Vestibulodynia: Clinical characteristics, first-line treatments, and factors associated with escalation of treatment with EMG-guided injections of botulinum toxin in a retrospective french cohort study.

BACKGROUND: Vestibulodynia is a highly prevalent chronic pain disorder affecting the vulva having a major impact on women's physical, psychological, and sexual well-being. It remains an underrecognized disease that responds insufficiently to therapies such as physiotherapy and medication. AIM: To assess the global efficacy of first-line therapies and factors associated with treatment escalation in women with vestibulodynia. PATIENTS AND METHODS: This retrospective cohort study was conducted at the dermatology outpatient clinic of the University Hospital in Besancon (France) between 2013 and 2017 and follow-up until 2021. RESULTS: Among 132 patients, the mean [standard deviation] age at diagnosis was 27.2 [±9.45] years, with an average duration of symptoms of 42.3 [±37.92] months. Most cases comprised provoked (75.0%) or secondary (72.7%) vestibulodynia. At least one comorbid pain or psychologic condition was identified respectively in 63 (47.7%) and 23 patients (54.5%). Vulvar hyperesthesia associated with pelvic floor muscle dysfunction was present in 121 patients (91.6%) and vulvar erethism was noted in 94 patients (71.2%). First-line treatments consisted of pelvic floor physiotherapy with biofeedback in 85% of patients, associated with amitriptyline in 36% of cases, and of additional lidocaine cream in 17%. Fifty-two patients (39%) presented at least a good response to first-line treatment, with only 21 (15%) being in complete remission, irrespective of therapeutic strategy (p = 0.25). Botulinum toxin injections were performed in 54 patients. Patients with either primary vestibulodynia (p = 0.04) or spontaneous vestibulodynia (p = 0.03) were more likely to receive this treatment. CONCLUSION: Our study highlights the current lack of efficacy of first-line treatments in vestibulodynia. Considering the high prevalence of muscular dysfunction, botulinum toxin injections are of particular interest despite a lack of randomized controlled trials in this indication.

French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

[Acquired angioedema due to C1-inhibitor deficiency: CREAK recommendations for diagnosis and treatment]. / Angiœdèmes par déficit acquis en C1-inhibiteur : recommandations du CREAK pour le diagnostic et la prise en charge.

Acquired angioedema with C1-inhibitor deficiency is a rare and peculiar entity belonging to the spectrum of bradykinin angioedemas. It usually occurs in subjects over 60 years old, and is mostly associated with a B-cell lymphoid hemopathy or a monoclonal gammopathy. The diagnosis relies on at least one angioedema episode, lasting more than 24 h, and on the decrease of functional C1-inhibitor. Low C1q is observed in 90% of patients, and an anti C1-inhibitor antibody is found in 50% of patients. The treatment of severe attacks relies on icatibant or C1-inhibitor perfusions. Long term prophylaxis in patients with frequent attacks requires treatment of the associated hemopathy if so. In case of idiopathic angioedema, tranexamic acid and danazol may be used, provided that there is-no thrombophilia; as well as rituximab as second-line treatment. Inhibitors of kallikrein still need to be evaluated in this therapeutic indication.

Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

[Resistant and progressive cutaneous lupus erythematosus treated with belimumab: A retrospective monocentric study]. / Lupus érythémateux cutanés réfractaires traités par bélimumab : étude descriptive monocentrique.

BACKGROUND: Belimumab is currently approved for the treatment of active systemic lupus erythematosus (SLE). The aim of our study was to evaluate the efficacy of belimumab in the treatment of cutaneous lupus erythematosus (CLE), resistant to conventional therapy. PATIENTS AND METHODS: Seven patients with resistant and progressive LEC and treated with belimumab were retrospectively analyzed. The efficacy and safety of belimumab were evaluated with the CLASI, RCLASI and DLQI scores, after 6 to 12 months of treatment. RESULTS: Eighty-three percent of patients demonstrated a significant clinical improvement based on the CLASI and RCLASI activity scores, including 1 complete and 4 partial responses, without worsening of CLASI and RCLASI damage scores. Eighty percent of patients also showed an improvement of their quality of life (DLQI). Oral corticosteroids were discontinued in all patients. Tolerance was acceptable with only one serious adverse event (bacteriema). CONCLUSION: Our study suggests the clinical efficiency of belimumab in a series of 7 patients presenting a resistant and progressive CLE.

[Anogenital granulomatosis as extradigestive Crohn disease: Efficiency of adalimumab therapy]. / Maladie de Crohn de localisation ano-génitale exclusive traitée par adalimumab.

INTRODUCTION: Anogenital granulomatosis is a rare disease which is actually considered as a metastatic lesion of Crohn disease (CD). OBSERVATION: A 53-year-old woman presented with intermittent vulvar and anoperineal lesions since adolescence, seeping and painful during sexual intercourse. We observed an infiltrative and asymmetric oedema of labia majora, perianal oedematous vegetative pseudo-marisca, and groin fold and perianal linear "knife-like" ulcerations. Pathological analysis revealed noncaseating giant cell granulomas. The diagnosis of CD was made. Investigations did not show any intestinal involvement. Anti-TNFα therapy with adalimumab was dramatically efficient. CONCLUSION: Anogenital granulomatosis often precedes intestinal lesions but may also be isolated as in our case. Although treatment is difficult, anti-TNFα seem promising tools.

Hunters select for behavioral traits in a large carnivore.

Human harvest can induce selection on life history and morphological traits, leading to ecological and evolutionary responses. Our understanding of harvest-induced selection on behavioral traits is, however, very limited. Here, we assessed whether hunters harvest, consciously or not, individuals with specific behavioral traits. We used long-term, detailed behavioral and survival data of a heavily harvested brown bear (Ursus arctos) population in Sweden. We found that hunters harvested male bears that were less active during legal hunting hours and had lower movement rates. Also, hunters harvested male and female bears that used habitats closer to roads. We provide an empirical example that individual behavior can modulate vulnerability to hunting and that hunters could exert a selective pressure on wildlife behaviors. This study increases our understanding of the complex interactions between harvest method, human behavior, and animal behavior that are at play in harvest-induced selection and provides better insight into the full effects of human harvest on wild populations.

A rare ectopic localization of pleomorphic adenoma.

INTRODUCTION: Pleomorphic adenoma (PA) is the most common benign salivary gland tumor, frequently affecting the major salivary glands but also the palatal or labial minor salivary glands. Pleomorphic adenomas affecting the retromolar trigone have seldom been reported with only few cases described in the literature. OBSERVATION: We present the case of a young female patient who presented with this rare localization of pleomorphic adenoma and its subsequent management. DISCUSSION: Pleomorphic adenoma of the retromolar trigone is a rare occurrence. Nevertheless, when faced with a swelling of the retromolar trigone, a diagnosis of pleomorphic adenoma should not be omitted from the differential.

[Acquired C1 esterase inhibitor deficiency via bradykinin-mediated angioedema: Four cases]. / Angiœdème bradykinique par déficit en C1 Inhibiteur acquis : quatre cas.

BACKGROUND: Acquired C1-esterase inhibitor (C1-INH) deficiency angioedema (C1-INH-AAE) is a form of bradykinin-mediated angioedema. This rare disorder is due to acquired consumption of C1-INH, hyperactivation of the classic pathway of human complement, and potentially fatal recurrent angioedema symptoms. Clinical symptoms of C1-INH-AAE are very similar to those of hereditary angioedema (HAE) but usually appear after the fourth decade of life and induce abdominal pain less frequently. Laboratory tests are essential in establishing the diagnosis with low levels or abnormal structure and function of C1-INH. Most patients present C1-INH autoantibodies. Furthermore, C1q is reduced in AAE, contrary to HAE. The long-term prognosis is determined by associated hematologic malignancies. PATIENTS AND METHODS: We report 4 cases of C1-INH-AAE associated with lymphoproliferative disorders referred to the Reference Centre for Angioedema of Besançon, France. The patients were aged between 60 and 77 years. C1 INH antibodies were found in three patients. Symptoms were triggered by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) in 3 patients. Hematologic malignancy was present at diagnosis (one case of chronic lymphoid leukemia) or was diagnosed during follow-up (one case of indolent marginal zone non-Hodgkin lymphoma and two cases of monoclonal gammopathy). DISCUSSION: C1-INH-AAE induced by ACE inhibitors or ARBs may be associated with hematologic malignancies. This form of revelation does not necessarily indicate a diagnosis of ACE or ARBs angioedema, and screening should therefore be performed for C1 Inh and C1q. An underlying hematologic malignancy should be routinely sought and the long-term prognosis determined.

Hunting promotes spatial reorganization and sexually selected infanticide.

Harvest can affect the ecology and evolution of wild species. The removal of key individuals, such as matriarchs or dominant males, can disrupt social structure and exacerbate the impact of hunting on population growth. We do not know, however, how and when the spatiotemporal reorganization takes place after removal and if such changes can be the mechanism that explain a decrease in population growth. Detailed behavioral information from individually monitored brown bears, in a population where hunting increases sexually selected infanticide, revealed that adult males increased their use of home ranges of hunter-killed neighbors in the second year after their death. Use of a hunter-killed male's home range was influenced by the survivor's as well as the hunter-killed male's age, population density, and hunting intensity. Our results emphasize that hunting can have long-term indirect effects which can affect population viability.

Evolutionary potential of morphological traits across different life-history stages.

Despite accumulating examples of selection acting on heritable traits in the wild, predicted evolutionary responses are often different from observed phenotypic trends. Various explanations have been suggested for these mismatches. These include within-individual changes across lifespan that can create important variation in genetic architecture of traits and selection acting on them, but also potential problems with the methodological approach used to predict evolutionary responses of traits. Here, we used an 8-year data set on tree swallow (Tachycineta bicolor) to first assess the effects of differences among three nestling life-history stages on the genetic (co)variances of two morphological traits (body mass and primary feather length) and the selection acting on them over three generations. We then estimated the evolutionary potential of these traits by predicting their evolutionary responses using the breeder's equation and the secondary theorem of selection approaches. Our results showed variation in strength and direction of selection and slight changes in trait variance across ages. Predicted evolutionary responses differed importantly between both approaches for half of the trait-age combinations we studied, suggesting the presence of environmentally induced correlations between focal traits and fitness possibly biasing breeder's equation predictions. Our results emphasize that predictions of evolutionary potential for morphological traits are likely to be highly variable, both in strength and direction, depending on the life stage and method used, thus mitigating our capacity to predict adaptation and persistence of wild populations.

Towards robust evolutionary inference with integral projection models.

Integral projection models (IPMs) are extremely flexible tools for ecological and evolutionary inference. IPMs track the distribution of phenotype in populations through time, using functions describing phenotype-dependent development, inheritance, survival and fecundity. For evolutionary inference, two important features of any model are the ability to (i) characterize relationships among traits (including values of the same traits across ages) within individuals, and (ii) characterize similarity between individuals and their descendants. In IPM analyses, the former depends on regressions of observed trait values at each age on values at the previous age (development functions), and the latter on regressions of offspring values at birth on parent values as adults (inheritance functions). We show analytically that development functions, characterized this way, will typically underestimate covariances of trait values across ages, due to compounding of regression to the mean across projection steps. Similarly, we show that inheritance, characterized this way, is inconsistent with a modern understanding of inheritance, and underestimates the degree to which relatives are phenotypically similar. Additionally, we show that the use of a constant biometric inheritance function, particularly with a constant intercept, is incompatible with evolution. Consequently, current implementations of IPMs will predict little or no phenotypic evolution, purely as artefacts of their construction. We present alternative approaches to constructing development and inheritance functions, based on a quantitative genetic approach, and show analytically and through an empirical example on a population of bighorn sheep how they can potentially recover patterns that are critical to evolutionary inference.

[CONDYDAV: A multicentre observational study of patients presenting external genital warts in France]. / CONDYDAV : étude observationnelle multicentrique des patients présentant des condylomes dans les dispensaires antivénériens en France.

BACKGROUND: Since 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear. OBJECTIVES: To determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination. PATIENTS AND METHODS: In this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France. RESULTS: A total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil® and one with Cervarix®. Cryotherapy was the preferred treatment. CONCLUSION: With the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.