Royal North Shore Hospital Research Articles

Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study—Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury

Accelerated sub-lesional bone loss is common in the first 2–3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An ‘acute interventional cohort’ (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A ‘chronic non-interventional cohort’ (n = 9) with TSCI (duration 1–5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the ‘acute’ cohort had higher serum CTx, P1NP and sclerostin concentrations, while the ‘chronic’ cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48 months. Left distal femoral and proximal tibial BMD declined by mean ~ 6–13% at 12 months and ~ 20–23% at 48 months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

Reducing noise in radioactive iodine activity selection: the utility of an online clinical calculator.

Noise, an unwanted variability in judgement, is ubiquitous in medicine, including in the prescription of radioactive iodine (RAI). Building upon our recently developed predictive risk model, we created an online clinical support tool to facilitate the translation of our model into clinical practice. The aim of this study is to assess the utility of an online clinical support tool to reduce noise in the treatment for patients with DTC. The tool was accessible via weblink or a QR code. Activity recommendations were applied to the calculators four risk catgeories: 0GBq for very low risk, 1GBq for low risk; 4GBq for intermediate risk, and 6GBq for high risk. The tool was applied prospectively to 103 patients who received RAI at Royal North Shore Hospital between 2021-2022, and retrospectively to 393 patients treated with RAI between 2017-2021. A significant difference was observed in administered activity between the 2021-2022 vs 2017-2021cohorts in patients stratified as intermediate (median activity 3.95GBq, IQR 2.03-4.04 vs 4GBq, 4-4), and high risk (4.07GBq, 3.95-5.7 vs 6GBq, 6-6) with p-values of 0.01 and <0.01 respectively. No difference was seen in low risk patients (2.01GBq, 1.03-3.98 vs 1GBq, 1-4,p = 0.30). Additionally, no clinically significant recurrence was observed between the two cohorts (6.6% vs 4.5%,p = 0.628). Optimal risk classification and activity recommendation continues to be established; our data suggests providing risk stratification and activity recommendation in an easy to access online tool can reduce noise and variability in activity prescription for patients with DTC.

Efficacy and safety of pentosan polysulfate sodium in people with symptomatic knee osteoarthritis and dyslipidaemia: protocol of the MaRVeL trial

IntroductionKnee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate...

Globe trauma associated with falls at Australian tertiary centres.

Falls frequently cause globe and adnexal trauma, particularly in the elderly. The morbidity decreases confidence, independence and quality of life. We aimed to improve the understanding of fall-related globe and adnexal trauma and the involvement of ophthalmology at two tertiary trauma centres. A retrospective medical record review was conducted at Royal North Shore Hospital and Royal Prince Alfred Hospital of patients admitted with fall-related globe and/or adnexal trauma between January 2015 and December 2019. International Classification of Disease Tenth Revision codes were used to identify patients for inclusion. Medical records were reviewed to extract data on demographics, trauma, ocular examination and referrals to ophthalmology. From January 2015 to December 2019, 346 patients, 186 were female (54%) and median age 76 years (interquartile range 24 years), were admitted to Royal North Shore Hospital and Royal Prince Alfred Hospital with fall-related globe and/or adnexal trauma. One hundred and twenty-five (36%) suffered globe trauma with 48 (14%) classified as severe. Patients over 65 years old had at least three risk factors contributing to falls. Alcohol and illicit substances were involved in 20% of falls and occurred predominantly in younger populations. There were significantly more patients with globe trauma if orbital/mid-facial fractures were present (55% vs 36%, P < 0.001). Fall-related globe and adnexal trauma were more common in the elderly. Alcohol and illicit substances have a role in falls in younger populations. Thorough ocular assessment is required especially in mid-facial/orbital trauma to exclude globe trauma. Further, research is required to determine the effect of fall prevention strategies in preventing globe trauma.

Burn related globe and adnexal trauma at trauma centres

IntroductionPrompt management of burn-related globe trauma can prevent long term complications. Delays in diagnosis may occur when globe trauma is associated with life-threatening injuries. We aimed to improve the understanding of the epidemiology, acute assessment and management of burns-related globe and adnexal trauma admitted to two trauma centres in Sydney, Australia. MethodAdmitted patients with burns-related globe and/or adnexal trauma were retrospectively reviewed at Royal North Shore Hospital (RNSH) and Royal Prince Alfred Hospital (RPAH) between January 2015 and December 2019. The International Classification of Disease, Tenth Revision codes was used to search and identify patients. Medical records were reviewed to extract data on demographics, injuries, ocular examination and ophthalmology involvement. ResultsOver the 5-years, 101 patients with globe and/or adnexal burns-related trauma were admitted to RNSH or RPAH. Median age was 37years. Most patients were male (76%) and were injured while at home or work (74%). Patients with chemical exposure were more likely to have globe trauma (100% vs 72%, p < 0.001) and severe globe trauma (54% vs 32%, p = 0.028). On initial review by emergency staff, 14 patients were not referred to ophthalmology, of these there were 2 patients where the diagnosis was delayed. ConclusionGlobe trauma is common in patients with chemical exposure. Thorough ocular assessment within the acute setting is vital to diagnose globe trauma. We investigated hospitals with specialised burn staff, further research is required to understand the management of globe trauma in hospitals without such resources. SynopsisChemicals in household-products can cause severe globe trauma. Globe trauma can occur alongside large burns leading to delay in its diagnosis and management. Ophthalmology can assist in the early diagnosis and management of globe trauma.

Globe and adnexal trauma at Australian trauma centres

IntroductionIn multisystem trauma, the assessment and management of globe and adnexal trauma is often complex. Ophthalmology input may assist managing such patients. To understand the role of ophthalmology in tertiary trauma centres we report on the management of globe and adnexal trauma at two tertiary trauma centres in Sydney, Australia. MethodA retrospective case series was completed at Royal North Shore Hospital (RNSH) and Royal Prince Alfred Hospital (RPAH) on patients admitted between January 2015 and December 2019. International Classification of Disease, Tenth Revision codes, diagnostic and procedural coding data were used to identify patients admitted with globe and/or adnexal trauma. Data extracted from medical records included demographics, mechanism of injury, ocular examination and specialist ophthalmic referral. ResultsOver 5-years, 773 patients, average age of 53.2years and 62% male, were admitted to RNSH and RPAH with globe and/or adnexal trauma. Most patients (83%) first presented to RNSH or RPAH. The most common mechanism of injury was falls (45%) followed by burns (13%). Two-hundred and thirty-five patients had multisystem trauma, of these patients, 121 (51%) suffered globe trauma with 49 (21%) classified as severe. Three patients were not diagnosed initially due to delayed ophthalmology referral. ConclusionFalls followed by burns were common causes of globe and adnexal trauma in Sydney, Australia. The presence of orbital/mid-facial injury may indicate a patient has globe trauma. In multisystem trauma, globe trauma may be diagnosed late or not identified. Ophthalmology review has an important role in diagnosing and managing globe trauma in multisystem trauma.

Postoperative analgesia for upper gastrointestinal surgery: a retrospective cohort analysis

BackgroundThoracic epidural analgesia is commonly used for upper gastrointestinal surgery. Intrathecal morphine is an appealing opioid-sparing non-epidural analgesic option, especially for laparoscopic gastrointestinal surgery.MethodsFollowing ethics committee approval, we extracted data from the electronic medical records of patients at Royal North Shore Hospital (Sydney, Australia) that had upper gastrointestinal surgery between November 2015 and October 2020. Postoperative morphine consumption and pain scores were modelled with a Bayesian mixed effect model.ResultsA total of 427 patients were identified who underwent open (n = 300), laparoscopic (n = 120) or laparoscopic converted to open (n = 7) upper gastrointestinal surgery. The majority of patients undergoing open surgery received a neuraxial technique (thoracic epidural [58%, n = 174]; intrathecal morphine [21%, n = 63]) compared to a minority in laparoscopic approaches (thoracic epidural [3%, n = 4]; intrathecal morphine [12%, n = 14]). Intrathecal morphine was superior over non-neuraxial analgesia in terms of lower median oral morphine equivalent consumption and higher probability of adequate pain control; however, this effect was not sustained beyond postoperative day 2. Thoracic epidural analgesia was superior to both intrathecal and non-neuraxial analgesia options for both primary outcomes, but at the expense of higher rates of postoperative hypotension (60%, n = 113) and substantial technique failure rates (32%).ConclusionsWe found that thoracic epidural analgesia was superior to intrathecal morphine, and intrathecal morphine was superior to non-neuraxial analgesia, in terms of reduced postoperative morphine requirements and the probability of adequate pain control in patients who underwent upper gastrointestinal surgery. However, the benefits of thoracic epidural analgesia and intrathecal morphine were not sustained across all time periods regarding control of pain. The study is limited by its retrospective design, heterogenous group of upper gastrointestinal surgeries and confounding by indication.

Economic analysis of patient-related effects of an interdisciplinary pain self-management program.

Active Day Patient Treatment (ADAPT) is a well-established 3 week intensive cognitive-behavioural, interdisciplinary pain management program for patients with disabling chronic pain. The aim of this analysis was to conduct an economic analysis of patient-related effects of ADAPT using hospital administrative data, specifically, to compare the costs and health outcomes for patients 1 month after participating in the program, with the preprogram period when they were receiving standard care. This retrospective cohort study included 230 patients who completed ADAPT (including follow-ups) between 2014 and 17 at the Pain Management and Research Centre at the Royal North Shore Hospital in Sydney, Australia. Data on pain-related healthcare utilization and costs before and after the program were assessed. Primary outcome measures were labour force participation for patients' average weekly earnings and cost per clinically meaningful change in Pain Self-efficacy Questionnaire, Brief Pain Inventory (BPI) Severity, and BPI interference scores (n = 224). We estimated patients, on average, earned $59 more each week at 1 month follow-up compared with baseline. The cost per clinically meaningful change in pain severity and interference score based on the BPI severity and BPI interference were AU$9452.32 (95% CI: $7031.76-$12,930.40) and AU$3446.62 (95% CI: $2851.67-$4126.46), respectively. The cost per point improvement and per clinically meaningful change in the Pain Self-efficacy Questionnaire were $483 (95% CI: $411.289-$568.606) and $3381.02, respectively. Our analysis showed a better health outcome, reduced healthcare services' cost, and reduced number of medications taken 1 month after participating in ADAPT.

Independent Validation of the International Grading System for Medullary Thyroid Carcinoma: A Single Institution Experience

Medullary thyroid carcinoma (MTC), an uncommon C cell thyroid malignancy, accounts for a disproportionate number of thyroid cancer deaths. To predict MTC clinical behavior, the recent international MTC grading system (IMTCGS) was published combining features from the Memorial Sloan Kettering Cancer Center and Royal North Shore Hospital grading systems that incorporates mitotic count, necrosis, and Ki67 proliferative index (Ki67PI). The IMTCGS appears promising, but independent validation data are limited. Here, we applied the IMTCGS to our institutional MTC cohort and assessed its ability to predict clinical outcomes. Our cohort comprised 87 MTCs (30 germline and 57 sporadic). Slides for each case were reviewed by 2 pathologists and histologic features recorded. Ki67 immunostaining was performed on all cases. Each MTC was graded with the IMTCGS based on tumor necrosis, Ki67PI, and mitotic count. Cox regression analysis was performed to assess the impact of various clinical and pathological data on disease outcomes, including overall survival (OS), disease-free survival, disease-specific survival (DSS), and distant metastasis-free survival. In our MTC cohort, 18.4% (n = 16/87) were IMTCGS high grade. IMTCGS grade was strongly prognostic for OS, disease-free survival, DSS, and distant metastasis-free survival on univariate analysis and multivariable analysis in both the entire MTC cohort and in the sporadic subset. Among the individual IMTCGS parameters, while all 3 were associated with poorer survival outcomes on univariate analysis, necrosis had the strongest association with all survival parameters on multivariable analysis, whereas Ki67PI or mitotic count was associated only with OS and DSS. This retrospective study independently demonstrates that the IMTCGS is valid for grading MTCs. Our findings support incorporating IMTCGS into routine pathology practice. IMTCGS grading may help clinicians to better predict the prognosis of MTC. Future studies may shed light on how MTC grading should impact treatment protocols.

Surgical management of high-grade pancreatic injuries: Insights from a high-volume pancreaticobiliary specialty unit.

The management of high-grade pancreatic trauma is controversial. To review our single-institution experience on the surgical management of blunt and penetrating pancreatic injuries. A retrospective review of records was performed on all patients undergoing surgical intervention for high-grade pancreatic injuries [American Association for the Surgery of Trauma (AAST) Grade III or greater] at the Royal North Shore Hospital in Sydney between January 2001 and December 2022. Morbidity and mortality outcomes were reviewed, and major diagnostic and operative challenges were identified. Over a twenty-year period, 14 patients underwent pancreatic resection for high-grade injuries. Seven patients sustained AAST Grade III injuries and 7 were classified as Grades IV or V. Nine underwent distal pancreatectomy and 5 underwent pancreaticoduodenectomy (PD). Overall, there was a predominance of blunt aetiologies (11/14). Concomitant intra-abdominal injuries were observed in 11 patients and traumatic haemorrhage in 6 patients. Three patients developed clinically relevant pancreatic fistulas and there was one in-hospital mortality secondary to multi-organ failure. Among stable presentations, pancreatic ductal injuries were missed in two-thirds of cases (7/12) on initial computed tomography imaging and subsequently diagnosed on repeat imaging or endoscopic retrograde cholangiopancreatography. All patients who sustained complex pancreaticoduodenal trauma underwent PD without mortality. The management of pancreatic trauma is evolving. Our experience provides valuable and locally relevant insights into future management strategies. We advocate that high-grade pancreatic trauma should be managed in high-volume hepato-pancreato-biliary specialty surgical units. Pancreatic resections including PD may be indicated and safely performed with appropriate specialist surgical, gastroenterology, and interventional radiology support in tertiary centres.

Neoadjuvant BRAF-Directed Therapy Is Associated with Favorable Surgical and Survival Outcomes in Patients with BRAF-Mutated Anaplastic Thyroid Cancer

Clinical ThyroidologyVol. 35, No. 5 Thyroid CancerNeoadjuvant BRAF-Directed Therapy Is Associated with Favorable Surgical and Survival Outcomes in Patients with BRAF-Mutated Anaplastic Thyroid CancerShejil Kumar, Matti L Gild, and Venessa TsangShejil Kumar Department of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, Sydney, New South Wales, Australia.Search for more papers by this author, Matti L Gild Department of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, Sydney, New South Wales, Australia. Faculty of Medicine and Health Sciences, University of Sydney, Sydney, New South Wales, Australia.Search for more papers by this author, and Venessa Tsang Department of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, Sydney, New South Wales, Australia. Faculty of Medicine and Health Sciences, University of Sydney, Sydney, New South Wales, Australia.Search for more papers by this authorPublished Online:12 May 2023https://doi.org/10.1089/ct.2023;35.208-211AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 35Issue 5May 2023 Information© Copyright 2023, Mary Ann Liebert, Inc.To cite this article:Shejil Kumar, Matti L Gild, and Venessa Tsang.Neoadjuvant BRAF-Directed Therapy Is Associated with Favorable Surgical and Survival Outcomes in Patients with BRAF-Mutated Anaplastic Thyroid Cancer.Clinical Thyroidology.May 2023.208-211.http://doi.org/10.1089/ct.2023;35.208-211Published in Volume: 35 Issue 5: May 12, 2023PDF download

Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.

Phaeochromocytoma and paraganglioma are highly heritable tumours; half of those associated with a germline mutation are caused by mutations in genes for Krebs's cycle enzymes, including succinate dehydrogenase (SDH). Inheritance of SDH alleles is assumed to be Mendelian (probability of 50% from each parent). The departure from transmission of parental alleles in a ratio of 1:1 is termed transmission ratio distortion (TRD). We sought to assess whether TRD occurs in the transmission of SDHB pathogenic variants (PVs). This study was conducted with 41 families of a discovery cohort from Royal North Shore Hospital, Australia, and 41 families from a validation cohort from St. Bartholomew's Hospital, United Kingdom (UK). Inclusion criteria were a clinically diagnosed SDHB PV and a pedigree available for at least two generations. TRD was assessed in 575 participants with the exact binomial test. The transmission ratio for SDHB PV was 0.59 (P = 0.005) in the discovery cohort, 0.67 (P < 0.001) in the validation cohort, and 0.63 (P < 0.001) in the combined cohort. No parent-of-origin effect was observed. TRD remained significant after adjusting for potential confounders: 0.67 (P < 0.001) excluding families with incomplete family size data; 0.58 (P < 0.001) when probands were excluded. TRD was also evident for SDHD PVs in a cohort of 81 patients from 13 families from the UK. The reason for TRD of SDHB and SDHD PVs is unknown, but we hypothesize a survival advantage selected during early embryogenesis. The existence of TRD for SDHB and SDHD has implications for reproductive counselling, and further research into the heterozygote state.

A proof-of-concept randomized controlled trial of follow-up mental health care for traumatic injury patients following hospital discharge

IntroductionTraumatic injuries account for a huge burden of disease. Many patients develop persistent mental health problems in the months following hospital discharge. This proof-of-concept trial investigated whether Stepped Care comprising follow-up assessment telephone calls and appropriate referral information would lead to better mental health and functioning in traumatic injury patients. MethodsPatients admitted to the Trauma Service at Royal North Shore Hospital were randomized to either Stepped Care (n = 84) or Treatment as Usual (n = 90). All patients were assessed for anxiety, depression, and posttraumatic stress prior to hospital discharge. Those in Stepped Care received a telephone call at 1-month and 3-months after hospital discharge in which they were administered a brief assessment; patients who reported mental health or pain difficulties were provided with information for local specialists to address their specific problem. All patients were independently assessed by telephone interview 9- months after hospital discharge for posttraumatic stress disorder (PTSD) (primary outcome), as well as for anxiety, depression, disability, and pain. ResultsThere were 58 (73%) patients that could be contacted at either the 1-month or 3-month assessments. Of those contacted, 28 patients (48% of those contacted) were referred for specialist assistance. There were no differences between treatment arms on PTSD symptoms at follow-up [F1,95 = 0.55, p = 0.46]. At the 9-month assessment, patients in the Stepped Care condition reported significantly less anxiety [F1,95 = 5.07, p = 0.03] and disability [F1,95 = 4.37, p = 0.04] relative to those in Treatment as Usual. At 9 months there was no difference between conditions on depression [F1,95 = 1.03, p = 0.31]. There were no differences between conditions on self-reported pain difficulties. ConclusionsThis proof-of-concept trial suggests that brief screening assessments of traumatic injury patients following hospital discharge, combined with appropriate referral information, may lead to better functional outcomes. Further research is needed with larger sample sizes and greater verification of referral uptake to validate this finding.

Editors' Note: Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

Investigators at the Mitochondrial Disease Clinic at Royal North Shore Hospital (Sydney, Australia) prospectively recruited 242 patients who satisfied the Nijmegen criteria for possible, probable, or definite mitochondrial disease (MD). The investigators tested the variant detection rate for a variety of mitochondrial disorders using whole-genome sequencing (WGS) of peripheral blood. Disease-causing variants were found in 53.7% of tested individuals. With more widespread availability and the decreasing cost of WGS, it may become more frequently used as a first-line diagnostic approach in patients with suspected MD. Dr. Schon acknowledged one rare MD, alpha-methylacyl-CoA racemase deficiency, which has been reported in slightly more than a dozen cases to date. Although it may be rare, Dr. Schon maintains that the condition is likely underdiagnosed. The authors agreed and emphasized that dietary restriction of pristanic acid may lessen the risk of severe neurologic disease and manifestations such as seizures and stroke-like episodes. The growing use of technologies such as WGS may facilitate earlier identification and effective treatment of patients with this and other MDs, especially with enriched populations. Investigators at the Mitochondrial Disease Clinic at Royal North Shore Hospital (Sydney, Australia) prospectively recruited 242 patients who satisfied the Nijmegen criteria for possible, probable, or definite mitochondrial disease (MD). The investigators tested the variant detection rate for a variety of mitochondrial disorders using whole-genome sequencing (WGS) of peripheral blood. Disease-causing variants were found in 53.7% of tested individuals. With more widespread availability and the decreasing cost of WGS, it may become more frequently used as a first-line diagnostic approach in patients with suspected MD. Dr. Schon acknowledged one rare MD, alpha-methylacyl-CoA racemase deficiency, which has been reported in slightly more than a dozen cases to date. Although it may be rare, Dr. Schon maintains that the condition is likely underdiagnosed. The authors agreed and emphasized that dietary restriction of pristanic acid may lessen the risk of severe neurologic disease and manifestations such as seizures and stroke-like episodes. The growing use of technologies such as WGS may facilitate earlier identification and effective treatment of patients with this and other MDs, especially with enriched populations.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Outcomes of Papillary Thyroid Microcarcinoma Presenting with Palpable Lateral Lymphadenopathy.

Purpose: Papillary thyroid microcarcinoma (PTMC) is typically indolent in nature, allowing management with active surveillance protocols. Occasionally, a more aggressive phenotype can present and may lead to poor outcomes such as patients presenting with clinically significant lateral lymphadenopathy (cN1b). Prior analysis of the outcomes of this cohort is largely from papillary thyroid cancer (PTC) (>1 cm) or from institutions where use of radioactive iodine (RAI) is limited. Hence, we aim to describe the outcomes of patients with PTMC who presented with palpable cN1b disease, treated with total thyroidectomy and RAI. Methodology: We performed a retrospective cohort study. Outcomes of patients with PTMC who presented with palpable lateral lymph node (LN) metastases (microPTC cN1b) treated between 1997 and 2020 at Royal North Shore Hospital were compared with two control groups' outcomes: patients with clinically detected PTMC without evidence of involved LNs (microPTC cN0) and with larger PTC (>10 mm) who presented with palpable lateral lymphadenopathy (larger PTC cN1b). We assessed clinicopathological variables, postoperative risk stratification, rates of disease recurrence, reoperative surgery, and structural disease-free survival (DFS). Results: In total, 1534 PTMCs were diagnosed following thyroid surgery in the study period; of these, 157 (10%) were clinically detected microPTC cN0 and 26 microPTC cN1b (1.7%). There were 138 patients in the larger PTC cN1b control group. All cN1b patients were treated with total thyroidectomy and adjuvant RAI. Mean size of the largest LN deposit was similar between the microPTC cN1b and larger PTC cN1b groups (23 vs. 27 mm, p = 0.11). Patients with microPTC cN1b were more likely to have biochemical or structural persistence or recurrence compared with microPTC cN0 (19%, 5/26 vs. 3.8%, 6/157, p = 0.002) but less likely than larger PTC cN1b patients (19%, 5/26 vs. 42%, 58/138, p = 0.04). All patients in the microPTC cN1b group who had an excellent response to initial therapy (85%, 22/26) were disease free at last follow-up. The rate of reoperation was similar for the microPTC cN1b and microPTC cN0 groups (4%, 1/26 vs. 2%, 3/157, p = 0.461) and significantly lower than the larger PTC cN1b group (4%, 1/26 vs. 26%, 36/138, p = 0.002). Five-year DFS estimates were significantly better for microPTC cN1b patients than for larger PTC cN1b patients (94% vs. 59%, p = 0.001). Conclusions: MicroPTC cN1b patients treated with thyroidectomy and adjuvant RAI have inferior clinical outcomes compared with microPTC cN0 patients but have better outcomes than their larger PTC cN1b counterparts with respect to disease persistence and recurrence. Response to initial therapy provides valuable prognostication in microPTC cN1b patients: if these patients had an excellent response to initial treatment, they achieved long-term DFS in this series.

Selpercatinib Treatment of RET-Mutated Thyroid Cancers Is Associated With Gastrointestinal Adverse Effects

ContextMetastatic medullary thyroid carcinoma (MTC) and radioactive iodine–refractory differentiated thyroid carcinoma (RAI-R DTC) have poor prognosis and limited treatment options. Selpercatinib (LOXO-292), a selective kinase inhibitor targeting the RET gene, has shown a 69% to 79% objective response rate in this cohort with benefits in other tumors including lung cancer harboring the same oncogenic driver. Published reports describe only 17% of patients experiencing gastrointestinal (GI) adverse effects (AEs), which is in contrast to our local experience.ObjectiveHere we characterize the AEs and correlate them with radiological and histopathological findings.MethodsSequential patients enrolled in LIBRETTO-001 at Royal North Shore Hospital, Sydney, Australia, with available imaging (n = 22) were recruited. Patients had regular visits with AEs documented and computed tomography (CT) scans every 3 months. CT at screening, at time of GI AE, and at most recent follow-up were reviewed and scored. Endoscopic examination was performed in 5 patients.ResultsOf 22 patients in this cohort, the majority had somatic RET alterations (n = 18), most commonly p.Met918Thr (n = 14). Ten patients (50%) developed GI AEs. Dose reduction was required in 8 of the 10 patients, but none discontinued therapy. The majority had stable disease (n = 17). Gastric and small-bowel edema was evident in symptomatic patients after a median time of 67 weeks’ treatment. Histological correlation in 5 patients revealed mucosal edema correlating with radiological evidence of congestion and edema.ConclusionGI AEs with selpercatinib may be more common than previously described. Most are self-limiting but often require dose adjustments. Histological evidence of mucosal edema observed in conjunction with the radiological findings of congestion and wall thickening suggest bowel-wall edema is a predominant mechanism of abdominal pain in these patients.

Recent SARS-CoV-2 infection: too early to vaccinate?

Recent SARS-CoV-2 infection: too early to vaccinate?

Sublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink?

HomeCirculationVol. 145, No. 11Sublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink? No AccessArticle CommentaryRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessArticle CommentaryRequest AccessFull TextSublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink? Avedis A. Ekmejian, MBBS, MSc, Ravinay Bhindi, MBBS, MSc, PhD and Gemma A. Figtree, MBBS, DPhil Avedis A. EkmejianAvedis A. Ekmejian Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (A.A.E., R.B., G.A.F.). Search for more papers by this author , Ravinay BhindiRavinay Bhindi Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (A.A.E., R.B., G.A.F.). Cardiovascular Discovery Group, Kolling Institute of Medical Research (R.B., G.A.F.), University of Sydney, Australia. Search for more papers by this author and Gemma A. FigtreeGemma A. Figtree Correspondence to: Gemma A. Figtree, MBBS, DPhil, Royal North Shore Hospital, Cardiovascular Discovery Group, Kolling Institute, University of Sydney, Level 12, Kolling Institute of Medical Research, 10 Westbourne Street, St Leonards, 2065, Australia. Email E-mail Address: [email protected] Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (A.A.E., R.B., G.A.F.). Cardiovascular Discovery Group, Kolling Institute of Medical Research (R.B., G.A.F.), University of Sydney, Australia. Charles Perkins Centre (G.A.F.), University of Sydney, Australia. Search for more papers by this author Originally published14 Mar 2022https://doi.org/10.1161/CIRCULATIONAHA.121.058008Circulation. 2022;145:791–792"Sublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink?." Circulation, 145(11), pp. 791–792FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 792.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Gemma A. Figtree, MBBS, DPhil, Royal North Shore Hospital, Cardiovascular Discovery Group, Kolling Institute, University of Sydney, Level 12, Kolling Institute of Medical Research, 10 Westbourne Street, St Leonards, 2065, Australia. Email gemma.[email protected]edu.au

Clinical and molecular profile of young adults with early-onset colorectal cancer: Experience from four Australian tertiary centers.

Patients with early-onset colorectal cancer (EO-CRC) have unique characteristics. Contemporary data on the pathological and molecular features, and survival of EO-CRC are limited in the Australian context. To determine the demographic, histopathological and molecular characteristics of adults with EO-CRC, and their survival. We conducted a retrospective study of adults aged 18-49 years with EO-CRC who were referred to the Illawarra Shoalhaven Local Health District, South Eastern Sydney Local Health District and Royal North Shore Hospital in New South Wales, Australia, between 2014 and 2018. Of 257 patients included, 94 (37%) patients presented with de novo metastatic CRC, 80% patients had near-average risk family history and 89% had a symptomatic presentation. In 159 patients with nonmetastatic disease at diagnosis, stage III disease (OR 3.88 [95% CI: 1.13-13.3]; p=.03) and the presence of perineural invasion (PNI) (OR 6.63 [95% CI: 2.21-19.84]; p=.001) were risk factors associated with the development of metastatic disease. Among 94 patients with de novo metastatic disease, 43 (43%) and 12 (14%) patients harbored a KRAS or BRAF V600E mutation, respectively. The median overall survival was 29.6 months (95% CI: 20.4-38.7). BRAF mutation was associated with inferior survival (HR 3.00 [95% CI: 1.30-6.94]; p=.01). The prevalence of KRAS and BRAF mutations in our cohort is similar to the overseas experience. Stage III disease at diagnosis, presence of PNI and BRAF mutation are adverse prognostic indicators. A better understanding of the molecular landscape is needed for this patient cohort, so as to better tailor prevention strategies, screening and treatment pathways.