Cutaneous basophil infiltration in atopic dermatitis is associated with abundant epidermal infiltration of helper T cells: A preliminary retrospective study.

Atopic dermatitis (AD) is a heterogenous inflammatory skin disorder. Our previous study revealed that basophil infiltration in skin is observed in approximately 60% of AD cases. However, the clinical and histological characteristics of AD associated with basophil infiltration remain unclear. We examined basophil infiltration by immunohistochemical staining of 38 specimens from 34 patients who underwent skin biopsies to diagnose AD from April 2016 to September 2021 at Tokyo Medical and Dental University Hospital. The patients/specimens were divided into two groups, 17 patients/21 specimens associated with little or no basophil infiltration (basophil-low group) and 17 patients/17 specimens associated with marked basophil infiltration (basophil-high group). The clinical characteristics of the patients (age, sex, complications, blood biomarkers, skin symptoms, and treatment) and histological features of the specimens were compared between the groups. Basophil-high patients were significantly younger than basophil-low patients. Blood basophil counts were higher in basophil-high patients than in basophil-low patients. CD4+ T-cell infiltration was more marked in basophil-high specimens than in basophil-low specimens. CD4+ T cells infiltrated into the dermis as well as into the epidermis only in the basophil-high specimens. Thus, basophil-high AD can be characterized by skin lesions associated with abundant helper T-cell infiltration in younger patients.

Towards understanding Müller-Weiss disease from an analysis of 95 cases.

BACKGROUND: The single existing classification of Müller-Weiss Disease (MWD), based solely upon Méary's angle, serves neither as guide for prognosis nor treatment. This accounts for lack of gold standard in its management. METHODS: Navicular compression, medial extrusion, metatarsal lengths, Kite's, lateral and dorsoplantar talo-first metatarsal angles were measured in 95 feet with MWD. Joints involved, presence and location of navicular fracture were recorded. RESULTS: Group 1 "early-onset" MWD feet (n = 11) had greatest compression and medial extrusion, and lowest Kite's angles. All except 1 were index minus and had lateral navicular fracture. Only 1 had moderate degeneration at the talonavicular joint (TNJ) with none requiring surgery yet. Group 2 "Müller-Weissoid" feet (n = 23) had radiologically normal navicular in their fifties and developed MWD on average 5 years later. They had the lowest compression and extrusion, and highest Kite's angles. None had complete fracture. All had TNJ arthritis, with early changes at lateral naviculocuneiform joint (NCJ) in 43%. Group 3 "late-onset" MWD presented in the sixth decade. Only TNJ was involved in Group 3 A (n = 16). Group 3B (n = 20) affected TNJ more than NCJ and had the greatest number of Maceira stage V disease. Group 3 C "reverse Müller-Weiss disease", which affected NCJ more than TNJ (n = 25), had greatest midfoot abduction and overlength of the second metatarsal. No fracture occurred in group 3 A compared to 65% and 32% in groups 3B and 3 C, respectively. CONCLUSIONS: With need to compare like-for-like pathology, the proposed classification provides a common platform for reporting outcomes of different treatments. We theorize pathogenetic pathways in the various groups.

Decreased peripheral basophil counts in urticaria and mouse model of oxazolone-induced hypersensitivity, the latter suggesting basopenia reflecting migration to skin.

A decrease in the number of basophils in the peripheral blood, or basopenia, has been noted, reflecting the activity of chronic spontaneous urticaria (CSU). Infiltration of basophils into the skin has also been reported, but the mechanism of basopenia in CSU has not been clarified. The phenomenon of basopenia during the active phase of urticaria was confirmed, and basophil numbers increased following symptom improvement in 15 out of 17 patients treated with omalizumab and in 13 of 15 patients treated with antihistamines. Our examination by immunostaining also revealed basophil infiltration of the CSU lesions, as in previous reports, but since most of our patients were already taking oral steroids, it was not considered appropriate to examine the relationship between basophil numbers in tissue and peripheral blood. Then, we used mouse model of contact hypersensitivity with a single application of oxazolone, which is known to stimulate basophil infiltration, and investigated basophil counts in the skin, peripheral blood, and bone marrow. In this model, a decrease in peripheral blood basophil numbers was observed one day after challenge, but not after 2 days, reflecting supplementation from the bone marrow. Indeed, when cultured basophils expressing GFP were transplanted into the peripheral blood, GFP-positive basophil numbers in the peripheral blood remained low even after 2 days of challenge. Despite differences among species and models, these results suggest that one reason for the decrease of basophils in the peripheral blood in CSU may involve migration of circulating basophils into the skin.

A Prospective Study Assessing Wound Complications in a Series of Foot and Ankle Patients Treated With Enoxaparin: A Baseline for Future Studies.

Background and objective Low-molecular-weight heparin (LMWH) prophylaxis has now become the gold-standard practice in patients requiring lower limb immobilization. We had noticed an increase in the incidence of wound-healing problems at our center, and the severity of the problems was found to be worse in patients undergoing foot and ankle surgery since we had adopted this practice. In this study, we aimed to describe the incidence and severity of wound-healing problems in this group of patients. Methods This was a prospective study and we collected data on the frequency and severity of wound problems occurring in patients undergoing a variety of foot and ankle operations. All patients underwent a standard agreed-on method of wound closure and dressings. Wounds were reviewed after two weeks and wound characteristics were noted using a rigid proforma. The primary outcome measure was to determine the incidence of delayed wound healing (DWH) and wound infections requiring antibiotics. Secondary outcomes were the characteristics of each delayed-healing wound. Results A total of 158 patients met the inclusion criteria of the study. One patient was not given postoperative LMWH and was excluded from the final analysis. Seven patients (4.5%) were noted to have DWH and four patients (2.6%) had a wound infection at the two-week postoperative follow-up. None of the patients required a second operation. Among patients with wound-healing problems, wound contour irregularities were noted in 51% and margin separation was noted in 65%. Conclusion The overall incidence of wound-healing problems such as DWH and wound infections was low in patients receiving prophylactic LMWH for foot and ankle surgery. Where postoperative wound problems did occur, these were associated with poor wound characteristics such as margin separation or contour irregularity. Further studies should be conducted to ascertain if the use of LMWH leads to problems with wound appearance.

The management of osteoporotic acetabular fractures: Current methods and future developments.

Acetabular fractures in the elderly are challenging. Management is complicated by patients' poor physiological status and osteoporotic bone. Analysis of the management of these patients must be separated from the treatment of younger patients. Conservative management continues to have a role in patients who sustain fractures that are non-displaced and are considered stable with weight bearing mobilisation, and in those patients considered too medically frail to undergo surgical intervention. The mainstay of current surgical intervention is open reduction and internal fixation (ORIF) and variations of ORIF and total hip arthroplasty (THA), or fix and replace. Fix and replace is being increasingly favoured in those patients who display poor prognostic factors for long term joint survival after ORIF. Percutaneous fixation has the theoretical benefits of minimally invasive surgery and the potential to make any subsequent THA less complicated. However, it requires specialised fluoroscopic skills and is not suitable for all fracture patterns. There are a number of developments being reported. The use of a reinforcement ring and THA in has been reported in a number of centres, as has the use of trabecular metal acetabular implants. A coned hemi pelvic prosthesis and THA has been described in our centre, with promising early results. The potential for 3D printing to improve preoperative planning and reduce intra-operative time is also being explored. The aim of this review is to provide a summary of the literature supporting current and future treatment methods, tips on reduction techniques and an overview of the treatment algorithm of these patients in our unit.

Penile calciphylaxis: A retrospective case-control study.

BACKGROUND: Calciphylaxis is a rare disorder characterized by skin necrosis caused by calcium deposition within vessels, thrombosis, and subsequent tissue ischemia. Penile involvement may rarely occur. OBJECTIVE: To identify risk factors, diagnosis, management, and mortality of patients with penile calciphylaxis. METHODS: A retrospective medical record review was conducted of 16 patients with penile calciphylaxis treated at 2 large urban tertiary care centers between January 2001 and December 2019. A control group of 44 male patients with nonpenile calciphylaxis at the same institution was included. RESULTS: The median survival of patients with penile calciphylaxis was 3.8 months (interquartile range, 27.0 months). Mortality was 50% at 3 months and 62.5% at 6 months for penile calciphylaxis, and 13.6% at 3 months and 29.5% at 6 months for controls (P = .008). Patients with penile calciphylaxis were less likely to be obese (P = .04) but more likely to have hyperparathyroidism (P = .0003) and end-stage renal disease (P = .049). LIMITATIONS: Retrospective study design and small sample size. CONCLUSIONS: This study further defines the disease course of penile calciphylaxis, which has high mortality. Imaging may be used to aid diagnosis. Risk factors include end-stage renal disease, hyperparathyroidism, and normal body mass index.

Use of teledermatology by dermatology hospitalists is effective in the diagnosis and management of inpatient disease.

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

Detection of Mast Cells and Basophils by Immunohistochemistry.

Staining cells or tissues with basic dyes was the mainstay of mast cell and basophil detection methods for more than a century following the first identification of these cell types using such methods. These techniques have now been largely supplanted by immunohistochemical procedures with monoclonal antibodies directed against unique constituents of these cell types. Immunohistochemistry with antibodies specific for the granule protease tryptase provides a more sensitive and discriminating means for detecting mast cells than using the classical histochemical procedures, and using antibodies specific for products of basophils (2D7 antigen and basogranulin) has allowed detection of basophils that infiltrate into tissues. The application of immunohistochemistry to detect more than one marker in the same cell has underpinned concepts of mast cell heterogeneity based on differential expression of chymase and other proteases. The double labeling procedures employed have also provided a means for investigating the expression of cytokines and a range of other products. Protocols are here set out that have been used for immunohistochemical detection of mast cells and basophils and their subpopulations in human tissues. Consideration is given to pitfalls to avoid and to a range of alternative approaches.

Rapidly Progressive Osteoarthritis and Acetabular Bone Loss Outcomes for Patients Undergoing Primary Total Hip Replacement.

Rapidly progressive osteoarthritis (RPO) is a rare condition which is poorly understood. Limited published literature is available. Reported here is a cohort of patients with RPO and acetabular bone loss who underwent primary THA. Risk factors, degree of acetabular bone loss and outcomes are presented. A typical case of RPO is described and investigations discussed. A retrospective audit was undertaken. 49 patients over an 18-year period were included. RPO patients were significantly older (P < 0.01) and had a lower BMI (P = 0.03). The mean acetabular bone loss in this cohort was 10.0 mm. Pathogenesis and risk factors for developing RPO remain unclear and future research is necessary. Repeat imaging in patients with deteriorating symptoms is important and urgent surgery is required maintain bone stock.

Eosinophils, basophils and type 2 immune microenvironments in COPD-affected lung tissue.

Although elevated blood or sputum eosinophils are present in many patients with COPD, uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils. Basophils have remained virtually unexplored in COPD. This study mapped tissue-infiltrating eosinophils, basophils and eosinophil-promoting immune mechanisms in COPD-affected lungs.Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades Global Initiative for Chronic Obstructive Lung Disease stages I-IV; never-smokers/smokers served as controls. Automated immunohistochemistry and in situ hybridisation identified immune cells, the type 2 immunity marker GATA3 and eotaxins (CCL11, CCL24).Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD. The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3+ cells, including type 2 helper T-cell lymphocytes and type 2 innate lymphoid cells. A similarly localised and interleukin-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice. Both mice and patients displayed spatially confined eotaxin signatures with CCL11+ fibroblasts and CCL24+ macrophages.In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that is likely to have implications for personalised treatment.

Staphylococcus aureus internalization in mast cells in nasal polyps: Characterization of interactions and potential mechanisms.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps is a common chronic condition. The exact cause of nasal polyps remains unknown. Recently, we made the novel observation of intracellular localization of Staphylococcus aureus within mast cells in nasal polyps. OBJECTIVE: This follow-up study aimed to further characterize interactions between S aureus and mast cells in this setting and elucidate potential internalization mechanisms with particular emphasis on the role of staphylococcal enterotoxin B (SEB). METHODS: A prospective study was performed using an explant tissue model with ex vivo inferior turbinate mucosa obtained from patients with chronic rhinosinusitis with nasal polyps (n = 7) and patients without CRS (n = 5). Immunohistochemistry was used to characterize S aureus uptake into mast cells and investigate the effects of SEB on this process. An in vitro cell-culture model was used to investigate mast cell-S aureus interactions by using a combination of fluorescent in situ hybridization, confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, and proliferation assays. RESULTS: S aureus was captured by extracellular traps and entered mast cells through phagocytosis. Proliferating intracellular S aureus led to the expansion and eventual rupture of mast cells, resulting in release of viable S aureus into the extracellular space. The presence of SEB appeared to promote internalization of S aureus into mast cells. CONCLUSION: This study provides new insights into the interactions between S aureus and mast cells, including the internalization process, and demonstrates a prominent role for SEB in promoting uptake of the bacteria into these cells.

A Prospective Randomized Study Comparing Postoperative Pain, Biological Fixation, and Clinical Outcomes Between Two Uncemented Rotating Platform Tibial Tray Designs.

BACKGROUND: With the demand for arthroplasty increasing worldwide year on year, there is a drive to improve prosthesis longevity. Biological fixation from cementless implants has been one method of trying to achieve this. We hypothesized that the addition of a hydroxyapatite (HA) coating and 4 pegs to a porous-coated tibial tray would provide a reduction in time to implant osseointegration, allowing for normal physiological stress transfer, thus improving early postoperative pain and rehabilitation as well as the elimination of radiolucent lines (RLLs). METHODS: A prospective, randomized controlled single-blinded study was undertaken, comparing postoperative pain, radiographic evidence of biological fixation, and clinical outcomes between patients undergoing primary total knee arthroplasty with either LCS Complete POROCOAT (porous coating only) or LCS Complete DUOFIX (porous coating plus HA and pegs) knee systems (DePuy Synthes, Warsaw, IN). In total, 197 patients (205 knees) were recruited into the study between November 2006 and November 2008 and have been followed for up to 10 years. RESULTS: There were no clinically significant differences in pain or patient-reported outcome measures when comparing the 2 designs but the tibial tray with pegs and HA showed fewer RLLs at all time points. There was no correlation between RLLs and pain and no instances of loosening or osteolysis in either group. There was 1 revision for infection in the porous coating only group. CONCLUSION: The tray design with HA and additional fixation pegs did not confer any benefit in terms of reduced early postoperative pain or improved patient-reported outcomes, although it did result in significantly fewer RLLs. Both implants demonstrated excellent survivorship. With a cementless porous-coated tibial component, nonprogressive RLLs should be considered normal.

Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells.

BACKGROUND: An increased degree of mast cell (MC) degranulation and damage to the epithelial lining are prominent features of bronchial asthma. In asthmatic airways, it seems likely that epithelial cells will be exposed to increased concentrations of proteases from MC, though their actions on the epithelium are still not very clear. METHODS: Bronchial rings from human lung tissue or 16HBE cell monolayer were incubated with MC chymase in different doses or various inhibitors. The sections of paraffin-embedded tissue were haematoxylin-eosin stained and computerized by image analysis for epithelial damage-scale-evaluation; the cell viability, proliferation, adhesion and lactate dehydrogenase activity release were assayed; the expressions of gelatinases, cell junction molecules and structure proteins of 16HBE were examined. RESULTS: Mast cell chymase was found to provoke profound changes in the morphology of bronchi epithelial layer. Following incubation with chymase, there was 40% reduction in the length of epithelium that was intact, with detachment of columnar epithelial cells and basal cells. Chymase reduced epithelial cell proliferation and induced cell detachment, which were associated with the changes in secretion and activation of matrix metalloproteinase-2/9. In intact epithelial cell layers, immunocytochemistry study revealed that chymase reduced the expressions of occludin, claudin-4, ZO-1, E-cadherin, focal adhesion kinase and cytokeratin. Overall data of this study indicated that MC chymase can influence tissue remodelling, disrupt epithelial cell junctions, inhibit wound healing and impair the barrier function of epithelium, resulting in dysfunction of airway wall and ECM remodelling in pathogenesis of asthma. CONCLUSION: Mast cell chymase plays a key role in inducing the damage to bronchial epithelium in asthma.

Catastrophic ceramic liner failure-The subtle signs of a non-engaged ceramic liner.

Ceramic earrings have an established and successful history in total hip replacement. Occasionally, these articulations have problems, which include squeaking and implant fracture.