Approximately 30–70% of patients who have undergone allogeneic  hematopoietic stem cell transplantation (HSCT) eventually experience chronic graft-versus-host disease (cGVHD). Patients who develop steroid-refractory (SR)-cGVHD are the most severely impacted due to significant disease and financial burden. There remains an unmet need for safe, efficacious, and accessible treatments for these patients. The objective of this study was to determine the cost effectiveness of ruxolitinib for treatment of SR-cGvHD from the Singapore healthcare system perspective.Based on data from the REACH3 randomized open-label trial, a semi-Markov model was developed to evaluate cost-effectiveness of ruxolitinib compared with investigators' choice of best alternative therapy (BAT) for treatment of patients > 12 years of age with SR-cGVHD in Singapore over a 40-year time horizon. The model only considered direct medical-care costs related to the treatment of SR-cGVHD and reported them in Singapore Dollars (SGD). Half-cycle correction was applied to all costs and outcomes, which were discounted at 3%. Probabilistic sensitivity analysis (PSA), one-way sensitivity analysis (OWSA), and scenario analysis were conducted to explore the drivers of uncertainty in the model.In the deterministic base case, more life years  and quality-adjusted life years  were gained with ruxolitinib than BAT at higher costs  leading to an incremental cost-effectiveness ratio (ICER) of SGD 677/QALY. At a willingness-to-pay threshold of SGD 75,000/QALY gained, PSA found that ruxolitinib had a 78.52% probability of being cost-effective. Findings were sensitive to variations in non-responder utilities in the BAT arm and duration of BAT treatment in the OWSA, or comparison to either methotrexate (MTX) or mycophenolic acid as a single comparator in the scenario analysis. ICERs remained lower than SGD 75,000/QALY in all other tested variations and scenarios.Ruxolitinib is likely to be cost-effective from Singapore healthcare system’s perspective for patients with SR-cGVHD, which is promising in the management of patients with unmet clinical needs.The online version contains supplementary material available at 10.1186/s12962-023-00444-w. Hematopoietic stem cell transplantation (HSCT) remains an important therapy for long term remission of many malignant and nonmalignant hematological disorders , 2. The Graft-versus-host disease (GVHD) is a complication that occurs following allo-HSCT and is a major driver of posttransplant morbidity and mortality . GVHD maWhile standard first-line treatment for cGVHD involves the use of corticosteroids, 50% of patients with cGVHD develop steroid-refractory cGVHD (SR-cGVHD) after transplantation , 9. TherIn the REACH3 (NCT03112603) trial, ruxolitinib, a potent, selective, and orally bioavailable JAK1/2 inhibitor, has shown promising efficacy in treating SR-cGVHD after allo-HSCT . In thisCost-effectiveness is becoming a major consideration for reimbursement and healthcare resource allocation to maximise healthcare outcomes. Cost-effectiveness evidence, in addition to efficacy and safety data, influences the reimbursement decision-making process, thereby impacting the number of patients who can gain access to and benefit from novel treatments. The objective of this study is to evaluate the cost-effectiveness of ruxolitinib versus BAT from the Singapore healthcare system’s perspective.A semi-Markov model was developed using Microsoft Excel® to capture all costs and outcomes associated with ruxolitinib and BAT for the treatment of patients with SR-cGVHD. To capture initial mortality and QoL prior to response assessment, patients first passed through a series of six 28-day tunnel states Fig. . MirroriDuring each subsequent 28-day cycle, patients in the ORR health state could either remain in the ORR health state, progress to the NR health state, or die. Similarly, patients in the NR health state could either remain in the same health state or die during each model cycle. Patients who progressed into the NR health state were assumed to have received BAT as subsequent treatment.Overall survival (OS) and DoR for patients in ORR and NR health states were determined by post hoc analysis of the individual patient-level data (IPD) obtained in the REACH3 trial. Survival models  were fit to the IPD using R 3.6.167 and the flexsurvreg function of the flexsurv package . Cox proThe model was designed to capture all costs and life years (LYs) and quality-adjusted LYs (QALYs) gained. A lifetime horizon of 40 years was deemed appropriate as < 1% of patients remained alive in the parametric survival extrapolations. This 40-year time horizon is consistent with that used in other health technology assessments , 16.Half-cycle correction was applied to all costs and QALYs, which were discounted at 3% on an annual basis (beginning at the end of the first year) as per recommendations by the Singapore Health Technology Assessment agency, Agency for Care Effectiveness (ACE) . The modAs some of the alternative treatment options for investigators to choose from in the BAT arm of the REACH3 trial are not routinely used in Singapore, the relevant composition of the BAT arm was determined based on local clinical practice. The composition of BAT in the current analysis included ECP (60%), rituximab (5%), MTX (15%), MMF (15%), and ibrutinib (5%).Per ACE guidance , only diA post hoc analysis of IPD from the REACH3 trial was conducted to determine QoL associated with response to treatment. As a patient’s QoL changes over time, three sets of EuroQoL five-dimensional instrument (EQ-5D) values were considered for ORR and NR at (a) disease baseline (applies from disease baseline up to the response assessment timepoint), (b) Week 24–Week 56 , and (c) Week 56 and onward   to account for the joint uncertainty of the underlying parameter estimates. The common distributions used in the probabilistic analyses were beta, gamma, log-normal, normal, and Dirichlet. The choice of distribution was based on the recommendations by Briggs et al. . In the Deterministic one-way sensitivity analysis is used to help decision makers understand the impact of changes in the value of specific parameters on model findings. A one-way sensitivity analysis (OWSA) was conducted by applying a 20% variation to the default values for all costs, utilities, proportions, and duration of AE onset, as well as parameters used for parametric survival extrapolation. Variables with the largest impact on findings were presented in a tornado diagram.Scenario analyses were performed to test the impact of uncertainty around key model inputs and assumptions  ruxolitinib Fig. . A 20% iMultiple scenarios were considered to explore the sensitivity of cost-effectiveness findings to the underlying assumptions Table . The appICERs were observed to be greater than SGD 75,000/QALY when ruxolitinib was compared to single comparators mycophenolate mofetil  and methotrexate . ICERs remained lower than SGD 75,000/QALY for all the other scenarios explored. Ruxolitinib dominated BAT in the scenarios when: time horizon was set to 30 years; alternative clinically reasonable parametric survival curve was used for survival extrapolation; DoT was determined using Kaplan–Meier curves from the REACH3 trial either by individual treatment arm; a societal perspective was considered; or ruxolitinib was compared to ECP as a single comparator.P < 0.001) [Allo-HSCT is a resource extensive procedure, costing approximately SGD 150,000 for a single patient . To ensu< 0.001) . This ma< 0.001) . It is cThe approval of ruxolitinib offers a promising and novel treatment to meet the needs of patients with SR-cGVHD. In the REACH3 trial, ruxolitinib demonstrated a higher overall response than BAT at Week 24 (49.7% vs. 25.6%), higher best overall response (76.4% vs. 60.4%), longer DoR, and longer failure-free survival . PatientIn this analysis, we synthesized results from the REACH3 trial into the Singaporean context, demonstrating that ruxolitinib is likely to be cost-effective compared with BAT for the treatment of SR-cGVHD over a 40-year time horizon. Gains in health were attributable to increased overall response to ruxolitinib compared with BAT, leading to 0.86 incremental LYs and 0.80 incremental QALYs. Ruxolitinib was found to be associated with additional costs of SGD 540 due to higher initial drug acquisition costs that were partially offset by lower subsequent treatment and healthcare resource utilization costs. In line with ACE guidance, this study did not account for (direct and indirect) nonmedical costs such as childcare, years of labor lost due to the disease, or its treatment . This omParameter uncertainty was explored using PSA, which found that ruxolitinib had a 78.52% probability of being cost-effective at a WTP threshold of SGD 75,000/QALY. We further aimed to investigate the robustness of model findings to several structural assumptions via OWSA and scenario analysis. Most of the parameter variations and scenarios explored were consistent with our base case, with ruxolitinib associated with ICERs lower than SGD 75,000/QALY and even dominating BAT in certain scenarios. OWSA revealed that our model was sensitive to variations in NR utility in the BAT arm, with a 20% increase in post-Day 56 BAT NR utilities, leading to BAT dominating ruxolitinib. The cost-effectiveness of ruxolitinib was sensitive to subsequent treatment costs. Variations to favoring BAT for DoT for the BAT arm , subsequent treatment costs for BAT , and subsequent treatment costs for RUX  were the next largest drivers of uncertainty in the OWSA.The choice of comparator was also a significant factor that influenced the cost-effectiveness of ruxolitinib. Scenario analysis showed that ruxolitinib was associated with ICERs > SGD 75,000/QALY when compared against single comparators MMF  and MTX . These individual comparisons are highly uncertain as the REACH3 trial was not powered to investigate the differences in efficacy, AEs, or drug dosing between ruxolitinib and individual interventions. When compared with a treatment mix of interventions based on the composition of the BAT used in REACH3, ICERs associated with ruxolitinib  remained lower than SGD 75,000/QALY.A previous cost-effectiveness study evaluating SR-cGVHD treatments in adult patients by Yalniz et al. compared the cost per response type  and cost per organ system-specific response , findingDespite our best efforts to present a comprehensive cost-effectiveness analysis, we acknowledge that our study faced several inherent limitations. Our model did not account for differential risks of mortality and complications attributable to heterogeneity of patient characteristics, disease subtypes or underlying diseases that necessitated initial treatment with allo-HSCT. Furthermore, AEs and complications captured in the model were not explicitly modeled through separate health states, but as a one-time average cost and disutility that was applied at the median time-to-event. Due to the limited sample size of REACH3 trial, a robust subgroup analysis was deemed to be unfeasible, however, these concerns are partially addressed as the survival curves collected during the REACH3 trial would have already captured the increased mortality associated with underlying disease or treatment-related complications. Future studies exploring the heterogeneity of responses to ruxolitinib would provide critical information that can aid in addressing these concerns in subsequent models.In this model, we assumed that patients in the NR health-state would continue to be treated with BAT. Subsequent therapy prescribed after initial treatment with ruxolitinib or BAT is highly variable, and multiple options may be chosen depending on the patient. While we recognize that previous treatment would influence subsequent treatment choice, in this study we were unable to account for previous treatment when determining subsequent treatment due to limited availability of data on local treatment distributions. Uncertainty around subsequent treatment cost has been tested in our OWSA and at all values tested, ICERs remained lower than the WTP of 75,000 SGD/QALY. Future studies would benefit from employing a more comprehensive model capable of patient level analysis.As long-term survival data from the REACH3 trial are immature, the accuracy of this model is dependent on the accuracy of the survival extrapolation. While we acknowledge the inherent uncertainty associated with such survival extrapolations, model findings were found to be robust in our uncertainty analysis. In the OWSA, although ICER values were sensitive to variations in parameters used to determine the survival extrapolation curve, none of the variations led to ICERs greater than SGD 75,000/QALY. Similarly, the scenario analysis, which explored alternative approaches to survival extrapolation, found that ICERs remained lower than SGD 75,000/QALY in all the tested scenarios.While this study has found that ruxolitinib likely represents a cost-effective option for treatment of SR-cGVHD in Singapore, it does not provide information about the affordability of the intervention. To further substantiate our findings, a budget impact analysis could be conducted to provide information on the total costs of reimbursing this intervention to inform a healthcare payer’s reimbursement decision.SR-cGVHD is a major driver of mortality and morbidity following allo-HSCT. Supplementing the efficacy and safety findings from the REACH3 trial, we found that ruxolitinib is likely to be a cost-effective option for the treatment of Singaporean patients > 12 years of age who develop SR-cGVHD following allo-HSCT. Ruxolitinib shows promise in bridging the efficacy gap in the treatment landscape of this patient group, and we believe improving access to this drug will facilitate better outcomes for these patients.Additional file 1. Table S1: Choice of parametric models used for extrapolation in the base case and their respective formulas. Table S2: Parameters of model fit for parametric survival extrapolation. Table S3: Costs and resources used while treating patients with SR-cGVHD in Singapore (Singapore dollar). Table S4: Health state utility values. Table S5: Utility decrements and duration of event for disease complication and AE event. Table S6: List of scenarios and variables evaluated in the costeffectiveness model. Table S7: Variations in one way sensitivity analysis that cause a switch to dominant or dominated ICER. Fig. S1: Comparison of response outcomes.


This study aimed to investigate the association between 15 min of daily moderate-to-vigorous physical activity (MVPA) and subsequent muscle strength and balance in older adults. Data concerning community-dwelling older Taiwanese adults  were collected during the baseline period (2018) and at a 12-month follow-up survey (2019). Time spent performing MVPA was objectively assessed using a triaxial accelerometer (ActiGraph wGT3x-BT) at baseline. Upper and lower limb muscle strength were measured using handgrip strength and a five-times sit-to-stand test, respectively. Balance was assessed using a one-leg standing test. The 12-month variations in muscle strength and balance were calculated through subtracting follow-up data from baseline data. A forced entry-adjusted logistic regression analysis was conducted. In total, 65.2% of participants engaged in at least 15 min of daily MVPA in the baseline survey. After adjusting for confounders, older adults who achieved 15 min of daily MVPA during the baseline period were more likely to maintain or improve balance performance . Performing 15 min of daily MVPA was found to benefit older adults’ subsequent balance performance but not muscle strength. Worldwide, humans are living longer than ever before. Global Health Observatory data indicate that the global average life expectancy in 2016 was 72 years . While oEnsuring physical function in older adults involves improving or maintaining muscle strength to support optimal functional performance and independence in later life ,13,14, gPhysical activity (PA) is well documented as facilitating the improvement and maintenance of physical function in older adults and is essential in postponing morbidity associated with aging ,23,24,25The study participants were comprised of community-dwelling older adults from 28 neighborhoods in the Taipei metropolitan area (including Taipei City and New Taipei City) in Taiwan who were able to walk independently. In the Taipei metropolitan area, 29.1% of the population are aged >65 years, comprising the highest population of older adults among all cities in Taiwan . Therefore, older adults living in the Taipei metropolitan area were targeted for inclusion in this study. We collected baseline data from April to September 2018 and follow-up data 12 months later, from April to September 2019. Baseline data collection included: (i) a self-administered questionnaire , (ii) a performance-based physical function test , and (iii) an accelerometer-assessed activity (accelerometer worn for seven days consecutively). Performance-based physical function tests were conducted during the follow-up survey.n = 24) and independent walking ability (n = 5). A total of 170 participants completed self-administered questionnaires, of whom, 148 completed an on-site examination and wore an accelerometer for seven days. After data cleaning, 127 participants provided complete data for analysis. After our follow-up estimation 12 months later, participants who could not be reached, who were unable to attend, or who were unwilling to attend were excluded (n = 38). Complete data concerning 89 participants were included in this study. No recommendation was given to the participants in terms of PA after baseline, and no PA was registered at follow-up. A flowchart of the participant recruitment process is shown in In total, 218 potential participants were randomly recruited using convenience sampling. Of these, 19 declined to attend the on-site examination and 29 did not meet the inclusion criteria for age . The validity and reliability of triaxial accelerometer models for estimating PA have previously been reported , and ourMuscle strength was measured using two physical function tests, namely, a handgrip strength test for upper limb strength and a five-times sit-to-stand test (STS) for lower body strength.(a)Upper limb strength (hand grip strength test)To estimate upper limb strength, a Jamar Plus+ Digital Hand Dynamometer was used to assessed handgrip strength. This hand grip strength tool is a validated instrument for obtaining rapid results concerning an individual’s general muscle strength . We cond(b)Lower limb strength (five-times STS tests)To estimate lower body strength, we used the five-times STS test , which iA one-leg standing test was used to estimate balance in older adults. One-leg balance performance is a simple and easily conducted predictor of harmful falls and can be easily incorporated into the comprehensive functional evaluation of older adults . To perfWe calculated the 12-month variations in muscle strength and balance through subtracting follow-up data from baseline strength and balance data. When a value was zero or positive, it was categorized as maintenance/improvement in muscle strength and balance. When a value was negative, it was categorized as a ‘decline’ in muscle strength and balance.2), accelerometer wear time, and sedentary time (>100 counts/min) [The covariates in this study included age, sex, education level, marital status, employment, living status, health behavior , self-reported health status, the presence of certain comorbidities , body mass index  ,45.p < 0.05.Complete data from 89 participants constituted the data for all analyses. Chi-square tests were performed to compare the proportional differences between the two participant groups (those reaching 15 min of MVPA per day and those who did not). Logistic regression analysis was used to determine the association between achieving 15 min of objectively measured MVPA per day and changes in muscle strength and balance. Additionally, forced entry-adjusted logistic regression was conducted to estimate the odds ratios (ORs) of maintaining and improving muscle strength and balance according to the definition of achieving 15 min of MVPA from baseline data. Model 1 was not adjusted for. After adjusting for sociodemographic characteristics (yielding Model 2), other potential confounders were further adjusted for in terms of sedentary behavior and accelerometer wear time (Model 3). Adjusted ORs and 95% confidence intervals (CIs) were calculated for each variable. All statistical analyses were conducted using IBM SPSS  software, and the level of significance was set at p = 0.001; OR 6.000, 95% CI 2.08–17.32, p = 0.001; respectively, Model 1). After adjusting for socio-demographic variables (Model 2), only the one-leg standing test correlated with the 15 min MVPA ; the STS was no longer significant. Furthermore, the one-leg standing test remained positively associated with the minimum MVPA after adjusting for other potential confounders .Logistic regression analyses were performed to investigate the association between achieving 15 min/day of exercise and subsequent muscle strength and balance, with the results shown in This prospective study aimed to investigate the association between a minimum amount of MVPA (15 min/day) and the subsequent performance of older adults in terms of muscle strength and balance over a 12-month follow-up period. Our findings indicated that older adults who engaged in 15 min of daily MVPA in the baseline phase were more likely to maintain or improve their standing balance than those who did not. These novel findings add further support to Wen et al.’s finding that a minimum amount of MVPA had health benefits in relation to non-communicable diseases and mortality . Our finBalance concerns the ability to maintain equilibrium when moving or stationary , which iIn our study, neither upper nor lower limb strength was associated with the minimum amount of daily MVPA. A previous cross-sectional study showed that older adults who engaged in just five minutes of daily MVPA had a better performance in handgrip and five-time STS tests , which iOur study had several strengths. Accelerometer-assessed PA data provided accurate evidence of daily MVPA accumulation among older adults. Moreover, our 12-month follow-up evaluation ensured that the outcome variables were measured twice, which provided stronger evidence for a cause-and-effect relationship between the minimum amount of MVPA and changes in physical function among older adults. Nevertheless, our study had several limitations. Although an accelerometer can detect older adults’ micro-movements accurately and provide objective intensity and activity counts, the types of PA performed  were not identifiable. Moreover, owing to convenience sampling of community-dwelling older adults in Taipei City only, our results are not readily generalizable. Regarding the recruitment procedure, healthy older adults were more likely to participate; hence, our findings should be interpreted with caution. We were able to conclude that an objectively measured minimum amount of MVPA tended to maintain and even improve subsequent balance in older adults. However, this minimum amount was not found to be related to subsequent muscle strength in our study. Nevertheless, our study suggests that any PA intervention or fundamental exercise prescription aimed at balance or falls prevention in older adults should incorporate at least 15 min of PA/day.Furthermore, when health promoters or policymakers develop strategies to prevent functional decline in an aging population, the recommended minimum amount of MVPA should be considered.Fifteen minutes of daily MVPA was found to be beneficial for older adults’ subsequent balance performance, but not beneficial in terms of improving muscle strength.


Correction: Biomaterials Research 27, 22 (2023)https://doi.org/10.1186/s40824-023-00358-xIn the article “Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration”, which was published in Biomaterials Research on March 20th, 2023 , we woulThe article was initially made available as a preprint publication on February 25th, 2023, before its final publication in Biomaterials Research. The content and findings of the article remain unchanged.We regret any inconvenience or misunderstanding this error may have caused. Please note that this correction is being made to ensure accurate documentation of the publication history and does not affect the integrity or validity of the research presented.


We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA).We performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database.We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17–41) days, while in the no or mild BPD group, it was 6 (3–10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV , late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA).In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD. With the increasing survival rates of preterm infants, the incidence of bronchopulmonary dysplasia (BPD) has remained steady or increasing , 2. Modewww.snn-med.com), and our previous study showed that about 41.9% of preterm infants [< 32 weeks of gestational age (GA)] received initial IMV. The incidence of BPD in the noninvasive ventilation failure group of very preterm infants can reach up to 37.6% , LONS , and PDA  might have increased the risk of moderate-to-severe BPD onset , duration of initial noninvasive ventilation (days), LONS, PDA, and IVH grade 3–4 for the MLR analysis (Table P = 0.000)  Fig. . After 200) Fig. .Fig. 3ROThis cohort study included 6538 very preterm infants with GA of 23–31 weeks. Among them, 8.2% of infants had a GA of ≤ 26 weeks. We identified that 49.5% of enrolled infants were prescribed initial IMV support, and 12.6% developed moderate-to-severe BPD. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17–41) days, while in no or mild BPD, it was 6 (3–10) days. This study suggests the current status of initial IMV support and exhaustively describes the relationship between prolonged duration of initial IMV and occurrence of moderate-to-severe BPD in a large-sample prospective cohort. The findings of this investigation emphasize the severity of a longer duration of initial IMV and the urgent need for quality improvement of respiratory management in neonates, which are crucial for guiding clinical practice on the prevention of moderate-to-severe BPD in Chinese NICUs.In the present study, the incidence rate of moderate-to-severe BPD was 12.6% in neonates born at 23–31 weeks of gestation. According to the Vermont Oxford Network (VON), about 10% of infants born with GA between 22 and 29 weeks died before 36 weeks of PMA; 36.9% developed grade 1 or 2 BPD, and 3.7% presented grade 3 BPD in the United States  that theIn this study, preterm infants with moderate-to-severe BPD were associated with more complicated adverse outcomes, including a longer length of hospital stay, an older GA, and greater body weight at discharge. According to the published literature, middle- and long-term follow-up of moderate-to-severe BPD showed poor health and neurodevelopmental outcomes compared with preterm peers without or with mild BPD. Schmidt et al. found that preterm infants with BPD have more than doubled odds of late death or neurodevelopmental disability when compared with preterm infants without BPD –20. MoreThe American Academy of Pediatrics Guidelines-2014 for respiratory support at birth and the European Guidelines-2016 for the prevention and treatment of NRDS have strongly recommended the implementation of preventive continuous positive airway pressure (CPAP) immediately after birth with subsequent selective surfactant administration in very preterm infants; if a ventilator is needed, rapid extubation is preferred to prolonged ventilation. The proportion of very preterm infants requiring initial IMV support was 49.5% in the whole cohort and 89.1% in moderate-to-severe BPD subjects. A retrospective cohort study from Spain between 2015 and 2019 reported that the proportion of preterm infants with GA of < 32 weeks requiring initial IMV support was approximately 31.8% . In thisThe comparison of baseline data between our study and previous studies confirmed that GA, BW, and effective initial resuscitation were significant risk factors for developing moderate-to-severe BPD . After mFurthermore, we found that LONS and PDA increased the risk of moderate-to-severe BPD, which was consistent with previous reports. In a retrospective, population-based cohort study, Lapcharoensap et al. detected a reduction in rates of nosocomial infections associated with declining rates of BPD . Many stThe major strengths of our study are as follows. This was a large prospective cohort involving very preterm infants with a GA of 23–31 weeks. This study showed the incidence of moderate-to-severe BPD and the multicenter application status of initial IMV, demonstrating the causal relationship between the incidence of moderate-to-severe BPD and the duration of initial IMV at different GAs. Furthermore, the results of this study suggest that in addition to alveolar developmental arrest of premature infants leading to “new BPD”, iatrogenic factors still affect the occurrence and development of BPD, which should not be ignored. The occurrence of moderate-to-severe BPD is still related to NICU management, especially respiratory management, implying that clinicians still need to pay attention to and optimize respiratory management in very preterm infants and shorten the duration of initial IMV as much as possible. In addition, our study was based on a clinical research database that collected data according to internationally standardized definitions. Hence, our data source was reliable and strictly quality controlled, ensuring the accuracy of the variables in this study.However, our study also suffers from several limitations. First, the NICHD consensus in 2001 was followed to define different stages of BPD severity and to exclude those infants who died before 36 weeks of PMA, which might have included some infants with severe BPD, thereby introducing selection bias to this study. Second, we did not analyze variations in IMV applications among different NICUs. We are planning to implement a survey on initial respiratory management strategies in multicenter NICUs to identify possible reasons for the application of prolonged IMV while exploring optimized respiratory management to prevent the occurrence of moderate-to-severe BPD. In addition, the specific modes and parameters of invasive mechanical ventilation were not analyzed in this study. We plan to conduct in-depth analysis and discussion on different ventilator modes and parameters in the following study.In conclusion, the duration of initial IMV was relatively longer in very preterm infants in this regional multicenter study. A longer duration of initial IMV was associated with significantly higher incidences of moderate-to-severe BPD. Optimization of early respiratory management in very premature infants may play an important role in reducing the occurrence of moderate-to-severe BPD, which deserves further study. Next, we will explore the possible reasons for the longer duration of initial IMV, analyze the potential influencing factors of self-exposure and NICU management, and strive to carry out continuous quality improvement of NICU management factors.


Xpert MTB/RIF Ultra (Ultra) is a widely used rapid front-line tuberculosis and rifampicin-susceptibility testing. Mycobacterium Growth Indicator Tube (MGIT) 960 liquid culture is used as an adjunct but is vulnerable to contamination. We aimed to assess whether Ultra can be used on to-be-discarded contaminated cultures.vs MTBDRplus on a later isolate). We calculated potential time-to-diagnosis improvements and also evaluated the immunochromatographic MPT64 TBc assay.We stored contaminated MGIT960 tubes  originally inoculated at a high-volume laboratory in Cape Town, South Africa, to diagnose patients with presumptive pulmonary tuberculosis. Patients who had no positive tuberculosis results  at contamination detection and had another, later specimen submitted within 3 months of the contaminated specimen were selected. We evaluated the sensitivity and specificity of Ultra on contaminated growth from the first culture for tuberculosis (next-available non-contaminated culture result reference standard) and rifampicin resistance  cultures from 2186 patients were contaminated. 1068 (49%) of 2186 patients had no other specimen submitted. After 319 exclusions, there were 799 people with at least one repeat specimen submitted; of these, we included in our study 246 patients (31%) with a culture-positive repeat specimen and 429 patients (54%) with a culture-negative repeat specimen. 124 patients (16%) with a culture-contaminated repeat specimen were excluded. When Ultra was done on the initial contaminated growth, sensitivity was 89% (95% CI 84–94) for tuberculosis and 95% (75–100) for rifampicin-resistance detection, and specificity was 95% (90–98) for tuberculosis and 98% (93–100) for rifampicin-resistance detection. If our approach were used the day after contamination detection, the time to tuberculosis detection would improve by a median of 23 days (IQR 13–45) and provide a result in many patients who had none. MPT64 TBc had a sensitivity of 5% (95% CI 0–25).Ultra on AFB-negative growth from contaminated MGIT960 tubes had high sensitivity and specificity, approximating WHO criteria for sputum test target product performance and exceeding drug susceptibility testing. Our approach could mitigate negative effects of culture contamination, especially when repeat specimens are not submitted.The European & Developing Countries Clinical Trials Partnership, National Institutes of Health. Mycobacterium tuberculosis complex (MTBC) limits of detection.4 One hitherto underappreciated benefit of these tests is that targeted MTBC DNA detection can occur in the presence of contaminating DNA.Rapid molecular tests are essential in the fight against tuberculosis. WHO endorsed Xpert MTB/RIF Ultra  and Truenat  as initial tests for all patients with signs and symptoms of tuberculosis due to short turnaround times and low 4 symptomatic patients with recent previous tuberculosis where upfront use of molecular, WHO-recommended rapid diagnostic tests should be avoided5 ,6 special groups such as children, or to multiply bacilli for drug susceptibility testing.8 Furthermore, given high rates of tuberculosis in people with risk factors that do not meet the threshold for symptomatic tuberculosis,9 such people are increasingly targeted as part of universal testing strategies by tuberculosis control programmes, including in South Africa.10 Culture has an important role in these people as they often have an early-stage disease and low numbers of bacilli.11Despite limitations, including expense and time to result, mycobacterial culture is frequently performed for initial tuberculosis diagnosis often following a negative smear microscopy or Ultra result. Reasons for still doing culture in the era of molecular diagnostics are multifactorial and setting-dependent but include clinically justified scenarios that involve presumptive tuberculosis patients with a negative Ultra and HIV ,13 Furthermore, as shown during the COVID-19 pandemic, supply chain disruptions can damage Ultra capacity;14 forcing programmes to revert to culture. The Mycobacterium Growth Indicator Tube 960 system  is the preferred culture method due to sensitivity and automatability.On an important practical note, GeneXpert capacity is itself uneven within tuberculosis programmes and many settings, even where Ultra is included in routine care, still partly rely on culture.15 However, high contamination rates, often attributable to low sodium hydroxide (NaOH) concentrations, have been reported: 30% in Zambia,16 24% in Burkina Faso,17 17% in South Africa,18 and 15% in Ethiopia.19 After contamination, laboratories should issue a request to health workers to resubmit a new specimen for reinvestigation. This consumes resources, creates a potential care cascade gap and delays diagnoses, including of drug-resistance.Before MGIT960 culture, specimens are decontaminated, centrifuged, and resuspended in buffer; an aliquot of which is used for inoculation. Decontamination differentially reduces bacterial culturability , making contamination less probable. MGIT960 growth is automatically monitored and, after a tube is flagged as growth-positive, an acid-fast stain is done. If acid-fast bacilli (AFBs) are observed, an antigen or molecular test is done to confirm the presence of MTBC bacteria. If growth occurs but no AFBs are observed, that specimen is reported as culture-contaminated and discarded. A MGIT960 contamination rate of 3–8% is generally considered acceptable.20 We evaluated the sensitivity, specificity, and potential effect of Ultra applied to contaminated MGIT960 growth for the detection of tuberculosis and rifampicin susceptibility.The impact of MGIT960 contamination might be mitigated if AFB-negative growth did not signify the end of a specimen’s journey. Ultra is logical to evaluate; it has well established superior sensitivity compared with smear microscopy on respiratory specimens; it determines rifampicin susceptibility; it is largely automated; and it is often underused, despite being scaled-up in many settings.In this diagnostic accuracy evaluation study, we used specimens processed in the National Health Laboratory Service (NHLS) Green Point Tuberculosis Laboratory in Cape Town (South Africa). At this laboratory, Ultra is used as the first diagnostic test in presumptive tuberculosis patients and is not used for patients on treatment. Culture is done for paediatric and HIV-positive patients with presumptive tuberculosis when the initial Ultra is negative or in people with recent previous tuberculosis (≤2 years). Culture is also done on patients with Ultra-positive and rifampicin-resistant or rifampicin-resistance indeterminate results. Demographics including age, sex, HIV-status, and tuberculosis-status are collected if available.21 0·5 mL of the NALC–NaOH-processed specimens are inoculated into a MGIT960 tube supplemented with polymyxin B (400 units per mL), amphotericin B (40 μg/mL), nalidixic acid (160 μg/mL), trimethoprim (40 μg/mL), and azlocillin 21 and incubated for maximum 35 days. After a tube is automatically flagged as growth-positive by the machine (200 growth units), Ziehl-Neelsen microscopy is done to detect AFBs on unconcentrated growth. MTBC bacteria identification from AFB-positive growth is done by MTBDRplus  or the immunochromatographic MPT64 TBc assay  according to the respective manufacturer’s instructions. If only non-AFBs are observed the cultures are reported per programmatic policy as “culture contaminated with no further result to follow”.As part of routine procedures, specimens for culture were processed using the standard N-acetyl-L-cysteine (NALC)–NaOH procedure for decontamination .plus, and TBc) on specimens or isolates up to 3 months after initial contamination detection  were extracted . For inclusion in diagnostic accuracy analyses, patients were required to have at least one positive or negative culture result from these later specimens. We did not preferentially select patients based on results from a later specimen other than culture. We excluded patients with a known smear-positive, Ultra-positive, or culture-positive result up to 12 months before the initial contamination report (which would suggest the contaminated specimen was submitted for treatment monitoring) and those who had no later culture-positive or culture-negative results , and we ignored culture results from any specimens submitted either on the same day as the specimen found to be contaminated or while that specimen was still undergoing incubation . If patients had more than one contaminated culture, the earliest was selected for Ultra or TBc. We included contaminated cultures regardless of whether they were initially tested with Ultra, if Ultra was not positive. We collected meta-data on age, sex, HIV-status, and tuberculosis status if programmatically available.For this study, contaminated cultures with no AFB from a smear on growth from a respiratory specimen  were consecutively collected between June 1 and Aug 31, 2019, and stored at 2–8°C. Results of routine tuberculosis investigations  and the NHLS Academic Affairs, Research and Quality Assurance (PR2119347). As we used programmatically submitted de-identified remnant material that would be discarded the need for written informed consent was waived.After eligible contaminated cultures were selected contaminated cultures were separated based on their later culture result and a subset (later-culture positives and later-culture negatives), most of which either had an initial Ultra-negative sputum result or were not tested by Ultra was consecutively selected and processed for Ultra. 6 mL of contaminated culture were centrifuged (3000 × g 15 min) and the supernatant was discarded, leaving approximately 0·7 mL of pellet, which was resuspended in 1·4 mL sample reagent . The concentrated contaminated culture was then tested by Ultra according to our standard operating procedure  pp 2–6. plus rifampicin-resistant on a subsequent isolate; reference standard susceptible cases were definite tuberculosis and MTBDRplus rifampicin-susceptible.If at least one subsequent culture was MTBC-positive the patient was designated as definite tuberculosis. If there was no MTBC-confirmed growth and no other MTBC-positive cultures during the follow-up period, the patient was designated as non-tuberculosis. For rifampicin susceptibility, reference standard resistant cases had definite tuberculosis and were MTBDR1 Using the prtest command in Stata (version 17), we compared Ultra sensitivity and specificity between patients with previous tuberculosis (confirmed on a specimen submitted less than 4 years but more than 1 year before the contaminated specimen) with those with no previous tuberculosis to evaluate whether, as observed with sputum,22 specificity diminished. Using Excel, we visualised how positive predictive values (PPVs) and negative predictive values (NPVs) change with the frequency of tuberculosis and rifampicin-resistance in people who had another specimen. Tuberculosis frequency was defined as the proportion of individuals with culture-positive specimens in those patients who had another specimen submitted within 3 months of the first contaminated culture and for whom that later specimen was culture-positive or culture-negative. For rifampicin-resistance, frequency was the proportion of patients who had a MTBDRplus-rifampicin-resistant specimen among those who had another specimen submitted within 3 months that was culture-positive and MRBDRplus tuberculosis-positive. We included sequential contaminated samples until high precision was achieved for sensitivity and specificity (≤5% CI widths on either side of the point estimates).23 Sensitivity and specificity changes were evaluated if trace results  were recategorised as negative or excluded.Sensitivity and specificity of Ultra and TBc on contaminated cultures for tuberculosis and rifampicin susceptibility were estimated using 2 × 2 tables with 95% CIs .We designated patients with a contaminated culture who had no record of any repeat specimen in the follow-up period as lost to follow-up. Diagnostic delay caused by contamination was defined as days between report of the initial contamination result and, if not lost to follow-up, the earliest next-positive result  on a later repeat specimen. If patients had repeat specimen results and none were positive, the earliest culture-negative result date was used. The difference in the initial specimen culture contamination report date (plus 1 day) and the repeat specimen culture result date was defined as the potential improved turnaround times.The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.Between June 1, 2019, and Aug 31, 2019, 36 684 specimens from 26 929 unique patients were processed for diagnostic culture . 18 936 Of all 36 684 specimens, 27 921  were culture-negative, 6361  were culture-positive, and 2402  were culture-contaminated (without AFBs).1068 (49%) of 2186 patients with a culture-contaminated specimen had no further specimens submitted  p 7. Aft338 patients, 163 with culture-positive repeat specimens and 175 culture-negative repeat specimens, were selected for Ultra testing. Three specimens (1%) from these patients yielded a non-actionable Ultra result . Ultra detected tuberculosis in 144 (89% ) of 161 patients with initially contaminated cultures and culture-positive repeat specimens (true positives); ten (7%) of these were in the trace, 12 (8%) in the very low, 37 (26%) in the low, 39 (27%) in the medium, and 46 (32%) in the high Ultra semiquantitation categories, respectively. Of the non-trace categories, 21 (16%) of 133 patients were Ultra rifampicin-resistant. Ultra detected tuberculosis in nine (5%) of 174 patients with contaminated cultures with culture-negative repeat specimens .For tuberculosis detection, sensitivity was 89%  and specificity was 95% . For rifampicin-resistance detection, sensitivity was 95%  and specificity was 98% .If trace calls were reclassified to negative, sensitivity decreased to 83%  and specificity improved to 99% .vs 24 [17%] of 144; p<0·0001) and hence specificity reduced in people with previous tuberculosis . This result did not change with different trace recategorisation strategies  overall, 23 days (13–45) for patients whose repeat culture was positive and 49 days (42–64) for those whose repeat culture was negative . For rifFrom the 20 randomly selected MGIT960 tubes where Ultra had detected tuberculosis, one was tuberculosis-positive by TBc, resulting in a sensitivity of 5% (95% CI 0–25). The 20 tubes where Ultra did not detect MTBC were all TBc-negative.This study is the first to describe rescuing a result from contaminated cultures using a WHO-recommended rapid molecular test, Ultra. We found that Ultra on contaminated cultures is comparable to Ultra on sputum for tuberculosis and rifampicin-resistance detection, and that this could reduce delays in diagnosis associated with the need to collect and culture a second specimen or, even more importantly, generate a diagnostic result (with high sensitivity and specificity) where there is none due to non-submission of a repeat specimen. Moreover, we identified many patients receiving multiple cultures simultaneously or in quick succession, which indicates wasteful testing. Together, these findings have implications for improving tuberculosis and drug-resistant tuberculosis diagnosis and can reduce some of the disadvantages of using liquid culture.2 By contrast, TBc performed poorly on AFB-negative contaminated MGIT960 cultures relative to Ultra. Furthermore, the Ultra approach had lower non-actionable result rates (not Ultra-positive or Ultra-negative) than those reported by other studies in our setting,2 probably because culture growth, although contaminated, is more homogenous than sputum. We modelled how the predictive value of our approach would change at different rates of definite tuberculosis and rifampicin resistance to offer a framework for different settings to consider rolling out our approach, and showed that these predictive values mirrored those widely accepted for Ultra on sputum. The high tuberculosis (and rifampicin-resistance) frequency in people who were initially culture-contaminated was surprising, but could be confounded by differences in the types of individuals who are likely to have a repeat specimen retrieved (vs those who are not) or by tuberculosis-associated perturbations in the respiratory microbiome that increase culture of contaminating organisms,25 about neither of which we have information.Our approach detected nine of ten tuberculosis cases, a sensitivity approximating those previously reported for sputum Ultra.22 however, this possibility requires further investigation.We evaluated the effect of different trace handling strategies on sensitivity and specificity but these resulted in small specificity improvements at a cost of missed definite tuberculosis. False-positive results (Ultra-positive on the contaminated culture and subsequently culture-negative) might be due to old MTBC DNA because our approach had slightly diminished specificity in patients with previous tuberculosis (patients who complete treatment can continue to be Xpert-positive for years thereafter);plus on the repeat-culture isolate. The two patients with discordant rifampicin susceptibility results by Ultra (resistant) and MTBDRplus (susceptible) could be due to heteroresistance, although Ultra melt curves did not show heteroresistance . For the patient with a rifampicin-susceptible contaminated culture by Ultra and rifampicin-resistant by MTBDRplus, three repeat specimens were submitted for culture and MTBDRplus (two were MTBDRplus susceptible and the last resistant).For rifampicin resistance, Ultra on contaminated culture had high concordance with MTBDRWhile our approach will probably reduce time to diagnosis, its most notable effect is likely to be in the many patients who do not have a repeat specimen submitted. Their tuberculosis diagnoses  is lost by the system. We also observed over-requesting of cultures, with many simultaneous or repeat cultures in rapid succession in approximately 30% of patients. The combination of loss from the care cascade and algorithm non-compliance indicates an important area for improvement in quality of care and highlights the potential usefulness of refining specimen gatekeeping systems by, for example, denying a culture request if another culture is underway or was recently completed. Our approach could partly mitigate these issues by reducing need to submit another specimen for culture if Ultra salvaged a result from a contaminated culture.A first limitation of our approach is that Ultra was done on a different specimen to the reference and changes in concentration of bacilli in between samplings could lead to discordance; however, this would favour the reference standard (the index test was done on the early more paucibacillary specimen), meaning our estimates are probably underestimations. Second, it is impossible to exclude the possibility of patients having started treatment between provision of the specimen for culture and a repeat. However, treatment would render patients culture-negative and result in poor specificity—a phenomenon we did not observe. Third, given the pragmatic nature of our study, there was a large degree of missingness (due to no subsequent programmatic culture), but the high missingness demonstrates our approach’s potential value in preventing pre-treatment loss to follow-up. Fourth, our laboratory uses a 35-day MGIT960 incubation period due to limited space, which might have affected the reference standard. Fifth, TBc might have performed better on AFB-positive contaminated growth or if concentrated contaminated growth was tested (as done for Ultra). Sixth, the usefulness of our approach scales with the extent of cultures’ deployment (and contamination rate) and the value of our findings is limited where these are rare, but the added value of our approach will be increased in high-burden settings with higher sample contamination rate than ours (7%). Lastly, our work should be viewed as a proof of concept and should be validated in other settings and using other PCR tests.In conclusion, Ultra on contaminated cultures is highly accurate to diagnose tuberculosis and rifampicin resistance. As Ultra’s cost approximates that of culture and our approach has many potential advantages , we strongly advocate for laboratories that experience contamination in tuberculosis diagnostic cultures to consider implementing our approach, in addition to maintaining their contamination rate within an acceptable range.1


On the other hand, subtotal resection may be associated with higher tumor recurrence. We evaluated the correlation between intra-operative assessment of residual tumor and early and follow-up imaging. (2) Methods: The charts of all patients undergoing primary surgery for sporadic vestibular schwannoma during the study period were retrospectively reviewed. Data regarding surgeons’ assessments of the extent of resection, and the residual size of the tumor on post-operative day (POD) one and follow-up MRI were extracted. (3) Results: Of 109 vestibular schwannomas meeting inclusion criteria, gross-total resection (GTR) was achieved in eighty-four, near-total (NTR) and sub-total resection (STR) in twenty-two and three patients, respectively. On follow up imaging, volumetric analysis revealed that of twenty-two NTRs, eight were radiographic GTR and nine were radiographic STR (mean volume ratio 11.9%), while five remained NTR (mean volume ratio 1.8%). Of the three STRs, two were radiographic GTR while one remained STR. Therefore, of eighteen patients with available later follow up MRIs, radiographic classification of the degree of resection changed in six. (4) Conclusions: An early MRI (POD#1) establishes a baseline for the residual tumor that may be more accurate than the surgeon’s intraoperative assessment and may provide a beneficial point of comparison for long-term surveillance. Vestibular schwannoma is a slow growing benign neoplasm of the eighth cranial nerve, commonly referred to as acoustic neuroma. The tumors are rare  but are the most common tumor of the temporal bone. VS usually presents with hearing loss; less common presenting symptoms include vestibulopathy, facial numbness, headache, or other neurologic signs and symptoms.Recent decades have been witness to significant changes in the management of vestibular schwannomas. Improvements in understanding the natural history of vestibular schwannomas and enhancements in magnetic resonance imaging (MRI) techniques along with favorable long-term outcomes of radiosurgery have transformed the vestibular schwannoma treatment algorithms ,2,3,4. WWhen incomplete resection is performed, the estimated residual size and shape is used as a baseline for long-term follow-up. The residual tumor is usually observed with serial MRIs for regrowth, which may necessitate treatment by radiosurgery or revision microsurgery. Surgeons’ assessment of a near- or sub-total resection may not be consistent with how much tumor is actually left behind. This intra-operative assessment can be inaccurate as demonstrated in a previous published study  in whichWhile practices among vestibular schwannoma surgeons vary, at our institution, an MRI is obtained on post-operative day one in all patients undergoing vestibular schwannoma resection. In this study, we aimed to assess the correlation between the intra-operative assessment of a residual tumor and early post-operative MRI findings by reviewing the data from our cohort of vestibular schwannomas. Furthermore, we compared the immediate and follow-up post-operative images to evaluate for changes in tumor shape and size with time. The results from this study can provide a better understanding of the differences between intra-operative assessment of residual size and post-operative MRI findings. This study was approved by our local Institutional Review Board (IRB# SV-018-21). Upon approval, a retrospective chart review was performed on patients who underwent surgery for vestibular schwannomas between October 2017 and October 2019 at our tertiary referral center. Patients with neurofibromatosis type II, revision cases, and those without available pre- or post-operative MRIs were excluded. Data regarding patient demographics, surgical approach, extent of resection (EOR), and intra-operative assessment of residual size were extracted from the charts. Intra-operative degree of resection was reported as gross-total resection (GTR), near-total resection (NTR), or sub-total resection (STR). A GTR was determined when the surgeon was confident of complete tumor removal. NTR was determined when only a thin layer of the tumor capsule was left on the facial nerve or other structures, and this was estimated to be less than 5% of the original tumor volume. Other cases were considered STR. A surgical endoscope was routinely used in cases where the lateral border of the tumor could not be directly visualized .www.horosproject.org, accessed on 1 October 2019) was used to compute the volume of the pre-operative tumor and those of any residual tumors if present. Volumetric analysis was performed on post-contrast, T1 weighted images. The presence of a residual tumor was confirmed by comparing these images to pre-contrast T1 and fluid-attenuated inversion recovery (FLAIR) as well as other available sequences to rule out hemorrhage or edema. The perimeter method was used to calculate the volumes [Patients’ pre- and post-operative MRIs were obtained and analyzed. Our institution’s protocol is to obtain an MRI of the brain with and without contrast, including fat suppression, on post-operative day one. This post-operative MRI was used to evaluate for the presence of any radiographic residual tumor and then compared to the patient’s last available follow up MRI. Horos DICOM image analysis software , radiographic NTR , or radiographic STR . The correlation between the radiographic and intra-operative assessments of the degree of resection were then compared. The shapes of the residual tumors were further analyzed and classified as linear or nodular. Statistical analysis was performed using SPSS 1.0 . Nonparametric tests were used given the skewed distribution of samples. A A total of two hundred and three patients undergoing surgery for VSs during the study period were identified, excluding patients with neurofibromatosis type II, revision cases, and those with unavailable MRI images. A total of 109 cases of primary vestibular schwannoma surgeries were analyzed. The mean age was 52.7 years (range 19–79) and 35.8% were males. The surgical approach was translabyrinthine in sixty-nine (63.3%), middle fossa in thirty (27.5%), retrosigmoid in nine (8.3%), and transotic in one (0.9%). Based on the intra-operative assessments by the senior neurosurgeon, GTR was achieved in eighty-four (77.1%) while a residual was left behind in twenty-five cases (22.9%), consisting of twenty-two NTRs (20.2%) and three STRs (2.8%). The main reason for leaving a residual was severe adherence to the facial nerve in all cases. The intra-operative estimate of residual size varied from 1 to 10 mm.3 (range 0.02–24.97 cm3). The tumors that underwent GTR had a significantly smaller volume  than those with a residual . This difference was not statistically significant between tumors that underwent NTR and STR (p = 0.9). As detailed in The average pre-operative volume was 3.23 cmVolumetric analysis of residual tumors on the immediate post-operative MRI revealed that of twenty-two near-total cases, eight were radiographic GTR and nine were radiographic STR (mean volume ratio 11.9%), while five remained radiographic NTR (mean volume ratio 1.8%). Of the three sub-total cases, two were radiographic GTR while one remained radiographic STR. Of cases with a radiographic residual, seven had linear and eight had nodular residuals. 3 (median 7.30 cm3) compared to a mean volume of 5.27 cm3 (median 2.89 cm3) in tumors that were considered as radiographic NTRs and GTRs. This difference, however, did not reach statistical significance (p = 0.27).A sub-analysis was performed on the pre-operative volumes of the tumors for which residual size was underestimated intra-operatively. These tumors had undergone NTR but were recategorized as radiographic STR based on the immediate post-operative MRI. The mean volume of these tumors was 8.93 cmAll patients had follow-up imaging. Follow-up post-operative MRI (ranging 3 to 22 months) was available for eighteen patients with residual tumors (sixteen NTRs and two STRs). Lack of a residual tumor was confirmed via follow-up MRIs obtained around 3 and/or 12 months post-operatively on all patients in whom the intra-operative assessment was consistent with gross-total resection. As seen in The present study revealed a disparity between the intra-operative assessment of tumor residual size and post-operative radiographic assessments in some cases. When the surgeon was confident in removing the entire tumor, post-operative MRI confirmed GTR. However, when a residual was left behind, the degree of resection was recategorized in 76% of the cases after the post-operative MRI was reviewed. These findings are consistent with a previous study that evaluated residual tumors on post-operative MRIs in fifty vestibular schwannomas including fifteen NTRs and eight STRs. About 73% of the NTRs were actually noted to be radiographic STR, while all STRs were also radiographic STR [2 and 2 mm thick along the facial nerve or brain stem [Surgeons’ intra-operative assessment is mainly subjective and limited by the location of the residual tumor and extent of the surgical field. The definitions of NTR and STR can also vary between institutions. In our practice, a resection is considered near-total if (a) only a thin, linear layer of the tumor capsule is left on the facial nerve (or other structures), and (b) this residual tumor is estimated to be less than 5% of the original tumor volume. While the 5% volume ratio as the threshold to differentiate between NTR and STR has been used in the literature ,8, otherain stem ,10. Anotain stem . As seenOur data show that an immediate post-operative MRI can be helpful in establishing the shape and size of the residual and provides a better estimate of the degree of resection than the surgeon’s estimation. In the literature, there is no consensus regarding the timing of the first MRI after vestibular schwannoma resection. A 2005 survey of the American Neurotology Society (ANS) and North American Skull Base Society members revealed that 2.3% of neurotologists and 23.4% of neurosurgeons obtained an MRI on post-operative day one, whereas 21.6% of neurotologists and 61.7% of neurosurgeons obtained the first MRI within a year . A more While the timing and interval of the first post-operative MRI varies between surgeons and institutions, an early MRI during the post-operative inpatient stay could provide additional information to the surgeon. This immediate MRI is obtained on day one after the surgery at our institution. On the MRIs obtained months after the surgery, it may be difficult to differentiate scar tissue from a growing residual tumor ,14. An MPreservation of the facial nerve integrity may necessitate leaving a small residual vestibular schwannoma that is then followed by serial MRIs. Intra-operative assessment of the residual size may be inaccurate given its subjective nature. In our series, post-operative MRI changed the assessment of the degree of resection in 76% of the cases where a residual tumor was left behind. While there is no consensus on the timing of the first post-operative MRI among institutions, an early post-operative MRI establishes a baseline for the residual tumor prior to scar formation and could provide a critical point of comparison for long-term surveillance.


P = 0.36). Adjusted linear regression analysis did not indicate an influence of OPT on RNFL thickness or on HC-BCVA  following intravenous methylprednisolone (IVMP) on visual outcome parameters in optic neuritis (ON) has never been explored. In the present retrospective study, we investigated whether OPT after IVMP affects the structural and functional visual outcomes of inaugural clinically isolated syndrome (CIS)- or multiple sclerosis (MS)-ON. Adult patients with acute, inaugural, unilateral CIS- or MS-ON, treated with IVMP in Germany and Israel were stratified into patients treated with IVMP alone—versus IVMP and OPT. Inclusion criteria were age ≥18, CIS or MS diagnosis according to McDonald criteria 2017, available visual acuity (VA) at nadir before treatment initiation and at follow-up ≥5 months, as well as a spectral domain optic coherence tomography (OCT) data scan at follow-up. Exclusion criteria included recurrent ON, concomitant ophthalmological comorbidities, optical coherence tomography (OCT) of insufficient quality and ON-related escalation therapy after IVMP. The structural outcome was defined as the average retinal nerve fiber layer (RNFL) difference between the ON-affected and the unaffected eye, while the functional outcome was defined as the final high-contrast best-corrected VA (HC-BCVA) at follow-up compared to nadir. The comparative analysis was performed using linear regression analysis, adjusted for sex, age, and days-to-treatment. Fifty-one patients met the inclusion criteria . The mean age was 33.9 (±10.23) years. Twenty-six patients (51%) received OPT following IVMP. There was no difference in nadir HC-BCVA between the groups (0.39 No OPT; 0.49 With OPT,  Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve. ON is a common symptom of clinically isolated syndrome (CIS) and multiple sclerosis (MS) . CurrentWe performed a retrospective study of patients with acute ON associated with CIS or MS, followed between 2011–2021 at two tertiary referral neuroimmunology centers in Germany and Israel. Both studies adhered to the declaration of Helsinki and were approved by independent medical ethical committees. The German cohort comprised patients who were enrolled in one of two prospective, observational cohort studies  at the Experimental and Clinical Research Center (ECRC) at Charité –Universitätsmedizin Berlin, Germany. The Israeli cohort included patients who were followed by the neuro-ophthalmology and neuroimmunology clinics at Rabin Medical Center, Israel. The study protocol was approved by the Rabin Medical Center Institutional Review Board, with a waiver of informed consent due to the retrospective nature of the study .Inclusion criteria were age ≥18, diagnosis of a first-ever episode of unilateral acute ON and a subsequent diagnosis of CIS or MS, treatment with IVMP, complete ophthalmological assessment including available high-contrast best corrected visual acuity (HC-BCVA) at nadir before treatment initiation and at follow-up ≥5 months, as well as a spectral domain optic coherence tomography (OCT) data scan at follow-up. CIS and MS patients were diagnosed according to the 2017 McDonald diagnostic criteria . Myelin Data recorded at nadir were biological sex, age at onset, HC-BCVA , time- lapse from symptoms onset to the beginning of IVMP, and acute steroid regimen. Data collected at follow-up included HC-BCVA and OCT parameters  thickness (measured in microns) for both the affected and unaffected eye).Early Treatment Diabetic Retinopathy Study (EDTRS) charts and given as a decimal value, which was converted into a Logarithm of the Minimal Angle of Resolution (LogMAR) units. At follow-up, HC-BCVA was performed at the ECRC, Berlin, using EDTRS charts and converted into LogMAR units. For the Israeli cohort, HC-BCVA was measured by trained ophthalmologists using Snellen charts and converted into LogMAR units.HC-BCVA was measured during the acute phase of ON at nadir before treatment within the hospital setting, as part of the clinical routine. HC-BCVA was examined by trained ophthalmologists using OCT was carried out for the affected and unaffected eyes for all patients at follow-up. In the German cohort, OCT was performed using the Heidelberg Spectralis OCT in the N-Site module. In the Israeli cohort, OCT was performed using the Cirrus HD-OCT , using the Optic Disc 200 × 200 protocol to obtain the average RNFL thickness. At both centers, OCT measurements were carried out by certified ophthalmic technicians. Scans were obtained using a single device, in dim room light, with the patient’s pupils dilated. OCT results are reported in accordance with the APOSTEL 2.0 guidelines .For analysis, patients were stratified into two groups: those who received IVMP alone (No OPT) compared to patients who received OPT after IVMP treatment (With OPT). Two outcomes were selected for this study; the average RNFL thickness of the affected eye compared to that of the unaffected eye (in percentages), and the HC-BCVA at final follow-up .Descriptive demographic data was analyzed using summary statistics . Patient characteristics were compared using two-sided t-tests for metric data as well as chi-square-tests for categorical data.To investigate the effect of OPT on RNFL values between the unaffected eye and the affected eye in percentages, a linear regression analysis was conducted, adjusted for sex, age at ON onset, and time from visual loss to treatment (in days). To analyze the impact of OPT on LogMAR differences between nadir and follow-up in the affected eye, a second linear regression analysis was performed, using the same set of predictor variables. Due to the exploratory nature of the study, no adjustment for multiplicity was conducted. Therefore, p-values and confidence intervals are interpreted in an exploratory, hypothesis-generating manner.We performed an a-priori power analysis to determine the required sample size for our study. We anticipated that the standard deviation of the RNFL differences, measured as a percentage, would be approximately 9%. We considered a clinical significance threshold of an 8% difference in RNFL values. To detect this difference with a two-sample, two-sided t-test at a significance level  of 5% and a desired statistical power of 80%, we calculated that we would need approximately 21 patients in each group.We identified 162 patients with first-ever acute ON who were subsequently diagnosed with CIS or MS see . One-hunIn total, 51 patients met our inclusion criteria. The mean age at onset was 33.96 years (±10.23). Thirteen subjects (25.5%) were males. Mean follow up time was 323 [±107] days. Patients were stratified according to whether they received OPT after IVMP treatment  with a mean age at onset of 31.44 [±8.36] and 36.38 [±11.39] years in each group, respectively (P = 0.08). Clinical and demographic characteristics are summarized in At follow-up of at least 5 months after onset, both groups demonstrated lower RNFL thickness in the affected eye compared to the unaffected eye (No OPT 88.81% ±8.26 vs. With OPT 89.29% ±9.63) see . HoweverHC-BCVA of the affected eye at nadir was similar in patients treated with either IVMP alone and in patients treated with OPT following IVMP  see . As an iAge at onset did not have an impact on RNFL thickness  or on HC-BCVA recovery . Male sex was the only parameter associated with a worse outcome in terms of RNFL thickness  but not for HC-BCVA outcome  that all ON events are clinically noticed and recalled by the patient, and 2) that the unaffected eye undergoes little to no RNFL thinning as part of the disease. We know well that both these assumptions have been disproven. Many ON events are clinically silent , 32 and Previous MS studies have shown that male patients tend to have worse clinical outcomes, faster disease progression and higher burden of destructive lesions on MRI studies relative to female patients , 35. In There are several limitations of this study. These include the relatively small sample size and the retrospective design of the study. The lack of randomization is another limitation that merits special consideration, because it may represent a bias to treat relatively more severe ON with OPT. However, HC-BCVA at nadir did not differ between the two groups, suggesting no severity bias towards the group of ON patients receiving OPT. The similarity in nadir and final HC-BCVA between the patients treated with OPT following IVMP and those treated with IVMP alone suggests that a lack of randomization did not affect the clinical outcome. Moreover, HC-BCVA alone is an insufficient indicator of residual deficits after ON. Another limitation is that we compared RNFL thickness between the affected and the unaffected eye at follow-up and not to RNFL at baseline as previously discussed. Last, we only included CIS- and MS-ON in the study, since MOG-IgG-and NMOSD-related ON should be treated differently, and steroid tapering is important to avoid ON relapses in antibody-mediated ON.Our exploratory study suggests that there is no benefit to structural or visual outcomes when adding oral prednisone taper to IVMP in patients with acute CIS—and MS-related ON. We are currently enrolling patients in a larger prospective study to validate our results using LC-BCVA, VEP, MRI and OCT with the aim to prevent unnecessary steroid use and related side effects .


Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns expressed by community leaders about the frequent diagnosis of Hp infection and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This follow-up study investigated changes in precancerous stomach pathologies after treatment to eliminate Hp infection among 69 project participants with follow-up data. Most participants who had successful treatment to eliminate Hp at baseline remained infection-free at follow-up and the prevalence of precancerous stomach pathologies was lower at follow-up than baseline. The more frequent improvements in precancerous stomach pathologies observed in participants who were Hp-negative at follow-up relative to those who were Hp-positive at follow-up suggests that treatment to eliminate Hp infection has the potential to reduce stomach cancer risk in participating communities.Community-driven projects have characterized health impacts of Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008–2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities.Community-driven projects have characterized  Helicobacter pylori (Hp), responsible for a large burden of disease across the globe, is a bacterium that inhabits the gastric epithelium ) and follow-up (26% [18/69]). Of note, the prevalence of Hp infection at baseline among the 69 follow-up participants was 75%, similar to the baseline prevalence among all 310 participants. Antimicrobial resistance status was available for 207 participants classified as Hp-positive by histology at baseline. The frequency of resistance was 34%  for metronidazole and 16%  for clarithromycin; 43%  of participants were resistant to one or more antibiotics and 12%  to two or more antibiotics. Among the 69 follow-up participants, 48 had antimicrobial resistance status for Hp infection at baseline. The follow-up group had similar baseline resistance frequencies: 40%  for metronidizole, 15% for clarithromycin , 44%  for one or more antibiotics and 15%  for two or more antibiotics. Antimicrobial resistance status at follow-up was available for 15 of the 18 participants who were Hp-positive at follow-up. One of the fifteen  was resistant to metronidazole, four  were resistant to clarithromycin and none were resistant to more than one antibiotic.Hp status at baseline and follow-up. Of the 69 participants, 52 were classified as positive at baseline, 47 (90%) of whom received treatment to eliminate Hp infection following the baseline gastroscopy. Of these 47, baseline treatment was successful in 34 (72%) and failed in 13 (28%). At follow-up, 51 (74%) participants were classified as Hp-negative and 18 (26%) as Hp-positive. Participants who were Hp-negative at follow-up included 16 of 17 (94%) participants who were Hp-negative at baseline, 27 of 34 (79%) with successful treatment at baseline, 6 of 13 (46%) with failed treatment at baseline and 2 of 5 (40%) who were Hp-positive at baseline and did not receive treatment. Participants who were Hp-positive at follow-up included 1 of 17 (6%) participants who were Hp-negative at baseline, 7 of 34 (21%) with successful treatment at baseline, 7 of 13 (54%) with failed treatment at baseline, and 3 of 5 (60%) who were Hp-positive at baseline and did not receive treatment. To avoid overemphasizing imprecise distinctions due to small group sizes, we stratified changes in gastric pathology only by Hp status at baseline and follow-up, without further stratifying by treatment status or treatment response. This data presentation makes sense because some participants with negative post-treatment breath tests may have had suppressed Hp infections that were not fully eliminated; in cases of reinfection, the time of reinfection onset is unknown; some participants could have received treatment elsewhere without our knowledge. Hp-negative at baseline and follow-up, none had active gastritis detected at baseline or follow-up and six (35%) had chronic gastritis detected at baseline or follow-up; among these six, chronic gastritis severity at follow-up was higher in three, unchanged in one and lower in two. Two of the seventeen (12%) participants had atrophic gastritis and intestinal metaplasia that was higher in severity at follow-up. Among the 34 participants who were Hp-positive at baseline and Hp-negative at follow-up, all 34 (100%) had chronic gastritis at baseline and 34 of 34 (100%) had lower chronic gastritis severity at follow-up; 33 (97%) had active gastritis at baseline and 33 of 33 (100%) had lower active gastritis severity at follow-up. Of these 34 participants, 14 (41%) had atrophic gastritis at baseline and 13 of 14 (93%) had lower atrophic gastritis severity at follow-up. Four of the thirty-four (12%) participants had intestinal metaplasia at baseline; intestinal metaplasia severity at follow-up was higher in two, unchanged in one and lower in one. Among the 18 participants who were Hp-positive at follow-up, all 18 (100%) had chronic gastritis and active gastritis at baseline; chronic gastritis severity at follow-up was lower in 7 (39%) and unchanged or higher in 11 (61%), while active gastritis severity at follow-up was lower in 5 (28%) and unchanged or higher in 13 (72%). In this group, 11 (61%) participants had atrophic gastritis at baseline; atrophic gastritis severity at follow-up was lower in 6 of 11 (55%) and unchanged or higher in 5 (45%). Seven participants with no atrophic gastritis observed at baseline had atrophic gastritis at follow-up. Nine of the eighteen (50%) had intestinal metaplasia at baseline; intestinal metaplasia severity at follow-up was lower in one of nine (11%), and unchanged or higher in eight of nine (89%). Eight participants with no intestinal metaplasia observed at baseline had intestinal metaplasia at follow-up.Among the 17 participants who were Hp resistance status, or time between baseline and follow-up gastroscopies. The probability of improved chronic gastritis severity increased with increased baseline Hp density as well as increased baseline chronic gastritis severity, perhaps because higher baseline severity corresponds to more opportunity for improvement. The frequency of improved chronic gastritis severity was relatively large among participants who completed treatment to eliminate Hp before follow-up, tested negative for Hp before follow-up, showed improvement in Hp density from baseline to follow-up and/or had no Hp observed in follow-up gastric biopsies. Among 50 participants with active gastritis detected at baseline, 36 (72%) had a lower active gastritis severity classification (including none) at follow-up. The frequency of improved active gastritis severity showed a similar pattern of association with participant characteristics as that observed for chronic gastritis, except it appeared more strongly associated with Hp density at follow-up than with baseline factors. Among 20 participants with atrophic gastritis detected at baseline, 19 (95%) had a lower atrophic gastritis severity classification (including none) at follow-up. All 20 of these participants completed treatment to eliminate Hp before follow-up and 17 (85%) had improved Hp density at follow-up; the small sample size did not permit assessment of factors associated with improved severity of atrophic gastritis.Hp before follow-up, did not test negative for Hp before follow-up and/or had moderate or marked Hp density at follow-up.Of seven participants with intestinal metaplasia detected at baseline, two had a lower intestinal metaplasia severity classification at follow-up, four had the same intestinal metaplasia severity at follow-up and one had a higher severity classification at follow-up. New onsets of intestinal metaplasia were observed in eight participants and new onsets of atrophic gastritis were observed in seven participants; six of these participants had new onsets of both atrophic gastritis and intestinal metaplasia. One participant with no atrophic gastritis and mild intestinal metaplasia at baseline had moderate atrophic gastritis and moderate intestinal metaplasia at follow-up. In total, 10 participants had a higher classification of atrophic gastritis, intestinal metaplasia or both at follow-up. The frequency of progression of atrophic gastritis and/or intestinal metaplasia among all 69 participants assessed at baseline was 14%; this frequency was relatively high in participants who did not complete treatment to eliminate Hp density at follow-up. For chronic gastritis, the next strongest predictor was completion of treatment to eliminate Hp before follow-up; for active gastritis, the next strongest predictor was Hp density at baseline, with the probability of improved active gastritis decreasing as baseline Hp density increased. For progression of atrophic gastritis and/or intestinal metaplasia, the strongest predictors were detection of Hp in gastric biopsies at baseline or follow-up, positively associated with progression, and treatment to eliminate Hp before follow-up, inversely associated with progression.Hp infection and associated gastric abnormalities among residents of three Arctic Indigenous communities at time points before and several years after they received treatment to eliminate Hp infection. The observed baseline Hp prevalence of 72% is in the range of estimates from other northern Indigenous communities in Canada (51–95%), Alaska (80%) and Greenland (58%) [Hp prevalence at follow-up of 26% was substantially lower, in the range of Hp prevalence estimates of 20–30% for major urban centers in Canada [This follow-up study estimated the prevalence of nd (58%) . The estn Canada ,39.Hp infection on gastric pathology. While most participants who were Hp-negative at baseline and follow-up had no evidence of abnormal gastric pathology at either time, participants who were Hp-positive at baseline and did not receive treatment to eliminate Hp showed predominantly unchanged or higher gastric pathology severity at follow-up. Most participants who were Hp-positive at baseline and Hp-negative at follow-up showed lower severity of gastric pathology at follow-up.Similarly, the prevalence of active gastritis, chronic gastritis and atrophic gastritis were all substantially lower at follow-up than baseline. The severity distribution of active, chronic, and atrophic gastritis also showed a notable shift toward reduced severity at follow-up. In particular, there was a substantial reduction in the prevalence of severe chronic gastritis from baseline to follow-up. Examination of within-individual change in gastritis severity shows evidence of the effect of Hp at baseline remained free of infection at follow-up. Among 33 participants who were Hp-negative after treatment at baseline, 7 were Hp-positive at follow-up, a reinfection proportion of 21% over an average follow-up of 7.2 (median = 9.1) years. For comparison, the estimated reinfection frequency over 2 years following successful Hp treatment in a study of urban Alaska Native gastroenterology patients was 14.6% [Hp isolated before and after treatment. Whether reinfections we observed are the result of true reinfection rather than a misclassified treatment outcome cannot be established in our study. In CANHelp community projects, however, the estimated prevalence of Hp infection in children is similar to that of adults [In this study, most participants who had successful treatment to eliminate as 14.6% . Authorsf adults , indicatHp-associated inflammatory changes of the gastric mucosa are reversible. In contrast, the results for intestinal metaplasia did not follow this pattern, though the small study size should be kept in mind. Most studies that have examined the reversibility of Hp-induced histopathological changes following elimination of Hp infection show chronic superficial gastritis to be reversible [Hp for prevention of gastric cancer highlights evidence consistent with the hypothesis that intestinal metaplasia is a “point of no return” in the carcinogenesis pathway [Hp elimination and a small progressive decrease in the grade of intestinal metaplasia over 5 or more years of annual follow-up after Hp elimination [Hp for 6 or more years following baseline therapy; reversal of intestinal metaplasia occurred to a much more limited extent, but Hp-negativity was associated with reduced progression of intestinal metaplasia to more advanced disease [For active and chronic superficial gastritis and atrophic gastritis, our results are compatible with the hypothesis that versible ,46,47,48versible . A recenmination . A Colom disease . In thisHp-negative at follow-up with reduced severity of gastric pathology. Also, the alignment of community of residence with length of follow-up prevented us from examining the effect of follow-up duration independent of community. Also, we did not examine diet or smoking as potential confounders because doing so would have further reduced our study size.Notable limitations of this study include the small study size at follow-up, largely due to the discomfort of unanesthetized gastroscopy. Loss-to-follow-up of participants with baseline pathology data was 78% combining all communities. This amount of loss-to-follow-up paired with likely differentiating characteristics of participants who were or were not willing to undergo gastroscopy for a second time may have selected disproportionately for participants who were Hp in the stomach because of its typical patchy colonization; furthermore, Hp can be difficult to visualize in tissue slides when bacterial density is low. We also acknowledge that observing Hp and gastric pathology status at just two time points could have resulted in missing changes in status that occurred between observations. This is a particular concern for chronic Hp infection: given Hp’s preferred niche of normal gastric tissue, colonizable tissue disappears as gastric disease progresses, resulting in the disappearance of Hp from areas of intestinal metaplasia and more advanced lesions [Hp infection onsets and eliminations during the follow-up period, and a few may have received treatment that was not reported to us.We note that some degree of misclassification of histopathology is unavoidable: biopsy sampling can miss  lesions . It is aDespite challenges, there are few population-based studies with long-term follow-up of gastric pathology. Furthermore, we are not aware of any others completed using a community-driven approach. Each project component, from project initiation to data analysis, was guided by local planning committee members who provided local knowledge and insight for grounding the research in the study population’s cultural and physical context; this approach encouraged participation from communities who were otherwise not represented in health research.Hp infection reduces the severity of Hp-associated gastric outcomes over the long term. Such evidence is needed to inform gastric cancer prevention strategies based on screening for Hp infection and offering treatment to those who test positive. In general, countries outside of east Asia have not implemented such prevention strategies, despite accumulating evidence that the elimination of Hp infection in people at elevated risk of gastric cancer is cost-effective for preventing gastric cancer  [Help community-driven projects have generated local evidence of relevance to clinical decision making about Hp infection specific to Arctic Indigenous communities. In particular, these projects have shown a high prevalence of severe chronic gastritis and atrophic gastritis in Hp-positive participants [This community-driven research provides encouraging evidence that the elimination of disease) . Among aicipants ; high pricipants ; and relicipants .Help projects to adapt current Canadian guidelines for northern and Indigenous populations in Canada [Hp infection reduces gastric cancer risk. We also recommend that endoscopic surveillance be considered for individuals who have intestinal metaplasia or severe atrophy along with another gastric cancer risk factor , especially if the intestinal metaplasia is extensive (in both gastric antrum and body) or severe [In addition to generating evidence for gastric cancer prevention approaches, we have used the information generated by the CANn Canada . Our guir severe .Hp density reduced during follow-up relative to those whose Hp density did not constitutes compelling evidence that treatment to eliminate Hp infection has the potential to reduce stomach cancer risk in participating communities.When drawing on the community project results to fill in evidence gaps for cancer prevention, due weight should be given to patients’ and communities’ motivation, values, preferences and circumstances, particularly where evidence is limited. Taken in this manner, the value to community members and health care practitioners of what can be learned from a small community-driven follow-up study is evident. Compared to no evidence from the target population, the more frequent observation of improvements in precancerous gastric pathology observed in participants whose