Subcutaneous Connective Tissue Research Articles

Tissue Contraction With Helium-Based Plasma Radiofrequency Technology: A Preliminary Report of Initial Ultrasound Findings

Abstract Background Application of helium-based plasma radiofrequency (RF; Renuvion, Apyx Medical, Clearwater, Florida, USA) in the subcutaneous plane results in tissue coagulation and contraction. While traditionally, impact of thermal devices on skin laxity is assessed by measuring changes in skin surface area, this indirect measure does not permit intraoperative assessment or differentiation of effects from various treatments. Objectives To determine the amount of soft tissue contraction achieved by multiple passes of helium plasma RF energy to the subcutaneous connective tissues following power-assisted liposuction (PAL). Methods In this single-center study, 4 subjects were assessed using real-time ultrasound measurements at baseline and following both PAL and each pass with helium plasma RF. Results Based on changes in the distance from the skin (dermal basement membrane) to Scarpa’s fascia, PAL produced an average reduction of 36.7% (SD 14.6, range 24.7%-58.6%) due to the fat removal. Contraction observed with helium plasma RF was greatest for the first pass, with a mean decrease of 27.0% (SD 19.6, range 4.5%-52.1%) in distance relative to distance measured following liposuction. Subsequent passes resulted in additional incremental contraction relative to prior treatment pass: 17.0% (5.1) for pass 2, 7.7% (17.5) for pass 3, and 7.1% (5.5) for pass 4. Overall, helium plasma RF resulted in an average contraction of 44.0% (SD 17.2, range 27.1%-59.4%) in the skin-to-Scarpa-fascia measurement. Conclusions Helium plasma RF improved tissue contraction following PAL by an average of 44% and data suggest that the greatest increase in tissue contraction is obtained by the first treatment pass.

Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration's adverse event reporting system databases.

This study aimed to investigate the real-world profile of adverse events (AEs) associated with gepant medications in the clinical treatment of migraines by analyzing data collected from the VigiAccess database and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. As novel migraine therapies, gepants act by targeting the calcitonin gene-related peptide (CGRP) pathway, demonstrating effective control of migraine attacks and good tolerability. Nonetheless, comprehensive real-world studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research. Leveraging these two international adverse event reporting system databases, we systematically gathered and analyzed reports of AEs related to gepant medications, such as rimegepant. Our focus encompasses but is not limited to severe, new, and rare adverse reactions induced by the drugs, as well as safety issues pertaining to the gastrointestinal, cardiovascular, hepatic, and renal systems. Through descriptive statistical analyses, we assessed the incidence and characteristics of AEs, compared AEs among gepants, and uncovered previously unknown AE information, all with the goal of providing a reference for the selection of clinical treatment regimens and AE monitoring. By extracting all AE reports concerning "rimegepant", "atogepant", and "ubrogepant" from the VigiAccess and FAERS database since its establishment up to 31 March 2024, a retrospective quantitative analysis was conducted. The reporting odds ratio (ROR) method were used to compare AEs among the three gepants. In the VigiAccess and FAERS databases, 23542 AE reports in total, respectively, were identified as being related to gepant medications. Among gastrointestinal system AEs, rimegepant had the greatest proportion and greatest signal strength; nausea was most severe and had the strongest signal in rimegepant AEs, whereas constipation was most prominent and had the strongest signal in atogepant AEs. In skin and subcutaneous tissue disorders, rash and pruritus were more frequently observed with rimegepant, followed by ubrogepant. Alopecia emerged as a novel AE, being more severe in rimegepant and secondarily in atogepant. Regarding cardiac disorders, the three gepants showed comparable rates of cardiac AEs, yet rimegepant exhibited the strongest AE signal. In musculoskeletal and connective tissue AEs, ubrogepant presented the most positive signals for skeletal muscle AEs. Furthermore, among the rare blood and lymphatic system disorder AEs, rimegepant had the highest number of reports of Raynaud's phenomenon and the strongest signal. The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets. Gepant medications exhibit similarities and differences in their safety profiles. Analysis of the two databases indicated the presence of AEs across various systems, including gastrointestinal disorders, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue disorders, organ-specific effects, and liver diseases. However, each drug displays distinct incidences and signal intensities for these AEs. Additionally, the study revealed a rare AE in the form of Raynaud's phenomenon. These findings suggest that during clinical use, individualized medication selection and AE monitoring should be based on the patient's physiological condition and specific characteristics.

Pharmacological properties and clinical development overview of pertuzumab (genetical recombination), trastuzumab (genetical recombination) and vorhyaluronidase alfa (genetical recombination) (PHESGO® combination for ‍subcutaneous injection MA, IN)

Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular HER2 signaling additively or synergistically. Their combination is widely recommended worldwide and has been established as a standard of care for HER2-positive breast cancer. However, improvement is required because of the prolonged time of intravenous infusion. Vorhyaluronidase alfa (rHuPH20) depolymerizes hyaluronan in the subcutaneous connective tissue. It's reported to increase the permeability and absorption levels of drugs. PHESGO® combination for subcutaneous injection MA/IN (PHESGO®) is a fixed-dose combination of pertuzumab, trastuzumab, and rHuPH20. A confirmatory phase III study (FeDeriCa) was conducted following a dose-finding phase I study (BO30185). Patients with HER2-positive early breast cancer were randomly assigned to receive either intravenous infusion of pertuzumab and trastuzumab or subcutaneous injection of PHESGO®, in combination with chemotherapy, to compare the pharmacokinetics (PK), efficacy and safety. A phase II study (PHranceSCa) was also conducted to assess patients' preference and satisfaction. Based on these results, population PK analysis, and other data, PHESGO® obtained marketing approval in Japan in September 2023 with indications for "HER2-positive breast cancer" and "advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection". By reducing the administration time, PHESGO® is expected to contribute to various needs of patients and improvement of their daily lives. Since drug preparation is not required, it can provide convenience to healthcare professionals, leading to stress reduction of medical resources as well.

Treatment-related adverse events of PD-1 versus PD-L1 inhibitors commonly used in lung cancer therapy: Analysis of real-world FAERS data.

e14598 Background: With the increasing utilization of immune checkpoint inhibitors (ICIs) in the dynamic landscape of cancer treatment, understanding immune-related adverse events (AEs) has become crucial for optimizing patient outcomes and therapeutic selection. In this study, we utilized the FDA Adverse Event Reporting System (FAERS) database to assess AEs reported with commonly used PD-1 and PD-L1 inhibitors in lung cancer therapy. Methods: We conducted a retrospective FAERS public database review to assess anti-PD-1 inhibitors (Pembrolizumab and Nivolumab) and anti-PD-L1 inhibitors (Atezolizumab and Durvalumab) reported AEs from January 2017 through September 30, 2023. We assessed disproportionality signals by calculating the reporting odds ratio (ROR) with a 95% confidence interval (CI). Significance was determined when the lower limit of the 95% CI exceeded 1. Results: In our analysis of 134,184 reported AEs, anti-PD-1 therapies had higher rates of cardiac AEs (ROR = 1.08; 95% CI: 1.03-1.14; P = 0.0015), vascular AEs (ROR = 1.23; 95% CI: 1.17-1.30; P < 0.0001), respiratory AEs (ROR = 1.30; 95% CI: 1.25-1.34; P < 0.0001), gastrointestinal AEs (ROR = 1.04; 95% CI: 1.01-1.08; P = 0.0117), hepatobiliary AEs (ROR = 1.12; 95% CI: 1.07-1.17; P < 0.0001), and renal and urinary AEs (ROR = 1.06; 95% CI: 1.01-1.11; P = 0.0195) compared to anti-PD-L1 therapies. Conversely, anti-PD-L1 therapies had higher rates of endocrine AEs (ROR = 1.31; 95% CI: 1.25-1.38; P < 0.0001), skin and subcutaneous tissue AEs (ROR = 1.43; 95% CI: 1.37-1.49; P < 0.0001), and musculoskeletal and connective tissue AEs (ROR = 1.33; 95% CI: 1.26-1.39; P < 0.0001) compared to anti-PD-1 therapies. Conclusions: Our study provides insights into the adverse event profiles of selected anti-PD-1 and anti-PD-L1 therapies in a real-world clinical setting. Further prospective studies are essential to enhance our understanding of the comparative safety profiles of these agents, guiding personalized treatment decisions and, ultimately, advancing patient outcomes.

Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis.

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.

Transcriptome Profiling Unveils Key Genes Regulating the Growth and Development of Yangzhou Goose Knob.

Goose is one of the most economically valuable poultry species and has a distinct appearance due to its possession of a knob. A knob is a hallmark of sexual maturity in goose (Anser cygnoides) and plays crucial roles in artificial selection, health status, social signaling, and body temperature regulation. However, the genetic mechanisms influencing the growth and development of goose knobs remain completely unclear. In this study, histomorphological and transcriptomic analyses of goose knobs in D70, D120, and D300 Yangzhou geese revealed differential changes in tissue morphology during the growth and development of goose knobs and the key core genes that regulate goose knob traits. Observation of tissue sections revealed that as age increased, the thickness of the knob epidermis, cuticle, and spinous cells gradually decreased. Additionally, fat cells in the dermis and subcutaneous connective tissue transitioned from loose to dense. Transcriptome sequencing results, analyzed through differential expression, Weighted Gene Co-expression Network Analysis (WGCNA), and pattern expression analysis methods, showed D70-vs.-D120 (up-regulated: 192; down-regulated: 423), D70-vs.-D300 (up-regulated: 1394; down-regulated: 1893), and D120-vs.-D300 (up-regulated: 1017; down-regulated: 1324). A total of 6243 differentially expressed genes (DEGs) were identified, indicating varied expression levels across the three groups in the knob tissues of D70, D120, and D300 Yangzhou geese. These DEGs are significantly enriched in biological processes (BP) such as skin morphogenesis, the regulation of keratinocyte proliferation, and epidermal cell differentiation. Furthermore, they demonstrate enrichment in pathways related to goose knob development, including ECM-receptor interaction, NF-kappa B, and PPAR signaling. Through pattern expression analysis, three gene expression clusters related to goose knob traits were identified. The joint analysis of candidate genes associated with goose knob development and WGCNA led to the identification of key core genes influencing goose knob development. These core genes comprise WNT4, WNT10A, TCF7L2, GATA3, ADRA2A, CASP3, SFN, KDF1, ERRFI1, SPRY1, and EVPL. In summary, this study provides a reference for understanding the molecular mechanisms of goose knob growth and development and provides effective ideas and methods for the genetic improvement of goose knob traits.

Comparison of three methods for collecting interstitial fluid from subcutaneous tissue in mini pigs

Interstitial fluid, owing to its similarity to blood components and higher sensitivity and specificity, finds widespread application in disease diagnosis and tumor marker detection. However, collecting interstitial fluid, particularly from the deep subcutaneous connective tissue, remains challenging.•This study aimed to compare three different collection methods - push-pull perfusion, multi-filament nylon thread implantation, and tissue centrifugation - for collecting interstitial fluid from the subcutaneous connective tissue layer of mini-pigs. High-performance ion chromatography was employed to analyze the conventional cation components in the samples and compare ion composition analysis between the different methods.•Results indicated that while the distribution of conventional cations in the interstitial fluid collected by the three methods was generally consistent, there were slight variations in the detection rates and concentrations of different ions. Hence, suitable collection methods should be selected based on the ions or collection sites of interest.

Radiation-induced morphea-an overview

Radiation-induced morphea is afibro-inflammatory remodelling process of the subcutaneous connective tissue caused by ionising radiation, most commonly in the context of breast cancer treatment. The underlying pathomechanisms and putative risk factors are unknown. Therefore, misdiagnosis and inappropriate treatment pose asignificant problem in the care of those patients. The aim of the study was to provide an overview as well as guidance for the diagnosis and treatment of radiation-induced morphea based on current case reports and review articles. Radiation-induced morphea is arare condition that represents an interdisciplinary challenge for (gynaecological) oncology, radiotherapy and dermatology. Frequent misdiagnoses include infection (erysipelas), cancer recurrence or radiation dermatitis. Early histological diagnosis and the initiation of anti-inflammatory therapy using topical glucocorticoids or calcineurin inhibitors in combination with phototherapy and/or methotrexate are the most relevant success factors for an adequate clinical response.

Lipedema Reduction Surgery Improves Pain, Mobility, Physical Function, and Quality of Life: Case Series Report.

Lipedema is a chronic inflammatory subcutaneous adipose-rich connective tissue disease affecting millions of women worldwide. Disproportionate fat accumulation on the extremities characterized by heaviness, tenderness, and swelling can affect function, mobility, and quality of life. Treatments include conservative measures and lipedema reduction surgery (LRS). Here, we report lipedema comorbidities and surgical techniques, outcomes measures, and complications after LRS. This is a single outpatient clinic retrospective chart review case series of comorbidities and complications in 189 women with lipedema. Bioelectrical impedance analyses, knee kinematics, gait, physical examinations, Patient-Reported Outcomes Measurement Information System, and RAND Short Form-36 questionnaires collected before and after LRS were analyzed for 66 of the 189 women. Hemoglobin levels were measured by transdermal hemoglobin monitor (Masimo noninvasive hemoglobin monitoring; Irvine, Calif.). Common comorbidities in 189 women were hypermobile joints (50.5%), spider/varicose veins (48.6/24.5%), arthritis (29.1%), and hypothyroidism (25.9%). The most common complication in 5.5% of these women after LRS was lightheadedness with a 2-g reduction or more in hemoglobin. After conservative measures and LRS in 66 women, significant improvements (P ≤ 0.0009) were found for: (1) knee flexion (10 degrees); (2) gait; (3) Patient-Reported Outcomes Measurement Information System T-score (16%); (4) mobility questions: gait velocity, rising from a chair, stair ascent; (5) RAND Short Form-36 scores: physical functioning, energy/fatigue, emotional well-being, social function, general health; (6) and Bioelectrical impedance analyses total and segmental body fat mass. LRS provided significant improvements to women with lipedema using direct physical measurements and validated outcome measures, comparable to those seen after total knee replacement.

A Case Report: High-Grade Urothelial Carcinoma in the Renal Pelvis with Complete Kidney and Ureter Duplication Featuring Heterologous Differentiation

This report describes a considerably rare case of high-grade urothelial carcinoma of the renal pelvis and ureter, presenting with heterologous differentiation, in a patient with bilateral duplicated kidneys. A 73-year-old male experienced intermittent gross hematuria for 5 months, accompanied by lower back and abdominal pain. Ultrasound and computed tomography scans revealed bilateral renal and ureteral duplication with multiple tumors in the left renal pelvis. A total nephroterectomy and bladder cuff resection were performed on the left two nephrons. Multiple space-occupying lesions were identified in the left renal pelvis and ureter. Histopathological examination showed poorly differentiated and diverse tumor cells, manifesting as sarcomatoid carcinoma, papillary adenocarcinoma, and infiltrating high-grade urothelial carcinoma. The tumor infiltrated the subcutaneous fibrous connective tissue of the renal pelvis and the full thickness of the ureter. Given the rarity of recurrent renal urothelial carcinoma with heterogeneous differentiation, comprehensive imaging and pathological assessments are vital to delineate the nature of the lesion and the direction of tissue pathological heterologous differentiation. These evaluations guide early radical surgical interventions, improving survival rates.

Evaluation of the biocompatibility of various self-adhesive resin cements on subcutaneous connective tissue: An in vivo study

Background: The purpose of the study was to examine the subcutaneous connective tissue reaction to three self-adhesive resin cements.
 Methods: Sixty-three polyethylene tubes were filled with three different self-adhesive resin cements (Group Z [Zirconite], Group P [Panavia SA], and Group H [High Q Bond]). Twenty-one polyethylene tubes remained empty and were used as controls (Group C). All tubes were implanted into the subcutaneous tissue of the 21 rats. Specimens from each cement type were obtained at 7, 30, and 90 days. Quantitative assessments of inflammatory cells were performed in 5 different areas of each specimen.
 Results: All animals survive during the follow-up periods except two rats. The mean values of inflammatory cells at 90 days were 14 (±1.8), 15.1 (±3.5), 96 (±12.1), 16 (±2.1) in Groups C, H, P, and Z, respectively. The thicknesses of the fibrous capsule decreased significantly with time in all groups except Group P.
 Conclusion: Biocompatibility of self-adhesive resin cements was material-dependent. High Q Bond and Zirconite exhibited satisfactory biocompatibility; however, Panavia demonstrated a moderate inflammatory response at 90 days.

Effects of catgut embedding and PGLA embedding at "Zusanli" (ST 36) on skin mast cells, substance P and histamine in healthy rats

To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding. One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells. There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05). Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.

Design and Study of Nanoceria Modified by 5-Fluorouracil for Gel and Polymer Dermal Film Preparation.

In this work we studied nanoceria (CeO2NPs) and nanoceria modified by 5-fluorouracil (5FU) as potential APIs. Nanoceria were synthesized by precipitation in a matrix of hydroxyethyl cellulose or hydroxypropylmethyl cellulose, using cerium (III) nitrate and meglumine. Nanoceria properties were estimated by UV, FTIR and X-ray photoelectron spectra; scanning electron and atomic force microscopy; powder X-ray diffraction patterns and energy dispersive X-ray microanalysis. The cytotoxicity of nanoceria and polymer-protected nanoparticles was evaluated using the established cell line NCTC clone 929 (C3H/An mouse, subcutaneous connective tissue, clone of L. line). The morphology and metabolic activity of nanoparticles at 10 μg∙mL-1 of cells was not significant. In addition, the cytotoxic effects of nanoceria were assessed on two human colorectal cancer cell lines (HT29 and HCT116), murine melanoma B16 cells and normal human skin fibroblasts. An inhibitory effect was shown for HCT116 human colorectal cancer cells. The IC50 values for pure CeO2NPs and CeO2NPs-5FU were 219.0 ± 45.6 μg∙mL-1 and 89.2 ± 14.0 μg∙mL-1, respectively. On the other hand, the IC50 of 5FU in the combination of CeO2NPs-5FU was 2-fold higher than that of pure 5FU, amounting to 5.0 nmol∙mL-1. New compositions of nanoceria modified by 5-fluorouracil in a polymer matrix were designed as a dermal polymer film and gel. The permeability of the components was studied using a Franz cell.

A clinical case of edematous syndrome: diagnostic search and treatment tactics of a complex patient in compliance with the internarial and domestic recommendations

Edematous syndrome is quite common in modern clinical practice. Swelling is one of the most common complaints that cause the patient to consult a doctor and often become the first clinical manifestation of many diseases. Fluid makes up approximately 3/5 of the human body weight, 70% of which is located in cells, and about 30% is extracellular. There is a constant exchange of electrolytes and other substances involved in metabolism between the cell and the extracellular fluid. Subcutaneous connective tissue under normal conditions contains a minimal amount of fluid. Edema fluid formed from blood plasma, which in pathological conditions under the influence of various factors is unable to retain water in the vascular bed, and water accumulates in excessive amounts in the tissues. Often, a patient refers to a doctor with the main complaint — the appearance of edema, and the correct interpretation of the origin of edema is important at this stage, because they are often a marker that reflects the severity and/or decompensation of the disease. Therefore, a detailed and comprehensive differential diagnosis of the edematous syndrome allows choosing the optimal tactics of the patient’s treatment.&#x0D; The authors present a clinical case of diagnostic search and treatment tactics for edematous syndrome based on global and national recommendations. Patient V., 1983 year of birth, on May 8th, 2023, visited a nephrologist at the L. T. Mala National Therapy Institute. She believed that kidney disease caused swelling of her face and lower limbs. However, considering the long history of intestinal dysfunction, protein loss and edema, the case was revised as a manifestation of gastroenterological pathology. The patient was referred to a gastroenterologist. An extensive diagnostic search was conducted, which allowed not only to establish the correct diagnosis, but also to administer an effective therapy.

Effect of acupuncture pretreatment of "Quchi"(LI11) and "Xuehai" (SP10) on mast cells and IL-33/ST2 in rats with urticaria

To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01，P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.

In Vivo Assessment of the Calcium Salt-Forming Ability of a New Calcium Silicate-Based Intracanal Medicament: Bio-C Temp

Calcium salt precipitation induced by intracanal medicaments contributes to the formation of apical hard tissue during apexification. This study compared the calcium salt-forming ability of a new calcium silicate-based intracanal medicament (Bio-C Temp) with that of two commercial calcium hydroxide pastes (Calcipex Plane II and Vitapex) in a rat subcutaneous implantation model. Polytetrafluoroethylene tubes containing each of the three materials were subcutaneously implanted in 4-week-old male Wistar rats. After 28 days, the composition and amount of calcium salts formed at the material-tissue interface were assessed using micro-Raman spectroscopy, X-ray diffraction, and elemental mapping. The tested materials produced white precipitates that had Raman spectra with peaks corresponding to hydroxyapatite and calcite. X-ray diffraction detected hydroxyapatite formation on Calcipex Plane II and Vitapex implants, as well as calcite formation on all three materials. Elemental mapping revealed that Bio-C Temp generated significantly smaller calcium- and phosphorus-rich calcified regions within the subcutaneous connective tissue than Vitapex. These results indicate that Bio-C Temp produced less calcium salt in rat subcutaneous tissue than Vitapex, although all materials formed hydroxyapatite and calcite in rat subcutaneous tissue. Bio-C Temp could be less effective than Vitapex in promoting apical hard tissue formation during apexification.

A Case of Myiasis in a Bitting Wound in a Red Fox (Vulpes vulpes)

In this case report, a female adult red fox (Vulpes vulpes) found exhausted by the villagers in rural area of Eskişehir constituted the study material. A rare myiasis disease was diagnosed in the Red Fox (Vulpes vulpes) who was examined in the Surgery Clinic of the Veterinary Health Application and Research Center. Myiasis is a clinically important condition that can lead to a wide variety of diseases caused by fly larvae. In the case under consideration, multiple puncture wounds containing skin and subcutaneous connective tissues were detected in the thoracic region. The exhausted fox was restrained without the need for any anesthetic procedure, and the wound area was shaved, wound debridement was performed with polyvinyl iode and the larvae were removed manually with forceps. The treatment was terminated with a favorable prognosis, as the red fox was compliant with the treatment during the examination and recovery period and no extra systemic and wound complications were encountered. In conclusion, myiasis, which is rarely formed in the injuries of red foxes encountered in the wild, and the formation of a rapid recovery process with a routine treatment were discussed in order to inform our colleagues and readers and increase their experience.

Unusual Site for Fibro-lipoma – A Case Report

Lipomas and Sebaceous cysts are the most common lumps found in the subcutaneous area. Fibro-lipoma a rare benign tumor, is comprises of both fibrous connective tissues and adipose cells. Although it can be anywhere in the human body, where these tissues are present. But they are rare in the lower extremities. The differential diagnosis of lump in the foot may be challenging, especially when access to special imaging tools is limited in some practice. We are reporting a solitary large fibro-lipoma on the dorsal aspect of the foot in a middle-aged male patient. Keywords: Lumps, Fibro-lipoma, Subcutaneous Connective Tissues, Adipose Cells, Dorsal Aspet Foot, How to Cite This: Yousaf A, Abbas S. Unusual Site for Fibro-lipoma – A Case Report. Isra Med J. 2022; 14(3): 127-128. DOI: https://doi.org/10.55282/imj.cr96

Assessing reliability and validity of different stiffness measurement tools on a multi-layered phantom tissue model

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools’ (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75–0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable.

MANAGING THE MOST COMMON COMPLICATIONS OF RADIATION THERAPY IN PATIENTS WITH HEAD AND NECK CANCER

Radiation therapy is widely used approach in treatment of head and neck cancer, unfortunately it leaves consequences that are influencing the patients’ life in a negative way. During and after the treatment with ionizing irradiation it affects not only the malignant area that is being treated, but also the surrounding tissues and organs that are located near the region that is targeted (oral mucosa, jaw bones, teeth, salivary glands, surrounding muscles and the temporomandibular joints), leaving changes in their structure and functions. Many of the patients that are treated, have not been prepared optimally for the radiation treatment, what also affects the post operative condition of their tissues and organs that are located nearby to the radiation treated area. The aim of this study was to define the most common postradiation complications in patients with head and neck cancer and to evaluate the efficiency of the solutions that are used to manage them. For this study were analyzed in details 37 published articles on the studied topic, the research was done online using the data bases NCBI, Cochrane Library, Medline, PubMed and Webmd. The inclusion criteria were: studies made in vivo; studies written in English; case reports on head and neck cancer patients; surveys on patients after radiation therapy; studies on patients with intraoral complications from after radiation therapy. Results showed that radiation induced complications in the head and neck cancer patients can be classified in three groups as early, intermediate and late changes. The most common changes were found in the tissues (mucosa, skin, subcutaneous connective tissues, salivary glands, the bone tissues and the teeth), resulting with: hyposalivation (xerostomia), mucositis, opportunistic infections, radiation caries, dysphagia, altered taste and difficulties with the chewing and swallowing. Many studies have shown that the percent of damage on the oral mucosa is strongly related to the radiation dose and the type of ionizing irradiation that patients are being treated with. Treatment consists of application of lubricants; usage of substitutes for saliva; and stimulants for the saliva production, with preparations like pilocarpine and cevimeline, and electro stimulation. The loss of the taste after the treatment can be partial or total. Mostly affected are the sour and bitter tastes, rarely the sweet and the salty taste, and very rare is total loss on all of the flavors. Fortunately in most of the studied cases has been show that the changes in the taste were reversible after a period of time, in some cases a few months and in others it can happen even up to a few years until it reaches total recovery. It is crucial to implement more solutions and to find new ways to manage the complications that follow after the irradiation, so the quality of the life in these patients can be spared in any possible way. Using the new approaches such as IMRT and VMAT on these patients, could also improve their condition after the treatment, and reduced dosage of the irradiation also could be tested and implemented if it is possible.