Body mass index’s effect on CRSwNP extends to pathological endotype and recurrence.

BACKGROUND: Elevated body mass index (BMI) has been recognized as an important contributor to corticosteroid insensitivity in chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to delineate the effects of elevated BMI on immunological endotype and recurrence in CRSwNP individuals. METHODOLOGY: A total of 325 patients with CRSwNP undergoing FESS were recruited and stratified by BMI. H&E staining was employed for histological evaluation. Characteristics of inflammatory patterns were identified by immunohistochemical staining. The predictive factors for recurrence were determined and evaluated by multivariable logistic regression analysis and the receiver operating characteristic (ROC) curves across all subjects and by weight group. RESULTS: In all patients with CRSwNP, 26.15% subjects were classified as overweight/obese group across BMI categories and exhibited a higher symptom burden. The upregulated eosinophil/neutrophil-dominant cellular endotype and amplified type 2/ type 3 coexisting inflammation was present in overweight/obese compared to underweight/normal weight controls. Additionally, a higher recurrent proportion was shown in overweight/obese patients than that in underweight/normal weight cohorts. Multivariable logistic regression analysis identified BMI as an independent predictor for recurrence. The predictive capacity of each conventional parameter (tissue eosinophil and CLCs count, and blood eosinophil percentage) alone or in combination was poor in overweight/obese subjects. CONCLUSIONS: Overweight/obese CRSwNP stands for a unique phenotype and endotype. Conventional parameters predicting recurrence are compromised in overweight/obese CRSwNP, and there is an urgent need for novel biomarkers that predict recurrence for these patients.

Fluorescence-guided cancer surgery-A new paradigm.

Fluorescence-guided surgery is an emerging and promising operative adjunct to assist the surgeon in various aspects of oncosurgery, ranging from assessing perfusion, identification, and characterization of tumors and peritoneal metastases, mapping of lymph nodes/leaks, and assistance for fluorescence-guided surgery (FGS). This study aims to provide an overview of principles, currently available dyes, platforms, and surgical applications and summarizes the available literature on the utility of FGS with a focus on abdomino-thoracic malignancies.

Does dual-energy CT differentiate benign and malignant ovarian tumours?

AIM: To assess the ability of dual-energy computed tomography (DECT) to distinguish benign from malignant ovarian tumours (OTs). MATERIALS AND METHODS: Following approval of the institutional review board, the institutional database was mined for treatment-naive patients who underwent primary cytoreduction for OT. Thirty-seven patients were included and divided into those with benign OTs (n = 11) and malignant OTs (n = 26), including high-grade (n = 20) and low-grade (n = 6) malignant OTs. Advanced processing and region of interest delineation on the ovarian mass were performed using the preoperative staging DECT examination using the Advantage Workstation. The pixel-level data of the CT attenuation values at 50, 70, and 120 keV and the effective atomic number (Zeff), water content (WC), and iodine content (IC) in the ovarian mass were recorded. The Wilcoxon rank-sum test was used to compare CT attenuation data at different voltages, Zeff, and WC and IC levels between benign and malignant OTs and between high- and low-grade malignant OTs. Simple logistic regression was used to correlate the imaging characteristics with malignant status and grade. RESULTS: Malignant OTs had significantly higher Zeff and IC compared with benign OTs. The threshold values for the diagnosis of malignant OT were IC≥9.74 (100 µg/cm3) with 81% sensitivity and 73% specificity and Zeff ≥8.16 with 85% sensitivity and 73% specificity. High-grade OTs had significantly higher WC compared with low-grade OTs, and a threshold of ≥1,013.92 mg/cm3 differentiated them with 80% sensitivity and 83% specificity. CONCLUSION: DECT may be a tool to help distinguish malignant and benign OTs and predict tumour grade.

Can MRI help assess aggressiveness of endometrial cancer?

AIM: To identify potential magnetic resonance imaging (MRI) biomarkers to predict the aggressiveness of endometrial cancer. MATERIALS AND METHODS: Seventy-one patients with endometrial cancer who underwent MRI staging were analysed retrospectively. The signal intensity (SI) of the tumours was assessed on sagittal T2-weighted imaging (WI) and sagittal T1WI sequences). The depth of myometrial invasion, tumour grade and subtype, lymphovascular invasion, and microsatellite stability status were assessed histopathologically, and these findings were compared with MRI findings using logistic regression. The log-rank test was used to assess differences in survival among groups defined by different MRI measurements. RESULTS: Tumours with qualitative higher signal than that of normal myometrium on the late T1WI DCE image sequences were more likely to have lymphovascular space invasion (p<0.001). Tumours that had a higher SI tumour ratio (T1 post-contrast arterial/T1 precontrast) had a higher chance of being microsatellite stable (odds ratio 2.36). The SI ratio of the tumour to the myometrium showed that lower T2 tumour/T2 myometrial ratio correlated with ≥50% depth of myometrial invasion as determined by imaging (p=0.006). Endometrial tumours showing a SI of >209 on delayed T1WI sequences had longer recurrence-free survival than those with tumours showing a SI ≤209 (p=0.014). Tumour subtype and grade were not associated with MRI findings. CONCLUSION: The SI of endometrial cancer on MRI may be used to predict the aggressiveness of the tumour and microsatellite stability status. Further studies are needed to confirm these findings.

Biosynthesis of Gold and Silver Nanoparticles Using Extracts of Callus Cultures of Pumpkin (Cucurbita maxima).

The potential of callus cultures and field-grown organs of pumpkin (Cucurbita maxima) for the biosynthesis of nanoparticles of the noble metals gold and silver has been investigated. Biosynthesis of AuNPs (gold nanoparticles) and AgNPs (silver nanoparticles) was obtained with flowers of C. maxima but not with pulp and seeds. With callus cultures established in MS-based medium the biogenesis of both AuNPs and AgNPs could be obtained. At 65 °C the biogenesis of AuNPs and AgNPs by callus extracts was enhanced. The AuNPs and AgNPs have been characterized by UV-visible spectroscopy, TEM, DLS and XRD. Well-dispersed nanoparticles, which exhibited a remarkable diversity in size and shape, could be visualized by TEM. Gold nanoparticles were found to be of various shapes, viz., rods, triangles, star-shaped particles, spheres, hexagons, bipyramids, discoid particles, nanotrapezoids, prisms, cuboids. Silver nanoparticles were also of diverse shapes, viz., discoid, spherical, elliptical, triangle-like, belt-like, rod-shaped forms and cuboids. EDX analysis indicated that the AuNPs and AgNPs had a high degree of purity. The surface charges of the generated AuNPs and AgNPs were highly negative as indicated by zeta potential measurements. The AuNPs and AgNPs exhibited remarkable stability in solution for more than four months. FTIR studies indicated that biomolecules in the callus extracts were associated with the biosynthesis and stabilisation of the nanoparticles. The synthesized AgNPs could catalyse degradation of methylene blue and exhibited anti-bacterial activity against E. coli DH5α. There is no earlier report of the biosynthesis of nanoparticles by this plant species. Callus cultures of Cucurbita maxima are effective alternative resources of biomass for synthesis of nanoparticles.

Fabrication of flexible thin polyurethane membrane for tissue engineering applications.

Thin and flexible polymeric membranes play a critical role in tissue engineering applications for example organs-on-a-chip. These flexible membranes can enable mechanical stretch of the engineered tissue to mimic organ-specific biophysical features, such as breathing. In this work, we report the fabrication of thin (<20 µm), stretchable, and biocompatible polyurethane (PU) membranes. The membranes were fabricated using spin coating technique on silicon substrates and were mounted on a frame for ease of device integration and handling. The membranes were characterized for their optical and elastic properties and compatibility with cell/tissue culture. It was possible to apply up to 10 kilopascal (kPa) pressure to perform cyclic stretch on 4 mm-diameter membranes for a period of 2 weeks at 0.2 hertz (Hz) frequency without mechanical failure. Adenocarcinomic human alveolar basal epithelial (A549) cells were cultured on the apical side of the PU membrane. The morphology and viability of the cells were comparable to those of cells cultured on standard tissue culture plates. Our experiments suggest that the stretchable PU membrane will be broadly useful for various tissue engineering applications in vitro.

Prevalence and trends in the antimicrobial susceptibility pattern of Salmonella enterica serovars Typhi and Paratyphi A among children in a pediatric tertiary care hospital in South India over a period of ten years: a retrospective study.

The aim of this study was to determine the prevalence and trends in the antimicrobial resistance of typhoidal salmonellae in children and adolescents at a pediatric tertiary care hospital in South India. Typhoidal salmonellae were isolated from 483 of the 77,713 blood cultures received during the ten-year study period (2007-2016). Isolates were speciated by conventional biochemical reactions and serotyping. Antimicrobial susceptibility testing was performed and interpreted according to the British Society for Antimicrobial Chemotherapy (BSAC)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The overall blood culture isolation rates of Salmonella enterica serovars Typhi and Paratyphi A in children were 0.5% (408 cases) and 0.1% (73 cases), respectively, with the highest isolation rates in school [299 (61.9%)] and preschool children [113 (23.4%)]. A decreasing prevalence of enteric fever was seen from 2012 to 2015, with a sudden surge in 2016. From 2011 onwards, a high fluoroquinolone resistance (90-100%) was observed. Multidrug resistance was observed in only four (0.9%) S. Typhi isolates. 100% susceptibility to third-generation cephalosporins and azithromycin was noted. Enteric fever as seen in a pediatric tertiary care hospital in India affects children and adolescents of all age groups, with greater isolation rates in school children, followed by those in preschool years, calling for targeted interventions against these age groups. The study findings support the use of third-generation cephalosporins and azithromycin as first-line therapy and ampicillin and co-trimoxazole as step-down therapy in pediatric enteric fever. However, continued local surveillance should be done to detect antimicrobial resistance trends to optimize treatment.

Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study.

OBJECTIVE: To explore the impact of risk-adjustment on surgical complication rates (CRs) for benchmarking gynaecological oncology centres. DESIGN: Prospective cohort study. SETTING: Ten UK accredited gynaecological oncology centres. POPULATION: Women undergoing major surgery on a gynaecological oncology operating list. METHODS: Patient co-morbidity, surgical procedures and intra-operative (IntraOp) complications were recorded contemporaneously by surgeons for 2948 major surgical procedures. Postoperative (PostOp) complications were collected from hospitals and patients. Risk-prediction models for IntraOp and PostOp complications were created using penalised (lasso) logistic regression using over 30 potential patient/surgical risk factors. MAIN OUTCOME MEASURES: Observed and risk-adjusted IntraOp and PostOp CRs for individual hospitals were calculated. Benchmarking using colour-coded funnel plots and observed-to-expected ratios was undertaken. RESULTS: Overall, IntraOp CR was 4.7% (95% CI 4.0-5.6) and PostOp CR was 25.7% (95% CI 23.7-28.2). The observed CRs for all hospitals were under the upper 95% control limit for both IntraOp and PostOp funnel plots. Risk-adjustment and use of observed-to-expected ratio resulted in one hospital moving to the >95-98% CI (red) band for IntraOp CRs. Use of only hospital-reported data for PostOp CRs would have resulted in one hospital being unfairly allocated to the red band. There was little concordance between IntraOp and PostOp CRs. CONCLUSION: The funnel plots and overall IntraOp (≈5%) and PostOp (≈26%) CRs could be used for benchmarking gynaecological oncology centres. Hospital benchmarking using risk-adjusted CRs allows fairer institutional comparison. IntraOp and PostOp CRs are best assessed separately. As hospital under-reporting is common for postoperative complications, use of patient-reported outcomes is important. TWEETABLE ABSTRACT: Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison.

Is MRI helpful in assessing the distance of the tumour from the internal os in patients with cervical cancer below FIGO Stage IB2?

AIM: To determine the ability of magnetic resonance imaging (MRI) in detecting tumour-free margins from the internal os (IO). MATERIALS AND METHODS: A database search yielded 79 women with early-stage cervical cancer who underwent radical hysterectomy and preoperative MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI in assessment of ≤5 and >5 mm IO involvement were calculated with histopathological surgical specimen findings considered to be the reference standard. A main and subset analysis was performed. The subset analysis included only those patients who would have been considered for radical trachelectomy. RESULTS: For predicting a distance between the tumour and the IO of ≤5 mm, MRI had a sensitivity of 73%, a specificity of 98.3%, a PPV of 95%, a NPV of 88.1%, and an accuracy of 89.8% for the main analysis, and sensitivity of 81.8%, a specificity of 93.2% a PPV of 69.2% a NPV of 96.5% and an accuracy of 91.4% for the subset analysis. CONCLUSION: MRI has high specificity, NPV, and accuracy in detecting tumour from the IO, making MRI suitable for treatment planning in patients desiring trachelectomy to preserve fertility.

Predictors of complications in gynaecological oncological surgery: a prospective multicentre study (UKGOSOC-UK gynaecological oncology surgical outcomes and complications).

BACKGROUND: There are limited data on surgical outcomes in gynaecological oncology. We report on predictors of complications in a multicentre prospective study. METHODS: Data on surgical procedures and resulting complications were contemporaneously recorded on consented patients in 10 participating UK gynaecological cancer centres. Patients were sent follow-up letters to capture any further complications. Post-operative (Post-op) complications were graded (I-V) in increasing severity using the Clavien-Dindo system. Grade I complications were excluded from the analysis. Univariable and multivariable regression was used to identify predictors of complications using all surgery for intra-operative (Intra-op) and only those with both hospital and patient-reported data for Post-op complications. RESULTS: Prospective data were available on 2948 major operations undertaken between April 2010 and February 2012. Median age was 62 years, with 35% obese and 20.4% ASA grade ⩾3. Consultant gynaecological oncologists performed 74.3% of operations. Intra-op complications were reported in 139 of 2948 and Grade II-V Post-op complications in 379 of 1462 surgeries. The predictors of risk were different for Intra-op and Post-op complications. For Intra-op complications, previous abdominal surgery, metabolic/endocrine disorders (excluding diabetes), surgical complexity and final diagnosis were significant in univariable and multivariable regression (P<0.05), with diabetes only in multivariable regression (P=0.006). For Post-op complications, age, comorbidity status, diabetes, surgical approach, duration of surgery, and final diagnosis were significant in both univariable and multivariable regression (P<0.05). CONCLUSIONS: This multicentre prospective audit benchmarks the considerable morbidity associated with gynaecological oncology surgery. There are significant patient and surgical factors that influence this risk.

Biogenic synthesis of gold and silver nanoparticles by seed plants.

Nanoparticles have an enormous range of biomedical and environmental applications and can be used for development of various nanodevices for diagnostics and drug delivery. Biogenic production of nanoparticles, that is of silver and gold, by seed plants, especially flowering plants, has evoked considerable interest in the last decade. Different organs of plants as well as callus cultures have been used for the production of these metal nanoparticles. It is possible to regulate the geometry of the nanoparticles by modifying the experimental parameters. In many cases the phytosynthesized gold and silver nanoparticles have been demonstrated to be potentially useful for treatment of various diseases. The production of gold and silver nanoparticles by diverse species of seed plants and their biological activity are discussed in this article.

Congenital Stenosis of the Spine-A Cross-Sectional Study of 1019 Whole-Spine Computed Tomography Scans to Determine Prevalence and Association Among Multilevel, Tandem, and Triple Region Stenosis.

BACKGOUND: Patients with congenital stenosis of the spine (CSS) present with clinical symptoms at an early age and fewer degenerative hypertrophic changes than the more common degenerative cohort. Literature is lacking in the true prevalence of CSS affecting the 3 segments of the spine in isolation, as well as in tandem in the Indian subcontinent. METHODS: Anteroposterior spinal canal diameter in axial plane computed tomography at the midvertebral level was measured in asymptomatic patients with whole-spine computed tomography. Spinal canal stenosis was defined as a diameter of <12 mm for the cervical region, <12 mm for the thoracic region, and <13 mm for the lumbar region. Single-level and multilevel stenosis, as well as tandem and triple-region stenosis, were evaluated. RESULTS: The results show the prevalence of CSS as 16.6%, 11.5%, and 20.1% involving the cervical, thoracic, and lumbar spine, respectively. Single-level stenosis affected 90.6%, 94%, and 79.8% of the patients with cervical, thoracic, and lumbar CSS, respectively. Tandem stenosis affected 10.4% of the population (n = 104), with cervicolumbar stenosis being the most prevalent (n = 51, 5%). The presence of CSS in any one segment of the spine was significantly associated with the presence of stenosis at one of the other segments (P < 0.05). Triple-region stenosis was seen in 0.3% (n = 3) patients. CONCLUSIONS: The prevalence of cervical, thoracic, lumbar and tandem stenosis from our study is established at 16.6%, 11.5%, 20.1%, and 10.4%. Additionally, our study demonstrates the association between stenosis of the different regions of the spine.

Neuromonitoring Signal Changes in Degenerative Cervical Myelopathy: An Analysis of Risk Factors for Signal Drops During Posterior Cervical Decompression.

OBJECTIVE: To analyze intraoperative neuromonitoring data of patients with degenerative cervical myelopathy undergoing cervical laminectomy and assess the incidence of signal drops and their risk factors. METHODS: This retrospective observational study included patients with degenerative cervical myelopathy who underwent cervical laminectomy with intraoperative neuromonitoring between July 2018 and March 2023. We analyzed the signal changes for any correlation with the type of pathology (ossified posterior longitudinal ligament vs. cervical spondylotic myelopathy [CSM]) and clinical (severity of myelopathy, duration of symptoms) and radiological (length of cord signal changes and K-line) parameters. RESULTS: Of 100 degenerative cervical myelopathy cases, 55 were diagnosed as OPLL and 45 as CSM. Signal drops were recorded in 26 patients-14 persistent drops and 12 transient drops. True positive drops were seen in 4 patients (2 OPLL and 2 CSM), 3 of whom had sustained bimodal drops (both somatosensory evoked potentials and motor evoked potentials). Signal drops were significantly more frequent with OPLL compared with CSM (P < 0.01). Ten of 14 persistent signal drops and 9 of 12 transient drops were seen in patients in OPLL. Continuous OPLL, negative K-line, hill type OPLL, severity of myelopathy, and longer duration of symptoms were risk factors for signal drops. CONCLUSIONS: Patients with cervical OPLL have a higher incidence of false positive and transient signal drops after decompression compared with patients with CSM. Longer duration of symptoms, high-grade myelopathy, continuous OPLL, hill type OPLL, and negative K-line were risk factors for signal drops.

Does Magnetic Resonance Imaging Predict Neurological Deficit in Patients with Traumatic Lower Lumbar Fractures?

STUDY DESIGN: A retrospective cohort study. PURPOSE: This study aimed to understand the role of magnetic resonance imaging (MRI) in predicting neurological deficits in traumatic lower lumbar fractures (LLFs; L3-L5). OVERVIEW OF LITERATURE: Despite studies on the radiological risk factors for neurological deficits in thoracolumbar fractures, very few have focused on LLFs. Moreover, the potential utility of MRI in LLFs has not been evaluated. METHODS: In total, 108 patients who underwent surgery for traumatic LLFs between January 2010 and January 2020 were reviewed to obtain their demographic details, injury level, and neurology status at the time of presentation (American Spinal Injury Association [ASIA] grade). Preoperative computed tomography scans were used to measure parameters such as anterior vertebral body height, posterior vertebral body height, loss of vertebral body height, local kyphosis, retropulsion of fracture fragment, interpedicular distance, canal compromise, sagittal transverse ratio, and presence of vertical lamina fracture. MRI was used to measure the canal encroachment ratio (CER), cross-sectional area of the thecal sac (CSAT), and presence of an epidural hematoma. RESULTS: Of the 108 patients, 9 (8.3%) had ASIA A, 4 (3.7%) had ASIA B, 17 (15.7%) had ASIA C, 21 (19.4%) had ASIA D, and 57 (52.9%) had ASIA E neurology upon admission. The Thoracolumbar Injury Classification and Severity score (p =0.000), CER (p =0.050), and CSAT (p =0.019) were found to be independently associated with neurological deficits on the multivariate analysis. The receiver operating characteristic curves showed that only CER (area under the curve [AUC], 0.926; 95% confidence interval [CI], 0.860-0.968) and CSAT (AUC, 0.963; 95% CI, 0.908-0.990) had good discriminatory ability, with the optimal cutoff of 50% and 65.3 mm2, respectively. CONCLUSIONS: Based on the results, the optimal cutoff values of CER >50% and CSAT >65.3 mm2 can predict the incidence of neurological deficits in LLFs.

Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.

The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation. Here we show that drug-resistant EGFR mutations manipulate the assembly of ligand-free, kinase-active oligomers to promote and stabilize the assembly of oligomer-obligate active dimer sub-units and circumvent the need for ligand binding. We reveal the structure and assembly mechanisms of these ligand-free, kinase-active oligomers, uncovering oncogenic functions for hitherto orphan transmembrane and kinase interfaces, and for the ectodomain tethered conformation of EGFR. Importantly, we find that the active dimer sub-units within ligand-free oligomers are the high affinity binding sites competent to bind physiological ligand concentrations and thus drive tumor growth, revealing a link with tumor proliferation. Our findings provide a framework for future drug discovery directed at tackling oncogenic EGFR mutations by disabling oligomer-assembling interactions.

Patient-reporting improves estimates of postoperative complication rates: a prospective cohort study in gynaecological oncology.

BACKGROUND: Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS: A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contemporaneously into an online database. Patients were sent follow-up letters to capture postoperative complications. Grade II-V (Clavien-Dindo classification) patient-reported postoperative complications were verified from hospital records. Postoperative complication rate was defined as the proportion of surgeries with a Grade II-V postoperative complication. RESULTS: Patient replies were received for 1462 (68%) of 2152 surgeries undertaken between April 2010 and February 2012. Overall, 452 Grade II-V (402 II, 50 III-V) complications were reported in 379 of the 1462 surgeries. This included 172 surgeries with 200 hospital-reported complications and 231 with 280 patient-reported complications. All (100% concordance) 36 Grade III-V and 158 of 280 (56.4% concordance) Grade II patient-reported complications were verified on hospital case-note review. The PCR using hospital-reported data was 11.8% (172 out of 1462; 95% CI 11-14), patient-reported was 15.8% (231 out of 1462; 95% CI 14-17.8), hospital and verified patient-reported was 19.4% (283 out of 1462; 95% CI 17.4-21.4) and all data were 25.9% (379 out of 1462; 95% CI 24-28). After excluding Grade II complications, the hospital and patient verified Grade III-V PCR was 3.3% (48 out of 1462; 95% CI 2.5-4.3). CONCLUSION: This is the first prospective study of postoperative complications we are aware of in gynaecological oncology to include the patient-reported data. Patient-reporting is invaluable for obtaining complete information on postoperative complications. Primary care case-note review is likely to improve verification rates of patient-reported Grade II complications.