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}
Necmiye Şengel, Zeynep Köksal, Aysegül Küçük, Şaban Cem Sezen, Işın Güneş, Muharrem Atlı, Gülay Kip, Seda Gökgöz Acar, Abdullah Özer, Mustafa Kavutçu, Mustafa Arslan
{"title":"Comparison of ozone administration routes on liver, lung, and brain damage after spinal cord ischemia-reperfusion injury.","authors":"Necmiye Şengel, Zeynep Köksal, Aysegül Küçük, Şaban Cem Sezen, Işın Güneş, Muharrem Atlı, Gülay Kip, Seda Gökgöz Acar, Abdullah Özer, Mustafa Kavutçu, Mustafa Arslan","doi":"10.5493/wjem.118828","DOIUrl":"10.5493/wjem.118828","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord ischemia-reperfusion injury (IRI), which can occur as a result of temporary aortic occlusion during resection of thoracoabdominal aneurysms, can be an unpredictable and devastating complication of aortic surgery. There are no specific medications or guidelines for the prevention and treatment of spinal cord IRI (SCIRI). It is now known that IRI not only exacerbates local tissue damage when blood flow is restored but also affects distant organs, such as the liver, lungs, and brain, through mediators released into the systemic circulation. Studies show that ozone pretreatment reduces oxidative damage by increasing antioxidant capacity, promotes anti-inflammatory signaling, improves blood circulation, and ameliorates IRI. Our study is one of the first to examine the effects of ozone on remote organs (liver, lung, and brain) when administered <i>via</i> different routes (intrathecal, intraperitoneal, rectal) in a spinal cord ischemia-reperfusion model.</p><p><strong>Aim: </strong>To determine whether ozone administered by different routes offers multiorgan protection in SCIRI.</p><p><strong>Methods: </strong>Thirty adult Wistar albino rats were randomly divided into five groups (<i>n</i> = 6, each): A control (C group), an IR group, an IR rectal ozone (IRRO) group, an IR intrathecal ozone (IRITO), and an IR intraperitoneal ozone (IRIPO). In the IR groups, the spinal cord IR models (a 30-minute ischemia period was applied to the infrarenal abdominal aorta using an atraumatic vascular clamp, and then a 120-minute reperfusion period was applied by removing the clamp) were applied. An ozone-oxygen mixture of 1 mg/kg (50 μg/mL) was administered by rectal insufflation to the IRRO group, 0.7 mg/kg (50 μg/mL) <i>via</i> the peritoneum to the IRIPO group, and 20 μL (20 μg/mL) intrathecally to the IRITO group 30 minutes before midline laparotomy. At the end of the reperfusion procedure, histopathological and biochemical analyses of liver, lung, and brain tissues were performed.</p><p><strong>Results: </strong>Liver tissue malondialdehyde (MDA) levels were significantly lower, and catalase (CAT) enzyme activities were significantly higher in the IRRO, IRITO, and IRIPO groups than in the IR group. Histopathologically, we had favorable results from all three ozone applications compared to the IR group. Lung tissue MDA levels were significantly lower, and CAT enzyme activities were significantly higher in the IRITO and IRIPO groups than in the IR group. We had more positive results in the IRRO group than in the IR group, but the difference was not found to be significant. Histopathologically, we obtained significantly more positive results in the IRITO and IRIPO groups compared with the IR group regarding all the criteria we evaluated. Our results in the IRRO group were also positive. Brain tissue MDA levels were significantly lower and CAT enzyme activities significantly higher in the IRITO and IRIPO groups than in the ","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"118828"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378460","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":"Letter to the Editor: Urinary infection in European guidelines 2025 <i>vs</i> microbiology culture results in the management of urinary infection.","authors":"Mohamed Wishahi, Mohamed Badawy","doi":"10.5493/wjem.v16.i2.115894","DOIUrl":"10.5493/wjem.v16.i2.115894","url":null,"abstract":"<p><p>We read with great interest the study by Yadav <i>et al</i> published in the <i>World Journal of Experimental Medicine</i>, which postulated a nomogram including patient's critical factors, other than urine sample. European Association of Urology (EAU) published the guidelines on urological infection 2025. The EAU guidelines 2025 of urinary infections (UIs) has classified in two distanced categories: Localized UTs and systemic UTs according to specific patient's symptoms and clinical signs, this new practical classification replaced previous concept of non-complicated urinary tract infection (UTI) against complicated UTI. The new EAU classification categorizes UIs as either localized or systemic, according to the presence of specific clinical signs and symptoms, this new practical classification replaced previous concept of non-complicated UTI against complicated UTI, irrespective of the results of bacteriological findings. In the new classification of UIs, the classification is based on clinical set-up on which the practitioner or urologist will manage the patient. Management of UIs is crucial to consider the urinary and gut microbiota. It was established recently that antibiotic use affects microbiota homeostasis in the gut and urinary tract that will initiate dysbiosis.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"115894"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378496","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":"Detection of intracellular bacterial communities and biofilms in urinary tract infections with <i>Escherichia coli</i> using staining protocols.","authors":"Swathi Pandey, Arul Senghor Kadalangudi Aravaanan, Emmanuel Bhaskar, Santhi Silambanan","doi":"10.5493/wjem.v16.i2.119306","DOIUrl":"10.5493/wjem.v16.i2.119306","url":null,"abstract":"<p><strong>Background: </strong>Urinary tract infections (UTIs) are prevalent worldwide, and <i>Escherichia coli</i> (<i>E. coli</i>) is the most common causative agent. The ability of the bacteria to form intracellular bacterial communities (IBCs) and biofilm is a major reason for UTIs. Studies have indicated that the persistence of uropathogenic <i>E. coli</i> as IBCs and biofilms has been implicated in UTIs. However, IBCs are not routinely identified by standard diagnostic methods.</p><p><strong>Aim: </strong>To compare the various staining techniques for the detection of IBCs in urine samples from <i>E. coli</i> culture-positive UTI patients with the biofilm-forming capability of the isolates.</p><p><strong>Methods: </strong>The study included 73 patients with <i>E. coli</i> culture-confirmed UTI. Before antibiotic treatment midstream urine sample was collected, and the sediment was obtained by centrifugation. The samples were visualized using Sternheimer-Malbin, Wright-Giemsa, Safranin, and immunofluorescence staining to detect IBCs. Formation of biofilms was analyzed by the tube method. Descriptive statistics were used.</p><p><strong>Results: </strong><i>E. coli</i> clusters were seen by light microscopy using various stains. However, immunofluorescence staining showed a better picture in the form of bright intracellular signals, which indicate bacterial aggregates. Biofilm assay showed an association with intracellular colonization.</p><p><strong>Conclusion: </strong>The various staining techniques help in the identification of uropathogenic <i>E. coli</i> as IBCs inside superficial epithelial cells. These bacteria are also capable of forming biofilms, which resists action of antibiotics. Thus, IBCs and biofilms are rich reservoirs of organisms in the urinary bladder, paving the way for chronic treatment-resistant UTIs. This study requires further larger studies to substantiate these findings.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"119306"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378447","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":"Quantitative assessment of STAT3 and HPV16 E6 transcripts using Flow-FISH approach for early detection of progressive cervical lesions.","authors":"Arun Chhokar, Udit Joshi, Tanya Tripathi, Bindiya Gupta, Madeeha Mudassir, Divya Janjua, Apoorva Chaudhary, Joni Yadav, Nikita Aggarwal, Vinita K Jaggi, Alok C Bharti","doi":"10.5493/wjem.v16.i2.118250","DOIUrl":"10.5493/wjem.v16.i2.118250","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated signal transducer and activator of transcription 3 (STAT3) signaling is a key feature of human papillomavirus (HPV)-driven cervical carcinogenesis. Our earlier work demonstrated elevated STAT3 expression plays a regulatory role in oncogenic transcription of HPV16 E6/E7. A combined analysis of STAT3 and HPV E6/E7 mRNA by fluorescence <i>in situ</i> hybridization (FISH) showed diagnostic clinical relevance in screening for pre-cancerous cervical lesions. However, use of FISH does not provide clear objective diagnostic threshold to establish accurate signal positivity.</p><p><strong>Aim: </strong>To assess the feasibility of FISH for quantitative detection of STAT3 and HPV E6/E7 transcripts using a flow cytometry-based approach.</p><p><strong>Methods: </strong>HPV-negative (C33a), HPV16-positive (SiHa) and HPV18-positive (HeLa) cervical cancer cell lines were analyzed for STAT3 and HPV E6/E7 transcript expression using FISH approach. Signal specificity and distribution were assessed by fluorescence microscopy using target-specific and scrambled probes. The same probes were further evaluated using flow cytometry-based FISH to determine their suitability for quantitative transcript detection.</p><p><strong>Results: </strong>Fluorescence microscopy revealed strong and discrete STAT3-associated signals in SiHa and HeLa cells, whereas C33a cells exhibited comparatively diffuse fluorescence. Scrambled control probes produced minimal background staining, supporting the specificity of STAT3 probe. HPV16 E6 probe also produced detectable signals but comparable fluorescence intensity was observed across all cell lines irrespective of HPV status and was similar to scrambled probe controls. Moreover, when assessed by flow cytometry-based FISH, the same probes displayed limited performance. STAT3-positive populations were low and accounted for approximately 10% of cells, while no clearly distinguishable HPV16 E6-positive population could be identified in any of the tested cell lines. These findings indicate that optimized microscopy-based FISH assay may not be directly compatible with flow-based transcript detection platforms.</p><p><strong>Conclusion: </strong>Therefore, re-optimization of assay is required for quantitative transcript detection for HPV-associated cervical cancer screening using flow cytometry-based FISH. The manuscript addresses the bottlenecks and potential strategies to mitigate the issues.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"118250"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378466","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}
Charalampos Milionis, Emmanouil Zoumakis, Ioannis Ilias
{"title":"Letter to the Editor: Endocrine determinants of diabetic ketoacidosis outcomes in type 2 diabetes and insights into Gymnema sylvestre actions.","authors":"Charalampos Milionis, Emmanouil Zoumakis, Ioannis Ilias","doi":"10.5493/wjem.v16.i2.121192","DOIUrl":"10.5493/wjem.v16.i2.121192","url":null,"abstract":"<p><p>We read with great interest the recent articles by Chandrabalan <i>et al</i> on diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) and by Kodiyatar <i>et al</i> on adjuvant herbal therapies. These articles provide important insights into DKA in T2DM, both at a clinical and experimental level. However, further endocrine aspects need to be addressed. In one study a paradoxical relationship between pre-admission metformin use and reduced in-hospital mortality from DKA was noted; this may be related to preserved beta-cell function and a more favorable incretin-glucagon axis rather than a pharmacological effect <i>per se</i>. However, important endocrine effectors such as C-peptide, glucagon, and incretin hormones were not measured. Furthermore, currently available antidiabetic agents, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have not been taken into account despite their possible effects on ketogenesis. An additional and underappreciated complexity is the concurrent occurrence of acute pancreatitis (AP) in DKA patients (DKA-AP), a complication that may affect at least 15% of DKA cases and that can neutralize key clinical and biochemical features of each condition, confounding diagnosis and worsening prognosis. At the same time, studies on Gymnema sylvestre have shown promising effects on glycemia and metabolism, while their endocrine effects have not been fully characterized. Recent data have shown possible effects of this herbal preparation on glucocorticoid receptors, suggesting a possible impact on the hypothalamus-pituitary-adrenal axis. We propose that future studies take into account detailed hormonal profiles and systematic screening for concurrent AP, which could help to further clarify the pathophysiology and mechanisms of currently available agents in T2DM-associated DKA.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"121192"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378522","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}
Snehal M Deshmukhe, Chanda R Vyawahare, Poonam V Suryawanshi, Manisha M Ratnaparkhi, Nageswari R Gandham
{"title":"Unveiling the antibiotic resistance pattern in <i>Staphylococcus aureus</i>: A systematic review (2013-2024).","authors":"Snehal M Deshmukhe, Chanda R Vyawahare, Poonam V Suryawanshi, Manisha M Ratnaparkhi, Nageswari R Gandham","doi":"10.5493/wjem.v16.i2.118252","DOIUrl":"10.5493/wjem.v16.i2.118252","url":null,"abstract":"<p><strong>Background: </strong><i>Staphylococcus aureus</i> (<i>S. aureus</i>) is one of the six highly pathogenic nosocomial bacteria. These bacteria develop or evolve with several antibiotic resistance mechanisms and therefore known to escape antibiotic treatments. Several reports suggest that multidrug resistance in <i>S. aureus</i> is increasing worldwide over the time. Indian population is comprised of diverse ethnic group residing different geographical regions. Recent reports revealed that antibiotic resistance in <i>S. aureus</i> isolates vary in different regions of India.</p><p><strong>Aim: </strong>To identify antibiotic resistance pattern in <i>S. aureus</i> in India.</p><p><strong>Methods: </strong>In the present study, we overviewed resistance in <i>S. aureus</i> isolates to different antibiotics. We searched for the research articles on antibiotic resistance in <i>S. aureus</i> from India using Scopus, Google scholar, and PubMed databases (Prospero registration No. PROSPERO 2025CRD420251153034). We identified a total of 26 articles published during 2013 to 2024 in English language. We extracted the information about the location of the study, antibiotics used and percentage of the resistant isolates.</p><p><strong>Results: </strong>Among 26 studies, most of the studies were reported from northern India (31%), southern India (27%) and eastern India (27%), followed by western India (11%) and Pan India (4%). The findings highlight very high resistance to beta-lactam antibiotics, particularly penicillin and methicillin, reflecting a substantial burden of methicillin-resistant <i>S. aureus</i>. Fluoroquinolones and macrolides also showed elevated resistance levels, whereas linezolid, teicoplanin, chloramphenicol, and doxycycline retained comparatively better activity.</p><p><strong>Conclusion: </strong>The present review, demonstrated geographical region wise trends of antibiotic resistance in <i>S. aureus</i> from India, which will be useful in designing the further studies investigating antibiotic resistance patterns.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"118252"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378480","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}
Christos Savvidis, Costas Thomopoulos, Ioannis Ilias
{"title":"Melatonin supplementation, hyperprolactinemia, and incident heart failure: A proposed prolactin-mediated pathway for cardiovascular risk.","authors":"Christos Savvidis, Costas Thomopoulos, Ioannis Ilias","doi":"10.5493/wjem.v16.i2.120754","DOIUrl":"10.5493/wjem.v16.i2.120754","url":null,"abstract":"<p><p>The problem of heart failure (HF) is complicated and is continuously growing, making the need for novel solutions critical. The role of melatonin, widely used as an over-the-counter medication for sleep disorders, has been historically researched for its cardioprotective actions based on its established antioxidant properties. Recent preliminary evidence, however, points to a possibly alarming association: A statistically significant increased risk of new onset HF, HF requiring hospitalization, and all-cause mortality was observed in association with long-term melatonin therapy (one year or longer in duration), in adult patients suffering from insomnia. However, these were reported in a single, as-yet unpublished conference abstract that has not undergone peer review or independent validation. This hypothesis-generating observation warrants careful investigation of possible mechanisms. In this article we speculatively propose a plausible - but as yet unconfirmed - mechanistic pathway mediated through prolactin (PRL). Melatonin may increase the release of PRL through its modulation of hypothalamic dopaminergic neurons, though whether this effect is sustained with long-term use remains an unresolved critical knowledge gap. This is particularly relevant given that peripartum cardiomyopathy, a dangerous, pregnancy-related variant of HF, has as its central mechanism the cardiotoxic effect of a cytotoxic 16-kDa fragment of PRL. We hypothesize that chronic exogenous melatonin use might - if it were shown to sustain hyperprolactinemia - provide excess PRL that could theoretically be cleaved to the cardiotoxic 16-kDa fragment in patients with pre-existing oxidative stress and cardiovascular risk factors, in a manner analogous to peripartum cardiomyopathy. This speculative mechanism should be tested in prospective mechanistic and clinical studies, with appropriate adjustment for confounders including insomnia severity.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"120754"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378530","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}
Muhammad Abdul Mabood Khalil, Nihal Mohammed Sadagah, Hinda Hassan Khideer Mahmood, Fadel Alrowaie, Abdullah Mohammed Almansour, Rayan Mohammed H Alghamdi, Lama Alghamdi, Rawan A Al-Ghamdi, Ammar Elgadi, Salem H Al-Qurashi
{"title":"Forgotten compartment: Impact of tubulointerstitial inflammation and damage on renal outcomes in lupus nephritis from Saudi Arabia.","authors":"Muhammad Abdul Mabood Khalil, Nihal Mohammed Sadagah, Hinda Hassan Khideer Mahmood, Fadel Alrowaie, Abdullah Mohammed Almansour, Rayan Mohammed H Alghamdi, Lama Alghamdi, Rawan A Al-Ghamdi, Ammar Elgadi, Salem H Al-Qurashi","doi":"10.5493/wjem.v16.i2.119440","DOIUrl":"10.5493/wjem.v16.i2.119440","url":null,"abstract":"<p><strong>Background: </strong>Lupus nephritis (LN) is a significant cause of kidney morbidity in patients with systemic lupus erythematosus. While glomerular lesions are the primary focus of current classifications, tubulointerstitial involvement may significantly influence renal outcomes. There is limited data on tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) in Middle Eastern populations.</p><p><strong>Aim: </strong>To examine the clinical, pathological, and prognostic significance of coexisting TII and TID in patients with biopsy-proven LN from Saudi Arabia.</p><p><strong>Methods: </strong>We retrospectively analyzed 100 patients with biopsy-confirmed LN. Patients were stratified into those with TII + TID (<i>n</i> = 48) and those without (<i>n</i> = 52). Baseline demographics, clinical features, laboratory and immunological data, and histopathological findings, including modified National Institutes of Health (NIH) activity and chronicity scores, were collected. Multivariable logistic regression identified predictors of TII + TID. Renal response during follow-up was evaluated using Kaplan-Meier analysis, and predictors of adverse composite outcomes were assessed using Cox regression.</p><p><strong>Results: </strong>Patients with TII + TID had lower baseline estimated glomerular filtration rate (77.7 ± 37.4 mL/minute/1.73 m<sup>2</sup> <i>vs</i> 98.2 ± 52.7 mL/minute/1.73 m<sup>2</sup>; <i>P</i> = 0.028) and higher low-density lipoprotein cholesterol (LDL-C; 3.01 ± 1.88 mmol/L <i>vs</i> 1.78 ± 1.82 mmol/L; <i>P</i> = 0.006). They also had higher modified NIH activity (6.17 ± 3.90 <i>vs</i> 3.13 ± 3.18; <i>P</i> < 0.001) and chronicity scores (4.21 ± 1.74 <i>vs</i> 1.85 ± 2.44; <i>P</i> < 0.001). Proliferative classes, especially class III (35.4% <i>vs</i> 15.4%) and class IV + V (20.8% <i>vs</i> 15.4%; <i>P</i> = 0.024), were more common in this group. Independent predictors of TII + TID included class III (OR = 150.42; <i>P</i> = 0.006), class IV + V (OR = 44.11; <i>P</i> = 0.03), LDL-C (OR = 2.26; <i>P</i> = 0.004), fibrinoid necrosis [Exp(B) = 2.29; <i>P</i> = 0.041], and interstitial inflammation [Exp(B) = 73.29; <i>P</i> < 0.001]. Patients with TII + TID had slower and reduced rates of achieving renal remission. Higher baseline serum creatinine, older age, elevated C-reactive protein (CRP), and the presence of hyaline deposits were associated with worse composite renal outcomes. In contrast, total glomerulosclerosis showed an inverse association in the subgroup but not in the overall cohort.</p><p><strong>Conclusion: </strong>TII and damage are common in LN and are closely associated with proliferative glomerular lesions, fibrinoid necrosis, and adverse renal outcomes. The presence of TII + TID, along with baseline creatinine, CRP, and hyaline deposits, identifies patients at higher risk for poor renal prognosis. These findings highlight the importance of evaluating the tubulointerstitial compartment for risk ","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"119440"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378515","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":"Beyond distance and heart rate: Reading 6-minute walk test <i>via</i> blood pressure variability in chronic heart failure.","authors":"Wen-Lu Xing, Tong Liu","doi":"10.5493/wjem.v16.i2.116315","DOIUrl":"10.5493/wjem.v16.i2.116315","url":null,"abstract":"<p><p>The six-minute walk test (6MWT) remains a tool for assessing exercise capacity in heart failure, with six-minute walk distance as the endpoint. To enhance interpretability, vital signs such as heart rate and blood pressure may also be recorded in accordance with technical statements. However, beta-blockers often blunt heart-rate-based readouts during the 6MWT, thereby reducing the interpretability of six-minute walk distance. Akimova <i>et al</i> recently published a study in <i>World Journal of Experimental Medicine</i>, which identified blood pressure variability (BPV) as a minutes-scale recovery signal during a paired 6MWT. The index targets the 20-minute post-exercise recovery window and uses point-to-point systolic blood pressure change to help characterize cardiac reserve and to enhance interpretation of the 6MWT. The measure is low cost and easy to implement, and BPV remains associated with imaging indices such as left ventricular ejection fraction in beta-blocked heart failure populations. Importantly, this should be viewed as an early, proof-of-concept insight. Future work should confirm these findings in multicenter prospective studies, define operational protocols and thresholds for BPV, and explore relationships with clinical outcomes, thereby further enhancing the value of minutes-scale BPV.</p>","PeriodicalId":75340,"journal":{"name":"World journal of experimental medicine","volume":"16 2","pages":"116315"},"PeriodicalIF":0.0,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378482","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}