Non-invasive detection of regulatory T cells with Raman spectroscopy.

Regulatory T cells (Tregs) are a type of lymphocyte that is key to maintaining immunological self-tolerance, with great potential for therapeutic applications. A long-standing challenge in the study of Tregs is that the only way they can be unambiguously identified is by using invasive intracellular markers. Practically, the purification of live Tregs is often compromised by other cell types since only surrogate surface markers can be used. We present here a non-invasive method based on Raman spectroscopy that can detect live unaltered Tregs by coupling optical detection with machine learning implemented with regularized logistic regression. We demonstrate the validity of this approach first on murine cells expressing a surface Foxp3 reporter, and then on peripheral blood human T cells. By including methods to account for sample purity, we could generate reliable models that can identify Tregs with an accuracy higher than 80%, which is already comparable with typical sorting purities achievable with standard methods that use proxy surface markers. We could also demonstrate that it is possible to reliably detect Tregs in fully independent donors that are not part of the model training, a key milestone for practical applications.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients.

While several effective therapies for critically ill patients with COVID-19 have been identified in large, well-conducted trials, the mechanisms underlying these therapies have not been investigated in depth. Our aim is to investigate the association between various immunosuppressive therapies (corticosteroids, tocilizumab and anakinra) and the change in endothelial host response over time in critically ill COVID-19 patients. We conducted a pre-specified multicenter post-hoc analysis in a Dutch cohort of COVID-19 patients admitted to the ICU between March 2020 and September 2021 due to hypoxemic respiratory failure. A panel of 18 immune response biomarkers in the complement, coagulation and endothelial function domains were measured using ELISA or Luminex. Biomarkers were measured on day 0-1, day 2-4 and day 6-8 after start of COVID-19 treatment. Patients were categorized into four treatment groups: no immunomodulatory treatment, corticosteroids, anakinra plus corticosteroids, or tocilizumab plus corticosteroids. The association between treatment group and the change in concentrations of biomarkers was estimated with linear mixed-effects models, using no immunomodulatory treatment as reference group. 109 patients with a median age of 62 years [IQR 54-70] of whom 72% (n = 78) was male, were included in this analysis. Both anakinra plus corticosteroids (n = 22) and tocilizumab plus corticosteroids (n = 38) were associated with an increase in angiopoietin-1 compared to no immune modulator (n = 23) (beta of 0.033 [0.002-0.064] and 0.041 [0.013-0.070] per day, respectively). These treatments, as well as corticosteroids alone (n = 26), were further associated with a decrease in the ratio of angiopoietin-2/angiopoietin-1 (beta of 0.071 [0.034-0.107], 0.060 [0.030-0.091] and 0.043 [0.001-0.085] per day, respectively). Anakinra plus corticosteroids and tocilizumab plus corticosteroids were associated with a decrease in concentrations of complement complex 5b-9 compared to no immunomodulatory treatment (0.038 [0.006-0.071] and 0.023 [0.000-0.047], respectively). Currently established treatments for critically ill COVID-19 patients are associated with a change in biomarkers of the angiopoietin and complement pathways, possibly indicating a role for stability of the endothelium. These results increase the understanding of the mechanisms of interventions and are possibly useful for stratification of patients with other inflammatory conditions which may potentially benefit from these treatments.

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Predictors of Quality of Life Decline in Patients with Oligometastases treated with Stereotactic Ablative Radiotherapy: Analysis of the Population-Based SABR-5 Phase II Trial.

AIMS: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline. RESULTS: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance. CONCLUSIONS: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

Optimization of Dry-Jet Wet Spinning of Regenerated Cellulose Fibers Using [mTBDH][OAc] as a Solvent.

Superbase-based ionic liquids (ILs) have demonstrated excellent dissolution capability for cellulose, and employing the dry-jet wet spinning process, high-tenacity regenerated textile fibers have been made. Among a range of superbase-based ILs, [mTBDH][OAc] exhibited not only good spinnability but also exceptional recyclability, making it highly suitable for a closed-loop production of regenerated cellulose fibers. To further optimize the spinning process, we investigated the influence of the cellulosic raw materials and the IL with residual water on spinnability and fiber properties. In addition, single-filament spinning and multifilament spinning using spinnerets with different hole densities were investigated to reveal the upscaling challenges of the dry-jet wet spinning process. The air gap conditions, for example, temperature and moisture concentration were simulated using COMSOL multiphysics. The results indicate that the presence of a small amount of water (3 wt%) in the IL has a positive effect on spinnability, while the mechanical properties of the fibers remain unchanged.

Mindfulness-based therapy for smoking cessation and mental health: a randomised controlled trial.

INTRODUCTION: Effective smoking cessation programmes are essential for assisting smokers in quitting, indirectly lowering mortality and morbidity associated with smoking. Numerous studies have indicated positive outcomes when using mindfulness treatment (MT) to treat psychological or behavioural health issues. Although to date, no study has looked at the effectiveness of online MT for quitting smoking while addressing mental health, particularly among the Asian population. Therefore, this study compares the efficiency of online MT to traditional counselling therapy (CT) in aiding smoking cessation programmes while also addressing mental health. MATERIALS AND METHODS: A randomised control study with a two-group, single-blind design and baseline evaluation was selected. Social media sites were used to advertise for participants, who were then admitted after meeting the requirements. Participants who met the eligibility requirements were randomly split into two groups. Each group received a total of three sessions of online therapy (MT or CT), once every two weeks, as well as one phone call per week as reinforcement. At the beginning and end of the intervention, participants completed questionnaires (1st week and 5th week). Generalized Estimating Equation (GEE) statistical analysis was used to analyse all the variables. RESULTS: The MT group experienced a statistically significant decrease in cigarette consumption (ß: -3.50, 95% Wald CI: - 4.62, -2.39) compared to the CT group over time. Furthermore, the MT group demonstrated significant improvements in their scores for the AAQ-2, anxiety, stress, depression and mindfulness compared to the CT group. CONCLUSION: Online MT is more successful at assisting smokers in lowering their daily cigarette intake and supporting their mental health during the smoking cessation process. Further longitudinal comparisons of the effectiveness of online MT should be undertaken using online platforms in future studies.

Relationships between longitudinal changes in body composition and bone mineral density in middle-to-older aged Australians.

There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD). In 3671 participants aged 46-70 years at baseline, ∆lean mass was a stronger determinant than ∆fat mass of ∆BMD over 6 years. Maintained or increased lean mass may slow down age-related bone loss. PURPOSE: There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD) with ageing. We examined these in the Busselton Healthy Ageing Study. METHODS: We studied 3671 participants (2019 females) aged 46-70 years at baseline with body composition and BMD assessments by dual-energy x-ray absorptiometry at baseline and after ~6 years. Relationships between changes in total body mass (∆TM), lean mass (∆LM) and fat mass (∆FM) with ∆BMD at total hip, femoral neck and lumbar spine were evaluated using restricted cubic spline modelling (accounting for baseline covariates) and mid-quartile least square means were compared. RESULTS: ∆TM was positively associated with ∆BMD of total hip and femoral neck in both sexes, and spine in females; in females but not males, associations plateaued at ∆TM above ~5kg for all sites. In females, ∆LM was positively associated with ∆BMD of all three sites with plateauing of the relationship at ∆LM above ~1kg. Women in the highest quartile of ∆LM (Q4, mid-quartile value +1.6 kg) had 0.019-0.028 g/cm2 less reduction in BMD than those in the lowest quartile (Q1, -2.1 kg). In males, ∆LM was positively associated with ∆BMD of total hip and femoral neck; men in Q4 (+1.6 kg) had 0.015 and 0.011 g/cm2 less bone loss, respectively, compared with Q1 (-2.7 kg). ∆FM was positively associated with ∆BMD of total hip only in both sexes. CONCLUSION: ∆LM is a stronger determinant than ∆FM of ∆BMD. Maintained or increased LM is associated with less age-related bone loss.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.

Olfactory dysfunction is common in classical infratentorial superficial siderosis of the central nervous system.

BACKGROUND: Established features of classical infratentorial superficial siderosis (iSS) include hearing loss, impaired balance, myelopathy and, less commonly, cognitive compromise. Olfactory function may be affected but dedicated studies are lacking. This study aimed to assess the prevalence of olfactory dysfunction in iSS and correlate it with auditory and cognitive functions. METHODS: Ten participants with iSS completed the University of Pennsylvania Smell Identification Test (UPSIT). The scores were compared with population norms; regression analysis was performed to evaluate associations between the scores and hearing thresholds (3-frequency average, 3FA) or the number of cognitive domains impaired. Imaging was reviewed for haemosiderin distribution and to exclude other causes of olfactory and hearing dysfunction. RESULTS: Eight of ten participants were male; the mean (standard deviation, SD) age was 52.5 (14.5) years. Olfactory hypofunction was identified in all participants and in six (60%) was moderate or completely absent. The mean UPSIT score of 25.5 (7.8) was significantly worse than population norms (difference in means - 10.0; 95% CI - 15.6 to - 4.4). Linear regression identified an association between UPSIT and hearing thresholds (R = 0.75; p = 0.013). The score decreases by 0.157 units (95% CI - 0.31 to - 0.002; p = 0.048) per unit increase in 3FA, after adjusting for hearing loss risk factors. There was no statistically significant association between UPSIT and cognitive function (R = 0.383; p = 0.397). CONCLUSION: We report a high prevalence of olfactory dysfunction in iSS, the severity of which correlated with hearing loss. Olfaction appears to be a core feature of the iSS clinical syndrome that should be assessed routinely.

Vessel wall magnetic resonance and arterial spin labelling imaging in the management of presumed inflammatory intracranial arterial vasculopathy.

Optimal criteria for diagnosing and monitoring response to treatment for infectious and inflammatory medium-large vessel intracranial vasculitis presenting with stroke are lacking. We integrated intracranial vessel wall MRI with arterial spin labelling into our routine clinical stroke pathway to detect presumed inflammatory intracranial arterial vasculopathy, and monitor disease activity, in patients with clinical stroke syndromes. We used predefined standardized radiological criteria to define vessel wall enhancement, and all imaging findings were rated blinded to clinical details. Between 2017 and 2018, stroke or transient ischaemic attack patients were first screened in our vascular radiology meeting and followed up in a dedicated specialist stroke clinic if a diagnosis of medium-large inflammatory intracranial arterial vasculopathy was radiologically confirmed. Treatment was determined and monitored by a multi-disciplinary team. In this case series, 11 patients were managed in this period from the cohort of young stroke presenters (<55 years). The median age was 36 years (interquartile range: 33,50), of which 8 of 11 (73%) were female. Two of 11 (18%) had herpes virus infection confirmed by viral nucleic acid in the cerebrospinal fluid. We showed improvement in cerebral perfusion at 1 year using an arterial spin labelling sequence in patients taking immunosuppressive therapy for >4 weeks compared with those not receiving therapy [6 (100%) versus 2 (40%) P = 0.026]. Our findings demonstrate the potential utility of vessel wall magnetic resonance with arterial spin labelling imaging in detecting and monitoring medium-large inflammatory intracranial arterial vasculopathy activity for patients presenting with stroke symptoms, limiting the need to progress to brain biopsy. Further systematic studies in unselected populations of stroke patients are needed to confirm our findings and establish the prevalence of medium-large artery wall inflammation.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

Octyl cyanoacrylate skin adhesive with or without subcuticular suture for skin closure after implantable venous port placement for oncology patients: a propensity-score matching analysis.

AIM: To compare peri-operative outcomes of skin closure with octyl cyanoacrylate (OCA) skin adhesive (Dermabond) with or without subcuticular sutures after deep dermal suturing for implantable venous port placement closure. MATERIALS AND METHODS: Seven hundred and ninety-two single-lumen implantable venous port insertions for chemotherapy were reviewed from September 2019 to March 2021 in a retrospective single-centre study. Propensity-score matching by a 1:1 nearest neighbour algorithm was conducted to control for confounding baseline differences. Distances were determined by logistic regression. Propensity-score matching was performed based on the following variables: age at procedure, gender, race, operator's seniority, use of anchoring polypropylene suture (PROLENE), port model, and volume of intra-operative local analgesia. The primary outcome was wound dehiscence at the first follow-up (∼1 week). RESULTS: The 792 port insertions were conducted in 302 males (38.1%), median age 63 years (IQR: 54-69). Of the 656 wounds closed with subcuticular sutures and skin adhesive, 136 were matched in a 1:1 fashion against procedures closed without a subcuticular suture. No significant differences were demonstrated in pain scores, bleeding, swelling, bruising, fever, wound dehiscence, and discharge at postoperative day 1 (POD1) and at first follow-up between the groups (all p>0.05). Of note, no significant differences in wound dehiscence at first follow-up was found in both unmatched (p=0.133) and matched cohorts (McNemar-Bowker's χ2 = 1.167, p=0.761). CONCLUSION: These findings suggest that the omission of subcuticular sutures during implantable venous port closure may not compromise peri-operative outcomes when OCA skin adhesives were used.

Role of pre-operative ureteral stent on outcomes of retrograde intra-renal surgery (RIRS): systematic review and meta-analysis of 3831 patients and comparison of Asian and non-Asian cohorts.

PURPOSE: To evaluate the outcomes of pre-stented (PS) versus non-pre-stented (NPS) patients who have undergone retrograde intrarenal surgery (RIRS) for renal calculi with subgroup analysis of Asian and non-Asian cohorts. METHODS: Protocol is registered in PROSPERO, CRD42021261123. Eligible studies identified from four electronic databases. Meta-analysis was done to enumerate the outcomes of RIRS in between PS and NPS. Secondary sub-analysis was done to look for differences in outcomes in Asian and non-Asian cohorts. RESULTS: Fourteen studies involving 3831 patients (4 prospective, 10 retrospective studies) were included. PS patients experienced higher success rates of ureteral access sheath (UAS) insertion than NPS (RR 1.09, 95% CI 1.05-1.13, p < 0.00001). PS patients had lower risk of ureteral injuries from UAS placement (RR 0.69, 95% CI 0.50-0.96, p = 0.03). No significant differences in intra- and postoperative complications between two groups were found. Stone-free rate (SFR) outcomes for residual fragment (RF) cut-off of < 1 mm and < 4 mm favoured the PS patients (RR 1.10, 95% CI 1.04-1.17, p = 0.002 for < 4 mm, RR1.10, 95% CI 1.02-1.19, p = 0.02 for < 1 mm). In the subgroup analysis, PS Asian patients had similar SFR as NPS patients for SFR(< 4 mm) but non-Asian population showed better outcomes in the PS patients for SFR(< 4 mm) (RR 1.31, 95% CI 1.13-1.52, p = 0.0005). CONCLUSIONS: This meta-analysis suggests that pre-stenting results in a higher success for UAS placement, minimising intraoperative ureteric injury, with higher overall SFR for any RF cut-off in PS cohorts. In non-Asian cohort, significant differences occurred at SFR < 4 mm but not for SFR < 1 mm. No difference was seen in our Asian cohort for any SFR cut-off in both PS and NPS patients.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.

Lactobacillus intestinalis YT2 restores the gut microbiota and improves menopausal symptoms in ovariectomized rats.

There are many studies focusing on the alleviation of menopausal symptoms; however, little is known about the role of gut microorganisms in menopausal symptoms. Ovariectomized (OVX) rats were administered a novel strain (YT2) of Lactobacillus intestinalis (a species with significantly reduced abundance in OVX rats) and the potential probiotic effect on the improvement of menopausal symptoms was evaluated. Of note, the gut microbial composition completely shifted after ovariectomy in rats. Treatment with L. intestinalis YT2 significantly alleviated menopausal symptoms, such as increased fat mass, decreased bone mineral density, increased pain sensitivity, depression-like behaviour, and cognitive impairment. Additionally, the administration of L. intestinalis YT2 restored the intestinal microbial composition, including an increased Firmicutes/Bacteroides ratio. L. intestinalis YT2 also promoted gut barrier integrity by increasing the mRNA levels of tight junction-related markers. In conclusion, L. intestinalis YT2 treatment alleviated menopausal symptoms via the modulation of the gut microbiota. Importantly, these results suggest that L. intestinalis YT2 should be considered as a therapeutic probiotic agent for menopausal women.