Concord Repatriation General Hospital

Technical advancements in abdominal flap-based autologous breast reconstruction (ABR) have focussed on minimizing abdominal wall morbidity. However, no consensus exists on the technique that maximises abdominal function, particularly in cases of bilateral ABR. This systematic review critically appraises the literature to assess abdominal wall function following abdominal flap-based ABR. A literature search was performed following PRISMA guidelines. Four databases (Embase (via Ovid), Medline (via Ovid), Cochrane Library and PubMed) were searched. The primary outcome was abdominal wall function following abdominal flap-based ABR measured by sit-up performance, manual muscle function testing, isokinetic dynamometry and ultrasound. 38 studies were included comparing various types of abdominally-based autologous flaps used for breast reconstruction. Sit-up ability was highest in DIEP group (87%) when compared to free TRAM (25%) and pedicled TRAM (12%). Bilateral DIEP had higher combined mean upper rectus and lower rectus abdominis function scores (4.54) compared to bilateral free TRAM (3.87), where 5 represents normal function. Bilateral ABR demonstrated worse abdominal function compared with unilateral ABR in all flap types. DIEP flaps yield superior abdominal muscle function outcomes compared to TRAM flaps of all types, particularly when performing bilateral ABR. Future research should aim to standardise abdominal function measurement and reporting of intra-operative variables, such as the length of fascial and muscle incisions, the number of abdominal motor nerve branches sacrificed, and the use of abdominal mesh to enable more complete understanding of the impact of abdominal flap-based ABR on abdominal wall function.

Abstract Charcot-Marie-Tooth (CMT) neuropathy is a clinically and genetically heterogeneous group of diseases characterised by the length dependent axonal degeneration of peripheral nerves. We previously mapped a rare form of X-linked CMT, CMTX3, to a 5.7-Mb interval on chromosome Xq26.3-q27.1 and excluded the coding region of all known genes in the linkage interval for mutations. Whole genome sequencing subsequently identified a 78-kb region of chromosome 8q24.3, that had been duplicated and inserted into the CMTX3 locus between the genes HAPSTR2 and SOX3 . The 78-kb insertion, which contains a partial transcript of ARHGAP39 , fully segregated in families with CMTX3 and was absent in neurologically normal controls. To retain the CMTX3 insertion and investigate its consequences in appropriate neuronal tissue, we generated induced pluripotent stem cells (iPSC) from CMTX3 fibroblasts. Using bulk RNA sequencing of patient-derived spinal motor neurons, ARHGAP39 was deemed non-pathogenic by excluding both the formation of novel fusion transcripts and dosage effects from the partial duplication. Subsequent NanoString expression analyses of candidate genes within the CMTX3 locus, across different stages of neuronal differentiation, identified spatiotemporal dysregulation of SOX3. NanoString showed reduced SOX3 expression in patient iPSC. RNA sequencing detected SOX3 downregulation in CMTX3 neuroepithelial progenitor cells, which was further confirmed by quantitative proteomics. Given the early onset and relatively rapid progression of CMTX3, these data prioritise SOX3 as a leading candidate gene, consistent with its role as one of the earliest transcription factors expressed in the developing nervous system and a key regulator of neuronal fate.

To compare the ALGO Smart Pump (ALGO), operating in Adaptive Pulsatile Aspiration (APA™) and Static modes, with the Penumbra ENGINE during in-vitro mechanical thrombectomy, and to determine whether adaptive pulsatile aspiration improves complete clot ingestion (CCI) and reduces aspiration time across catheters sizes and catheter-to-artery (C/A) ratios. Apre-specified integrative analysis of two previously completed in-vitro thrombectomy studies was conducted using astandardized middle cerebral artery occlusion model. Atotal of 720 thrombectomy procedures were performed by two experienced operators using twelve commercial catheters (six small-bore, six large-bore). Three aspiration modalities were tested: ALGO APA™, ALGO Static, and Penumbra ENGINE continuous aspiration (n = 30 per catheter-pump pairing). The primary endpoint was CCI; secondary endpoint was aspiration time. Outcome analysis included two-way ANOVA and Chi-squared tests, with catheter, operator, and C/A ratio terms. The ALGO demonstrated ahigher median CCI rate than Penumbra (81.4% vs. 56.1%, χ2(1) = 52.364, p < 0.001). Aspiration times were significantly shorter with ALGO, particularly in APA™ mode (43.8 s vs. 60.6 s, p < 0.001). Two-way ANOVA demonstrated significant interaction between catheter size and pump type (p < 0.001), with ALGO notably improving small-bore catheter performance. CCI correlated positively with catheter-to-artery (C/A) ratio across both systems, with ALGO maintaining higher success across all ratios. Adaptive pulsatile aspiration enhances clot ingestion efficiency and reduces aspiration time in an in-vitro thrombectomy model, particularly for smaller catheters. These findings support further translational studies on optimizing aspiration dynamics to enhance first-pass success in endovascular stroke therapy.

BACKGROUND:The pullback pressure gradient (PPG) is a novel physiological metric that quantifies coronary artery disease patterns as focal or diffuse on a scale from 0 to 1. This study assessed the relationship between PPG and residual angina at 1 year.METHODS:PPG Global is a prospective, investigator-initiated, single-arm, multicenter study that enrolled patients with at least 1 lesion with a fractional flow reserve ≤0.80 intended to be treated with percutaneous coronary intervention. After the PPG calculation, physicians could revise treatment assignment to medical therapy or coronary artery bypass graft surgery instead of percutaneous coronary intervention. Focal and diffuse disease were defined based on the median PPG value of 0.62. Patient-reported outcomes were assessed using the Seattle Angina Questionnaire at baseline and 1-year follow-up.RESULTS:The study included 947 patients with PPG and the Seattle Angina Questionnaire at 1 year. The mean age was 67.6±10.2 years, 24% were female, and 29% had diabetes. At 1 year, patients with focal coronary artery disease reported less angina than those with diffuse disease (Seattle Angina Questionnaire angina frequency score, 95.3±9.9 versus 92.5±15.0; P=0.006). PPG was independently associated with improvement in angina (P=0.017).CONCLUSIONS:In patients with flow-limiting coronary artery disease, a focal disease pattern defined by high PPG was associated with greater symptomatic relief at 1 year compared with diffuse disease (low PPG). By capturing the underlying pathophysiologic distribution of epicardial disease and its relation to post-treatment symptom relief, PPG may support a more tailored revascularization decision-making and percutaneous coronary intervention strategy.

355 Background: IKS014 is an ADC targeting HER2 that comprises a humanized IgG1 antibody conjugated to the monomethyl auristatin F payload, via a novel β-glucuronidase-cleavable linker. IKS014 has been evaluated by a separate sponsor in trials conducted exclusively in China. Preliminary signs of anti-tumor activity, including objective responses in various tumor types, were previously noted at doses ≥ 1.0 mg/kg (≥ 40 mg/m 2 ). Methods: IKS014-01 is a non-randomized, open-label, multicenter trial of IKS014 in participants with advanced solid tumors that express HER2 (NCT05872295). The trial is divided into two parts: Part I, a dose-escalation portion (DE) and Part II which includes 4 disease-specific Expansion Cohorts. Data from the DE portion is presented. The DE portion is intended to establish the MTD and/or a recommended dose for IKS014 monotherapy to be evaluated in Part II and to provide initial safety, efficacy, PK, PD, and immunogenicity data. Key exclusion criteria include clinically significant cardiovascular, pulmonary, or hepatic disease; or active central nervous system involvement. Participants in the DE portion must have HER2+ (IHC3+, IHC2+/ISH+) or HER2 low (IHC2+/ISH- or IHC1+) expressing solid tumors. IKS014 is infused once every 3 weeks. Participants were enrolled into cohorts of increasing dose levels using a standard 3+3 design and monitored for DLTs during Cycle 1. Results: As of July 2025, 62 patients have been treated with IKS014 across five dose levels (40, 60, 90, 120 and 105 mg/m 2 ) including 4 enrichment cohorts, during Part I DE. Among the safety population (across all dose levels and tumor indications); the most common treatment-related adverse events in descending order were dry eye, hypokalemia, keratitis, dry mouth, nausea, pneumonitis, fatigue, alopecia, decreased appetite, and aminotransferase increased. Per protocol, the MTD has not been achieved as only one dose limiting toxicity (DLT) has been observed to date. A DLT of Grade 3 Infusion Reaction was seen in 1 of 21 patients treated at the 120 mg/m 2 dose level. Encouraging anti-tumor activity was seen across all dose levels and in various tumor indications such as breast, esophageal, ovarian and gallbladder cancer and in patients with HER2+ and HER2 low tumors. Of interest, 10 patients with HER2+ esophageal cancer, who had received prior therapy (median 3, range 1-6), have been enrolled in the study. All patients had received prior HER2-targeting therapies such as trastuzumab or trastuzumab emtansine. Among these 10 patients, 5 have achieved a response and 3 demonstrated stable disease &gt; 6 months resulting in a clinical benefit rate (CBR) of 80% with IKS014. Conclusions: These early signs of activity and the high CBR in this small subset of pretreated patients with esophageal cancer warrant further exploration. Clinical trial information: NCT05872295 .

Breathlessness is a common symptom linked to various respiratory and cardiac conditions, often causing delays in diagnosis and management in primary care. This study aimed to develop an algorithm using Bayesian Networks (BN) to predict ten conditions associated with presentations of breathlessness. The study included individuals aged 16years and older with breathlessness recorded as the reason for visiting a general practitioner (GP) between 2002 and 2024 in 50 practices in the United Kingdom (UK). Thirty-four characteristics including demographic, symptoms, comorbidities and medication histories were considered as predictors. A total of 384,994 breathlessness episodes from 136,215 patients were analysed, with 55% being female and 42% aged over 60years. The BN achieved good performance with area under the curve (ROC-AUC) values ranging from 0.68 for non-pneumonia lower respiratory tract infections (LRTI) to 0.94 for heart failure. The algorithm demonstrated strong predictive performance and could help GPs prioritise early and targeted diagnostic tests for the most likely causes of breathlessness, potentially reducing both diagnostic delays and costs.

Objective:We evaluated Australian adults’ knowledge on the risk factors and complications of hypertension to identify areas of poor understanding.Methods:In 2024, an adapted validated hypertension-knowledge survey was distributed to participants who had used kiosk BP stations in retail stores across metropolitan and remote Australia. Kiosk stations collected measured and self-reported data.Results:A total of 826 participants (51% male; mean age 52 ± 16 years; 36% with a history of hypertension) completed the survey. Participants generally demonstrated a good understanding of hypertension risk factors, with 90% recognizing that being overweight increases risk, and that exercise helps lower BP. Twenty-seven percent were unaware that hypertension is usually asymptomatic; 41% did not know that stress is not its main cause; and 42% were unaware of the importance of medication adherence. Seventy-three percent and 77% were unaware of the increased risk of dementia and kidney disease, respectively.People with a history of hypertension (vs. no hypertension; P = 0.01) and those in outer regional areas (vs. major cities, inner regional, or remote; P = 0.011) had better knowledge. Individuals who were unemployed or had lower educational backgrounds (both P < 0.001) had poorer knowledge. Kiosk BP readings and the use of antihypertensive medications were not associated with knowledge scores.Conclusions:Public misconceptions regarding hypertension persist. With three in four participants unaware that hypertension increases the risk of dementia and kidney disease, and with limited understanding of the importance of medication adherence, educational efforts are essential, particularly among people who are unemployed or have lower educational backgrounds.