Skin Biopsy Research Articles

Metagenomics reveals unique gut mycobiome biomarkers in psoriasis.

In present, the diagnosis of psoriasis is mainly based on the patient's typical clinical manifestations, dermoscopy and skin biopsy, and unlike other immune diseases, psoriasis lacks specific indicators in the blood. Therefore, we are required to search novel biomarkers for the diagnosis of psoriasis. In this study, we analyzed the composition and the differences of intestinal fungal communities composition between psoriasis patients and healthy individuals in order to find the intestinal fungal communities associated with the diagnosis of psoriasis. We built a machine learning model and identified potential microbial markers for the diagnosis of psoriasis. The results of AUROC (area under ROC) showed that Aspergillus puulaauensis (AUROC=0.779), Kazachstania africana (AUROC=0.750) and Torulaspora delbrueckii (AUROC=0.745) had high predictive ability (AUROC>0.7) for predicting psoriasis, While Fusarium keratoplasticum (AUROC=0.670) was relatively lower (AUROC<0.7). The strategy based on the prediction of intestinal fungal communities provides a new idea for the diagnosis of psoriasis and is expected to become an auxiliary diagnostic method for psoriasis.

EXPLORING THE CLINICAL SPECTRUM AND INDIVIDUALIZED DRUG THERAPY IN PEMPHIGUS VULGAR IS: A CASE SERIES

Pemphigus Vulgaris (PV) is a rare, chronic, life-threatening immunopathogenic disease that is characterized by flaccid, easily ruptured intraepithelial bullae, mostly found on the skin and mucous membranes. Attempting to keep the treatment plan of this potentially deadly disorder in primary focus, we have observed five patients with Pemphigus vulgaris. All patients have been presented with oral lesions or ulcers resulting in difficulty in swallowing. Patient one had a family history of the disease, while the other patients did not present any family history. All five patients had diverse ways of dealing with the disease before getting hospitalized. Microcytic anaemia and hypoalbuminemia have been found in all of them. Patients 1 and 3 had leucocytosis, while patient three had platelets in clumps with Hypercobalaminemia and the presence of ketone bodies in urine analysis. The Desmoglein I and Desmoglein III Antibody along with Punch biopsy results, confirmed the diagnosis. All patients were given systemic corticosteroids on hospitalization, but the case series observed variations in the dosages emphasizing individualized drug therapy. Some developed psychological impairment, some had generalized headaches or cardiac impairment, while ophthalmic involvement was seen in the other patients. Healthcare providers should do close monitoring while providing individualized drug therapy to prevent any systemic involvement and further complications.

Effect of benralizumab on inflammation in skin after intradermal allergen challenge in patients with moderate to severe atopic dermatitis

BackgroundAtopic dermatitis is a skin barrier dysfunction characterized by tissue eosinophilia. Objective: In patients with atopic dermatitis (AD) we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge. Methods20 patients with moderate to severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses q4wk 30 mg subcutaneous benralizumab (n=9) to placebo (n=11). Allergen and saline control intradermal challenges were conducted before and after treatment with skin biopsies collected 24 hours after challenge. Early (ECR) and late cutaneous responses (LAR) were measured by skin wheal size. Eosinophils and IL-5Rα -bearing cells including eosinophil progenitor cells (EoP), basophils and mast cells were measured in papillary dermis by immunofluorescence microscopy, and EoP, hemopoietic progenitor cells (HPC) and ILC2 were measured in blood by flow cytometry. Outcomes were compared between placebo and benralizumab treatment groups using Mann-Whitney U-test. ResultsBenralizumab reduced eosinophils in blood (p<0.0001), and allergen challenged skin as measured by H&E and EG2 (p<0.05). Benralizumab lowered levels of EoP, mast cells and basophil numbers in skin, as well as EoP, HPC and ILC2s in blood (all p<0.05). There was a trend for improvement in the ECR response (p=0.095), but no effect on the LCR. ConclusionIn patients with moderate to severe AD, benralizumab treatment significantly inhibited accumulation of eosinophils and other IL-5Rα expressing cells in the papillary dermis after intradermal allergen challenge. Targeting IL-5Rα positive cells did not modulate the size of the allergen-induced skin wheal. (ClincialTrials.gov number, NCT03563066).

Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats

ObjectiveTo assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DesignWistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. ResultsThe 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). ConclusionNaltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.

Functional effects of the spatial-varying lens mechanical properties in accommodation

Lens biomechanical properties are critical for our eyes to accommodate. While it is well understood that lens mechanical properties change with age, different experimental techniques have been used over the years, with varying results on how the lens modulus changes. In this study, we developed a spatial-varying elasticity model to characterize the overall elastic modulus of the lens and establish its effect on accommodation. First, to validate the model, ex vivo porcine lenses underwent compression testing using biopsy punches of different diameters to change the percentage of nucleus within samples. Importantly, we found that, indeed, changing nucleus/cortex spatial ratio produces dramatic (∼7-fold) increase in overall sample modulus. Comparing the model with human lens spatial ratios, we demonstrate how changing spatial mechanics are more influential than peak modulus changes on overall elastic modulus. Next, in vivo clinical measurements of the spatial-varying lens modulus were used to generate a simplified mechanical-optical model of accommodation. We defined an ellipsoid lens with patient-derived modulus and geometry measurements, and a statics simulation and ray tracing analysis were performed through the deformed and undeformed lens. The resulting accommodation estimates agree with general accommodation expectations.

PRIMARY CUTANEOUS ASPERGILLOSIS IN A 13-YEAR-OLD BOY WITH BONE MARROW APLASIA: CASE REPORT

Cutaneous aspergillosisis a rare condition, and while rare in immunocompetent individuals, it predominantly affects immunosuppressed patients, particularly those with hematological-oncological disorders within the pediatric demographic. Herein, we present a 13-year-old boy under follow-up for bone marrow aplasia. The child developed long-lasting fever and papulous and ulcerous indurated skin lesions on his whole body. Blood count showed agranulocytosis with neutrophils count of 10/μl. Thoracic, abdominal and pelvic Computed Tomography (CT) scan has revealed bilateral alveolar syndrome in the lungs. Skin biopsy revealed cutaneous aspergillosis. Despite treatment, the boys condition did not improve, and he passed away 2 weeks following his hospital admission because of septic shock. Cutaneous aspergillosis is due to Aspergillus flavus and A. fumigatus, for primary and secondary (invasive) cases, respectively. The rapid progression of this disease from the initial cutaneous infectious region necessitates prompt medical intervention to avoid increasing the risk of mortality. This condition typically manifests after the fungus is directly inoculated through skin contact with contiguous infected areas or via hematogenous spread from a remote mycotic site to the skin.

Molecular analysis of human tick-bitten skin yields signatures associated with distinct spatial and temporal trajectories - A proof-of-concept study

Tick-associated diseases present challenges due to tridirectional interactions among host-specific responses, tick toxins and salivary proteins as well as microbes. We aimed to uncover molecular mechanisms in tick-bitten skin samples (cases) and contralateral skin samples (controls) collected simultaneously from the same participants, using spatial transcriptomics. Cases and controls analysed using NanoString GeoMx Digital Spatial Profiler identified 274 upregulated and 840 downregulated differentially expressed genes (DEGs), revealing perturbations in keratinization and immune system regulation. Samples of skin biopsies taken within 72 h post tick-bite DEGs had changes in protein metabolism and viral infection pathways as compared to samples taken 3 months post tick-bite, which instead displayed significant perturbations in several epigenetic regulatory pathways, highlighting the temporal nature of the host response following tick bites. Within-individual signatures distinguished tick-bitten samples from controls and identified between-individual signatures, offering promise for future biomarker discovery to guide prognosis and therapy.

The Diagnostic Accuracy of Electrical Impedance Spectroscopy-Assisted Colposcopy, HPV mRNA Test, and P16/Ki67 Immunostaining as CIN2+ Predictors in Greek Population.

To evaluate the diagnostic accuracy of Electrical Impedance Spectroscopy (EIS)-assisted colposcopy in detecting CIN2+ Greek women towards standalone colposcopy, HPV mRNA testing, and p16/Ki67 immunostaining. We conducted a cross-sectional observational study at the Cervical Pathology Clinic of the 2nd Obstetrics-Gynecology University Department of Hippokration Hospital Thessaloniki involving 316 patients from January 2022 to August 2023. All participants provided liquid-based cervical samples for cytology, HPV mRNA testing, and p16/Ki67 immunostaining. Subsequently, participants underwent both standalone colposcopy and EIS/ZedScan-assisted colposcopy, followed by cervical punch biopsies. The incorporation of EIS significantly enhanced the sensitivity of colposcopy, increasing it from 54.17% to 100%, equivalent to that of HPV mRNA testing and p16/Ki67 immunostaining, while achieving a high specificity (95.45%). The specificities observed with EIS/ZedScan-assisted and standalone colposcopy were notably superior to those of HPV-related biomarkers (HPV mRNA test and p16/Ki67 immunostaining). When compared to standalone colposcopy, HPV mRNA testing, and p16/Ki67 immunostaining, EIS/ZedScan-assisted colposcopy demonstrated the most favorable combination of Positive and Negative Predictive Values, at 90.57% and 100%, respectively. The inclusion of EIS/ZedScan in colposcopy led to the detection of 44 additional cases of true CIN2+ (100% of the total CIN2+ confirmed histologically) that were missed by standalone colposcopy. This discovery suggests a 45.83% increase in the detection of CIN2+ cases. The integration of EIS with colposcopy has demonstrated effectiveness in detecting cervical lesions, resulting in a significant detection increase of CIN2+ cases while offering optimal levels of sensitivity, specificity, and predictive values for CIN2+ detection.

Phenotyping peripheral neuropathies with and without pruritus: a cross-sectional multicenter study.

Pruritus often escapes physicians' attention in patients with peripheral neuropathy (PNP). Here we aimed to characterize neuropathic pruritus in a cohort of 191 patients with PNP (large, mixed, or small fiber) and 57 control subjects with deep phenotyping in a multicenter cross-sectional observational study at 3 German sites. All participants underwent thorough neurological examination, nerve conduction studies, quantitative sensory testing, and skin biopsies to assess intraepidermal nerve fiber density. Patients filled in a set of questionnaires assessing the characteristics of pruritus and pain, the presence of depression and anxiety, and quality of life. Based on the severity of pruritus and pain, patients were grouped into 4 groups: "pruritus," "pain," "pruritus and pain," and "no pruritus/no pain." Although 11% (21/191) of patients reported pruritus as their only symptom, further 34.6% (66/191) reported pruritus and pain. Patients with pain (with or without pruritus) were more affected by anxiety, depression, and reduced quality of life than control subjects. Patients with pruritus (with and without pain) had increases in cold detection threshold, showing Aδ-fiber dysfunction. The pruritus group had lower intraepidermal nerve fiber density at the thigh, concomitant with a more proximal distribution of symptoms compared with the other PNP groups. Stratification of patients with PNP by using cross-sectional datasets and multinominal logistic regression analysis revealed distinct patterns for the patient groups. Together, our study sheds light on the presence of neuropathic pruritus in patients with PNP and its relationship with neuropathic pain, outlines the sensory and structural abnormalities associated with neuropathic pruritus, and highlights its impact on anxiety levels.

Pigment epithelium derived factor drives melanocyte proliferation and migration in neurofibromatosis café au lait macules

AbstractBackgroundRASopathies, which include neurofibromatosis type 1 (NF1), are defined by Ras/mitogen‐activated protein kinase (Ras/MAPK) pathway activation. They represent a group of clinically related disorders often characterised by multiple Café au Lait Macules (CALMs).ObjectivesTo determine, using in depth transcriptomic analysis of NF1 melanocytes from CALM and unaffected skin, (1) the gene(s) responsible for melanocyte proliferation and migration, and (2) the activated signalling pathway(s) in NF1 melanoma.MethodsClassical NF1 (n = 2, who develop tumours) and 3bp deletion NF1 (p. Met992del, who do not develop tumours) (n = 3) patients underwent skin biopsies from CALM and unaffected skin. Melanocytes were isolated and propagated, with five replicates from each tissue sample. DNA and RNA were extracted for mutational analysis and transcriptomic profiling with six replicates per sample. Mechanistic determination was undertaken using melanocyte and melanoma cell lines.ResultsAll CALMs in NF1 were associated with biallelic NF1 loss, resulting in amplification of Ras/MAPK and Wnt pathway signalling. CALMs were also associated with reduced SERPINF1 gene expression (and pigment epithelium‐derived factor (PEDF) levels, the reciprocal protein), a known downstream target of the master regulator of melanocyte differentiation microphthalmia‐associated transcription factor (MITF), leading to increased melanocyte proliferation, migration and invasion. In classical NF1 and melanoma, but not 3bp deletion NF1, there was also activation of the PI3K/AKT pathway. Pigment epithelium‐derived factor was found to reduce cell proliferation and invasion of NF1 melanoma.ConclusionsMelanocyte proliferation and migration leading to CALMs in NF1 arises from biallelic NF1 loss, resulting in RAS/MAPK pathway activation, and reduced expression of the tumour suppressor PEDF. Activation of the PI3K/AKT pathway in classical NF1 and NF1 melanoma may facilitate tumour growth.

Altering CO2 Laser Pulse Energy Settings Did Not Influence Differential Gene Transcription in Normal Skin in a Red DurocPig Model.

Fractional ablative CO2 lasers are used clinically to treat cutaneous burn scars with reported varying degrees of effectiveness. It was hypothesized that different laser pulse energy settings may lead to differential gene transcription in a porcine model. Uninjured skin from red Duroc pigs was treated with a fractional ablative CO2 laser set to 70, 100, or 120 mJ across the abdomen (n = 4 areas per treatment). Punch biopsies of both treated and untreated sites were taken before treatment (baseline), at 30 min, and at each hour for 6 h and stored in All-Protect tissue reagent. The biopsies were then used to isolate RNA, which was subsequently used in qRT-PCR for eight genes associated with wound healing and the extracellular matrix: CCL2, IL6, FGF2, TIMP1, TIMP3, COL1A2, MMP2, andDCN. RPL13a was used as a housekeeping gene to normalize the eightgenes of interest. One-way ANOVA tests were used to assess for differences among laser pulse energies and two-way ANOVA tests were used to assess the differences between treated and untreated areas. While six of the eight genes were upregulated after treatment (p < 0.05), there were no significant differences in gene expression between the different laser pulse energies for any of the eight genes. While laser treatment is correlated with a positive and significant upregulation for six of the eight genes 4 h after intervention, the pulse energy settings of the laser did not lead to a statistically significant difference in gene transcription among the treatment areas. Different laser pulse energies may not be required to induce similar cellular responses in a clinical setting.

Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

The global resurgence of syphilis necessitates vaccine development. We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

(096) UNDERSTANDING THE RELATIONSHIP BETWEEN CHRONIC PAIN AND DEPRESSION IN LOCALIZED PROVOKED VULVODYNIA

Abstract Introduction Localized provoked vulvodynia (LPV) is a disease characterized by chronic pain in the vulva in response to touching the vulvar vestibular epithelium. As with other chronic pain disorders, vulvodynia is often found accompanied with depression, and depressive symptoms aggravate pain severity and persistence. While there is clear evidence of a connection between chronic vulvar pain and depression, the mechanism of this bidirectional relationship is largely unknown. Accumulating evidence suggests that inflammation plays a central role in depression. Since the pathophysiology of LPV also involves inflammation, we aim to better understand these relationships by pharmacologically inhibiting the enzyme that plays a key role in both inflammation and depression: soluble epoxide hydrolase (sEH). Objective To elucidate the role of sEH in localized provoked vulvodynia, which might be involved in the chronic pain and depression comorbidity prevalent in vulvodynia patients, and discuss the clinical significance of using sEH inhibitors, such as 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), for patients suffering from this condition. Methods Vulvar punch biopsies obtained from painful sites within the vulvar vestibule and non-painful sites within the external vulva of 6 LPV patients and 6 age/race-matched healthy controls were used to generate a library of primary fibroblast strains. Cells were treated with the inflammatory instigator interleukin-1β (IL-1β) and TPPU. Quantitative PCR, Western blotting, and enzyme-linked immunosorbent assays were used to assess the effects of sEH inhibition. Statistical analysis was performed using GraphPad Prism 10.0.2. Comparisons among groups were performed using the one-way analysis of variance (ANOVA) or two-way ANOVA, followed by post-hoc Tukey test. Results Vulvodynia patients produce increased levels of pro-inflammatory cytokines, namely interleukin-6 (IL-6) and prostaglandin E2 (PGE2), when compared with controls. Interestingly, mRNA (P = 0.0091) and protein (P = 0.0198) levels of sEH were significantly lower in the painful vestibule of these patients. When sEH was inhibited with TPPU, we observed a significant decrease in IL-6 levels (P = &amp;lt;0.0001), but not PGE2 (P = 0.6452). These preliminary findings are of fundamental importance as cytokines can directly contribute to the development of depressive symptoms. Conclusions Patients with vulvodynia are more likely to develop depressive symptoms than patients without vulvar pain. Likewise, patients with depression are more likely to develop vulvodynia than patients without depression. Our results suggest that sEH may play a role in this bidirectional mechanism, which could serve as a novel therapeutic target for chronic pain and depression comorbidity. Disclosure No.

Upper Blepharoplasty through Infrabrow Skin Excision to Treat Dermatochalasis with Lateral Hooding and Medial Orbital Fat Loss in Selected Patients.

Dermatochalasis with lateral hooding and medial orbital fat loss are common signs of aging in the upper eyelid. Removing the excess skin in this area through infrabrow skin excision can effectively lift the loose skin of the upper eyelid and minimizes visible scarring. Additionally, we have identified three compartments of orbital fat prolapse based on orbital anatomy. Transferring volume from the lateral compartment to the intermediate region can flatten the lateral upper eyelid and create medial fullness, which ultimately rejuvenates the upper eyelid. This study presents an operative method for correcting age-related changes in the upper eyelid using this technique. A total of 34 eyelids from 17 patients underwent a surgical procedure involving infrabrow skin excision, along with repositioning and lifting of lateral orbital fat. The inclusion criteria consisted of patients with moderate to severe upper eyelid dermatochalasis, coupled with middle fat loss and lateral hooding. To correct lateral hooding and restore midfacial fullness, lateral orbital fat was repositioned to an intermediate position, and the orbicularis oculi muscle was fold-sutured to the corrugator supercilii muscle. The mean age of the patients was 55.59 ± 3.20 years, with a range of 48 to 61 years. The mean follow-up period was 9.94 ± 1.35 months, ranging from 8 to 12 months. Patients were evaluated at 1-month, 3-month, and 6-month intervals. The Strasser system was used to evaluate the surgical outcomes at 3 months. All patients achieved good surgical outcomes, expressed through satisfactory cosmetic improvements, and improved visual field. The procedure effectively corrected lateral hooding and loss of middle orbital fat through infrabrow skin excision. No complications, such as wound dehiscence, lagophthalmos, noticeable scarring, ocular dyskinesia, or sensory changes, were observed. The combination of infrabrow skin excision, repositioning of lateral orbital fat, and lifting of the orbicularis oculi muscle effectively addresses moderate to severe dermatochalasis, lateral hooding, medial fat loss, and improves elasticity of the anterior wall of the upper lid in our patients. This procedure can produce satisfactory and long-lasting aesthetic results with an inconspicuous scar beneath the brow.

Necrotizing Soft Tissue Infection Management: a Clinical Case Study

Necrotizing soft tissue infection is a rare (0.4 cases per 100,000 population) but very severe pathology with a mortality rate up to 10%. The paper presents a clinical case of successful management of necrotizing soft tissue infection of the right arm, lateral wall of the chest and abdomen. The dynamics of the wound process was controlled by clinical, bacteriological, X-ray and ultrasound examinations. The cause of necrotizing soft tissue infection in this patient was the associated anaerobic nonclostridial and aerobic flora. Numerous surgical interventions were used to manage the patient; they were aimed at the excision of the necrotic tissue at the start of treatment, plastic surgery of postoperative wounds with local tissues was used at the end of treatment. The progression of the necrotic process was stopped after the third intervention. In addition to surgical treatment, the patient received antibacterial, detoxification, and immunostimulating therapy. Despite numerous staged surgeries with the excision of the necrotic skin, subcutaneous fat and fascia, it was possible to completely restore the patient’s ability to work.

Collodion Baby And Cholestasis: A Rare Case Report

Collodion baby with cholestasis is an uncommon condition. The term "collodion baby" refers to newborns with thick skin covering their entire body. Neonatal cholestasis is a form of conjugated cholestasis hyperbilirubinemia caused by reduced bile flow. The condition causes persistent jaundice (over two weeks) and elevated conjugated bilirubin. Genetic abnormalities or gene mutations have been reported in neonatal ichthyosis syndrome with cholestasis. A case report of a collodion baby, a rare congenital condition characterized by a parchment-like membrane covering the entire body, was brought to Dr. Soetomo General Academic Hospital. Prolonged jaundice was one of the other findings. A skin biopsy found characteristics consistent with the diagnosis of collodion in a newborn. The paediatric team managed this case, which was treated in collaboration with a dermatologist. This case showed that newborn collodion syndrome required skin care, cholestasis screening, and jaundice management from birth.

Anti-Inflammatory, Wound Healing, and Anti-Diabetic Effects of Pure Active Compounds Present in the Ryudai Gold Variety of Curcuma longa.

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

Assessment of Skin Biopsy as a Diagnostic Biomarker in CSF1R-Related Disorder.

To validate a recently published study in which skin biopsy was reported as a valuable alternative to brain biopsy in diagnosing CSF1R-related disorder (CSF1R-RD). Blinded evaluation of skin samples was performed by independent reviewers using light and electron microscopy collected from a group of CSF1R variant carriers (n = 10) with various genotypes (mono and biallelic), different stages of the disease (asymptomatic and symptomatic), and exposed to different therapies (glucocorticoids, hematopoietic stem cell transplantation, and TREM2 agonist), and from a group of healthy controls (n = 5). Biopsies from patients with CSF1R-RD at various disease stages were indistinguishable from controls determined using light microscopy and electron microscopy. We found no distinctive axonal pathology in skin biopsies collected from CSF1R variant carriers at all stages of the disease. Our results are consistent with clinical and neurophysiologic features of the CSF1R-RD, in that peripheral nervous system involvement has not been reported. Studies aiming to discover new biomarkers are important, but the results must be validated with larger numbers of patients and healthy controls. Based on blinded light and electron microscopic studies of skin biopsies, there is no evidence that CSF1R-RD is associated with distinctive changes in cutaneous peripheral nerves. This suggests that skin biopsy is not useful in diagnosis of CSF1R-RD. This study provides Class III evidence that skin biopsy does not distinguish those with CSF1R-RD, or carriers, from normal controls.

Diagnostic Utility of Immunofluorescence on Formalin-Fixed Paraffin-Embedded Skin Biopsy

Abstract Background: When immunofluorescence on the frozen section is insufficient or unavailable, salvage immunofluorescence techniques can be used on formalin-fixed, paraffin-embedded tissue. The goal of the current investigation was to evaluate the diagnostic value of paraffin immunofluorescence following proteinase K digestion on skin biopsy samples in comparison to fresh frozen immunofluorescence. Materials and Methods: It was standardized and compared to the immunofluorescence on fresh frozen tissue (IF-Frozen) for paraffin immunofluorescence by proteinase K digestion of formalin-fixed paraffin-embedded skin biopsies (IF-FFPE). The study included 50 native skin biopsy cases, and fluorescein isothiocyanate-labeled IgA, IgG, IgM, and C3 intensity levels were evaluated in each case. Results: A total of 50 cases of native skin biopsy were included in the study, and their intensities for IgA, IgG, IgM, and C3 antibodies were compared. The average staining intensities in each disease group for the antibodies had equal intensity or had a minor difference (1+)/significant difference (2+). Paraffin immunofluorescence, proteinase K digestion had the best correlation, that is, had either equal or minor difference (1+) with fresh frozen immunofluorescence. The difference of 2+ intensity of antibodies between IF-FFPE and IF-Frozen was noted mainly in C3 antibody on paraneoplastic pemphigus. IF-FFPE showed a sensitivity of 100%, 97.6%, 100%, and 81.6% for IgA, IgG, IgM, and C3, respectively, whereas the specificity was 100% for IgA, IgG, IgM, and C3. Limitations: Small sample size and and the employment of one method of antigen retrieval in IF-FFPE. Conclusion: Immunofluorescence techniques done on formalin-fixed paraffin-embedded tissue can serve as salvage techniques in cases where immunofluorescence on the frozen section may not be adequate or may not be available.

Acute Interstitial Inflammation on Skin Biopsies and Positive Tissue Cultures in Cellulitis Patients Are Associated a Worse Prognosis.

Cellulitis is a significant public health burden and lacks a gold standard for diagnosis. Up to 1/3 of patients are incorrectly diagnosed. The skin biopsy has been proposed as the gold standard. In this study, we evaluate the histopathologic characteristics and tissue culture positivity of biopsies in patients diagnosed with cellulitis seen by our inpatient dermatology consultation service. This retrospective cohort study examined patients who were hospitalized with a skin and soft tissue infection at our institution between 2011 and 2020 and underwent a skin biopsy. Those with a positive tissue culture were more likely to die within 30 days compared with those with negative tissue cultures (26% vs. 6%, P = 0.048). Patients who died within 30 days were more likely to have acute interstitial inflammation as a feature on histopathology (38%, P = 0.03). Single institutional design, unintentional exclusion of patients with organism-specific diagnosis, and selection for a medically complex patient population because of the nonroutine collection of biopsies. Positive tissue cultures and histopathology showing acute interstitial space inflammation on skin and soft tissue infection (SSTI) biopsies are associated with increased mortality and thus may serve as indicators of poor prognosis.