Long-term survival and toxicity in patients with neuroendocrine tumors treated with 177 Lu-octreotate peptide radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has shown favorable results in neuroendocrine tumors (NETs). Long-term safety and efficacy data for 177 Lu-octreotate PRRT, particularly in combination with chemotherapy, is lacking. METHODS: The authors conducted a retrospective review of the long-term toxicity and survival outcomes of 104 patients with advanced NETs treated on 4 phase 2 clinical trials with Lutetium-177-octreotate (177 Lu-octreotate) PRRT, mostly in combination with chemotherapy. Median follow-up was 68 months, which represents the longest follow-up study of 177 Lu-octreotate PRRT for NETs to date. RESULTS: Median progression-free survival (PFS) was 37 months, and median overall survival (OS) was 71 months. Five- and 10-year OS were 62% and 29%, and 5- and 10-year PFS were 36% and 21%, respectively, demonstrating 177 Lu-octreotate can provide durable responses. PRRT was well tolerated with 1.9% of patients developing chronic renal impairment and 1% of patients developing long-term thrombocytopenia. Interestingly, there was a relatively high rate of myelodysplasia (MDS)/leukemia (6.7%), possibly attributable to the longer follow-up (with all except 1 case occurring more than 4 years after PRRT treatment) or to the addition of concurrent chemotherapy. CONCLUSIONS: Lutetium-177-Octreotate PRRT remains an efficacious and well tolerated treatment in long-term follow-up. For clinicians deciding on the timing of PRRT for individual patients, the 6.7% long-term risk of MDS/leukemia needs to be balanced against the 21% PFS at 10 years.

Postoperative hypothermia is associated with reduced length of stay in adult acute burn survivors.

BACKGROUND: The hypermetabolic response after a burn predisposes patients to hypothermia due to dysfunction of thermoregulation. Traditionally, hypothermia is avoided actively in burn care due to reported complications associated with low body temperature. The likelihood of hypothermia with acute burn surgery is compounded by general anesthesia, exposure of wound areas and prolonged operation times. However, we find limited studies exploring the effects of perioperative hypothermia on length of stay in the adult burn population. OBJECTIVE: To determine associations between postoperative hypothermia and hospital length of stay in adult burns patients. METHOD: This retrospective cohort study involved patients admitted to the State Adult Burn Unit in Western Australia between 1st January 2015 to 28th February 2021. All adults who underwent surgery for acute burn, and had postoperative recovery room body temperature recorded, were included in the study. In this study, we defined normothermia as >36.5C and hypothermia as < 36.0 °C with mild, moderate, and severe hypothermia being 35.0-35.9 °C, 34.0-34.9 °C and < 34.0 °C, respectively. Patients with hyperthermia were excluded. Multivariable general linear models explored if hypothermia was independently associated with length of stay. RESULTS: Among 1486 adult patients, 1338 (90%) were normothermic postoperatively, with temperatures >36.0C. We included 148 (10%) patients with hypothermia (temperature <36.0 °C) postoperatively. Most burns in the study population were minor: 96% had burns < 15% TBSA. Data modelling demonstrated that hypothermia was associated with a shorter length of hospital stay (coefficient = -0.129, p = 0.041). CONCLUSION: In adult acute burn patients, postoperative hypothermia was associated with reduced length of stay after surgery. The positive results of this study indicate that a review of the core temperature targets with acute burn surgery, and timing of burn patient cooling practices in general is warranted.

Post-CT-guided lung biopsy optimisation of the observation period by identifying patients at risk of delayed pneumothorax.

INTRODUCTION: Identify the risk factors for delayed pneumothorax after lung biopsy. METHODS: A retrospective study of 355 CT-guided lung biopsies was performed at Fiona Stanley Hospital, Western Australia over 42 months. A comprehensive range of patient, lesion and procedural variables were recorded. All post-procedural complications including time, size of pneumothorax and post-biopsy radiographs were reviewed. Lasso logistic regression model was utilised to determine factors predicting patient complications. RESULTS: A total of 167 patients (47%) developed a pneumothorax, in which 34% were significant, requiring longer observation or drain insertion. The majority of pneumothoraces occurred within the first hour (86%), with 90% detected at the time of the procedure. Then, 12% were detected more than 3 h post-procedure, of which 8 patients (5%) had a significant delayed pneumothorax. Factors increasing the likelihood of significant pneumothorax include the length of lung traversed, smaller nodule size, surrounding emphysema, increased age and lateral patient position with the lesion in the non-dependent aspect. Increasing patient age, longer length of lung traversed and smaller nodule diameter increase the risk of delayed onset of pneumothorax (more than 3 h). CONCLUSION: The results of this study align with other studies indicating it is safe to discharge stable patients within an hour post-lung biopsy. However, specific risk factors, including age, small lesion size and deep lesions, may identify patients who could benefit from a longer observation period.

Comparing fluorodeoxyglucose positron emission tomography with computed tomography in staging for nodal and distant metastasis in urothelial/bladder cancer.

Objectives: We aim to assess the clinical value of 18F-fluorodeoxyglucose positron (18F-FDG-PET) scan in detecting nodal and distant metastasis compared with computed tomography (CT) scan in patients with urothelial carcinoma or bladder cancer, aiming to improve staging accuracy and thereby better prognosticate and determine therapy. Methods: A retrospective review of 75 patients with invasive bladder cancer (≥T1) who were staged with both CT and 18F-FDG-PET within an 8-week interval was performed for the period between 2015 and 2020. Seventy-two per cent (54/75) had formal pelvic lymph node (LN) dissection or biopsy of lesions suspicious for metastases. FDG-PET definitions for positive sites were assessed depending on SUV Max (nodes with SUVmax >4 at any size, SUV > 2 for lymph nodes >8 mm, or any SUV if the lymph node was >10 mm on axial images). For CT scanning, enlarged LN by RECIST 1.1 criteria (>10 mm) as well as qualitative findings suggesting metastasis were considered positive. The analysis was based on the comparison of CT and 18F-FDG-PET findings to histopathology results from LN dissection or biopsies. Results: Sensitivity, specificity, positive predictive values (PPV) and negative predictive value (NPV) of CT versus FDG-PET for detecting metastasis, in patients who underwent pelvic LN dissection or biopsy of lesions suspicious of metastases, were 46.6% (95% CI: 21%-70%) versus 60% (95% CI: 32%-84%), 100% (95% CI: 91%-100%) versus 83.78% (95% CI: 69%-94%), 100% (95% CI: 63%-100%) versus 60% (95% CI: 32%-84%), and 82.2% (95% CI: 68%-92%) versus 83.78% (95% CI: 69%-94%), respectively. 7/75 (9.3%) patients avoided cystectomy due to 18F-FDG-PET features of metastases that were not detected by CT. Conclusion: FDG-PET may be more sensitive than CT for metastases in the staging of bladder cancer, which resulted in significant avoidance of aggressive local management in cases with occult metastasis.

Correction: Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.0283394.].

Discordance between clinical and pathologic staging and the timeliness of care of non-small cell lung cancer patients diagnosed with operable tumors.

AIM: This study was performed to evaluate concordance between clinical and pathologic staging of non-small cell lung cancer (NSCLC) in our hospital network. METHODS: We retrospectively reviewed records of 417 patients with NSCLC who received curative surgery and whose pathology was evaluated in our hospital between 2016 and 2021. Cytology, tissue pathology, and associated clinical, surgical, and imaging information were retrieved from hospital digital records. RESULTS: The cohort included 214 female and 203 male patients aged 20.6-85.8 years. Median times among staging computed tomography and surgery (105 days [interquartile range (IQR) 77.0-143.0]), positron emission tomography and surgery (78.5 days [IQR 56.0-109.0]), and endobronchial ultrasound-guided transbronchial needle aspiration and surgery (59 days [IQR 42-94]) indicated that Australian guidelines of <42 days between original referral and commencement of treatment were not being met in the majority of cases. Discordance between clinical TNM (cTNM) and pathologic TNM staging was 25.9%, including 18.4% cases that were clinically understaged and two patients with undetected stage IVA disease. cTNM understaging was significantly associated with time between the final staging investigation and surgery (p = .023), pleural (p < .05) and vessel (p < .05) invasion, and diagnosis of high-grade adenocarcinoma (p = .001). CONCLUSION: Discordance between clinical and pathologic staging of NSCLC is associated with tumor histopathologic characteristics and treatment delays. Although tumor factors that lead to discordant staging cannot be controlled, reduced time to surgery may have resulted in better outcomes for some patients in this potentially curable lung cancer cohort.

The risk of osteopenia/osteoporosis and psoriatic disease: A systematic review.

Background: Psoriasis (Ps) is a multisystem inflammatory disease associated with several comorbidities; however, its effect on bone health remains uncertain. This systematic review aimed to evaluate the risks of osteopenia (OPe) and osteoporosis (OP) in psoriasis. Methods: A systematic search was performed for published studies evaluating cutaneous Ps and psoriatic arthritis (PsA) compared with healthy control groups utilizing a validated bone mineral density (BMD) assessment score. Meta-analysis was performed using a random-effects model; pooled estimates and their confidence intervals (CIs) were calculated. For analysis, Ps and PsA groups were combined due to the small number of studies. Results: Twenty-one studies were included for final analysis; three Ps only, 15 PsA and three both. There was a significant difference between psoriatic disease (combination Ps and PsA group) compared with controls relating to an association with OP/OPe, with an overall odds ratio (OR) of 1.71 (95% CI 1.07-2.74: p-value = 0.026). The Ps group had significantly lower BMD than the control group at both the lumbar spine and femoral neck (mean difference -0.04; 95% CI -0.090 to 0.002 and -0.03; 95% CI -0.059 to 0.003 respectively). Conclusion: Putative risks of OPe and OP in both Ps and PsA are supported but not confirmed. Significant heterogeneity of reported data limits definitive conclusions in this meta-analysis. This review contributes to the further understanding of Ps as a multisystem disease and future management of potential comorbidities, but highlights key gaps in the literature. Further studies addressing standardised OP reporting, specific disease group characteristics comparing Ps with PsA, patient characteristics and medication use, are required in order to make more certain conclusions with greater clinical impact.

Hepatic steatosis: Ultrasound assessment using attenuation imaging (ATI) with liver biopsy correlation.

INTRODUCTION: Hepatic steatosis duration and severity are risk factors for liver fibrosis and cardiometabolic disease. We assessed the diagnostic accuracy of attenuation imaging (ATI), compared with histologic hepatosteatosis grading in adults with varied suspected liver pathologies. METHODS: Liver biopsy was performed on 76 patients (51 women, 25 men) with non-malignant diffuse parenchymal liver disease, within 4 weeks of multiparametric liver ultrasound including attenuation imaging (ATI). Skin-liver capsule distance (SCD) and body mass index (BMI) were measured. Histologic steatosis was graded none (S0), mild (S1), moderate (S2) or severe (S3). We compared histology and sonographic parameters. RESULTS: The median patient age was 50.5 (range 18-83) years and BMI 28.9 kg/m2 (interquartile range 24.0-33.3). The distribution of histologic steatosis grade was S0 (44%), S1(17%), S2(30%) and S3(9%). Median ATI value for each biopsy steatosis grade was 0.60 (IQR: 0.52-0.65), 0.65 (IQR: 0.6-0.71), 0.83 (IQR: 0.74-0.90) and 0.90 (IQR: 0.82-1.01) dB/cm/MHz for S0, S1, S2 and S3, respectively. The AUC of ATI for detection of any steatosis (S1-S3) and moderate to severe steatosis (S2-S3) was 0.85 (95% CI: 0.75-0.91) and 0.91 (95% CI: 0.83-0.99) with cut-offs of 0.55 and 0.62 dB/cm/MHz. ATI threshold of 0.74 dB/cm/MHz was able to discriminate between S0-S1 and S2-3 with accuracy, CI and kappa statistic of 0.8889, 0.65-0.98 and 0.7534. CONCLUSION: We found a good correlation between ATI and steatosis grade. The most accurate discrimination was between none to mild (S0-1) and moderate to severe (S2-3) steatosis.

A retrospective, cross-sectional analysis of delirium in burn injury compared to other surgical specialities.

BACKGROUND: Delirium is an acute cerebral disorder characterised by a disturbance in cognition, attention, and awareness. Often, it's undiagnosed and associated with increased morbidity and mortality. For burn patients, the reported prevalence ranges from 16% to 39%, with a multifactorial aetiology, increasing when intensive care is required. A direct comparison of delirium between surgical specialities has not been made. AIM: 1. To audit the use of the 4AT for those who become delirious during their stay. 2. Assess the proportion of patients diagnosed with delirium during hospitalisation by surgical specialities. 3. Identification of the factors associated with delirium in surgical patients. METHODS: Investigators at a single centre conducted a two-phase study. An initial retrospective audit of delirious patients under burns, general, and orthopaedic specialities over 16months, as defined by ICD-10 coding, identified compliance screening with the 4 A's Test. This informed the design of a retrospective, observational cohort study to compare factors associated with delirium and statistical comparison between four specialities to identify delirium-associated factor, where an analysis corrects for age. RESULTS: 37% of patients with an ICD-10 code indicating delirium had a 4AT test completed. Speciality, number of operations, LOS, ICU hours, age, and discharge destination were all statistically significant independent variables. When all other variables were equal, burns had the highest predicted probability of delirium diagnosis. CONCLUSIONS: Further analysis to identify and diagnose across the specialties is required. From a patient viewpoint, their LOS, ICU hours, and operations are increased for patients coded as delirious compared to non-delirious across the specialities. On a hospital level, the mean difference in cost for a delirious compared to a non-delirious patient is AU$9317. Despite the low incidence of delirium amongst the observed specialities, burns patients were most likely to develop delirium when demographic and clinical profiles were the same, and were more likely to develop delirium at a younger age and if in ICU.

Specialist pharmacist consultations with cancer patients in a pharmacist-led anticancer clinic.

BACKGROUND: Prescription-related errors and misinterpretation of oral cancer treatment instructions can lead to significant harm or fatal outcomes for patients. The impact of specialist pharmacist-led consultation for patients taking oral antineoplastic medicines (OAMs) across a range of cancer types in an Australian setting has not been studied. AIM: To evaluate the impact of specialist cancer pharmacist patient consultation in a pharmacist-led anticancer clinic across a range of cancer types and evaluate health service staff perceptions of these consultations. METHOD: Retrospective data were collected from electronic patient medical records from 2017 to 2020 at a Western Australian quaternary hospital. The impacts of pharmacist clinical interventions were classified using a validated tool and specialist interdisciplinary panel consensus. An online staff survey was conducted using Qualtrics. RESULTS: Of 246 patients reviewed, 76 (30.8%, p < .001) had received a clinical intervention of which 48 (63.2%) were classified as high-extreme and 28 (36.8%) as low-moderate impact (p = .021). Patients on ≥5 concurrent medications or > 65 years may represent high risk groups. Thirty-seven clinical staff were surveyed (37/55; 67.3%) and all strongly agreed/ agreed pharmacist consultation improved patient understanding and medication management confidence (p < .001). All cancer center staff (26/26) strongly agreed/agreed the clinic added value to the cancer service (p < .001), and 96.2% perceived it improved patient outcomes (p < .001). CONCLUSIONS: Specialist pharmacist-led patient consultation for patients on OAM regimens may protect patients from high and extreme risk of harm. Specialist interdisciplinary staff supported this service.

A survey of operating theatre staff on the impact of automated medication dispensing systems in operating theatres in an Australian hospital.

There is a lack of published literature investigating the impact of anaesthesia-specific automated medication dispensing systems on theatre staff. This study aimed to investigate the perspectives of theatre staff from multiple disciplines on their experience using anaesthesia stations three years after implementation at our Western Australian quaternary hospital institution. A web-based survey was distributed to 440 theatre staff, which included consultant anaesthetists, anaesthetic trainees, nurses, anaesthetic technicians and pharmacists, and 118 responses were received (response rate 26.8%). Eighty-one percent of the anaesthetic medical staff responders reported that the anaesthesia stations were fit for purpose and 66.67% of the anaesthetic medical staff reported that they were user friendly. Sixty-seven percent of anaesthetic medical staff agreed that controlled medication (e.g. schedule 8 and schedule 4 recordable) transactions were more efficient with the anaesthesia stations, and 66.67% agreed that the anaesthesia stations improved accountability for these transactions. Sixty-seven percent of anaesthetic medical staff preferred to use anaesthesia stations and 21.2% of all the responders preferred a manual medication trolley (P ≤ 0.001). This survey of user experience with anaesthesia stations was found to be predominantly positive with the majority of theatre staff and anaesthetic medical staff preferring anaesthesia stations.

Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone. METHODS: This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months. RESULTS: 14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire 'emotional wellbeing' sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events. CONCLUSIONS: Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.

Perioperative Management and Outcomes of Hip Fracture Patients with Advanced Chronic Kidney Disease.

Aims: To explore clinical characteristics, perioperative management and outcomes of Hip Fracture patients with advanced Chronic Kidney Disease (HF-aCKD) compared to the general Hip Fracture population without aCKD (HF-G) within a large volume tertiary hospital in Western Australia. Methods: Retrospective chart review of patients admitted with hip fracture (HF) to a single large volume tertiary hospital registered on Australian and New Zealand Hip Fracture Registry (ANZHFR). We compared baseline demographic and clinical frailty scale (CFS) of HF-aCKD (n = 74), defined as eGFR < 30 mls/min/1.73 m2, with HF-G (n = 452) and determined their outcomes at 120 days. Results: We identified 74 (6.97%) HF patients with aCKD. General demographics were similar in HF-aCKD and HF-G populations. 120-days mortality for HF-aCKD was double that of HF-G population (34% vs 17%, P = .001). For dialysis patients, 120-days mortality was triple that of HF-G population (57%). Except for the fit category of HF-aCKD group, higher CFS was associated with higher 120-days mortality in both groups. Of all HF-aCKD patients, 96% had operative intervention and 48% received blood transfusion. There were no new starts to dialysis peri-operatively. Each point reduction in eGFR below 12 mL/min/1.73 m2 was associated with 3% increased probability of death in hospital. Conclusions: 120-days mortality was double in HF-aCKD and triple in HF-dialysis that of the HF-G within our institution. Clinical frailty scale can be useful in predicting mortality after HF in frail aCKD patients. High rate of blood transfusions was observed in HF-aCKD group. Further studies with larger HF-aCKD numbers are required to explore these associations in detail.

Delirium in hospitalised adults with acute burns - A systematic review.

INTRODUCTION: Delirium is a potentially modifiable, acutely altered mental state, commonly characterised as a hospital-acquired complication. Studies of adult inpatients with acute burns with and without delirium identify causative risks related to the injury or treatment and outcomes related to the patient and healthcare system. We compare patients with and without delirium, providing a high-level quantitative synthesis of delirium risks and outcomes to inform guidelines and future research. METHODS: A systematic review, meta-analysis and GRADE evaluation of risks and outcomes associated with delirium in adults with acute burns was conducted using PRISMA guidelines and PROSPERO protocol CRD42021283055. The Newcastle-Ottawa Scale was used to assess quality. RESULTS: Investigators reviewed ten studies. ASA score ≥ 3, Total Body Surface Area Percentage (TBSA)> 10%, surgery done, ICU admission, hospital and also Intensive Care Unit (ICU) lengths of stay all had statistically significant associations with delirium, with low-very low certainty on GRADE evaluation. Limitations were heterogeneous studies, review methodology and study bias. CONCLUSION: Delirium represents a significant risk to comorbid patients with burns that are hospitalised, receive ICU care, and surgery. Further research is indicated to precisely categorise delirium along the clinical journey to identify modifiable factors, prevention, and proactive therapy.