Macquarie University Hospital

Purpose The aim of this study is to evaluate the impact of graft size and time between injury to surgery (TBIS) on static anterior tibial translation (SATT) and dynamic anterior tibial translation (DATT) after anterior cruciate ligament (ACL) reconstruction. Methods A consecutive series of patients treated with primary ACL reconstruction using hamstring autograft was reviewed. Preoperative SATT, DATT and posterior tibial slope (PTS) were measured with a previously validated technique by two independent reviewers on lateral weight‐bearing knee radiographs. Regression analysis was performed to assess the relationship between postoperative—preoperative SATT difference (Δ SATT) and postoperative—preoperative DATT difference (Δ DATT) with graft size and TBIS. Results In total, 66 patients were included in this study. The mean preoperative SATT and DATT were 2.41 (standard deviation [SD] 2.98) and 9.09 (SD 3.19), respectively. The mean postoperative SATT and DATT were 2.14 (SD 2.47) and 5.28 (SD 2.55), respectively. The mean graft size was 8.4 mm (SD 8.4; range 7.75–10), and the median TBIS was 3 months (range 1–275). Linear regression analysis showed no correlation between graft size and Δ SATT (p = 0.060) and Δ DATT (p = 0.979) and no correlation between TBIS and Δ SATT (p = 0.817) and Δ DATT (p = 0.811). Conclusion Our results suggest that larger graft sizes or shorter times between injury and reconstruction do not impact the reduction of SATT or DATT following ACL reconstruction. Level of Evidence Level IV, retrospective cohort study.

Background Psoriasis is a risk factor for cardiovascular disease (CVD). This risk is independent and incremental to traditional cardiovascular (CV) risk factors, but clinician and patient perspectives on this risk are unclear. This study aims to assess the knowledge, perceptions, and practice of clinicians and patients with respect to psoriasis and CVD. Methods This cross‐sectional study consisted of a self‐administered questionnaire capturing demographic characteristics, knowledge of the association between psoriasis and CVD, and perspectives on CV screening and management. This was distributed to members of relevant Australasian Speciality Medical Colleges, speciality societies, and psoriasis patients in public and private clinic settings. Survey data were assessed using descriptive statistics. Logistic regression was used to investigate the relationship between categorical variables and the outcome variable, for example, to determine factors predictive of clinician knowledge and perceptions. For all analyses, a p ‐value of less than 0.05 was considered statistically significant. Results A total of 298 clinicians (dermatologists (86), rheumatologists (56), cardiologists (53), general practitioners (103)) and 102 patients with psoriasis were surveyed. Regarding clinician knowledge of the association between psoriasis and CVD, dermatologists and rheumatologists indicated knowledge of this association (98.8%) (85/96) and 91.1% (51/56) respectively, while only 54.7% (29/53) of cardiologists and 29.1% (30/103) of GPs indicated knowledge of this association. Only 23.5% (24/102) of patients surveyed indicated knowledge of this association. Clinicians with a higher proportion of their caseload including psoriasis patients were significantly more likely to be aware of the association between psoriasis and CVD (OR 3.05 [1.64, 5.68]; p < 0.001). Most clinicians nominated GPs as best placed to facilitate CV risk factor screening and management (dermatologists 80.2% (69/86); rheumatologists 83.9% (47/56); cardiologists 75.5% (40/53); GPs 88.3% (91/103)). Patients preferred specialist input and multidisciplinary care for CVD risk management; 34.3% (35/102) nominated a cardiologist as the preferred clinician, and 23.5% (24/102) indicated preference for a multidisciplinary team. Limitations The possibility of sampling and response bias, inherent in the study design, is acknowledged; however, responses are likely representative of clinician and patient sentiments on this issue and in keeping with similar study findings. Conclusion Clinician and patient knowledge of the relationship between psoriasis and CVD needs to be improved. The establishment of a national consensus approach to address this gap in clinical care is needed.

Panurethral strictures comprise about 4.9% of urethral stricture disease presentations and can have a significant impact on patient quality of life (1). The definition of “panurethral” is debated in the literature; however, one definition describes any single or multifocal diseased area of the penile and/or bulbar urethra measuring ≥8 cm in length. Normal connective tissue is replaced by dense fibrosis with reduction in collagen, smooth muscle, and nitric oxide content in the diseased tissue (2). The penile inversion technique allows repair of panurethral strictures and lengthy penile urethral strictures with high success rates (3).

Purpose of Review This review evaluates the surgical management of male urinary incontinence (UI) following radiation therapy (RT) for prostate cancer, focusing on artificial urinary sphincters (AUS) and male urethral slings. It aims to assess recent evidence on the impact of RT on surgical treatment options for post-prostatectomy incontinence. Recent Findings Recent findings indicate that male urethral slings have lower success rates and higher complication rates in patients who have undergone prior RT. Conversely, although the AUS is the gold standard for treating post-prostatectomy UI, it also exhibits poorer outcomes and higher complication rates in post-RT patients compared to those without RT. Some recent studies suggest that administering RT after AUS implantation is associated with better continence outcomes, without increasing the risk of complications. Various techniques have also recently been developed to address urethral atrophy and persistent UI following AUS implantation, including the use of tunica albuginea flaps and downsizing to a 3.5 cm AUS cuff. It must be noted that despite increased complications, quality of life outcomes remains very favourable for patients who are post-RT and undergoing AUS implantation. The 7th International Consultation on Incontinence strongly recommends AUS as the surgical option for the post-prostatectomy incontinent male who has undergone RT. Summary In summary, AUS implantation significantly enhances continence and quality of life for RT patients, despite the increased risk of complications. Optimising outcomes in managing male UI post-RT requires tailored surgical approaches, thorough preoperative assessments, and realistic patient counselling.

439 Background: N+C showed significant benefits vs S in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for patients (pts) with previously untreated aRCC from the phase 3 CheckMate 9ER trial ( N Engl J Med 2021; 384:829–41). We report final results for the trial with a long-term follow-up (min, >5 y), including updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety. Methods: Pts with aRCC were randomized to receive first-line N 240 mg every 2 wk + C 40 mg QD or S 50 mg QD (4 wk of each 6-wk cycle) until disease progression or unacceptable toxicity (2 y N max.). The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Median follow-up was 67.6 (range, 60.2–80.2) mo. In ITT pts (N+C, n = 323; S, n = 328), PFS favored N+C vs S (hazard ratio [HR], 0.58 [95% CI, 0.49–0.70]). Median (95% CI) PFS (mPFS) was 16.4 (12.5–19.3) vs 8.3 (7.0–9.7) mo, respectively; 60-mo PFS rates were 13.6% vs 3.6%. OS also favored N+C vs S (HR, 0.79 [95% CI, 0.65–0.96]). Median (95% CI) OS (mOS) was 46.5 (40.6–53.8) vs 35.5 (29.2–42.8) mo, respectively; 60-mo OS rates were 40.9% vs 35.4%. ORR was greater with N+C vs S (55.7% vs 27.4%; complete response [CR], 13.9% vs 4.6%). Duration of response (DOR) rates at 60 mo with N+C vs S were 22.0% vs 10.0%, respectively. Efficacy by IMDC risk groups is reported in the Table. In all treated pts (n = 320 each arm), any-grade (grade ≥ 3) treatment-related adverse events occurred in 97.5% (67.8%) vs 93.1% (55.3%) with N+C vs S. No new deaths due to study drug toxicity occurred since the last database lock. Additional subgroup analyses will be presented. Conclusions: Long-term efficacy benefit was observed with N+C over S in this final follow-up from CheckMate 9ER. There were no new safety signals. The results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . FAVN+C; n = 74 FAVS; n = 72 INTN+C; n = 188 INTS; n = 188 PoorN+C; n = 61 PoorS; n = 68 PFS HR (95% CI) 0.67 (0.46–0.97) - 0.63 (0.50–0.80) - 0.36 (0.23–0.56) - mPFS (95% CI), mo 21.4 (12.8–24.6) 12.8 (9.4–16.6) 16.6 (11.3–21.7) 8.5 (6.9–10.4) 9.9 (5.9–17.7) 4.2 (2.9–5.7) 60-mo PFS rate, % 15.1 3.9 12.7 4.7 15.7 0 OS HR (95% CI) 1.08 (0.70–1.66) - 0.86 (0.67–1.11) - 0.49 (0.33–0.74) - mOS (95% CI), mo 53.7 (40.8–70.7) 58.9 (46.1–NE) 47.4 (38.2–55.8) 36.2 (25.7–46.3) 34.8 (21.4–53.4) 10.5 (6.8–20.7) 60-mo OS rate, % 46.3 49.4 41.2 38.2 33.1 12.9 ORR (95% CI), % 66.2 (54.3–76.8) 43.1 (31.4–55.3) 55.9 (48.4–63.1) 27.7 (21.4–34.6) 42.6 (30.0–55.9) 10.3 (4.2–20.1) CR, % 16.2 6.9 15.4 4.8 6.6 1.5 60-mo DOR rate, % a 22.0 NE 19.0 13.0 37.0 0 FAV, IMDC favorable; INT, IMDC intermediate; NE, not estimable; poor, IMDC poor. a Based on pts with objective response.

Introduction: Although idiopathic granulomatous mastitis (GM) of the breast is a benign condition, it can be locally aggressive and frequently chronic, causing significant pain and distress to the patient. Treatment often involves multiple disciplines including general practice, breast surgery/physicians, rheumatology and/or immunology. Traditional options for treatment include observation, oral steroids, methotrexate and/or surgery, all with variable outcomes. A more recent alternative treatment option involves intralesional steroid injections. Methods: Using PRISMA methodology, a systematic review of intralesional steroid injection for the management of GM was conducted. Medline, PubMed, Embase and Cochrane databases were searched for original studies reporting treatment protocols and clinical outcomes, published up to the end of September 2023. Results: Nine eligible studies reported outcomes in 474 patients undergoing treatment of GM with intralesional injections. All studies reported success (improvement in clinical and/or imaging appearance) with intralesional injections. Studies that had a comparison group showed statistically significantly fewer side effects compared to oral steroids or surgical management. The recurrence rate was less for intralesional injections than for other treatments in all studies except one. No studies included patient-reported outcomes. Conclusion: There is consistent evidence for the safety, efficacy and low recurrence rate with intralesional steroid injections for GM. The existing literature is heterogenous with respect to injection protocols, and the optimal protocol is unclear. Future research should compare the various steroid agents and dose/frequency of administration. Future studies should include cost analysis and patient-reported outcomes to ensure that the treatment is cost-effective and acceptable to people with idiopathic GM.

Purpose Perceived cancer-related cognitive impairment (CRCI) has been reported in prostate cancer survivors. Little is known about how CRCI impacts occupational functioning in working-aged prostate cancer survivors (PCS). This study aimed to investigate the association between CRCI and occupational functioning in PCS. Methods Data from 51 PCS, who were employed at the time of diagnosis, undergoing hormonal treatments (e.g., androgen deprivation therapy) or ‘watchful waiting’/ ‘active surveillance’, were analysed. An online survey assessed CRCI using the FACT-Cog Perceived Cognitive Impairments (PCI20) subscale, the EORTC-QLQ-30 two-item cognitive functioning scale, and a single ‘Yes/No’ CRCI item (i.e., were ‘changes in thinking (e.g., memory, attention)’ experienced as a treatment side effect). PCS also indicated ‘Yes/No’ to changes to their ability to work, performance of work duties, and decreased work hours. Logistic regression analyses examined the relationship between CRCI measures and occupational outcomes. Results Of the 51 PCS, 19 (37%) endorsed experiencing cognitive side effects from treatment. The single ‘Yes/No’ CRCI question was significantly associated with perceived changes in work ability and ability to perform work duties at the same level. PCI20 and the EORTC-QLQ-30 cognitive functioning scale were not significantly associated with any occupational outcomes. Conclusion Perceived CRCI is associated with adverse changes to occupational functioning and is important to consider when PCS are making plans to return-to-work following treatment. Implications for Cancer Survivors Prostate cancer survivors may experience cognitive changes, which may impact their work ability.

We assessed the performance of large language models’ summarizing clinical dialogues using computational metrics and human evaluations. The comparison was done between automatically generated and human-produced summaries. We conducted an exploratory evaluation of five language models: one general summarisation model, one fine-tuned for general dialogues, two fine-tuned with anonymized clinical dialogues, and one Large Language Model (ChatGPT). These models were assessed using ROUGE, UniEval metrics, and expert human evaluation was done by clinicians comparing the generated summaries against a clinician generated summary (gold standard). The fine-tuned transformer model scored the highest when evaluated with ROUGE, while ChatGPT scored the lowest overall. However, using UniEval, ChatGPT scored the highest across all the evaluated domains (coherence 0.957, consistency 0.7583, fluency 0.947, and relevance 0.947 and overall score 0.9891). Similar results were obtained when the systems were evaluated by clinicians, with ChatGPT scoring the highest in four domains (coherency 0.573, consistency 0.908, fluency 0.96 and overall clinical use 0.862). Statistical analyses showed differences between ChatGPT and human summaries vs. all other models. These exploratory results indicate that ChatGPT’s performance in summarizing clinical dialogues approached the quality of human summaries. The study also found that the ROUGE metrics may not be reliable for evaluating clinical summary generation, whereas UniEval correlated well with human ratings. Large language models may provide a successful path for automating clinical dialogue summarization. Privacy concerns and the restricted nature of health records remain challenges for its integration. Further evaluations using diverse clinical dialogues and multiple initialization seeds are needed to verify the reliability and generalizability of automatically generated summaries.

Background The penile suspensory ligament (PSL) plays a significant role in penile support and erection and its injury or congenital absence may result in functional impairment of erectile function. Aim To describe the diagnosis and surgical repair technique for PSL abnormalities and overall outcomes. Methods A comprehensive review of the literature was performed to understand the anatomic relevance of the PSL and historical management of PSL defects. A contemporary method for PSL repair is described using a transverse infrapubic incision with placement of midline anchoring (non-absorbable braided) sutures between the tunica albuginea (TA) and symphysis pubis to correct penile position and instability. Outcomes Surgical success defined as degree of penile curvature and penile stability for sexual intercourse as well as patient and partner satisfaction rates were reviewed. Results Though limited in number, available case series in the literature indicate a success rate between 85-100%, and more recent reviews fall in the 85-91% range. Patient satisfaction rates vary from 82-88%, but some series included patients with penile dysmorphic disorder and Peyronie’s disease, which are known to have higher dissatisfaction rates related to the underlying etiology itself. In patients with venogenic erectile dysfunction (ED), resolution was 100% but de novo ED occurred in 3-5%; these cases were all successfully managed medically. Clinical Implications This review addresses the diagnosis of PSL abnormalities and demonstrates a simple but effective repair technique to significantly improve erectile stability in men with acceptable risk. Strengths and Limitations This is a comprehensive review of the available research on PSL abnormalities that outlines its diverse patient presentation and a systematic method to diagnosis and repair PSL defects. The patient satisfaction rates are reasonably high but given the relatively rarity of this entity, larger longitudinal multi-institutional studies are required to further elucidate risks of de novo ED, penile shortening, and functional outcomes over the long-term. Conclusion PSL repair using permanent anchoring sutures or a fascial graft between the pubic symphysis and the TA of the corpora cavernosa is a safe and efficacious way to restore an important part of the penile suspensory apparatus that helps stabilize the penis during erection for normal sexual function.

Background/Aims There are spare data on comparative medication efficacy in fistulizing Crohn's disease (FCD), particularly with immunomodulator co-therapy. Persistence is a unique way to assess real-world outcomes. Methods The persistence of all dispensed biological agents were analysed from the Australian Pharmaceutical Benefits Scheme (PBS) registry data 2005-2021 for FCD. Propensity score matching was performed to account for baseline cohort imbalance. Results There were 5,739 lines of therapy in 4,466 patients over the 16-year period with 17,144 patient-years of follow-up; via therapy 2,605/5,739 (45.4%) used adalimumab and 3,134/5,739 (54.6%) used infliximab; 1,697/5,739 (29.6%) used thiopurine co-therapy at induction, whilst 242/5,739 (4.2%) used methotrexate. As a first-line biologic (biologic-naïve), infliximab showed superior overall- and corticosteroid-free persistence to adalimumab ( P =0.0002 and P =0.0021 respectively). Used after first-line (biologic-exposed), there was no difference between agents for overall persistence ( P =0.064) though infliximab showed greater corticosteroid-free persistence ( P =0.030). Co-induction with thiopurine was associated with improved overall- and corticosteroid-free persistence ( P =0.0002 and P =0.045 respectively). After propensity score matching, infliximab showed superior overall and corticosteroid-free persistence compared to adalimumab in bio-naïve ( P <0.0001 and P =0.0016 respectively), not in bio-exposed patients ( P =0.12 and P =0.074 respectively). Thiopurine was associated with superior overall- and corticosteroid-free persistence use, though no difference was seen with methotrexate. Conclusion The PANIC cohort with real-world data of non-hierarchical prescribing of biological agents supports the superiority of infliximab over adalimumab in bio-naïve FCD patients, but did not show a therapeutic difference in bio-exposed FCD. Thiopurine co-therapy was independently associated with improved biological agent persistence in FCD.

Background: Giant cell tumor of bone (GCTB) is a locally aggressive tumor. It accounts for only 5% of all bony tumors. Early diagnosis, and follow-up for recurrence is often difficult due to a lack of biogenetic markers. Giant cells are multinucleated epithelioid cells derived from macrophages. Histologically, giant cells are also present in other pathologies of bone, e.g., aneurysmal bone cyst, chondroblastoma, giant cell granuloma, and malignant giant cell tumor, etc. Similarly, radiographic findings overlap with other osteolytic lesions, making the diagnosis and prognosis of giant cell tumor very challenging. Aims and Objectives: The purpose of this study was to explore biological and genetic markers which can be used for detection, differentiation, recurrence, and prognosis of GCTB. This will help to better understand the clinical outcome of GCTB and minimize the need for interventions. Methods: We conducted a literature search using Google, Google Scholar, PubMed, Wiley Library, Medline, Clinical trials.org, and Web of Science. Our search strategy included MeSH terms and key words for giant cell tumor and biogenetic markers from date of inception to September 2020. After excluding review articles, 246 duplicates, and non-relevant articles, we included 24 articles out of 1568 articles, summarizing the role of biogenetic markers in the prognosis of GCT. Results: P63 is 98.6% sensitive and relatively specific for GCT as compared to other multinucleated giant cells containing neoplasms. MDM2 (mouse double minute 2 homolog), IGF1 (insulin-like growth factor 1), STAT1 (signal transducer and activator of transcription 1), and RAC1 (Ras-related C3 botulinum toxin substrate 1) are associated with GCTB recurrence, and might serve as biomarkers for it. Increased expression of the proteins STAT5B, GRB2, and OXSR1 was related to a higher probability of metastasis. H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of giant cell tumor of bone (GCTB) and chondroblastoma from other giant cell-containing tumors. A neutrophil to lymphocyte ratio (NLR) > 2.70, platelet to lymphocyte ratio (PLR) > 215.80, lymphocyte to monocyte ratio (LMR) ≤ 2.80, and albumin to globulin ratio (AGR) < 1.50 were significantly associated with decreased disease-free survival (DFS) (p < 0.05). Large amounts of osteoclast-related mRNA (cathepsin K, tartrate-resistant acid phosphatase, and matrix metalloproteinase9) in GCTs (p < 0.05) are associated with the grade of bone resorption. We propose that subarticular primary malignant bone sarcomas with H3.3 mutations represent true malignant GCTB, even in the absence of a benign GCTB component. IMP3 and IGF2 might be potential biomarkers for GCT of the spine in regulating the angiogenesis of giant cell tumor of bone and predicting patients’ prognosis. Conclusions: This review study shows serological markers, genetic factors, cell membrane receptor markers, predictive markers for malignancy, and prognostic protein markers which are highly sensitive for GCT and relatively specific for giant cell tumor. MDM2, IGF1, STAT1, RAC1 are important makers in determining recurrence, while P63 and H3F3A differentiate GCT from other giant cell-containing tumors. STAT5B, GRB2, and OXSR1 are significant in determining the prognosis of GCT. Apart from using radiological and histological parameters, we can add them to tumor work-up for definitive diagnosis and prognosis.

Purpose To report visual and refractive outcomes and intraoperative and postoperative complications after pars plana vitrectomy (PPV) with retropupillary implantation of an iris clip intraocular lens (IOL). Methods This is a retrospective case series of patients who underwent secondary retropupillary intraocular lens insertion combined with pars plana vitrectomy to treat aphakia secondary to a dislocated nucleus lens (group A); or IOL dislocation (group B). Patient demographics, preoperative visual and refractive outcomes, intraoperative factors, postoperative visual and refractive outcomes, and complications within the follow-up period ranging from 6 months up to 3 years postoperative, were recorded. Results In total, 57 eyes of 50 patients were included with a follow-up range of 6 months to 3 years. The overall mean age was 77.0 years (range 28 to 99 years), with 26/50 (52%) of patients being male. There were 13/57 (22.8%) patients in group A and 44/57 (77.2%) patients in group B. The single most common identifiable cause for lens dislocation was pseudoexfoliation, which was seen in 13/57 (22.8%) of eyes. The mean improvement in visual acuity (baseline and final follow) was 0.72 logMAR (1.09 logMAR to 0.37 logMAR) in all patients, 1.12 logMAR (1.64 logMAR to 0.52 logMAR) in group A, and 0.60 logMAR (0.91 logMAR to 0.31 logMAR) in group B. In 46 eyes (80.7%), postoperative refractive errors were within ±1.00 dioptres (D) of the target refraction, with a mean difference of 0.36D from target refraction. Complications included corneal edema (35.1%), hyphema (26.3%), anterior chamber inflammation (26.3%), vitreous hemorrhage (14%), elevated intraocular pressure (IOP, 12.3%) and cystoid macular edema (CME, 5.3%). All these complications were managed with topical medical therapy and did not require further surgical intervention. One eye from group A was the only eye that developed retinal detachment (RD) or endophthalmitis. No patients had IOL dislocation in the postoperative follow-up period, which ranged from 6 months to 3 years. Conclusions Retropupillary implantation of an iris clip IOL with pars plana vitrectomy is an efficient, predictable, and stable surgical option for aphakic eyes without capsular support. Postoperative corneal edema, hyphema, and anterior chamber inflammation are common but usually resolve without the need for further surgical intervention.