Category: Nevin Manimala

Front Oncol. 2021 Jun 3;11:681130. doi: 10.3389/fonc.2021.681130. eCollection 2021.

ABSTRACT

Glioblastoma (GBM) is the most common and aggressive type of tumour arising from the central nervous system. GBM remains an incurable disease despite advancement in therapies, with overall survival of approximately 15 months. Recent literature has highlighted that GBM releases tumoural content which crosses the blood-brain barrier (BBB) and is detected in patients’ blood, such as circulating tumour cells (CTCs). CTCs carry tumour information and have shown promise as prognostic and predictive biomarkers in different cancer types. Currently, there is limited data for the clinical utility of CTCs in GBM. Here, we report the use of spiral microfluidic technology to isolate CTCs from whole blood of newly diagnosed GBM patients before and after surgery, followed by characterization for GFAP, cell-surface vimentin protein expression and EGFR amplification. CTCs were found in 13 out of 20 patients (9/20 before surgery and 11/19 after surgery). Patients with CTC counts equal to 0 after surgery had a significantly longer recurrence-free survival (p=0.0370). This is the first investigation using the spiral microfluidics technology for the enrichment of CTCs from GBM patients and these results support the use of this technology to better understand the clinical value of CTCs in the management of GBM in future studies.

PMID:34150645 | PMC:PMC8210776 | DOI:10.3389/fonc.2021.681130

Front Oncol. 2021 Jun 4;11:684781. doi: 10.3389/fonc.2021.684781. eCollection 2021.

ABSTRACT

MOTIVATION: The evolution of complex diseases can be modeled as a time-dependent nonlinear dynamic system, and its progression can be divided into three states, i.e., the normal state, the pre-disease state and the disease state. The sudden deterioration of the disease can be regarded as the state transition of the dynamic system at the critical state or pre-disease state. How to detect the critical state of an individual before the disease state based on single-sample data has attracted many researchers’ attention.

METHODS: In this study, we proposed a novel approach, i.e., single-sample-based Jensen-Shannon Divergence (sJSD) method to detect the early-warning signals of complex diseases before critical transitions based on individual single-sample data. The method aims to construct score index based on sJSD, namely, inconsistency index (ICI).

RESULTS: This method is applied to five real datasets, including prostate cancer, bladder urothelial carcinoma, influenza virus infection, cervical squamous cell carcinoma and endocervical adenocarcinoma and pancreatic adenocarcinoma. The critical states of 5 datasets with their corresponding sJSD signal biomarkers are successfully identified to diagnose and predict each individual sample, and some “dark genes” that without differential expressions but are sensitive to ICI score were revealed. This method is a data-driven and model-free method, which can be applied to not only disease prediction on individuals but also targeted drug design of each disease. At the same time, the identification of sJSD signal biomarkers is also of great significance for studying the molecular mechanism of disease progression from a dynamic perspective.

PMID:34150649 | PMC:PMC8212786 | DOI:10.3389/fonc.2021.684781

Front Oncol. 2021 Jun 4;11:658690. doi: 10.3389/fonc.2021.658690. eCollection 2021.

ABSTRACT

BACKGROUND: Many clinical studies have shown that patients with non-small cell lung carcinoma (NSCLC) can benefit from immune checkpoint inhibitor (ICI) therapy; however, PD-L1 and tumor mutation burden (TMB), which are recommended by the NCCN guidelines, are still insufficient in predicting the response to and prognosis of immunotherapy. Given the widespread use of ICIs, it is important to find biomarkers that can predict immunotherapy outcomes in NSCLC patients, and the exploration of additional effective biomarkers for ICI therapy is urgently needed.

METHODS: A total of 33 stage II-IV NSCLC patients were included in this study. We analyzed immune markers in biopsy and surgical tissue resected from these patients before treatment with ICIs. We examined the infiltration of immune cells and expression of PD-L1 in immune cells using fluorescent multiplex immunohistochemistry (mIHC) stained with CD8/CD68/CD163/PD-L1 antibodies.

RESULTS: In this cohort, we observed that the levels of CD8+ T cells, CD8+PD-L1+ T cells, and CD68+CD163+ M2 macrophages in the total region were independent prognostic factors for progression-free survival (PFS) in NSCLC patients treated with ICIs (HR=0.04, P=0.013; HR=17.70, P=0.026; and HR=17.88, P=0.011, respectively). High infiltration of CD8+ T cells and low infiltration of CD8+PD-L1+ T cells throughout the region were correlated with prolonged PFS (P=0.016 and P=0.02, respectively). No statistically significant difference was observed for CD68+CD163+ M2 macrophages. The joint parameters CD8+ high/CD8+PD-L1+ low, CD8+ high/CD68+CD163+ low and CD8+PD-L1+ low/CD68+CD163+ low predicted better PFS than other joint parameters (P<0.01, P<0.01, and P<0.001, respectively), and they also demonstrated stronger stratification than single biomarkers. The response rate of patients with high infiltration of CD8+ T cells was significantly higher than that of those with low infiltration (P<0.01), and the joint parameters CD8+/CD8+PD-L1+ and CD8+/CD68+CD163+ also demonstrated stronger stratification than single biomarkers.

CONCLUSIONS: This retrospective study identified the predictive value of CD8+PD-L1+ T cells, CD8+ T cells, and CD68+CD163+ M2 macrophages in NSCLC patients who received ICIs. Interestingly, our results indicate that the evaluation of joint parameters has certain significance in guiding ICI treatment in NSCLC patients.

PMID:34150625 | PMC:PMC8213070 | DOI:10.3389/fonc.2021.658690

Front Oncol. 2021 Jun 4;11:665235. doi: 10.3389/fonc.2021.665235. eCollection 2021.

ABSTRACT

BACKGROUND: Gliomas are the most common and aggressive tumors of the central nervous system. A robust and widely used blood-based biomarker for glioma has not yet been identified. In recent years, a plethora of new research on blood-based biomarkers for glial tumors has been published. In this review, we question which molecules, including proteins, nucleic acids, circulating cells, and metabolomics, are most promising blood-based biomarkers for glioma diagnosis, prognosis, monitoring and other purposes, and align them to the seminal processes of cancer.

METHODS: The Pubmed and Embase databases were systematically searched. Biomarkers were categorized in the identified biomolecules and biosources. Biomarker characteristics were assessed using the area under the curve (AUC), accuracy, sensitivity and/or specificity values and the degree of statistical significance among the assessed clinical groups was reported.

RESULTS: 7,919 references were identified: 3,596 in PubMed and 4,323 in Embase. Following screening of titles, abstracts and availability of full-text, 262 articles were included in the final systematic review. Panels of multiple biomarkers together consistently reached AUCs >0.8 and accuracies >80% for various purposes but especially for diagnostics. The accuracy of single biomarkers, consisting of only one measurement, was far more variable, but single microRNAs and proteins are generally more promising as compared to other biomarker types.

CONCLUSION: Panels of microRNAs and proteins are most promising biomarkers, while single biomarkers such as GFAP, IL-10 and individual miRNAs also hold promise. It is possible that panels are more accurate once these are involved in different, complementary cancer-related molecular pathways, because not all pathways may be dysregulated in cancer patients. As biomarkers seem to be increasingly dysregulated in patients with short survival, higher tumor grades and more pathological tumor types, it can be hypothesized that more pathways are dysregulated as the degree of malignancy of the glial tumor increases. Despite, none of the biomarkers found in the literature search seem to be currently ready for clinical implementation, and most of the studies report only preliminary application of the identified biomarkers. Hence, large-scale validation of currently identified and potential novel biomarkers to show clinical utility is warranted.

PMID:34150629 | PMC:PMC8211985 | DOI:10.3389/fonc.2021.665235

Indian J Otolaryngol Head Neck Surg. 2021 Jun;73(2):160-166. doi: 10.1007/s12070-020-01935-5. Epub 2020 Jul 7.

ABSTRACT

The transoral vestibular approach (TOVA) is the shortest route for endoscopic thyroidectomy (ET) to approach the thyroid and is a totally scar free procedure, hence it has a clear cosmetic advantage not only over conventional open thyroid surgery but also over other remote access approaches for ET like axilla, breast and chest wall approaches. The aim of this study was to evaluate the feasibility, safety and our initial outcomes of TOVA and highlight the advantages of 3D endoscopic equipment in remote access thyroid surgery. We reviewed our prospectively maintained database who underwent ET. 42 patients who fulfilled the stringent inclusion criteria were offered TOVA. We have used novel Trans-vestibular approach with 3D technology for endoscopic thyroid surgery in all cases. Clinico-demographic profile, investigations, operative details, histopathology and postoperative complications and follow-up data were analyzed by using statistical analysis with SPSS19.00 version. Out of 203 ET operated during study period, 42 (20.69%) patients were operated through TOVA. Hemithyroidectomy were performed in all the patients. There were 3 men and 39 women (M:F = 1:13). Mean tumor size was 3.54 ± 1.17 cm. All patients were euthyroid. All patient had cytological diagnosis of Bethesda category II-IV and all underwent hemithyroidectomy. Mean operation time was 107.71 ± 17.60 min and post-operative length of hospital stay was 2.90 ± 1.28 days. Besides magnification, 3D endoscopy provided excellent depth perception which helped in precise dissection in the restricted space and aided in identification and preservation of the two most vital structures i.e. recurrent laryngeal nerve and parathyroid glands. As most of our patients present with larger goitres, not many patients desirous of ET can be offered TOVA. This novel TOVA has fairly stringent inclusion criteria, however it is the only approach which offers completely scarless endoscopic thyroidectomy and should be offered to eligible patients desirous of ET.

PMID:34150590 | PMC:PMC8163932 | DOI:10.1007/s12070-020-01935-5

Indian J Otolaryngol Head Neck Surg. 2021 Jun;73(2):188-192. doi: 10.1007/s12070-020-02329-3. Epub 2021 Jan 7.

ABSTRACT

Facial nerve identification is considered to be a crucial step in parotid surgery as inadvertent injury to the nerve will lead to facial paralysis. Multiple landmarks are described in literature to identify the facial nerve during parotid surgery but controversies remain as the consistency and accuracy of these landmarks vary. Numerous studies exist in literature but they fail to address a single landmark that is most reliable to identify the facial nerve during parotid surgery. The purpose of this study is to find reliable landmarks for identification of the main trunk of facial nerve during parotid surgery by evidence gathered by cadaveric dissection and intraoperative study during parotid surgery and develop a systematic approach to identify the facial nerve trunk. This prospective study included 41 cadavers (82 parotid regions) and 20 patients with parotid pathology who underwent parotidectomy. We evaluated the feasibility of our C-M-S technique to identify the main trunk of facial nerve in both anatomical and surgical study. The relationship of landmarks (tragal pointer, tympanomastoid suture, superior border of posterior belly of digastric muscle) to the facial nerve trunk was assessed and the shortest distance between them from the facial trunk was measured using a slide caliper. The measurements were compared between the anatomical and surgical study. The main trunk of facial nerve was successfully identified in all cases using C-M-S technique in both anatomical and surgical study. Distance of facial nerve trunk to tragal pointer was more in the cadaveric sample (13.04 ± 5.238 mm) compared to live patients (9.95 ± 3.967 mm) with statistically significant difference (p = 0.036). The mean distance of tympanomastoid suture and posterior belly of digastric muscle to the facial nerve trunk was similar in anatomical and surgical study with p value of 0.877 and 0.083 respectively. The tympanomastoid suture, posterior belly of digastric muscle and tragal pointer are the most useful landmarks for facial nerve identification during parotid surgery. In our study we found that the tympanomastoid suture line is the most consistent landmark present in all our cases and being closest to the facial nerve trunk in both anatomical and surgical study. Further we recommend using the “C-M-S technique” in order to locate the main trunk of the facial nerve.

PMID:34150593 | PMC:PMC8163908 | DOI:10.1007/s12070-020-02329-3

Res Synth Methods. 2021 Jun 20. doi: 10.1002/jrsm.1505. Online ahead of print.

ABSTRACT

In meta-analysis based on continuous outcome, estimated means and corresponding standard deviations from the selected studies are key inputs to obtain a pooled estimate of the mean and its confidence interval. We often encounter the situation that these quantities are not directly reported in the literatures. Instead, other summary statistics are reported such as median, minimum, maximum, quartiles, and study sample size. Based on available summary statistics, we need to estimate estimates of mean and standard deviation for meta-analysis. We developed a R Shiny code based on approximate Bayesian computation (ABC), ABCMETA, to deal with this situation. In this article, we present an interactive and user-friendly R Shiny application for implementing the proposed method (named ABCMETAapp). In ABCMETAapp, users can choose an underlying outcome distribution other than the normal distribution when the distribution of the outcome variable is skewed or heavy tailed. We show how to run ABCMETAapp with examples. ABCMETAapp provides a R Shiny implementation. This method is more flexible than the existing analytical methods since estimation can be based on five different distribution (Normal, Lognormal, Exponential, Weibull, and Beta) for the outcome variable. This article is protected by copyright. All rights reserved.

PMID:34148300 | DOI:10.1002/jrsm.1505

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Jun 25;24(6):505-512. doi: 10.3760/cma.j.cn.441530-20210226-00084.

ABSTRACT

Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.

PMID:34148315 | DOI:10.3760/cma.j.cn.441530-20210226-00084

Aust J Rural Health. 2021 Jun 20. doi: 10.1111/ajr.12720. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the pattern of prescribing long-acting reversible contraception by Australian general practitioner registrars across different classifications of rurality/urbanicity.

METHODS: A study nested within the Registrar Clinical Encounters in Training ongoing cohort study of Australian general practitioner registrars’ in-consultation experience.

DESIGN: A cross-sectional analysis of Registrar Clinical Encounters in Training data collected 2010-2017. Type of contraception prescribed by general practitioner registrars to women aged 12-55 for contraception-related indications was documented. Chi-square statistical analysis was performed to assess association of specific long-acting reversible contraception methods with rurality/urbanicity.

SETTING/PARTICIPANTS: General practitioner registrars enrolled in the Australian General Practice Training program in regional training providers/organisations participating in Registrar Clinical Encounters in Training.

MAIN OUTCOME MEASURES: Long-acting reversible contraception was defined as etonogestrel implant, copper intrauterine device, levonorgestrel intrauterine device and medroxyprogesterone injection.

RESULTS: In all 1737 registrars recorded 4073 registrar rounds of data from 2010 to 2017 (response rate 96%). Type of long-acting reversible contraception prescribed differed significantly across Australian Statistical Geography Standards classification of rurality (Pearson’s χ² = 17, P = .002). Women living in outer regional/remote/very remote regions are prescribed proportionately more medroxyprogesterone injection and less levonorgestrel intrauterine device compared to major cities/inner regional areas.

CONCLUSIONS: Long-acting reversible contraception methods prescribed differ across different classifications of rurality. Women living in more rural/remote regions might have access difficulties for the levonorgestrel intrauterine device.

PMID:34148268 | DOI:10.1111/ajr.12720

Aust J Rural Health. 2021 Jun 20. doi: 10.1111/ajr.12716. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess and compare rates of severe on-farm injury for older (> 50 years) and younger (15-49 years) cohorts, on NSW farms.

DESIGN: Descriptive retrospective epidemiological study of the New South Wales Trauma Registry (Institute of Trauma and Injury Management – ITIM) for persons injured on a farm.

SETTING: New South Wales, Australia.

PARTICIPANTS: Cases involving persons (≥15 years), with data on the NSW Trauma Registry (2012-16).

MAIN OUTCOME MEASURES: Comparison of injury rates and severity between younger (15-49 years) and older (50+ years) cohorts over the 2012-16 period based on Injury Severity Scores (ISS).

RESULTS: Older males are injured at a rate that is roughly 18% higher than younger males and 13% higher than the overall injury rate. Older individuals also have significantly longer hospital stays post-injury (P = 0.01), with this being most pronounced for older men (P < 0.01). There was no statistically significant difference in ISS demonstrated between the age cohorts (P = 0.64), except for younger women having higher median ISS than their older female counterparts (P = 0.02).

CONCLUSION: Overall, the general trends displayed support the contention that older males are more likely to incur a severe on-farm injury than their younger counterparts. This provides support for a preventative focus targeting older farmers in NSW.

PMID:34148277 | DOI:10.1111/ajr.12716