Colorectal cancer remains one of the most common malignancies worldwide, and while radical surgery is highly effective when the disease has not spread to distant organs, stage III disease, defined by lymph node involvement, carries a recurrence rate of 20 to 30 percent. Adjuvant chemotherapy after surgery has been proven in randomized controlled trials to reduce this risk and improve survival. However, the picture becomes murkier in patients aged 70 and older. As people age, comorbidities accumulate and organ function declines, making chemotherapy harder to tolerate and raising the risk of serious adverse events. Notably, there is no consistent evidence that adding oxaliplatin provides additional benefit in this age group, suggesting that the therapeutic effect of adjuvant chemotherapy may be limited for many elderly patients.

This uncertainty creates a real clinical dilemma. Physicians must weigh the possibility of a survival benefit against the substantial burden chemotherapy can impose on an older body. The Japanese research team, led by Tomoya Tago and Yasuyuki Takamizawa, set out to determine whether simple blood-derived markers, calculated from tests already ordered in routine care, could identify which elderly patients are most likely to benefit from postoperative chemotherapy and which might safely avoid it.

The study included patients aged 70 or older who underwent radical resection of pathologically confirmed stage III colorectal adenocarcinoma at the National Cancer Center Hospital between January 2000 and December 2017. After excluding those with other primary cancers, prior neoadjuvant therapy, or incomplete data, 308 patients remained, of whom 177 received adjuvant chemotherapy and 131 did not. Because patients selected for chemotherapy were significantly younger and likely healthier than those who were not, the researchers used propensity score matching to balance the two groups on sex, age, body mass index, comorbidities, tumor location and stage, histology, and preoperative tumor marker levels. This produced 78 matched pairs with well-balanced baseline characteristics.

The survival benefit of adjuvant chemotherapy held up after matching. The five-year recurrence-free survival rate was 76.6 percent in the chemotherapy group versus 62.8 percent in the non-treatment group, with a hazard ratio of 0.537. Five-year overall survival was 84.1 percent versus 73.9 percent, with a hazard ratio of 0.495. Both differences were statistically significant, confirming that adjuvant chemotherapy remains worthwhile for properly selected elderly patients overall.

The most striking findings emerged when the researchers stratified the matched cohort by nine preoperative and postoperative immuno-nutritional and inflammatory markers, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index, geriatric nutritional risk index, controlling nutritional status score, Glasgow Prognostic Score, and modified Glasgow Prognostic Score. Two postoperative markers showed significant interactions with chemotherapy benefit: the lymphocyte-to-monocyte ratio and the C-reactive protein-to-albumin ratio.

In patients with a high postoperative LMR, defined by the study’s cut-off of 5.27, adjuvant chemotherapy produced a dramatic improvement. Five-year recurrence-free survival reached 84.4 percent in the treated group versus just 53.0 percent in the untreated group, a hazard ratio of 0.27. Overall survival showed an even starker contrast: 92.1 percent versus 68.0 percent, with a hazard ratio of 0.16. Yet in patients with a low postoperative LMR, chemotherapy provided essentially no advantage, with five-year recurrence-free survival of 69.2 percent versus 72.9 percent, and overall survival of 76.9 percent versus 80.4 percent, both comparisons statistically indistinguishable.

The CAR told a similar story. Patients with a high postoperative CAR, above the cut-off of 0.026, derived marked benefit from chemotherapy, with five-year recurrence-free survival of 79.0 percent versus 47.8 percent and overall survival of 88.0 percent versus 62.4 percent. In those with a low CAR, the survival curves of treated and untreated patients were nearly superimposable. The biological rationale is rooted in tumor-host interactions: lymphocytes mount anti-tumor immune responses and their preservation is associated with better drug responsiveness, whereas systemic inflammation, marked by elevated C-reactive protein relative to albumin, reflects a cytokine-driven state regulated by interleukin-1, interleukin-6, and tumor necrosis factor-alpha that generally portends poorer outcomes. Because postoperative samples in this study were collected uniformly four to eight weeks after surgery, once acute inflammatory responses from the operation had subsided, the markers likely captured the patient’s intrinsic baseline immunity at the moment chemotherapy would begin, rather than residual tumor-driven inflammation.

The clinical appeal of these markers lies in their simplicity and cost. Unlike circulating tumor DNA, which shows promise for predicting treatment efficacy but remains expensive and not yet widely implementable, LMR and CAR can be calculated from standard complete blood counts and chemistry panels already obtained in routine follow-up. The authors suggest that these values could serve as supplementary information alongside age, performance status, and comorbidities when the indication for adjuvant chemotherapy is being considered, helping individualize decisions rather than uniformly determine them.

The researchers acknowledge important limitations. The study was retrospective and single-center, so selection bias and institution-specific treatment practices cannot be fully excluded, and the derived cut-off values may not generalize elsewhere. Standardized comorbidity assessment tools such as the Charlson Comorbidity Index and Geriatric-8 were not consistently available, data on chemotherapy completion rates and adverse events were incomplete, and molecular information on RAS, BRAF, and microsatellite instability status was lacking for much of the study period. Even so, because the cohort included elderly patients with common comorbidities, it reflects a population closer to real-world practice than the highly selected patients enrolled in clinical trials. The authors conclude that postoperative LMR and CAR are promising predictors of adjuvant chemotherapy efficacy in this growing patient population and hope the work will spur development of novel biomarkers for guiding treatment decisions in elderly cancer care.

Subject of Research: Predicting adjuvant chemotherapy efficacy in elderly stage III colorectal cancer patients using immuno-nutritional and inflammatory blood markers

Article Title: Predicting the Efficacy of Adjuvant Chemotherapy Using Immuno‐Nutritional and Inflammatory Markers in Elderly Patients With Stage III Colorectal Cancer

Article References: Tago, T., Takamizawa, Y., Kato, T., Nagata, H., Moritani, K., Tsukamoto, S., & Kanemitsu, Y. (2026). Predicting the Efficacy of Adjuvant Chemotherapy Using Immuno‐Nutritional and Inflammatory Markers in Elderly Patients With Stage III Colorectal Cancer. Annals of Gastroenterological Surgery, 10(5), 1575-1585. https://doi.org/10.1002/ags3.70235

Image Credits: AI Generated

DOI: 10.1002/ags3.70235

Keywords: colorectal cancer, adjuvant chemotherapy, elderly patients, lymphocyte-to-monocyte ratio, C-reactive protein-to-albumin ratio, immuno-nutritional markers, inflammatory markers, propensity score matching, recurrence-free survival, biomarkers, National Cancer Center Hospital, Annals of Gastroenterological Surgery

The research team, led by Keito Yamaguchi of Tokyo University of Science together with Xueqing Bo of Kochi University of Technology and colleagues, set out to answer a deceptively simple question that has long eluded empirical scrutiny: does having a neighborhood park nearby actually change how alive a place feels and functions? Urban vibrancy, the researchers emphasize, is not a single number. It is a multidimensional phenomenon reflected in the movement of people, the presence of families, the hum of commerce, and the texture of daily social life. Rather than collapsing all of this into one index, the team measured three distinct dimensions: pedestrian flows derived from anonymized mobile phone location data, annual retail sales as an economic signal, and the population of children aged zero to fourteen as an indicator of family-oriented residential vitality.

What makes the study methodologically distinctive is its effort to overcome a chronic weakness in park research: the fact that parks are not randomly distributed across cities. Areas with parks may differ systematically from areas without them in population density, land use, transit access, and commercial concentration, so a naive comparison of the two would tell us little. To address this, the researchers borrowed tools from causal inference, most notably propensity score matching, a technique introduced by Rosenbaum and Rubin in the 1980s. Each station catchment area, defined as an 800-meter circular buffer around a railway station corresponding roughly to a ten-minute walk, was assigned a propensity score: the estimated probability that an area with its particular urban characteristics would contain at least one neighborhood park. Areas with parks were then matched to statistically comparable areas without them, allowing the researchers to estimate adjusted differences in outcomes while accounting for 64 covariates covering facilities, land use, population, zoning, and transportation.

The balancing diagnostics were encouraging. After matching, 62 of the 64 covariates showed standardized mean differences below the conventional 0.25 threshold, and the propensity score distributions of the treated and control groups overlapped closely across nearly the entire range. In practical terms, this means that station areas with neighborhood parks were compared against station areas that looked remarkably similar in every observed respect except the presence of the park itself. The treatment group comprised 187 station catchment areas containing at least one neighborhood park, while 506 areas served as controls. Because the study rests on observational, cross-sectional data, the authors are careful throughout to describe their results as adjusted associations rather than definitive causal effects, a caution that reflects the possibility that parks were deliberately placed in areas already attractive to families or already bustling with activity.

Within those constraints, the results are striking. Station catchment areas with neighborhood parks contained approximately 116 more children on average than their matched counterparts, a statistically significant difference with a 95 percent confidence interval ranging from about 37 to 195 additional children. This suggests that neighborhood parks are associated with residential environments that draw and retain households with young children, whether by providing spaces for play and parent-child interaction or by signaling a family-friendly neighborhood character. The finding resonates with a long line of research showing that access to quality green space influences where families choose to live and how children use their surroundings, but it is among the first to quantify this relationship at the scale of an entire megaregion while adjusting so extensively for confounding urban conditions.

The second significant result concerned the daily rhythms of commuting. On weekdays, station areas with neighborhood parks recorded roughly 392 more worker pedestrians than comparable areas without parks, a difference that was statistically significant. The researchers interpret this as evidence that neighborhood parks function as what they call micro-rest spaces within workday activity patterns: venues for short walks, lunch breaks, informal rest, and movement between offices and surrounding facilities. In a metropolis where railway stations anchor the daily lives of millions of commuters, even a modest park may meaningfully improve the walking environment during the hours when foot traffic peaks. Notably, the holiday estimate for worker pedestrian flow was positive but not statistically significant, hinting that the park effect on mobility is specific to the structure of the working week.

Just as informative are the results that did not materialize. Annual retail sales showed no significant association with park presence, and neither did pedestrian flows among visitors or residents on either weekdays or holidays. Commercial vitality, the authors argue, is governed by forces far beyond a single green amenity: commercial agglomeration, station size, accessibility, land-use composition, and regional centrality all dwarf the influence of a neighborhood park. This indicator-specific pattern challenges the popular assumption that parks universally energize their surroundings. Instead, the study suggests that neighborhood parks occupy a particular niche in the urban ecosystem, supporting family-oriented residential vitality and weekday worker mobility rather than driving commerce or attracting visitors from afar.

To test whether these findings held beyond the matched sample, the team applied two additional estimators of the average treatment effect across all 693 station areas: inverse probability weighting and a doubly robust learner that combines propensity score modeling with Random Forest regression, a machine-learning method capable of capturing nonlinear relationships among dozens of urban covariates. The two methods broadly agreed on the direction of effects for worker and resident pedestrian flows, both producing positive estimates, with weekday worker flow again showing the clearest signal. But for retail sales and visitor flows, the methods diverged, even producing estimates of opposite signs, a discrepancy the authors attribute to sensitivity in model specification, weighting, and treatment effect heterogeneity. These supplementary results are presented as exploratory evidence, and the diagnostics, including weight distributions and cross-fitted propensity score overlap, support the numerical stability of the estimates without eliminating all uncertainty.

The study is candid about its limitations, and these are worth understanding. The 800-meter circular buffer is an operational simplification that ignores street networks, topography, and physical barriers, and catchment areas of nearby stations may overlap, raising questions of spatial dependence. The datasets are not perfectly aligned in time: park presence and most covariates date from around 2011 to 2014, while the pedestrian flow data come from 2018, drawn from the KDDI Location Analyzer platform based on GPS data from consenting mobile phone subscribers. Carrier choice may introduce sampling bias, and the classification of pedestrians into workers, residents, and visitors relies on inferred home and workplace locations. The treatment variable captures only whether at least one neighborhood park exists, not its size, quality, facilities, or accessibility. And because the analysis excludes stations in wards, towns, and villages, the findings may not generalize to Tokyo’s densest 23 special wards.

Even with these caveats, the implications for urban planning are substantial. As metropolitan areas worldwide grapple with aging populations, declining social interaction, and the uneven distribution of urban functions, the study suggests that neighborhood parks deserve recognition not merely as recreational amenities but as a form of social infrastructure woven into the fabric of daily life. In Japan, where parks double as disaster evacuation hubs and venues for civic activity, their role is arguably even more multifunctional than elsewhere. The research does not claim that planting a park will automatically generate urban vibrancy; rather, its contribution depends on interaction with surrounding land use, pedestrian networks, and residential character. What the evidence does support is a more targeted vision: neighborhood parks as anchors of family-friendly residential environments and as small but meaningful waypoints in the working day of millions of commuters. Future work, the authors suggest, should employ longitudinal designs such as difference-in-differences, network-based catchment definitions, and detailed park-characteristic data to identify precisely which kinds of parks, in which kinds of places, deliver the greatest benefit. For now, the message from Tokyo is clear and refreshingly precise: green spaces close to home matter most for the families who live there and the workers who pass through, and that is a finding worth building on.

Subject of Research: The association between neighborhood park presence and multiple indicators of urban vibrancy in Tokyo metropolitan station catchment areas, analyzed using propensity score matching and machine learning.

Article Title: Effects of neighborhood parks on urban vibrancy in metropolitan Tokyo using propensity score matching and machine learning

Article References: Yamaguchi, K., Bo, X., Terabe, S., Yaginuma, H., Ajito, M., & Inagaki, K. (2026). Effects of neighborhood parks on urban vibrancy in metropolitan Tokyo using propensity score matching and machine learning. Discover Cities, 3(1), Article 181. https://doi.org/10.1007/s44327-026-00346-5

Image Credits: AI Generated

DOI: 10.1007/s44327-026-00346-5

Keywords: urban parks, urban vibrancy, Tokyo, propensity score matching, machine learning, pedestrian flow, station catchment area, child population, retail sales, causal inference, urban planning, mobile phone location data

Inhaled corticosteroids are the cornerstone of modern asthma management. Unlike in COPD, where steroid inhalers are reserved for a specific subgroup of patients with an eosinophilic phenotype, international guidelines from the Global Initiative for Asthma recommend inhaled corticosteroids at every step of asthma severity, from mild disease treated on an as-needed basis to severe disease requiring daily maintenance therapy. That ubiquity is precisely why the question of interclass safety differences matters so much in asthma: unlike in COPD, where a concerning safety profile might prompt a clinician to simply withdraw the steroid, withdrawing inhaled corticosteroids from a patient with asthma is not a realistic therapeutic option. Any meaningful difference in pneumonia risk between drug classes would therefore have immediate and unavoidable implications for prescribing decisions worldwide.

The motivation for the study traces back to a robust body of COPD literature. Systematic reviews and meta-analyses have consistently found that budesonide/formoterol combinations are associated with fewer pneumonia events than salmeterol/fluticasone combinations, and subsequent nationwide cohort studies have reinforced the conclusion that fluticasone propionate raises pneumonia risk relative to budesonide in that population. A repeat systematic review published nine years after the first reached the same conclusion, describing a likely clinically important interclass difference. Researchers have even documented downstream economic consequences, with patients treated with fluticasone incurring higher COPD-related, pneumonia-related, and all-cause health care costs than those treated with budesonide. Whether this pharmacological divergence extended to asthma, however, remained genuinely uncertain.

The evidence in asthma was sparse and contradictory. A Swedish cohort found that fluticasone propionate was associated with increased pneumonia risk, but only when compared against patients with asthma who were not using the drug, not against budesonide users. A Canadian quasi-cohort study suggested that both budesonide and fluticasone were linked to elevated pneumonia risk in asthma. Meanwhile, analyses of randomized trial data found no increased pneumonia risk among patients with asthma taking budesonide at all. Compounding the confusion, studies comparing steroid users with non-users in asthma suffer from a fundamental design flaw: because guidelines recommend maintenance inhaled corticosteroids for all moderate to severe disease, such comparisons effectively pit patients with mild asthma against those with severe disease, confounding drug effects with underlying illness severity.

To sidestep that bias, the research team, led by Wang Chun Kwok and James Chung Man Ho of the University of Hong Kong together with colleagues at the University of South Carolina, restricted their analysis to adults with moderate to severe asthma at Global Initiative for Asthma steps 3 to 5, all of whom required regular maintenance inhaled corticosteroid combined with a long-acting beta-agonist. Drawing on the Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority, a network covering more than 90 percent of the territory’s population through 43 hospitals and 123 outpatient clinics, the investigators identified 16,170 eligible patients treated in 2018 and followed them through the end of 2023. Of these, 7,169 patients, or 44.3 percent, were prescribed budesonide; 7,853, or 48.6 percent, received fluticasone propionate; and 1,148, or 7.1 percent, received fluticasone furoate. The cohort had a mean age of 63.1 years, was 35.4 percent male, and included just over half of patients at the most severe treatment step.

The researchers evaluated pneumonia across three tiers of severity: all pneumonia events requiring emergency department visits or hospitalization, pneumonia severe enough to require admission to a medical ward, and pneumonia requiring intensive care unit admission. Over the follow-up period, 1,675 patients, or 10.4 percent of the cohort, developed pneumonia, with nearly identical proportions in the two treatment groups: 10.2 percent among budesonide users and 10.5 percent among fluticasone users. Hospitalized pneumonia affected 8.9 percent of patients overall, while only 42 patients, roughly 0.3 percent, developed pneumonia severe enough to require intensive care.

Across every analytical framework the team applied, the results pointed in the same direction. Using budesonide as the reference group, the adjusted odds ratio for all pneumonia events among fluticasone users was 0.95, with a 95 percent confidence interval of 0.85 to 1.06 and a p-value of 0.32. The adjusted incidence rate ratio was 1.05, and the adjusted hazard ratio for time to first pneumonia event was 0.94, none of which reached statistical significance. For hospitalized pneumonia, the adjusted odds ratio was 0.95 and the adjusted hazard ratio 1.03, both non-significant. Even for the rarest and most severe outcome, pneumonia requiring ICU admission, the adjusted odds ratio of 1.08 and hazard ratio of 1.06 were statistically indistinguishable between the drugs. To guard against confounding, the team also performed propensity score matching on age, sex, treatment step, comorbidity burden, steroid dose, and vaccination status for influenza and pneumococcal disease; the matched analysis reproduced the null result. Subgroup analyses isolating fluticasone furoate and fluticasone propionate individually against budesonide likewise found no significant differences.

Why would an interclass difference so prominent in COPD vanish in asthma? The authors point to fundamental differences in the two patient populations. Patients with COPD who qualify for inhaled corticosteroids tend to be older, heavy smokers with multiple comorbidities and a history of exacerbations driven by respiratory pathogens, making them intrinsically vulnerable to pneumonia. Patients with asthma, by contrast, are generally younger, more often non-smokers, and carry fewer comorbidities, and steroid initiation in asthma is dictated by disease severity rather than exacerbation history. With a baseline pneumonia incidence of only about 10 percent over five years in this asthma cohort, the researchers argue that any true interclass difference, if it exists at all, is likely too small to carry meaningful clinical weight, even in a dataset of this size and with follow-up extending across five years.

The study does carry limitations worth noting. The cohort was overwhelmingly Chinese, which may limit generalizability to other populations, although the authors observe that COPD studies of the same question have yielded consistent findings across countries. Lung function parameters and symptom burden were not directly assessed, with treatment step serving as the recognized proxy for asthma severity, and mild pneumonia cases managed entirely in outpatient settings were excluded because such events are inconsistently coded in medical records, a trade-off the investigators made to preserve diagnostic validity. The study also included only adults, leaving pediatric populations, who face distinct viral pneumonia risks, as a target for future research.

For practicing clinicians, the practical message is straightforward. In moderate to severe asthma, the choice between budesonide-based and fluticasone-based fixed-dose combinations should be guided by asthma control, device preferences, and each drug’s broader side-effect profile, not by fear of pneumonia. The shadow cast by COPD safety data, it turns out, does not extend to the asthma clinic, and patients can take some comfort in knowing that the workhorse anti-inflammatory inhalers they depend on daily differ far less in infection risk than the older literature might have suggested.

Subject of Research: Comparative pneumonia risk of budesonide versus fluticasone inhaled corticosteroids among patients with moderate to severe asthma

Article Title: Comparing Pneumonia Risks of Budesonide with Fluticasone Among Patients with Asthma in Hong Kong: A Territory-Wide Retrospective Study

Article References: Kwok, W. C., Zhou, L., Ma, T. F., Ngai, S. M., Leung, R. Y. H., Tam, T. C. C., & Ho, J. C. M. (2026). Comparing Pneumonia Risks of Budesonide with Fluticasone Among Patients with Asthma in Hong Kong: A Territory-Wide Retrospective Study. Advances in Therapy. https://doi.org/10.1007/s12325-026-03776-0

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03776-0

Keywords: asthma, inhaled corticosteroids, budesonide, fluticasone, pneumonia, COPD, Hong Kong, GINA guidelines, retrospective cohort study, respiratory medicine, drug safety, propensity score matching