study, (1) risk scores calculated for the parent compounds only and (2) a combined pesticide-metabolite risk score. In both cases the results are assessed for two locations with differing soil and hydrological properties. The method developed in this paper can be adapted by pesticide users to assess and compare pesticide risk at site level using pesticide hazard scores. Farm advisors, water quality monitors, and catchment managers can apply this method to screen pesticides for human health risk at a regional or national level.