To evaluate the six-month effectiveness and safety of rituximab biosimilars compared to the originator in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and outcomes following originator to biosimilar switching. We recruited adults with GPA or MPA treated with the rituximab originator or a biosimilar for induction or maintenance, or who switched from originator to biosimilar maintenance (2018-2023). Participants either started the treatment within the preceding six months or were recruited from vasculitis research cohorts. Outcomes included six-month remission (Birmingham Vasculitis Activity Score [BVAS] version 3 of 0), relapse (BVAS rise after achieving remission requiring treatment), vasculitis damage, and serious adverse events (SAEs). We studied 207 participants from 9 centers: 132 starting induction (58 originator and 74 biosimilar), 59 starting maintenance (23 originator and 36 biosimilar), and 16 in the "switch" group. Mean age was 56.7 years (SD 17.5), 52% were female, 80% were White, and 70% had GPA. At six months from induction, 51 of 53 (96%) originator and 66 of 73 (90%) biosimilar recipients achieved remission (difference 6%, 95% confidence interval [CI] -4% to 15%), whereas at three months (exploratory) 48 of 51 (94%) and 57 of 72 (79%) recipients, respectively, had achieved remission (difference 15%, 95% CI 2% to 26%). All individuals in the maintenance and "switch" subgroups were in remission at six months. One minor relapse occurred in each of the induction groups and in the originator maintenance group. Change in vasculitis damage and SAEs were not significantly different between groups. This study found no significant differences in six-month outcomes between the rituximab originator and biosimilars for induction of GPA and MPA, with no concerning early signals in those initiating maintenance or switching from the originator to a biosimilar.
High temperature is one of the major environmental stressors that severely affects plant growth. Paris polyphylla var. yunnanensis, a traditional Chinese herbal medicine, is sensitive to high temperature. However, the underlying mechanisms of its response to high temperature remain unclear. In this study, we investigated the physiological and proteomic change of P. polyphylla var. yunnanensis under different treatments (25°C, 30°C, 35°C, 40°C). Our results showed that high temperature directly impaired photosynthesis and disrupted metabolism, evidenced by reduced chlorophyll and photosynthetic rate, as well as accumulated proline and increased conductivity. A total of 893 differentially expressed proteins (DEPs) were identified, with significant changes in the expression levels of enzymes associated with protein processing and synthesis. Additionally, the expression levels of key proteins involved in the circadian pathway and the glutathione pathway were also notably upregulated. Dynamic changes in the endocytosis and autophagy-related proteins ATG3 and ATG8C were also observed, suggesting that these processes may play a significant protective role under high-temperature stress. Overall, this study provides an important starting point for improving the heat tolerance of P.polyphylla var. yunnanensis through genetic engineering.
/aim: Traditional orthopedic disability assessment relies on complex guidelines and is prone to evaluator error and inefficiency. This study evaluated whether a retrieval-augmented generation (RAG) AI assistant (NotebookLM) improves accuracy and efficiency in guideline-based impairment rating compared with manual consultation. In this prospective comparative study, 50 anonymized case-based clinical scenarios representing common musculoskeletal impairments were developed. Four orthopedic specialists evaluated all scenarios using two methods: manual guideline consultation and NotebookLM-assisted assessment restricted to the same regulation. The starting method was randomized, with each evaluator assessing 25 scenarios per method. The primary outcome was accuracy against an expert reference standard; the secondary outcome was time per scenario. AI-assisted evaluation achieved higher accuracy than manual consultation (91% vs 68%; absolute difference, 23 percentage points, 95% CI 12.3 to 33.7; χ2(1) = 14.849, p < .001). Generalized estimating equations confirmed an independent association between the AI-assisted method and correct ratings (adjusted OR 4.76, 95% CI 3.24-6.98, p < .001). Mean evaluation time decreased from 131 to 37 seconds per scenario (mean difference, 94.36 seconds, 95% CI 74.38 to 114.34; p < .001). A RAG-based AI assistant improved both accuracy and efficiency in orthopedic impairment rating under controlled conditions. These findings suggest meaningful clinical utility in structured, guideline-bound workflows, although further external validation in routine clinical practice is necessary before broader adoption can be recommended.
Alpha-1 antitrypsin deficiency (A1ATD) is characterized by reduced levels of protease inhibitor alpha-1 antitrypsin, most commonly manifesting with liver disease in childhood, and/or pulmonary disease starting in the 3rd decade of life. Childhood-onset lung disease in A1ATD has almost never been reported. An 11-month-old boy with a history of neonatal cholestasis and A1ATD phenotype PiZZ presented with prolonged fever of unknown origin. A computed tomography chest was obtained, given continued diagnostic uncertainty and the history of A1ATD, showing paramediastinal right upper lobe consolidation, as well as basilar centrilobular emphysema in the left lower lobe, likely secondary to the patient's A1ATD. The patient had no respiratory symptoms and clinically recovered with antibiotics. Pediatric development of emphysema has been rarely described, and this is the earliest documented case to date at 11 months of age. This is also the first finding of asymptomatic emphysema in childhood A1ATD, demonstrating that disease progression may be chronic and may transition from asymptomatic to symptomatic disease.
The 1,3-diol unit is an extremely important functional group motif, and significant effort has gone into development of methods to access it with definition of relative and absolute stereochemistry. Conventionally, stereochemical complexity is built up in a stepwise manner alongside functional group interconversion. It is interesting to consider an unconventional approach whereby the diol may be synthesized nonselectively and the stereoisomers "descrambled" by a chiral catalyst in a subsequent step. We report studies toward this goal using a cinchona alkaloid-derived hydrogen atom abstraction catalyst. This catalyst permits selective hydrogen atom abstraction from a given stereoisomer out of, in some cases three or four, depending on diol substitution. The relative rates of abstraction from different stereoisomers determine the ultimate product outcome after hydrogen atom delivery from an achiral thiol. Symmetrical 1,3-diols participate in a kinetic resolution process whereby one enantiomer is converted to the meso diastereomer with extremely high selectivity, a rare example of a kinetic resolution involving conversion of one enantiomer to an achiral diastereomer. Nonsymmetrical 1,3-diols exhibit different outcomes depending on substitution, and their behavior is systematically explored. Notably, sterically differentiated substrates can allow high ee of both syn and anti diastereomers to be achieved from racemic starting material. On the basis of mechanistic studies, a unified rationalization of the behavior of 1,3-diols of various types with our catalyst is presented, and we additionally evaluate the analogous chiral 1,2-diols, uncovering promising outcomes with nonsymmetrical diols.
The PRISM study is a nationwide, multicenter, prospective observational study in Japan evaluating the real-world efficacy and safety of systemic therapies for unresectable hepatocellular carcinoma (HCC). HCC patients starting systemic therapy are prospectively enrolled, enabling assessment of outcomes and tolerability across treatment lines. By capturing all patients treated in routine practice, the study is expected to provide a clear picture of the actual treatment outcomes in Japan. We analyzed the first 1,000 patients enrolled between July 2020 and July 2022, focusing on outcomes of first-line therapy and subsequent patterns. Data on demographics, tumor stage, liver function, regimens, survival, and adverse events (AEs) were prospectively collected and centrally monitored. Survival was estimated by Kaplan-Meier method, and tumor responses were assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). Of 935 evaluable patients, 82.8% received atezolizumab + bevacizumab (Atezo+Bev) and 15.2% lenvatinib as first-line therapy. Median overall survival and progression-free survival were 21.8 and 7.7 months for Atezo+Bev, respectively, and 20.8 and 6.7 months for lenvatinib, with overall survival numerically longer than that reported in pivotal clinical trials, while progression-free survival remained comparable. Objective response rates were 29.6% (RECIST) and 35.0% (mRECIST) for Atezo+Bev, 24.6% and 35.2% for lenvatinib, and 0% and 6.3% for sorafenib by RECIST and mRECIST, respectively. Grade ≥3 treatment-related AEs occurred in 21.6% and 22.9%, with safety profiles consistent with prior reports. Approximately 50% of patients received second-line therapy, most often lenvatinib after Atezo+Bev and vice versa, with a median progression-free survival of ∼4 months; later-line regimens yielded even shorter benefit. The PRISM study confirms the real-world reproducibility of Atezo+Bev and lenvatinib in Japan, demonstrating their feasibility across diverse patient populations. Ongoing follow-up and subgroup analyses, particularly in special populations, are expected to help optimize long-term outcomes.
Amid persistently low blood pressure (BP) control rates and pervasive therapeutic inertia, we evaluated trends in pre- and posttreatment BP before and after 2 major disruptions (the 2017 target‑lowering guideline and the COVID‑19 pandemic) to assess their impact on early hypertension management. This retrospective cohort study of national Veterans Health Administration data included outpatient adults newly diagnosed with hypertension and starting antihypertensive medication between November 13, 2014, and May 31, 2023 (index date). Patients were stratified into 3 periods corresponding to preguideline/prepandemic (Period 1), postguideline/prepandemic (Period 2), and postguideline/postpandemic (Period 3), and into 3 pretreatment systolic BP (SBP) groups based on the average of ≥2 measurements in the 90-day preindex period (<140, 140-160, or ≥160 mm Hg). Across periods, multivariable analyses evaluated: (1) mean posttreatment SBP (mean of measurements from days 180-365 postindex); and (2) posttreatment BP control (<140/90 or <130/80 mm Hg). Among 271 496 Veterans (mean age, 62 years; 92% male; 66% non-Hispanic White), 39%, 32%, and 29% were in Periods 1, 2, and 3, respectively. Adjusted posttreatment SBP across periods was 128, 135, and 142 mm Hg for the <140, 140 to 160, and ≥160 groups, respectively. Rates of posttreatment BP control <140/90 mm Hg across Periods 1, 2, and 3, respectively, were 82.3%, 83.3%, and 84.2% (SBP <140 group); 64.1%, 66.1%, and 67.3% (140-160 group); and 46.4%, 47.0%, and 48.6% (≥160 group). For BP control <130/80 mm Hg, rates were 38.2%, 40.0%, and 39.9% (SBP <140 group); 20.7%, 22.0%, and 22.6% (140-160 group); and 15.1%, 15.4%, and 15.2% (≥160 group). Despite the target-lowering guideline and the care-disrupting pandemic, BP levels and control among Veterans remained largely unchanged. At 1 year, only half to two-thirds achieved BP <140/90 mm Hg, and few reached <130/80 mm Hg, underscoring persistent clinical inertia and the need to improve early hypertension management in the Veterans Health Administration.
We report a case of immune-related aseptic meningitis (irAE meningitis) presenting with multiple cranial nerve symptoms during immune checkpoint inhibitor therapy for lung adenocarcinoma. A 72-year-old woman diagnosed with left lower lobe lung adenocarcinoma initiated combination therapy consisting of carboplatin, paclitaxel, bevacizumab, and atezolizumab. Paclitaxel was subsequently discontinued due to peripheral neuropathy, and maintenance therapy with bevacizumab and atezolizumab followed. Eight months after starting treatment (after four cycles of atezolizumab maintenance), the patient presented with a three-week history of dysgeusia, anosmia, trismus, and neck pain. Cerebrospinal fluid (CSF) analysis revealed lymphocytic and monocytic pleocytosis, while cytological examination showed no malignant cells and bacterial cultures were negative. Brain and neck magnetic resonance imaging (MRI) showed no alternative etiologies. Intravenous prednisolone led to a rapid resolution of all symptoms. The patient was diagnosed with irAE meningitis with concomitant cranial nerve involvement, including the olfactory (I), trigeminal (V), facial (VII), and/or glossopharyngeal (IX) nerves. Intravenous prednisolone led to a rapid resolution of all symptoms. Although irAE meningitis is a known rare adverse event, cases complicated by multiple cranial nerve symptoms are extremely uncommon. This case highlights the phenotypic diversity of neurotoxicity associated with immune checkpoint inhibitors.
Minimal disease activity (MDA) has recently been introduced as comprehensive treatment target in atopic dermatitis (AD), integrating both clinician- and patient-reported outcomes. Evidence on the real-world feasibility and impact of achieving MDA on quality of life (QoL) remains limited. This analysis evaluated the association between MDA achievement and QoL outcomes in patients with moderate-to-severe AD receiving upadacitinib (UPA) in real-world clinical practice. This interim analysis used data from the ongoing, prospective, multicenter, non-interventional UP-TAINED study (NCT05139836) in Germany. Analyses included all patients without treatment interruptions during the first 12 months (n = 259). Disease control was classified as optimal, moderate, or none. Optimal control (MDA) was defined as Eczema Area and Severity Index (EASI) ≤ 3 and Worst Pruritus Numeric Rating Scale (WP-NRS) ≤ 0/1; moderate control as EASI ≤ 3 with WP-NRS 2-3 or EASI > 3-7 with WP-NRS ≤ 3; and no control as EASI > 7 or WP-NRS > 3. QoL outcomes were assessed using validated patient-reported measures. MDA was achieved by 38.2% of patients at month 1 and by 42.1% at month 12. Those achieving MDA reported substantially greater improvements across all QoL measures compared with patients with moderate or no disease control. QoL outcomes were comparable between patients starting UPA at 15 mg or 30 mg. The most frequent adverse events were AD, acne, and corona virus disease 2019 (COVID-19) infection; the safety profile was consistent and no new safety signals were identified. Achieving MDA was associated with markedly improved QoL in real-world AD management, supporting MDA as a feasible and clinically meaningful treatment goal in routine practice. ClinicalTrials.gov Identifier, NCT05139836.
 This clinical and radiological pilot study aimed to evaluate soft and hard tissue dimensional changes at extraction sites using digital technology.  Ten teeth were extracted from seven patients referred for simple tooth extractions. Cone-beam computed tomography (CBCT) scans and digital impressions were obtained before tooth extraction and four months after extraction. Virtual models were initially aligned using Medit® Design software (Medit, Seoul, Republic of Korea) and subsequently superimposed onto CBCT images using BlueSkyPlan® software (Blue Sky Bio, LLC, Grayslake, IL, USA). Horizontal and vertical measurements of soft and hard tissue dimensional changes were performed using BlueSkyPlan®. Vertical measurements were obtained at the buccal, central socket, and palatal/lingual aspects. Horizontal measurements were taken at four levels, 2 mm apart, starting at the initial ridge level (L0).  Horizontal gingival retraction was 27.40% at L0 and 11.58% at L2. Horizontal hard tissue resorption was 24.39% at L0 and 30.09% at L2. A significant difference in mean soft tissue thickness (at L0 and L2) and hard tissue thickness (at all levels) was observed before and after extraction (p < 0.05). The mean vertical soft tissue retraction was 0.94 ± 0.48 mm buccally and 1.21 ± 0.93 mm lingually. Mean vertical hard tissue resorption was 1.92 ± 1.23 mm buccally and 1.71 ± 0.88 mm lingually. However, no significant differences were observed between buccal and palatal/lingual vertical soft and hard tissue dimensional changes.  This study showed that extensive bone resorption and gingival retraction generally occur within four months after tooth extraction. These post-extraction dimensional changes should be considered when establishing surgical and prosthetic treatment plans.
For a class of translation-invariant free-fermion systems including those with uniform nearest-neighbor hopping) on a d-dimensional L×⋯×L hypercubic lattice, we prove that, starting from an arbitrary pure initial state, the system equilibrates with respect to the coarse-grained density within a timescale of order L. This scaling is optimal, since there exist initial states whose equilibration requires time of order L. Our result establishes O(L) as the equilibration timescale, as is expected in normal macroscopic systems with a conserved quantity, such as total number of particles.
What is this summary about? This summary describes two studies in people with sickle cell disease, or SCD. Both studies looked at a medicine called voxelotor, also known as Oxbryta®, which was previously available for treating people with SCD. This is a summary of an article published in Blood Advances. What were the results of the studies? In the RETRO and PROSPECT studies, researchers looked at people with SCD taking voxelotor in everyday, real-world medical practice. In other words, they took voxelotor as part of their usual care when it was available for prescription in the United States. In RETRO, 216 participants were enrolled and the length of voxelotor treatment was about 1 year, on average. In PROSPECT, 265 participants were enrolled, and the length of voxelotor treatment was almost 3 years, on average. After taking voxelotor, participants had increases in hemoglobin, the protein in red blood cells that carries oxygen. Their red blood cells also broke apart less quickly when taking voxelotor. The most common symptom related to SCD was acute pain crisis, but participants did not experience it more often after starting voxelotor. What do the results mean? All medicines are tested in clinical trials before they are approved as treatments. However, it is always important to study a medicine in real-world medical practice as well. In RETRO and PROSPECT, the effects of voxelotor were like the effects seen in the clinical trials, and researchers did not see any unexpected symptoms related to SCD or unexpected side effects related to the study drug.
Among molecular imaging techniques, 19F magnetic resonance imaging (19F MRI) is particularly attractive due to deep penetration and multiplexed molecular imaging. However, the further development of 19F MRI remains constrained by its limited sensitivity, which largely depends on fluorinated probe design and more fundamentally on the availability of high-performance fluorinated moieties that define probe signal intensity. Here we systematically establish 3,5-bis(2-hexafluoro-isopropoxy)phenyl (BHFIP) as a structurally simple yet highly capable fluorinated moiety for 19F MRI probe design. Starting from 1,3-bis(2-hexafluoro-isopropoxy)benzene, a simple two-step nitration-reduction procedure afforded 3,5-bis(2-hexafluoro-isopropoxy)aniline (BHFIP-NH2), a modifiable BHFIP-based building block. Besides its high fluorine loading of 12 chemically equivalent fluorine atoms, BHFIP was found to possess an intrinsically short 19F longitudinal relaxation time (T1), together enabling exceptionally high 19F MRI sensitivity. Its 19F chemical shift at approximately - 75 ppm is clearly distinguishable from those of established highly fluorinated moieties, supporting multiplexed 19F MRI. The two hydroxyl groups of BHFIP contribute to water solubility and enable O-modification, while BHFIP-NH2 further provides an additional amino handle for N-modification. Representative incorporation of BHFIP-NH2 into 19F MRI probes further verified that the advantages of BHFIP can be retained in functional probe molecules. This work establishes BHFIP as a promising fluorinated moiety for high-sensitive and multifunctional 19F MRI probes.
The discovery and development of high-performance catalysts, which is crucial across all catalysis areas, requires advanced technologies and innovative approaches. Recently, machine learning (ML) has shown promise in accelerating this process, but its capability and examples of discovery of truly novel catalysts have remained limited. In this study, we describe an ML approach that goes beyond the traditional element pool, incorporating elements that have not been previously studied, to develop highly efficient catalysts for ethanol synthesis via CO2 hydrogenation. Starting with an initial data set of 58 catalysts (274 data points obtained at reaction temperatures ranging from 240-400 °C), we conducted 24 iterations of a closed-loop discovery system (ML predictions + experimental validation), testing a total of 555 catalysts (2477 data points), and building a large experimental data set. More than 50 catalysts with superior activity were discovered through this data-driven approach. The multielemental Pd(0.8)-Au(0.3)/K(2.5)-Sr(1)-Fe(20)-Zn(4)-Cd(2)-Yb(1)-Re(1)/CeO2(25%)-ZrO2 catalyst, where the numbers in parentheses represent weight percent (wt %), was identified as the most effective catalyst for ethanol synthesis (ethanol space-time yield: 8.2 mmol gcat-1 h-1 with a CO2 conversion of 57.6% and an ethanol selectivity of 23.2% under reaction conditions of 360 °C, 4 MPa, 12 L gcat-1 h-1, H2/CO2 = 3/1). Comprehensive characterizations, including in situ/operando techniques such as X-ray absorption spectroscopy (XAS), ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), enable us to highlight the critical roles of each constituting element in improving ethanol synthesis efficiency.
Numerous factors may influence the optimal rollout of new gonococcal antibiotics. We compared 8 rollout strategies using a gonorrhea transmission model and ranked strategies by the number of gonococcal infections and clinically useful antibiotic lifespan. Rankings were most sensitive to the starting ceftriaxone resistance prevalence and screening frequency.
Lacunar stroke can cause cognitive decline and dependency. The LACI-2 (Lacunar Intervention Trial-2) trial showed that 12 months of treatment with isosorbide-mononitrate (ISMN) or cilostazol improved these outcomes. We tested whether this effect was present at 6 months. LACI-2 was a prospective randomized open-label blinded-end point 2×2-factorial phase-2b trial assessing feasibility, safety, and proof-of-concept of 1 year of ISMN (40-60 mg) or cilostazol (200 mg). Participants aged >30 years had clinical lacunar stroke, compatible neuroimaging, and capacity to consent. The primary clinical outcome was the composite of stroke, myocardial infarction, dependency (modified Rankin Scale score >2), cognitive impairment (Diagnostic and Statistical Manual version 5, 7-level >0) and death; key secondary outcomes included the composite components, mood and stroke impact scale. Global analysis of the stroke impact scale was analyzed using the Wei-Lachin test with result given as Mann-Whitney difference. Baseline characteristics were balanced across 363 participants: median age 64 (56-72) years, 31% female, and median onset to randomization 79 (27-244) days. At 6 months, participants allocated to ISMN versus control had fewer composite events (adjusted odds ratio [OR], 0.74 [95% CI, 0.55-0.99]) and improved stroke impact (Mann-Whitney difference, -0.15 [95% CI -0.25 to -0.05]). Cilostazol versus control improved cognition (Diagnostic and Statistical Manual version 5, 7-level scale, adjusted common OR, 0.64 [95% CI, 0.41-0.99]). ISMN/cilostazol versus control improved cognition (Diagnostic and Statistical Manual version 5, 7-level adjusted common OR, 0.40 [95% CI, 0.21-0.78]), mood (Zung adjusted mean difference, -6.94 [95% CI, -12.25 to -1.64]) and global stroke impact (Mann-Whitney difference, -0.23 [95% CI, -0.37 to -0.09]). A reduction in the composite outcome, cognitive impairment, dependency, and stroke impact was seen within 6 months of starting ISMN or cilostazol. URL: www.isrctn.com; Unique Identifier: ISRCTN14911850.
Irritability, characterised by heightened negative affect and emotional dysregulation, is clinically significant but understudied during antidepressant treatment. This study examined changes in irritability among patients with depression and anxiety disorders starting antidepressants. It also explored whether these changes were independent of improvements in depression and anxiety and if baseline irritability predicted outcomes. Eighty adults with depression or anxiety were followed for two months. Assessments at baseline, 2, 4 and 8 weeks included the Brief Irritability Test, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale. Statistical analyses assessed irritability changes and their association with outcomes. Irritability significantly decreased over time, independent of reductions in depression and anxiety (p < 0.001). Baseline irritability predicted depression (β = 0.185, p = 0.009) and anxiety (β = 0.195, p = 0.019) scores at two months. Irritability reductions did not differ significantly between selective serotonin reuptake inhibitors (p = 0.237). Irritability decreases independently of depressive and anxiety symptom improvements during antidepressant treatment. Baseline irritability predicts depression and anxiety levels at two months. Addressing irritability may enhance treatment and warrants further investigation. Irritability improves during antidepressant treatment, independent of depression and anxiety.Baseline irritability predicts worse depression and anxiety after two months.Significant reductions in irritability occur within two weeks of treatment.Monitoring irritability may guide treatment and benefit non-depressed patients.Further studies are needed on other antidepressants and their long-term effects.
Selecting and modifying the most appropriate therapeutic exercises at the optimal therapeutic parameters for each individual patient is a skill that can be challenging to learn and apply effectively. In this perspective, an integrative framework is presented that provides a straightforward paradigm on which to have a starting point for clinical decisions about therapeutic exercise in musculoskeletal conditions. The therapeutic exercise framework is based on a combination of three foundational constructs - physical stress on tissue, stages of tissue healing, and tissue-specific mechanobiology - all considered in the context of person-centered care. These three foundational components of the framework are interconnected, enabling clinicians to more precisely identify a patient's potential loading tolerance, implement safe and evidence-based timelines, and optimize stress-strain zones. The ultimate purpose of applying these concepts is to build tissue capacity, using the framework as a guide, to either rehabilitate injured tissue or develop more robust tissue that can manage greater functional demands.
Elevated red blood cell distribution width (RDW) is increasingly found to be associated with adverse health outcomes in older adults. We leveraged a randomized clinical trial that was investigating responses to supervised exercise (EX) with or without a topical testosterone gel (T) following hip fracture surgery to evaluate the role of RDW as a biomarker predictive of musculoskeletal outcomes. We conducted ancillary analyses of 105 women ( ≥  65 years) enrolled in the Starting a Testosterone and Exercise Program after Hip Injury (STEP-HI) clinical trial. Outcomes included muscle mass, strength measured by maximum hand grip strength and one-repetition maximum (1-RM) leg press, and physical performance assessed by six-minute walk distance, four-meter walk, and short physical performance battery (SPPB). Linear mixed-effects models were used to model each outcome at baseline, 3, and 6 months in each treatment group with baseline RDW. In the EX+T treatment group only, we observed an inverse association between RDW and SPPB at baseline, 3, and 6 months (ß = -0.266 SD per 1% increase in RDW, 95% CI [-0.499, -0.033], p = 0.02) follow-up, as well as between RDW and 1-RM leg press at 3 and 6 months (ß = -0.437 SD per 1% increase in RDW, 95% CI [-0.737, -0.136], p = 0.002) follow-up. Our findings suggest that lower RDW may be associated with greater functional benefit from a combination of supervised exercise and testosterone treatment after hip fracture surgery. These results support the concept of Precision Gerontology, which emphasizes the benefits of improving outcomes in older adults through improved targeting of inter-individual heterogeneity.