Recalcitrant Disease Research Articles

Hidradenitis suppurativa: Evaluating activity patterns and predictors of recalcitrant course-A population-based study.

Epidemiological evidence regarding the course and activity patterns of hidradenitis suppurativa (HS) is yet to be delineated. To identify activity patterns of HS throughout the time axis and to outline predictors of recalcitrant disease course. A population-based retrospective cohort study was performed to follow patients with HS (n=4417) throughout the initial 10 years following their diagnosis. The disease was considered active in a certain month if one of the following criteria was fulfilled: (i) purchase of an HS-related drug, (ii) admission to a dermatological ward and (iii) referral to a dermatological consultation in an emergency room. Patients with a recalcitrant disease were defined as those with ≥5 years of follow-up with ≥6 'active months' each. Patients with an indolent course were defined as those experiencing ≥9 years of follow-up with ≤1 'active months' each. The average (SD) number of months in which patients had an active disease was 1.37 (1.28) months per year. While 98 (2.2%) patients pursued a recalcitrant course, 1390 (31.5%) went through an indolent disease course. Older age (≥38 years; adjusted OR, 6.17; 95% CI, 3.33-11.43), Arab ethnicity (adjusted OR, 2.04; 95% CI, 1.20-3.48), low socioeconomic status (adjusted OR, 1.64; 95% CI, 1.03-2.60), obesity (adjusted OR, 3.47; 95% CI, 2.25-5.34) and smoking (adjusted OR, 2.65; 95% CI, 1.57-4.47) were found to independently predict recalcitrant course of HS. Mild course is more frequently encountered than severe course among Israeli patients with HS. Modifiable risk factors of recalcitrant course should be carefully addressed.

Identifying predictors of systemic immunosuppressive treatment of vulvovaginal lichen planus: A retrospective cohort study of 122 women.

Between 20% and 40% of women with vulvovaginal lichen planus (VLP) fail to respond to first-line ultra-potent topical corticosteroid treatment and require systemic immunosuppression to control disease. No data exist regarding risk factors for patients with severe VLP requiring systemic immunosuppression. We aimed to identify clinical features that predict women with VLP who are at risk of severe, recalcitrant disease requiring eventual escalation to systemic treatment. A chart review was performed on a cohort of 122 adult women with VLP followed prospectively for 15 years by the same clinician in a private dermatology practice in Australia between 1 January 2004 and 1 October 2021. Uni- and multivariable binary logistical regression analyses were performed to identify clinical features distinguishing women eventually requiring systemic treatment of VLP against those whose VLP was controlled with topical corticosteroids alone. The mean age at diagnosis of VLP was 61 years, with 35 women (28.7%) requiring systemic treatment of VLP. A multivariable regression model utilising 'Age at Diagnosis' (adjusted OR=0.97, 95% CI 0.94-0.99), 'Non-Caucasian Ethnicity' (adjusted OR=10.3, 95% CI 2.27-73.9) and 'Vulvar Pruritus' (adjusted OR=2.69, 95% CI 1.11-6.86) demonstrated moderate predictive capacity, with specificity and sensitivity for predicting whether a patient will require systemic treatment for VLP of 95.3% and 40.5%, respectively. Our findings may indicate women with VLP who are younger, of non-Caucasian ethnicity, and presenting with vulval pruritus are the highest risk of severe disease requiring systemic immunosuppressive treatment and may benefit most from earlier initiation of systemic treatment.

Laryngotracheal stenosis: Mechanistic review.

BackgroundThe purpose of this review article is to summarize the existing literature surrounding wound healing mechanisms in laryngotracheal stenosis.MethodsA review of general wound healing pathophysiology, followed by a focused review of iatrogenic laryngotracheal stenosis (iLTS) and idiopathic subglottic stenosis (iSGS) as conditions of aberrant wound healing.ResultsiLTS is the scarring of the laryngotracheal complex, coming secondary to injury from prolonged intubation. iSGS is a chronic fibroinflammatory scarring and narrowing of the subglottic airway in the absence of any obvious preceding injury or trauma. They are both thought to result from a prolonged and dysregulated wound healing response that promotes the deposition of pathologic scar in the airway.ConclusionsUnderstanding the mechanisms that underlie wound healing will help identify and intervene on the process early in its development and discover future therapies that target individual wound healing mechanisms limiting the incidence of this recalcitrant disease process.

Arthroscopic Resection of Symptomatic Tibial Tubercle Ossicles for Recalcitrant Osgood-Schlatter Disease Using a 2-Portal Technique

Arthroscopic resection of symptomatic unfused tibial tubercle ossicles causing chronic anterior knee pain due to recalcitrant Osgood-Schlatter disease has been shown to be a reproducible arthroscopic technique. Although a number of other surgical techniques have been described, including ossicle excision and tubercle-plasty, drilling of the tibial tubercle, bone peg insertion to induce fusion, open excision of loose fragments, direct bursoscopic ossicle resection, and closing-wedge tubercle osteotomy, with varied outcomes, this technique offers a minimally invasive approach with low risk. Complications including injury to the patellar tendon and scarring of the anterior fat pad have been previously reported, but this approach can be performed with minimal fat pad debridement and direct visualization of the patellar tendon during all resections. This article presents a technique for arthroscopic resection and debridement of unfused ossicles in patients with chronic anterior knee pain due to Osgood-Schlatter disease by use of minimally invasive arthroscopic techniques that are used in standard knee arthroscopy and should be familiar to most arthroscopists.

The facilitating effect of blue light on the antifungal agent susceptibilities of passaged conidia from the ocular-derived Fusarium solani species complex.

The eye is a light-receiving organ and has anatomical advantages to accept phototherapy. Fungi colonizing on the eyes, which cause ocular mycoses, are affected by daily blue light and could easily accept additional light irritation. Ocular mycoses are recalcitrant and blindness-causing eye diseases, and antifungal agent treatments are insufficient. Our team previously found that blue light could inhibit Fusarium solani hyphal growth but promote conidiation. Here, we investigated the antifungal susceptibilities and biological characteristics of the passaged conidia. Twelve Fusarium solani strains (11 ocular-derived strains and 1 standard laboratory strain) were inoculated under blue light (0.5 mW/cm2) and darkness conditions, respectively, to obtain the passaged conidia of blue light group (n = 12) and darkness group (n = 12). Two groups were tested to determine the growth abilities and in vitro antifungal susceptibilities to five antifungal drugs (voriconazole (VRC), amphotericin B (AMB), terbinafine (TRB), caspofungin (CAS), and 5-flucytosine (5FC)), which were examined by microscopy for morphological observation and spectrophotometry for turbidity analysis. The results showed that blue light group passaged conidia were more sensitive to antifungal drugs (AMB, VRC, TRB, and CAS) compared to darkness group. The MIC50 of VRC significantly decreased after blue light treatment (P < 0.05). The fungal inhibition rate significantly increased for VRC, AMB, and TRB in the low concentration range (P < 0.05 or P < 0.01). Blue light did not affect germination or hyphal extension of passaged conidia. These results suggested that blue light could facilitate fungal inhibition effect of AMB, VRC, TRB, and CAS and may improve the therapeutic efficiency in VRC and AMB clinical applications. Blue light phototherapy may provide a new adjuvant approach for the treatment of ocular mycosis.

Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine.

Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease.

Efficacy and safety of balloon dilation of eustachian tube in children: Systematic review and meta-analysis

ObjectivesEustachian tube dysfunction is a common condition that may lead to otitis media with effusion, hearing loss and developmental delays in children. We sought to determine the efficacy and safety of balloon dilation of the eustachian tube (BDET) in the pediatric population. Data sourcesOriginal studies of BDET in a pediatric population were identified in PubMed, Embase, Web of Science, Cochrane, Clinicaltrials.gov and CINAHL. MethodsOutcomes of efficacy included audiometric findings and adverse events were summarized for each study. ResultsSeven articles were included involving 408 children with a mean age of 9.9 years old (95%CI 8.8, 11.1) and a mean follow up of 19.2 months (95%CI 15, 23). Type B tympanograms decreased after BDET from 64.2% (95%CI 53.3, 73.8) to 16.1% (95%CI 8.5, 28.4). Air-bone gap (ABG) decreased after BDET from a mean of 25.3 dB (95%CI 18.9, 31.6) to 10.2 dB (95%CI 8.9, 11.5). The pooled estimate of adverse events after BDET was 5.1% (95%CI 3.2, 8.1), the majority being self-limited epistaxis with no major adverse events reported. Three studies compared BDET to ventilation tube insertion; analysis of post-operative ABG showed a greater decrease in the BDET group (mean difference −6.4 dB; 95%CI -9.8, −3.1; p = 0.002). ConclusionAlthough there are no prospective randomized control trials, BDET ± tympanostomy tube placement may produce outcomes that are comparable to tympanostomy tube placement in the treatment of otitis media with effusion in the pediatric population. Most children undergoing the procedure are those with recalcitrant disease. The procedure is safe with the most common complication being epistaxis.

Is Patch Test Necessary in Children to Solve the Clinical Conundrum of Foot Eczema.

Foot eczema in children is a commonly encountered condition but is associated with diverse etiology, thereby posing a diagnostic challenge. These include atopic eczema, juvenile plantar dermatoses, irritant contact dermatitis, and allergic contact dermatitis. Because of the diverse etiology, it is often difficult to distinguish between the conditions clinically, thereby warranting patch testing for the correct diagnosis. The study was conducted to determine the frequency of positive patch tests among children with foot eczema and to compare them with children with and without atopy. This was a prospective observational study done on 86 children aged 4 to 17 years presenting with foot eczema in whom patch testing was done using Indian standard series and footwear series and patients' own footwear. The clinical diagnosis of foot eczema in our study was allergic contact dermatitis (37%), followed by atopic eczema (30%), juvenile plantar dermatoses (17%), and lichen simplex chronicus (15%). Patch test positivity was present in 36% of the cases with clinical relevance in 65% of the cases. The common allergens were rubber allergens and disperse dyes. Of the children who were patch tested, highest patch test positivity rates were seen in allergic contact dermatitis (50%) and juvenile plantar dermatoses (53%). No significant differences were observed with regard to patch test positivity or relevance between children with and without atopy. The diagnosis of foot eczema in children cannot be made on clinical grounds alone, and patch testing should be recommended in children with any morphological pattern of foot eczema irrespective of presence or absence of atopy, especially in those with long-standing and recalcitrant disease with frequent exacerbations.

Non-invasively Imageable Tibia-tumor-fragment Implantation Experimental-bone-metastasis Mouse Model of GFP-expressing Prostate Cancer.

Although the 5-year survival rate for localized prostate cancer is nearly 100%, prognosis for patients with metastases, of which the bone is the most common site, is poor. In order to evaluate efficacy of treatments against metastatic prostate cancer, experimental tibia-bone-metastasis mouse models of prostate cancer have been previously established. In the present study, we used a novel procedure for establishment of an experimental tibiabone metastasis mouse model, with human PC-3 prostate cancer expressing green fluorescent protein (GFP), that more closely matches prostate cancer growing in the bone. PC-3 human prostate cancer cells, labeled with GFP, were initially subcutaneously injected into the flank of five male nude mice to obtain tumor tissues. Once the tumor tissue grew larger than 10 mm in diameter, the tumor tissue was harvested and minced into fragments of 1 mm3 A 1-mm hole was made in the proximal left tibia of eight male nude mice, using the tip of a 5-mm blade, and a tumor fragment was implanted into the hole for an exact fit. Tumor size was measured once a week, by non-invasive imaging of GFP fluorescence. The mice were sacrificed four weeks after tumor implantation. Tumors grew in 8 out of 8 mice (100%). All tumors were non-invasively detectable with GFP fluorescence, through the skin. Increased tumor growth in the tibia was observed every week. The establishment in the tibia of the novel experimental bone-metastatic mouse model of human prostate cancer enables facile screening, in a clinically-relevant system, of improved therapeutics for this recalcitrant disease.

Clinical and Molecular Outcomes After Combined Intense Pulsed Light Therapy With Low-Level Light Therapy in Recalcitrant Evaporative Dry Eye Disease With Meibomian Gland Dysfunction.

Dry eye disease (DED) is a leading cause of ocular morbidity worldwide. This study evaluates the effects of combined light therapy [intense pulsed light (IPL) and low-level light therapy (LLLT)] on clinical and molecular outcomes in evaporative DED with meibomian gland dysfunction (MGD). This prospective study evaluated 94 eyes (47 subjects) with chronic MGD treated with combined light therapy. Patients underwent a detailed evaluation of MGD and DED using the Ocular Surface Disease Index, dry eye tests-tear breakup time and Schirmer test, ocular surface staining, meibomian gland expressibility scoring, and meibography. Patients underwent a single session of combined light therapy (IPL + LLLT treatment) using the Eye-light device. All these tests were repeated at 3 and 6 months after treatment. Tear fluid and ocular surface wash samples were collected from a subset of patients before and after treatment for cellular and secreted immune factor profiling by flow cytometry. Combined light therapy (IPL + LLLT) demonstrated a marked improvement in the clinical metrics studied. Three months after treatment, Ocular Surface Disease Index showed a significant reduction in 95.6% ( P < 0.0001), tear breakup time increased in 72.3% ( P < 0.0001), and meibomian gland expressibility scoring increased in 80.8% ( P < 0.0001) of the eyes. These effects were observed to be sustained during the 6-month follow-up visit. Significant ( P < 0.05) reduction in tear fluid levels of interleukin-1β, interleukin-17F, and MMP9; MMP9/TIMP1 ratio; and ocular surface B-cell proportions was observed. Combined light therapy shows promising results in patients with chronic MGD and DED, even in recalcitrant cases. Clinical and molecular factor alterations support the improved symptomatology and reduced inflammation.

The effect of age on self-rated skin pain in patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a recalcitrant chronic inflammatory skin disease characterized by recurrent and painful nodules that negatively affect health-related quality of life. Pain is the most disabling symptom of HS, but data on HS pain remain limited. We previously observed a dissociation between pain and number of HS lesions with regards to increasing age. To further explore this observation, we investigated the relationship between experienced HS pain and age, adjusting for other relevant factors that might affect pain assessment. We conducted a retrospective cohort study (n = 342) using data from the Registry for Hidradenitis Suppurativa database. Multiple linear regression analysis was performed for self-evaluated pain (measured on a 0-10 numerical rating scale [NRS]) as an outcome with age and adjusted for the effects of sex, BMI, smoking status, lesion count and percentage of lifetime spent with HS symptoms. The multiple linear regression showed that age was associated with a decreased pain level of 0.31 NRS points/year (95%CI: -0.062; -0.0088; p = 0.044) and number of nodules was associated with an increased pain level of 0.081 NRS points/nodule (95%CI: 0.00077; 0.16; p = 0.048). Percentage of lifetime spent with HS symptoms was not found to significantly affect pain levels. This study supports our hypothesis that older HS patients report decreased levels of pain, independent of disease severity, which may be due to factors such as demyelination of nerve fibres, reduced painful physical activity, improved coping, or associated co-morbidities that distract from HS-related pain.

Subcutaneous Tocilizumab for Thyroid Eye Disease

Purpose: To demonstrate the efficacy of subcutaneous tocilizumab (TCZ-SC) treatment for recalcitrant thyroid eye disease (TED) refractory to intravenous methylprednisolone (MP) and oral methotrexate (MTX).Case summary: (Case 1) A 52-year-old man, smoker, with hyperthyroidism presented with a 3-months history of TED. The initial clinical activity score (CAS) was 5 (total score of 7). High-dose intravenous MP and oral MTX failed to improve the symptoms. He was treated with four doses of 162 mg TCZ-SC at an interval of 2 weeks. Pre-treatment laboratory test results were within normal limits. CAS was reduced to 2 weeks after the final injection, and there were no recurrences during the 6-month follow-up. (Case 2) A 37-year-old woman, non-smoker, with a 3-months history of hyperthyroidism presented with conjunctival injection and upper eyelid erythema. The initial CAS was 4, and thyroid-stimulating immunoglobulin level was raised (475% of normal). The symptoms did not improve with 7.5 g intravenous MP and oral MTX. The patient was treated with 162 mg TCZ-SC. Pre-treatment laboratory test results were within normal limits. CAS was reduced to 1 after the final injection, and there were no recurrences during the 6-months follow-up.Conclusions: TCZ-SC improves symptoms of corticosteroid-resistant TED, and may be a reasonable option in recalcitrant TED cases. However, further studies are required to justify the use of TCZ-SC for TED.

Combinatorial therapy with immunosuppressive, immunomodulatory and tear substitute eyedrops (“Triple Play”) in Recalcitrant Immunological Ocular Surface Diseases

PurposeThe current paradigm for therapy of recalcitrant ocular surface diseases (OSD) consists of a sequential, step-up treatment approach. A combinatorial topical therapy (anti-inflammatory/immunosuppressive [steroid] with immunomodulatory [pooled human immune globulin] and tear substitute [serum]) that simultaneously targets several immunological pathways may be more efficacious. This report evaluates if the combinatorial therapy resulted in clinical benefit in patients with recalcitrant OSD. MethodsWe performed a retrospective case study of patients receiving topical, preservative-free, compounded formulations of steroids, pooled human immune globulin, and serum tears. Outcome measures included visual acuity, ocular surface disease index (OSDI), ocular discomfort score, subjective global assessment (SGA), corneal staining, conjunctival redness, and slit lamp photographs. ResultsPatients consisted of one male and 11 females ranging in age from 27 to 87 years old. Pathologies included ocular graft-versus-host disease (n = 4), Sjögren's syndrome (n = 3), ocular cicatricial pemphigoid (n = 1), pemphigus vulgaris (n = 1), peripheral ulcerative keratitis (n = 1), Stevens-Johnson syndrome (n = 1), and giant papillary conjunctivitis (n = 1). All patients were “improved” or “much improved” on SGA after combinatorial therapy. There was a clinically meaningful reduction in OSDI, ocular discomfort, corneal staining, and conjunctival injection. Additionally, three patients had improvement in their visual acuity (one from 20/400 to 20/20). Adverse effects included increased intraocular pressure in two patients, presumably due to topical steroid use. ConclusionsCombinatorial therapy provides clinical benefit by reducing the symptoms and signs in recalcitrant OSD. Our study provides the rationale for performing prospective clinical trials to evaluate the efficacy of combinatorial therapy for treating recalcitrant OSD.

Updates and Insights in the Diagnosis and Management of DRESS Syndrome.

Purpose of ReviewTo provide updates on recent advances in the diagnosis and management of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.Recent FindingsThe number of identified HLA allele associations with DRESS continues to grow. There is increasing evidence indicating viral infection, reactivation, and cross-reactivity may play key roles in disease. Translational work illuminated JAK/STAT activation in recalcitrant disease. There is expanding recognition of rapid-onset DRESS resulting from specific drugs.SummaryDRESS is a severe form of adverse drug reaction with potential for significant morbidity and mortality. Recent research advances may improve clinical care. HLA screening can now be performed to prevent disease in susceptible patients and may help identify culprit drugs in the near future. Viral testing should be performed on every patient, and if positive, patients potentially treated with antiviral therapy. JAK inhibitors may be an effective treatment option for DRESS. Early onset of disease relative to drug exposure should not exclude the diagnosis of DRESS.

Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma.

Simple SummaryNext-generation sequencing of head and neck squamous cell carcinoma has revealed multiple new gene mutations, while simultaneously confirming the role of others in head and neck cancer tumorigenesis. The ever-expanding number of actionable druggable targets has fuelled a plethora of clinical trials assessing various pharmacotherapeutics in the management of this group of cancers. This review paper summarizes the state of play of molecular therapies used in head and neck oncology with particular focus dedicated to current FDA-approved drugs and emerging therapies undergoing advanced clinical trials.Head and neck cancer affects nearly 750,000 patients, with more than 300,000 deaths annually. Advances in first line surgical treatment have improved survival rates marginally particularly in developed countries, however survival rates for aggressive locally advanced head and neck cancer are still poor. Recurrent and metastatic disease remains a significant problem for patients and the health system. As our knowledge of the genomic landscape of the head and neck cancers continues to expand, there are promising developments occurring in molecular therapies available for advanced or recalcitrant disease. The concept of precision medicine is underpinned by our ability to accurately sequence tumour samples to best understand individual patient genomic variations and to tailor targeted therapy for them based on such molecular profiling. Not only is their purported response to therapy a factor of their genomic variation, but so is their inclusion in biomarker-driven personalised medicine therapeutic trials. With the ever-expanding number of molecular druggable targets explored through advances in next generation sequencing, the number of clinical trials assessing these targets has significantly increased over recent years. Although some trials are focussed on first-line therapeutic approaches, a greater majority are focussed on locally advanced, recurrent or metastatic disease. Similarly, although single agent monotherapy has been found effective in some cases, it is the combination of drugs targeting different signalling pathways that seem to be more beneficial to patients. This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in this area while also summarising ongoing efforts to bring more molecular therapies into clinical practice.

Review article: Topical antibiotic treatments for acute otitis externa: Emergency care guidelines from an ear, nose and throat perspective.

Acute otitis externa (AOE), also known as ‘swimmer's ear’, is a common acute problem. It is one of the most common ED presentations. Atypical organisms, recalcitrant disease and antibiotic options contribute to making AOE a clinical challenge. There are a number of red flags associated with AOE which require consideration when treating patients with AOE. We discuss an evidence‐based approach to management of AOE in the emergency setting, with indications for specialist referral.

Combined therapy of ocular surface disease with plasma rich in growth factors and scleral contact lenses

PurposeTo review safety and efficacy of combined plasma rich in growth factors (PRGF) eye drops and scleral contact lens (SCL) therapy in patients with ocular surface disease. MethodsPatients with ocular surface disease of various etiologies were screened for at least 3 months of concurrent treatment with PRGF and SCL. Retrospective pre- and post-treatment measurements were collected, including patient satisfaction, severity and frequency of dry eye symptoms measured by a modified Symptom Assessment in Dry Eye (SANDE) questionnaire, visual acuity, and number of concurrent treatments. Results26 patients with ocular surface disease were included in the study with 20 patients answering the questionnaire (77% response rate). There were no adverse events reported. Most patients thought the combined therapy was better than previous treatments and would recommend to others (80%, 90% respectively). SANDE scores significantly decreased after use of concurrent therapy. There was a small but significant decrease in the number of other concurrent treatments. Visual acuity was unchanged. ConclusionsThis retrospective cohort study found PRGF used in combination with SCL is safe and significantly decreases symptoms in patients with recalcitrant ocular surface disease.

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease

PurposeAspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy. Clinical biomarkers predicting response to intranasal LAS, long-term side effects and consequences of discontinuing treatment have been evaluated.MethodsA retrospective analysis of a database of 60 N-ERD patients seen between 2012 and 2020 was performed in March 2021. They were followed up at 3-months, 1-, 2- and 3-years with upper and lower airway functions assessed at each follow-up.ResultsHigher nasal airflow and smell scores were found at each follow-up in patients taking LAS (p < 0.001 and p = 0.048 respectively). No influence of LAS on pulmonary function measurements was observed. Patient on intranasal LAS showed a lower rate of revision sinus surgery when compared to those who discontinued the treatment (p < 0.001). None of the variables studied was found to influence LAS treatment response.ConclusionOur study demonstrates the clinical effectiveness of long-term intranasal LAS in the management of N-ERD in terms of improved nasal airflow and olfaction and a reduced need for revision sinus surgery. Intranasal LAS is safe, being associated with a lower rate of side effects when compared to oral ATAD. However, discontinuation of the treatment at any stage is associated with a loss of clinical benefit.

Methotrexate for generalized granuloma annulare: A 60% response rate in a retrospective case series of 15 patients

Methotrexate for generalized granuloma annulare: A 60% response rate in a retrospective case series of 15 patients

Effects of Visfatin on Intracellular Mechanics and Catabolism in Human Primary Chondrocytes through Glycogen Synthase Kinase 3β Inactivation.

Osteoarthritis (OA) is still a recalcitrant musculoskeletal disease on account of its complex biochemistry and mechanical stimulations. Apart from stimulation by external mechanical forces, the regulation of intracellular mechanics in chondrocytes has also been linked to OA development. Recently, visfatin has received significant attention because of the clinical finding of the positive correlation between its serum/synovial level and OA progression. However, the precise mechanism involved is still unclear. This study determined the effect of visfatin on intracellular mechanics and catabolism in human primary chondrocytes isolated from patients. The intracellular stiffness of chondrocytes was analyzed by the particle-tracking microrheology method. It was shown that visfatin damages the microtubule and microfilament networks to influence intracellular mechanics to decrease the intracellular elasticity and viscosity via glycogen synthase kinase 3β (GSK3β) inactivation induced by p38 signaling. Further, microtubule network destruction in human primary chondrocytes is predominantly responsible for the catabolic effect of visfatin on the cyclooxygenase 2 upregulation. The present study shows a more comprehensive interpretation of OA development induced by visfatin through biochemical and biophysical perspectives. Finally, the role of GSK3β inactivation, and subsequent regulation of intracellular mechanics, might be considered as theranostic targets for future drug development for OA.