Nevin Manimala

Neurol Sci. 2025 Jul 16. doi: 10.1007/s10072-025-08349-7. Online ahead of print.

ABSTRACT

BACKGROUND: International trials suggested the efficacy of therapeutic window enlarged for mechanical thrombectomy (MT) in acute ischemic stroke (AIS). Real-life studies seem to confirm this opportunity. We aimed to evaluate the therapeutic window enlargement impact in an about 1.5 million residents region to determine if our drip-and-ship organization could ensure favorable clinical outcome and safety for patients treated more than 6 h after stroke onset.

METHODS: All AIS patients attending the Emergency Department of the only Marche region hub hospital who underwent MT were enrolled. We collected epidemiological, clinical and radiological variables. We used the National Institutes of Health Stroke Scale (NIHSS) to assess patients and calculated delta (NIHSS) as the difference between admission and discharge NIHSS scores. We examined patients undergoing MT with an onset-to-groin time (OGT) of less and greater than 6 h.

RESULTS: Delta (NIHSS) showed a statistically significant difference between patients who underwent MT within and after 6 h from symptom onset, with notable improvement in the first group. The overall prevalence of post-procedural intracranial bleeding did not significantly differ between the two groups (32.3% vs. 38.2%; p = 0.266). The risk of in-hospital deaths significantly increased among patients treated after 6 h.

CONCLUSIONS: Our results suggest satisfactory AIS outcomes even when treated several hours after the symptoms’ onset, despite a significant increase in the number of in-hospital deaths. However, the better results obtained with earlier IT and MT confirm the “golden hour” concept. Our findings show that our stroke organization provides a good clinical opportunity for patients treated within an extended therapeutic window.

PMID:40668465 | DOI:10.1007/s10072-025-08349-7

J Assoc Res Otolaryngol. 2025 Jul 16. doi: 10.1007/s10162-025-00998-x. Online ahead of print.

ABSTRACT

PURPOSE: Permanent hearing loss primarily results from the inability of the mammalian cochlea to replace lost inner ear hair cells. However, neonatal mice exhibit a unique capacity: isolated cochlear floor cells can efficiently proliferate in vitro and form organoids that harbor new hair cells and supporting cell populations. In this study, we isolated extracellular vesicles (EVs) from organoids and analyzed the miRNAs derived from them to identify gene regulatory elements that coordinate proliferation and regeneration.

METHOD: We utilized cochlear floor cells from postnatal day two mice and optimized the culture conditions to efficiently grow organoids that exhibit progenitor properties. Next, we isolated EVs from the culture media of organoids in their proliferative state. We analyzed miRNAs contained in these EVs to identify potential regulators that drive or modulate organoid cell proliferation. The miRNA sequencing data from organoid EVs were compared with miRNAs identified in EVs obtained from the culture supernatant of P2 mouse cochlear ducts.

RESULTS: We identified 184 miRNAs in organoid EVs and 176 miRNAs in cochlear duct EVs. A total of 122 miRNAs differed more than twofold between these groups, with 12 miRNAs (10 upregulated and 2 downregulated in organoid EVs) exhibiting statistically significant differences. The target genes of these twelve differentially expressed miRNAs are associated with pathways related to pluripotent stem cell regulation, cell proliferation, ear development, and cell fate modulation. This indicates that the miRNAs in organoid-derived EVs may impact processes associated with cell proliferation and the generation of inner ear cell types.

CONCLUSION: Our study comprehensively inventoried miRNAs contained in EVs released by growing inner ear organoids. Our differential miRNA expression analysis provides insight into regulatory mechanisms that promote cochlear floor cell proliferation and organoid formation, which could be leveraged in miRNA-based therapeutic approaches.

PMID:40668461 | DOI:10.1007/s10162-025-00998-x

Eur J Orthop Surg Traumatol. 2025 Jul 16;35(1):307. doi: 10.1007/s00590-025-04419-w.

ABSTRACT

BACKGROUND: Lateral epicondylitis (tennis elbow) is a common musculoskeletal condition characterized by lateral elbow pain and functional impairment. While both extracorporeal shockwave therapy (ESWT) and ultrasound therapy are frequently used interventions, their relative effectiveness remains uncertain. This systematic review and meta-analysis aimed to compare the efficacy of ESWT versus ultrasound therapy in improving pain and functional outcomes in patients with lateral epicondylitis through a systematic review and meta-analysis of randomized controlled trials (RCTs).

METHODS: Searches were conducted across databases including Scopus, Web of Science, PubMed, and Cochrane Central up until August 2024. We selected studies comparing ESWT and ultrasound for lateral epicondylitis. The primary outcome was pain intensity, assessed using the visual analog scale (VAS). The secondary outcome was functional status, evaluated using the patient-rated tennis elbow evaluation (PRTEE) score. The Cochrane Risk of Bias (ROB2) tool was used to assess evidence quality, and data analysis was performed using RevMan 5.4.

RESULTS: Nine RCTs involving 654 participants were included. ESWT demonstrated significantly greater pain reduction than ultrasound (MD = – 0.90, 95% CI [- 1.28, – 0.52], p < 0.0001). However, there was no statistically significant difference in functional outcomes as measured by PRTEE (MD = – 5.28, 95% CI [- 10.61, 0.04], p = 0.05). Substantial heterogeneity was noted for both outcomes.

CONCLUSION: ESWT appears more effective than ultrasound therapy in reducing pain in lateral epicondylitis. However, this superiority does not extend to functional improvement. Given the observed heterogeneity and borderline statistical significance in functional outcomes, further high-quality trials are warranted.

PMID:40668449 | DOI:10.1007/s00590-025-04419-w

Lasers Med Sci. 2025 Jul 16;40(1):318. doi: 10.1007/s10103-025-04569-7.

ABSTRACT

This systematic review aims to evaluate the efficacy of laser-based photobiomodulation therapy (PBMT) in reducing pain associated with dental injections. The review addresses the research question: “What is the effect of PBMT on pain levels during local anesthetic injections in dental patients compared to control interventions?”. A comprehensive search was conducted across PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases. Studies included were prospective or retrospective clinical trials involving PBMT for pain control during dental injections. The quality of studies was assessed using the revised Cochrane Risk of Bias 2 tool. Data were extracted on patient demographics, laser parameters, and pain outcomes. A total of 14 studies were included in this systematic review, with 6 focusing on children and 8 on adults. In children, three studies indicated that PBMT effectively reduced pain, with a significant difference according to the Wong-Baker FACES Pain Rating Scale (WFPRS) but not on the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. Conversely, three studies found no significant differences between PBMT and topical anesthesia. In adults, five studies demonstrated a pain-reducing effect of PBMT, though one study reported a statistically significant difference that did not achieve clinical significance. The meta-analysis revealed a statistically significant overall effect of PBMT on pain reduction in both children and adults (p < 0.05). This systematic review of the literature suggests that PBMT may help reduce discomfort associated with dental injections in both adults and children. Nonetheless, further investigation is warranted to arrive at a more definitive conclusion on this topic.

PMID:40668432 | DOI:10.1007/s10103-025-04569-7

Lab Chip. 2025 Jul 16. doi: 10.1039/d4lc01092b. Online ahead of print.

ABSTRACT

In this article, we study the height distribution of phoretically active microparticles exposed to external flow. Sedimented particles hover under light illumination and experience a stronger shear force proportional to the elevation height of the particle. Due to the natural variation in the phoretic activity of individual particles, their hovering heights also vary, resulting in an observed velocity distribution along the flow streamline. Furthermore, the hovering height results from a many-body problem of long-ranged phoretic effects of individual particles. Indeed, the mean velocity and its distribution depend on particle concentration: as the concentration increases, both the mean velocity and the width of the velocity distribution decrease, until a certain concentration is reached beyond which both remain constant. This results from overlapping chemical product gradient of an individual particle with its neighbors, basically decreasing with increasing concentration – and so the phoretic activity and hovering height. Besides, during the hovering we observe a localized dilution having an impact on the light-induced velocity changes of the microparticles.

PMID:40667569 | DOI:10.1039/d4lc01092b

JCO Oncol Adv. 2025 Jul 9;2(1):e2400101. doi: 10.1200/OA-24-00101. eCollection 2025.

ABSTRACT

PURPOSE: The vast majority of cervical cancer is preventable through human papillomavirus vaccination and screening with cytology or DNA testing. After decades of progress, recent cervical cancer trends in Western populations show a plateau or modest increase in incidence rates. Further investigation is required to understand the drivers of these emerging trends. In this study, we examined age-specific cervical cancer incidence rates in Canada from 1992 to 2022.

METHODS: Data were obtained from the Canadian Cancer Registry maintained by Statistics Canada, which included cancer cases, population counts, and incidence rates of cervical cancer by age and province for the period 1992 to 2022. Joinpoint regression analysis was used to estimate temporal incidence trends across age groups.

RESULTS: Cervical cancer incidence rates in Canada decreased among women age 25-34 years and those 65 years and older since 1992. Incidence rates among women age 35-44 years and 45-54 years have increased by 1.1% (95% CI, 0.5 to 2.5) and 1.6% (95% CI, -0.1 to 8.6) per year since 2001 and 2012, respectively. In 2022, the highest incidence rate of cervical cancer was among women age 35-44 years (18.1 per 100,000 women), which is comparable with rates in 1992.

CONCLUSION: Cervical cancer incidence rates have been increasing in recent years among women age 35-54 years. This cohort may be falling into a cancer prevention gap. Targeted public health interventions are warranted to address the rising incidence of cervical cancer among this cohort of Canadian women.

PMID:40667567 | PMC:PMC12258797 | DOI:10.1200/OA-24-00101

Am J Cancer Res. 2025 Jun 15;15(6):2618-2630. doi: 10.62347/RLWT8295. eCollection 2025.

ABSTRACT

Osteosarcoma is a prevalent primary malignant bone tumor in young adults and adolescents, characterized by a high recurrence rate despite advancements in chemotherapy and surgical methods. This study investigated the effects of integrating high-dose methotrexate with cisplatin and paclitaxel on survival outcomes in osteosarcoma patients, and to identify prognostic factors influencing these outcomes. A retrospective analysis was conducted on 208 osteosarcoma patients treated between January 2013 and December 2018. Patients were divided into two groups: standard chemotherapy group (SC, n = 104) and cisplatin + paclitaxel + high-dose methotrexate (CPM, n = 104). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary endpoints included efficacy assessments. Kaplan-Meier survival curves were used to assess survival distributions, and statistical analyses were performed using SPSS 29.0. The CPM group demonstrated significantly longer PFS (16.85 ± 3.40 months vs. 15.72 ± 3.21 months, P = 0.015) and higher 5-year OS rates (54.81% vs. 40.38%, P = 0.037) compared to the SC group. Completion of chemotherapy and a response rate greater than 90% were identified as strong positive prognostic indicators. In contrast, pathologic fractures at diagnosis, lung metastases, and elevated lactate dehydrogenase levels were associated with poorer outcomes. Multivariate analysis underscored chemotherapy response and treatment adherence as independent survival predictors. The combination of cisplatin and paclitaxel with high-dose methotrexate significantly improves PFS and OS compared to standard chemotherapy. Moreover, treatment completion and achieving a chemotherapy response greater than 90% are critical factors for favorable prognosis.

PMID:40667547 | PMC:PMC12256419 | DOI:10.62347/RLWT8295

Ann Appl Stat. 2025 Jun;19(2):1314-1331. doi: 10.1214/25-aoas2013. Epub 2025 May 28.

ABSTRACT

Semi-continuous data frequently arise in clinical practice. For example, while many surgical patients still suffer from varying degrees of acute postoperative pain (POP) sometime after surgery (i.e., POP score > 0), others experience none (i.e., POP score = 0), indicating the existence of two distinct data processes at play. Existing parametric or semi-parametric two-part modeling methods for this type of semi-continuous data can fail to appropriately model the two underlying data processes as such methods rely heavily on (generalized) linear additive assumptions. However, many factors may interact to jointly influence the experience of POP non-additively and non-linearly. Motivated by this challenge and inspired by the flexibility of deep neural networks (DNN) to accurately approximate complex functions universally, we derive a DNN-based two-part model by adapting the conventional DNN methods with two additional components: a bootstrapping procedure along with a filtering algorithm to boost the stability of the conventional DNN, an approach we denote as sDNN. To improve the interpretability and transparency of sDNN, we further derive a feature importance testing procedure to identify important features associated with the outcome measurements of the two data processes, denoting this approach fsDNN. We show that fsDNN not only offers a statistical inference procedure for each feature under complex association but also that using the identified features can further improve the predictive performance of sDNN. The proposed sDNN- and fsDNN-based two-part models are applied to the analysis of real data from a POP study, in which application they clearly demonstrate advantages over the existing parametric and semi-parametric two-part models. Further, we conduct extensive numerical studies and draw comparisons with other machine learning methods to demonstrate that sDNN and fsDNN consistently outperform the existing two-part models and frequently used machine learning methods regardless of the data complexity. An R package implementing the proposed methods has been developed and is available in the Supplementary Material (Zou et al, 2025) and is also deposited on GitHub (https://github.com/BZou-lab/fsDNN).

PMID:40667518 | PMC:PMC12263096 | DOI:10.1214/25-aoas2013

Front Pharmacol. 2025 Jul 1;16:1608657. doi: 10.3389/fphar.2025.1608657. eCollection 2025.

ABSTRACT

BACKGROUND: With the increasing clinical use of tirzepatide, its safety profile has garnered significant attention. This article systematically reviews case reports of tirzepatide-associated adverse drug reactions (ADRs) to summarize their characteristics.

METHOD: We searched PubMed, Web of Science, ScienceDirect, Wiley Online, and Embase databases for case reports on tirzepatide adverse events using the keywords: “tirzepatide”, “adverse reaction”, “adverse event”, “side effect”, “safety”, “case report”, “induced”, “associated”, and “related”. Statistical analysis was performed on the identified cases.

RESULTS: A total of 43 cases of tirzepatide ADR were identified from 37 articles. Among these patients (24 female, 19 male; mean age 50.23 ± 17.24 years), 19 involved concomitant medications affecting multiple systems. ADR was reported in each dosage of tirzepatide, with the most occurring at 2.5-5 mg (16 cases), and primarily occurred within 1-6 months of initiation. Regarding rechallenge, 15 patients discontinued tirzepatide, three continued use, and one reduced the dose. ADR involved seven gastrointestinal tract and endocrine systems, including liver and gallbladder, circulation, nerve, skin, and urinary. Notable manifestations included ketoacidosis, liver injury, hypotension, intestinal obstruction, and allergic reactions. Among them, ketoacidosis and common peroneal neuropathy causing foot sagging, acute appendicitis, lower limb venous thrombosis, gastric outlet obstruction, gastric emptying delay, and acute liver injury were not mentioned in the drug instructions. ADR correlation assessment was performed for 8 patients:4 cases of cardiovascular events and ketoacidosis were all evaluated as “probable” using the Naranjo scale, 3 cases of liver injury were assessed by RUCAM (2 case as “possible”, 1 cases as “probable”), 1 case did not specify the evaluation method, with the result being “highly probable”. All 43 patients underwent ADR correlation re-evaluation:32 cases (74.42%) were assessed as “probable”,11 cases (25.58%) were assessed as “possible”.

CONCLUSION: Tirzepatide-associated ADRs most commonly occur within the first 6 months of treatment, primarily affecting the digestive, endocrine, liver, and gallbladder systems. Enhanced monitoring of liver and kidney function is warranted, especially in patients concurrently taking other potentially hepatotoxic or nephrotoxic medications. Additionally, intensified therapeutic drug monitoring is recommended for patients with cardiovascular disease, those requiring weight-based dosing adjustments, and those experiencing rapid weight loss.

PMID:40667509 | PMC:PMC12259682 | DOI:10.3389/fphar.2025.1608657

Front Pharmacol. 2025 Jul 1;16:1587440. doi: 10.3389/fphar.2025.1587440. eCollection 2025.

ABSTRACT

PURPOSE: Glaucoma, characterized by progressive retinal ganglion cell (RGC) degeneration and optic nerve atrophy, remains a leading global cause of irreversible blindness, despite advancements in clinical management. While current therapies predominantly focus on lowering intraocular pressure (IOP), neuroprotective strategies to preserve visual function remain an unmet clinical need. Stem cells exhibit high proliferative capacity and multilineage differentiation potential, demonstrating notable efficacy in glaucoma treatment. Emerging preclinical evidence further highlights dual neuroprotective mechanisms (i.e., paracrine neurotrophic support and cellular replacement) of stem cell-based interventions. Accordingly, this systematic review and meta-analysis evaluated the therapeutic efficacy and safety of stem cell transplantation in experimental glaucoma models, with a focus on functional outcomes (IOP modulation), structural preservation (RGC survival, and nerve fiber layer integrity), and neuroprotective efficacy.

METHODS: A systematic literature retrieval from multiple online databases (e.g., PubMed, Web of Science, Embase, Cochrane Library, Scopus, CNKI, WFSD, VIP, and CBM) was conducted through 3 January 2025, to identify relevant animal experimental studies. After the assessment of the risk of bias in the listed articles, this study further computed effect sizes of stem cell transplantation on indices such as IOP, RGC count. Statistical analyses were completed using RevMan 5.3.

RESULTS: In the meta-analysis involving 19 studies, the stem cell transplantation group had significantly lower IOP (MD = -1.55,95% CI = -2.62 to -0.47) at weeks 3 and 4, higher RGC count at weeks 2, 3, and 4 (MD = 23.06,95%CI = 18.22-27.89), and greater nerve fiber layer thickness (MD = 10.69, 95%CI = 9.44-11.94) compared to the control group. Meanwhile, the stem cell transplantation group also had higher retinal BDNF expression at weeks 2 and 4 (MD = 0.75,95%CI = 0.67-0.83), GDNF expression at weeks 1, 2, 3, and 4, and IGF-1 expression (MD = 0.49,95%CI = 0.39-0.58). None of these studies reported any adverse systemic events.

CONCLUSION: This meta-analysis provides preclinical evidence supporting stem cell transplantation as a multimodal therapeutic strategy for glaucoma, demonstrating significant efficacy in IOP modulation, neurostructural preservation, and neurotrophic factor expression. Given the severity of glaucoma-induced ocular structural damage, it underscores the significance of stem cell transplantation as a secure and promising therapeutic option with notable neuroprotective potential, despite existing translational challenges regarding optimal cell sources, delivery routes, and long-term safety profiles.

SYSTEMATIC REVIEW REGISTRATION: www.inplasy.com, identifier 202520023.

PMID:40667506 | PMC:PMC12259681 | DOI:10.3389/fphar.2025.1587440