Pathophysiology and management of sensitive skin: position paper from the special interest group on sensitive skin of the International Forum for the Study of Itch (IFSI)

The special interest group on sensitive skin of the International Forum for the Study of Itch previously defined sensitive skin as a syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus and tingling sensations) in response to stimuli that normally should not provoke such sensations. This additional paper focuses on the pathophysiology and the management of sensitive skin. Sensitive skin is not an immunological disorder but is related to alterations of the skin nervous system. Skin barrier abnormalities are frequently associated, but there is no cause and direct relationship. Further studies are needed to better understand the pathophysiology of sensitive skin – as well as the inducing factors. Avoidance of possible triggering factors and the use of well-tolerated cosmetics, especially those containing inhibitors of unpleasant sensations, might be suggested for patients with sensitive skin. The role of psychosocial factors, such as stress or negative expectations, might be relevant for subgroups of patients. To date, there is no clinical trial supporting the use of topical or systemic drugs in sensitive skin. The published data are not sufficient to reach a consensus on sensitive skin management. In general, patients with sensitive skin require a personalized approach, taking into account various biomedical, neural and psychosocial factors affecting sensitive skin.     

Validation of PATHFx 2.0: An open-source tool for estimating survival in patients undergoing pathologic fracture fixation

Treatment decisions in patients with metastatic bone disease rely on accurate survival estimation. We developed the original PATHFx models using expensive, proprietary software and now seek to provide a more cost-effective solution. Using open-source machine learning software to create PATHFx version 2.0, we asked whether PATHFx 2.0 could be created using open-source methods and externally validated in two unique patient populations. The training set of a well-characterized, database records of 189 patients and the bnlearn package within R Version 3.5.1 (R Foundation for Statistical Computing), was used to establish a series of Bayesian belief network models designed to predict survival at 1, 3, 6, 12, 18, and 24 months. Each was externally validated in both a Scandinavian (n = 815 patients) and a Japanese (n = 261 patients) data set. Brier scores and receiver operating characteristic curves to assessed discriminatory ability. Decision curve analysis (DCA) evaluated whether models should be used clinically. DCA showed that the model should be used clinically at all time points in the Scandinavian data set. For the 1-month time point, DCA of the Japanese data set suggested to expect better outcomes assuming all patients will survive greater than 1 month. Brier scores for each curve demonstrate that the models are accurate at each time point. Statement of Clinical Significance: we successfully transitioned to PATHFx 2.0 using open-source software and externally validated it in two unique patient populations, which can be used as a cost-effective option to guide surgical decisions in patients with metastatic bone disease.     

MRI T2-Hyperintense Signal Structures in the Cervical Spinal Cord: Anterior Median Fissure versus Central Canal in Chiari and Control—An Exploratory Pilot Analysis

BACKGROUND AND PURPOSE:Cervical spine axial MRI T2-hyperintense fluid signal of the anterior median fissure and round hyperintense foci resembling either the central canal or base of the anterior median fissure are associated with a craniocaudad sagittal line, also simulating the central canal. On the basis of empiric observation, we hypothesized that hyperintense foci, the anterior median fissure, and the sagittal line are seen more frequently in patients with Chiari malformation type I, and the sagittal line may be the base of the anterior median fissure in some patients.MATERIALS AND METHODS:Saggital line incidence and the incidence/frequency of hyperintense foci and anterior median fissure in 25 patients with Chiari I malformation and 25 contemporaneous age-matched controls were recorded in this prospective exploratory study as either combined (hyperintense foci+anterior median fissure in the same patient), connected (anterior median fissure extending to and appearing to be connected with hyperintense foci), or alone as hyperintense foci or an anterior median fissure. Hyperintense foci and anterior median fissure/patient, hyperintense foci/anterior median fissure ratios, and anterior median fissure extending to and appearing to be connected with hyperintense foci were compared in all, in hyperintense foci+anterior median fissure in the same patient, and in anterior median fissure extending to and appearing to be connected with hyperintense foci in patients with Chiari I malformation and controls.RESULTS:Increased sagittal line incidence (56%), hyperintense foci (8.5/patient), and anterior median fissure (4.0/patient) frequency were identified in patients with Chiari I malformation versus controls (28%, 3.9/patient, and 2.7/patient, respectively). Increased anterior median fissure/patient, decreasing hyperintense foci/anterior median fissure ratio, and increasing anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified in Chiari subgroups. A 21%–58% increase in observed anterior median fissure extending to and appearing connected to hyperintense foci in the entire cohort and multiple sagittal line subgroups compared with predicted occurred.CONCLUSIONS:In addition to the anticipated increased incidence/frequency of sagittal line and hyperintense foci in patients with Chiari I malformation, an increased incidence and frequency of anterior median fissure and anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified. We believe an anterior median fissure may contribute to a saggital line appearance in some patients with Chiari I malformation. While thin saggital line channels are usually ascribed to the central canal, we believe some may be due to the base of the anterior median fissure, created by pulsatile CSF hydrodynamics.

Axial MR imaging of the cervical spine frequently demonstrates hyperintense, linear, anatomically, sagittally-oriented T2 fluid signal of the anterior median fissure (AMF) and hyperintense foci (HIF) resembling the central canal or the base of the AMF.^1-3 These axial T2 findings may be associated with a channel-like T2-hyperintense craniocaudad line on images parallel to the sagittal plane (a sagittal line [SL]), simulating the central canal (Fig 1).^4,5 A previous analysis of HIF, AMF, and a thin SL in a population without Chiari I malformation provided not only a baseline for their identification but also a confirmation of a relationship between not only the AMF and HIF but also their relationship to the SL.¹ It found the following:

1. HIF were greater in number than AMFs, but AMFs increase in the presence of increasing HIF, suggesting an anatomic relationship.
2. SLs were associated with greater numbers of both HIF and AMF/patient (pt.) versus no SL, 6.7 versus 2.7/pt. and 3.3 versus 2.0/pt., respectively. SL presence correlated more closely to HIF than to AMF presence within the entire 358-patient group.
3. When HIF and AMF were classified as combined (concurrent HIF and AMF, with ≥1 of each both present in the same patient [HIF+AMF]) or continuous (AMF appearing to extend to and join an HIF [AMF>HIF]), HIF and AMF/pt. each differed numerically and patients with an SL had more combined HIF+AMF and continuous AMF>HIF than patients without an SL.
4. In patients with both SL and combined HIF+AMF (a circumstance allowing the possibility of a relationship of all 3 structures), HIF become proportionally fewer compared with AMFs. In patients with an SL actually exhibiting continuous AMF>HIF, the HIF/AMF ratio decreased further.

Open in a separate windowFIG 1.A patient with Chiari I with 19 HIF up to 3 mm in diameter, 1 AMF, no AMF>HIF, and an SL of various hyperintensity and diameter from C4 through T1, consistent with hydromyelia.While it is expected that manifestations of the central canal as an SL and HIF are more frequent in patients with Chiari syndrome type I,⁶ past experience leads us to hypothesize that AMFs are also seen more frequently in patients with Chiari I malformation and that the SL or channel may represent the base of a wide AMF, rather than the central canal, in some patients (Figs 1 and ​and2).2). Therefore, we performed an exploratory prospective analysis of HIF, AMF, and SL in patients with Chiari I malformation to examine their relationships.Open in a separate windowFIG 2.Postdecompressive craniectomy patient with Chiari I with 9 HIF, 4 AMFs, 1 AMF>HIF, and sharp and hyperintense SLs at C6–C7 and less hyperintense, sharp, and defined SLs at C2–C6.     

Ospemifene plus fractional CO2 laser: a powerful strategy to treat postmenopausal vulvar pain

Abstract

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO₂ laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60?mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene?+?laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene?+?laser group compared with the laser treatment group (?87% vs???34%, respectively), and the vestibular health score started declining faster in the ospemifene?+?laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.     

C.B‐17 SCID mice develop epicardial calcinosis with unaltered cardiac function

Inbred mouse strains are the most widely used mammalian model organism in biomedical research owing to ease of genetic manipulation and short lifespan; however, each inbred strain possesses a unique repertoire of deleterious homozygous alleles that can make a specific strain more susceptible to a particular disease. In the current study, we report dystrophic cardiac calcinosis (DCC) in C.B‐17 SCID male mice at 10 weeks of age with no significant change in cardiac function. Acquisition of DCC was characterized by myocardial injury, fibrosis, calcification, and necrosis of the tissue. At 10 weeks of age, 38% of the C.B‐17 SCID mice from two different commercial colonies exhibited significant calcinosis on the ventricular epicardium, predominantly on the right ventricle. The frequency of calcinosis was more than 50% for mice obtained from Taconic's Cambridge City colony and 25% for mice obtained from Taconic's German Town colony. Interestingly, the DCC phenotype did not affect cardiac function at 10 weeks of age. No differences in echocardiography or electrocardiography were observed between the calcinotic and non‐calcinotic mice from either colony. Our findings suggest that C.B‐17 SCID mice exhibit DCC as early as 10 weeks of age with no significant impact on cardiac function. This strain of mice should be cautiously considered for the study of cardiac physiology.