Nevin Manimala

J Robot Surg. 2021 Oct 30. doi: 10.1007/s11701-021-01324-2. Online ahead of print.

ABSTRACT

The purpose is to report the United Kingdom’s largest single-centre experience of robotically assisted laparoscopic radical prostatectomies (RALP), using the neurovascular structure-adjacent frozen-section (NeuroSAFE) technique. We describe the utilisation and outcomes of this technique. This is a retrospective study from 2012 to 2019 on 520 patients undergoing NeuroSAFE RALP at our Institution. Our Institution’s database was analysed for false-positive frozen-section (FS) margins as confirmed on paraffin histopathological analysis: functional outcomes of potency, continence, and biochemical recurrence (BCR). The median (range) of console time was 145 (90-300) min. In our cohort, positive FS was seen in 30.7% (160/520) of patients, with a confirmatory paraffin analysis in 91.8% of our patients’ cohort (147/160). The neurovascular bundles (NVBs) that underwent secondary resection contained tumour in 26.8% (43/160) of the cases. Biochemical recurrence (BCR) was 6.7% (35/520), of which FS was positive in 40% (14/35) of those cases. There were insufficient evidence of a statistical association of urinary incontinence and positive surgical margin rates according to NS or NVB resection. NeuroSAFE enables intraoperative confirmation of the oncologic safety of a NS procedure. Patients with a positive FS on NeuroSAFE can be converted to a negative surgical margin (NSM) by ipsilateral wide resection. This spared 1 in 4 men from positive margins posterolaterally in our series. Limitations are the absence of a matched contemporary cohort of NS RALP without NeuroSAFE in our centre.

PMID:34716876 | DOI:10.1007/s11701-021-01324-2

Mol Cell Biochem. 2021 Oct 30. doi: 10.1007/s11010-021-04279-y. Online ahead of print.

ABSTRACT

MN/CA9 is a cell surface glycoprotein and a tumor-associated antigen. It plays a crucial role in the regulation of cell proliferation and oncogenesis. There is no ideal tumor marker currently available for renal cell carcinoma (RCC) with sufficient sensitivity and specificity. Therefore, we studied MN/CA9 gene expression in the tumor tissue, apparently normal kidney tissue, preoperative blood, and urine samples of patients with RCC. We included thirty cases of renal tumors (26 RCC and 4 benign tumors) in the study. We applied an RT-PCR assay for MN/CA9 gene expression to 26 RCC kidney tumor samples and four benign kidney tumor tissue samples. We also evaluated MN/CA9 gene expression in preoperative blood and urine samples of 15 of these cases. Additionally, thirty-five grossly normal renal tissue samples, including 21 from kidneys with RCC, were also evaluated for gene expression. The RT-PCR analysis revealed that twenty-one out of 26 RCC tissue samples showed MN/CA9 gene expression compared to three out of 35 non-malignant renal tissue samples (p < 0.05). Two out of four benign renal tissue samples also expressed this gene. We also observed MN/CA9 gene expression in nine out of 15 blood samples and four out of 15 urine samples. All patients with urinary MN/CA9 gene expression showed expression in blood and tumor tissue samples. We found a correlation in terms of MN/CA9 expression between blood and tumor tissue samples of RCC patients as those who exhibit MN/CA9 expression in blood were also positive at the tumor tissue levels. The difference in MN/CA9 gene expression in tumor tissue, blood, and urine samples in relation to the stage of the disease, nuclear grade, and histological cell-type was not statistically significant. However, all the three patients who had metastatic RCC had MN/CA9 gene expression in their blood. The existence of a tumor-associated antigen such as MN/CA9 may present a possible target for molecular diagnosis and management of RCC.

PMID:34716861 | DOI:10.1007/s11010-021-04279-y

Oral Maxillofac Surg. 2021 Oct 30. doi: 10.1007/s10006-021-01014-1. Online ahead of print.

ABSTRACT

PURPOSE: Biomarkers represent objective indicators of normal processes, pathology, or responses to therapeutic intervention. The purpose of this study is to evaluate the levels of proinflammatory cytokines in synovial fluid of the temporomandibular joint (TMJ) and to investigate whether there is a correlation between elevated levels and disease progression.

MATERIALS AND METHODS: This is a prospective study that included patients who were diagnosed with internal derangement according to magnetic resonance imaging and were classified according to Wilkes’s classifications. After failing to improve with conservative treatment, they were referred for TMJ arthroscopy. During arthroscopy, synovial fluid was collected for biomarker analyses that included the investigation of levels of proinflammatory cytokines: tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF). The Mann-Whitney U test was used for differences between subgroups for TNF-α, IL-6, and VEGF.

RESULTS: During the study period, 22 patients presented with a TMJ disorder and met the criteria of the study. There was a statistically significant correlation between the levels of VEGF, TNF-a, and osteoarthritis (P < 0.05). There was also a statistically significant correlation between TNF-a levels and a higher degree of chondromalacia (P = 0.019).

CONCLUSION: An increase in inflammatory cytokines coupled with chondromalacia propose a more aggressive degenerative disease.

PMID:34716857 | DOI:10.1007/s10006-021-01014-1

Cancer Metastasis Rev. 2021 Oct 30. doi: 10.1007/s10555-021-10001-7. Online ahead of print.

ABSTRACT

BACKGROUND: Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.

METHODS: Statistical correlations for all RTK family members’ expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.

RESULTS: Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.

CONCLUSIONS: Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.

PMID:34716856 | DOI:10.1007/s10555-021-10001-7

Int J Biometeorol. 2021 Oct 30. doi: 10.1007/s00484-021-02214-w. Online ahead of print.

ABSTRACT

This work aimed to evaluate the thermal comfort provided by shading structures in free-range systems under a tropical environment, based on microclimate variables of nets with different materials. During the experiment, the unshading area; the natural shading of a native tree species to the Brazilian Savanna; and the artificial 80% shadings nets: black polypropylene, heat-reflective aluminized, and association of both were evaluated. The shading structures were analyzed in paddocks at the Água Limpa Farm from the University of Brasília, where dry-bulb, wet-bulb, black globe temperatures, and wind speed were collected for the micrometeorological characterization from 8:00 am to 4:00 pm. From the temperatures, the vapor pressures and the humidities were calculated. The shortwave radiation was calculated through the sum of direct, diffuse, and reflected radiations. The mean radiant temperature, radiant heat load, and black globe temperature and humidity index were calculated. The internal and external surface temperatures of the nets and the soil temperature were measured every 30 min. The data were analyzed with aid of the statistical analysis system. The air temperature varied according to the shortwave radiation, from 25.6 °C at 8:00 am to 29.6 °C at 1:00 pm, with a decrease over the hours. Despite the air temperature of the trees showed the lowest average, the nets association structure was the most reduced all the thermal comfort indexes. The heat-reflective net presented the lowest soil temperature at all hours (under 26.1 °C). In general, the shadings proved to be efficient in promoting thermal comfort in free-range systems.

PMID:34716805 | DOI:10.1007/s00484-021-02214-w

Eur J Nutr. 2021 Oct 30. doi: 10.1007/s00394-021-02711-z. Online ahead of print.

ABSTRACT

PURPOSE: This study evaluated the postprandial effects following consumption of buckwheat, fava bean, pea, hemp and lupin compared to meat (beef); focussing on biomarkers of satiety, gut hormones, aminoacids and plant metabolites bioavailability and metabolism.

METHODS: Ten subjects (n = 3 men; n = 7 women; 42 ± 11.8 years of age; BMI 26 ± 5.8 kg/m²) participated in six 1-day independent acute interventions, each meal containing 30 g of protein from buckwheat, fava bean, pea, hemp, lupin and meat (beef). Blood samples were collected during 24-h and VAS questionnaires over 5-h.

RESULTS: Volunteers consumed significantly higher amounts of most amino acids from the meat meal, and with few exceptions, postprandial composition of plasma amino acids was not significantly different after consuming the plant-based meals. Buckwheat meal was the most satious (300 min hunger scores, p < 0.05).Significant increase in GLP-1 plasma (AUC, iAUC p = 0.01) found after hemp compared with the other plant-based meals. Decreased plasma ghrelin concentrations (iAUC p < 0.05) found on plant (hemp) vs. meat meal. Several plasma metabolites after hemp meal consumption were associated with hormone trends (partial least squares-discriminant analysis (PLS-DA): 4-hydroxyphenylpyruvic acid, indole 3-pyruvic acid, 5-hydoxytryptophan, genistein and biochanin A with GLP-1, PYY and insulin; 3-hydroxymandelic acid and luteolidin with GLP-1 and ghrelin and 4-hydroxymandelic acid, benzoic acid and secoisolariciresinol with insulin and ghrelin. Plasma branched-chain amino acids (BCAAs), (iAUC, p < 0.001); and phenylalanine and tyrosine (iAUC, p < 0.05) were lower after buckwheat comparison with meat meal.

CONCLUSION: Plants are valuable sources of amino acids which are promoting satiety. The impact of hemp and buckwheat on GLP-1 and, respectively, BCAAs should be explored further as could be relevant for aid and prevention of chronic diseases such as type 2 diabetes. Study registered with clinicaltrial.gov on 12th July 2013, study ID number: NCT01898351.

PMID:34716790 | DOI:10.1007/s00394-021-02711-z

Z Rheumatol. 2021 Oct 30. doi: 10.1007/s00393-021-01119-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the relative effectiveness and safety of Janus kinase (JAK) inhibitors in active psoriatic arthritis (PsA) patients.

MATERIALS AND METHODS: A Bayesian network meta-analysis was performed using data from randomized controlled trials (RCTs) to evaluate the effectiveness and safety of upadacitinib 30 mg, upadacitinib 15 mg, tofacitinib 10 mg, tofacitinib 5 mg, and filgotinib 200 mg in active PsA patients.

RESULTS: Five RCTs including 2539 patients fulfilled the inclusion criteria. The surface under the cumulative ranking curve (SUCRA) revealed that filgotinib 200 mg had the highest probability of reaching a 20% American College of Rheumatology (ACR20) response rate, followed by upadacitinib 30 mg, upadacitinib 15 mg, tofacitinib 10 mg, tofacitinib 5 mg, and placebo. Upadacitinib 30 mg had the highest probability of achieving the ACR50 and ACR70 response rates, followed by upadacitinib 15 mg, filgotinib 200 mg, tofacitinib 10 mg, tofacitinib 5 mg, and placebo. The SUCRA rating based on the Psoriasis Area and Severity Index response rate of at least 75% (PASI75) showed that tofacitinib 10 mg had the highest probability of achieving this response, followed by upadacitinib 15 mg, filgotinib 200 mg, tofacitinib 5 mg, and placebo. Safety analyses evaluated adverse events (AEs) and serious adverse events (SAEs), but no statistically relevant differences were found.

CONCLUSION: Based on the ACR response rates, filgotinib 200 mg and upadacitinib 30 mg were the most effective, whereas tofacitinib 10 mg was the most effective treatment for PsA based on PASI75. However, treatment options were similar with regard to AEs and SAEs.

PMID:34716775 | DOI:10.1007/s00393-021-01119-8

Eur J Clin Pharmacol. 2021 Oct 30. doi: 10.1007/s00228-021-03238-2. Online ahead of print.

ABSTRACT

PURPOSE: Adverse drug events are related to negative outcomes in healthcare, including hospitalization, increased duration of hospital stay and death. The aim of this study was to conduct a systematic review to evaluate hospitalizations and deaths related to adverse drug events worldwide, reported in studies with national coverage.

METHODS: The protocol was registered in PROSPERO (CRD42020157008). We performed a systematic search on Medline, Embase, CINAHL, LILACS, and the Cochrane Library (until March 2020) using pre-specified terms. We included published studies that reported data on hospitalizations and/or deaths related to adverse drug events from a national perspective and the use of secondary data as a source of information. Two reviewers independently extracted and synthesized data. The quality of the studies was assessed using an adapted version of the Joanna Briggs Institute critical appraisal checklist for prevalence studies. Narrative summaries of findings were undertaken.

RESULTS: Among 59,336 citations, 62 studies were included for data extraction and synthesis. Among these studies, 41 studies included the outcome of hospitalization, 16 included the death outcome, and five included both outcomes. Administrative databases regarding discharges and registries of vital statistics were the most common sources of information. The relative frequency of hospitalizations ranged from 0.03% to 7.3%, and from 9.7 to 383.0/100,000 population, whereas mortality rate ranged from 0.1 to 7.88/100,000 population.

CONCLUSION: Our study highlights information about adverse drug events using large administrative databases in a national scenario and provides an overview of databases and methods implemented to detect adverse drug events.

PMID:34716774 | DOI:10.1007/s00228-021-03238-2

Sci Rep. 2021 Oct 29;11(1):21293. doi: 10.1038/s41598-021-99727-6.

ABSTRACT

Quantifying changes in DNA and RNA levels is essential in numerous molecular biology protocols. Quantitative real time PCR (qPCR) techniques have evolved to become commonplace, however, data analysis includes many time-consuming and cumbersome steps, which can lead to mistakes and misinterpretation of data. To address these bottlenecks, we have developed an open-source Python software to automate processing of result spreadsheets from qPCR machines, employing calculations usually performed manually. Auto-qPCR is a tool that saves time when computing qPCR data, helping to ensure reproducibility of qPCR experiment analyses. Our web-based app ( https://auto-q-pcr.com/ ) is easy to use and does not require programming knowledge or software installation. Using Auto-qPCR, we provide examples of data treatment, display and statistical analyses for four different data processing modes within one program: (1) DNA quantification to identify genomic deletion or duplication events; (2) assessment of gene expression levels using an absolute model, and relative quantification (3) with or (4) without a reference sample. Our open access Auto-qPCR software saves the time of manual data analysis and provides a more systematic workflow, minimizing the risk of errors. Our program constitutes a new tool that can be incorporated into bioinformatic and molecular biology pipelines in clinical and research labs.

PMID:34716395 | DOI:10.1038/s41598-021-99727-6

Sci Rep. 2021 Oct 29;11(1):21333. doi: 10.1038/s41598-021-00780-y.

ABSTRACT

Inventories of seismically induced landslides provide essential information about the extent and severity of ground effects after an earthquake. Rigorous assessment of the completeness of a landslide inventory and the quality of a landslide susceptibility map derived from the inventory is of paramount importance for disaster management applications. Methods and materials applied while preparing inventories influence their quality, but the criteria for generating an inventory are not standardized. This study considered five landslide inventories prepared by different authors after the 2015 Gorkha earthquake, to assess their differences, understand the implications of their use in producing landslide susceptibility maps in conjunction with standard landslide predisposing factors and logistic regression. We adopted three assessment criteria: (1) an error index to identify the mutual mismatches between the inventories; (2) statistical analysis, to study the inconsistency in predisposing factors and performance of susceptibility maps; and (3) geospatial analysis, to assess differences between the inventories and the corresponding susceptibility maps. Results show that substantial discrepancies exist among the mapped landslides. Although there is no distinct variation in the significance of landslide causative factors and the performance of susceptibility maps, a hot spot analysis and cluster/outlier analysis of the maps revealed notable differences in spatial patterns. The percentages of landslide-prone hot spots and clustered areas are directly proportional to the size of the landslide inventory. The proposed geospatial approaches provide a new perspective to the investigators for the quantitative analysis of earthquake-triggered landslide inventories and susceptibility maps.

PMID:34716368 | DOI:10.1038/s41598-021-00780-y