Tag: nevin manimala

Ophthalmology. 2023 Sep 11:S0161-6420(23)00631-0. doi: 10.1016/j.ophtha.2023.09.006. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal Voretigene Neparvovec (VN, Luxturna®) treatment.

DESIGN: Single center, retrospective, longitudinal, consecutive case series.

PARTICIPANTS: Patients with RPE65-IRD treated by one surgeon (FGH) between 02-2020 and 03-2022 with VN and oral immunosuppression according to the manufacturer´s recommendation.

METHODS: Retrospective analysis of surgical and clinical records, ancillary testing and retinal imaging following VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 24 months post treatment.

MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann Visual Fields (GVF), chromatic full-field-stimulus-threshold testing (FST), scotopic and photopic 2-Color-Threshold Perimetry (2CTP), multimodal retinal imaging.

RESULTS: 30 eyes / 19 patients were analyzed (10 pediatric <20y, 20 adult (range 8-40 y, median follow-up 15 months, range 1-32). The fovea was completely or partially detached in 16, attached in 12, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (p <0.05), and did not change significantly independent of age. Meaningful loss of BCVA (≥0.3 logMAR) occurred in 4/18 adult eyes, meaningful gain (≥-0.3 logMAR) in 2/18 adult and 2/8 pediatric eyes. LLVA and scotopic 2CTP improved considerably in pediatrics. Scotopic blue FST improved at all ages, more in pediatrics (8/8 eyes gain ≥ 10 dB, p<0.05). In pediatrics, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13/26 eyes at the site of the bleb and/or peripheral of vascular arcades. FST improvements did not correlate with development of chorioretinal atrophy at M12. Mean central retinal thickness was 166.7 μm (±25.45) at baseline (30 eyes) and 157.69 μm (±30.3) at M12 (26 eyes). Eight adult patients were treated unilaterally. The non-treated eyes did not show meaningful changes during follow-up.

CONCLUSIONS: These real-world data show effectiveness of VN therapy with stable median BCVA and mean retinal thickness, and improvements of LLVA, FST and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes.

PMID:37704110 | DOI:10.1016/j.ophtha.2023.09.006

Chemosphere. 2023 Sep 11:140146. doi: 10.1016/j.chemosphere.2023.140146. Online ahead of print.

ABSTRACT

As the third largest river in the world, microplastic pollution in the Yangtze River basin is currently attracting worldwide attention. However, fragmented research information is insufficient to reveal the occurrence and driving mechanisms of microplastics throughout the Yangtze River basin. Building on a systematic review of 20 existing publications, this study constructed a dataset including microplastic data from 366 samples in the Yangtze River basin through a data filtering process, and data on natural conditions and anthropogenic activities from 101 basin municipalities. Further, multivariate statistical analysis was utilized to enhance the understanding of the abundance, composition and drivers of microplastics within the basin. Differences in microplastic abundance among the sampling sites were up to 5 orders of magnitude, with the highest abundance value found in the upstream city of Chengdu. The comprehensive diversity index used to describe the composition characteristics of microplastics ranged from 0.31 to 0.68, slightly higher than the national average. Based on a statistical analysis framework, natural conditions and anthropogenic activities were shown to jointly drive the distribution of microplastics, and the dominant driver shifted between the two with spatial variation. In the upstream, anthropogenic activities dominated by GDP (r = 0.85, P < 0.01) were the main positive factor. In the middle and downstream, natural conditions and anthropogenic activities had comparable driving forces as the stability of natural resistance increased, and both were positively correlated with microplastics. Combining the constructed normalized stepwise linear regression model with GIS spatial analysis, the basin-wide application demonstrated that microplastic pollution in the upstream and delta deserved more attention. After coupling the distance factors, microplastic pollution was concentrated in the middle and downstream of the Yangtze River basin, covering important drinking water sources. This study provided important data support for subsequent targeted microplastic reduction and treatment.

PMID:37704083 | DOI:10.1016/j.chemosphere.2023.140146

Ageing Res Rev. 2023 Sep 11:102071. doi: 10.1016/j.arr.2023.102071. Online ahead of print.

ABSTRACT

BACKGROUND: Exercise is a promising nonpharmacological treatment for improving depression in older adults with MCI, but it is unclear which exercises are most effective. The objectives of this study were to compare and rank the effectiveness of various exercise interventions for depression in mild cognitive impairment (MCI) and to investigate the effects of exercise on depression.

METHODS: The PRISMA-NMA guidelines were applied to the development and reporting of review criteria. The Cochrane Library, Web of Science, PsycINFO, PubMed, EMBASE, CINAHL, and Scopus databases were systematically searched by combining search terms for randomized controlled trial studies (RCTs) published in English from individual databases with the earliest available date set to March 10, 2023. Two evaluators independently selected and evaluated eligible studies of changes in depression in older adults with MCI after an exercise intervention. A protocol for this systematic review was registered in PROSPERO (Registration number: CRD42022377052).

RESULTS: A network meta-analysis was conducted on 15 eligible RCTs consisting of 4271 subjects, including aerobic (n = 6), mind-body (n = 6) and multicomponent (n = 3) exercise trials. Compared to controls, mind-body exercise showed the strongest improvement in depressive symptoms (SMD = -0.63, 95% CI: -1.13, -0.14), followed by aerobic (SMD = -0.57, 95% CI: -0.88, -0.26) and multicomponent exercise (SMD = -0.53, 95% CI: -1.02, -0.03). Notably, there were no statistically significant differences between exercise types: aerobic vs. mind-body (SMD = 0.06, 95% PrI: -0.71, 0.84), multicomponent vs. mind-body (SMD = 0.11, 95% PrI: -0.75, 0.97), or multicomponent vs. aerobic (SMD = 0.04, 95% PrI: -0.771, 0.86).

CONCLUSIONS: In this review, we found that mind-body exercise was most effective when compared to conventional controls and that multiple exercise modalities (aerobic, mind-body, and multicomponent exercise) had beneficial and comparable effects in reducing depressive states in older adults with MCI. These findings may guide clinical geriatric stakeholders and allied health professionals in providing more scientifically optimal exercise prescriptions for older adults with MCI. In the future, more high-quality, long-term clinical trials are needed to support the exploration of longer-term dynamic effects.

PMID:37704052 | DOI:10.1016/j.arr.2023.102071

Spine J. 2023 Sep 11:S1529-9430(23)03378-8. doi: 10.1016/j.spinee.2023.09.006. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: Decompression surgery is a treatment option for patients with degenerative cervical myelopathy (DCM). Surgical decisions primarily depend on clinical symptoms and radiological examinations. The diagnostic and prognostic significance of evoked potential tests for surgical outcomes in patients with DCM has not been thoroughly examined.

PURPOSE: To identify the diagnostic and prognostic significance of preoperative evoked potential tests in patients with DCM who underwent decompression surgery.

STUDY DESIGN: This was a retrospective observational study.

PATIENT SAMPLE: One hundred two consecutive patients who underwent evoked potential tests and surgical treatment between January 2016 and December 2020 in a single spine center and had a minimum follow up of six months.

OUTCOME MEASURES: Japanese Orthopedic Association (JOA) scores obtained preoperatively and 6 months after surgery.

METHODS: This study evaluated the preoperative central motor conduction time (CMCT), somatosensory evoked potentials (SSEP), and Japanese Orthopedic Association (JOA) scores obtained preoperatively and 6 months after surgery.

RESULTS: Abnormal CMCT findings were observed in 94 patients (92.2%). Abnormal SSEPs were observed in 77 patients (75.5%). There was a statistically significant correlation between preoperative JOA score and abductor pollicis brevis (APB)-CMCT (r=-0.546, p=0.000), tibialis anterior (TA)-CMCT (r=-0.517, p<=0.000), median nerve (MN)-SSEP (r=-0.353, p=0.001), and tibial nerve (TN)-SSEP (r=-0.349, p=0.003). There were significant differences in recovery rates associated with diabetes mellitus (DM), preoperative severity of myelopathy, TA-CMCT, MN-SSEP, and TN-SSEP. Stepwise multiple regression analysis showed that the major factors affecting the clinical outcomes were TN-SSEP (β=0.327, p=0.004), preoperative JOA score (β=0.278, p=0.012), and DM (β=0.241, p=0.025).

CONCLUSIONS: Evoked potential testing is a functional diagnostic tool that can indicate the severity of myelopathic symptoms in patients with DCM. Additionally, preoperative TN-SSEP may have significant prognostic value in predicting postoperative clinical outcomes. Thus, preoperative evoked potential tests could be helpful for determining suitable surgical treatment candidates and forecasting postoperative prognosis.

PMID:37704047 | DOI:10.1016/j.spinee.2023.09.006

Appl Clin Inform. 2023 Sep 13. doi: 10.1055/a-2174-7820. Online ahead of print.

ABSTRACT

BACKGROUND: Patient-centered clinical decision support (PC CDS) aims to assist with tailoring decisions to an individual patient’s needs. Patient-generated health data (PGHD), including physiologic measurements captured frequently by automated devices, provide important information for PC CDS. The volume and availability of such PGHD is increasing, but how PGHD should be presented to clinicians to best aid decision-making is unclear.

OBJECTIVE: Identify best practices in visualizations of physiologic PGHD, for designing a software application as a PC CDS tool.

METHODS: We performed a scoping review of studies of PGHD dashboards that involved clinician users in design or evaluations. We included only studies that used physiologic PGHD from single patients for usage in decision-making.

RESULTS: We screened 468 titles and abstracts, 63 full-text papers, and identified 15 articles to include in our review. Some research primarily sought user input on PGHD presentation, other studies garnered feedback only as a side effort for other objectives (e.g., integration with electronic health records [EHRs]). Development efforts were often in the domains of chronic diseases and collected a mix of physiologic parameters (e.g., blood pressure and heart rate) and activity data. Users’ preferences were for data to be presented with statistical summaries and clinical interpretations, alongside other non-PGHD data. Recurrent themes indicated that users desire longitudinal data display, aggregation of multiple data types on the same screen, actionability, and customization. Speed, simplicity, and availability of data for other purposes (e.g., documentation) were key to dashboard adoption. Evaluations were favorable for visualizations using common graphing or table formats, although best practices for implementation have not yet been established.

CONCLUSIONS: Although the literature identified common themes on data display, measures, and usability, more research is needed as PGHD usage grows. Ensuring that care is tailored to individual needs will be important in future development of clinical decision support.

PMID:37704021 | DOI:10.1055/a-2174-7820

J Struct Biol. 2023 Sep 11:108024. doi: 10.1016/j.jsb.2023.108024. Online ahead of print.

ABSTRACT

Single particle analysis (SPA) in cryo-electron microscopy (cryo-EM) is highly used to obtain the near-atomic structure of biological macromolecules. The current methods allow users to produce high-resolution maps from many samples. However, there are still challenging cases that require extra processing to obtain high resolution. This is the case when the macromolecule of the sample is composed of different components and we want to focus just on one of them. For example, if the macromolecule is composed of several flexible subunits and we are interested in a specific one, if it is embedded in a viral capsid environment, or if it has additional components to stabilize it, such as nanodiscs. The signal from these components, which in principle we are not interested in, can be removed from the particles using a projection subtraction method. Currently, there are two projection subtraction methods used in practice and both have some limitations. In fact, after evaluating their results, we consider that the problem is still open to new solutions, as they do not fully remove the signal of the components that are not of interest. Our aim is to develop a new and more precise projection subtraction method, improving the performance of state-of-the-art methods. We tested our algorithm with data from public databases and an in-house data set. In this work, we show that the performance of our algorithm improves the results obtained by others, including the localization of small ligands, such as drugs, whose binding location is unknown a priori.

PMID:37704013 | DOI:10.1016/j.jsb.2023.108024

Urology. 2023 Sep 11:S0090-4295(23)00783-5. doi: 10.1016/j.urology.2023.08.033. Online ahead of print.

ABSTRACT

OBJECTIVE: To study whether varicocele repair would improve sperm capacitation and probability of generating a pregnancy.

METHODS: Data were collected prospectively of 40 consecutive adult men who presented with infertility confirmed by semen analysis and found to have a varicocele on exam or ultrasound who underwent unilateral or bilateral subinguinal microscopic varicocelectomy. We recorded pre and post-operative SA, Cap-Score, and PGP with a 3-month follow up. Values were compared using paired t-test and Wilcox rank-sum test.

RESULTS: Results showed a 17.4% relative increase in Cap-Score (23% to 27% capacitation), 25% relative increase in probability of generating a pregnancy (PGP) (24% to 30%), as well as statistically significant improvements in sperm concentration, motility, and total sperm count postoperatively.

CONCLUSION: This study confirms that microsurgical varicocelectomy significantly improves sperm capacitation ability and improves the expected probability of generating a pregnancy within three rounds of intrauterine insemination (IUI). The improvement in sperm capacitation ability may help explain how varicocele repair may improve the chance of pregnancy, regardless of standard semen parameter improvements.

PMID:37704009 | DOI:10.1016/j.urology.2023.08.033

Ann Thorac Surg. 2023 Sep 11:S0003-4975(23)00934-7. doi: 10.1016/j.athoracsur.2023.09.002. Online ahead of print.

ABSTRACT

BACKGROUND: Active primary lung malignancy remains a strong contraindication to lung transplantation (LTx). However, outcomes are unclear for patients with early-stage non-small cell lung cancer (NSCLC) who undergo LTx. We hypothesize that patients with early stage NSCLC incidentally discovered in the explanted lungs have comparable survival to LTx recipients without incidental cancer identified.

METHODS: We performed a single-center retrospective analysis of all LTx recipients from May 2007 to September 2021 with incidental cancer identified in the explanted lungs by pathologist report. Survival statistics were estimated using Kaplan-Meier analysis.

RESULTS: Of the 1,586 LTx performed, 23 (1.5%) patients were found to have incidental lung cancer in the explanted lungs. The most common indications for LTx were interstitial lung disease (n=13) and chronic obstructive pulmonary disease (n=7), and the most common histological diagnosis was adenocarcinoma (n=14). In the cohort with Stage I disease (n=9), the 1-year and 5-year unadjusted KM survival rates were 88.9% and 51.9%, respectively. The 1-year and 5-year survival rates for transplants without incidental cancer findings at LTx during this period were 86.7% and 59.4%, respectively, and did not differ significantly between the two strata (p=0.96).

CONCLUSIONS: One- and 5-year survival rates were comparable between LTx recipients with incidentally noted pathological Stage I NSCLC and contemporary recipients without cancer. All cancer-related mortality occurred in recipients with incidentally noted advanced NSCLC. These results suggest that patients with pathological Stage I lung cancer at the time of transplant have outcomes comparable to those without cancer findings at the time of transplant.

PMID:37704001 | DOI:10.1016/j.athoracsur.2023.09.002

J Thorac Oncol. 2023 Sep 11:S1556-0864(23)00806-7. doi: 10.1016/j.jtho.2023.09.004. Online ahead of print.

ABSTRACT

INTRODUCTION: The study aimed to prospectively investigate the bidirectional association between cardiovascular disease (CVD) and lung cancer, and whether this association differs across genetic risk levels.

METHODS: This study prospectively followed 455,804 participants from the UK Biobank cohort who were free of lung cancer at baseline. Cox proportional hazards models were used to estimate hazard ratio (HR) for incident lung cancer according to CVD status. In parallel, similar approaches were used to assess the risk of incident CVD according to lung cancer status among 478,756 participants free of CVD at baseline. The bidirectional causal relations between these conditions were assessed using Mendelian randomization (MR) analysis. Besides, polygenic risk scores were estimated by integrating genome-wide association studies identified risk variants.

RESULTS: During 4,007,477 person-years of follow-up, 2,006 incident lung cancer cases were documented. Compared with participants without CVD, those with CVD had HRs [95% confidence interval (CI)] of 1.49 (1.30-1.71) for non-small cell lung cancer (NSCLC), 1.80 (1.39-2.34) for lung squamous cell carcinoma (LUSC), and 1.25 (1.01-1.56) for lung adenocarcinoma (LUAD). After stratified by smoking status, significant associations of CVD with lung cancer risk were observed in former smokers (HR: 1.44, 95% CI: 1.20-1.74) and current smokers (HR: 1.38, 95% CI: 1.13-1.69), but not in never smokers (HR: 0.98, 95% CI: 0.60-1.61). Additionally, CVD was associated with lung cancer risk across each genetic risk level (P_{heterogeneity} = 0.336). In the second analysis, 32,974 incident CVD cases were recorded. Compared with those without lung cancer, the HRs (95% CI) for CVD were 2.33 (1.29-4.21) in NSCLC, 3.66 (1.65-8.14) in LUAD, and 1.98 (0.64-6.14) in LUSC. In particular, participants with lung cancer had a high risk of incident CVD in high genetic risk level (HR: 3.79, 95% CI: 1.57-9.13). No causal relations between these conditions were observed in MR analysis.

CONCLUSIONS: CVD is associated with an increased risk of NSCLC including LUSC and LUAD. NSCLC, particularly LUAD, is associated with a higher CVD risk. Awareness of this bidirectional association may improve prevention and treatment strategies for both diseases. Future clinical demands will require a greater focus on cardiac oncology.

PMID:37703998 | DOI:10.1016/j.jtho.2023.09.004

Transplant Cell Ther. 2023 Sep 11:S2666-6367(23)01515-4. doi: 10.1016/j.jtct.2023.09.001. Online ahead of print.

ABSTRACT

INTRODUCTION: Extracorporeal photopheresis (ECP) has shown efficacy in graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with off-line ECP in our institution, in order to validate this treatment schedule and analyze predictive factors.

MATERIALS AND METHODS: All consecutive adult patients with steroid-dependent or steroidrefractory GVHD receiving off-line ECP were included in this single center, retrospective study. ECP was performed with Spectra Optia®, processing one total blood volume, with a frequency of twice a week for acute GVHD and once a week for chronic GVHD, and tapered individually according to clinical response. Cumulative incidence of response, including complete responses (CR) and partial responses (PR), were compared among patients grouped by different baseline, apheresis and disease characteristics.

RESULTS: Between January 2015 and May 2022, 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of sessions. GVHD responded in 78% of patients (acute GVHD 57% CR and 4% PR, chronic GVHD 39% CR and 48% PR). Overall survival was statistically longer for acute GVHD patients responding to ECP than for those who did not (67.5% vs. 26% at one year, respectively; P = 0.037). Severity was an independent predictor of response in acute GVHD whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in chronic GVHD.

DISCUSSION: This treatment schedule is effective for GVHD. Further investigation is required to identify ECP-specific predictive factors, as findings are not homogeneous among different studies.

PMID:37703997 | DOI:10.1016/j.jtct.2023.09.001