Mariam A Ibrahim, Bassant Abdelhameed, Amir Beltagi, Mohammad Masoud, Sara Abdel-Aal Mohamed, Ahmed A Khalifa
{"title":"Convection-based <i>vs</i> conduction-based cooling in rehabilitation: A cadaveric porcine study of surface and intra-articular temperature reduction.","authors":"Mariam A Ibrahim, Bassant Abdelhameed, Amir Beltagi, Mohammad Masoud, Sara Abdel-Aal Mohamed, Ahmed A Khalifa","doi":"10.5493/wjem.124656","DOIUrl":"https://doi.org/10.5493/wjem.124656","url":null,"abstract":"<p><strong>Background: </strong>Postoperative inflammation after joint injury or surgery contributes to pain, edema, and delayed functional recovery. Cryotherapy is commonly used to alleviate pain and modulate inflammatory responses; however, the effectiveness of various cooling modalities in reducing temperatures in deeper periarticular and intra-articular tissues remains uncertain.</p><p><strong>Aim: </strong>To compare the cooling performance of a convection-based cryotherapy system with two circulating-pad cooling systems in reducing temperature at various tissue depths.</p><p><strong>Methods: </strong>A cadaveric porcine knee model was used to assess comparative thermal transfer in periarticular tissues and the joint space. Thermocouples were placed at three sites: Subdermal, intramuscular, and intra-articular. Four experimental cooling conditions were evaluated by using: SootheAway 1 (SA1), SootheAway 2 (SA2), ThermoCuff (convection-based), and ambient control. Each cooling session lasted 60 minutes using a target coolant/air temperature of 35 °F (1.6 °C). The prespecified primary endpoint was the change in temperature at 20 minutes (ΔT20 = T20 - T0).</p><p><strong>Results: </strong>ThermoCuff produced a larger observed early temperature reduction through the tested compartments. At the subdermal level, ΔT20 was -14.8 °C with ThermoCuff compared with -8.4 °C for SA2, -3.9 °C for SA1, and -1.8 °C for ambient exposure. Intramuscular cooling was modest with ThermoCuff (-1.8 °C) and SA2 (-1.3 °C), whereas SA1 showed warming (+6.5 °C). At the intra-articular level, ThermoCuff achieved the highest temperature reduction (-10.0 °C), compared with -3.9 °C for SA2 and -3.3 °C for ambient exposure; SA1 showed warming (+4.8 °C).</p><p><strong>Conclusion: </strong>In the cadaveric porcine knee model, the convection-based system achieved better early cooling than the circulating-pad systems, especially at the subdermal and intra-articular levels. These preliminary preclinical findings support the hypothesis that cooling modality might affect the depth and magnitude of thermal transfer under controlled laboratory conditions and require <i>in vivo</i> confirmation before clinical translation.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"124656"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matteo Capobianco, Francesco Cappellani, Ehimare Enaholo, Marco Zeppieri
{"title":"Corneal nerve imaging in systemic neuropathy: A minireview of experimental and precision medicine applications.","authors":"Matteo Capobianco, Francesco Cappellani, Ehimare Enaholo, Marco Zeppieri","doi":"10.5493/wjem.126036","DOIUrl":"https://doi.org/10.5493/wjem.126036","url":null,"abstract":"<p><p>Small-fiber neuropathy is a common complication of metabolic, neurodegenerative, and treatment-related disorders. Early detection can be challenging because established diagnostic approaches may be invasive, resource-intensive, or relatively insensitive to early small-fiber injury. Corneal confocal microscopy (CCM) is a rapid, noninvasive imaging technique that enables quantitative assessment of the corneal subbasal nerve plexus and has been proposed as a biomarker of peripheral small-fiber damage. This minireview critically evaluates the role of CCM for early detection, diagnostic testing, prognostic stratification, longitudinal follow-up, and treatment response assessment in systemic neuropathies, particularly diabetic peripheral neuropathy (DPN). Evidence is strongest in DPN, in which CCM consistently demonstrates group-level corneal nerve loss; however, individual diagnostic performance is only moderate and varies according to patient spectrum, reference standard, sampling protocol, analysis method, and diagnostic threshold. Evidence in other neurologic diseases, including Parkinson's disease, multiple sclerosis, and chemotherapy-induced peripheral neuropathy, is less robust. Advancements in automated image analysis and artificial intelligence have improved reproducibility and efficiency of corneal nerve quantification in recent years. Nevertheless, widespread implementation in the clinics is still hampered by methodological heterogeneity, lack of full standardization, and absence of universally validated diagnostic and prognostic cut-off points. CCM is therefore a promising tool for translational research and precision medicine, but population-level differences in corneal nerve parameters should not be interpreted as establishing an individual diagnosis. At present, CCM should complement rather than replace established clinical, neurophysiological, functional, and pathological assessments, including quantitative sensory testing and skin biopsy when clinically indicated. Before integration into clinical practice can be recommended, multi-center prospective studies utilizing standardized acquisition and analysis protocols, validated thresholds, and clinically meaningful patient outcomes are required.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"126036"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Culture conversion and drug susceptibility in drug-resistant pulmonary tuberculosis with type 2 diabetes mellitus on oral regimens.","authors":"Yogita Vats, Ajay Kumar Verma, Jyoti Bajpai, Surya Kant, Parul Jain, Darshan Bajaj, Anand Srivastava, Ram Avadh Singh Kushwaha, Santosh Kumar, Rajiv Garg, Ankit Kumar, Akshyaya Pradhan","doi":"10.5493/wjem.122305","DOIUrl":"https://doi.org/10.5493/wjem.122305","url":null,"abstract":"<p><strong>Background: </strong>The simultaneous existence of multidrug-resistant pulmonary tuberculosis (MDR-PTB) and type 2 diabetes mellitus (T2DM) represents a rising threat in high-burden countries such as India. Diabetes has been associated with impaired immune responses and delayed bacteriological clearance, thereby compromising treatment outcomes in patients with multidrug-resistant tuberculosis receiving all-oral longer regimens.</p><p><strong>Aim: </strong>Impact of T2DM on clinical profile, radiological severity, drug resistance patterns, and sputum culture conversion in MDR-PTB.</p><p><strong>Methods: </strong>This prospective observational study included 264 adults with microbiologically confirmed MDR-PTB treated at a tertiary care center in North India over a 12-month period. The participants were classified as diabetic, pre-diabetic, or non-diabetic according to the American Diabetes Association 2023 criteria. Clinical, radiological, microbiological, and drug susceptibility data were analyzed. Time to culture conversion and treatment outcomes were compared across groups using appropriate statistical tests.</p><p><strong>Results: </strong>Patients with diabetes were older and had higher rates of dyspnea and hemoptysis. Radiologically, they demonstrated significantly higher rates of bilateral lung involvement and lower zone involvement. A higher bacillary load and increased prevalence of <i>inhA</i> and <i>katG</i> mutations were observed among patients with diabetes. Mean time to sputum culture conversion was significantly prolonged in patients with diabetes (132.9 ± 22.3 days) compared with pre-diabetic patients (112.6 ± 7.6 days) and non-diabetic patients (96.9 ± 10.8 days) (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>T2DM adversely affects bacteriological response, radiological severity, and treatment outcomes in patients with MDR-PTB on all-oral longer regimens.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"122305"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olamide Wilson Fasakin, Ayoola Awosika, Funmilayo Mercy Ojo, Ayodeji Samuel Boboye
{"title":"Effects of Kalanchoe pinnata, exercise, and stimulation on neuroinflammation, redox homeostasis, and neuropathic pain in a Wistar-rat model.","authors":"Olamide Wilson Fasakin, Ayoola Awosika, Funmilayo Mercy Ojo, Ayodeji Samuel Boboye","doi":"10.5493/wjem.124614","DOIUrl":"https://doi.org/10.5493/wjem.124614","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain is a persistent, treatment-resistant condition driven not only by peripheral nerve injury but also by maladaptive neuroplasticity in central pain-regulatory networks. Evidence increasingly points to dysfunction in the prefrontal cortex (PFC), a vital area for top-down control of pain, emotions, and autonomic functions, as a key factor in maintaining pain hypersensitivity.</p><p><strong>Aim: </strong>To examine the combined effects of Kalanchoe pinnata (KP), treadmill exercise, and vagus nerve stimulation (VNS) on neuroinflammation, redox homeostasis, and neuropathic pain in a rat model.</p><p><strong>Methods: </strong>Neuropathic pain was induced <i>via</i> partial sciatic nerve ligation. KP was administered orally at an effective dose of 100 mg/kg. Rats were assigned to 7 groups: (1) Sham; (2) Partial sciatic nerve ligation-neuropathic pain-induced; (3) Gabapentin; (4) KP alone; (5) KP + exercise; (6) KP + VNS; and (7) KP + exercise + VNS. Pain behaviors were assessed using mechanical allodynia and thermal hyperalgesia tests. Biochemical analysis of the PFC measured oxidative stress markers, pro-inflammatory cytokines [nuclear factor-kappa B, tumor necrosis factor alpha, interleukin (IL)-1β, IL-6], anti-inflammatory cytokine (IL-10), nitric oxide, monoaminergic and cholinergic biomarkers. Molecular analysis measured nuclear factor erythroid 2-related factor 2, heme-oxygenase 1, Kelch-like ECH-associated protein 1, B-cell lymphoma 2 associated X-protein, B-cell lymphoma 2, caspase-3, brain-derived neurotrophic factor, and cAMP response element-binding protein in the PFC.</p><p><strong>Results: </strong>Results showed that treatments significantly (<i>P</i> < 0.05) reduced pain behaviors compared to untreated controls. Treatments also significantly (<i>P</i> < 0.05) decreased lipid peroxidation, lowered pro-inflammatory cytokine levels, increased antioxidant activity, and restored the balance between neuronal and apoptotic processes. The combination therapies produced greater biochemical normalization than KP monotherapy, suggesting enhanced therapeutic responses through multimodal intervention. The triple treatment produced the most notable effects, significantly normalizing multiple inflammatory and redox parameters.</p><p><strong>Conclusion: </strong>KP alleviated neuropathic pain, and the enhancement with exercise and VNS highlights the potential of multimodal strategies targeting cortical pain-control networks. This therapeutic approach demonstrates potential as a multimodal preclinical strategy for neuropathic pain management and warrants further investigation.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"124614"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.","authors":"Tapesh Lalotra, Arunagiri Gunasekar, Naveen Jeyaraman, Arulkumar Nallakumarasamy, Sathish Muthu, Viji Devanand, Madhan Jeyaraman","doi":"10.5493/wjem.120531","DOIUrl":"https://doi.org/10.5493/wjem.120531","url":null,"abstract":"<p><p>Osteoclastic bone diseases represent a significant health burden, especially in an aging population, due to imbalances in bone homeostasis that result in postmenopausal osteoporosis, inflammatory arthritis, malignancy-induced bone disease and secondary metabolic conditions, which result in fragility fractures, disability and death. Although advances in imaging and pharmacology have enhanced management, existing diagnostic strategies have poor sensitivity in detecting early-stage pathological changes or fracture risk. The NF-kappaB/receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) pathway is important in bone turnover regulation, which is dysregulated in bone degradation, leading to increased osteoclast numbers and bone degradation. Circular levels of RANKL and OPG, particularly the RANKL/OPG ratio, have shown potential as biomarkers for early diagnosis, monitoring, and evaluating therapeutic response, with the RANKL/OPG ratio reflecting the balance of osteoclastogenic activity in the bone microenvironment and correlating with bone mineral density, fracture risk, and bone pathology. It exhibits lower biological variability and enhanced sensitivity for early disease detection compared with individual markers. This review assesses the experimental, translational and clinical evidence for the predictive and monitoring potential of RANKL and OPG, and correlations between various imaging techniques and circulating biomarkers to gain insight into disease progression. We explore and discuss the limitations with regards to methodological issues, assay variability and biological variability, and the therapeutic implications of modulating the RANKL/OPG axis, highlighting its potential in informing treatment approaches and improving outcomes in bone resorptive diseases.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"120531"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone-specific alkaline phosphatase as a marker of bone formation: Clinical and imaging correlates.","authors":"Pooja Jayaraman Thirunavukkarasu, Arunagiri Gunasekar, Naveen Jeyaraman, Arulkumar Nallakumarasamy, Viji Devanand, Sanjeevi Bharadwaj, Madhan Jeyaraman","doi":"10.5493/wjem.121518","DOIUrl":"https://doi.org/10.5493/wjem.121518","url":null,"abstract":"<p><p>Bone-specific alkaline phosphatase (BSAP) is a biochemical marker of bone formation, reflecting osteoblast function and bone turnover. Unlike bone mass and structure measurements using dual-energy X-ray absorptiometry or high-resolution peripheral quantitative computed tomography, BSAP does not directly measure bone mass or microarchitecture but provides dynamic information on bone metabolism. BSAP has high specificity for bone formation with low biological variability and consistent levels across many clinical conditions, making it a reliable biochemical indicator of bone turnover, especially early response to anabolic treatment and in high-turnover bone conditions. Biologically, BSAP is synthesized by osteoblasts and is important in matrix maturation and mineralisation. In clinical practice, BSAP increases with anabolic treatment, often before changes in bone density, and is thus a predictor of early treatment response. Low levels of BSAP are found in conditions with delayed fracture healing, such as hypophosphatasia, and high levels are found in high-turnover conditions such as Paget's disease. BSAP also has a role in conditions such as chronic kidney disease, where it can discriminate between states of bone turnover. However, its use is hampered by variability between laboratories, the absence of reference ranges, and the lack of normative data in different populations. Novel methods combining BSAP with innovative imaging techniques have the potential to improve personalised diagnosis, but need further research. This review highlights the potential of BSAP as an adjunct biomarker in use in early diagnosis, monitoring therapeutic intervention and overall assessment of bone metabolism for clinical decision making in metabolic bone diseases in conjunction with imaging.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"121518"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Putri Nila Kandi, M Harun Iskandar, Harry Akza Putrawan, Risna Halim Mubin, Syakib Bakri, Hasyim Kasim, Suriani Alimuddin, Resha Dermawansyah Rusman, Arifin Seweng
{"title":"Bacterial load and transforming growth factor-beta: Predicting the extent of lung damage in pulmonary tuberculosis patients.","authors":"Putri Nila Kandi, M Harun Iskandar, Harry Akza Putrawan, Risna Halim Mubin, Syakib Bakri, Hasyim Kasim, Suriani Alimuddin, Resha Dermawansyah Rusman, Arifin Seweng","doi":"10.5493/wjem.120424","DOIUrl":"https://doi.org/10.5493/wjem.120424","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary tuberculosis (TB) remains a significant global health burden, with disease severity determined by the complex interplay between pathogen burden and host immune responses. Mycobacterial load and serum transforming growth factor-beta (TGF-β) are parameters potentially associated with disease progression and pulmonary tissue damage. TGF-β, as an immunoregulatory cytokine, plays a dual role in TB pathogenesis by suppressing protective immunity while contributing to fibrotic tissue remodeling. Despite their clinical relevance, the direct correlation between bacterial load, serum TGF-β, and radiological lesion extent in newly diagnosed patients remains insufficiently clarified in high-burden clinical settings.</p><p><strong>Aim: </strong>To analyze the correlation between bacterial load, serum TGF-β, and radiological lesion extent in newly diagnosed pulmonary TB patients.</p><p><strong>Methods: </strong>This observational study employed a cross-sectional design involving 60 newly diagnosed pulmonary TB patients at Haji Regional General Hospital, Makassar. Laboratory examinations were conducted at the Hasanuddin University Medical Research Laboratory, Faculty of Medicine. Bacterial load was assessed using semi-quantitative categories of the Xpert MTB/RIF rapid molecular test, serum TGF-β levels were measured using the enzyme-linked immunosorbent assay, and radiological lesion extent was classified based on chest radiography into minimal <i>vs</i> moderate-extensive categories. Bivariate statistical tests were performed for analysis.</p><p><strong>Results: </strong>A total of 60 newly diagnosed pulmonary TB patients were enrolled, with the majority being male (44 patients, 73.3%) and 16 female patients (26.7%). In terms of age, 70.0% were below 60 years and 30.0% were 60 years or older. Based on body mass index, 41.7% were underweight, 51.7% normal weight, and 6.7% overweight. Moderate-extensive lesions were observed in 85.0% of patients, while 56.7% had medium-high bacterial load. A statistically significant association was found between bacterial load and lesion extent (<i>P</i> = 0.032), with the medium-high group demonstrating a markedly higher risk of moderate-extensive lesions (odds ratio = 5.895; 95% confidence interval: 1.109-31.340). No significant associations were identified between serum TGF-β levels and lesion extent (<i>P</i> = 0.676) or bacterial load (<i>P</i> = 0.622).</p><p><strong>Conclusion: </strong>High bacterial load predicts severe radiological lung damage in TB, but systemic TGF-β does not reflect disease extent, suggesting localized activity and need for further tissue-level investigation.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"120424"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayrton Bangolo, Sarvarinder Gill, Lili Zhang, Jiahe Zhao, Behzad Amoozgar, Ronit Reich-Slotky, Justin Tran, Tri Vo, Gabby Mariblanca, Xenia Balulescu, Sean Mcknight, Nidhi Patel, Aidan Reed, Sukhmani Kaur, Shalini Subramanian, Julie Katyal, Christo Manikkuttiyil, Morgan Chakov, Alisa Nguyen, Sanjana Pashine, Andre Khalil, Steven Mathew, Ravdeep Gill, Varun Andrews, Philip Ordonez, Benjamin Olson, Marianne Koleng, Rajin Persaud, Hrithik S Saride, Mikhail Dharsi, Romon Thach, Winnie Chen, Mahad Shahid, Simcha Weissman, David Siegel, Harsh Parmar, Noa Biran, David H Vesole, Pooja Phull
{"title":"Real-world outcomes for multiple myeloma patients after apheresis for planned chimeric antigen receptor T-cell therapy.","authors":"Ayrton Bangolo, Sarvarinder Gill, Lili Zhang, Jiahe Zhao, Behzad Amoozgar, Ronit Reich-Slotky, Justin Tran, Tri Vo, Gabby Mariblanca, Xenia Balulescu, Sean Mcknight, Nidhi Patel, Aidan Reed, Sukhmani Kaur, Shalini Subramanian, Julie Katyal, Christo Manikkuttiyil, Morgan Chakov, Alisa Nguyen, Sanjana Pashine, Andre Khalil, Steven Mathew, Ravdeep Gill, Varun Andrews, Philip Ordonez, Benjamin Olson, Marianne Koleng, Rajin Persaud, Hrithik S Saride, Mikhail Dharsi, Romon Thach, Winnie Chen, Mahad Shahid, Simcha Weissman, David Siegel, Harsh Parmar, Noa Biran, David H Vesole, Pooja Phull","doi":"10.5493/wjem.125753","DOIUrl":"10.5493/wjem.125753","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor T-cell (CAR-T) therapy is highly active in relapsed/refractory multiple myeloma (RRMM), but manufacturing creates an obligatory waiting period between apheresis and infusion. Patients may deteriorate, progress or die during this window. Analyses that begin follow-up at infusion exclude these patients entirely and cannot describe the experience of all patients who enter the CAR-T pathway.</p><p><strong>Aim: </strong>To describe, in an intention-to-collect fashion, the outcomes of all RRMM patients who underwent T-cell apheresis for planned CAR-T therapy; to characterise the apheresis-to-infusion interval and the reasons for, and correlates of, failure to reach infusion; and to report progression-free survival (PFS) and overall survival (OS) anchored at the date of apheresis. The study was descriptive; it was not designed to estimate the causal effect of CAR-T infusion on survival.</p><p><strong>Methods: </strong>Retrospective single-centre cohort of all RRMM patients undergoing T-cell apheresis for CAR-T at Hackensack University Medical Center between 1 January 2021 and 30 April 2024. PFS and OS were calculated from apheresis by the Kaplan-Meier method with Greenwood 95% confidence intervals (CIs) and numbers at risk. Groups were compared with the log-rank test; baseline characteristics with the Wilcoxon rank-sum and Fisher exact tests. Because infusion is a post-baseline, time-dependent event, the association between infusion and survival was additionally examined using a Mantel-Byar time-dependent Cox model and a 60-day landmark analysis. Correlates of non-infusion were examined by univariable logistic regression; multivariable modelling was not performed owing to the small number of events.</p><p><strong>Results: </strong>Of 99 patients undergoing apheresis, 87 (87.9%, 95%CI: 79.8-93.6) were infused and 12 (12.1%, 95%CI: 6.4-20.2) were not. Median follow-up was 14.0 months [interquartile range (IQR): 8.2-20.7]. Median apheresis-to-infusion interval was 54 days (IQR 46-62; range 37-202; <i>n</i> = 84 evaluable). Contrary to our preliminary report, baseline disease phenotype differed significantly between groups: Extramedullary disease was present in 9/12 (75.0%) non-infused <i>vs</i> 17/87 (19.5%) infused patients (<i>P</i> < 0.001), and plasma cell leukaemia in 3/12 (25.0%) <i>vs</i> 3/87 (3.4%) (<i>P</i> = 0.017). Age, prior lines of therapy (median 5 in both), high-risk cytogenetics (36.4% <i>vs</i> 34.1%) and Revised International Staging System distribution did not differ. The commonest reasons for non-infusion were progressive disease or myeloma-related death (7/12, 58.3%), non-myeloma death (2/12, 16.7%), manufacturing or collection failure (2/12, 16.7%) and infection (1/12, 8.3%). The median time from apheresis to the attrition event was 44 days (IQR 30-72). Median PFS from apheresis was 17.5 months (95%CI: 12.7-21.6) in infused patients <i>vs</i> 1.5 months (95%CI: 0.8-2.3) in no","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"125753"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marina A Senchukova, Azamat T Ishemgulov, Sergey N Letuta, Natalia V Saidler, Dmitry G Tagabilev
{"title":"Changes in the metabolism of axillary lymph node cells as a predictor of regional metastasis in breast cancer.","authors":"Marina A Senchukova, Azamat T Ishemgulov, Sergey N Letuta, Natalia V Saidler, Dmitry G Tagabilev","doi":"10.5493/wjem.125128","DOIUrl":"https://doi.org/10.5493/wjem.125128","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have shown that the delayed luminescence of erythrosine (DLE) indicators differs between tumor and nontumor breast tissue in patients with breast cancer (BC).</p><p><strong>Aim: </strong>To study the features of metabolism of axillary lymph node (ALN) cells and their relationship with regional metastasis in BC patients.</p><p><strong>Methods: </strong>This prospective, single-center, observational cohort study included 69 patients with newly diagnosed BC. DLE indicators were measured for 152 ALNs. DLE decay kinetics were recorded using flash photolysis. A control circuit interfaced the analog measuring devices and digital data processing systems. Eighty-eight and 74 ALN samples were stained with antibodies against vascular cell adhesion molecule-1 (VCAM-1) and C-X-C motif chemokine receptor 4 (CXCR4), respectively. Statistical calculations were performed using Statistica version 12.0 software.</p><p><strong>Results: </strong>Singlet oxygen-sensitized delayed fluorescence (SOSDF) indicators were significantly lower, whereas phosphorescence and thermally activated delayed fluorescence indicators were significantly higher in ALNs with metastases than in those without metastases (<i>P</i> < 0.0001). Pronounced VCAM-1 expression in ALNs was significantly more common in patients with tumor grade 3 and human epidermal growth factor receptor 2 (HER2) overexpression and in patients with HER2-positive BC. Pronounced CXCR4 expression in lymph node (LN) follicles was detected significantly more often in patients with metastases in ALNs and with lymphovascular invasion. The intensity of delayed phosphorescence positively correlated with both VCAM-1 and CXCR4 expression in the LN follicles, and VCAM-1 expression in the LN follicles was negatively correlated with SOSDF and positively correlated with the duration of delayed phosphorescence.</p><p><strong>Conclusion: </strong>These results indicate that metastatic LNs exhibit greater oxygen consumption by tumor cells and that changes in tumor cell metabolism are associated with increased CXCR4 and VCAM-1 expression in ALNs.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 3","pages":"125128"},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rupak Desai, Darsh Patel, Abhishek Prasad, Navya Mandalapu, Jai Nagarajan, Ananth Guddeti, Sourabh Khatri, Warda Shahnawaz, Abdul Aleem, Adil S Mohammed, Umera Yasmeen, Muhammad Usman Ghani
{"title":"Genetic and biological determinants of pulmonary embolism: Insights from Mendelian randomization studies.","authors":"Rupak Desai, Darsh Patel, Abhishek Prasad, Navya Mandalapu, Jai Nagarajan, Ananth Guddeti, Sourabh Khatri, Warda Shahnawaz, Abdul Aleem, Adil S Mohammed, Umera Yasmeen, Muhammad Usman Ghani","doi":"10.5493/wjem.v16.i2.121046","DOIUrl":"10.5493/wjem.v16.i2.121046","url":null,"abstract":"<p><p>Pulmonary embolism (PE) is a common and potentially fatal thromboembolic disease contributing to a major global public health burden. Its pathogenesis involves multiple hemodynamic, inflammatory, metabolic, and genetic factors. The multifactorial nature of PE makes it difficult to infer the direct effects of risk factors using conventional statistical approaches because of potential confounding and reverse causality. Mendelian randomization (MR) uses genetic variants as instrumental variables to strengthen causal inference. This narrative review synthesizes the available MR literature concerning potential causative factors of PE, with particular emphasis on genetic and biological pathways. MR evidence suggests that matrix metalloproteinases (MMP)-19 may be associated with increased PE susceptibility, whereas MMP-12 may be associated with decreased susceptibility. Impaired kidney function showed a positive association with PE risk, and reduced HLA-DR<sup>+</sup> NK cell traits were linked to PE pathogenesis. Among gut microbiota, <i>Clostridium innocuum</i> was associated with increased PE risk, whereas <i>Butyricicoccus</i> and <i>Actinobacteria</i> showed protective associations. No consistent causal associations were identified for type 2 diabetes, atrial fibrillation, or epigenetic age acceleration. Larger multiethnic studies integrating multi-omics data are needed to clarify mechanisms underlying PE pathogenesis.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"121046"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}