Laser and Light-Based Therapies for Hirsutism Management in Women With Polycystic Ovarian Syndrome: A Systematic Review.

Importance: Hirsutism represents a significant concern for women with polycystic ovary syndrome (PCOS), with deleterious psychological effects warranting acknowledgment and a clear imperative to provide effective management. To our knowledge, this is the first review to exclusively examine the effectiveness of laser and light-based therapies in addressing hirsutism in women with PCOS. Objective: To synthesize the existing literature regarding the effectiveness of laser and light hair reduction therapies, either as stand-alone treatments or in combination with systemic agents, in treating hirsutism for women with PCOS. Evidence Review: A systematic literature review was performed using MEDLINE, Embase, EMCARE, and CINAHL according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Articles written in English, reporting on patients who met pre-established inclusion criteria were selected. Objective and subjectively measured outcomes relating to the effect of laser or light-based hair reduction therapies on hirsutism were abstracted. Heterogeneity among included studies precluded a meta-analysis, necessitating a narrative synthesis. Findings: Six studies reporting data on 423 individual patients with PCOS who underwent laser or light-based hair reduction therapies were included: 4 randomized clinical trials and 2 cohort studies. Alexandrite laser demonstrated significant improvements in hirsutism severity and psychological outcomes, particularly at high-fluence application. Alexandrite laser was also found to be more effective than intense pulsed light (IPL). The combination of diode laser with either metformin or combined oral contraceptive pill was superior to the application of diode laser alone, just as the addition of metformin to IPL demonstrated superior results to IPL treatment alone. Overall, most interventions were well tolerated. The overall certainty of evidence across all outcomes and comparisons was limited in part due to the observational nature of some studies. Conclusions and Relevance: This systematic review highlights the potential of laser and light hair reduction therapies, both as stand-alone treatments and in combination with other pharmacological agents in PCOS. However, this review was limited by low certainty of the evidence, few studies evaluating effectiveness and safety in those with skin of color, and heterogeneity in outcome assessment. Future studies are needed to provide more robust evidence among diverse individuals with PCOS and hirsutism.

Benefits and Challenges of Treat-to-Target in Inflammatory Bowel Disease.

There is notable disparity between symptomatology and disease activity in a significant proportion of patients with inflammatory bowel disease (IBD), and escalation of treatment based on symptoms alone can fail to significantly alter the course of disease. The STRIDE-II position statement, published in 2021 by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organisation for the Study of IBD (IOIBD) provides the most current recommendations for a treat-to-target (T2T) approach in IBD. Despite the benefits offered by a T2T approach in IBD, there are numerous drawbacks and current limitations to its widespread implementation in real-world clinical practice. Owing to the lack of a standardised definition of MH, outcome data are heterogeneous and limit the comparability of existing data. Further, studies investigating the likelihood of achieving MH with a T2T approach are limited and largely retrospective. Evidence of the real-world feasibility of tight monitoring is currently minimal and demonstrates sub-optimal adherence among patients. Further, the few studies on the acceptability and uptake of a T2T approach in real-world practice demonstrate the need for increased acceptability on both patients' and clinicians' behalf. Real-world applicability is further limited by the need for repeated endoscopic assessments of MH as well as a lack of guidance on how to incorporate the various treatment targets into therapeutic decision-making. We aim to review the benefits and challenges of the T2T approach and to discuss potential solutions to further patient care.

Cyclosporine as an alternative immunosuppressant for steroid-resistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a multiorgan reaction associated with a broad range of commonly used medications. Most cases of DRESS syndrome resolve with cessation of the inciting agent; however, use of systemic immunosuppression, most commonly with oral corticosteroids, is also recommended in cases with visceral organ involvement.We report a case of steroid-resistant relapsing-remitting DRESS syndrome secondary to sulfasalazine. Our patient experienced significant flare of symptoms of DRESS syndrome with multiple attempts to wean prednisolone. Initiation of cyclosporine as an alternative immunosuppressive agent to long-term corticosteroids has resulted in a 6-month remission in both dermatological and hepatic sequelae of DRESS syndrome.

Rate of early hospital readmission amongst cirrhotic patients is high in Australia: experience from a single liver transplant centre.

BACKGROUND AND AIMS: The 30-day hospital readmission rate in cirrhotic patients has been demonstrated to be up to 40% in international studies, but is not well studied in Australia. The aim of the current study was to report on the rate and cause of 30-day hospital readmission from a single liver transplant referral centre, including a cost analysis of readmissions. METHODS: This was a retrospective study of consecutive cirrhotic patients admitted to a liver transplant centre in Victoria, Australia, between 1 January 2019 and 31 December 2019. Cases were identified through International Classification of Diseases, Tenth Revision, 10 coding for cirrhosis and its complications. Baseline demographic data, liver-related complications and unrelated extra-hepatic comorbidities, laboratory values and prognostic scores were collected from the electronic medical record. RESULTS: One hundred seventy-nine (63% men; median age at index admission, 59 years) patients who were admitted 427 times during the study period were included in the final analysis. The 30-day hospital readmission rate was 46%, with the majority of readmissions attributable to fluid overload (29%), miscellaneous reasons (27%) and infection (20%). One fifth of readmissions were considered preventable. History of variceal haemorrhage was found to be an independent predictor of 30-day hospital readmission. The annual cost of readmission is over AU$2.7 million and the median cost of hospital readmission was about AU$9000. CONCLUSIONS: The 30-day hospital readmission rate of 46% is higher than previously reported and almost half of cases were caused by either fluid overload or infection.

Sensitivity of two Australian melanoma risk tools to identify high-risk individuals among people presenting with their first primary melanoma.

AIMS: Regular skin examinations for early detection of melanoma are recommended for high-risk individuals, but there is minimal consensus regarding what constitutes 'high-risk'. Melanoma risk prediction models may guide this. We compared two online melanoma risk prediction tools: Victorian Melanoma Service (VMS) and Melanoma Institute Australia (MIA) risk tools; to assess classification differences of patients at high-risk of a first primary melanoma. METHODS: Risk factor data for 357 patients presenting with their first primary melanoma were entered into both risk tools. Predicted risks were recorded: 5-year absolute risk (VMS tool and MIA tool); 10-year, lifetime, and relative risk estimates (MIA tool). Sensitivities for each tool were calculated using the same high-risk thresholds. The MIA risk tool showed greater sensitivity on comparison of 5-year absolute risks (90% MIA vs 78% VMS). Patients had significantly higher odds of being classified as high or very-high risk using the MIA risk tool overall, and for each patient subgroup. Using either tool, patients of male gender or with synchronous multiple first primary melanomas were more likely to be correctly classified as high- or very-high risk using 5-year absolute risk thresholds; but tumour invasiveness was unrelated to risk. Classification differed when using the MIA risk categories based on relative risk. CONCLUSIONS: Both melanoma risk prediction tools had high sensitivity for identifying individuals at high-risk and could be used for optimising prevention campaigns. The choice of which risk tool, measure, and threshold for risk stratification depends on the intended purpose of risk prediction, and ideally requires information on specificity.

Reduced melanoma referrals during COVID-19 lockdown.

As the COVID-19 pandemic has reduced face-to-face medical consultations, reduced diagnoses of thin melanomas and delayed presentations of thick melanomas were anticipated.

Expansion of Hydra actinoporin-like toxin (HALT) gene family: Expression divergence and functional convergence evolved through gene duplication.

Hydra actinoporin-like toxin 1 (HALT-1) was previously shown to cause cytolysis and haemolysis in a number of human cells and has similar functional properties to the actinoporins equinatoxin and sticholysin. In addition to HALT-1, five other HALTs (HALTs 2, 3, 4, 6 and 7) were also isolated from Hydra magnipapillata and expressed as recombinant proteins in this study. We demonstrated that recombinant HALTs have cytolytic activity on HeLa cells but each exhibited a different range of toxicity. All six recombinant HALTs bound to sulfatide, while rHALT-1 and rHALT-3 bound to two additional sphingolipids, lysophosphatidic acid and sphingosine-1-phosphate as indicated by the protein-lipid overlay assay. When either tryptophan133 or tyrosine129 of HALT-1 was mutated, the mutant protein lost binding to sulfatide, lysophosphatidic acid and sphingosine-1-phosphate. As further verification of HALTs' binding to sulfatide, we performed ELISA for each HALT. To determine the cell-type specific gene expression of seven HALTs in Hydra, we searched for individual HALT expression in the single-cell RNA-seq data set of Single Cell Portal. The results showed that HALT-1, 4 and 7 were expressed in differentiating stenoteles. HALT-1 and HALT-6 were expressed in the female germline during oogenesis. HALT-2 was strongly expressed in the gland and mucous cells in the endoderm. Information on HALT-3 and HALT-5 could not be found in the single-cell data set. Our findings show that subfunctionalisation of gene expression following duplication enabled HALTs to become specialized in various cell types of the interstitial cell lineage.