Category: Nevin Manimala

J Neurosurg Pediatr. 2021 Jul 23:1-12. doi: 10.3171/2021.2.PEDS20810. Online ahead of print.

ABSTRACT

OBJECTIVE: The safety of stereo-electroencephalography (SEEG) has been investigated; however, most studies have not differentiated pediatric and adult populations, which have different anatomy and physiology. The purpose of this study was to assess SEEG safety in the pediatric setting, focusing on surgical complications and the identification of patient and surgical risk factors, if any. The authors also aimed to determine whether robot assistance in SEEG was associated with a change in practice, surgical parameters, and clinical outcomes.

METHODS: The authors retrospectively studied all SEEG cases performed in their department from December 2014 to March 2020. They analyzed both demographic and surgical variables and noted the types of surgery-related complications and their management. They also studied the clinical outcomes of a subset of the patients in relation to robot-assisted and non-robot-assisted SEEG.

RESULTS: Sixty-three children had undergone 64 SEEG procedures. Girls were on average 3 years younger than the boys (mean age 11.1 vs 14.1 years, p < 0.01). The overall complication rate was 6.3%, and the complication rate for patients with left-sided electrodes was higher than that for patients with right-sided electrodes (11.1% vs 3.3%), although the difference between the two groups was not statistically significant. The duration of recording was positively correlated to the number of implanted electrodes (r = 0.296, p < 0.05). Robot assistance was associated with a higher number of implanted electrodes (mean 12.6 vs 7.6 electrodes, p < 0.0001). Robot-assisted implantations were more accurate, with a mean error of 1.51 mm at the target compared to 2.98 mm in nonrobot implantations (p < 0.001). Clinical outcomes were assessed in the first 32 patients treated (16 in the nonrobot group and 16 in the robot group), 23 of whom proceeded to further resective surgery. The children who had undergone robot-assisted SEEG had better eventual seizure control following subsequent epilepsy surgery. Of the children who had undergone resective epilepsy surgery, 42% (5/12) in the nonrobot group and 82% (9/11) in the robot group obtained an Engel class IA outcome at 1 year (χ2 = 3.885, p = 0.049). Based on Kaplan-Meier survival analysis, the robot group had a higher seizure-free rate than the nonrobot group at 30 months postoperation (7/11 vs 2/12, p = 0.063). Two complications, whose causes were attributed to the implantation and head-bandaging steps, required surgical intervention. All complications were either transient or reversible.

CONCLUSIONS: This is the largest single-center, exclusively pediatric SEEG series that includes robot assistance so far. SEEG complications are uncommon and usually transient or treatable. Robot assistance enabled implantation of more electrodes and improved epilepsy surgery outcomes, as compared to those in the non-robot-assisted cases.

PMID:34298516 | DOI:10.3171/2021.2.PEDS20810

J Neurosurg. 2021 Jul 23:1-12. doi: 10.3171/2020.12.JNS203652. Online ahead of print.

ABSTRACT

OBJECTIVE: Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort.

METHODS: Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters).

RESULTS: The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2 ± 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator.

CONCLUSIONS: The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

PMID:34298512 | DOI:10.3171/2020.12.JNS203652

J Neurosurg Pediatr. 2021 Jul 23:1-11. doi: 10.3171/2021.2.PEDS2121. Online ahead of print.

ABSTRACT

OBJECTIVE: Endoscopic third ventriculostomy (ETV), with or without choroid plexus cauterization (±CPC), is a technique used for the treatment of pediatric hydrocephalus. Rigid or flexible neuroendoscopy can be used, but few studies directly compare the two techniques. Here, the authors sought to compare these methods in treating pediatric hydrocephalus.

METHODS: A systematic MEDLINE search was conducted using combinations of keywords: “flexible,” “rigid,” “endoscope/endoscopic,” “ETV,” and “hydrocephalus.” Inclusion criteria were as follows: English-language studies with patients 2 years of age and younger who had undergone ETV±CPC using rigid or flexible endoscopy for hydrocephalus. The primary outcome was ETV success (i.e., without the need for further CSF diversion procedures). Secondary outcomes included ETV-related and other complications. Statistical significance was determined via independent t-tests and Mood’s median tests.

RESULTS: Forty-eight articles met the study inclusion criteria: 37 involving rigid endoscopy, 10 involving flexible endoscopy, and 1 propensity scored-matched comparison. A cumulative 560 patients had undergone 578 rigid ETV±CPC, and 661 patients had undergone 672 flexible ETV±CPC. The flexible endoscopy cohort had a significantly lower average age at the time of the procedure (0.33 vs 0.53 years, p = 0.001) and a lower preoperatively predicted ETV success score (median 40, IQR 32.5-57.5 vs 62.5, IQR 50-70; p = 0.033). Average ETV success rates in the rigid versus flexible groups were 54.98% and 59.65% (p = 0.63), respectively. ETV-related complication rates did not differ significantly at 0.63% for flexible endoscopy and 3.46% for rigid endoscopy (p = 0.30). There was no significant difference in ETV success or complication rate in comparing ETV, ETV+CPC, and ETV with other concurrent procedures.

CONCLUSIONS: Despite the lower expected ETV success scores for patients treated with flexible endoscopy, the authors found similar ETV success and complication rates for ETV±CPC with flexible versus rigid endoscopy, as reported in the literature. Further direct comparison between the techniques is necessary.

PMID:34298514 | DOI:10.3171/2021.2.PEDS2121

Comput Methods Programs Biomed. 2021 Jul 13;208:106269. doi: 10.1016/j.cmpb.2021.106269. Online ahead of print.

ABSTRACT

Background and Objective Electrocardiogram (ECG) quality assessment is significant for automatic diagnosis of cardiovascular disease and reducing the massive workload of reviewing continuous ECGs. Hence, how to design an appropriate algorithm for objectively evaluating the multi-lead ECG recordings is particularly important. Despite the deep learning methods performing well in many fields, as a data-driven method, it may not be entirely suitable for ECG analysis due to the difficulty in obtaining sufficient data and the low signal-to-noise ratio of ECG recordings. In this study, with the aim of providing an accurate and automatic ECG quality assessment scheme, we propose an innovative ECG quality assessment algorithm based on hand-crafted statistical features and deep-learned spectral features. Methods In this paper, a novel approach, combining the deep-learned Stockwell transform (S-Transform) spectrogram features and hand-crafted statistical features, is proposed for ECG quality assessment. Firstly, a double-input convolutional neural network (CNN) is established. Then, the S-Transform with a novel online augmentation scheme is performed on the multi-lead raw ECG signal received from one input layer to obtain proper time-frequency representation. After that, the CNN with three convolutional layers is employed to extract robust deep-learned features automatically. Simultaneously, the hand-crafted statistical features, including lead-fall, baseline drift, and R peak features, are calculated and fed into another input layer for feature fusion training. Finally, the deep-learned and hand-crafted features are concatenated and further fused by a fully connected layer for quality classification. Furthermore, a log-odds analysis scheme combining with a gradient-based method can localize the abnormal zone in time, frequency, and spatial domains. Results and Conclusion Our proposed method is evaluated on a publicly available database with 10-fold cross-validation. The experimental results demonstrate that the proposed assessment algorithm reached a mean accuracy of 93.09%, a mean F1-score of 0.8472, and a sensitivity of 0.9767. Moreover, comprehensive experiments indicate that the fusion of CNN features and statistical features has complementary advantages and ideal interpretability, achieving end-to-end multi-lead ECG assessment with satisfying performance.

PMID:34298474 | DOI:10.1016/j.cmpb.2021.106269

Biosens Bioelectron. 2021 Jul 13;192:113502. doi: 10.1016/j.bios.2021.113502. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) are essential intercellular communicators that are of increasing interest as diagnostic biomarkers. Exploring their biological functions and clinical values, however, remains challenging due to their small sizes and high heterogeneity. Herein, we report an ultrasensitive method that employs target-initiated construction of DNA nanostructure to detect single EVs with an input as low as 100 vesicles/μL. Taking advantage of both DNA nanostructure labeling and EV membrane staining, the method can also permit calibration-free analysis of the protein profiles among different EV samples, leading to clear EV differentiation by their cell of origin. Moreover, this method allows co-localization of dual protein markers on the same EV, and the increased number of EVs carrying dual tumor proteins present in human serum could differentiate cancer patients at the early developmental stage from healthy controls. Our results demonstrate the great potential of this single-EV visualization method in non-invasive detection of the EV-based protein biomarkers for cancer diagnosis and treatment monitoring.

PMID:34298496 | DOI:10.1016/j.bios.2021.113502

J Neurosurg Spine. 2021 Jul 23:1-12. doi: 10.3171/2020.12.SPINE201527. Online ahead of print.

ABSTRACT

OBJECTIVE: Rod fracture (RF) after adult spinal deformity (ASD) surgery is reported in approximately 6.8%-33% of patients and is associated with loss of deformity correction and higher reoperation rates. The authors’ objective was to determine the effect of accessory supplemental rod (ASR) placement on postoperative occurrence of primary RF after ASD surgery.

METHODS: This retrospective analysis examined patients who underwent ASD surgery between 2014 and 2017 by the senior authors. Inclusion criteria were age > 18 years, ≥ 5 instrumented levels including sacropelvic fixation, and diagnosis of ASD, which was defined as the presence of pelvic tilt ≥ 25°, sagittal vertical axis ≥ 5 cm, thoracic kyphosis ≥ 60°, coronal Cobb angle ≥ 20°, or pelvic incidence to lumbar lordosis mismatch ≥ 10°. The primary focus was patients with a minimum 2-year follow-up.

RESULTS: Of 148 patients who otherwise met the inclusion criteria, 114 (77.0%) achieved minimum 2-year follow-up and were included (68.4% were women, mean age 67.9 years, average body mass index 30.4 kg/m2). Sixty-two (54.4%) patients were treated with traditional dual-rod construct (DRC), and 52 (45.6%) were treated with ASR. Overall, the mean number of levels fused was 11.7, 79.8% of patients underwent Smith-Petersen osteotomy (SPO), 19.3% underwent pedicle subtraction osteotomy (PSO), and 66.7% underwent transforaminal lumbar interbody fusion (TLIF). Significantly more patients in the DRC cohort underwent SPO (88.7% of the DRC cohort vs 69.2% of the ASR cohort, p = 0.010) and TLIF (77.4% of the DRC cohort vs 53.8% of the ASR cohort, p = 0.0001). Patients treated with ASR had greater baseline sagittal malalignment (12.0 vs 8.6 cm, p = 0.014) than patients treated with DRC, and more patients in the ASR cohort underwent PSO (40.3% vs 1.6%, p < 0.0001). Among the 114 patients who completed follow-up, postoperative occurrence of RF was reported in 16 (14.0%) patients, with mean ± SD time to RF of 27.5 ± 11.8 months. There was significantly greater occurrence of RF among patients who underwent DRC compared with those who underwent ASR (21.0% vs 5.8%, p = 0.012) at comparable mean follow-up (38.4 vs 34.9 months, p = 0.072). Multivariate analysis demonstrated that ASR had a significant protective effect against RF (OR 0.231, 95% CI 0.051-0.770, p = 0.029).

CONCLUSIONS: This study demonstrated a statistically significant decrease in the occurrence of RF among ASD patients treated with ASR, despite greater baseline deformity and higher rate of PSO. These findings suggest that ASR placement may provide benefit to patients who undergo ASD surgery.

PMID:34298503 | DOI:10.3171/2020.12.SPINE201527

Reprod Biol. 2021 Jul 20;21(3):100536. doi: 10.1016/j.repbio.2021.100536. Online ahead of print.

ABSTRACT

Cervical cancer markedly threatens women’s health worldwide and currently ranks fourth leading cause of cancer mortality in women according to recent global cancer statistics. Recent advances have proven that not only tumor suppressor and oncogenes but also non-coding RNAs including micro RNAs (miRNAs) have significant impact in the development and progression of cervical cancers. Previous studies have identified many cancer-specific miRNAs for the early detection of cervical cancers. However, the diagnostic and prognostic use of autophagy-associated miRNAs for the cervical squamous cell cancer (SCC) cases and high-grade squamous intraepithelial lesion (HSIL) have not been uncovered. In the present study, we revealed that miRNAs are differentially expressed in both cervical SCC and HSIL. A total of 35 HSIL, 35 cervical SCC and 30 healthy controls were enrolled for the present study. Total RNA including miRNAs were isolated from the FFPE tissue samples and miRNA expression levels were quantified by quantitative PCR. Predicted miRNA targets of autophagy related genes were determined using miRNA-target prediction algorithms. MiR-143, miR-372, miR-375 and miR-30c were markedly downregulated in HSIL and cervical SCC. MiR-130a was significantly upregulated in the cervical SCC group compared to HSIL and control groups. MiR-30a, miR-520e, miR-548c and miR-372 were significantly associated with the overall survival of cervical SCC patients and these miRNAs were determined to be significant diagnostic markers as revealed by ROC analysis. Together, these results indicate that autophagy-associated miRNAs are potentially valuable for the differential diagnosis and targeted therapy to cervical cancer.

PMID:34298410 | DOI:10.1016/j.repbio.2021.100536

Epilepsy Res. 2021 Jul 15;176:106726. doi: 10.1016/j.eplepsyres.2021.106726. Online ahead of print.

ABSTRACT

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is becoming a first-line surgical therapy for mesial temporal lobe epilepsy (mTLE) due to good seizure control and low complication risk. However, seizure outcomes after MRgLiTT remain highly variable and there is a need to improve patient selection and post-operative prognostication. In this retrospective study, we investigated whether the pre-operative MRI-derived apparent diffusion coefficient (ADC), used as a marker of tissue pathology in the mesial temporal structures could help predict seizure outcome.

METHODS: Thirty-five patients who underwent MRgLiTT at our institution between 2014 and 2019 were included in the study. Demographic and clinical data were retrospectively collected. Seizure outcome was defined as good (ILAE Class I-II) and poor (ILAE Class III-VI). Volumetrics were performed on pre-ablation hippocampus and amygdala. Ablation volumes, and the proportion of ablated hippocampus and amygdala calculated via their respective mean voxel-wise ADC intensities were quantified from pre-operative and intra-operative post-ablation MRIs and statistically compared between the two outcome cohorts. Univarate and multivariate regression analysis was performed to identify demographic, clinical, and radiographic predictors of seizure outcome.

RESULTS: Mean age at LiTT was 36 years and 14 (40 %) were female. Mean follow-up duration was 1.90 ± 0.17 years. Twenty-seven (77 %) patients had mesial temporal sclerosis. There was no significant difference in the ablation volumes and proportion of ablated volume of hippocampus and amygdala between the two outcome groups. Patients with good seizure outcome had significantly higher normalized ADC intensities in the ablated mesial temporal structures compared to those with poor outcome (0.01 ± 0.08 vs.-0.29 ± 0.06; p = 0.015).

CONCLUSIONS: mTLE patients with higher ADC intensities in the ablated regions of the hippocampus and the amygdala are more likely to have good seizure outcome following MRgLiTT. Our results suggest that pre-operative ADC analysis may improve both patient selection and epileptogenic zone targeting during MRgLiTT. Further investigation with large, prospective cohorts is needed to validate the clinical utility of ADC in improving seizure outcome following MRgLiTT.

PMID:34298428 | DOI:10.1016/j.eplepsyres.2021.106726

Eur J Cancer. 2021 Jun 30;154:246-252. doi: 10.1016/j.ejca.2021.06.029. Online ahead of print.

ABSTRACT

BACKGROUND: Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive.

MATERIAL AND METHODS: This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma.

RESULTS: Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31^st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19.

CONCLUSIONS: Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

PMID:34298375 | DOI:10.1016/j.ejca.2021.06.029

Eur J Cancer. 2021 Jul 20;154:277-287. doi: 10.1016/j.ejca.2021.05.039. Online ahead of print.

ABSTRACT

PURPOSE: The analysis of circulating tumor DNA (ctDNA), a fraction of total cell-free DNA (cfDNA), might be of special interest in retinoblastoma patients. Because the accessibility to tumor tissue is very limited in these patients, either for histopathological diagnosis of suspicious intraocular masses (biopsies are proscribed) or for somatic RB1 studies and genetic counseling (due to current successful conservative approaches), we aim to validate the detection of ctDNA in plasma of non-hereditary retinoblastoma patients by molecular analysis of RB1 gene.

EXPERIMENTAL DESIGN: In a cohort of 19 intraocular unilateral non-hereditary retinoblastoma patients for whom a plasma sample was available at diagnosis, we performed high-deep next-generation sequencing (NGS) of RB1 in cfDNA. Two different bioinformatics/statistics approaches were applied depending on whether the somatic RB1 status was available or not.

RESULTS: Median plasma sample volume was 600 μL [100-1000]; median cfDNA plasma concentration was 119 [38-1980] and 27 [11-653] ng/mL at diagnosis and after complete remission, respectively. In the subgroup of patients with known somatic RB1 alterations (n = 11), seven of nine somatic mutations were detected (median allele fraction: 6.7%). In patients without identified somatic RB1 alterations (n = 8), six candidate variants were identified for seven patients.

CONCLUSIONS: Despite small tumor size, blood-ocular barrier, poor ctDNA blood release and limited plasma sample volumes, we confirm that it is possible to detect ctDNA with high-deep NGS in plasma from patients with intraocular non-hereditary retinoblastoma. This may aid in diagnosis of suspicious cases, family genetic counseling or follow-up of residual intraocular disease.

PMID:34298378 | DOI:10.1016/j.ejca.2021.05.039