Nevin Manimala

Curr Neurol Neurosci Rep. 2024 Feb 28. doi: 10.1007/s11910-024-01335-0. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: This review summarizes previous and ongoing neuroprotection trials in multiple system atrophy (MSA), a rare and fatal neurodegenerative disease characterized by parkinsonism, cerebellar, and autonomic dysfunction. It also describes the preclinical therapeutic pipeline and provides some considerations relevant to successfully conducting clinical trials in MSA, i.e., diagnosis, endpoints, and trial design.

RECENT FINDINGS: Over 30 compounds have been tested in clinical trials in MSA. While this illustrates a strong treatment pipeline, only two have reached their primary endpoint. Ongoing clinical trials primarily focus on targeting α-synuclein, the neuropathological hallmark of MSA being α-synuclein-bearing glial cytoplasmic inclusions. The mostly negative trial outcomes highlight the importance of better understanding underlying disease mechanisms and improving preclinical models. Together with efforts to refine clinical measurement tools, innovative statistical methods, and developments in biomarker research, this will enhance the design of future neuroprotection trials in MSA and the likelihood of positive outcomes.

PMID:38416311 | DOI:10.1007/s11910-024-01335-0

Brain Topogr. 2024 Feb 28. doi: 10.1007/s10548-024-01038-2. Online ahead of print.

ABSTRACT

Over the past years, different studies provided preliminary evidence that Disorganized Attachment (DA) may have dysregulatory and disintegrative effects on both autonomic arousal regulation and brain connectivity. However, despite the clinical relevance of this construct, few studies have investigated the specific alterations underlying DA using electroencephalography (EEG). Thus, the main aim of the current study was to investigate EEG microstate parameters of DA in a non-clinical sample (N = 50) before (pre) and after (post) the administration of the Adult Attachment Interview (AAI). Two EEG eyes-closed Resting State (RS) recordings were performed before and after the AAI, which was used for classifying the participants [i.e., Disorganized/Unresolved (D/U) or Organized/Resolved (O/R) individuals] and to trigger the attachment system. Microstates parameters (i.e., Mean Duration, Time Coverage and Occurrence) were extracted from each recording using Cartool software. EEG microstates clustering analysis revealed 6 different maps (labeled A, B, C, D, E, F) in both groups (i.e., D/U and O/R individuals) and in both conditions (i.e., pre-AAI and post-AAI). In the pre-AAI condition, compared to O/R individuals, D/U participants showed a shorter Mean Duration and Time Coverage of Map F; in the post-AAI condition, a significant reduction in the Mean Duration of Map E was also observed in D/U individuals. Finally, in the “within” statistical analysis (i.e., pre-AAI vs. post-AAI), only the D/U group exhibited a significant increase in Time Coverage of Map F after the AAI. Since these maps are associated with brain networks involved in emotional information processing and mentalization (i.e., Salience Network and Default Mode Network), our result might reflect the deficit in the ability to mentalize caregiver’s interaction as well as the increased sensitivity to attachment-related stimuli typically observed in individuals with a D/U state of mind.

PMID:38416284 | DOI:10.1007/s10548-024-01038-2

Environ Monit Assess. 2024 Feb 28;196(3):315. doi: 10.1007/s10661-024-12459-8.

ABSTRACT

The estimation of exposures to humans from the various sources of radiation is important. Radiation hazard indices are computed using procedures described in the literature for evaluating the combined effects of the activity concentrations of primordial radionuclides, namely, ²³⁸U, ²³²Th, and ⁴⁰ K. The computed indices are then compared to the allowed limits defined by International Radiation Protection Organizations to determine any radiation hazard associated with the geological materials. In this paper, four distinct radial basis function artificial neural network (RBF-ANN) models were developed to predict radiation hazard indices, namely, external gamma dose rates, annual effective dose, radium equivalent activity, and external hazard index. To make RBF-ANN models, 348 different geological materials’ gamma spectrometry data were acquired from the literature. Radiation hazards indices predicted from each RBF-ANN model were compared to the radiation hazards calculated using gamma spectrum analysis. The predicted hazard indices values of each RBF-ANN model were found to precisely align with the calculated values. To validate the accuracy and the adaptability of each RBF-ANN model, statistical tests (determination coefficient (R²), relative absolute error (RAE), root mean square error (RMSE), Nash-Sutcliffe Efficiency (NSE)), and significance tests (F-test and Student’s t-test) were performed to analyze the relationship between calculated and predicted hazard indices. Low RAE and RMSE values as well as high R², NSE, and p-values greater than 0.95, 0.71, and 0.05, respectively, were found for RBF-ANN models. The statistical tests’ results show that all RBF-ANN models created exhibit precise performance, indicating their applicability and efficiency in forecasting the radiation hazard indices of geological materials. All the RBF-ANN models can be used to predict radiation hazard indices of geological materials quite efficiently, according to the performance level attained.

PMID:38416264 | DOI:10.1007/s10661-024-12459-8

Maxillofac Plast Reconstr Surg. 2024 Feb 28;46(1):6. doi: 10.1186/s40902-024-00419-8.

ABSTRACT

BACKGROUND: The size of dental implants is a key success factor for appropriate osseointegration. Using shorter implants allows the possibility of avoiding complex surgical procedures and reduces the morbidity of treatment. Shorter implants also enable implant-prosthetic rehabilitation after maxillofacial reconstructions where only limited bone is available. In this study, the success rates of short implants were examined and compared to those of standard-sized implants.

METHODS: Patients who received dental implants between 2007 and 2016 at the Department of Oro-Maxillofacial Surgery and Stomatology Semmelweis University were enrolled in the study. Several clinical parameters were recorded and supplemented with radiological examinations. The data were statistically analysed.

RESULTS: Thirty-four patients with a total of 60 implants were included. The average time after prosthetic loading was 39.33 ± 21.96 months in the group with 8-mm implants and 41.6 ± 27.5 months in the group with > 8-mm implants. No significant differences were observed between the two groups in terms of probing depth (short implants, 2.84 ± 0.09 mm; standard implants, 2.91 ± 0.35 mm) or mean marginal bone loss (short implants, 1.2 ± 1.21-mm mesially and 1.36 ± 1.47-mm distally; standard implants: 0.63 ± 0.80-mm mesially and 0.78 ± 0.70-mm distally).

CONCLUSIONS: In this study, the success rate of short dental implants was comparable to that of standard-sized implants. Consequently, it can be claimed that the long-term success of short dental implants does not differ significantly from the long-term success of standard implants.

PMID:38416263 | DOI:10.1186/s40902-024-00419-8

Gastric Cancer. 2024 Feb 28. doi: 10.1007/s10120-024-01477-7. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant.

METHODS: In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10 mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

RESULTS: During 8 years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09-1.30) for HDL-C < 30 mg/dL, 1.07 (95% CI 1.03-1.12) for HDL-C of 30-39 mg/dL, and 1.07 (95% CI 1.03-1.12) for HDL-C of 40-49 mg/dL comparing to HDL-C of 60-69 mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12-1.51) for HDL-C of 70-79 mg/dL, 1.84 (1.53-2.22) for HDL-C of 80-89 mg/dL, 2.10 (1.67-2.61) for HDL-C ≥ 90 mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04-1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers.

CONCLUSIONS: Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.

PMID:38416240 | DOI:10.1007/s10120-024-01477-7

Graefes Arch Clin Exp Ophthalmol. 2024 Feb 28. doi: 10.1007/s00417-024-06421-0. Online ahead of print.

ABSTRACT

PURPOSE: To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD).

METHODS: Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023.

RESULTS: A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: – 31 μm, IQR: 55, p < 0.0001 and median difference: – 21 μm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 μm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 μm, IQR: 64, p = 0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed.

CONCLUSIONS: Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation.

STUDY REGISTRATION: ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.

PMID:38416237 | DOI:10.1007/s00417-024-06421-0

J Med Virol. 2024 Mar;96(3):e29468. doi: 10.1002/jmv.29468.

ABSTRACT

Cervical human papillomavirus (HPV) infection is believed to increase the risks of pregnancy failure and abortion, however, whether the uterine cavity HPV infection reduces pregnancy rate or increases miscarriage rate remains unclarified in infertile women undergoing assisted reproductive technology (ART) treatment. Therefore, we aimed to assess ART outcomes in the presence of intrauterine HPV. This was a hospital-based multicenter (five reproductive medicine centers) matched cohort study. This study involved 4153 infertile women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection treatment in five reproductive medicine centers between October 2018 and 2020. The spent embryo transfer media sample with endometrium tissue were collected and performed with flow-through hybridization and gene chips to detect HPV DNA. According to basic characteristics, HPV-positive and negative patients were matched in a ratio of 1:4 by age, body mass index transfer timing, transfer type, and number of embryos transferred. The primary outcome was pregnancy and clinical miscarriage rates in the transfer cycle underwent HPV detection. 92 HPV-positive and 368 HPV-negative patients were screened and analyzed statistically. Univariate analysis showed uterine cavity HPV infection resulted in lower rates of ongoing pregnancy (31.5% vs. 44.6%; p = 0.023), implantation (32.3% vs. 43.1%; p = 0.026), biochemical pregnancy (47.8% vs. 62.5%; p = 0.010), and clinical pregnancy (40.2% vs. 54.3%; p = 0.015) compared with HPV negative group. The infertile female with positive HPV also had a slightly higher frequency of biochemical miscarriage (15.9% vs. 13.0%; p = 0.610) and clinical miscarriage (24.3% vs. 15.5%; p = 0.188). These findings suggest that HPV infection in the uterine cavity is a high risk for ART failure. HPV screening is recommended before ART treatment, which may be benefit to improving pregnancy outcome.

PMID:38415499 | DOI:10.1002/jmv.29468

Curr Med Imaging. 2024 Feb 26. doi: 10.2174/0115734056290762240209071656. Online ahead of print.

ABSTRACT

INTRODUCTION: The diagnosis and characterization of vertebral compression fractures are very important for clinical management. In this evaluation, which is usually performed with diagnostic (conventional) imaging, the findings are not always typical or diagnostic. Therefore, it is important to have new information to support imaging findings. Texture analysis is a method that can evaluate information contained in diagnostic images and is not visually noticeable. This study aimed to evaluate the magnetic resonance images of cases diagnosed with vertebral compression fractures by the texture analysis method, compare them with histopathological data, and investigate the effectiveness of this method in the differentiation of benign and malignant vertebral compression fractures.

METHODS: Fifty-five patients with a total of 56 vertebral compression fractures were included in the study. Magnetic resonance images were examined and segmented using Local Image Feature Extraction (LIFEx) software, which is an open-source program for texture analysis. The results were compared with the histopathological diagnosis.

RESULTS: The application of the Decision Tree algorithm to the dataset yielded impressively accurate predictions (≈95% in accuracy, precision, and recall).

CONCLUSION: Interpreting tissue analysis parameters together with conventional magnetic resonance imaging findings can improve the abilities of radiologists, lead to accurate diagnoses, and prevent unnecessary invasive procedures. Further prospective trials in larger populations are needed to verify the role and performance of texture analysis in patients with vertebral compression fractures.

PMID:38415478 | DOI:10.2174/0115734056290762240209071656

Curr Med Imaging. 2024 Feb 27. doi: 10.2174/0115734056258544231115103528. Online ahead of print.

ABSTRACT

BACKGROUND: In the last few years, coronavirus disease 2019 (COVID-19) has changed human lifestyle, behavior, and perception of life. This disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). In the literature, there are limited studies about the late renal effects of COVID-19 that reflect the systemic involvement of this disease.

AIM: In the present study, we aimed to compare sonoelastographic changes in both kidneys between patients who had totally recovered from COVID-19 and healthy individuals using strain wave elastography (SWE).

METHODS: This study was conducted between June 2021 and May 2022 in Kahramanmaraş City Hospital Department of Radiology. File and archive records were retrospectively evaluated. Basic demographic, laboratory, and renal ultrasonography (USG) and sonoelastographic findings were screened and noted. Two groups were defined to compare sonoelastographic findings. Post-long COVID-19 group had 92 post-long COVID-19 patients, and the comparator group had 9 healthy individuals”. Both groups’ demographic, laboratory, and ultrasound-elastographic findings were assessed.

RESULTS: The post-long COVID-19 group had a higher renal elastographic value than the comparator group (1.52 [0.77-2.3] vs. 0.96 [0.54-1.54], p<0.001). There were no statistically significant differences between the two groups in terms of age (p=0.063), gender (p=0.654), or body mass index (BMI) (p=0.725), however, there was a significant difference observed between the two groups in the renal strain ratio (RSR). According to an ROC analysis, an RSR cutoff of >1.66 predicted post-long COVID-19 with 44.9% sensitivity and 81.9% specificity. (AUC=0.655, p<0.001). A separate ROC analysis was performed to predict post-long COVID-19 with a BMI cutoff of <33.52, kg/m2 sensitivity of 92.4% and specificity of 17% (AUC=0.655, p<0.001).

CONCLUSION: We demonstrated that renal parenchymal stiffness increases with SWE in post-long COVID-19 patients.

PMID:38415466 | DOI:10.2174/0115734056258544231115103528

Curr Med Imaging. 2024 Feb 27. doi: 10.2174/0115734056278130231218073650. Online ahead of print.

ABSTRACT

INTRODUCTION: A recently developed deep-learning-based automatic evaluation model provides reliable and efficient Cobb angle measurements for scoliosis diagnosis. However, few studies have explored its clinical application, and external validation is lacking. Therefore, this study aimed to explore the value of automated assessment models in clinical practice by comparing deep-learning models with manual measurement methods.

METHODS: The 481 spine radiographs from an open-source dataset were divided into training and validation sets, and 119 spine radiographs from a private dataset were used as the test set. The mean Cobb angle values assessed by three physicians in the hospital’s PACS system served as the reference standard. The results of Seg4Reg, VFLDN, and manual measurement were statistically analyzed. The intra-class correlation coefficients (ICC) and the Pearson correlation coefficient (PCC) were used to compare their reliability and correlation. The Bland-Altman method was used to compare their agreement. The Kappa statistic was used to compare the consistency of Cobb angles at different severity levels.

RESULTS: The mean Cobb angle values measured were 35.89° ± 9.33° with Seg4Reg, 31.54° ± 9.78° with VFLDN, and 32.23° ± 9.28° with manual measurement. The ICCs for the reliability of Seg4Reg and VFLDN were 0.809 and 0.974, respectively. The PCC and MAD between Seg4Reg and manual measurements were 0.731 (p<0.001) and 6.51°, while those between VFLDN and manual measurements were 0.952 (p<0.001) and 2.36°. The Kappa statistic indicated VFLDN (k= 0.686, p< 0.001) was superior to Seg4Reg and manual measurements for Cobb angle severity classification.

CONCLUSION: The deep-learning-based automatic scoliosis Cobb angle assessment model is feasible in clinical practice. Specifically, the keypoint-based VFLDN is more valuable in actual clinical work with higher accuracy, transparency, and interpretability.

PMID:38415463 | DOI:10.2174/0115734056278130231218073650