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PubMed2026

Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants.

TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25-800 mg under fasting conditions and multiple doses of 50-200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04890535.

Humans↗

PubMed2026

To Treat or Not to Treat: Navigating Early-Stage CLL in the Era of Targeted Therapy.

Chronic lymphocytic leukemia (CLL) is most frequently diagnosed at early, asymptomatic stages (Rai 0/Binet A), in which a watch-and-wait strategy remains the standard of care, based on historical trials demonstrating no overall survival benefit from early treatment. Over the past two decades, however, substantial advances in genomic profiling-including immunoglobulin heavy-chain variable region (IGHV) mutational status, TP53 disruption, recurrent gene mutations, and complex karyotype-have uncovered marked biological heterogeneity among early-stage patients and substantially improved prediction of disease progression. In parallel, targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors and venetoclax-based combinations have transformed the management of symptomatic CLL, raising renewed interest in whether early intervention might favorably alter the natural history of biologically high-risk disease. In this review, we critically examine the evolution of prognostication in early-stage CLL, integrate contemporary molecular and clinical risk models, and summarize evidence from both historical chemotherapy-era studies and modern early-intervention trials. We discuss key unresolved controversies, including reliance on surrogate endpoints, the risks of overtreatment, and the persistent absence of an overall survival benefit across all early-treatment strategies. Finally, we outline future research priorities, including refined genomic stratification, minimal residual disease-driven (MRD)-driven approaches, and combination targeted therapies currently under investigation. Despite renewed interest in preemptive treatment, available evidence supports continued observation for asymptomatic patients outside clinical trials.

Humans↗

PubMed2026

The effect of metformin on the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in adults with tuberculosis.

Metformin is under investigation as adjunctive host-directed therapy for tuberculosis (TB), which might interact with first-line TB treatment. We used population pharmacokinetic modeling to assess whether metformin alters first-line TB-drug pharmacokinetics in HIV/TB-coinfected adults without diabetes. Rifampicin, isoniazid, and pyrazinamide pharmacokinetics were investigated in participants from a randomized clinical trial of adjunctive metformin (500 mg twice daily to week 12) in adults starting HIV-associated TB treatment. Antiretroviral therapy (ART)-naïve participants initiated dolutegravir-based ART within 8 weeks. Intensive and semi-intensive sampling was conducted at week 5; concentration-time data were analyzed using non-linear mixed-effects modeling. Data from 78 individuals (43 receiving metformin, median weight 60.8 kg, 62.8% male, 79.5% on ART) were analyzed. Rifampicin and pyrazinamide were described by one-compartment models with linear elimination; typical clearances were 15.8 L/h (95% CI: 13.5-18.7) and 3.88 L/h (95% CI: 3.54-4.08), respectively. Isoniazid followed a two-compartment model with a mixture model for acetylator status; clearance was 10.5 L/h (95% CI: 9.44-11.9) in slow acetylators and 28.8 L/h (95% CI: 25.6-31.0) in fast/intermediate acetylators. Metformin reduced isoniazid bioavailability by 15.6% (95% CI: 4.45-26.4%, P < 0.009) and rifampicin bioavailability by 24.0% (95% CI: 7.83-36.3%, P < 0.007), decreasing the area under the curve from 0 to 24 h from 18.2 to 15.6 mg·h/L and from 35.9 to 27.1 mg·h/L, respectively. No significant effect on pyrazinamide was detected. We found that non-diabetic patients on metformin had lower isoniazid and rifampicin bioavailability. Lowered rifampicin exposure might be clinically relevant; simulations suggest that this could be offset by a single 150 mg rifampicin dose.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04930744.

Humans↗

PubMed2026

Targeting TP53 in triple-negative breast cancer: Molecular pathogenesis, therapeutic implications, and emerging pharmacological strategies.

Triple-negative breast cancer (TNBC) remains a highly aggressive and therapeutically challenging subtype, defined by the absence of oestrogen, progesterone, and HER2 expression. Tumour Protein 53 (TP53) mutations represent the most frequent genetic alteration, occurring in over 80% of cases and driving tumour initiation, progression, and therapeutic resistance. Mutant p53 proteins not only lose canonical tumour-suppressive functions but also often acquire gain-of-function (GOF) oncogenic properties that promote metastasis, genomic instability, and resistance to mechanisms like ferroptosis. This review examines the biological role of TP53 in TNBC pathogenesis and evaluates emerging pharmacological strategies aimed at targeting these vulnerabilities. Key approaches include the pharmacological reactivation of mutant p53 using small molecules such as APR-246, COTI-2, and the mutation-specific reactivator rezatapopt (PC14586), which has shown significant clinical tumour reduction in Y220C-mutant patients. Other strategies involve targeted protein degradation, the exploitation of synthetic lethal interactions (e.g., Chk1 or Aurora kinase B inhibition), and the use of natural products like cryptolepine or piperine derivatives. Recent clinical evidence further highlights the potential of combining epigenetic agents like decitabine with chemotherapy in TP53-mutant populations. Integrating TP53 mutation status into biomarker-driven treatment paradigms is a pivotal step toward achieving precision oncology and improving clinical outcomes for patients with TNBC.

Precision oncology↗

PubMed2026

Clinical Performance in Critical Care Simulation under Sleep Deprivation: Effects of Power Napping in the Recovery Napping Protocol for Anesthesiologist Performance (R-NAP) Randomized Controlled Trial.

BACKGROUND: Sleep deprivation is common among anesthesia residents and impairs both technical and nontechnical skills such as leadership. Napping is recommended in fatigue management across healthcare and other safety-sensitive sectors, yet its effectiveness for healthcare providers remains underexplored. This study evaluated whether a 30-min nap opportunity improved simulated crisis performance after a 24-h shift. METHODS: Residents were tested twice: once rested and once using a 24-h shift to induce partial sleep deprivation. Between sessions, they were trained in fatigue management. In the sleep-deprived condition, they were randomized to a nap opportunity or a control condition. Actigraphy objectively assessed sleep and nap duration. The primary endpoint was overall simulated clinical performance (0 to 200; combined technical and nontechnical scores). Secondary endpoints were technical and nontechnical subscales. Group effects were primarily tested using intention-to-treat regression models adjusted for rested performance, previous sleep, and critical care experience. RESULTS: Thirty-five residents were enrolled (nap opportunity, n = 19; control, n = 16). In the primary analysis sample (n = 27), clinical performance was 14.8 points higher after the nap opportunity compared with controls (95% CI, 2.8 to 26.9; P = 0.018), corresponding to a 7.4% improvement. Technical skills did not differ significantly between groups, although more sleep was associated with better technical performance. Nontechnical skills were higher in the nap opportunity condition (+11.0 points; 95% CI, 2.2 to 19.8; P = 0.016), including significant effects of leadership and resource utilization. Exploratory analyses suggested associations between longer nap duration and multiple performance domains, strongest for technical skills ( P = 0.010). CONCLUSIONS: Napping appears to enhance clinical performance, while the nap opportunity, nap duration, and previous sleep deprivation each influenced technical and nontechnical performance in distinct ways. These findings support integrating napping and recovery into medical education and scheduling.

Adult↗

PubMed2026

Phentermine/Topiramate in Obese, Diabetic Uric Acid Stone Formers: An Open-Label Randomized Feasibility Trial.

PURPOSE: The purpose of this study was to determine whether medical treatment of obesity, diabetes, and low urine pH with combination phentermine/topiramate affects uric acid (UA) kidney stone burden. MATERIALS AND METHODS: Participants with obesity, diabetes mellitus, normal renal function, urine pH < 5.8, and stone analysis ≥ 80% UA were block randomized (2:1 ratio) to phentermine 18.75 mg/topiramate 100 mg vs pragmatic controls for an 18-month, prospective, open-label feasibility study with dose escalation. The primary outcome was change in CT stone volume. Secondary outcomes included medication adherence; patient safety; and change in anthropometrics, laboratory studies, and body composition. RESULTS: Nineteen participants (age 62.1 ± 9.8 years; 68% male; mean BMI = 36.3 ± 2.9 kg/m2) were randomized, and 15 completed the study with 73% pill adherence and no serious adverse events. Stone volume by intention-to-treat analysis fell by 52% in the intervention group and rose by 8.6% in the control group (P = .10), with per-protocol analysis demonstrating statistically significant stone volume reduction (P = .02). At study end and compared with means of controls, the intervention group had greater weight loss (-10.2 vs +2.9 kg), reduction in hemoglobin A1c levels (-0.2 vs +0.5), lower 24-hour urine citrate (309 ± 81 vs 951 ± 782 mg), and lower UA supersaturation (0.7 ± 1.1 vs 1.8 ± 1.0), along with higher 24-hour urine pH (6.2 ± 0.5 vs 5.5 ± 0.4) and calcium phosphate supersaturation (0.9 ± 0.8 vs 0.2 ± 0.1; all P < .05). CONCLUSIONS: Among obese participants with diabetes mellitus and UA nephrolithiasis, phentermine/topiramate was well tolerated and demonstrated significant stone burden reductions by per-protocol analysis. The intervention group also had greater weight loss, higher urinary pH, and lower hemoglobin A1c and urinary citrate levels. These data provide a framework to study the impact of this novel alternative UA therapy on a wider range of patients with obesity and diabetes.

Aged↗

PubMed2026

The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency and promotes leaf regeneration.

Transformation is an indispensable tool for plant genetics and functional genomics. Although stable transformation in maize is no longer a major obstacle, there remains a need for accessible and efficient methods for academic laboratories. Here, we present the GGB system, a rapid and efficient approach optimized for immature embryo transformation in B104 and other maize lines. This system combines two distinct morphogenetic regulators, the wheat GRF4-GIF1 chimera and the maize BABY BOOM (BBM) transcription factor (hence the name "GGB") with a modified QuickCorn protocol, enabling regeneration of transformed maize plantlets in c. 2 months with an efficiency 7-fold higher than when compared to either morphogenic factor used in isolation. Expression of both regulators did not significantly affect development, eliminating the need to excise them after regeneration. However, transmission of the transgenic GGB construct through pollen was significantly reduced, potentially aiding transgenic line containment. We show that the GGB system is adaptable for CRISPR-Cas9 editing and reporter line generation. Furthermore, stable GGB transformants exhibited high leaf regeneration capacity via somatic embryogenesis. RNA-seq time-course profiling of GGB leaf cultures identified additional factors that could promote regeneration and led to the discovery of asparagine and trehalose as additional media components that significantly enhanced leaf regeneration.

Zea mays↗

PubMed2026

A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans↗

PubMed2026

Randomized controlled trial comparing 7-day fexuprazan-based and 14-day rabeprazole-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Fexuprazan is a newly developed potassium-competitive acid blocker used for the treatment of acid-related gastrointestinal diseases; however, clinical data regarding its efficacy in Helicobacter pylori eradication are lacking. This study evaluated the efficacy and safety of a 7-day fexuprazan-based triple therapy regimen compared with a 14-day rabeprazole-based triple therapy regimen for H. pylori infection in Korean patients. METHODS: A randomized controlled single-center study was conducted to compare the eradication rates between 7-day fexuprazan (40 mg)-based triple therapy (with 1 g amoxicillin and clarithromycin 500 mg administered twice daily) and 14-day rabeprazole (20 mg)-based triple therapy for H. pylori eradication. The primary endpoint was the success rate of H. pylori eradication, determined using the 13C-urea breath test. Safety outcomes were also evaluated. RESULTS: A total of 79 patients were randomly assigned to the fexuprazan and rabeprazole groups. In the full analysis set, eradication rates were 80.00% (32/40) in the fexuprazan group and 82.05% (32/39) in the rabeprazole group. In the per-protocol set, eradication rates were 83.78% (31/37) and 88.89% (32/36), respectively (P = 1.000 and P =.737). The overall incidence of treatment-emergent adverse events was 70.00% (28/40) in the fexuprazan group and 66.67% (26/39) in the rabeprazole group, with no significant difference between groups (P =.812); both regimens were well tolerated. Among patients with clarithromycin-susceptible strains in full analysis set, eradication rates were 93.10% (27/29) in the fexuprazan group and 87.09% (27/31) in the rabeprazole group (P =.672). In the per-protocol set, eradication rates for susceptible strains were 96.42% (27/28) in the fexuprazan group and 93.10% (27/29) in the rabeprazole group (P = 1.000). CONCLUSION: Seven-day fexuprazan-based triple therapy demonstrated eradication efficacy comparable with that of 14-day rabeprazole-based therapy in treatment-naïve Korean patients with H. pylori infection. The fexuprazan-based regimen showed a similar safety profile and comparable incidence of adverse events with that of the rabeprazole-based regimen.

Humans↗

PubMed2026

Complete genome sequence of the Anaplasma phagocytophilum clinical isolate NCH-1.

Anaplasma phagocytophilum is an obligate intracellular gram-negative bacterium and etiologic agent of human granulocytic anaplasmosis. A. phagocytophilum genomic sequencing has historically been performed via short-read platforms. Our optimized bacterial isolation protocol combined with Nanopore sequencing produced a single, closed 1,481,805 bp circular A. phagocytophilum strain NCH-1 chromosome.

Anaplasma phagocytophilum↗

PubMed2026

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using χ2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6 months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p < 0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p > 0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans↗

PubMed2026

Effectiveness of Yoga and Combined Exercise in Female With Rheumatoid Arthritis: Randomized Controlled Trial.

BACKGROUND: Although exercise is beneficial for Rheumatoid Arthritis (RA), the comparative efficacy of different modalities for patients in clinical remission remains unclear. This study compared the short- and long-term effects of yoga versus a combined exercise programme on pain, balance, mobility, fatigue, depression, and quality of life in females with RA in remission. METHODS: In this single-blind, randomized controlled trial, 74 female participants were allocated to yoga (n = 25), combined exercise (n = 25), or a usual care control group (n = 24). The intervention groups underwent an 8-week supervised programme. Clinical assessments, including the Visual Analogue Scale (pain), Berg Balance Scale, Timed Up and Go Test, Beck Depression Inventory, Fatigue Severity Scale, and Short Form-36, were conducted at baseline, post-intervention (8 weeks), and follow-up (20 weeks). RESULTS: Both intervention groups demonstrated significant improvements in all outcome measures compared with the control group at post-treatment and follow-up (p < 0.05). Notably, the yoga group exhibited superior outcomes compared to the combined exercise group in reducing pain intensity (median reduction of 4.00 vs. 2.00 points; p < 0.001, η2 = 0.724), as well as in physical function, balance, fatigue, depression, and quality of life at the 20-week follow-up. These benefits may be partly attributed to the incorporation of breathing and relaxation techniques inherent to yoga practice. CONCLUSIONS: Both 8-week yoga and combined exercise programs are effective in managing residual symptoms in females with RA in clinical remission. However, yoga appears to provide superior benefits in pain management and psychosocial well-being, supporting its integration into multidisciplinary RA management protocols, particularly for addressing psychosocial burden in patients achieving remission. TRIAL REGISTRATION: This study was retrospectively registered at NCT07072754 (clinicaltrials.gov).

Humans↗

PubMed2026

Pricing Combination Therapies: A Systematic Review of Value Attribution, Cost-Sharing Mechanisms and Policy Frameworks.

BACKGROUND: Combination therapies are increasingly central to modern pharmacotherapy, particularly in oncology and other high-burden diseases. However, pharmaceutical pricing and reimbursement systems remain largely designed for single-product-single-indication interventions. When multiple patented medicines are used together, especially when owned by different manufacturers, conventional pricing frameworks may struggle to align prices with the value of the combination while preserving incentives for innovation and timely patient access. OBJECTIVE: To identify, describe, and critically assess the methods, models, and policy frameworks proposed in the literature to establish prices for combination therapies, with particular attention to value attribution mechanisms, cost-sharing arrangements between manufacturers, and budget impact considerations. METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines and a pre-registered Open Science Framework protocol. Searches were performed in MEDLINE, Scopus, Web of Science, EconLit, CRD databases, and grey literature sources for publications up to July 2025. Eligible studies analysed pricing approaches, economic models, reimbursement mechanisms, or policy frameworks relevant to combination therapies, including more recent multi-indication pricing literature. Given the heterogeneity of the literature, findings were synthesized using a structured narrative and thematic approach. RESULTS: Sixty-nine studies met the inclusion criteria. The literature was dominated by conceptual and policy analyses, with relatively few empirical or implementation-oriented studies. Value attribution emerged as the central methodological challenge in pricing combination therapies. Several complementary approaches were proposed to operationalise value attribution, including adaptations of indication- or pathway-based pricing, manufacturer cost-sharing arrangements, managed entry agreements, and outcome-based reimbursement mechanisms. Empirical evidence suggests that health systems continue to rely primarily on pragmatic and often partial solutions rather than fully specified pricing frameworks. A complementary review of the multi-indication pricing literature indicates that, although the two fields address different pricing problems, they share important methodological and institutional lessons that can inform the development of pricing frameworks for combination therapies. CONCLUSIONS: The literature provides a growing repertoire of conceptual approaches for pricing combination therapies but limited empirical evidence on implementation. Pricing frameworks should place value attribution at their core while combining complementary policy mechanisms adapted to national pricing and reimbursement systems. Lessons from multi-indication pricing provide a valuable foundation but require additional governance mechanisms to address value attribution, multi-manufacturer negotiation, and implementation challenges specific to combination therapies.

Journal Article↗

PubMed2026

MIS-TLIF Versus Open TLIF in Combined Lumbar Stenosis and Low-Grade Spondylolisthesis : Of Discharge Timing and Treatment Pricing.

STUDY DESIGN: An open-label, randomized, noninferiority clinical trial. OBJECTIVE: To determine the effectiveness of the MIS-TLIF over the O-TLIF in patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis by comparing the clinical efficacy and safety. SUMMARY OF BACKGROUND DATA: In patients with combined lumbar spinal stenosis and spondylolisthesis, it remains uncertain whether minimally invasive fusion surgery is noninferior to the open approach. MATERIALS AND METHODS: We conducted an open-label, noninferiority trial involving patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis. Patients were randomly assigned in a 1:1 ratio to undergo either MIS-TLIF or open TLIF surgery. The primary endpoint was the reduction in the Oswestry disability index (ODI) score from baseline to three months postsurgery, with a noninferiority margin of 12 points. Secondary outcomes included three-month changes from baseline in back and leg pain, neuropathic pain, satisfaction with treatment, intraoperative data, and cost-effectiveness. RESULTS: In the modified intention-to-treat population, the mean difference was 0.4, with the corresponding 90% CI of -5.7 to 6.5, having a lower bound below the noninferiority margin of 12. Similar results were obtained by analysis of the per-protocol population. 82.8% of patients achieved the MCID for the ODI. Results for secondary outcomes (clinical scales, complications) showed no significant differences between the treatment groups (all P >0.05). Although the open TLIF group had a hospital stay that was 1.5 days longer ( P =0.005) and required additional analgesia more frequently ( P =0.026), direct costs were 10.5% higher in the MIS-TLIF group ( P <0.001). CONCLUSIONS: This is the first high-quality study comparing open TLIF and MIS-TLIF with a validated primary endpoint. Among patients with combined lumbar degenerative stenosis and degenerative spondylolisthesis, MIS-TLIF resulted in clinical outcomes at three months that were noninferior to those with open TLIF.

Humans↗

PubMed2026

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans↗

PubMed2026

Impact of creatine supplementation alone or combined with exercise on inflammatory and clinical outcomes in chronic musculoskeletal pain treated in the rheumatological field: a systematic review.

Creatine supplementation has demonstrated ergogenic and anabolic effects in healthy and clinical populations. However, its potential therapeutic role in individuals with chronic musculoskeletal pain treated in rheumatological contexts remains unclear. The aim was to evaluate the efficacy and safety of creatine supplementation on pain, physical function/disability, quality of life, muscle strength, skeletal muscle mass, and inflammatory markers in people with chronic musculoskeletal pain usually treated from the rheumatological field. A systematic review was conducted following PRISMA guidelines. Searches were performed in MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE up to July 2026. Eligible studies were randomized or nonrandomized clinical trials that provided creatine supplementation alone or in combination with exercise as a treatment compared to a control or placebo group. Eight studies (n = 189) were included, encompassing fibromyalgia, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis. Creatine dosages varied from chronic low-dose to loading protocols (20 g/d, 2-5 g/d). Combined creatine plus resistance training may improve strength, skeletal muscle mass, and quality of life beyond exercise alone in osteoarthritis. Trials on fibromyalgia suggest an increase in muscle strength, but inconsistent effects on pain. Rheumatoid arthritis studies suggest gains in skeletal muscle mass and, in pilot studies, reduced disease activity. No major adverse events were reported. In conclusion, creatine supplementation alone may be insufficient to obtain clinical benefits, while combined with resistance exercise it could offer potential benefits for muscle strength, skeletal muscle mass and certain aspects of quality of life in these clinical conditions. However, evidence on pain and inflammation remains limited; Furthermore, the response across different clinical conditions is heterogeneous, highlighting the need for larger, high-quality trials.

Humans↗

PubMed2026

Effects of blood flow restriction training combined with plyometric training on lower limb muscle strength and motor unit recruitment in basketball players: An experimental study.

OBJECTIVE: Previous studies have shown that plyometric training (PT) improves neuromuscular function and explosive power but not maximal strength. Blood flow restriction training (BFR) combined with low-intensity resistance training (RT) increases muscle mass and strength. This study investigated the effects of PT, and BFR combined with PT on lower-limb muscle function. METHODS: Twenty elite basketball players were randomly assigned to two groups: PT-alone group (PT, n = 10) and BFR combine with PT group (PT-BFR, n = 10). All participants underwent bodyweight-based plyometric training three times per week for eight weeks. Peak torque values for hip and knee flexion and extension, as well as root mean square (RMS) values derived from electromyography, were measured before and after the intervention. RESULTS: After the 8-week intervention, both groups showed significant improvements in knee flexion and extension peak torque at 180°/s (all p < 0.01). Between-group comparisons revealed greater gains in the PT-BFR group for hip extension and flexion at 60°/s (p = 0.036-0.002; ηp2 = 0.225-0.233). RMS of the rectus femoris increased significantly more in the PT-BFR group than in the PT group (right: p = 0.004, ηp2 = 0.385; left: p = 0.020, ηp2 = 0.266), whereas no significant changes were observed in the gastrocnemius, tibialis anterior, or biceps femoris (all p > 0.05). CMJ height also improved more in the PT-BFR group, with a significant group × time interaction (p = 0.042, ηp2 = 0.210). CONCLUSION: Both training protocols enhanced bilateral lower-limb strength, with notable gains in the non-dominant leg; however, the magnitude did not differ substantially between groups. In contrast, compared with PT alone, BFR combined with PT produced superior enhancements in lower-limb muscle strength and neuromuscular recruitment. These findings suggest that when PT is employed to improve explosive power, it may be effectively combined with BFR to further augment muscular strength.

Humans↗

PubMed2026

Effects of different resistance exercise programs on upper limb functional recovery in postoperative breast cancer patients.

PURPOSE: To investigate the effects of grip strength exercise combined with upper limb resistance exercise on upper limb functional rehabilitation in patients after breast cancer surgery. METHODS: A total of 111 patients who underwent either modified radical mastectomy with ALND or breast-conserving surgery with ALND were randomly assigned to a control group, an upper limb resistance exercise group, and a combined grip and upper limb resistance exercise group. Grip strength was measured at baseline, 16 weeks after intervention, and at 3- and 6-month follow-ups, while shoulder function was assessed using the Constant-Murley Scale (CMS). RESULTS: There were no statistically significant differences in grip strength or CMS scores among the groups before intervention (P > 0.05). At the post-intervention, 3-month, and 6-month follow-ups, compared with the control group, both resistance training protocols significantly improved patients' joint range of motion, pain, muscle strength, total CMS score, and grip strength (P < 0.05). Compared with the upper limb resistance exercise group, the combined grip and upper limb resistance exercise group demonstrated superior grip strength at the 6-month follow-up (P < 0.05), as well as more significant improvements in joint range of motion, pain, muscle strength, and total CMS scores (P < 0.05). CONCLUSION: A 16-week resistance exercise program effectively improves upper limb function in post-surgical breast cancer patients, with the combined grip and upper limb resistance exercise program yielding superior outcomes.

Humans↗