Effects of photobiomodulation therapy on muscle function in individuals with multiple sclerosis.

BACKGROUND: In people with multiple sclerosis (pwMS), muscle fatigue and weakness are common issues that can interfere with daily activities. Photobiomodulation therapy (PBMT), comprising light in a 600-1100 nm bandwidth, is a low-level laser therapy thought to improve muscle performance in non-disease populations, in part, by improving mitochondrial function and thus, might be beneficial in pwMS. Given this potential, we aimed to investigate the effects of PBMT on muscle performance in pwMS, both in the short-term and over an extended period. METHODS: This study consisted of two parts with a randomized double-blind crossover design. In study I, muscle function was assessed in four sessions before and after PBMT in ambulatory pwMS (N = 17, F = 14) as follows: maximal voluntary contraction (MVC) and muscle fatigue of the right tibialis anterior (TA) muscle was compared at baseline and following a two-min submaximal fatiguing contraction. Then, PBMT was administered to the belly of TA muscle at different doses of energy of an active device (40 J, 80 J, 120 J) or placebo. The muscle function assessment was then repeated. OUTCOME VARIABLES: muscle force recovery (%), muscle fatigue (%). Statistical tests included McNemar's exact test, Wilcoxon signed-rank test, and the Friedman test. In study II, a subgroup from study I (N = 12, F = 11) received individualized doses (i.e., best dose-effect observed in study I) of active, or placebo PBMT, which was administered on the TA muscle for two weeks. Muscle function assessments were performed pre- and post-PBMT in four sessions similar to study I. OUTCOME VARIABLES: Baseline strength (N), endurance time (s), and muscle fatigue (%). The Wilcoxon signed-rank test was used for statistical analysis. Values are reported as mean (SD). RESULTS: In study I, participants who received a high dose of PBMT showed significant improvement in force recovery (101.89 % (13.55 %)) compared to the placebo group (96.3 % (18.48 %); p = 0.03). Muscle fatigue did not significantly improve with either active PBMT or placebo. In study II, active PBMT resulted in a significant improvement in muscle strength compared to both the baseline (pre-PBMT = 162.70 N (37.52 N); post-PBMT = 185.56 N (33.95 N); p = 0.01) and the placebo group (active PBMT: mean-change = 22.87 N (23.67 N); placebo: mean-change = -4.12 N (31.95 N); p = 0.02). Endurance time and muscle fatigue did not show significant improvement with either active PBMT or placebo. CONCLUSION: Our findings suggest that an individualized dose of PBMT might improve muscle performance, including force recovery and strength in individuals with mild-moderate MS. Therefore, PBMT might be a novel therapeutic modality, either as a standalone treatment or in combination with other interventions, to improve muscle performance in pwMS.

Global Variation in Magnetic Resonance Imaging Quality of the Prostate.

Background High variability in prostate MRI quality might reduce accuracy in prostate cancer detection. Purpose To prospectively evaluate the quality of MRI scanners taking part in the quality control phase of the global PRIME (Prostate Imaging Using MRI ± Contrast Enhancement) trial using the Prostate Imaging Quality (PI-QUAL) standardized scoring system, give recommendations on how to improve the MRI protocols, and establish whether MRI quality could be improved by these recommendations. Materials and Methods In the prospective clinical trial (PRIME), for each scanner, centers performing prostate MRI submitted five consecutive studies and the MRI protocols (phase I). Submitted data were evaluated in consensus by two expert genitourinary radiologists using the PI-QUAL scoring system that evaluates MRI diagnostic quality using five points (1 and 2 = nondiagnostic; 3 = sufficient; 4 = adequate, 5 = optimal) between September 2021 and August 2022. Feedback was provided for scanners not achieving a PI-QUAL 5 score, and centers were invited to resubmit new imaging data using the modified protocol (phase II). Descriptive comparison of outcomes was made between the MRI scanners, feedback provided, and overall PI-QUAL scores. Results In phase I, 41 centers from 18 countries submitted a total of 355 multiparametric MRI studies from 71 scanners, with nine (13%) scanners achieving a PI-QUAL score of 3, 39 (55%) achieving a score of 4, and 23 (32%) achieving a score of 5. Of the 48 (n = 71 [68%]) scanners that received feedback to improve, the dynamic contrast-enhanced sequences were those that least adhered to the Prostate Imaging Reporting and Data System, version 2.1, criteria (44 of 48 [92%]), followed by diffusion-weighted imaging (20 of 48 [42%]) and T2-weighted imaging (19 of 48 [40%]). In phase II, 36 centers from 17 countries resubmitted revised studies, resulting in a total of 62 (n = 64 [97%]) scanners with a final PI-QUAL score of 5. Conclusion Substantial variation in global prostate MRI acquisition parameters as a measure of quality was observed, particularly with DCE sequences. Basic evaluation and modifications to MRI protocols using PI-QUAL can lead to substantial improvements in quality. Clinical trial registration no. NCT04571840 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almansour and Chernyak in this issue.

The ARTS (Avoiding Risks of Thrombosis and Bleeding in Surgery) Trial: Lessons Learnt in Setting Up an International Multicentre Clinical Trial of an Investigational Medicinal Product in the UK.

We describe our experience in setting up the UK arm of the ARTS trial and highlight regulatory and funding challenges in relation to an international multicentre setting for an investigational medicinal product.

Audit, Feedback, and Education to Improve Quality and Outcomes in Transurethral Resection and Single-Instillation Intravesical Chemotherapy for Nonmuscle Invasive Bladder Cancer Treatment: Protocol for a Multicenter International Observational Study With an Embedded Cluster Randomized Trial.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancers. It is common and costly. Cost and detriment to patient outcomes and quality of life are driven by high recurrence rates and the need for regular invasive surveillance and repeat treatments. There is evidence that the quality of the initial surgical procedure (transurethral resection of bladder tumor [TURBT]) and administration of postoperative bladder chemotherapy significantly reduce cancer recurrence rates and improve outcomes (cancer progression and mortality). There is surgeon-reported evidence that TURBT practice varies significantly across surgeons and sites. There is limited evidence from clinical trials of intravesical chemotherapy that NMIBC recurrence rate varies significantly between sites and that this cannot be accounted for by differences in patient, tumor, or adjuvant treatment factors, suggesting that how the surgery is performed may be a reason for the variation. OBJECTIVE: This study primarily aims to determine if feedback on and education about surgical quality indicators can improve performance and secondarily if this can reduce cancer recurrence rates. Planned secondary analyses aim to determine what surgeon, operative, perioperative, institutional, and patient factors are associated with better achievement of TURBT quality indicators and NMIBC recurrence rates. METHODS: This is an observational, international, multicenter study with an embedded cluster randomized trial of audit, feedback, and education. Sites will be included if they perform TURBT for NMIBC. The study has four phases: (1) site registration and usual practice survey; (2) retrospective audit; (3) randomization to audit, feedback, and education intervention or to no intervention; and (4) prospective audit. Local and national ethical and institutional approvals or exemptions will be obtained at each participating site. RESULTS: The study has 4 coprimary outcomes, which are 4 evidence-based TURBT quality indicators: a surgical performance factor (detrusor muscle resection); an adjuvant treatment factor (intravesical chemotherapy administration); and 2 documentation factors (resection completeness and tumor features). A key secondary outcome is the early cancer recurrence rate. The intervention is a web-based surgical performance feedback dashboard with educational and practical resources for TURBT quality improvement. It will include anonymous site and surgeon-level peer comparison, a performance summary, and targets. The coprimary outcomes will be analyzed at the site level while recurrence rate will be analyzed at the patient level. The study was funded in October 2020 and began data collection in April 2021. As of January 2023, there were 220 hospitals participating and over 15,000 patient records. Projected data collection end date is June 30, 2023. CONCLUSIONS: This study aims to use a distributed collaborative model to deliver a site-level web-based performance feedback intervention to improve the quality of endoscopic bladder cancer surgery. The study is funded and projects to complete data collection in June 2023. TRIAL REGISTRATION: ClinicalTrials.org NCT05154084; https://clinicaltrials.gov/ct2/show/NCT05154084. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42254.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Small Renal Cell Carcinomas after Image-Guided Cryoablation or Radio-Frequency Ablation.

There is a lack of cheap and effective biomarkers for the prediction of renal cancer outcomes post-image-guided ablation. This is a retrospective study of patients with localised small renal cell cancer (T1a or T1b) undergoing cryoablation or radiofrequency ablation (RFA) at our institution from 2003 to 2016. A total of 203 patients were included in the analysis. In the multivariable analysis, patients with raised neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) pre-operatively, post-operatively and peri-operatively are associated with significantly worsened cancer-specific survival, overall survival and metastasis-free survival. Furthermore, an increased PLR pre-operatively is also associated with increased odds of a larger than 25% drop in renal function post-operatively. In conclusion, NLR and PLR are effective prognostic factors in predicting oncological outcomes and peri-operative outcomes; however, larger external datasets should be used to validate the findings prior to clinical application.

Comparing biparametric to multiparametric MRI in the diagnosis of clinically significant prostate cancer in biopsy-naive men (PRIME): a prospective, international, multicentre, non-inferiority within-patient, diagnostic yield trial protocol.

INTRODUCTION: Prostate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach. METHODS: Prostate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial. TRIAL REGISTRATION NUMBER: NCT04571840.

Decision Regret in Patients with Localised Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Treatment choice for localised prostate cancer remains a significant challenge for patients and clinicians, with uncertainty over decisions potentially leading to conflict and regret. There is a need to further understand the prevalence and prognostic factors of decision regret to improve patient quality of life. OBJECTIVE: To generate the best estimates for the prevalence of significant decision regret localised prostate cancer patients, and to investigate prognostic patient, oncological, and treatment factors associated with regret. EVIDENCE ACQUISITION: We performed a systematic search of MEDLINE, Embase, and PsychINFO databases including studies evaluating the prevalence or patient, treatment, or oncological prognostic factors in localised prostate cancer patients. A pooled prevalence of significant regret was calculated with the formal prognostic factor evaluation conducted per factor identified. EVIDENCE SYNTHESIS: Significant decision regret was present in a pooled 20% (95% confidence interval 16-23) of patients across 14 studies and 17883 patients. This was lower in active surveillance (13%), with little difference between those who underwent radiotherapy (19%) and those who underwent prostatectomy (18%). Evaluation of individual prognostic factors demonstrated higher regret in those with poorer post-treatment bowel, sexual, and urinary function; decreased involvement in the decision-making process; and Black ethnicity. However, evidence remains conflicting, with low or moderate certainty of findings. CONCLUSIONS: A significant proportion of men experience decision regret after a localised prostate cancer diagnosis. Monitoring those with increased functional symptoms and improving patient involvement in the decision-making process through education and decision aids may reduce regret. PATIENT SUMMARY: We looked at how common regret in treatment decisions is after treatment for early-stage prostate cancer and factors linked with this. We found that one in five regret their decision, with those who had experienced side effects or were less involved in the decision-making process more likely to have regret. By addressing these, clinicians could reduce regret and improve quality of life.

Virtual classroom proficiency-based progression for robotic surgery training (VROBOT): a randomised, prospective, cross-over, effectiveness study.

Robotic surgery training has lacked evidence-based standardisation. We aimed to determine the effectiveness of adjunctive interactive virtual classroom training (VCT) in concordance with the self-directed Fundamentals of Robotic Surgery (FRS) curriculum. The virtual classroom is comprised of a studio with multiple audio-visual inputs to which participants can connect remotely via the BARCO weConnect platform. Eleven novice surgical trainees were randomly allocated to two training groups (A and B). In week 1, both groups completed a robotic skills induction. In week 2, Group A received training with the FRS curriculum and adjunctive VCT; Group B only received access to the FRS curriculum. In week 3, the groups received the alternate intervention. The primary outcome was measured using the validated robotic-objective structured assessment of technical skills (R-OSAT) at the end of week 2 (time-point 1) and 3 (time-point 2). All participants completed the training curriculum and were included in the final analyses. At time-point 1, Group A achieved a statistically significant greater mean proficiency score compared to Group B (44.80 vs 35.33 points, p = 0.006). At time-point 2, there was no significant difference in mean proficiency score in Group A from time-point 1. In contrast, Group B, who received further adjunctive VCT showed significant improvement in mean proficiency by 9.67 points from time-point 1 (95% CI 5.18-14.15, p = 0.003). VCT is an effective, accessible training adjunct to self-directed robotic skills training. With the steep learning curve in robotic surgery training, VCT offers interactive, expert-led learning and can increase training effectiveness and accessibility.

Is It PRIME Time for Biparametric Magnetic Resonance Imaging in Prostate Cancer Diagnosis?

The PRIME (PRostate Imaging using Mri +/- contrast Enhancement) study is evaluating whether quicker, cheaper, and less invasive biparametric magnetic resonance imaging (bpMRI) is noninferior to multiparametric MRI in diagnosing clinically significant prostate cancer (PCa). If the study results confirm that bpMRI is not inferior, it could become the new standard of care for PCa diagnosis and streamline the diagnosis pathway so that all men who need MRI have access to this diagnostic tool.

Posterior Circulation Ischaemic Stroke.

Posterior circulation ischaemic stroke (PCIS) is a disease of high mortality and morbidity. They account for 20-25% of all ischaemic strokes. However, it is relatively under-researched and requires more clinical attention, since it carries worse functional outcomes. Vertigo, visual disturbances and sensory/motor disturbances are commonly observed in patients with PCIS. Large artery atherosclerosis and embolism are the main causes of PCIS, while there is growing evidence that vertebrobasilar dolichoectasia is a key associative factor. Hypertension is the most common risk factor, while diabetes mellitus is more specific to PCIS. PCIS is diagnosed through a range of neuroimaging techniques, which respectively examine structural brain abnormalities, vascular patency and perfusion. PCIS, in line with ischaemic stroke in general, necessitates medical treatment and lifestyle modifications. This includes smoking cessation, weight control, and alterations in dietary habits. Aspirin use also significantly improves survival outcomes. While intravascular and intra-arterial thrombolysis improve clinical outcomes, this is not proven conclusively for stenting and angioplasty. Future research on PCIS can focus on multi-centre epidemiological studies, clinically significant anatomical variants, and collateralisation.

Implications and effects of COVID-19 on diagnosis and management of prostate cancer.

PURPOSE OF REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty on the optimal management for prostate cancer (PCa). This narrative review aims to shed light on the optimal diagnosis and management of patients with or suspected to have PCa. RECENT FINDINGS: Faecal-oral or aerosol transmission is possible during prostate procedures; caution must be in place when performing digital rectal examinations, transrectal ultrasound-guided prostate biopsies and prostate surgeries requiring general anaesthesia. Patients must also be triaged using preoperative polymerase chain reaction tests for COVID-19. COVID-19 has accelerated the adoption of multiparametric Magnetic Resonance Imaging (MRI), reducing the need for prostate biopsy unless when absolutely indicated, and the risk of COVID-19 spread can be reduced. Combined with prostate-specific antigen (PSA) density, amongst other factors, multiparametric MRI could reduce unnecessary biopsies in patients with little chance of clinically significant PCa. Treatment of PCa should be stratified by the risk level and preferences of the patient. COVID-19 has accelerated the development of telemedicine and clinicians should utilise safe and effective teleconsultations to protect themselves and their patients. SUMMARY: COVID-19 transmission during prostate procedures is possible. Patients with a Prostate Imaging-Reporting and Data System (PI-RADS) of <3 and PSA density <0.15 ng/ml/ml are deemed low-risk and are safe to undergo surveillance without MRI-targeted biopsy. Intermediate- or high-risk patients should be offered definitive treatment within four months or 30days of diagnosis to avoid compromising treatment outcomes; three-month courses of neoadjuvant androgen deprivation therapy can be considered when a delay of surgery is anticipated.

Stick to Milan: Infeasibility of the Brazil-Milan Criteria in recommending patients with hepatocellular carcinoma for liver transplantation.

This article discusses the infeasibility of adhering to the Brazil-Milan Criteria for determining whether patients with hepatocellular carcinoma (HCC) should be offered liver transplantation. The Criteria are currently used widely in Brazil. However, since they expand the net of the transplant-eligible population, and that transplantation is shown to improve clinical outcomes in HCC patients relative to other treatments, they are inherently attractive and may be adopted by other countries in determining whether HCC patients should receive liver transplantation. I argue that the Criteria unjustifiably disregard the number of tumour nodules found in the patient. This number may be indicative of the recurrence potential of the disease, since these nodules can originate from different clonal populations. The greater the number, the higher the risk these nodules are associated with clones which contain genetic mutations conferring even greater potential for proliferation and dissemination. Clusters of tumour cells may be micro-disseminated to vascular structures surrounding the liver, as well as extrahepatic systems. This increases recurrence potential and reduces the benefit of liver transplantation in these patients. Thus, HCC patients harbouring fewer but larger tumour nodules may present with a more favourable genomic and epigenomic profile than those with more, albeit smaller, tumour nodules. Patients with more tumour nodules may reap greater clinical benefit if initiated on systemic therapy early, rather than wait for a suitable donor liver. Although the Criteria are reached by consensus, with reference to findings from recent studies, as well as scientific theory, it is ripe for review.

Effects of Delayed Radical Prostatectomy and Active Surveillance on Localised Prostate Cancer-A Systematic Review and Meta-Analysis.

External factors, such as the coronavirus disease 2019 (COVID-19), can lead to cancellations and backlogs of cancer surgeries. The effects of these delays are unclear. This study summarised the evidence surrounding expectant management, delay radical prostatectomy (RP), and neoadjuvant hormone therapy (NHT) compared to immediate RP. MEDLINE and EMBASE was searched for randomised controlled trials (RCTs) and non-randomised controlled studies pertaining to the review question. Risks of biases (RoB) were evaluated using the RoB 2.0 tool and the Newcastle-Ottawa Scale. A total of 57 studies were included. Meta-analysis of four RCTs found overall survival and cancer-specific survival were significantly worsened amongst intermediate-risk patients undergoing active monitoring, observation, or watchful waiting but not in low- and high-risk patients. Evidence from 33 observational studies comparing delayed RP and immediate RP is contradictory. However, conservative estimates of delays over 5 months, 4 months, and 30 days for low-risk, intermediate-risk, and high-risk patients, respectively, have been associated with significantly worse pathological and oncological outcomes in individual studies. In 11 RCTs, a 3-month course of NHT has been shown to improve pathological outcomes in most patients, but its effect on oncological outcomes is apparently limited.

Variations in intrinsic breast cancer characteristics in screen-detected breast cancer patients aged between 45 and 69 and above the age of 70.

BACKGROUND: Increasing age is a well-recognized risk factor for breast cancer. With an increase in life expectancy of women, more older patients are diagnosed with breast cancer. This study aimed to identify the variations in breast cancer attributes and mortality in different age groups in New Zealand. METHODS: This was a retrospective study of data from the Auckland Breast Cancer Register between 1 June 2000 and 28 February 2017. Patients who were diagnosed through Breast Screen were included. Group A included those aged between 45 and 69 years. Group B included individuals with an age of 70 years or above. RESULTS: From June 2000 to February 2017, a total of 6304 new cases of new breast cancer were diagnosed through Auckland Breast Screen, with 5788 patients in group A and 516 patients in group B. Group B was more likely to have the lower grade invasive cancers, with fewer grade 3 cancers. Oestrogen receptor positivity was more pronounced in group B, along with progesterone receptor positivity. Conversely, HER-2 receptor was less likely to be positive in group B. There was a significantly higher breast cancer-related mortality in group B (6.0% versus 2.7%). Mortality related to other causes was also much higher in group B as compared to that in group A (12.8% versus 2.5%). CONCLUSION: Women aged 70 years or above generally tend to have a more favourable type of breast cancer, with a lower tumour grade, oestrogen and progesterone receptor positivity, and lower rate of HER-2 overexpression.

Graft injury and re-transplantation in liver transplant patients with COVID-19.

This article discusses the current scene of liver transplantation (LT) in light of the impact of COVID-19, with particular emphasis on the possibility of graft injury and re-transplantation in LT patients infected with SARS-CoV-2. A major concern is whether such patients experience a more severe form of disease which may lead to a higher risk of acute, irreversible liver injury. If this is serious, it may necessitate re-transplantation. This article aims to raise awareness in this relatively under-researched domain. More studies are required to evaluate this issue since it has strong implications in healthcare resource allocation and clinical decision-making. Several potential research directions are proposed, including the possibility of prolonging bridging therapy for non-urgent LT cases: patients with hepatocellular carcinoma; and whether hepatoprotective agents play a role in liver-sparing during SARS-CoV-2 infection. There is also substantial discussion of the relevance of lung injury in LT patients with COVID-19 since it is not uncommon regarding the high expression of ACE2 receptors in the lungs, and that lung injury remains the major cause of death in patients with chronic liver disease.