Early onset metastatic colorectal cancer in Australia.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.

Evaluation of a machine learning tool for the early identification of patients with undiagnosed psoriatic arthritis - A retrospective population-based study.

Background: Psoriatic arthritis (PsA), an immune-mediated chronic inflammatory skin and joint disease, affects approximately 0.27% of the adult population, and 20% of patients with psoriasis. Up to 10% of psoriasis patients are estimated for having undiagnosed PsA. Early diagnosis and treatment can prevent irreversible joint damage, disability and deformity. Questionnaires for screening to identify undiagnosed PsA patients require patient and physician involvement. Objective: To evaluate a proprietary machine learning tool (PredictAI™) developed for identification of undiagnosed PsA patients 1-4 years prior to the first time that they were suspected of having PsA (reference event). Methods: This retrospective study analyzed data of the adult population from Maccabi Healthcare Service between 2008 and 2020. We created 2 cohorts: The general adult population ("GP Cohort") including patients with and without psoriasis and the Psoriasis cohort ("PsO Cohort") including psoriasis patients only. Each cohort was divided into two non-overlapping train and test sets. The PredictAI™ model was trained and evaluated with 3 years of data predating the reference event by at least one year. Receiver operating characteristic (ROC) analysis was used to investigate the performance of the model, built using gradient boosted trees, at different specificity levels. Results: Overall, 2096 patients met the criteria for PsA. Undiagnosed PsA patients in the PsO cohort were identified with a specificity of 90% one and four years before the reference event, with a sensitivity of 51% and 38%, and a PPV of 36.1% and 29.6%, respectively. In the GP cohort and with a specificity of 99% and for the same time windows, the model achieved a sensitivity of 43% and 32% and a PPV of 10.6% and 8.1%, respectively. Conclusions: The presented machine learning tool may aid in the early identification of undiagnosed PsA patients, and thereby promote earlier intervention and improve patient outcomes.

Initial experience of TAS-102 chemotherapy in Australian patients with Chemo-refractory metastatic colorectal cancer.

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.

Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Use of high-resolution thermography as a validation measure to confirm epidural anesthesia in mice: a cross-over study.

BACKGROUND: Effective epidural anesthesia is confirmed in humans by sensory assessments but these tests are not feasible in mice. We hypothesized that, in mice, infrared thermography would demonstrate selective segmental warming of lower extremities following epidural anesthesia. METHODS: We anesthetized 10 C57BL/6 mice with isoflurane and then inserted a PU-10 epidural catheter under direct surgical microscopy at T11-12. A thermal camera (thermal sensitivity ±0.05°C, pixel resolution 320x240 pixels, and spatial resolution 200 µm) recorded baseline temperature of front and rear paws, tail and ears. Thermography was assessed at baseline and 2, 5, 10, and 15 min after an epidural bolus dose of 50 µL bupivacaine 0.25% or 50 µL saline (control) using a cross-over design with dose order randomized and investigators blinded to study drug. Thermal images were recorded from video and analyzed using FLIR software. Effect over time and maximal effect (Emax) were assessed by repeated measures ANOVA and paired t-tests. Comparisons were between bupivacaine and control, and between lower vs upper extremities. RESULTS: Epidural bupivacaine caused progressive warming of lower compared with upper extremities (P <0.001), typically returning to baseline by 15 min after administration. Mean (±SD) Emax was +3.73 (±1.56) °C for lower extremities compared with 0.56 (±0.68) °C (P=0.03) for upper extremities. Following epidural saline, there was no effect over time (Emax for lower extremities -0.88 (±0.28) °C compared with the upper extremities -0.88 (±0.19) °C (P >0.99). CONCLUSIONS: Thermography is a useful tool to confirm epidural catheter placement in animals for which subjective, non-noxious, sensory measures are impossible.

Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss.

Bone loss in astronauts during spaceflight may be a risk factor for osteoporosis, fractures and renal stone formation. We previously reported that the bisphosphonate alendronate, combined with exercise that included an Advanced Resistive Exercise Device (ARED), can prevent or attenuate group mean declines in areal bone mineral density (aBMD) measured soon after ~ 6-month spaceflights aboard the International Space Station (ISS). It is unclear however if the beneficial effects on postflight aBMD were due to individual or combined effects of alendronate and ARED. Hence, 10 additional ISS astronauts were recruited who used the ARED (ARED group) without drug administration using similar measurements in the previous study, i.e., densitometry, biochemical assays and analysis of finite element (FE) models. In addition densitometry data (DXA and QCT only) were compared to published data from crewmembers (n = 14-18) flown prior to in-flight access to the ARED (Pre-ARED). Group mean changes from preflight (± SD %) were used to evaluate effects of countermeasures as sequentially modified on the ISS (i.e., Pre-ARED vs. ARED; ARED vs. Bis+ARED). Spaceflight durations were not significantly different between groups. Postflight bone density measurements were significantly reduced from preflight in the Pre-ARED group. As previously reported, combined Bis+ARED prevented declines in all DXA and QCT hip densitometry and in estimates of FE hip strengths; increased the aBMD of lumbar spine; and prevented elevations in urinary markers for bone resorption during spaceflight. ARED without alendronate partially attenuated declines in bone mass but did not suppress biomarkers for bone resorption or prevent trabecular bone loss. Resistive exercise in the ARED group did not prevent declines in hip trabecular vBMD, but prevented reductions in cortical vBMD of the femoral neck, in FE estimate of hip strength for non-linear stance (NLS) and in aBMD of the femoral neck. We conclude that a bisphosphonate, when combined with resistive exercise, enhances the preservation of bone mass because of the added suppression of bone resorption in trabecular bone compartment not evident with ARED alone.