A cross-shaped terahertz metamaterial absorber for brain cancer detection.

The article presents, for the first time, a terahertz metamaterial absorber (TMA) designed in the shape of a cross consisting of four orthogonally positioned horn-shaped patches in succession, to detect brain cancer cells. The design exhibits the property of mu-negative material, indicating magnetic resonance. The proposed TMA has achieved an impressive absorption rate of 99.43% at 2.334 THz and a high Q-factor of 47.15. The sensing capability has been investigated by altering the refractive index of the surrounding medium in the range of 1.3 to 1.48, resulting in a sensitivity of 0.502 THz/RIU. The proposed TMA exhibits complete polarization insensitivity, highlighting this as one of its advantageous features. The adequate sensing capability of the proposed TMA in differentiating normal and cancerous brain cells makes it a viable candidate for an early and efficient brain cancer detector. This research can be the foundation for future research on using THz radiation for brain cancer detection.

A census of general surgery consultants in England and Wales: implications for the current and future surgical workforce.

INTRODUCTION: This study aimed to describe the composition of the current general surgical consultant body in England and Wales and quantify levels of inequality within it as well as describe future workforce challenges. METHODS: This is an observational study of all general surgical departments in England and Wales. Consultant general surgeons were identified and data regarding their gender, country of undergraduate medical education, subspecialty and private practice were recorded. RESULTS: Of the 2,682 consultant general surgeons in England and Wales identified for this study, just 17% are women, with gender inequality most marked in university teaching hospitals and among certain subspecialties. Almost 40% of consultants did not obtain their primary undergraduate degree in the United Kingdom and there are considerably fewer surgeons who studied abroad in university teaching hospitals. Over 40% of current general surgical consultants have been qualified for more than three decades and there is no equivalent sized group of younger consultants. CONCLUSIONS: There remains considerable gender and racial inequality in the consultant general surgical workforce, with pockets of a lack of diversity within university or teaching hospital surgical departments and some subspecialties. The proportion of surgeons in their fourth decade of clinical practice represents the largest group of current practising consultants, which points towards an impending workforce crisis should senior clinicians seek to reduce activity or consider taking early retirement.

Atypical presentations of cutaneous tuberculosis: Series of 10 cases.

Cutaneous tuberculosis classically presents as Lupus vulgaris, scrofuloderma, tuberculosis verrucose cutis and tubercular abscess. Hypersensitivity reaction to the bacilli leads to Lichen scrofulosorum and papulonecrotic tuberculids. At the same time, it can have myriad of clinical presentations, many of which are still undescribed. It is important to regularly update ourselves with these unusual manifestations so as to ensure early treatment and reduction of overall morbidity. In this case series tuberculosis manifesting as rapidly progressing diffuse facial granulomas, sporotrichoid tuberculosis, tuberculosis mimicking squamous cell carcinoma, scrofuloderma as tubercular ulcer, lupus vulgaris with nasal septal perforation, lupus vulgaris resembling furuncle, psoriasis, dermatitis and BT Hansen are described in immunocompetent individuals. These cases highlight the importance of recognition of atypical forms of cutaneous tuberculosis to minimize scarring and dissemination of bacilli.

Nevus Lipomatosus Cutaneous Superficialis of Hoffmann and Zurhelle: a rare cutaneous hamartoma.

Nevus lipomatosus cutaneous superficialis (NLCS) is a rare idiopathic cutaneous hamartoma characterized by ectopic clusters of mature adipose tissues in dermis. It is classified into two types. Classical type presenting as multiple lesions with onset at birth or within third decade of life and solitary type with onset between third to sixth decade of life. Here we present a case of 45 years female with adult onset, asymptomatic, grouped, skin colored, soft sessile growth in zosteriform pattern on left buttock. We here intend to report rare case of classical Nevus Lipomatosus Cutaneous Superficialis.

Anal cancer survival: a socioeconomic analysis.

INTRODUCTION: Squamous cell carcinoma is the most common variant of anal malignancy. Certain disease-related factors have been established in determining survival. These include tumour size, differentiation and nodal involvement. Other factors such as HIV status, human papillomavirus infection, smoking and socioeconomic disparity may have important roles, however few data are available on the UK population. We aim to correlate social deprivation and survival of anal cancer patients at a tertiary centre. MATERIALS AND METHODS: All consecutive cases diagnosed with anal squamous cell carcinoma and treated as per local protocol between July 2010 and April 2017 were included. The pathological and demographical details were collected from a prospectively maintained database. Socioeconomic deprivation was defined for each postcode using the Index of Multiple Deprivation decile compiled by local governments in England. Survival was estimated using Kaplan-Meier analysis and Cox regression was used to investigate the effect of different factors on overall survival. RESULTS: A total of 129 patients with anal squamous cell carcinoma over a median follow-up of 43 months were included. Overall survival for the entire patient cohort was 87.7% (95% confidence interval, CI, 82.0-93.7%), 75.5% (95% CI 67.5-84.5%) and 68.9% (95% CI 59.7-79.6%) at one year, three years and five years, respectively. On multivariate analysis, Index of Multiple Deprivation and income do not significantly influence overall survival (p = 0.79, hazard ratio, HR, 1.07; 95% CI 0.61-1.63), (p = 0.99, HR=1.00; 95% CI 0.61-1.63), respectively. Increased risk of death was observed for male sex (p = 0.02, HR=2.80; 95% CI 1.02-5.50) and larger tumour size (p = 0.01, HR=1.64; 95% CI 1.12-2.41). CONCLUSION: In contrast to US studies, there is little difference in survival between the least deprived and most deprived groups. We attribute this to equal access to intensity-modulated radiation therapy-based chemoradiotherapy. Thus, a highly effective treatment made available to all mitigates any survival difference between socioeconomic groups.

Repeatability and reproducibility study of radiomic features on a phantom and human cohort.

The repeatability and reproducibility of radiomic features extracted from CT scans need to be investigated to evaluate the temporal stability of imaging features with respect to a controlled scenario (test-retest), as well as their dependence on acquisition parameters such as slice thickness, or tube current. Only robust and stable features should be used in prognostication/prediction models to improve generalizability across multiple institutions. In this study, we investigated the repeatability and reproducibility of radiomic features with respect to three different scanners, variable slice thickness, tube current, and use of intravenous (IV) contrast medium, combining phantom studies and human subjects with non-small cell lung cancer. In all, half of the radiomic features showed good repeatability (ICC > 0.9) independent of scanner model. Within acquisition protocols, changes in slice thickness was associated with poorer reproducibility compared to the use of IV contrast. Broad feature classes exhibit different behaviors, with only few features appearing to be the most stable. 108 features presented both good repeatability and reproducibility in all the experiments, most of them being wavelet and Laplacian of Gaussian features.

Pharmacophore-based identification and in vitro validation of apoptosis inducers as anticancer agents.

Ligand-based pharmacophore modelling and virtual screening along with in vitro screening were performed as a rational strategy for the identification of novel compounds as apoptosis inducers and anticancer agents from the chemical database. Known apoptosis inducers were selected from the literature for generation of pharmacophore models, which were subjected to validation using Receiver operating characteristic (ROC) and Günere-Henry (GH) scoring methods. Based on highest fitness score of 4680.61, ROC value of 0.872 and GH score of 0.758, pharmacophore model-2 was selected as the best model. Model-2 as 3D search query was searched against the IBS database to find novel compounds as hits. Three hits were selected with a QFIT value more than 82 for in vitro screening as apoptosis inducers and anticancer agents. In vitro anticancer activity was performed using resazurin cell variability assay, and apoptosis inducing activity was determined using caspase-3 activation and annexin-FITC assays. One of the retrieved hit, STOCK5S-44056 demonstrated IC50 value of 23.56 µM in cell variability assay, and had EC50 value of 26.95 µM in caspase-3 activation assay. STOCK5S-44056 also indicated late stage induction of apoptosis in annexin assay. The results of in vitro activity revealed that STOCK5S-44056 has a potential to become anticancer agents.

Mycetoma: reviewing a neglected disease.

Mycetoma caused by either filamentous fungi (eumycotic) or bacteria (actinomycotic) has recently been recognized by the World Health Organization as a neglected tropical disease. Although mycetoma is preventable and treatable, especially in the early stages, it carries high morbidity and a huge socioeconomic burden. Skin and subcutaneous tissue is affected, with a classic presentation of hard woody swellings, discharging sinuses and presence of grains (containing the causative organism). Variants with swelling without sinuses have also been described. Left untreated it may involve underlying bone and muscle, leading to permanent disability. Common actinomycotic species include Streptomyces somaliensis, Actinomadura madurae, Actinomadura pelletieri, Nocardia brasiliensis and Nocardia asteroides, while Madurella mycetomatis, Madurella grisea, Pseudoallescheria boydii and Leptosphaeria senegalensis are common eumycotic agents. Men are more commonly affected than women, and the leg is the most frequently affected site. Diagnosis in suspected lesions is made with the help of grain examination, microscopy, imaging (radiography, ultrasonography, magnetic resonance imaging) and culture, and more recently by molecular methods such as PCR and molecular sequencing. Molecular sequencing for both fungi and bacteria is important for rapid and correct diagnosis, especially in culture-negative cases. Treatment is long, more successful in actinomycetoma than eumycetoma, and may require a holistic approach comprising antimicrobials, surgery and rehabilitation. Mycetoma can be prevented by simple measures such as wearing protective garments and shoes, especially in rural areas and during outdoor activities.

Masson's Hemangioma of the Cheek: A Case Report.

We report a rare case of intravascular papillary endothelial hyperplasia (IPEH) of the cheek. This neoplasm, known as Masson's tumor, is an unusual vascular lesion of proliferating endothelial cells. It is usually confined to the lumen of preexisting vessels or vascular malformations. The principal significance of IPEH is its resemblance to a variety of benign and malignant diseases and possible misdiagnosis as such. Achieving a correct diagnosis is essential to avoid subjecting a patient to either unnecessarily aggressive or inadequate therapy. For this reason, awareness of this lesion is very important.

Short-term surgical outcomes and patient quality of life between robotic and laparoscopic extralevator abdominoperineal excision for adenocarcinoma of the rectum.

Introduction Some studies advocate a laparoscopic extralevator abdominoperineal excision (l-ELAPE) approach for low rectal cancer. The da Vinci™ robot (r-ELAPE) technique has potential to overcome some limitations of l-ELAPE, such as reduction of the learning curve and more precise tissue handling. It is unknown whether this approach results in improved surgical or quality of life outcomes compared with l-ELAPE. This study aimed to address this issue. Methods Consecutive patients having undergone either robotic or laparoscopic ELAPE for adenocarcinoma were studied. All operations were performed by two surgeons experienced in laparoscopic and recently introduced robotic surgery. Surgical outcomes were determined by postoperative histology and short-term complications. Quality of life was prospectively assessed using the European Organisation for Research and Treatment of Cancer QLC-CR30 and QLC-CR29 questionnaires. Results A total of 22 patients (11 r-ELAPE) with a median follow-up of 13 months (8 months robotic; 22 months laparoscopic) were studied. The groups were similarly matched for age, gender, American Society of Anesthesiologists status, preoperative chemoradiotherapy and tumour height. All had R0 resection. There was no significant difference in short-term surgical outcomes between groups. There was no significant difference in mean global health scores between the two groups (74 ± 14 r-ELAPE vs. 73 ± 10 l-ELAPE). The r-ELAPE group had a lower mean impotence score compared with the I-ELAPE group (55.5 ± 40 vs. 72.2 ± 44), although this was not statistically significant. Conclusions The newly introduced r-ELAPE was non-inferior to l-ELAPE in either patient quality of life or surgical outcomes. Robotic surgery could be particularly beneficial in the technically challenging area of low rectal cancer surgery with a shorter learning curve than laparoscopy.

Patient quality of life and short-term surgical outcomes between robotic and laparoscopic anterior resection for adenocarcinoma of the rectum.

PURPOSE: To compare patient quality of life (QoL) and short-term surgical outcomes between robotic anterior resection (r-AR) and laparoscopic (l-AR) approach. METHODS: Consecutive patients having undergone either robotic or laparoscopic AR for adenocarcinoma were studied. All operations were performed by two surgeons experienced in laparoscopic and recently introduced robotic surgery. Surgical outcomes were determined by post-operative histology and short-term complications. QoL was prospectively assessed using the EORTC QLC-CR30 and QLC-CR29 questionnaires. RESULTS: In total, 36 patients (18 r-AR) with a median follow-up of 12 months following surgery (9-month robotic and 20-month laparoscopic) were studied. The two groups were similarly matched for age and gender. Laparoscopic patients had a lower ASA grade (p = 0.02). There was no significant difference in surgical outcomes between groups. r-AR patients reported lower pain scales (2 ± 6 vs. 11 ± 13) (p = 0.04), lower levels of insomnia 0 vs. 8 ± 15 (p = 0.04) and a lower abdominal pain scale (2 ± 9 vs. 17 ± 27) (p = 0.04). Male impotence scores were higher in l-AR 33 ± 35 compared to r-AR 7 ± 21 (p = 0.03). CONCLUSION: Despite its recent introduction to our centre, the quality of oncological resection using the robotic surgery is comparable to laparoscopy. Lower impotence and QoL scores in patients after robotic procedure may be explained on the basis of better visualisation and precise tissue handling.

E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271.

Multiple myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro. Moreover, an increase in the mRNA levels of genes involved in the generation of E-selectin ligands was associated with inferior progression-free survival in the CoMMpass study. In vivo, E-selectin ligand-enriched cells induced a more aggressive disease and were completely insensitive to Bortezomib. Importantly, this resistance could be reverted by co-administration of GMI-1271, a specific glycomimetic antagonist of E-selectin. Finally, we report that E-selectin ligand-bearing cells are present in primary MM samples from BM and peripheral blood with a higher proportion seen in relapsed patients. This study provides a rationale for targeting E-selectin receptor/ligand interactions to overcome MM metastasis and chemoresistance.

Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population.

Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. AIM: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. RESULTS: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. CONCLUSIONS: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.

Multiparametric Evaluation in Differentiating Glioma Recurrence from Treatment-Induced Necrosis Using Simultaneous 18F-FDG-PET/MRI: A Single-Institution Retrospective Study.

BACKGROUND AND PURPOSE: Differentiating glioma recurrence from treatment-induced necrosis can be a challenge on conventional imaging. This study aimed to assess the diagnostic performance of each functional MR imaging and PET parameter derived by using simultaneous FDG-PET/MR imaging individually and in combination in the evaluation of suspected glioma recurrence. MATERIALS AND METHODS: Thirty-five treated glioma patients with 41 enhancing lesions (World Health Organization grade II = 9, III = 13, IV = 19) on MR imaging after an operation followed by radiation therapy and/or chemotherapy formed part of this study. Using PET/MR imaging, we calculated the normalized mean relative CBV, mean ADC, Cho/Cr, and maximum and mean target-to-background ratios. Statistical analysis was performed to determine the diagnostic performance of each parameter by receiver operating characteristic analysis individually and in combination with multivariate receiver operating characteristic analysis for the detection of glioma recurrence. Histopathology or clinicoradiologic follow-up was considered the criterion standard. RESULTS: Of 35 patients, 25 (30 lesions) were classified as having a recurrence and 10 (11 lesions) patients as having treatment-induced necrosis. Parameters like rCBVmean (mean relative CBV), ADCmean, Cho/Cr, and maximum and mean target-to-background ratios were statistically significant in the detection of recurrent lesions with an accuracy of 77.5%, 78.0%, 90.9%, 87.8%, and 87.8%, respectively. On multivariate receiver operating characteristic analysis, the combination of all 3 MR imaging parameters resulted in an area under the curve of 0.913 ± 0.053. Furthermore, an area under the curve of 0.935 ± 0.046 was obtained when MR imaging parameters (ADCmean and Cho/Cr) were combined with the PET parameter (mean target-to-background ratio), demonstrating an increase in diagnostic accuracy. CONCLUSIONS: Simultaneous PET/MR imaging with FDG offers correlative and synergistic multiparametric assessment of glioma recurrence with increased accuracy and clinical utility.

Is it time for a change in the approach to chemical burns? The role of Diphoterine® in the management of cutaneous and ocular chemical injuries.

A multitude of household and occupational compounds have the potential to induce chemical burns to the eye and skin. Without prompt intervention, irreversible visual loss and disfigurement may prevail. Diphoterine® and Hexafluorine® are amphoteric and hypertonic chelating solutions used in the management of general chemical and hydrofluoric acid burns, respectively. They rapidly neutralise both acid and alkali agents without heat release and limit diffusion, making them superior to water irrigation alone. However, although Diphoterine® and Hexafluorine® uptake is slowly increasing in industrial workplaces, there is a paucity of education and use in both emergency departments and plastic surgery units worldwide. Herein, we present a case report of combined ocular and cutaneous acid burn treated with Diphoterine®, together with a review of the current supporting literature.

A Sensitive Triple Quadrupole Liquid Chromatography Mass Spectrometric Method for the Estimation of Valproic Acid in K2EDTA Human Plasma using Furosemide as the Internal Standard.

A valproic acid is primarily being used in the treatment of epilepsy is a histone deacetylase inhibitor and it is under investigation for treatment of HIV and various cancer indications. A specific, sensitive and fast bioanalytical LC-MS/MS method was developed with furosemide as an internal standard (IS) and thoroughly validated for the quantitation of valproic acid using turbo ion spray in negative ion mode. The analyte and IS was extracted using protein precipitation. The chromatographic separation of analytes from extracted matrix was achieved using a Chromolith RP 18e (2.0×50 mm) column with a gradient mobile phase comprising of acetonitrile and purified water with acetic acid. The elution of both peaks was achieved within 5.2 min, with retention times of 2.55 min and 1.67 min for valproic acid and IS, respectively. Quantitation of valproic acid was achieved by the pseudo SRM transition pairs (m/z 142.8→m/z 142.8), and SRM transition pair (m/z 328.8 →m/z 204.6) for internal standard.The calibration standards of valproic acid showed linear over a range from 50 to 40 000 ng/mL, with a lower limit of quantitation of 50 ng/mL with accuracy of 3.74% and precision of 5.06%. The bias for inter- and intra-batch assays was 1.24-6.14% and 3.85-11.84%, respectively; while the corresponding precision was 2.56-16.37% and 1.29-11.34%, respectively. The developed method was used to monitor valproic acid levels in clinical samples. Because of higher sensitivity, this method can be used for therapeutic drug monitoring in pediatric subjects.