To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244.
The prospective, national, ...cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012–11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy FACT), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%.
In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms.
LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.
•This prospective cooperative group study demonstrated LLE symptoms were associated with poorer outcomes on PRO/QOL measures•Women with LLE symptoms reported lower health-related QOL, higher cancer distress (IES), and negative impact on daily life•Prospective trial to collect and follow sexual partner/activity status in newly diagnosed gynecologic cancer patients
Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains ...unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 µg/L), AOA2 (15-65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.
Background and purpose
Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of ...the cytokines interleukin (IL) 6 and IL‐10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients.
Methods
A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations.
Results
Forty‐three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL‐6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL‐6 level was higher in patients with active neurosarcoidosis than in non‐active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL‐6 concentration >50 pg/ml was associated with a higher risk of relapse or progression‐free survival (hazard ratio 3.60; 95% confidence interval 1.78–23.14). A refractory neurosarcoidosis patient was treated with an anti‐IL‐6 monoclonal antibody that produced a complete neurological response.
Conclusions
The CSF CD4/CD8 ratio and IL‐6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL‐6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL‐10 levels may be elevated in neurosarcoidosis.
Background and purpose: To prospectively investigate causes of death and the circumstances surrounding death in 302 patients with amyotrophic lateral sclerosis (ALS). The functional status of ...patients immediately before death was also determined.
Methods: Information was obtained from neurologists at ALS centres, patients’ files, and, when deaths occurred outside a medical facility, attending physicians.
Results: Most patients (63%) died in a medical facility. The most frequently reported cause of death was respiratory failure (77%), including terminal respiratory insufficiency (58%), pneumonia (14%), asphyxia due to a foreign body (3%) and pulmonary embolism (2%). Ten per cent of patients died from other causes: post‐surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%). The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside). At the time of death, only 55% of patients were receiving riluzole, 33% were undergoing non‐invasive ventilation, 3% had a tracheotomy and 37% a gastrostomy.
Conclusion: The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life.
Correlation between morphotypes and prognosis of canine lymphomas presented discordant results in literature, leading to some dilemma for application in clinical practice. The aim of this study was ...to present a systematic review of literature on the prognostic significance of morphotypes in canine lymphomas. Standardized Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) criteria were applied. Retrospective and prospective studies were included. Level of evidence was determined for each study. Some acceptable evidence suggested a significant prognostic impact of morphotypes in canine lymphomas. However, the evidence is not sufficiently robust to determine with precision the most appropriate classification scheme. Updated Kiel and World Health Organization (WHO) classifications seem to remain the most appropriate classification systems with regards to the number of available studies and their levels of evidence. Limitations included lack of randomized control trial, and relative lack of prospective studies available. Current recommended classification of canine lymphoma is the systematic determination of morphotype in each new case. The Updated Kiel and the WHO classifications adapted to dog both remain the schemes with the most valuable interest. Prospective studies in larger population, and international consensus to define precisely each morphotype, are warranted, with application of standardized staging method and treatment.
Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last ...three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.
Essentials
Pregnancy is a risk factor for thrombosis.
Management of thrombosis risk in pregnancy remains a challenge.
Prophylaxis needs to be personalized.
Our score may be a helpful tool for the ...management of pregnancies at high risk of thrombosis.
Summary
Background
Patients with thrombophilia and/or a history of venous thromboembolism (VTE) are at risk of thrombosis during pregnancy. A risk score for pregnancies with an increased risk of VTE was previously described by our group (Lyon VTE score).
Objectives
The aim of this prospective study was to assess the efficacy and safety of our score‐based prophylaxis strategy in 542 pregnancies managed between 2005 and 2015 in Lyon University Hospitals.
Patients/Methods
Of 445 patients included in the study, 36 had several pregnancies during the study period. Among these 445 patients, 279 had a personal history of VTE (62.7%), 299 patients (67.2%) had a thrombophilia marker, and 131 (29.4%) thrombophilic women had a personal history of VTE. During pregnancy, patients were assigned to one of three prophylaxis strategies according to the risk scoring system.
Results
In the antepartum period, low molecular weight heparin (LMWH) prophylaxis was prescribed to 64.5% of patients at high risk of VTE. Among them, 34.4% were treated in the third trimester only, and 30.1% were treated throughout pregnancy. During the postpartum period, all patients received LMWH for at least 6 weeks. Two antepartum‐related VTEs (0.37%; one with a score of < 3 and the other with a score of > 6) and four postpartum‐related VTEs (0.73%; three with scores of 3–5 and one with a score of > 6) occurred. No case of pulmonary embolism was observed during the study period. The rate of bleeding was 0.37%. No serious bleeding requiring transfusions or surgery occurred during the study period.
Conclusion
The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.
This study reports cytomorphological, histomorphological, and immunological characterization of 608 biopsy cases of canine malignant lymphoma, with epidemiological and clinical data, collected from 7 ...French veterinary pathology laboratories. It compares morphological characteristics of malignant lymphoma in canines, per the updated Kiel classification system, with those reported in humans, per the World Health Organization (WHO) classification system. Of tumors described, 24.5% and 75.5% were classified as low- and high-grade malignant lymphomas, respectively. Presenting clinical signs included generalized or localized lymphadenopathy (82.4%) and extranodal diseases (17.6%) involving the skin (12.34%) and other sites (5.26%). Immunohistochemistry confirmed 63.8% B-cell (CD3–, CD79a+), 35.4% T-cell (CD3+, CD79a–), and 0.8% null-cell (CD3–, CD79a–) lymphomas. Most B-cell cases (38.49%) were of high-grade centroblastic polymorphic subtype; most T-cell cases (8.55%), high-grade pleomorphic mixed and large T-cell lymphoma subtypes. Some B-cell tumors showed morphologic characteristics consistent with follicular lymphomas and marginal zone lymphomas per the Revised European American Classification of Lymphoid Neoplasms and WHO canine classification systems and the WHO human classification system. Unusual high-grade B-cell subtypes included an atypical high-grade small B-cell lymphoma (0.66%), Burkitt-type B-cell lymphoma (1.64%), plasmacytoid lymphoma (0.99%), and mediastinal anaplastic large B-cell lymphoma (0.16%). Unusual T-cell subtypes included a previously undescribed high-grade canine immunoblastic T-cell type (1.15%), a rare low-grade prolymphocytic T-cell lymphoma (0.16%), and a recently described high-grade canine T-cell entity—aggressive granulocytic large-cell lymphoma (0.16%). Marginal zone lymphomas were common (10.86%); follicular lymphomas were rare (0.49%). Canine primary cutaneous malignant lymphoma subtypes were present (11.84%). There was no significant difference between B- and T-cell malignant lymphoma in regard to canine age and sex. A significant overrepresentation of Boxers (24.19%) was found for T-cell lymphomas.
The existence of short-chain domains in heterogeneous bimodal PDMS networks has been confirmed visually, for the first time, through confocal fluorescence microscopy. The networks were prepared using ...a controlled reaction scheme where short PDMS chains were reacted below the gelation point into hyperbranched structures using a fluorescent silicone compatible cross-linker. The formation of the hyperbranched structures was confirmed by FTIR, super(1)H-NMR and size exclusion chromatography (SEC). The short-chain hyperbranched structures were thereafter mixed with long-chain hyperbranched structures to form bimodal networks with short-chain domains within a long-chain network. The average sizes of the short-chain domains were found to vary from 2.1 to 5.7 mu m depending on the short-chain content. The visualised network structure could be correlated thereafter to the elastic properties, which were determined by rheology. All heterogeneous bimodal networks displayed significantly lower moduli than mono-modal PDMS elastomers prepared from the long polymer chains. Low-loss moduli as well as low-sol fractions indicate that low-elastic moduli can be obtained without compromising the network's structure.
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