Subungual leiomyoma in the left thumb of a 16‐year‐old female

Cutaneous leiomyomata, which are benign smooth muscle neoplasms, commonly present as dermal‐based nodules or papules with smooth borders and firm consistency. Digital, particularly subungual leiomyomata are quite rare. A 16‐year‐old female presented to nail clinic complaining of discoloration of the lunula of the left thumbnail for 2.5 months. On initial examination, a pink longitudinal band was present in the center of the nail plate, with yellow discoloration and distal onycholysis. The patient had only mild tenderness with firm palpation, and did not recall trauma of the area. A nail matrix biopsy was performed to determine the etiology of the lesion. Microscopic examination demonstrated a well‐demarcated dermal‐based spindle‐cell fascicular proliferation. Bland cells exhibited eosinophilic cytoplasm and elongate nuclei with blunt ends and minimal cytologic atypia. Prominent nucleoli, mitoses or necrosis were not appreciated. Immunohistochemical stains for smooth muscle actin and caldesmon highlighted the cells. Contrarily, S‐100, epithelial membrane antigen, p63, factor XIIIa, CD34, CD68 and p75 were all negative. Ki‐67 showed a low proliferative index. The immunoprofile combined with the morphologic features were interpreted as subungual leiomyoma. Subungual leiomyoma is a very rare diagnosis. We seek to bring awareness and expedite the diagnosis in patients with this lesion.     

Intravenous immunoglobulin-mediated immunosuppression and the development of an IVIG substitute

Immunoglobulins are glycoproteins produced by the cells of the immune system. Their primary function is to protect the body from pathogenic infection. Moreover, a concentrated polyclonal mixture of immunoglobulin G (IgG), the so-called intravenous IgG (IVIG), has been used to treat various chronic and systemic disorders of the immune system. Studies on the effects of IVIG in autoimmune disease models have revealed that IgG Fc fragments confer protection against various autoimmune diseases. The identification of this IgG Fc immunomodulatory component is important for the development of IVIG substitutes. The focus of this review is to introduce one of the Fc regulatory entities and to provide a summary of the current knowledge of the putative general mechanisms underlying IVIG activity in vivo on the basis of these Fc fragments. We also address the recent insights into several approaches for the development of IVIG substitutes.     

Experimental study of the mechanical properties of human abdominal fascia

The aim of the study is to characterise mechanical properties of human abdominal fascia according to its direction of loading and localization. The one-dimensional tensile behaviour of human abdominal fascia and its orthotropy has been studied experimentally using human umbilical (UF) and transversalis fascia (FT). The specimens have been cut and stretched parallel and orthogonal to the main fibre bundles. 90 specimens 10 mm wide and up to 70 mm long have been tested. The following mechanical parameters, characterising tensile properties of human abdominal fascia, have been calculated from the obtained stress-stretch ratio curves: maximal stress T(L)(max), stretch ratio at maximal stress λ(T(max)), maximal stretch ratio at failure λ(max), and a secant modulus E(i). The tissue strips obtained from defined areas reveal break stress between 0.63 and 1.99 MPa for FT and 0.93-1.61 MPa for UF. The parameter estimation has shown that in the physiological strain range specimens from both type of fascia can be considered orthotropic material according to their secant module, maximum stress T(L)(max) and stretch at maximum stress. Anisotropy factor AF (ratio of the stress in longitudinal and transverse directions) has been used to establish the level of the orthotropy of material and its variations with the stretch ratio. The maximum AF is 4.3 for FT at 20% deformation and 3.3 for UF at 5% deformation. The differences between the mechanical properties of FT and UF according to localization are not statistically significant thus the mechanical properties of human abdominal fascia are not affected by the localization.     

Time-dependent properties of human umbilical fascia

This investigation is devoted to the study of the viscoelastic behavior of human abdominal fascia from the umbilical region. Seventeen samples 10 mm wide and up to 70 mm long were cut along the primary fiber direction (group FL) or perpendicular to it (group FT) and subjected to relaxation tests. The viscoelastic response of the tissue at three different strain levels (4%, 5%, and 6%) was investigated. The relaxation curves were fitted using a two-stage decaying exponential form. The following parameters were determined: initial stress σ(0), relaxation times τ(1) and τ(2), stress reduction Δσ, initial relaxation modulus E and equilibrium relaxation modulus E(eq), as well as the ratio E/E(eq). Fiber orientation and strain levels were varied to determine their influence on the viscoelastic properties of fascia. The results highlight the inherent viscoelastic mechanical properties of umbilical fascia. The values of the viscoelastic parameters determined for the longitudinal and transverse directions varied markedly. Significant differences were found between the two groups FL and FT for the initial stress at 5% and 6% strain (p < 0.038) and for the initial and equilibrium moduli at the 6% strain level (p < 0.046). The stress reduction in samples from the FL group (45-55%) was less than that in samples from the FT group (37-54%), but this difference was not significant (p > 0.388). The influence of strain level on the parameter values was not statistically significant (p > 0.121). The nonlinear response of the tissue was demonstrated over the chosen strain range.     

Effects of carob-bean gum thickened formulas on infants’ reflux and tolerance indices

AIM: To examine the effect of carob-bean gum (CBG) thickened-formulas on reflux and tolerance indices in infants with gastro-esophageal reflux (GER).METHODS: Fifty-six eligible infants (1-6 mo old) were randomly allocated to receive for two weeks a formula with either 0.33 g/100 mL (Formula A) or 0.45 g/100 mL (Formula B) of cold soluble CBG galactomannans respectively, or a formula with 0.45 g/100 mL of hot soluble CBG galactomannans (Formula C). No control group receiving standard formula was included in the study. Data on the following indices were obtained both at baseline and follow-up from all study participants: 24 h esophageal pH monitoring indices, anthropometrical indices (i.e., body weight and length) and tolerance indices (i.e., frequency of colics; type and frequency of defecations). From the eligible infants, forty seven were included in an intention-to-treat analysis to examine the effects of the two-week trial on esophageal 24 h pH monitoring, growth and tolerance indices. Repeated Measures ANOVA was used to examine the research hypothesis.RESULTS: Regarding changes in 24 h pH monitoring indices, significant decreases from baseline to follow-up were observed in the “Boix Ochoa Score” (i.e., an index of esophageal acid exposure), in the total number of visible refluxes and in all symptoms related indices due to acid reflux only for infants provided with Formula A, while no significant changes were observed for infants provided with Formulas B and C. In addition, the significant decreases observed in two symptoms related pH monitoring indices (i.e., “Symptom index for reflux” and “Percentage of all reflux”) for infants provided with Formula A were also found to differentiate significantly compared to the changes observed in the other two groups (P = 0.048 and P = 0.014 respectively). Concerning changes in anthropometric indices, body weight significantly increased among infants provided with Formulas A and C, but not for infants provided with Formula B. As far as tolerance indices were concerned, the numbers of total and diarrheic defecations increased significantly only in infants provided with Formula B and these changes were significantly higher compared to the decreases observed in infants fed with Formulas A and C (P = 0.003 and P = 0.015 respectively. Lastly the number of colics significantly decreased in all infants, irrespective of the tested formula.CONCLUSION: Formula A (i.e., 0.33 g/100 mL of cold galactomannans) was effective in reducing certain pH-monitoring indices of uncomplicated GER, increased body weight and was well-tolerated by infants.     

Analysis of heart rate variability and skin blood flow oscillations under deep controlled breathing

The effect of deep breathing controlled in both rate (0.25, 0.16, 0.1, 0.07, 0.05 and 0.03 Hz) and amplitude on the heart rate variability (HRV) and respiration-dependent oscillations of forearm/finger skin blood flow (SBF) has been studied in 29 young healthy volunteers. The influence of sympathovagal balance on the respiratory sinus arrhythmia (RSA) amplitude and respiratory SBF oscillations has been studied. The subjects with predominant parasympathetic tonus had statistically significant higher RSA amplitudes in the breathing rate region of 0.03–0.07 Hz than the subjects with predominant sympathetic tonus. In the finger-cushion zone, having a well-developed sympathetic vascular innervations, the amplitudes of respiratory SBF oscillations at breathing rates 0.05 and 0.07 Hz were higher in the group of subjects with predominant parasympathetic tonus. In the forearm skin, where the density of sympathetic innervations is low comparatively to that in the finger skin, no statistically significant differences in the amplitude of respiratory SBF oscillations were found concerning the two groups of subjects.     

MMR deficient undifferentiated/dedifferentiated endometrial carcinomas showing significant programmed death ligand-1 expression (sp 142) with potential therapeutic implications

BackgroundUterine undifferentiated (UEAC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They appear to pursue an aggressive clinical course with an advanced stage at presentation. Recently, it was discovered that the use of immunotherapeutic drugs targeting programmed cell death protein 1 (PD1)/programmed death ligand-1 (PD-L1) was associated with improved survival in several types of cancer (especially in patients with mismatch-repair (MMR) deficient patients). Whether these findings can be applied to UEAC/DEAC remains a question. Herein, the aim of this study is to evaluate the expression of PD-L1/PD-1 in UEAC/DEAC and its relationship to MMR status. This could offer useful therapeutic information.DesignReview of endometrial carcinoma (EC) diagnosed over the period of 2011 to 2017 in our institution identified 14 UEAC/DEAC cases (n=14). All cases had immunohistochemistry performed for MMR (MLH1, PMS2, MSH2 and MSH6), PD-L1 and PD-1. The protein expression was examined and in DEAC cases both the undifferentiated component and the low grade component were recorded separately. The expression of PD-L1 and PD-1 was scored in both the tumor and the peritumoral lymphocyte infiltration.ResultsOverall variable degrees of tumoral or immune stromal PD-L1 staining (from 1% to 5%), was present in 50.0% (7/14) of UC/DEACs. Seven cases (50%) were PD-1 positive (immune stromal). Five cases (35.7%) showed co-expression of PD-1 and PD-L1 (Figure 1). Worth noting is that PD-1 staining was exclusively present in peritumoral immune cells. Following this the 14 cases were further divided into MMR deficient and MMR proficient groups (Table 1). A total of 8 cases had MMR deficiency (57.1%). There was a statistically significant association for PD-L1 positivity in the MMR deficiency group (p=0.05). However there was no statistically significant differences regarding PD-1 positivity between MMR groups.ConclusionsPD-L1 and PD-1 were expressed in majority of MMR-deficient UEAC /DEAC cases. PD-L1 was not expressed in MMR-proficient carcinomas. These findings might help support potential immunotherapy trials in MMR-deficient UEAC /DEAC.