Tag: nevin manimala

Front Oncol. 2024 Nov 7;14:1415636. doi: 10.3389/fonc.2024.1415636. eCollection 2024.

ABSTRACT

INTRODUCTION: Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome primarily caused by germline TP53 pathogenic/likely pathogenic (P/LP) variants. Soft tissue and bone sarcomas are among the most frequently occurring of the many LFS-associated cancer types. Cancer screening recommendations for LFS are centered around annual whole-body MRI (wbMRI), the interpretation of which can be challenging. This study aims to characterize sarcoma topography in LFS.

METHODS: Study subjects included individuals from clinically and genetically ascertained cohorts of germline TP53 variant-carriers, namely the National Cancer Institute’s LFS longitudinal cohort study (NCI-LFS), the NCI Genetic Epidemiology of Osteosarcoma (NCI-GEO) study, and the germline TP53 Database.

RESULTS: Data was aggregated for a total of 160 sarcomas that had detailed topography available. Abdominal sarcomas and extremity osteosarcomas were among the most frequent locations of sarcomas. Chi-squared analyses showed no statistical differences in sarcoma topography based on age (pediatric vs adult) or sex (male vs female). A case series of sarcomas from the NCI-LFS study highlights the diagnostic challenges due to topography-related imaging.

DISCUSSION: While LFS-related sarcomas frequently occur in expected locations such as the extremities, they also occur in less typical sites, leading to difficulties in discerning between differential diagnoses on wbMRI and imaging. Prospective collection of detailed cancer topography in individuals with LFS will further aid in recommendations for radiologic interpretation and personalized screening in individuals with LFS.

PMID:39575416 | PMC:PMC11578819 | DOI:10.3389/fonc.2024.1415636

Front Digit Health. 2024 Nov 7;6:1198904. doi: 10.3389/fdgth.2024.1198904. eCollection 2024.

ABSTRACT

According to World Health Organization statistics, inappropriate medication has become an important factor affecting the safety of rational medication. In the gray area of medical insurance supervision, such as designated drugstores and medical institutions, there are lots of inappropriate medication phenomena regarding “big prescription for minor ailments.” A traditional clinical decision support system is mostly based on established rules to regulate inappropriate prescriptions, which are not suitable for clinical environments and require intelligent review. In this study, we model the complex relationships between patients, diseases, and drugs based on medical big data to promote appropriate medication use. More specifically, we first construct the medication knowledge graph based on the historical prescription big data of tertiary hospitals and medical text data. Second, based on the medication knowledge graph, we employ a Gaussian mixture model to group patient population representation as physiological features. For diagnostic features, we employ pre-training word vector Bidirectional Encoder Representations from Transformers to enhance the semantic representation between diagnoses. In addition, to reduce adverse drug interactions caused by drug combinations, we employ a graph convolution network to transform drug interaction information into drug interaction features. Finally, we employ the sequence generation model to learn the complex relationships between patients, diseases, and drugs and provide an appropriate medication evaluation for doctor prescriptions in small hospitals from two aspects: drug list and medication course of treatment. In this study, we utilize the MIMIC III dataset alongside data from a tertiary hospital in Fujian Province to validate our model. The results show that our method is more effective than other baseline methods in the accuracy of the medication regimen prediction of rational medication. In addition, it achieved high accuracy in the appropriate medication detection of prescription in small hospitals.

PMID:39575413 | PMC:PMC11578981 | DOI:10.3389/fdgth.2024.1198904

Foot Ankle Orthop. 2024 Nov 20;9(4):24730114241300160. doi: 10.1177/24730114241300160. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: Randomized controlled trials (RCTs) are the gold standard for treatment efficacy, but foot and ankle RCTs are often small or inconsistent. The Fragility Index (FI) evaluates the stability of significant findings. This study assessed the fragility of RCT outcomes for Achilles tendon pathology (ATP) interventions.

METHODS: This systematic review queried PubMed up to May 14, 2024, for RCTs on ATP interventions. RCTs with significant binary outcomes were included. Two reviewers assessed eligibility, extracted data, calculated FIs, and evaluated risk of bias. Frequency-weighted means were used for narrative synthesis.

RESULTS: Eleven RCTs with 4506 patients (mean cohort size: 409.64 ± 160.54) and a mean age of 36.97 ± 13.51 years (n = 4356; 96.67%) were included, covering 24 binary outcomes. The median FI across all outcomes was 3 (interquartile range 1-4; mean 3.92), indicating that changing the outcome of just a few patients could shift a study’s results from statistically significant to nonsignificant. Trials having an FI ≤3 comprised 58.33%. Three outcomes (12.5%) had an FI of zero after recalculating P values using the two-sided Fisher exact test. Half of the outcomes were robust. No RCT reported FIs or adjusted significance for multiple testing. Most studies (81.82%) performed 2 or more statistical tests, with an average of 30.81 ± 41.28 P values reported per study. The overall risk of bias was low in 1 study (9.09%) and moderate in 7 (63.64%). Most studies had low risk of bias in randomization (72.73%) and missing outcome data (90.91%).

CONCLUSION: The FI assesses the fragility of statistically significant binary results, revealing that many ATP RCTs have fragile outcomes due to small sample sizes. A median FI of 3 means that changing the outcome of 3 patients could shift a study’s results from statistically significant to nonsignificant.

PMID:39575398 | PMC:PMC11580056 | DOI:10.1177/24730114241300160

Front Pharmacol. 2024 Nov 7;15:1475021. doi: 10.3389/fphar.2024.1475021. eCollection 2024.

ABSTRACT

OBJECTIVE: This network meta-analysis aims to explore the efficacy and safety of neuroprotective agents in patients with ischemic stroke and attempts to identify which drug is the most effective in improving outcomes for patients with acute ischemic stroke (AIS) through a ranking method.

METHODS: We comprehensively searched the PubMed, Medline, Embase, Web of Science, and Cochrane library databases from their establishment to 30 June 2024. Data were extracted from the studies identified, and their quality was assessed using the Cochrane risk-of-bias tool or the Newcastle-Ottawa Scale (NOS). The outcome measures were for a favorable prognosis, based on the modified Rankin Scale score (mRS) or National Institutes of Health Stroker Scale (NIHSS) score, mortality, and adverse effect with different drug regimens. We utilized Stata version 16.0 and Review Manager (RevMan) version 5.3.0 for statistical analysis.

RESULTS: A total of 35 studies were included: 25 randomized control trials, eight retrospective studies, and two prospective studies. The total sample size was 18,423 cases and included nine interventions: citicoline, edaravone (EDV), edaravone dexborneol, cinepazide maleate, cerebrolysin, minocycline, ginkgolide, ginkgo diterpene lactone meglumine (GDLM), and conventional (CON) treatment. Our analysis revealed that, except for edaravone dexborneol, the ginkgolide, EDV, cinepazide maleate, citicoline, cerebrolysin, minocycline, and GDLM treatment schemes reduced the mortality of patients with AIS compared with CON. Each drug regimen significantly improved the neural function of these patients compared with CON, which from highest to lowest was citicoline + vinpocetine, GDLM, citicoline, edaravone dexborneol, cinepazide maleate, ginkgolide, EDV, and CON. Moreover, we also found that, except for citicoline, the ginkgolide, EDV, edaravone dexborneol, GDLM, and cinepazide maleate treatment schemes had a high total treatment effective rate in these patients, the order from highest to lowest being ginkgolide, EDV, edaravone dexborneol, GDLM, cinepazide maleate, CON, and citicoline. In terms of the ineffective rate, we found that, compared with CON, the edaravone dexborneol, EDV, citicoline, GDLM, ginkgolide, and cinepazide maleate treatment schemes all had a lower ineffective rate. Finally, our analysis revealed that, except for cinepazide maleate and ginkgolide, the EDV, minocycline, edaravone dexborneol, GDLM, citicoline, and cerebrolysin schemes all had a higher rate of adverse effect on patients compared to CON. Based on the impact of the adverse effect with different surgical interventions, we further analyzed the effect of these drug treatments by the total treatment effective rate combined with adverse effect, revealing that EDV, ginkgolide, and edaravone dexborneol were the safest and most effective treatments.

CONCLUSION: In patients with AIS, ginkgolide, EDV, cinepazide maleate, citicoline, cerebrolysin, minocycline, and GDLM were associated with a reduction in mortality rate. Moreover, ginkgolide, EDV, edaravone dexborneol, and GDLM treatment schemes revealed not only a high total treatment effective rate but also a low rate of treatment inefficacy. When considering the combination of the total treatment effective rate with adverse effect, EDV, ginkgolide, and edaravone dexborneol were revealed as the safest and most effective.

PMID:39575393 | PMC:PMC11578817 | DOI:10.3389/fphar.2024.1475021

Front Pharmacol. 2024 Nov 7;15:1473756. doi: 10.3389/fphar.2024.1473756. eCollection 2024.

ABSTRACT

BACKGROUND: This study analyzed the FDA’s Adverse Event Reporting System (FAERS) data to investigate the correlation between oral bisphosphonates (BPs) and oesophageal adverse events (AEs).

METHODS: We systematically extracted data on adverse reactions to oral alendronate, risedronate, and ibandronate from the FAERS database, covering the period from the 2004 Q1 to the 2023 Q4. The role_code of AEs mainly includes primary suspect (PS), secondary suspect (SS), concomitant (C), and interaction (I). This study targeted reports with a role_code of “PS.” According to the FDA deduplication rule, the latest FDA_DT is selected when the CASEID is the same, and the higher PRIMARYID is selected when the CASEID and FDA_DT are the same. Our analysis leveraged four statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS), to assess the relationship between oral bisphosphonates and oesophageal AEs. The Kaplan-Meier method was utilized to evaluate the cumulative incidence of oesophageal toxicity, while the log-rank test examined the temporal onset profiles of these toxicities. Additionally, the Pearson chi-squared test was employed to identify any significant differences in mortality and hospitalization rates associated with the oesophageal AEs caused by these medications.

RESULTS: The FAERS database had 41,590 AE reports for oral BPs, with 3,497 (8.41%) related to oesophageal AEs. Our findings indicate that oral BPs are disproportionately associated with an increased incidence of gastrointestinal system AEs at the system organ class (SOC) level. The adverse events identified at the preferred terms (PTs) level encompassed conditions such as gastroesophageal reflux disease, oesophagitis, and oesophageal pain. A significant divergence in the cumulative incidence of oesophageal AEs was observed among patients treated with the three different oral bisphosphonates, as confirmed by the log-rank test (p < 0.0001). Hospitalization rates varied significantly among patients receiving different BPs (p < 0.05), but no significant difference in mortality rates was found.

CONCLUSION: The study establishes a significant link between oral BPs and oesophageal toxicity, highlighting the need for further research into the mechanisms of BP-induced oesophageal toxicity and potential preventive measures.

PMID:39575385 | PMC:PMC11578700 | DOI:10.3389/fphar.2024.1473756

RSC Adv. 2024 Nov 21;14(50):37286-37298. doi: 10.1039/d4ra03069a. eCollection 2024 Nov 19.

ABSTRACT

Breast cancer is the fifth major cause of fatalities associated with cancer worldwide and in Pakistan, 34 066 female breast cancer cases were recorded in 2018. This study was designed to understand extracts of Cheiranthus cheiri (C. cheiri) and to evaluate the epigenetic modulation of microRNA expression for breast cancer therapy using a selected phyto-nanohybrid treatment. The phytochemical screening revealed the presence of potential phytochemicals and antioxidant scavenging activity in the C. cheiri extracts with a DPPH (2-diphenyl-1-picryl-hydroxyl) assay giving an IC₅₀ value of 20.63 μg mL^-1. GC-MS (gas chromatography-mass spectroscopy) analysis of the C. cheiri n-hexane extract detected 42 phytocompounds. Titanium oxide (TiO₂) nanoparticles were synthesized and characterized using XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDX (energy dispersive X-ray spectrometry) to confirm the synthesis of anatase (tetragonal) TiO₂. The prepared nanoparticles were conjugated with the selected plant i.e., C. cheiri. The resulting phyto-nanohybrid was used for the subsequent treatment of breast cancer induced in a female rat model. The treatment groups were as follows: doxorubicin as the standard treatment, C. cheiri, TiO₂ and the phyto-nano hybrid treatment. After 8 weeks of treatment, the groups induced to exhibit breast cancer (with and without treatment) and the control groups were dissected and analysed for histopathological, haematological and microRNA expression. Histopathological examination revealed chronic inflammation in the dilated ducts and tumour embolus formation, thus confirming the presence of breast cancer in the DMBA-induced female rat model. MicroRNA expression analysis showed a statistically significant decrease in levels of miR-205 in the plasma of the breast cancer rat model compared to the control (p < 0.05). After treatment with the phyto-nano hybrid, a statistically significant increase in the expression of miR-205 was observed in the rat models induced to exhibit breast cancer compared to the rat model without any treatment (p < 0.05). The downregulation of miR-205 in the plasma of the breast cancer exhibiting model, as compared to the control, and its upregulation after treatment with the selected phyto-nano hybrid indicated its diagnostic and prognostic significance. It is concluded that the phyto-nano hybrid used in this study is effective against breast cancer induced female rat model. All the results support the finding that the selected phyto-nano hybrid has great potential as a possible therapeutic agent for the treatment of breast cancer.

PMID:39575377 | PMC:PMC11580155 | DOI:10.1039/d4ra03069a

Cureus. 2024 Nov 19;16(11):e74049. doi: 10.7759/cureus.74049. eCollection 2024 Nov.

ABSTRACT

The optimal duration of antibiotic prophylaxis for patients undergoing primary hip or knee arthroplasty remains debated. We conducted a systematic review and meta-analysis to compare the outcomes of single-dose versus extended antibiotic prophylaxis. Studies assessing these strategies for periprosthetic joint infection (PJI), revision surgery, and superficial surgical site infections were selected from systematic searches in PubMed, Embase, and the Cochrane Library. Results were synthesized using random-effects meta-analysis models. Nine studies were included, covering 295,654 patients – 125,489 undergoing total knee arthroplasty and 172,055 undergoing total hip arthroplasty. A significant statistical difference in the incidence of PJI favored single-dose over extended antibiotic prophylaxis (OR 0.78; 95% CI 0.63-0.98; I² = 0%). Our meta-analysis suggests that a single-dose prophylactic antibiotic regimen may be preferable for reducing PJI incidence in primary total hip and knee arthroplasty.

PMID:39575360 | PMC:PMC11580755 | DOI:10.7759/cureus.74049

Endocr Regul. 2024 Nov 21;58(1):220-224. doi: 10.2478/enr-2024-0026. Print 2024 Jan 1.

ABSTRACT

Objective. The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes in the responsiveness of members of a cluster of seven measures in older persons with type 2 diabetes mellitus (T2DM) consuming flaxseed lignan complex (FLC). The cluster of seven are abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDLc), and increased plasma levels of triglycerides), increased low-density lipoprotein (LDL) oxidation and increased inflammation. All cluster members exacerbate T2DM. Methods. Sixteen patients with well-controlled T2DM participated in this double-blind randomized, placebo-controlled crossover study consisting of four visits. Apolipoprotein E genotyping was done at visit one. The cluster of seven, diet, exercise, smoking and medication use were assessed at each visit. Results. The 3/4 genotype showed a stronger downward trend in systolic blood pressure compared to the 3/3 genotype with no trend or significant difference in the 2/4 genotype. There was a downward trend in diastolic blood pressure in genotype 3/3 compared genotype 2/4, which showed no significant difference or trend. Only genotype 3/4 showed a significant drop in diastolic pressure compared to genotypes 2/4 and 3/3. HDLc only showed a downward trend in 3/4 relative to genotypes 2/4 and 3/3. LDL apolipoprotein B oxidation (LDL-Box) only showed an upward trend in 3/3 compared to genotypes 2/4 and 3/4. There were no other significant differences or trends by genotype in the cluster of seven. Conclusions. It appears that those with the 2/4 genotype may not benefit from FLC, those with 3/3 and 3/4 genotypes may benefit only in terms of systolic and diastolic pressures, those with the apo E 3/4 genotype should perhaps avoid FLC to manage HDLc, and those with the 3/3 genotype should perhaps avoid FLC to manage LDL apolipoprotein B oxidation.

PMID:39572875 | DOI:10.2478/enr-2024-0026

Endocr Regul. 2024 Nov 21;58(1):225-232. doi: 10.2478/enr-2024-0027. Print 2024 Jan 1.

ABSTRACT

Objective. Reduced calciferol (vitamin D) levels in pregnant women have been associated with an increased risk to infant health. Progesterone sustains pregnancy and reduces the risk of premature birth through its metabolites affecting myometrial contractility. Sex hormone-binding globulin protein (SHBG) is a biomarker of premature birth. The present study aimed to find out if early pregnancy levels of vitamin D, SHBG, and progesterone metabolites may predict preterm birth risk. Methods. Five hundred pregnant women aged 18-43 years during their 2nd and 3rd trimesters from multiple civilian regional medical centers in Lahore participated in the study. Blood samples taken from participants were used to determine vitamin D, SHBG, 11-deoxycorticosterone (DOC), and 16α-hydroxyprogesterone (16α-OHP) levels using specific ELISA kits. Statistical analysis was performed by one-way ANOVA using the latest GraphPad Prism software. Results. A significant decrease in vitamin D, DOC, and SHBG levels (p<0.001, p<0.001, and p<0.05, respectively) in the preterm birth cohorts in the 2nd and 3rd trimester was found compared to the corresponding control groups. Furthermore, 16α-OHP levels in the preterm birth cohorts in the 2nd and 3rd trimesters were significantly increased (p<0.001 and p=0.0062, respectively) compared to their control cohorts. Conclusion. The results of our study confirm that calciferol deficiency in pregnant women is associated with an increased risk of premature birth and indicate that SHBG and progesterone metabolites may be useful biomarkers for the early identification and prediction of preterm birth.

PMID:39572873 | DOI:10.2478/enr-2024-0027

Clin Oral Implants Res. 2024 Nov 21. doi: 10.1111/clr.14382. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the reliability and time efficiency of the conventional compared to the automatic artificial intelligence (AI) segmentation of the mandibular canal and registration of the CBCT with the model scan data, in relation to clinician’s experience.

MATERIALS AND METHODS: Twenty clinicians, 10 with a moderate and 10 with a high experience in computer-assisted implant planning, were asked to perform a bilateral localization of the mandibular canal, followed by a registration of the intraoral model scan with the CBCT. Subsequently, for each data set and each participant, the same operations were performed utilizing the AI tool. Statistical significance was assessed via a mixed model (using the PROC MIXED statement and the compound symmetry covariance structure).

RESULTS: The mean time for the segmentation of the mandibular canals and the registration of the models was 4.75 (2.03)min for the manual and 2.03 (0.36) min for the AI-automated operations (p < 0.001). The mean discrepancy in the mandibular canals was 0.71 (1.80) mm RMS error for the manual segmentation and 0.68 (0.36) RMS error for the AI-assisted segmentation (p > 0.05). For the registration between the CBCT and the intraoral scans, the mean discrepancy was 0.45 (0.16) mm for the manual and 0.37 (0.07) mm for the AI-assisted superimposition (p > 0.05).

CONCLUSIONS: AI-automated implant planning tools are feasible options that can lead to a similar or better accuracy compared to the conventional manual workflow, providing improved time efficiency for both experienced and less experienced users. Further research including a variety of software and data sets is required to be able to generalize the outcomes of the present study.

PMID:39572789 | DOI:10.1111/clr.14382