Is staging breast magnetic resonance imaging for invasive lobular carcinoma worthwhile?

BACKGROUND: Invasive lobular carcinoma (ILC) is challenging to stage accurately using mammography (MG) and ultrasound (US) with undiagnosed ipsilateral and contralateral cancer resulting in poor patient outcomes including return to surgery. Our institution employs routine staging breast MRI in ILC for this reason. However, increased time for further imaging/biopsies contributes to patient anxiety and potentially delays definite management. We aimed to quantify the frequency of staging MRI-detected additional lesions requiring biopsy or follow-up, the added cancer detection rate and MRI prompted change in surgical management. METHODS: An observational study on staging breast MRI for newly diagnosed ILC at a tertiary Western Australian hospital from January 2019 to August 2022. Standardized 3T MRI protocol was performed, double read by unblinded fellowship-trained radiologists. Histopathology from biopsy, surgery, or first annual surveillance was the reference standard for additional MRI-detected lesions. RESULTS: One hundred ten MRI studies demonstrated 49 (45%) patients had at least one additional clinically significant MRI-detected lesion. Thirty-one patients had an additional ipsilateral lesion detected, of which 18 (58%) proved malignant; 14 (45%) multifocal and 4 (13%) multicentric ILC. Additional work-up of MRI-detected lesions averaged a 9-day delay to definitive surgery compared to patients with a negative or definitively benign MRI. MRI changed surgical planning in 11 of 110 cases from breast conservation surgery (BCS) to mastectomy and there were two contralateral cancers diagnosed. BCS reoperation rate was 11%. CONCLUSION: Staging MRI for ILC identifies clinically significant lesions in nearly half of patients, predominantly ipsilateral multifocal disease, without significant delay to definitive surgery.

Long-Term Echocardiographic and Clinical Outcomes After Invasive and Non-Invasive Therapies for Sub-Massive and Massive Acute Pulmonary Embolism.

AIM: Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE. METHODS: Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital. RESULTS: In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment. CONCLUSION: Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting.

Adrenal washout CT in patients with no history of cancer: a waste of time?

PURPOSE: To validate the diagnostic performance of adrenal washout CT in patients without known malignancy in a Western Australian population. METHODS: A radiology information system (RIS) search for CT reports containing "adrenal" and "washout" across six networked metropolitan public hospitals between January 2005 and November 2021. Homogenous nodules ≥ 1 cm, ≥ 10 HU without a suspected functional component in patients without a history of malignancy were included. Reported absolute and relative washout percentages were recorded and re-measured from unenhanced, 60-s portal venous and 15-min delayed phase imaging and compared to either histopathological or CT follow up for growth (≥ 12 months) reference standards. RESULTS: 2653 studies were screened with 191 meeting inclusion criteria. 105 nodules underwent washout CT and then had either histopathological (12 patients) or CT follow up (93 patients) reference standards available. Reported absolute washout (aWO) estimated sensitivity and specificity for malignant/indeterminate nodules was low at 33% (95% CI 25-43%) and 77% (95% CI 68-84%) respectively. Reported relative washout (rWO) sensitivity and specificity were 56% (95% CI 46-65%) and 69% (95% CI 60-77%) respectively. Negative predictive values for both aWO and rWO were reassuring at 92% (95% CI 86-96%) and 94% (95%CI 88-97%). CONCLUSION: Our study validates a recent report suggesting that adrenal washout has poor sensitivity for and consequent limited utility to exclude malignancy in patients with no cancer history. However, patients with incidental adrenal nodules < 4 cm in size with benign washout can be reassured by the high negative predictive value and worked up to exclude functional adenoma and re-imaged in a year to confirm no growth.

Hot avulsion versus argon plasma coagulation for the management of the non-ensnarable polyp: A multicenter, randomized controlled trial.

Background and Aim: Snare resection of nonlifting colonic lesions often requires supplemental techniques. We compared the success rates of neoplasia eradication using hot avulsion and argon plasma coagulation in colonic polyps when complete snare polypectomy had failed. Methods: Polyps that were not completely resectable by snare polypectomy were randomized to argon plasma coagulation or hot avulsion for completion of resection. Argon plasma coagulation was delivered using a forward shooting catheter, using a nontouch technique (flow 1.2 L, 35 watts). Hot avulsion was performed by grasping the neoplastic tissue with hot biopsy forceps and applying traction away from the bowel wall while using EndoCut I or soft coagulation for avulsion. Surveillance colonoscopies were performed at 6, 12, and 18 months. Results: From November 2013 to July 2017, 59 patients were randomized to argon plasma coagulation (28) or hot avulsion (31). The median age was 69 (60-75), with 46% being female. The median residual tissue size was 10 mm (6-12). The residual adenoma rate at 6 months (hot avulsion 6% vs argon plasma coagulation 21% P = 0.09) and 18 months was not different between the groups (6.6% vs 3.6% P = 0.25). One patient in the argon plasma coagulation arm was diagnosed with metastatic cancer of likely colorectal origin despite benign histology in the original polypectomy specimen, supporting the importance of tissue acquisition. Conclusion: Both hot avulsion and argon plasma coagulation are effective and safe modalities to complete resection of non-ensnarable colonic polyps.

Percutaneous microwave ablation of T1a renal cell carcinomas: A 10-year single-center retrospective review.

INTRODUCTION: Partial nephrectomy is currently the preferred treatment option for T1a renal cell carcinomas (RCC), with nephron-sparing techniques, including microwave ablation, becoming more common in select patients. Primary aims are to document outcomes of microwave ablation for T1a RCCs in an Australian tertiary centre to add to the evidence for its safety and efficacy. METHODS: The prospectively maintained Sir Charles Gairdner Hospital Interventional Radiology database was retrospectively searched for all Renal Microwave ablations completed between June 2012 and February 2022. This database and a combination of hospital programmes including Agfa Impax PACS, Bossnet digital medical record and iSoft Clinical Manager were used to extract the relevant data which was anonymized and entered into an Excel spreadsheet for analysis. RESULTS: Forty-eight patients underwent microwave ablation for 50 tumours. Of these, there were two local and two distant recurrences. A fifth patient had metastases on presentation. Higher local recurrence rates were associated with larger tumour size (P = 0.043). Tumour proximity to the collecting system <4 mm was associated with higher rates of complications (P = 0.020). RENAL scores did not show statistically significant correlation with complications (P = 0.092) or local or distant recurrence. Notably, the study follow-up time was longer than many comparative studies (mean = 2796, ~7.66 years censoring for death and mean = 832 days, ~2.28 years not censoring for death). CONCLUSION: Consistent with the literature, this study further demonstrates that microwave ablation is a safe and efficacious option for treatment of T1a RCC.

Comparison of toric intraocular lens calculation with the integrated K method and three single biometric devices.

PURPOSE: To compare astigmatic outcomes using the Integrated K method and anterior surface keratometry from 3 different biometric devices. SETTING: Lions Eye Institute, Perth, Australia. DESIGN: Retrospective case series. METHODS: Eyes of patients who underwent uneventful cataract surgery were analyzed. Predicted postoperative astigmatism was calculated for Integrated K method, IOLMaster 700, Lenstar and Pentacam. The mean centroid error in predicted postoperative refractive astigmatism (PE), mean absolute PE and percentage of eyes within 0.5 diopter (D), 0.75 D and 1 D of absolute magnitude of PE were compared. A subset analysis was done where the difference in cylinder magnitude between the 2 methods was more than 0.25 D. Spherical prediction outcomes were also analyzed. RESULTS: 241 eyes of 139 patients were included in the study. The mean centroid PE of Integrated K method (-0.07 @ 69) was significantly different from IOLMaster and Pentacam. The mean absolute PE with Integrated K method (0.33 ± 0.17) was significantly lower than all 3 devices. The percentage of eyes within 0.5 D and 0.75 D of absolute magnitude of PE was 82% and 99% for Integrated K method, 76% and 95% for IOLMaster and Lenstar, and 60% and 86% for Pentacam. In the subset analysis, the improvement in accuracy of the Integrated K method compared with a single device was greater in terms of the percentage of eyes predicted within 0.5 D. The Integrated K method did not impact the spherical prediction outcomes. CONCLUSIONS: The integrated K method is more accurate and precise than anterior surface keratometry from a single biometric device.

Modified forced expiration technique using expiratory resistance in adults with cystic fibrosis.

BACKGROUND: Participation in airway clearance techniques (ACT) is important to minimise development of irreversible airway obstruction in patients with cystic fibrosis (CF). Positive expiratory pressure (PEP) and expiratory resistance devices (ERD) are often used as they can improve collateral ventilation and aid in the shearing of mucus from airways. This project looked to identify whether utilising an ERD during a forced expiration technique (FET) improves ease of expectoration, sputum amount and coughing frequency in patients with CF. METHOD: Patients with CF admitted for a respiratory exacerbation completed two sessions of 10 cycles of their usual ACT with half of the FET components performed with an ERD, half with FET alone. RESULTS: EOE, sputum wet weight, cough frequency and patient preference were similar between groups. Improved EOE without the ERD was found in participants who usually use PEP for their ACT regime. CONCLUSION: Combining the FET with a PEP mask did not improve EOE and other outcomes in this small study. Investigating the efficacy of this technique within a larger population is warranted.

Intravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial).

PURPOSE: To determine whether intravenous vitamin C compared with placebo, reduces vasopressor requirements in patients with vasoplegic shock. METHODS: Double-blinded, randomised clinical trial (RCT) conducted in two intensive care units in Perth, Australia. Vasopressor requirements at enrolment needed to be >10 µg/min noradrenaline after hypovolaemia was clinically excluded. Patients received either intravenous 1.5 g sodium ascorbate in 100 ml normal saline every 6 h for 5 days, or placebo (100 ml normal saline). The primary outcome was duration of vasopressor usage in hours. Secondary outcomes were ICU and hospital length of stay, and 28-day, ICU and hospital mortality. RESULTS: Of the 71 patients randomised (35 vitamin C, 36 placebo group), the median vasopressor duration was 44 h [95% CI, 37-54 h] and 55 h [95% CI, 33-66 h]) in the vitamin C and placebo groups (p = 0.057). ICU and hospital length of stay, mortality outcomes were similar between groups. CONCLUSIONS: In this RCT of patients with vasoplegic shock of at least moderate severity, the use of IV vitamin C compared with placebo did not significantly reduce the duration of vasopressors. TRIAL REGISTRATION: Prospective registration - trial number ACTRN12617001392358.

Magnetic resonance imaging (MRI) of normal human placentae.

INTRODUCTION: The MRI appearances of the human placenta in the absence of maternal or fetal pathology have not been extensively studied, with only a few studies reporting findings in the uncomplicated pregnancy. The purpose of this study is to review the placental MRI appearances in low-risk pregnancies in a prospective study. METHODS: A prospective observational study of placental MRI in low-risk pregnancies was initially planned, however recruitment was terminated early due to the COVID19 pandemic. The protocol was subsequently modified to compare the placental appearances in the enrolled cohort with pregnancies having had MRI for non-placental pathologies. The data from the two groups were then pooled to assess the range of normal placental appearances. RESULTS: Eighty-three pregnancies were prospectively assessed with MRI at a median gestation of 29 weeks (range 14-39) from a mixed group of prospective cases (n = 28) and retrospectively recruited obstetric MRI (n = 55). Placental thickness in the third trimester ranged from 18 to 35 mm. T2 heterogeneity was seen in 75% (25/33) at second trimester and by the third trimester 50% (25/50) were moderately or markedly heterogenous. T2 dark bands (>6 mm) were seen in 9% (3/33) and 20% (10/50) of second and third trimester pregnancies, respectively. Undetectable myometrium or loss of the subplacental myometrial plane was present in 15% (5/33) of second and 38% (19/50) of third trimester placentae. CONCLUSION: This qualitative study of normal placental MRI appearances expands the current knowledge base by confirming they vary, evolve with gestation, and can overlap with signs of placenta accreta spectrum.

Autorefraction as an Objective Method to Evaluate Accuracy of Intraocular Lens Calculation Formulas.

PURPOSE: To compare the spherical equivalent (SE) and astigmatic prediction error between subjective refraction (SUBref) and autorefraction (AUTOref) after cataract surgery to determine whether the latter is useful as an objective method to compare the accuracy of different methods of intraocular lens (IOL) power calculation. METHODS: Postoperative refraction was examined using two techniques: SUBref and AUTOref. The results of these two techniques were compared. Predicted postoperative refraction for spherical outcome was calculated with the Barrett Universal II (BUII), Haigis, Holladay I, SRK/T, Hoffer Q, and BUII with measured posterior corneal astigmatism (MPCA) formulas. Predicted postoperative refraction for astigmatic outcome was calculated with the Barrett Toric calculator, vergence-based toric calculator using the Holladay 1 formula for effective lens position, and Barrett Toric calculator MPCA formulas. Formula accuracy and ranking were compared between the two methods of refraction. RESULTS: Data were obtained from 219 eyes of 155 patients. Statistically significant differences were detected between SUBref and AUTOref for SE, J0, and J45 (P < .001). The spherical outcome formula analysis demonstrated no significant differences, whereas the predicted cylinder power analysis demonstrated significant differences within individual formulas between SUBref and AUTOref measures. The lowest median absolute error and the highest percentage of eyes achieving their refractive target for both SUBref and AUTOref were achieved with the BUII formula and the Barrett Toric calculator. CONCLUSIONS: AUTOref is a useful method with adequate accuracy to determine spherical and astigmatic outcome and equally or more effective in being able to discriminate between spherical outcome formulas. The AUTOref method can allow valuable studies to be conducted in less-than-optimal environments and provides the ability to compare studies without the confounding factors of SUBref. [J Refract Surg. 2022;38(9):580-586.].

Retrieval of olfactory fear memory alters cell proliferation and expression of pCREB and pMAPK in the corticomedial amygdala and piriform cortex.

The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using Pavlovian olfactory fear conditioning (OFC), a variant of the traditional tone-shock paradigm, this study explored the changes involved in its processing. We assessed the expression of neuronal plasticity markers phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB) and phosphorylated mitogen-activated protein kinase (pMAPK) 24 h and 14 days following OFC, in newborn neurons (EdU+) and in brain regions associated with olfactory memory processing; the olfactory bulb, piriform cortex, amygdale, and hippocampus. Here, we show that all proliferating neurons in the dentate gyrus of the hippocampus and glomerular layer of the olfactory bulb were colocalized with pCREB at 24 h and 14 days post-conditioning, and the number of proliferating neurons at both time points were statistically similar. This suggests the occurrence of long-term potentiation within the neurons of this pathway. Finally, OFC significantly increased the density of pCREB- and pMAPK-positive immunoreactive neurons in the medial and cortical subnuclei of the amygdala and the posterior piriform cortex, suggesting their key involvement in its processing. Together, our investigation identifies changes in neuroplasticity within critical neural circuits responsible for olfactory fear memory.

Randomised controlled trial on the effect of simethicone bowel preparation on rectal variability during image-guided radiation therapy for prostate cancer (SPoRT study).

INTRODUCTION: The purpose of this study was to assess whether simethicone reduces the rectal volume (RV) and gas volume (GV), to increase treatment accuracy and to decrease toxicity of prostate radiation therapy. METHODS: 30 patients were randomised to simethicone or no intervention. Cone-beam computed tomography (CBCT) scans were performed on Days 1-3 and weekly until completion of radiation. RV and GV were measured using volume delineation. Toxicity data were collected. RESULTS: 264 CBCTs were analysed. RV and GV were not significantly different in the simethicone group compared with the control group at each time point (P >0.05) after adjusting for Week 0 values as a covariate. The simethicone group showed an average reduction in RV and GV of 10% and 21%, respectively, compared with the control group (P >0.05). Standard deviations were calculated over 10 time points, which were grouped to represent the first 2-3 weeks of radiation therapy versus subsequent weeks. These were not significantly different between the simethicone and control group. However, there was a statistically significant decrease in the variability of RV at time points 6-10 compared with time points 1-5 within the simethicone group (P = 0.012), but no significant difference was found between these grouped time points in the control group (P = 0.581). The toxicity questionnaires showed no significant difference between the groups. CONCLUSIONS: Simethicone did not decrease the RV or GV overall. However, simethicone appeared to significantly decrease the RV variability from Week three onwards. This suggests that taking simethicone two to three weeks before starting radiation therapy may reduce RV variability, although a larger study is needed to confirm this.

Spiders and mushrooms: Reporting bowel endometriosis shape on preoperative MRI to flag surgical complexity.

INTRODUCTION: Preoperative imaging of patients with endometriosis allows adequate counselling, referral to appropriate centres of expertise and workforce planning. The objective of this study was to assess the feasibility of simplified three-category preoperative endometriosis MRI morphological descriptors to predict subsequent surgical management. METHODS: A single-centre observational study in 76 patients (median age 38 years, range 18-55) with preoperative endometriosis mapping MRI between 1 Jan 2015 and 31 Dec 2019. MRI studies were prospectively re-read blind-to-surgical outcome to categorise rectosigmoid morphology as normal, spider-shaped (linear T2-dark fibrotic bands) superficial endometriosis or typical crescentic or mushroom-shaped deep infiltrating endometriosis (DIE). Bowel motility was similarly categorised as normal, tethered or distorted/fixed. The reference standard was subsequent surgery within 3 years of MRI, categorised as no bowel surgery, adhesiolysis only or more complex surgeries. RESULTS: Despite three-quarters of surgical cases having normal bowel morphology on preoperative MRI (72%, 55/76; 12% linear superficial endometriosis, 10% crescentic and 5% mushroom-shaped DIE) more than half showed bowel tethering (54%, 41/76) or distortion/fixation (10%, 8/76) and most patients underwent adhesiolysis (79%, 60/76). Complex surgery such as bowel resection, laparotomy conversion or complex adhesiolysis is predicted by morphology (crescentic or mushroom-shaped DIE, P < 0.001) and motility (tethered or distorted bowel, P = 0.002) descriptors. CONCLUSIONS: Comprehensive and clinically relevant diagnostic reporting does not have to be convoluted to have clinical impact: in our study population, categorising bowel morphology as normal, spider-shaped (superficial) or crescentic/mushroom-(DIE) shaped and motility as normal, tethered (superficial) or distorted/fixed (deep endometriosis) correlates to subsequent surgical complexity.

MRI sliding sign: Using MRI to assess rectouterine mobility in pelvic endometriosis.

INTRODUCTION: Surgical excision of deep infiltrating endometriosis (DIE) is complex and associated with morbidity. Diagnostic imaging plays an important role in the preoperative workup. We sought to determine the utility of single sagittal T2-weighted MRI motion sequence in the preoperative assessment of pelvic mobility in patients with endometriosis. METHODS: An observational study at a single tertiary public referral centre in Australia. Eighty-one MRI studies from 1 May 2019 to 3 December 2019, were enrolled. Studies were included if they were performed to stage endometriosis, including a T2-weighted motion series, adequately covering a uterus, cervix and rectum. Fifty-seven studies met inclusion criteria. The reference standard was a contemporaneous transvaginal ultrasound (TVUS) reporting on pelvic organ mobility. Three subspecialist radiologists were then blindly asked to identify, on the cine loop: rectouterine immobility, superficial endometriosis (pelvic bowel adhesions), rectosigmoid Deep Infiltrating Endometriosis (DIE). Fleiss' Kappa assessed interobserver agreement. Consensus MRI sensitivity and specificity were estimated against the reference standard (TVUS). RESULTS: Median age was 35 years (range 19-51). Forty-three cases had a contemporaneous TVUS; 14 reporting a sliding sign, 29 with fixed pelves. Interobserver agreement was 'substantial' (k = 0.79) for absent MRI sliding sign and 'almost perfect' (k = 0.90) for absence of DIE. Consensus MRI had 90% sensitivity (95% CI 73-98%) for pelvic immobility at TVUS (absent sliding sign). Interobserver agreement and consensus MRI sensitivity were higher for adhesions and immobility than normal findings. CONCLUSION: An MRI motion sequence can identify patients with pelvic adhesions and immobility, helping determine surgical difficulty when TVUS is not diagnostic.

Gentamicin-Containing Collagen Implant May Reduce Surgical Site Infections After Open Infrainguinal Arterial Revascularization.

BACKGROUND: Deep-space surgical site infections carry significant morbidity and mortality. The evidence for gentamicin-containing collagen implants at reducing surgical site infections in open infrainguinal arterial surgery is limited. This study examined whether gentamicin-containing collagen implants reduces 30-day surgical site infections and their severity following open infrainguinal arterial surgery. METHODS: A retrospective observational cohort study that included all patients undergoing infrainguinal arterial bypass or endarterectomy between November 2015 and March 2019 at a single tertiary vascular unit. Patients with contaminated/infected surgical fields, surgical wounds treated with negative pressure therapy, or the usage of antimicrobial implants and dressings other than Collatamp GⓇ (Aralez Pharmaceuticals, Canada) were excluded. Patients with gentamicin-containing collagen implants placed abutting vasculature were compared against patients without gentamicin-containing collagen implants. Outcomes included the rate of surgical site infections and their severity within 30 days after the operation. RESULTS: In 159 procedures (mean age 67.7 years, 74.8% male, 33.3% diabetic, 16.4% chronic renal failure, 25.2% anticoagulated postoperatively, 32.7% with prosthetic implants), 55 (34.6%) procedures received gentamicin-containing collagen implants. There were significantly more males (85.5% vs. 69.2%; P = 0.025), higher rates of obesity (41.8% vs. 26.0%; P = 0.041), and hyperlipidemia (65.5% vs. 49.0%; P = 0.048) in the gentamicin-containing collagen implant group. In total, 6 (3.8%) procedures developed deep-space surgical site infections (1 with gentamicin-containing collagen implant, 5 without) and 13 (8.2%) had severe surgical site infections that required re-intervention (1 with gentamicin-containing collagen implant, 12 without). On logistic regression analysis, the absence of gentamicin-containing collagen implants statistically significantly increased the odds of overall surgical site infections (OR = 2.50; 95% CI 1.01 - 6.19; P = 0.047). There was no statistically significant difference in the odds of deep-space surgical site infections or the severity and need for reintervention of surgical site infections. CONCLUSIONS: This is the first study that examined the effect of gentamicin-containing collagen implants on the severity of surgical site infections in vascular surgery. Gentamicin-containing collagen implants may reduce the odds of overall surgical site infections. It did not reduce the odds of deep-space surgical site infections or the severity and reintervention rate of surgical site infections following infrainguinal arterial revascularization. Larger studies are required to achieve adequate power to assess for these outcomes.

Hospitalizations in solid tumor phase I clinical trial patients: Incidence, pattern and clinical outcomes at an Australian phase I clinical trial unit.

BACKGROUND: Participation in early-phase clinical trials has become a prominent part of medical oncology patient management. We examined the incidence and pattern of hospitalizations in early-phase clinical trial patients and the associated clinical outcomes. METHOD: We conducted a retrospective review of 194 patients with solid tumors treated on phase I clinical trials between July 2014 and October 2018 at a phase I trial unit. Unplanned hospitalizations occurring during the study period were characterized and correlated with treatment response and duration of trial participation. RESULTS: Among 194 patients, 104 hospitalizations were recorded involving 62 patients (31%). Nineteen percent of patients were hospitalized for cancer-related complications and 8% for treatment toxicity. No significant correlation was seen between the hospitalization and age, sex, tumor type, or trial drug. Best response to trial therapy was complete response, partial response, stable disease, and progressive disease in 5%, 11%, 37%, and 47% of patients, respectively. Median duration on trial was 86 days (range 0-1,412). Twenty-two patients (11%) remained on trial for more than 12 months. Overall, hospitalization did not impact treatment response or trial duration. However, cancer-related hospitalization was associated with significantly lower response (p < 0.001) and early patient attrition (p < 0.001). Resolution of the hospitalization event was associated with improved response (p = 0.002) and longer duration on trial (p < 0.001). The treatment related mortality was 0.5% (n = 1). CONCLUSION: Approximately one third of patients required hospitalization, most commonly for cancer-related complications which correlated with poorer clinical outcomes. Hospitalizations related to treatment toxicity were infrequent. A significant proportion of patients derived significant therapeutic benefit. Phase I clinical trials provide a valuable treatment option for patients with cancer.

Clinicopathological characteristics and clinical morbidity in high-risk head and neck cutaneous squamous cell carcinoma patients in Western Australia.

BACKGROUND: There is no registry data on morbidity and mortality of high-risk cutaneous squamous cell carcinoma (cSCC) in Australia. AIM: To examine the clinicopathological features, mortality and morbidity in high-risk cSCC patients in Western Australia (WA). METHODS: A retrospective cohort study was conducted through hospital record review on cSCC patients discussed at multidisciplinary meetings at the two largest WA hospitals between March 2015 and December 2016. RESULTS: Of 141 patients, 129 were evaluable, with median follow up of 43.9 (range 3.0-53.2) months. Patients were predominantly older males (84%) with significant comorbidities (Charlson Comorbidity Index (CCI) ≥5; 76%) and history of previous nonmelanoma skin cancer (57%) with advanced disease (57% stage IV without distant metastasis; American Joint Committee on Cancer, 7th edition). Pathological high-risk features were common including nodal extracapsular extension (47%) and cranial nerve involvement (16%). Clinical morbidity was significant with a median of 2 (range 0-13) excisions and 2 (range 0-21) cSCC-related hospitalisations for any cSCC event following the index case discussion. Recurrences of the primary index lesion occurred in 60% of patients and 20% had ≥2 recurrences. Median overall survival for patients with nonmetastatic disease was 39.8 (range 25.9-53.7) months and 16.1 (range 0.2-32.0) months for metastatic disease. CCI ≥5, advanced nodal stage and ≥2 recurrences were significantly associated with mortality on multivariable analyses (P < 0.05). Nodal extracapsular extension and any recurrences were identified as significant risk factors for disease-specific mortality on multivariable analyses (P < 0.05). CONCLUSION: High-risk cSCC patients have significant health needs represented by high-baseline comorbidities, multiplicity of cSCC events and the number of healthcare-associated interventions. There is an unmet need for robust cancer data collection.

Is staging breast magnetic resonance imaging prompted upgrade to mastectomy appropriate?

BACKGROUND: Breast magnetic resonance imaging (MRI) use for surgical staging is increasing, though remains controversial. We aimed to evaluate the accuracy of MRI in surgical decision-making to determine if mastectomy prompted by MRI was appropriate. METHODS: A single-centre observational study in Perth, Western Australia, with the inclusion of all preoperative and postoperative studies (e.g. involved margins after breast-conserving surgery) undergoing staging breast MRI from 1 January 2015 to 26 August 2019. A standard protocol using gadolinium contrast was used. The reference standard was postoperative histopathology or, for studies without additional surgery after MRI following breast-conserving surgery, the next and subsequent annual screening episodes. By reviewing the final histopathology, the medical case notes and multidisciplinary team decision process, we evaluated whether the reported MRI disease extent was accurate in prompting an appropriate upgrade to mastectomy. Outcomes are reported with descriptive statistics. RESULTS: Of 130 cancers staged with MRI; seven were excluded as information was incomplete, 104 were performed preoperatively and 19 postoperatively. The majority (60%) staged lobular carcinoma (invasive 59%, in situ 1%) compared to ductal carcinoma (invasive 31%, in situ 8%). For preoperative MRI, half (54% - 56/104) underwent subsequent mastectomy. Of these, MRI prompted mastectomy in 45% (25/56), all appropriate for disease extent. In the postoperative staging group, two mastectomies were performed, one planned before imaging, the other prompted when MRI diagnosed residual disease and confirmed on histopathology. No false-negative staging MRI was identified. CONCLUSIONS: In our cohort, MRI prompted an upgrade to mastectomy in 21% (26/123), appropriate for cancer extent.

Effects of voluntary exercise duration on myocardial ischaemic tolerance, kinase signaling and gene expression.

AIM: Exercise is cardioprotective, though optimal interventions are unclear. We assessed duration dependent effects of exercise on myocardial ischemia-reperfusion (I-R) injury, kinase signaling and gene expression. METHODS: Responses to brief (2 day; 2EX), intermediate (7 and 14 day; 7EX and 14EX) and extended (28 day; 28EX) voluntary wheel running (VWR) were studied in male C57Bl/6 mice. Cardiac function, I-R tolerance and survival kinase signaling were assessed in perfused hearts. KEY FINDINGS: Mice progressively increased running distances and intensity, from 2.4 ± 0.2 km/day (0.55 ± 0.04 m/s) at 2-days to 10.6 ± 0.4 km/day (0.72 ± 0.06 m/s) after 28-days. Myocardial mass and contractility were modified at 14-28 days VWR. Cardioprotection was not 'dose-dependent', with I-R tolerance enhanced within 7 days and not further improved with greater VWR duration, volume or intensity. Protection was associated with AKT, ERK1/2 and GSK3ß phosphorylation, with phospho-AMPK selectively enhanced with brief VWR. Gene expression was duration-dependent: 7 day VWR up-regulated glycolytic (Pfkm) and down-regulated maladaptive remodeling (Mmp2) genes; 28 day VWR up-regulated caveolar (Cav3), mitochondrial biogenesis (Ppargc1a, Sirt3) and titin (Ttn) genes. Interestingly, I-R tolerance in 2EX/2SED groups improved vs. groups subjected to longer sedentariness, suggesting transient protection on transition to housing with running wheels. SIGNIFICANCE: Cardioprotection is induced with as little as 7 days VWR, yet not enhanced with further or faster running. This protection is linked to survival kinase phospho-regulation (particularly AKT and ERK1/2), with glycolytic, mitochondrial, caveolar and myofibrillar gene changes potentially contributing. Intriguingly, environmental enrichment may also protect via similar kinase regulation.

Efficacy of Respiratory Physiotherapy Interventions for Intubated and Mechanically Ventilated Adults with Pneumonia: A Systematic Review and Meta-Analysis.

Purpose: A systematic review was conducted to investigate the effect of respiratory physiotherapy on mortality, quality of life, functional recovery, intensive care length of stay, duration of ventilation, oxygenation, secretion clearance, and pulmonary mechanics for invasively ventilated adults with pneumonia. Method: Five databases were searched for randomized trials published between January 1995 and November 2018. Study quality was assessed using a standardized Joanna Briggs Institute critical appraisal tool, and Review Manager software was used to pool the studies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the level of certainty of the evidence. Results: A total of 14 studies of moderate quality included 251 subjects with pneumonia. Eight studies were pooled for meta-analysis. Interventions that increased inspiratory volume appeared to benefit secretion clearance by nearly 2 grams (mean difference [MD] 1.97; 95% CI: 0.80, 3.14; very low GRADE evidence) and increase static lung compliance immediately after treatment by more than 5 millilitres/centimetre H20 (MD 5.40 mL/cm H2O; 95% CI: 2.37, 8.43; very low GRADE evidence) or by more than 6 millilitres/centimetre H2O after a 20- to 30-minute delay (MD 6.86 mL/cm H2O; 95% CI: 2.86, 10.86; very low GRADE evidence). No adverse events were found. Conclusions: Respiratory physiotherapy that increases tidal volume may benefit secretion clearance and lung compliance in invasively ventilated adults with pneumonia, but its impact on other outcomes, including mortality, length of stay, and other patient-centred outcomes, is unclear, and further research is required.

Objectif : analyse systématique pour explorer l'effet de la physiothérapie respiratoire sur la mortalité, la qualité de vie, le rétablissement fonctionnel, la durée de séjour en soins intensifs, la durée de la ventilation, l'oxygénation, la clairance des sécrétions et la mécanique pulmonaire d'adultes atteints de pneumonie sous assistance respiratoire invasive. Méthodologie : recherche dans cinq bases de données pour en extraire les études aléatoires publiées entre janvier 1995 et novembre 2018. Les chercheurs ont évalué la qualité des études à l'aide de l'outil d'évaluation critique standardisé du Joanna Briggs Institute et ont utilisé le logiciel Review Manager pour regrouper les études. Ils ont utilisé la méthode GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer le degré de certitude des données probantes. Résultats : au total, 14 études de qualité modérée incluaient 251 sujets atteints de pneumonie. Les chercheurs ont regroupé huit études en vue de la méta-analyse. Les interventions qui améliorent le volume inspiratoire semblaient accroître la clairance des sécrétions de près de 2 g (différence moyenne [DM] 1,97; IC à 95 % : 0,80, 3,14; données probantes GRADE très basses) et la compliance pulmonaire statique immédiatement après le traitement de plus de 5 millilitres par centimètre d'eau (DM 5,40 mL/cm d'eau; IC à 95 % : 2,37, 8,43; données probantes GRADE très basses) ou de plus de 6 millilitres par centimètre d'eau après une période de 20 à 30 minutes (DM 6,86 mL/cm d'eau; IC à 95 % : 2,86, 10,86; données probantes GRADE très basses). Aucun événement indésirable n'a été trouvé. Conclusion : la physiothérapie respiratoire qui accroît le volume courant peut contribuer à la clairance des sécrétions et à la compliance pulmonaire chez les adultes atteints de pneumonie sous assistance respiratoire invasive, mais ses effets sur d'autres résultats cliniques, comme la mortalité, la durée d'hospitalisation et d'autres résultats axés sur le patient ne sont pas clairement établis. D'autres recherches s'imposent.