Inflammatory Connective Tissue Research Articles

Correlating Ultrastructural Changes in the Invasion Area of Colorectal Cancer with CT and MRI Imaging.

The cancer invasion of the large intestine, a destructive process that begins within the mucous membrane, causes cancer cells to gradually erode specific layers of the intestinal wall. The normal tissues of the intestine are progressively replaced by a tumour mass, leading to the impairment of the large intestine's proper morphology and function. At the ultrastructural level, the disintegration of the extracellular matrix (ECM) by cancer cells triggers the activation of inflammatory cells (macrophages) and connective tissue cells (myofibroblasts) in this area. This accumulation and the functional interactions between these cells form the tumour microenvironment (TM). The constant modulation of cancer cells and cancer-associated fibroblasts (CAFs) creates a specific milieu akin to non-healing wounds, which induces colon cancer cell proliferation and promotes their survival. This review focuses on the processes occurring at the "front of cancer invasion", with a particular focus on the role of the desmoplastic reaction in neoplasm development. It then correlates the findings from the microscopic observation of the cancer's ultrastructure with the potential of modern radiological imaging, such as computer tomography (CT) and magnetic resonance imaging (MRI), which visualizes the tumour, its boundaries, and the tissue reactions in the large intestine.

Antinuclear Antibodies in Systemic Lupus Erythematous – Their Complex Role and Clinical Significance in Diagnosis

Antinuclear antibodies (ANA) are a wide group of proteins directed against autologous cellular components, primarily nucleic acids and histones. Their levels are assessed using immunofluorescence on Hep-2 cells or a solid-phase ANA screening immunoassay to subsequently obtain titer value with positive cut-point of ≥1:80. Studies show that ANA can be found in 13% of general population, but typically they are associated with autoimmune conditions and inflammatory connective tissue diseases for example: systemic lupus erythematosus (SLE), sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, juvenile idiopathic arthritis, systemic sclerosis, inflammatory myopathies. ANA detection is especially important for SLE, where 2 antibody types - anti-Sm and anti-dsDNA - serve as an entry diagnostic criterion. With increasing patient screening for those antibodies, it is important to determine that alone, positive ANA assays cannot confirm nor deny any disease and to classify their presence as a marker of a disease it is required to satisfy additional additive criteria approved in 2019 by European League Against Rheumatism/American College of Rheumatology. SLE diagnosis can be made when patient collects 10 points from clinical or immunologic domains described by EULAR/ACR, which makes SLE diagnosis challenging and therefore, describing the guidelines is vital to remain cautious about overestimation of the position positive ANA values hold in clinical practice.In conclusion the positive ANA test may be a basis for diagnosis, when additional symptoms occur, but alone does not hold any diagnostic significance and may lead to unnecessary stress for patient.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemicrats.

Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

History and Familial Aggregation of Immune-Mediated Diseases in Sarcoidosis: A Register-Based Case-Control-Family Study

An autoimmune component in the cause of sarcoidosis long has been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause is limited. Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis? We conducted a case-control family study (2001-2020). Patients with sarcoidosis (N= 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N= 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95%CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs. Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7%vs4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95%CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95%CI, 0.97-3.65), thyroiditis (OR, 1.72; 95%CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95%CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95%CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95%CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95%CI, 1.00-1.93). IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms.

Clinical profile, laboratory parameters and management outcomes in an eight-year-old female with childhood lupus nephritis

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disorder characterized by widespread inflammation of connective tissues affecting the skin, joints, kidneys, heart, lungs and nervous system. SLE is most often diagnosed in women during the second to fourth decades of life, but 15-20% cases are found in childhood. Renal involvement occurs in the majority of childhood onset SLE (cSLE) patients and is often fatal and hence constitutes an important determinant of prognosis. Multidisciplinary care is necessary for children with lupus nephritis in terms of immunosuppressive regimes with a common goal of achieving and maintaining renal remission. Despite a low prevalence rate of cSLE, it manifests with fatal complications like lupus nephritis in majority of cases. Renal biopsy is gold standard for staging of lupus nephritis, thus, deciding the modality of management and prognostication of cSLE.

Pattern of Autoimmune Connective Tissue Diseases Among Patients Attending Al-Thawra Teaching General Hospital, Sana'a-Yemen

Background: Connective tissue is also called connectivum. Many autoimmune diseases affect the connective tissue and blood vessels, are often referred to as connective tissue disorders. Autoimmune diseases currently are estimated to affect 2-5% of the population in the developed countries. Aim: The aim of this study was to determine the pattern of autoimmune inflammatory connective tissue diseases among patients attending Al-Thawra teaching general hospital, Sana'a-Yemen. Method: This study is observational prospective study conducted at Al-Thawra hospital, Sana'a-Yemen, department of internal medicine, duration of the study was 12 months. Sample size was 137. Results: The results showed that systemic lupus erythematosus, antiphospholipid syndrome and rheumatoid arthritis have the highest prevalence. The main clinical presentations are arthritis, leg swelling and dyspnea. The main drugs used are corticosteroids, low molecular weight heparin, and rituximab. The proportion of females to males is 3.55 to 1. The age range 20 – 30 years is the highest representing 47% of the total patients. Patients from Sana'a, Taiz, and Ibb being the most common. Illiterates represent 63%, housewives represent 72% of the total patients. Conclusion: We conclude that autoimmune connective tissue diseases affect 8% of the total patients admitted to the internal medicine department. SLE is the most common autoimmune connective tissue disease encountered and represents 43% of total cases. Arthritis and leg swelling are the most common clinical presentations encountered; both represents 48% of the total presentations. Corticosteroids are the most common prescribed drugs, 45%. The aetiology of autoimmune connective tissue diseases is still not fully known. Immuno-modulators are needed to regulate the immune system. Physiotherapy is recommended beside medical therapy.

P030 Multiple autoantibody formation post COVID-19 infection

Abstract Background/Aims COVID-19 has been linked to the formation of a number of autoantibodies. This case is an important reminder to clinicians interpreting autoantibody results in conjunction with clinical manifestations. A previously fit 51 year old gentleman, with no prior history of autoimmune disease required admission with respiratory symptoms in April 2020 consistent with COVID-19 infection. His acute respiratory illness was complicated by empyema and left-sided pneumothorax requiring left pleural decortication and adhesiolysis under (VATS). Persistent respiratory symptoms and fatigue lead to investigations for long COVID. Positive antibodies detected were dsDNA 166IU/ml, Proteinase 3 antibodies 20IU/ml, Myeloperoxidase antibodies 32IU/ml, IgG anticardiolipin antibodies 90IU/ml and Glomerular basement membrane antibodies 351 IU/ml. Negative autoantibodies included ANA, RF, aCCP, b2GPI, smooth muscle, AMA and myositis related antibodies. Methods There were no clinical signs or symptoms of inflammatory arthropathy, vasculitis, thrombosis or connective tissue disease. Other investigations included a CT thorax showing no new lung lesions, unremarkable urine dipstick, normal urine ACR, normal US abdomen, CT sinuses and MRI brain. Results Trial course of prednisolone was given therapeutically due to long COVID symptoms. There was no significant impact on symptoms/ autoantibody titres thus steroids were discontinued. The patient was followed closely by the rheumatology team for two years. During that time, the autoantibody levels gradually decreased, and he did not develop clinical signs of autoimmune disease. His long COVID symptoms persisted, and he remains under the long COVID clinical team. Conclusion COVID-19 infection is known to cause an immune response. There have been published cases of positive ANA, U1-snRNP anti-SS-B/La, ANCA, anti-phospholipid and anti-SRP antibody formation following COVID-19 infection. The link between the pathophysiology of COVID-19, autoantibody formation and the role of autoimmunity is still unclear. This man's case was unusual in the number and variety of autoantibodies formed post COVID, this has not been reported in the literature to date. Some of the autoantibodies detected are highly specific for certain conditions, for example anti-GBM antibodies have a high specificity for Goodpasture’s syndrome, thus this case also illustrates the need to interpret positive autoantibodies in the context of clinical findings and history. Disclosure S. Islam: None. N. Erb: None.

Micro-Computed Tomography Analysis of Peri-Implant Bone Defects Exposed to a Peri-Implantitis Microcosm, with and without Bone Substitute, in a Rabbit Model: A Pilot Study.

Peri-implantitis is an inflammatory condition characterized by inflammation in the peri-implant connective tissue and a progressive loss of supporting bone; it is commonly associated with the presence of biofilms on the surface of the implant, which is an important factor in the development and progression of the disease. The objective of this study was to evaluate, using micro-CT, the bone regeneration of surgically created peri-implant defects exposed to a microcosm of peri-implantitis. Twenty-three adult New Zealand white rabbits were included in the study. Bone defects of 7 mm diameter were created in both tibiae, and a cap-shaped titanium device was placed in the center, counter-implanted with a peri-implantitis microcosm. The bone defects received a bone substitute and/or a resorbable synthetic PLGA membrane, according to random distribution. Euthanasia was performed 15 and 30 days postoperatively. Micro-CT was performed on all samples to quantify bone regeneration parameters. Bone regeneration of critical defects occurred in all experimental groups, with a significantly greater increase in cases that received bone graft treatment (p < 0.0001), in all measured parameters, at 15 and 30 days. No significant differences were observed in the different bone neoformation parameters between the groups that did not receive bone grafts (p > 0.05). In this experimental model, the presence of peri-implantitis microcosms was not a determining factor in the bone volume parameter, both in the groups that received regenerative treatment and in those that did not.

In vivo healing of low temperature deproteinized bovine bone xenograft in a rabbit cranial model.

The physicochemical properties of grafting materials affect the quality of the osteointegration, resorption rate, and the new bone (NB) formation. This study assessed the physicochemical properties and integration of a low temperature deproteinized bovine bone xenograft (BBX), referred to as optimized MoaBone® (OMB). This novel BBX was physiochemically characterized both pre and post chemical bleaching and sterilization by gamma irradiation. OMB was compared to two commercial BBX; Bio-Oss® (BO) and MoaBone® (MB) using a rabbit cranial model. Residual graft and NB were quantified using histology and micro-computed tomography. Results showed that chemical treatment and gamma irradiation had limited effect on the surface texture. A significant decrease in the collagen content was detected post chemical treatment and in the carbonate content post gamma irradiation. There was no evidence of inflammatory infiltrate, necrosis, or connective tissue encapsulation, and a significant increase of NB in all grafted sites as compared to untreated defects could be observed. However, there was no statistically significant difference between the grafted sites. We conclude that chemical treatment and terminal sterilization strongly impact the final graft's properties. OMB graft showed equivalence with BO for in vivo bone formation and potentially results in lower levels of graft retention.

Unusual cause of the left main bronchus stenosis: relapsing polychondritis.

Relapsing polychondritis is a rare disease that causes inflammation and destruction of cartilage and connective tissue. It can be associated with other autoimmune rheumatologic and hematologic diseases. Herein, we report a 38-year-old male patient with relapsing polychondritis and diffuse stenosis of the left main bronchus.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Rapid diagnosis of systemic lupus erythematosus by Raman spectroscopy combined with spiking neural network

Multiple organs are affected by the autoimmune inflammatory connective tissue disease known as systemic lupus erythematosus (SLE). If not diagnosed and treated in a timely manner, it can lead to nephritis and damage to the blood system in severe cases, resulting in the patient's death. Therefore, correct and timely diagnosis and treatment are essential for patients. In this study, a framework based on neural network algorithm and Raman spectroscopy technique was established to diagnose SLE patients. Firstly, we pre-processed the obtained Raman data by three methods: baseline correction, smoothing processing and normalization methods, before using it as input for the model, and then ANN, ResNet and SNN classification models were established. The respective classification accuracies for SLE patients were 89.61%, 85.71%, and 95.65% for the three models, with corresponding AUC values of 0.8772, 0.8100, and 0.9555. The results of the experimental indicate that SNN possesses a good classification effect, and the number of model parameters is only 525,826, which is 414,221 less than that of ResNet model. Since the network only uses 0 and 1 to transmit information, and only has basic operations such as summation, compared with the second-generation artificial neural network, which simplifies the product operation of floating point numbers into multiple addition operations, the network has low energy consumption and is suitable for embedding portable Raman spectrometer for clinical diagnosis. This research highlights the significant potential for quick and precise SLE patient discrimination offered by Raman spectroscopy in conjunction with spiking neural networks.

Pseudo-chilblain lesions in children during the COVID-19 pandemic

Introduction and objective: During the COVID-19 pandemic, a range of uncommon cutaneous symptoms were observed, which were linked to the SARS-CoV-2 infection. These dermatological symptoms in the form of reddish or purple-coloured lesions on the fingers and toes, accompanied by blisters and ulcerations, were termed as “COVID fingers/toes” – a pseudo-chilblain cutaneous manifestation of COVID-19. The aetiopathogenesis of pseudo-chilblain lesions has not been conclusively determined. At first, SARS-CoV-2 infection was regarded as an evident cause of chilblains. Various studies conducted over a two-year period have not managed to plausibly confirm its direct implications. Materials and methods: The study was of a retrospective nature. The analysis involved clinical symptoms, results of selected laboratory tests, as well as capillaroscopy of the microcirculation in 15 children diagnosed with skin lesions of chilblain-like morphology. Results: All patients from the study population presented with lesions in distal body parts which were of erythematous or oedematous morphology, and resembled chilblains. None of the hospitalised patients suffered from fever or presented with other systemic symptoms. The reverse transcription polymerase chain reaction test for SARS-CoV-2 was negative in all the patients. SARS-CoV-2 antibodies were found in 5 out of 9 patients tested for their presence. Microcirculation abnormalities were diagnosed in 80% of the patients. In none of the children did capillaroscopy image correspond with microangiopathy characteristic of inflammatory connective tissue diseases. Frequent abnormalities found in more than two fingers/toes were: pericapillary oedema (57%), dilated capillaries (42.8%), venous stasis (35.7%), presence of branched and tortuous capillaries (28.5%). Conclusions: Pseudo-chilblain lesions observed during the SARS-CoV-2 pandemic are probably secondary to multifactorial epiphenomenon.

High Prevalence of IDH Mutation in Myeloid Neoplasm with Concomitant Autoimmune Rheumatic Disorders

BACKGROUND: The association between myeloid neoplasm (MN) and autoimmune rheumatological diseases (AIRD) is increasingly recognized. Furthermore, prolonged cytotoxic disease modifying anti-rheumatological drugs (DMARD) for AIRD may potentially induce therapy-related MN (t-MN), a lethal haematological malignancy with dismal outcomes. However, the genetic association and mechanism underpinning immune dysfunction in patients with between MN and AIRD is not fully elucidated. METHODS: In this collaborative study across the two disciplines and continents (Australia and USA), we assessed the burden of well-defined AIRD in a large cohort of MN (n=1702) that included myelodysplastic syndrome (MDS; n=861), acute myeloid leukaemia (AML; n=640), myeloproliferative neoplasm (MPN; n=89) and MDS/MPN overlap (n=112). We characterized the cytogenetic and mutational landscape of MN with AIRD (MN-AIRD) and without AIRD. In order to assess the mechanistic link between AIRD and MN, we investigated the bone marrow microenvironment in MN-AIRD vs. well-curated age matched controls. RESULTS: 132 (7.75%) of MN (n=1702) had concomitant AIRD. Although association of AIRD was observed across all subtypes of MN, enrichment of AIRD was observed in patients with MDS, MDS/MPN and MPN compared to AML (9.5% vs. 9.8% vs 10.1% vs. 4.67%; P &amp;lt;0.001). Inflammatory arthritis (n=65; 49.24%) followed by inflammatory connective tissue diseases (CTD, n=23; 17.42%), polymyalgia rheumatica (PMR, n=18; 13.63%) and vasculitis (n=16; 12.12%) were the most prevalent AIRD in the MN cohort. Notably, 87.7% of inflammatory arthritis were rheumatoid arthritis (RA; n=57). Striking survival differences were observed between t-MN without AIRD and MN-AIRD (14.0 vs. 33.7 months; P &amp;lt;0.0001) and t-MDS no-AIRD and MDS-AIRD (16.1 vs. 33.4 months, P =0.001). Chromosomal abnormalities including complex karyotype, monosomal karyotype, del 5q, del 7q, marker chromosome and TP53 mutations were enriched in t-MN following independent primary cancer (t-MN without AIRD). However striking enrichment of IDH1 and IDH2 (henceforth referred as IDH) mutations in MN with AIRD compared to MN without AIRD (20% vs. 11%, P =0.02), particularly in MDS-AIRD compared to MDS without AIRD (21% vs. 7%; P =0.001). The enrichment of IDH mutations were particularly prevalent in in MN cases with RA compared to other AIRD (34% vs. 11%; P =0.005). While IDH mutations were observed in only 8% and 6% of PMR and inflammatory CTD patients, respectively. Surprisingly higher frequency of IDH mutations was observed in evaluable seronegative compared to seropositive RA patients (62% vs. 0%; P =0.006). We also observed that majority of IDH mutations in seronegative RA were IDH1 (6/8; 75%) while IDH2 mutations were common other AIRD (6/6; 100%) ( P =0.009). We also assessed the impact of DMARDs on genomics of myeloid neoplasm. The majority of MN-AIRD patients treated with methotrexate did not harbor poor risk cytogenetic and mutation features such as complex karyotype, monosomal karyotype, del 5q, del 7q and/or TP53 mutation. In contrast, the majority of patients who had cyclophosphamide harbored high risk cytogenetic and molecular features. To assess pathogenic mechanisms linking MN and AIRD, we evaluated bone marrow microenvironment in myeloid neoplasm patients with and without AIRD. Bone marrow mesenchymal stromal cells (MSC) isolated from MN-AIRD were highly senescent compared to age matched healthy controls, MN without AIRD, with defective proliferating and differentiation capacity of MN-AIRD and secretion of highly proinflammatory cytokines and chemokines. CONCLUSIONS: In summary, our key findings include: 7.8% of MN were associated with AIRD with stronger association of AIRD with MDS and MDS/MPN compared to AML and striking enrichment of IDH mutations in MN with inflammatory arthritis compared to MN with other AIRD (29% vs 11%; P =0.02), especially in seronegative RA compared to seropositive RA (62% vs. 0%; P =0.006). In contrast to cyclophosphamide and azathioprine, majority of cases treated with methotrexate did not harbor poor risk cytogenetic and/or TP53 mutation. As methotrexate is widely used as an anchor drug in many rheumatology treatment regimens, this is a highly significant finding of clinical relevance.

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.

Characteristics and onset of presentation of pediatric stiff skin syndrome: A retrospective cohort study of 11 patients in a tertiary care center.

Stiff skin syndrome (SSS) is a rare disorder characterized by "rock hard" indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS. This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies. A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI)and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site. The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions.

Chronic subdural electrocorticography in nonhuman primates by an implantable wireless device for brain-machine interfaces.

Subdural electrocorticography (ECoG) signals have been proposed as a stable, good-quality source for brain-machine interfaces (BMIs), with a higher spatial and temporal resolution than electroencephalography (EEG). However, long-term implantation may lead to chronic inflammatory reactions and connective tissue encapsulation, resulting in a decline in signal recording quality. However, no study has reported the effects of the surrounding tissue on signal recording and device functionality thus far. In this study, we implanted a wireless recording device with a customized 32-electrode-ECoG array subdurally in two nonhuman primates for 15 months. We evaluated the neural activities recorded from and wirelessly transmitted to the devices and the chronic tissue reactions around the electrodes. In addition, we measured the gain factor of the newly formed ventral fibrous tissue in vivo. Time-frequency analyses of the acute and chronic phases showed similar signal features. The average root mean square voltage and power spectral density showed relatively stable signal quality after chronic implantation. Histological examination revealed thickening of the reactive tissue around the electrode array; however, no evident inflammation in the cortex. From gain factor analysis, we found that tissue proliferation under electrodes reduced the amplitude power of signals. This study suggests that subdural ECoG may provide chronic signal recordings for future clinical applications and neuroscience research. This study also highlights the need to reduce proliferation of reactive tissue ventral to the electrodes to enhance long-term stability.

Transcriptomic profiling of mare endometrium at different stages of endometrosis

In the current study, transcriptome profiles of mare endometrium, classified into categories I, IIA, and IIB according to Kenney and Doig, were compared using RNA sequencing, analyzed, and functionally annotated using in silico analysis. In the mild stage (IIA) of endometrosis compared to category I endometrium, differentially expressed genes (DEGs) were annotated to inflammation, abnormal metabolism, wound healing, and quantity of connective tissue. In the moderate stage (IIB) of endometrosis compared to category I endometrium, DEGs were annotated to inflammation, fibrosis, cellular homeostasis, mitochondrial dysfunction, and pregnancy disorders. Ingenuity pathway analysis (IPA) identified cytokines such as transforming growth factor (TGF)-β1, interleukin (IL)-4, IL-13, and IL-17 as upstream regulators of DEGs associated with cellular homeostasis, metabolism, and fibrosis signaling pathways. In vitro studies showed the effect of these cytokines on DEGs such as ADAMTS1, -4, -5, -9, and HK2 in endometrial fibroblasts at different stages of endometrosis. The effect of cytokines on ADAMTS members’ gene transcription in fibroblasts differs according to the severity of endometrosis. The identified transcriptomic changes associated with endometrosis suggest that inflammation and metabolic changes are features of mild and moderate stages of endometrosis. The changes of ADAMTS-1, -4, -5, -9, in fibrotic endometrium as well as in endometrial fibroblast in response to TGF-β1, IL-4, IL-13, and IL-17 suggest the important role of these factors in the development of endometrosis.

Genetic Disorders in Pediatric Rheumatology Clinic: When to Suspect, and Why?

Just under a decade ago, most children with genetic disorders received a phenotypic diagnosis, often by atlas matching. With advances in genomics (decoding of human genome, easy availability of genetic testing, and reduction in cost of tests), genotypic diagnosis is now a reality. Genetic diseases can lead to non-inflammatory arthritis that can mimic juvenile idiopathic arthritis (JIA). A small but growing number (as newer genes are discovered) of genetic diseases are being diagnosed in children with aseemingly inflammatory musculoskeletal diseases or connective tissue diseases. A high index of suspicion by the pediatrician is most important for early diagnosis of these genetic disorders. In a busy outpatientclinic, it is the atypical presentation of a disease in a child that suggests a possibility of underlying genetic autoinflammatory or autoimmune disease. Correct diagnosis helps the physician, child, parent, and community.

CT Patterns of Interstitial Lung Disease in Patients with Plaque Psoriasis: A Retrospective Case Series Study.

Background and Objectives: Recently published articles reported an association between psoriasis and interstitial lung diseases (ILDs). The aim of this study is to evaluate the differences in ILD computed tomography (CT) patterns between smoker and never smoker plaque psoriasis (PP) patients under topical treatment without psoriatic arthritis (PA), inflammatory bowel disease (IBD) or connective tissue diseases (CTDs). Matherials and Methods: Two radiologists evaluated chest CT examinations of 65 patients (33 smokers, 32 never smokers) with PP. Results: Usual interstitial pneumonia (UIP) pattern was diagnosed in 36 patients, nonspecific interstitial pneumonia pattern in 19, hypersensitivity pneumonitis in 7 and pleuropulmonary fibroelastosis (PPFE) in 3 patients. UIP pattern showed a statistically significant higher frequency in smoker patients (p = 0.0351). Respiratory symptoms were reported in 80% of patients. Conclusions: ILDs seems to represent a new comorbidity associated with psoriasis. Moreover, a statistically significant association between smokers and UIP pattern in PP patients is found. Respiratory symptoms should be evaluated in PP patients, in collaboration with a radiologist and a pneumologist. However, further studies are required to better understand the epidemiology of ILDs in PP patients.