Impact of intertendinous connections between the flexor digitorum brevis and longus on percutaneous tenotomy for the treatment of claw toes: an anatomic and ultrasound study.

PURPOSE: Selective percutaneous tenotomy of the flexor digitorum longus (FDL) is a treatment for claw toes that gives astonishingly good functional results despite tendon sacrifice. However, the involution of the FDL tendon stump after tenotomy is unknown. The aim of our study was to assess the involution of the tendon stump after selective percutaneous tenotomy of the FDL. METHODS: The study included two parts. In the clinical part, an ultrasound analysis of 15 FDL tenotomies in 7 patients was carried out 3 months post-surgery. In the anatomic part, the feet of 10 bodies donated to science were dissected and examined anatomically. RESULTS: The proximal stump of the FDL was located near the base of the proximal phalanx and moved synchronously with the flexor digitorum brevis (FDB).Separating the FDB and FDL revealed a large tissue connection between the plantar surface of the tendinous chiasm of the FDB and the dorsal part of the FDL. These connections had significant resistance ranging from 2 to 9 Newtons depending on the toe. Tenotomy of the FDL followed by proximal traction of it led to retraction of the stump up to the base of the proximal phalanx and transfer of its action to the FDB by tensioning the intertendinous structure. Histologically, these structures were mostly comprised of tendon connective tissue. Their vascular component was small. CONCLUSION: The presence of this intertendinous connection leads, in the case of isolated tenotomy of the FDL, to equivalent transfer of the latter to the FDB.

[How to test for NTRK gene fusions: A practical approach for pathologists]. / Recherche de fusions des gènes NTRK : guide pratique pour les pathologistes.

The recent availability of targeted anti-TRK therapies represents a new opportunity to treat patients with advanced cancers harboring NTRK gene fusions. In this article, we present an update on the practical modalities of implementing a "NTRK testing" to search for these fusions in view of the performances and availability of the different testing methods and the epidemiological characteristics of the tumors liable to present the NTRK1, NTRK2 or NTRK3 gene fusions.

Effectiveness and Safety of Anti-interleukin-17 Therapies in Elderly Patients with Psoriasis.

Anti-interleukin-17 agents have recently been developed for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practice. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including secukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stopped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injection site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years.

Stakeholders' Role and Actions in the Return-to-Work Process of Workers on Sick-Leave Due to Common Mental Disorders: A Scoping Review.

The lack of knowledge regarding the roles and actions of return to work (RTW) stakeholders create confusion and uncertainty about how and when to RTW after experiencing a common mental disorder (CMD). Purpose The purpose of this scoping review is to disentangle the various stakeholders' role and actions in the RTW process of workers on sick-leave due to CMDs. The research question is: What is documented in the existing literature regarding the roles and actions of the identified stakeholders involved in the RTW process of workers on sick-leave due to CMDs? Methods In conducting this scoping review, we followed Arksey and O'Malley's (Int J Soc Res Methodol 8:19-32, 2005) methodology, consisting of different stages (e.g., charting the data by categorizing key results). Results 3709 articles were screened for inclusion, 243 of which were included for qualitative synthesis. Several RTW stakeholders (n=11) were identified (e.g., workers on sick leave due to CMDs, managers, union representatives, rehabilitation professionals, insurers, return to work coordinators). RTW stakeholders' roles and actions inter- and intra-system were recommended, either general (e.g., know and understand the perspectives of all RTW stakeholders) or specific to an actor (e.g., the return to work coordinator needs to create and maintain a working alliance between all RTW stakeholders). Furthermore, close to 200 stakeholders' actions, spread out on different RTW phases, were recommended for facilitating the RTW process. Conclusions Eleven RTW stakeholders from the work, heath and insurance systems have been identified, as well as their respective roles and actions. Thanks to these results, RTW stakeholders and policy makers will be able to build practical relationships and collaboration regarding the RTW of workers on sick leave due to CMDs.

Return-to-Work Following Depression: What Work Accommodations Do Employers and Human Resources Directors Put in Place?

The magnitude of economic and social costs related to common mental disorders has a profound impact on the workplace. Returning to work following depression is, therefore, a major issue for all stakeholders involved (employee, employer, human resources director, union, physician, etc.). Considering their role in the organization, Human Resources Directors (HRD) and employers have a decisive impact on the return-to-work (RTW) process. Purpose This study aims to determine which RTW accommodations are implemented, following depression, by one of the central stakeholders: HRD and employers. Methods 219 HRD/employers participated in a semi-structured telephone interview about RTW of employees after depression. From that interview, the question related to this article was: Do you put in place work accommodations for employees after a sick leave due to depression (yes or no)? If their response was positive, we asked: If yes, what were the work accommodations? Results 170 HRD/employers specified accommodations. The most common categories identified were related to: work schedule, task modifications, job change and work environment change. Accommodations directly related to the employee or the colleagues were considerably less mentioned and those concerning other RTW stakeholders, including supervisor, were almost absent. Conclusion Our results suggest that accommodations directly related to work aspects seemed to predominate in our sample of HRD/employers when an employee returned-to-work following depression. The relational aspect and the involvement of the different stakeholders are also not prioritized to accommodate the RTW. These results contrast with employer best practice guidelines for the RTW of workers with common mental disorders.

An unusual ectopic thyroid tissue location & review of literature.

Ectopic thyroid is well-known pathology for several decades. Many locations have been described. Nowadays, only three cases of skull base location have been described in literature. In our case, we reported a single case of a 39-year-old male presenting with a supra-sellar and suprachiasmatic location. He presented no clinical symptoms, no endocrine alteration on biology and no skull base invasion which make this case unique compared to actual literature. Such diagnosis should always be an exclusion diagnosis as secondary neoplastic should be first ruled out.

A case of Pseudomyxoma Peritonei of an unexpected origin.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a complex and partially understood disease defined by mucin deposits in the peritoneal cavity, mostly of appendiceal origin caused by the rupture of a mucocele often containing Low or High grade Appendiceal Mucinous Neoplasm (LAMN/HAMN). Other origins include primitive ovarian mucinous cystadenoma or cystadenocarcinoma almost always with an associated teratoma, but to our knowledge no case of ovarian teratomatous appendiceal-like mucocele with LAMN has been reported as a cause of PMP. CASE PRESENTATION: A 25-year old female with infertility was diagnosed with an isolated left ovarian tumor in a context of PMP. Histological examination revealed an ovarian teratoma containing an appendiceal-like structure with mucocele and LAMN, without any associated lesion of the appendix on full histological analysis. Molecular characterization of the ovarian lesion showed co-KRAS and GNAS mutations, as described in PMP of appendiceal origin, while only KRAS mutations are reported in primitive ovarian mucinous tumor. CONCLUSIONS: Detection of co-KRAS and GNAS mutations in our case of ovarian teratomatous appendiceal-like mucocele with LAMN shows that when PMP derives from a mucinous ovarian lesion (with histological proof of none-appendiceal involvement), it is probably of a digestive teratomatous origin, emphasizing the need to actively search for tetatomatous signs in a context of ovarian PMP.

Pan-TRK Immunohistochemistry Is Highly Correlated With NTRK3 Gene Rearrangements in Salivary Gland Tumors.

AIMS: Secretory carcinoma (SC) is characterized by ETV6 rearrangements, most often ETV6-NTRK3 fusion. Given its histologic overlap with other salivary gland tumors (SGTs), SCs can be difficult to diagnose without genetic confirmation. A recently developed pan-TRK (tropomyosin receptor kinase) antibody shows promise for identifying tumors with NTRK (neurotrophic tyrosine kinase receptor 3) fusions. The aim of this study was to evaluate the utility of pan-TRK immunohistochemistry in distinguishing SCs from mimics and selecting patients eligible for TRK inhibitor clinical trials. We examined whole-tissue sections from 111 SGTs with molecular characterization, including 26 SCs (23 with ETV6-NTRK3 fusion and 3 with ETV6-RET fusion detected by ligation-dependent reverse transcription-polymerase chain reaction, next-generation sequencing and 85 non-SC SGTs (no ETV6-NTRK3 fusion). Immunohistochemistry was performed with a pan-TRK rabbit monoclonal antibody. When any pan-TRK staining (nuclear or cytoplasmic with any staining intensity) was considered to indicate positivity, 22 of 23 SCs with ETV6-NTRK3 fusion (95.7%) and 33 of 85 non-SC (38.8%) salivary neoplasms were positive, mainly basal cell adenoma, pleomorphic adenomas, adenoid cystic carcinomas, and epithelial-myoepithelial carcinomas. All SCs with ETV6-RET fusion were entirely negative. When only nuclear pan-TRK staining with any staining intensity was considered positive, 18 of 23 SCs with ETV6-NTRK3 fusion (78.3%) were positive, 11 among them with diffuse staining (>30% of cells). All non-SCs and SCs with ETV6-RET fusion were entirely negative. In comparison to molecular analysis (ligation-dependent reverse transcription-polymerase chain reaction, next-generation sequencing), nuclear pan-TRK IHC has a sensitivity of 78.3% and a specificity of 100% for diagnosing SCs with ETV6-NTRK3 fusion, 69% and 100% for SCs (all fusions). Pan-TRK is a reasonable screening test for diagnosing SCs among SGTs when taking only nuclear staining into account. Although pan-TRK expression is not entirely sensitive for SCs, nuclear staining is highly specific for SCs with ETV6-NTRK3 fusion. The lack of pan-TRK immunoreactivity in a subset of SCs is suggestive of atypical exons 4 to 14 or exons 5 to 14 ETV6-NTRK3 fusion or non-NTRK alternative fusion partners such as ETV6-RET. Pan-TRK staining can serve as a strong diagnostic marker to distinguish SC from it mimics and to select patients eligible for TRK inhibitor clinical trials.

[Issues and Solutions in Mental Health and Work: Managers Perspectives of a Large Health Organization]. / Enjeux et solutions en santé mentale et travail : le point de vue des gestionnaires d'une grande organisation de santé.

Mental health problems in the workplace represent an important issue for public organizations, particularly for people working in the health sector who have been confronted to multiple changes following the recent health system reform in Quebec. Managers need to take into consideration employee mental health within their organization in order to ensure productive and healthy employees. Managers are thus called upon to take on a role that includes prevention (e.g., detection of early warning signs), team management (e.g., working on recognition at work) and coaching employees in their tasks when returning to work following a sick leave due to a common mental disorder (e.g., depression). Although there is an abundant literature on the manager's role in the prevention of mental health problems in the workplace and the work rehabilitation of employees on sick leave due to a common mental disorder, to our knowledge, little research has been conducted on these issues regarding managers' perceptions working in large health organizations. Furthermore, potential solutions have not been explored in this context. Objective The purpose of the study is to document, from the managers' perspective within a large health organization in Quebec, the issues pertaining to mental health and work (from prevention to work rehabilitation), and the solutions to deal with them. Method As part of a participatory research project, researchers and collaborators of a large health organization conducted focus groups with managers on the theme of mental health and work: issues and solutions. A total of 83 managers spread out in 10 focus groups participated in this study. Results From these focus groups, 6 broad categories of issues related to mental health in the workplace emerged: 1) the management framework, 2) human, financial, material and information resource management, 3) management of mental health and tools, 4), stakeholders' collaboration, roles and actions, 5) employees' sense of belonging to the organization and, 6) work-life balance. From these broad conceptual categories, 23 specific issues and associated solutions emerged. Conclusions From this study, the general consensus was the need to have access to a series of tools (e.g., toolbox) in order to assist managers across the different steps, from sick-leave prevention, to rehabilitation and return to work. The results also highlighted the need to better define the roles of each stakeholder in this process. These results bring a new light to the issues and potential solutions perceived by managers dealing with mental health and work issues in a large health organization. These results could eventually be replicated in other settings or large organizations.

Real-World Effectiveness and Safety of Apremilast in Older Patients with Psoriasis.

INTRODUCTION: Apremilast is a drug recently developed for psoriasis. Few data are available on its use in the elderly. We evaluated the tolerance and effectiveness of apremilast used in daily practice for psoriasis treatment in older patients. METHODS: We performed a multicenter, retrospective study involving patients aged ≥ 65 years who had received apremilast as a psoriasis treatment. Demographic data and details regarding psoriasis and adverse events (AEs) were collected from patient medical records. RESULTS: 135 patients were included (mean age: 73.5 years). Treatment was stopped in 74 patients (54.8%) for AEs (n = 43, 56.6%), primary failures (n = 18, 23.4%), and relapses (n = 7, 9.2%). When patients were stratified by age at treatment initiation, the main cause of discontinuation in patients ≥ 75 years was AEs, whereas in patients aged 65-74 years it was primary failures (28.3%). Sixty-one patients reported AEs, mainly digestive (n = 49). Regarding effectiveness, 45.2% of patients reached PGA 0/1 between 3 and 6 months after treatment initiation. One-year apremilast continuation rates were better in the 65-74 and 75-84 years subgroups than in the > 85 years subgroup (p = 0.01). CONCLUSION: Apremilast seems to be an effective and safe therapeutic option for psoriasis in the elderly. The main AEs reported by patients did not seem to differ from those reported previously in younger populations. However, AEs were more frequent in patients > 75 years old leading to more frequent discontinuation of apremilast compared with younger patients, suggesting a higher level of vigilance is needed in the elderly.

L-carnosine as an enhancer to computerized cognitive behaviour therapy in Japanese workers, an unjustified claim.

This letter comments on the conclusion drawn by Shirotsuki et al. (2017) in their article entitled "The effect for Japanese workers of a self-help computerized cognitive behaviour therapy program with a supplement soft drink", recently published in BioPsychoSocial Medicine. The authors concluded that their drink, containing L-carnosine, enhances the effects of a computerized cognitive-behavioural therapy (CCBT) on the psychological well-being of healthy Japanese workers. Yet, we argue that their conclusion is unfounded given their results and the methodological shortcomings of their study. Briefly, while the authors reported improvement on the tension-anxiety subscale of the Profile of Mood States (POMS) in the CCBT only group, they also observed a lack of improvement on this subscale in the CCBT+L-carnosine group suggesting that the drink washes out this beneficial effect of CCBT. Methodological issues include the uncontrolled levels of L-carnosine metabolized by participants jeopardize the study's internal validity. Also, the clinical meaningfulness of the findings seems dubious as post-treatment scores remained within the range of the general Japanese population. Consequently, we argue that Shirotsuki et al.'s study should be re-conducted before drawing any valid conclusion.

FTY720: placebo-controlled study of the effect on cardiac rate and rhythm in healthy subjects.

The purpose of this double-blind, placebo-controlled study was to measure the effects of FTY720, a novel immunomodulator, on heart rate and rhythm in healthy volunteers. Subjects (n = 66) were randomized to FTY720 1.25 mg or 5 mg or placebo administered once daily for 7 days. Continuous telemetry revealed an acute, dose-dependent decrease in mean heart rate (10-bpm decrease vs placebo) following the first dose of FTY720, with a nadir generally 4 hours postdose. Although a persistent FTY720-related decrease in heart rate was measured from day 2 to day 7, additional doses of FTY720 after day 2 resulted in no further incremental decreases. Mean PR interval increased by approximately 8 to 10 msec in FTY720-treated subjects on day 1. FTY720 did not increase the QRS or QT interval. These results confirm that the first dose of FTY720 has a mild to moderate negative chronotropic effect.

Pharmacokinetics of enteric-coated mycophenolate sodium in stable pediatric renal transplant recipients.

This study aims to characterize the pharmacokinetics of mycophenolic acid (MPA) and its glucuronide metabolite (mycophenolic acid 7-O-glucuronide, MPAG) following single oral administration of enteric-coated mycophenolate sodium (EC-MPS, myfortic) at an approximate dose level of 450 mg/m(2) body surface area (BSA) to 25 stable renal transplant recipients (aged 5-16 yr), and to evaluate the safety and tolerability of EC-MPS in this pediatric population. Patients had been maintained on a cyclosporine emulsion, Neoral-based immunosuppressive regimen for at least 3 months and had received their first or second renal transplant more than 6 months prior to entry into the study. After a brief lag phase (t(lag) 0.75 h), MPA was rapidly absorbed (t(max) 2.5 h) and rapidly converted to MPAG (t(max) 3.25 h), with relatively high plasma concentrations of MPAG (C(max) 67.7 microg/mL) compared with MPA (C(max) 36.3 microg/mL). The elimination half-life for MPAG was slightly longer than for MPA (approximately 13 h vs. 8.5 h), and the apparent oral clearance of MPA was approximately 0.2 L/h/kg. The pharmacokinetics of MPA or MPAG were not affected by age, body weight or BSA, within the study population. The pharmacokinetic results for pediatric patients are comparable with those obtained previously in adults, although exposure based on AUC(0-infinity) was approximately 23% higher, and this finding may be a result of dosing on the basis of BSA, rather than body weight. The recommended dose of EC-MPS in pediatric patients is 400-450 mg/m(2) twice daily or, alternatively, approximately 10-14 mg/kg twice daily when used in combination with cyclosporine microemulsion.

Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co-administered enteric-coated mycophenolate sodium.

Enteric-coated mycophenolate sodium (EC-MPS) (myfortic) is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying the release of MPA until the small intestine. A randomized, calcineurin inhibitor crossover, steady-state pharmacokinetic study in stable renal transplant patients receiving EC-MPS demonstrated increased MPA exposure of 19% higher, MPA C(max,ss) 19% lower and MPA C(min,ss) approximately twofold higher with tacrolimus, than cyclosporine microemulsion. No study drug-related adverse events were recorded, but mean blood glucose concentration was higher in patients receiving tacrolimus (p = 0.031). The dose changes in relation to MPA exposure in patients is dependent on the clinical situation and may not always be warranted. These observations should be taken into consideration when switching from one calcineurin inhibitor to another, but the final dosage should be based on both this pharmacokinetic data and the clinical situation.