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European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2025
Femoral neck fractures are common injuries in elderly patients, often managed by bipolar hemiarthroplasty, especially in patients with preexisting functional or cognitive impairments. This study aimed to compare postoperative functional outcomes between the direct anterior approach (DAA) in the lateral decubitus position and the anterolateral approach (ALA) for bipolar hemiarthroplasty. This single-center, prospective, single-blinded randomized controlled trial enrolled 44 patients aged ≥ 60 years with displaced femoral neck fractures undergoing bipolar hemiarthroplasty. Participants were randomized into two groups: DAA or ALA, both performed in the lateral decubitus position. The primary outcome was postoperative Harris Hip Score (HHS) at 2, 6, and 18 weeks. Secondary outcomes included pain scores at 24 h postoperatively, operative time, intraoperative blood loss, leg length discrepancy (LLD), and length of hospital stay. The DAA group demonstrated significantly higher HHS at 2 weeks (74.0 vs. 60.3; P < 0.001), 6 weeks (82.8 vs. 77.6; P = 0.005), and 18 weeks (87.5 vs. 83.4; P = 0.03) compared to the ALA group. Additionally, the DAA group experienced lower 24-hour postoperative pain scores (2.7 vs. 4.3; P < 0.001), shorter operative times (49.0 vs. 70.8 min; P < 0.001), and reduced intraoperative blood loss (110.9 vs. 184.1 mL; P = 0.02). No significant differences were observed in LLD (P = 0.67) or hospital stay duration (P = 0.21). Performing bipolar hemiarthroplasty via the direct anterior approach in the lateral decubitus position results in improved early postoperative functional outcomes, reduced pain, and shorter operative time compared to the anterolateral approach, supporting its use as the preferred surgical technique in elderly patients.
Photodiagnosis and photodynamic therapy · 2025
The objective of this study was to compare the effectiveness of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) and loop electrosurgical excision procedure (LEEP) for treating cervical high-grade intraepithelial lesions (HSIL) in patients of childbearing age. We conducted a prospective study of 67 women diagnosed with cervical HSIL from January 2022 to June 2024 in Minhang Hospital, Affiliated to Fudan University. A total of 60 patients were finally included in this clinical trial. They were assigned to two groups. 30 cases received 5-ALA-PDT, and 30 cases underwent LEEP. All patients were followed up at 6 months and 12 months after treatment, including HPV testing, cytology, and colposcopy examination. 6 months after treatment, the HPV clearance rates in the 5-ALA-PDT group were similar to the LEEP group, both groups were 80.00 % (P = 1.00). The cure rates in both groups were 80.00 %, and the improvement rates were 20.00 % (P = 1.00). 12 months after treatment, the HPV clearance rate in the 5-ALA-PDT group was marginally higher than the rate observed in the LEEP group (90.00 % vs. 83.33 %, P = 0.448). The cure rate in the 5-ALA-PDT group was marginally higher than that in the LEEP group (86.67 % vs. 83.33 %, P = 0.718). The incidence of adverse reactions in the 5-ALA-PDT group was significantly lower than that in the LEEP group for the treatment of cervical HSIL (3.33 % vs. 30.00 %, P < 0.05). For patients of reproductive age with cervical HSIL, 5-ALA-PDT treatment for cervical HSIL is an effective and safe treatment option.
Biomolecules & biomedicine · 2025
Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication that poses significant risks to both mothers and their offspring, with genetic susceptibility believed to play a role in its pathogenesis. This study examined the association between the Pro12Ala (Pro [C]→Ala [G]) polymorphism in the peroxisome proliferator-activated receptor γ2 (PPARγ2) gene and the risk of developing GDM. A systematic literature search was conducted across databases including PubMed/Medline, Web of Science, Embase, and the Cochrane Library, identifying clinical studies that evaluated the relationship between the PPARγ2 Pro12Ala variant and GDM. Strict inclusion criteria ensured that all case groups comprised exclusively women diagnosed with GDM. Data on study characteristics, sample sizes, and allele frequencies were extracted, and meta-analyses were performed using RevMan 5.3 and Stata with Hartung-Knapp random-effects models. Fifteen studies were included in the analysis. The Pro12Ala polymorphism showed no significant association with GDM risk across allelic (Ala [G] vs. Pro [C]), dominant (CG+GG vs. CC), and recessive (GG vs. CG+CC) models (allelic: OR=0.90, 95% CI=0.75-1.08, p=0.26; dominant: OR=0.92, 95% CI=0.74-1.13, p=0.42; recessive: OR=0.82, 95% CI=0.54-1.25, p=0.33; all p>0.05). Subgroup analyses by ethnicity indicated a potential protective association of the Ala (G) allele with GDM in East Asian populations, while no significant associations were found in European or Middle Eastern populations; ethnicity was identified as a significant effect modifier (p<0.05). There were no meaningful differences in subgroups categorized by study quality and sample size. Sensitivity analyses confirmed the robustness of the findings, and small-study effects detected by Egger's test did not substantially alter the pooled estimates. In conclusion, the PPARγ2 Pro12Ala polymorphism was not significantly associated with GDM risk in the general population. The potentially protective trend observed in East Asian women warrants cautious interpretation due to concerns regarding multiple testing, allele-frequency variation, and limited statistical power.
Dermatology and therapy · 2026
Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unclear etiology, most often affecting postmenopausal women. It presents with itching, burning, pain, and progressive vulvar scarring and atrophy, leading to sexual dysfunction and increased risk of neoplastic transformation. High-potency corticosteroids are the standard first-line treatment, but many patients experience inadequate response or intolerance, resulting in recurrence. In such cases, 5-aminolevulinate (ALA) photodynamic therapy (PDT) may offer an alternative. The aim of this systematic review was to evaluate the effectiveness and safety of PDT in patients with VLS. Searches of PubMed, Scopus, and Web of Science identified 238 papers, of which 13 met the inclusion criteria, comprising 441 women with VLS. Among these, one was a randomized controlled trial, one a non-randomized comparative study, seven were single-arm trials, and four were retrospective analyses. The collective evidence showed that PDT, particularly using 5-ALA as a photosensitizer, improved clinical symptoms such as pain and itching, skin histology, patients' quality of life as measured with the Dermatology Life Quality Index, and sexual functioning as measured with the Female Sexual Function Index. Adverse events were mainly procedure-related and resolved spontaneously within a few days. PDT appears to be a promising therapeutic option for VLS, particularly in patients with refractory disease unresponsive to conventional treatments. However, evidence for ALA-PDT remains limited, as current studies are small, use variable protocols, and involve heterogeneous populations. Further research is needed to address these gaps. Available studies indicate that ALA-PDT is a safe, well-tolerated, and effective option for VLS, improving both symptoms and clinical signs, especially in refractory cases. Emerging evidence, including comparative and quality-of-life studies, supports its potential role in management, though large prospective trials are needed to refine protocols and establish guideline recommendations.
Prostaglandins, leukotrienes, and essential fatty acids · 2025
Exclusion of meat and fish from the diet can lead to low levels of omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFAs), leaving the body reliant on dietary intake of n-3 α-linolenic acid (ALA) for endogenous conversion. This study compared dried blood spot fatty acid profiles from a large cohort of pregnant Indian women in Bengaluru, Karnataka, with self-reported vegetarian (n = 332) or omnivorous (n = 691) diets in the first trimester, to those of pregnant Australian women (n = 454) at a similar gestational age. Indian vegetarians and omnivores showed similar fatty acid profiles in dried blood spots but both had markedly lower n-3 fatty acids (mean total n-3 values: Indian 2.01% and 2.36% of total fatty acids respectively; 4.75% in Australian) with ALA, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid all less than half the Australian values. Both Indian groups also had lower arachidonic acid levels (mean 7.65% and 7.91% respectively, vs 8.50% in Australian omnivores), and higher linoleic acid levels (mean 22.53% and 22.41% respectively, vs 19.96% in Australian omnivores) compared with the Australian participants. In general, the relationships between n-3 fatty acids were stronger in Indian vegetarians than Indian omnivores, and weakest in Australian omnivores. These findings suggest that regardless of diet, Indian women in early pregnancy have lower n-3 LCPUFA status than Australian pregnant women. Our data are consistent with the idea that increasing intake of n-3 ALA-rich oils and reducing n-6 linoleic acid-rich oils in the diet of Indian women could be an efficient way of increasing their n-3 LCPUFA status. CLINICAL TRIAL REGISTRATIONS: ORIP, Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729; BORN, Clinical Trials Registry-India CTRI/2020/08/027146.
International journal of molecular sciences · 2025
In this randomized clinical trial, we compared the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and topical clobetasol on the salivary antioxidant profile in patients with oral lichen planus (OLP) and explored their relationships with clinical outcomes. Ninety adults with OLP were randomly allocated to ALA-PDT (five weekly sessions) or clobetasol (twice daily for 14 days). Unstimulated whole saliva was collected at baseline (T0), immediately after treatment (T1), and at 3 (T3) and 6 months (T6). The activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (Px) and reduced glutathione (GSH) were determined, and nonparametric statistics were applied, including Friedman tests with Dunn's post hoc comparisons and Spearman's rank correlations. Both therapies induced an early decline in CAT, Px and GSH at T1, followed by partial recovery at later time points. SOD activity changed significantly over time in the clobetasol group, but not in the PDT arm. At T6, Px and GSH remained below baseline in both groups despite improvement from the immediate post-treatment nadir. No significant between-group differences were observed at individual time points, although GSH at T6 showed a non-significant trend favoring PDT. Exploratory analyses revealed modest, treatment-dependent associations between salivary antioxidant activity and lesion size, as well as between the former and pain intensity. Overall, ALA-PDT and topical clobetasol both modulated the salivary redox profile, primarily through short-term depletion of enzymatic and non-enzymatic antioxidants with incomplete recovery over 6 months, and no clear redox superiority of one modality over the other was demonstrated. These findings are hypothesis-generating and underscore the need for larger, longer-term studies with broader redox panels and more advanced between-group analyses.
Drug discoveries & therapeutics · 2026
The aim of this study is to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride/sodium ferrous citrate (5-ALA-HCl/SFC) in patients with adult-onset Still's disease (AOSD) refractory to glucocorticoids during the maintenance treatment period of a phase II investigator-initiated randomized, double-blind, parallel-group clinical trial. This multicenter, open-label, continuous trial was limited to participants from the preceding study, which was planned for 30 enrollees but was stopped early after four enrollees because of slow recruitment. The current trial maintained a 16-week treatment period and remained double-blind until the previous study database was locked and unblinded. Two dose groups were used: 5-ALA-HCl/SFC 100 and 300 mg. Participants previously assigned to placebo were re-randomized 1:1 to either dose group. The dosage and administration were identical to those of the previous protocol. The primary endpoint was the achievement of adapted ACR 30 at week 16. All four participants achieved the primary endpoints. Secondary outcomes, including the adapted ACR 90/100 and the change in serum ferritin levels, showed numerically greater improvement in the participant who received the high-dose compared with the other. Eleven adverse events occurred in three participants, including one serious event and one discontinuation; all were deemed unrelated to the study drug, and no deaths were reported. This study identified potential efficacy signals, particularly in the high-dose group. However, because of premature termination and a very limited sample size, the data were insufficient to establish the efficacy and safety profile of 5-ALA-HCl/SFC in refractory AOSD. Larger studies are required to confirm these findings.
Journal of dietary supplements · 2026
Ischemic cardiomyopathy (ICM) is caused by oxidative stress, inflammation, and apoptosis. Alpha-lipoic acid (ALA) has antioxidant and anti-inflammatory effects. However, its effects on left ventricular dysfunction and myocardial fibrosis remain unclear. This study aims to investigate the effects of ALA on cardiac inflammation, fibrosis, and myocardial function as an adjuvant therapy for ICM. This double-blind, randomized, placebo-controlled, single-center trial enrolled 67 diabetic patients with ICM, who were randomized to receive either ALA 600 mg once daily or placebo for three months, in addition to ICM medications. Both groups were evaluated for tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), tissue growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and some echocardiographic indices before and after treatment. Sixty patients (aged 45-75 years; 70% males) completed the study (ALA group n = 30; placebo group n = 30). After three months, the ALA group exhibited significantly lower levels of TNF-α [443 (326/515) vs. 499 (448/657) pg/ml], CRP [4.5 (4.2/6.1) vs. 11 (6.3/12.1) mg/l], TGF-β1 [161 (104/189) vs. 206 (158/248) pg/ml], and MMP-2 [1450 (1164/1894) vs. 1815 (1339/2133) pg/ml] (p < 0.05) compared to the placebo group. Furthermore, in the ALA group, there was a significant increase in LVEF [36% (34/40) vs. 28% (25/31.8)], whereas LVESD, LVEDD, and LAD were significantly decreased compared to the placebo group [4.7 (3.9/5.8) vs. 5.6 (5.1/5.6) cm; 6.1 ± 0.7 vs. 6.5 ± 0.5 cm; 4.2 (3.9/4.7) vs. 4.8 (4.4/5.1) cm] (p < 0.05), respectively. Adjunctive ALA therapy considerably reduced inflammation and improved cardiac function in patients with ICM. Additionally, our findings suggest that ALA may influence profibrotic signaling.
Photodiagnosis and photodynamic therapy · 2026
Intracranial lymphomas are rare tumors of the central nervous system, predominantly affecting elderly patients. While 5-aminolevulinic acid (5-ALA) fluorescence is well established in glioma surgery, its diagnostic role in intracranial lymphoma remains unclear, particularly regarding the effect of corticosteroid use. This study evaluated the diagnostic performance of 5-ALA-guided biopsy and its relationship with corticosteroid exposure. We conducted a retrospective case series and a systematic review. Adult patients who underwent stereotactic or open biopsy with 5-ALA guidance for radiologically suspected intracranial lymphoma at Gachon University Gil Medical Center (2022-2025) were analyzed. A comprehensive literature search (MEDLINE, EMBASE, Web of Science, Cochrane Library) through May 2025 identified studies reporting 5-ALA use in intracranial lymphoma biopsy. Diagnostic yield, fluorescence patterns, and corticosteroid effects were assessed. Five patients were included in the institutional series: strong fluorescence was observed in four and vague in one, with an overall positive predictive value of 80 %. Across 18 studies (170 patients), 5-ALA fluorescence was detected in 77.6 %, with 78 % pooled sensitivity and 22 % false-negative rate. Among 12 patients with documented corticosteroid use, discontinuation ≥7 days before biopsy correlated with higher fluorescence positivity, though not consistently with diagnostic success. 5-ALA fluorescence serves as a useful adjunct for intracranial lymphoma biopsy, enhancing sampling efficiency and procedural safety. However, fluorescence alone cannot ensure diagnostic adequacy, and frozen section confirmation remains necessary. Corticosteroid use does not uniformly suppress fluorescence but may influence diagnostic reliability.
The Journal of nutrition · 2026
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. While anti-vascular endothelial growth factor (anti-VEGF) therapies are available for neovascular AMD (nAMD), effective preventive strategies remain limited. Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have biological plausibility for retinal protection through structural roles in photoreceptor membranes and anti-inflammatory lipid mediator pathways. This study aimed to synthesize contemporary evidence regarding omega-3 fatty acids in AMD prevention, with emphasis on subtype-specific associations, differences by omega-3 species, and contrasts between dietary intake and supplementation evidence. This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidance and registered the protocol in PROSPERO (CRD420251122413). PubMed, ScienceDirect, and the Cochrane Library were searched from inception to August 2, 2025. Eligible studies included observational studies of dietary ω-3 PUFA exposure in adults aged 50 years or older with AMD outcomes. Random-effects models models were used to pool adjusted effect estimates comparing the highest versus lowest ω-3 exposure categories. Prespecified subgroup analyses were performed by AMD subtype (early AMD, advanced AMD, nAMD, and geographic atrophy [GA]) and ω-3 species (EPA, DHA, and alpha-linolenic acid [ALA]). Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Publication bias was evaluated using funnel plots and Egger's regression test. Eighteen studies were included. Higher ω-3 intake was associated with reduced odds of AMD overall (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96; p = 0.01), with moderate heterogeneity (I² = 61%). Subtype analyses demonstrated stronger associations for nAMD (OR 0.57, 95% CI 0.40-0.81) and GA (OR 0.65, 95% CI 0.45-0.94), and a smaller association for early AMD (OR 0.83, 95% CI 0.72-0.97), whereas advanced AMD was not significantly different between high and low intake groups (OR 0.81, 95% CI 0.49-1.33; p = 0.41). In ω-3 species analyses, higher EPA intake was associated with lower AMD odds (OR 0.61, 95% CI 0.38-0.97; p = 0.04), while DHA showed a borderline association (OR 0.73, 95% CI 0.53-1.01; p = 0.05); ALA was not associated with benefit (OR 1.00, 95% CI 0.84-1.20; p = 0.96). Time-to-event pooling showed no significant long-term risk reduction (hazard ratio [HR] 0.98, 95% CI 0.84-1.15; p = 0.83). Funnel plot asymmetry was observed, and Egger's test suggested small-study effects (p = 0.04). Higher dietary intake of marine-derived ω-3 PUFAs is associated with reduced odds of AMD. However, long-term risk reduction was not demonstrated in time-to-event analyses, and small-study effects were suggested. These findings support the possibility that dietary patterns emphasizing ω-3-rich seafood may contribute to AMD risk reduction, whereas the effectiveness of isolated ω-3 PUFA supplementation for AMD prevention remains uncertain and warrants confirmation in future prospective studies and larger randomized controlled trials with long-term follow-up.
Scientific reports · 2026
Skin barrier function impairment and inflammation promote allergen invasion through the skin, leading to sensitization and exacerbation of allergic diseases. Intake of linseed oil, an oil rich in alpha-linolenic acid (ALA), suppresses inflammation and allergic symptoms. To our knowledge, the effects of diacylglycerol-enriched ALA (ALA-DAG) oil intake on skin properties and allergic symptoms have not been evaluated. We performed a double-blind, randomized, placebo-controlled, parallel-group study of 60 individuals aged 20-59 years with mild skin discomfort, including dryness, itching, and redness, to investigate the effects of ALA-DAG intake on skin and allergic symptoms. Participants were divided into two groups treated with either 2.5 g/day of ALA-DAG or placebo oil for 8 weeks. The skin properties were measured at baseline and at 8 weeks. Allergic symptoms were measured at 4 and 8 weeks. Compared with placebo oil intake, ALA-DAG intake increased skin hydration in the cheek, reduced nasal congestion and nose itchiness, and decreased mite-specific immunoglobulin E in the blood. Subgroup analysis showed that participants who were positive for mite allergen sensitization had reduced facial redness after ingesting ALA-DAG. These findings suggest that ALA-DAG intake improves skin properties and alleviates allergic symptoms.
Journal of neurosurgery · 2026
Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis despite standard treatments. Emerging innovations, including photodynamic therapy (PDT), offer new hope by improving local tumor control and survival. The aim of this review was to systematically assess the clinical benefits of PDT as an adjunct to surgery for patients with GBM. A systematic review was conducted in September 2024 using PubMed, Scopus, Embase, and Web of Science, following PRISMA guidelines. Comparative cohort studies evaluating the safety and efficacy of PDT in patients with GBM were included. Oncological outcomes were assessed by comparing progression-free survival (PFS), overall survival (OS), and the difference in 1-year survival rates between the PDT and control groups. Statistical analysis was performed using a random-effects model, while study quality was evaluated with the ROBINS-I tool for nonrandomized studies. This review included 8 retrospective studies involving 772 patients with GBM (281 in the PDT group and 491 in the control group). Talaporfin sodium (TS) was used in 5 studies, while 5-aminolevulinic acid (5-ALA) was used in 3 studies. The analysis showed that PDT significantly improved the PFS (hazard ratio [HR] 0.66, 95% CI 0.50-0.86; p = 0.003) and OS (HR 0.57, 95% CI 0.46-0.70; p < 0.001) rates, leading to a notable increase of 25% in the 1-year survival rate compared with controls (95% CI 10%-40%, p = 0.001). There was no significant difference between TS and 5-ALA regarding OS outcomes (p = 0.32). Additionally, complication rates were similar between PDT-treated patients and controls (RR 1.28, 95% CI 0.66-2.46; p = 0.46), with transient cerebral edema reported in approximately one-tenth of treated patients. PDT significantly improved tumor control and extended survival for patients with GBM without increasing major complications. These findings support PDT as a promising adjunctive treatment during surgery. However, further randomized clinical trials are needed to validate its long-term efficacy and to optimize treatment protocols.
Photodiagnosis and photodynamic therapy · 2026
Vaginal Intraepithelial Neoplasia (VaIN) is a precancerous condition that can progress to vaginal cancer if untreated. Photodynamic Therapy (PDT), recognized for its minimally invasive nature and favorable side effect profile, is increasingly employed for VaIN treatment; however, comprehensive evidence synthesis on its efficacy and safety remains limited. This study aims to comprehensively evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in treating VaIN. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies evaluating PDT efficacy in VaIN. Primary outcomes were complete response (CR) rate and HPV clearance rate; secondary outcomes included recurrence rate and adverse events (AE). Meta-analysis was performed using Stata 18.0. Nine trials (421 patients) were included. Pooled outcomes: 6-month CR:87% (95% CI: 78%-94%), 12-month CR:84% (95% CI:76%-91%); 6-month HPV clearance:61% (95% CI:55%-66%), 12-month:73% (95% CI:67%-78%); 6-month HPV16/18 clearance:71% (95% CI:61%-80%), 12-month:76% (95% CI:63%-88%); 6-month recurrence:4% (95% CI:2%-8%), 12-month:7% (95% CI:0%-24%); AEs: Increased vaginal discharge (20%, 95% CI: 8%-36%), itching (25%, 95% CI: 1%-62%), burning sensation (23%, 95% CI: 1%-57%), abdominal pain (7%, 95% CI: 0%-21%), and mild vaginal bleeding (0%, 95% CI: 0%-3%). No serious AEs. ALA-PDT demonstrates high efficacy and favorable safety in treating VaIN. However, as current evidence primarily stems from single-arm studies, future high-quality multicenter randomized controlled trials are essential to confirm these findings and directly compare ALA-PDT with standard therapies.
Diabetes & metabolic syndrome · 2026
In this article, we perform a systematic review and meta-analysis evaluating the effects of alpha-lipoic acid (ALA) supplementation on biochemical, clinical, inflammatory, and functional parameters in patients with diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). A total of 15 articles were included, of which 12 were analyzed for outcomes. DPN is a chronic complication of Diabetes Mellitus (DM) characterized by symptoms, such as pain, sensory disturbances, and reduced quality of life. Currently, there is no definitive cure. Management focuses on controlling blood glucose and alleviating symptoms through pharmacological and non-pharmacological therapies. The aim of this study is to analyze the evidence regarding the efficacy of alpha-lipoic acid (ALA) supplementation in the management of DPN. A systematic search across multiple databases was conducted using keywords, such as "diabetes mellitus," "diabetes mellitus type I," "diabetes mellitus type II," "alpha-lipoic acid," and "ALA supplementation." A total of 15 studies met the inclusion criteria. Of the 23 outcomes analyzed, 19 showed significant differences in favor of alpha-lipoic acid (ALA) supplementation at different doses versus a placebo or other treatments. Notable improvements were observed in Total Symptom Score (TSS) paresthesia (SMD = -1.04; 95 % CI = -1.24 to -0.84; p < 0.00001), TSS numbness (SMD = -0.23; 95 % CI = -0.44 to -0.01; p = 0.04), and the Hamburg Pain Adjective List (HPAL) (SMD = -1.00; 95 % CI = -1.15 to -0.85; p < 0.00001), among others. These improvements were particularly evident for symptoms, such as paresthesia, numbness, and burning sensations, especially at a dose of 600 mg/day. In contrast, four of the outcomes HbA1c, nitric oxide levels, sural sensory nerve action potential, and peroneal motor nerve conduction velocity showed no significant changes. The evidence suggests that ALA, especially at 600 mg/day, is a safe and potentially effective adjunct therapy for symptom management in DPN, although its impact on nerve conduction and long-term glycemic control remains inconclusive.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2026
Glioblastoma intramedullary spinal cord metastasis (GISCM) is a rare sequela of high-grade astrocytoma and glioblastoma multiforme (GBM). Discrete intramedullary spinal cord metastases are less common than spinal leptomeningeal spread and may follow a more indolent course. Once identified as GISCM, palliative maximal safe resection of the tumor may be considered to alleviate neurological symptoms. Reports describing the surgical management of these rare lesions, including the use of emerging technologies that may aid in maximal safe resection, are sparse. A further understanding is also required regarding the course of disease and factors contributing to mortality in GISCM. We reviewed the intraoperative management and clinical course of three patients treated for GISCM at our institution between 2015 and 2024. We additionally conducted a PRISMA-guided systematic literature review of PubMed Central, MEDLINE, and Bookshelf databases through May 26th, 2025, including original patient reports of GISCM from cranial astrocytoma or GBM. The disease course, management strategies, and causes of mortality in previously reported cases were analyzed. Our institutional cohort had a mean time to spinal metastasis of 26.2 months from diagnosis of cranial disease (range 17.5-40.5 months), with a mean survival of 9.2 months following maximal safe resection of extramedullary components (range 7-12 months). In two cases, intraoperative Stimulated Raman Histology (SRH) was employed to facilitate the rapid identification of metastatic GBM, thereby influencing surgical strategy. In one case, 5-aminolevulinic acid (5-ALA) was used to differentiate between tumor and spinal cord parenchyma, facilitating maximal safe debulking without neurological injury. Literature review identified 38 prior reported cases of GISCM, with a median time to spinal diagnosis of 11.0 months and a median survival of 3.5 months thereafter. The cause of death in the review cohort often involved multiple factors, and when analyzed for contributing factors to death, 38.7% involved cranial progression, 38.7% involved progression of spinal disease, and 29.0% involved medical complications. Gait ataxia at presentation was associated with shorter survival in review patients, potentially reflecting advanced disease with extramedullary cord compression. GISCM represents an entity distinct from leptomeningeal disease and may be managed in conjunction with recurrent cranial disease. Surgical debulking is a technically feasible strategy that can be safely facilitated using tools employed in the management of intracranial GBM, facilitating maximal safe resection without compromising survival.
Food & function · 2026
Hemp seeds are high in polyunsaturated fatty acids (PUFAs) including gamma linolenic acid (GLA), stearidonic acid (SDA), alpha linolenic acid (ALA) and linoleic acid (LA). To date, limited evidence is available on hemp product consumption and particularly hemp seeds and oil in humans and its relation to cardiometabolic risk factors. The objective of present study was to examine the effects of hemp product consumption versus similar controls on circulating fatty acid profiles and cardiovascular disease (CVD) risk factors. A randomized, double-blinded, crossover trial with 30 normoglycemic adults (18-65 years) within a BMI range of 25-35 kg m-2 were included. Participants consumed both hemp products and controlled products over the course of 4 weeks each. As expected, ALA (18:3 n-3), GLA (18:3 n-6) and dihomo-γ-linolenic acid (DGLA, 20:3 n-6) were elevated after the hemp treatment than controls. Similarly, ALA, DGLA as well as eicosapentaenoic acid (EPA) levels were elevated after the hemp treatment than controls. No differences in serum lipid levels, glucose and insulin concentrations, blood pressure, or body composition were observed between treatments. Overall, consumption of hemp products modulated plasma and RBC fatty acids levels in a way which reflected the fatty acids these products are enriched in, without showing differences in major cardiometabolic risk factors. The present study demonstrated the human fatty acids profile response to consuming hemp products, novel functional foods rich in polyunsaturated fatty acids. The clinical trial registry number is NCT02400203 (https://clinicaltrials.gov).
Frontiers in oncology · 2026
Basal cell carcinoma (BCC) is the most prevalent non-melanoma skin cancer, with surgical excision as the gold standard-though it carries risks of cosmetic scarring and functional impairment. Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) emerges as a non-invasive alternative, yet evidence on its relative efficacy across superficial (sBCC) and nodular (nBCC) subtypes remains inconsistent. This systematic review and meta-analysis adhered to PRISMA 2020 guidelines, with a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science up to December 31, 2025. Eligible studies included randomized controlled trials (RCTs) and single-arm studies evaluating ALA-PDT/MLA-PDT for histologically confirmed sBCC or nBCC. Study quality was assessed via the Methodological Index for Non-Randomized Studies (MINORS) scale, and statistical analyses were performed using Review Manager 5.4. A comprehensive literature search identified 3832 records, with 55 eligible studies (41 for sBCC, 34 for nBCC) ultimately included, involving 2123 patients and 2995 lesions. For sBCC, the pooled complete response (CR) rate was 0.88 (95% CI: 0.85-0.91, p<0.00001) with high heterogeneity (I²=87%); no significant difference in CR rate was observed between ALA-PDT (0.87) and MAL-PDT (0.90) (p=0.47), and BF-200 ALA-PDT achieved a CR rate of 0.90. The pooled beauty effect rate for sBCC was 0.91 (95% CI: 0.87-0.95, p<0.00001), with a low pooled adverse event incidence of 0.08 (95% CI: 0.03-0.14, p=0.004) and a pooled recurrence rate of 0.13 (95% CI: 0.09-0.18, p<0.00001). For nBCC, the pooled CR rate was 0.75 (95% CI: 0.70-0.80, p<0.00001, I²=92%), with MAL-PDT (0.78) showing a statistically significant higher CR rate than ALA-PDT (0.69) (p=0.04); BF-200 ALA-PDT and AFL-MAL-PDT achieved CR rates of 0.89 and 0.84, respectively. The pooled beauty effect rate for nBCC was 0.90 (95% CI: 0.83-0.96, p<0.00001), with a pooled recurrence rate of 0.15 (95% CI: 0.10-0.20, p<0.00001); adverse event data were insufficient for pooling, with individual studies reporting mild, manageable local reactions. Subgroup analyses revealed that study design, light dose, and number of treatment sessions were the main factors contributing to heterogeneity in key outcomes. ALA/MAL-PDT is an effective and safe non-invasive therapeutic option for both sBCC and nBCC, with excellent cosmetic outcomes for both subtypes. MAL-PDT exhibits significantly superior efficacy in nBCC compared with ALA-PDT, while the two photosensitizers show comparable therapeutic effects in sBCC. Novel PDT formulations including BF-200 ALA-PDT and AFL-MAL-PDT demonstrate promising CR rates for BCC, providing new treatment alternatives for clinical practice. Standardization of treatment parameters (e.g., light dose, treatment sessions) and differentiation of study design types can effectively reduce heterogeneity in PDT efficacy evaluation, and ALA/MAL-PDT should be prioritized for patients seeking minimally invasive treatment, those with multiple lesions, or those with contraindications to surgical excision.
Journal of nutritional science and vitaminology · 2020
Oral mucositis refers to erythematous and ulcerative lesions of oral mucosa during chemo/radiotherapy. Treatment modalities were directed towards reduction in severity of oral mucositis. Zinc plays an important role to retard oxidative processes and is considered as the critical component in wound healing. To compare the efficacy of zinc alone with improvised zinc preparation in reducing the severity of oral mucositis. Improvised zinc was a combination of zinc oxide, amla, tulsi and curcumin at 1% therapeutic concentrations. Seventy-five subjects undergoing chemo/radiotherapy were randomly divided into three groups: Group A (25 subjects) had received topical 5% zinc oxide paste trice daily application after food for entire treatment period, initiated 2 d prior to radiotherapy. Group B (25) received improvised zinc preparations (1%) and instructed to apply same as group A. Group C (25) received standard treatment offered by cancer hospital. All the groups were assessed for oral mucositis using WHO grading system at 7th, 14th, 21st, 28th, 35th day by the oncologist and results were tabulated for statistical analysis. Severity of oral mucositis reduced in zinc and improvised zinc group (p=0.096) when compared with controls with significant p value (0.037). Comparison of improvised zinc preparation (1%) group with only zinc group revealed that severity of overall mucositis though was not significant, was less in improvised zinc group with p value (0.029, 0.013) at 28 and 35 d respectively. Improvised zinc administration during radiation therapy was beneficial in reduction of oral mucositis during cancer treatment.
Clinical oral investigations · 2021
Lactate dehydrogenase (LDH) is a critical intracellular enzyme responsible for anaerobic respiration in pyruvate metabolism which becomes detectable in extracellular spaces after cellular breakdown. This clinical investigation examined the effects of brushing with a test toothpaste containing natural ingredients, i.e., clove (Syzygium aromaticum), aloe vera (Aloe barbadensis), amla (Emblica officinalis), neem (Azadirachta indica), tulsi (Ocimum basillicum), and honey (from Apis mellifera), and 0.96% zinc (zinc oxide, zinc citrate) and 0.76% SMFP (1000 ppm F) in a calcium carbonate base formulated with natural ingredients (Ved Shakti, Colgate Palmolive India) and a fluoride toothpaste containing 0.76% SMFP (1000 ppm F) in a calcium carbonate base (Colgate Cavity Protection, Colgate Palmolive; henceforth control) on salivary LDH in conjunction with the assessments of dental plaque and gingivitis representing oral hygiene parameters. This double-blind, two-cell study enrolled 70 adults (age range 20-59 years). Subjects completed a washout and provided baseline saliva samples for LDH analysis and clinical assessments of dental plaque and gingivitis using the Turesky Modification of Quigley-Hein and Loe-Silness methods respectively. Subjects were randomly assigned to brush their teeth with either the test or control. Post-treatment sample collection and clinical evaluations were conducted after 3 weeks, 6 weeks, and 12 week sof brushing with all assessments conducted 12 h after hygiene. Statistical analyses were conducted independently for each parameter by t-test for within treatment evaluation and analysis of covariance (ANCOVA) for between treatment comparisons. At baseline, treatment groups demonstrated no significant differences for LDH or dental plaque and gingival index scores. Brushing with the test demonstrated progressive reductions in salivary LDH, plaque and gingival index scores over the study duration in comparison to the control. The test demonstrated reductions in LDH of 9.5-15.4% over the study period in comparison to the control representing statistically significant effects (p < 0.05). The test also demonstrated reductions in dental plaque that ranged between 6.4 and 16.2% over the study period and gingivitis reductions that ranged between 8.2 and 23.8% representing statistically significant results (p < 0.05). Brushing with a novel herbal toothpaste demonstrated significant reductions in salivary LDH representing improvements in cellular integrity with concurrent reductions in dental plaque and gingivitis as compared to the control dentifrice. Salivary LDH measurements offer a non-invasive and objective measurement of mucosal cellular integrity complementing other evaluations and clinical assessments such as plaque and gingival index scores.
Phytomedicine : international journal of phytotherapy and phytopharmacology · 2021
Specific treatment for COVID-19 is still an unmet need. Outcomes of clinical trials on repurposed drugs have not been yielding success. Therefore, it is necessary to include complementary approaches of medicine against COVID-19. This study was designed to evaluate the impact of traditional Indian Ayurvedic treatment regime on asymptomatic patients with COVID-19 infection. It is a placebo controlled randomized double-blind pilot clinical trial. The study was registered with Clinical Trial Registry-India (vide Registration No. CTRI/2020/05/025273) and conducted at the Department of Medicine in National Institute of Medical Sciences and Research, Jaipur, India. 1 g of Giloy Ghanvati (Tinospora cordifolia) and 2 g of Swasari Ras (traditional herbo-mineral formulation) and 0.5 g each of Ashwagandha (Withania somnifera) and Tulsi Ghanvati (Ocimum sanctum) were given orally to the patients in treatment group twice per day for 7 days. Medicines were given in the form of tablets and each tablet weighed 500 mg. While, Swasari Ras was administered in powdered form, 30 min before breakfasts and dinners, rest were scheduled for 30 min post-meals. Patients in the treatment group also received 4 drops of Anu taila (traditional nasal drop) in each nostril every day 1 h before breakfast. Patients in the placebo group received identical-looking tablets and drops, post randomization and double blinded assortments. RT-qPCR test was used for the detection of viral load in the nasopharyngeal and oropharyngeal swab samples of study participants during the study. Chemiluminescent immunometric assay was used to quantify serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and high sensitivity C-reactive protein (hs-CRP) on day 1 and day 7 of the study. By day 3, 71.1 % and 50.0 % patients recovered in the treatment and placebo groups, respectively. Treatment group witnessed 100 % recovery by day 7, while it was 60.0 % in the placebo group. Average fold changes in serum levels of hs-CRP, IL-6 and TNF-α in treatment group were respectively, 12.4, 2.5 and 20 times lesser than those in the placebo group at day 7. There was 40 % absolute reduction in the risk of delayed recovery from infection in the treatment group. Ayurvedic treatment can expedite virological clearance, help in faster recovery and concomitantly reduce the risk of viral dissemination. Reduced inflammation markers suggested less severity of SARS-CoV-2 infection in the treatment group. Moreover, there was no adverse effect observed to be associated with this treatment.