Publications by authors named "Frew J"

The pathogenesis of hidradenitis suppurativa is complex and multifaceted. Our understanding of disease mechanisms is in constant flux with new genetic, inflammatory, and microbiological insights upending previous paradigms and enlightening us as to the complex connections between different drivers of disease. This updated review integrates novel genetic insights from genome wide association studies, along with novel basic science data from single cell transcriptomic studies and recent interventional translational work to inform our evolving understanding of the disease.

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Current rheumatoid arthritis (RA) treatments do not restore immune tolerance. Investigating dendritic cell (DC) populations in human synovial tissue (ST) may reveal pathways to reinstate tolerance in RA. Using single-cell and spatial transcriptomics of ST biopsies, as well as co-culture systems, we identified condition- and niche-specific DC clusters with distinct functions.

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Hidradenitis Suppurativa is a burdensome inflammatory skin disease with significant quality of life impact. These management guidelines were developed to direct appropriate clinical management in the Australasian context. A systematic review was used for the basis of the consensus guidelines.

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Pyoderma gangrenosum is a severe ulcerative disease with a great need for novel therapies. A major barrier to the development of novel therapies is a lack of understanding of disease pathogenesis. We present the results of a proof-of-concept open-label clinical trial of IL-23p19 antagonism with tildrakizumab in pyoderma gangrenosum.

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Background/objectives: Surgical deroofing is an essential part of ongoing management of Hidradenitis Suppurativa, including persistent lesions non-responsive to medical therapy. The variables associated with delayed wound healing after surgical deroofing are contradictory within the literature due to the inclusion of heterogeneous surgical intervention methods. We aimed to assess the predictors of time to wound healing after surgical deroofing in HS.

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Article Synopsis
  • Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious skin reactions with high in-hospital mortality rates, ranging from 12-49%, prompting a need for better mortality prognostication.
  • This systematic review and meta-analysis examined factors that could predict mortality in SJS and TEN patients, focusing on predictors not included in the widely used SCORTEN scoring system.
  • The study found that conditions like preexisting renal disease, renal and respiratory involvement, diabetes, sepsis, comorbidity, and delayed hospitalization significantly increased the risk of death in these patients, providing valuable insights for clinical assessment.
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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to medications characterized by keratinocyte necrosis leading to loss of protective barrier function and increased susceptibility to infection. Infection is a major cause of morbidity, and septicemia is the leading cause of mortality in this population. This systematic review and meta-analysis aimed to determine infectious complications' prevalence and risk factors in adults with SJS and TEN.

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  • A study investigated whether stereotactic body radiotherapy (SBRT) is just as effective as standard radiotherapy for treating localized prostate cancer in terms of treatment failure rates.
  • The trial involved 874 men with early-stage prostate cancer, comparing SBRT (36.25 Gy in 5 sessions) to conventional radiotherapy (78 Gy in 39 sessions or 62 Gy in 20 sessions) over several weeks, focusing on the chance of being free from cancer progression after 5 years.
  • Results showed that SBRT was noninferior to standard treatment, with similar success rates in preventing cancer failure (95.8% for SBRT vs. 94.6% for control) but higher rates of genitour
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Background: Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory disease with significant impact upon quality of life. Generic quality-of-life measures suffer from decreased face validity and content validity, leading to the development of disease-specific quality-of-life measures such as the Hidradenitis Suppurativa Quality of Life (HiSQOL) outcome measure. The aim of this study was to validate the use of the HiSQOL in the Australian population and evaluate the quality-of-life impact in HS patients in Australia.

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Background: A significant proportion of US families are affected by substance use disorders. Both child- and adult- serving systems are called upon to care for families, yet the disciplines involved inherently have different priorities, preventing a true family-centered care model.

Objectives: The purpose of the scoping review was to explore the alignment of current national guidance related to the medical care of families affected by substance use disorders (SUD).

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Aims: To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA).

Material And Methods: This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression.

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Article Synopsis
  • Caucasian and Asian patients with hidradenitis suppurativa (HS) show notable differences in demographics such as age, gender, and body mass index (BMI), which may affect the effectiveness of treatments including biologics.
  • A study involving 170 patients in Australia found that Asian patients had lower BMI and higher disease severity, but both ethnic groups had similar treatment responses at Week 16.
  • Ultimately, the study concluded that ethnicity does not impact the effectiveness of the biologic drug adalimumab for HS when factoring in demographics and disease characteristics.
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Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens.

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Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)-alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive.

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Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia.

Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy.

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Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome.

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Article Synopsis
  • - The study examines inconsistencies in how healthcare providers and patients identify and count lesions associated with hidradenitis suppurativa (HS), highlighting potential issues in the existing clinical response measurement tool, HiSCR, and the impact of rater training on trial outcomes.
  • - An online survey of 47 members from the HISTORIC collaboration revealed significant variability in lesion classification, with many providers differing on whether lesions should be treated as single or multiple entities based on their morphology.
  • - Findings suggest a need for standardized, consensus-driven guidelines for rater training in HS clinical trials to improve consistency in lesion characterization and potentially enhance trial results.
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Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy.

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Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies.

Objectives: To explore the effects of spesolimab treatment in patients with HS.

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