How does deep learning/machine learning perform in comparison to radiologists in distinguishing glioblastomas (or grade IV astrocytomas) from primary CNS lymphomas?: a meta-analysis and systematic review.

BACKGROUND: Several studies have been published comparing deep learning (DL)/machine learning (ML) to radiologists in differentiating PCNSLs from GBMs with equivocal results. We aimed to perform this meta-analysis to evaluate the diagnostic accuracy of ML/DL versus radiologists in classifying PCNSL versus GBM using MRI. METHODOLOGY: The study was performed in accordance with PRISMA guidelines. Data was extracted and interpreted by two researchers with 12 and 23 years' experience, respectively, and QUADAS-2 tool was used for quality and risk-bias assessment. We constructed contingency tables to derive sensitivity, specificity accuracy, summary receiver operating characteristic (SROC) curve, and the area under the curve (AUC). RESULTS: Our search identified 11 studies, of which 8 satisfied our inclusion criteria and restricted the analysis in each study to reporting the model showing highest accuracy, with a total sample size of 1159 patients. The random effects model showed a pooled sensitivity of 0.89 [95% CI:0.84-0.92] for ML and 0.82 [95% CI:0.76-0.87] for radiologists. Pooled specificity was 0.88 [95% CI: 0.84-0.91] for ML and 0.90 [95% CI: 0.81-0.95] for radiologists. Pooled accuracy was 0.88 [95% CI: 0.86-0.90] for ML and 0.86 [95% CI: 0.78-0.91] for radiologists. Pooled AUC of ML was 0.94 [95% CI:0.92-0.96]and for radiologists, it was 0.90 [95% CI: 0.84-0.93]. CONCLUSIONS: MRI-based ML/DL techniques can complement radiologists to improve the accuracy of classifying GBMs from PCNSL, possibly reduce the need for a biopsy, and avoid any unwanted neurosurgical resection of a PCNSL.

Follow-up of colorectal cancer and patterns of recurrence.

Colorectal cancer is one of the commonest cancers detected as also amongst the most common causes of cancer death. Survival has improved due to better disease understanding and treatment; however, a substantial proportion of patients recur after curative intent therapy. In this article, we will discuss the imaging features of recurrent colorectal cancer and the role of the radiologist in its management.

Cardiovascular adverse events are associated with usage of immune checkpoint inhibitors in real-world clinical data across the United States.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause life-threatening cardiovascular adverse events (CVAEs) that may not be attributed to therapy. The outcomes of clinical trials may underestimate treatment-related adverse events due to restrictive eligibility, limited sample size, and failure to anticipate selected toxicities. We evaluated the incidence and clinical determinants of CVAEs in real-world population on ICI therapy. PATIENTS AND METHODS: Among 2 687 301 patients diagnosed with cancer from 2011 to 2018, 16 574 received ICIs for any cancer. Patients in the ICI and non-ICI cohorts were matched in a 1 : 1 ratio according to age, sex, National Cancer Institute comorbidity score, and primary cancer. The non-ICI cohort was stratified into patients who received chemotherapy (N = 2875) or targeted agents (N = 4611). All CVAEs, non-cardiac immune-related adverse events occurring after treatment initiation, baseline comorbidities, and treatment details were identified and analyzed using diagnosis and billing codes. RESULTS: Median age was 61 and 65 years in the ICI and non-ICI cohorts, respectively (P < 0.001). ICI patients were predominantly male (P < 0.001). Lung cancer (43.1%), melanoma (30.4%), and renal cell carcinoma (9.9%) were the most common cancer types. CVAE diagnoses in our dataset by incidence proportion (ICI cohort) were stroke (4.6%), heart failure (3.5%), atrial fibrillation (2.1%), conduction disorders (1.5%), myocardial infarction (0.9%), myocarditis (0.05%), vasculitis (0.05%), and pericarditis (0.2%). Anti-cytotoxic T-lymphocyte-associated protein 4 increased the risk of heart failure [versus anti-programmed cell death protein 1; hazard ratio (HR), 1.9; 95% confidence interval (CI) 1.27-2.84] and stroke (HR, 1.7; 95% CI 1.3-2.22). Pneumonitis was associated with heart failure (HR, 2.61; 95% CI 1.23-5.52) and encephalitis with conduction disorders (HR, 4.35; 95% CI 1.6-11.87) in patients on ICIs. Advanced age, primary cancer, nephritis, and anti-cytotoxic T-lymphocyte-associated protein 4 therapy were commonly associated with CVAEs in the adjusted Cox proportional hazards model. CONCLUSIONS: Our findings underscore the importance of risk stratification and cardiovascular monitoring for patients on ICI therapy.

A systematic review on the genetic analysis of paragangliomas: primarily focused on head and neck paragangliomas.

Head and neck paragangliomas Paragangliomas and pheochromocytomas are rare, mostly benign neuroendocrine tumors, which are embryologically derived from neural crest cells of the autonomic nervous system. Paragangliomas are essentially the extra-adrenal counterparts of pheochromocytomas. As such this family of tumors can be subdivided into head and neck paragangliomas, pheochromocytomas and thoracic and abdominal extra-adrenal paragangliomas. Ten out of fifteen genes that contribute to the development of paragangliomas are more susceptible to the development of head and neck paragangliomas when mutated. Gene expression profiling revealed that pheochromocytomas and paragangliomas can be classified into two main clusters (C1 and C2) based on transcriptomes. These groups were defined according to their mutational status and as such strongly associated with specific tumorigenic pathways. The influence of the main genetic drivers on the somatic molecular phenotype was shown by DNA methylation and miRNA profiling. Certain subunits of succinate dehydrogenase (SDHx), von Hippel-Lindau (VHL) and transmembrane protein 127 (TMEM127) still have the highest impact on development of head and neck paragangliomas. The link between RAS proteins and the formation of pheochromocytoma and paragangliomas is clear due to the effect of receptor tyrosine-protein kinase (RET) and neurofibromatosis type 1 (NF1) in RAS signaling and recent discovery of the role of HRAS. The functions of MYC-associated factor X (MAX) and prolyl hydroxylase 2 (PHD2) mutations in the contribution to the pathogenesis of paragangliomas still remain unclear. Ongoing studies give us insight into the incidence of germline and somatic mutations, thus offering guidelines to early detection. Furthermore, these also show the risk of mistakenly assuming sporadic cases in the absence of definitive family history in head and neck paragangliomas.

Partial maxillectomy for ameloblastoma of the maxilla with infratemporal fossa involvement: A combined endoscopic endonasal and transoral approach.

Ameloblastoma represents the most common epithelial odontogenic tumor. Because of the proximity of the maxillary tumors to the orbit and skull base, it should be managed as radically as possible. Maxillectomy, mainly via the transfacial or transoral approach, represents the most common type of surgical procedure. Drawback of these approaches is limited control of the superiomedial extent of the tumour in the paranasal area. We report the use of a combined endoscopic endonasal and transoral approach to manage maxillary plexiform ameloblastoma in a 48-year-old male patient. A combined endoscopic endonasal and transoral approach enabled the radical removal of tumour with a 1.5cm margin of radiographically intact bone with good control from both intrasinusal and intraoral aspects. Adequate visualization of the extent of the lesion (e.g. orbit, infratemporal fossa, anterior cranial base) had been achieved. Non-complicated healing was achieved. This technique of partial maxillectomy led to very good aesthetic and functional results. No recurrence had been noted during review appointments. The combination of endoscopic endonasal and transoral approach for a partial maxillectomy allows sufficient reduction of the defect, thus eliminating the necessity for reconstruction and reducing the morbidity associated with it.

Absence of BRAF mutation in pheochromocytoma and paraganglioma.

Pheochromocytomas and Paragangliomas (PHEO/PARA) are rare endocrine tumors originating from the adrenal medulla. More than 20 genes are involved in the tumorigenesis of these tumors, but a substantial part of the causative genetic events remains unexplained. A recent study has reported the presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. Other studies have not find this mutation. This study investigates the occurrence of the BRAF V600E mutation in these tumors.A cohort of 64 PHEO/PARA were screened for the BRAF V600E mutation using direct Sanger sequencing and QRT-PCR.All cases investigated displayed wild-type without V600E BRAF mutationTaken together with all previously screened tumors up to date, only 1 V600E BRAF mutation has been found among 427 PCCs. These findings imply that the V600E BRAF mutation is a rare event in PHEO/PARA.

Safety in out-of-hours operating in trauma and orthopaedics at a district general hospital.

INTRODUCTION According to the National Confidential Enquiry into Perioperative Deaths (NCEPOD), out-of-hours operating in trauma and orthopaedics should be reserved for life or limb threatening cases only. The aim of our study was to determine the nature of non-emergency work carried out in our trust at night in 2015. The overall efficacy and clinical safety of the services provided was evaluated. METHODS Surgical activity undertaken after 9pm was reviewed along with patient ASA (American Society of Anesthesiologists) grade, grade of operating surgeon and any complications that occurred following the procedure. Furthermore, the clinical urgency and safety of cases was assessed based on whether there was any record of life or limb threatening indications at the time of admission. RESULTS Overall, 131 procedures were performed after 9pm, with 102 performed between 9pm and midnight, and 29 after midnight. Consultants performed 16 cases and the remaining 115 cases were operated on by middle grades or specialty trainees. A fifth (20%) of the cases were genuinely life or limb threatening. A total of 123 procedures were classed as having good outcomes. The complication rate was 8%. CONCLUSIONS In our study, 80% of the procedures performed after 9pm could not be categorised as life or limb threatening. Appropriate NCEPOD classification would ensure that only life or limb threatening cases were listed for theatre after 9pm. Alternative methods of operating within working hours should be considered.

Septic arthritis of the temporomandibular joint caused by rare bacteria Raoultella ornithinolytica.

Septic arthritis of the temporomandibular joint (TMJ) is an unusual disease in adults. Inoculation of the pathogen may occur through traumatic or iatrogenic injuries, or more often by haematogenous spread from a distant focus. The cause of infection is unknown in most cases. A case of ostensibly mild septic arthritis of the TMJ with a good response to antibiotic therapy and lavage, but that finally led to fatal destruction of the joint structures in a 38-year-old female patient, is reported herein. The infection was caused by Raoultella ornithinolytica - a rare bacterial species in humans, which has not been reported previously in any patients with joint problems. The arthritis manifested 5 weeks after an arthroscopy procedure, so the cause was not clear.

RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4.

Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3'-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a 'miRNA sponge' to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.

A study on biochemical changes during cultivation of Rhizopus oryzae in deproteinized whey medium in relation to chitosan production.

UNLABELLED: The kinetics of cultivation of zygomycete filamentous fungus Rhizopus oryzae in deproteinized whey medium in relation to chitosan production was studied here to optimize chitosan production from R. oryzae as well as utilize whey, a by-product of sweetmeat industry as a cheap source of sugar in the cultivation process. Chitosan content of R. oryzae biomass was found to be increased with time during cultivation and reached maximum (13·6%) after 72 h and then declined steadily. Maximum 1·13 g of chitosan was obtained from one litre of deproteinized whey medium. Concentration of lactose in the medium was observed to be reduced from 45·0 to 11·7 g l(-1) during cultivation resulting in decrease in biochemical oxygen demand (BOD) of whey by approx. 60%, and this was important from environmental point of view before discharging whey into any water body. However, no significant change in pH or titratable acidity was noted during the entire course of cultivation, probably due to good buffering capacity of the medium. Molecular weight of chitosan varied from 130 to 230 kDa depending on the time of cultivation, but no significant change in degree of deacetylation of chitosan (approx. 87%) was found during cultivation. SIGNIFICANCE AND IMPACT OF THE STUDY: Whey is the largest by-product of dairy industries, and its disposal is a big environmental issue because of its high biological oxygen demand (BOD) value. This study will help to lower BOD value of whey by using it as a cultivation medium for fungus R. oryzae that contains chitosan, a very commercially important material on its cell wall. Moreover, the study on biochemical changes in whey during cultivation process with R. oryzae will help to understand the exact changes occurring in the medium and optimize cultivation process to isolate chitosan in larger extent with better and uniform physicochemical properties.

Optimization of fermentation conditions for green pigment production from Bacillus cereus M¹ 16 (MTCC 5521) and its pharmacological application.

UNLABELLED: Optimal culture conditions for the production of green pigment was investigated. The optimal culture condition for the production of an extracellular green pigment by growing Bacillus cereus M(1) 16 (MTCC 5521) in a complex medium containing (g l(-1) ) Peptone-4.0, Beef Extract-9.0, NaCl-7.0, MgSO4 .7H2 O-1.0 and KH2 PO4 -5.0 was as follows pH-7.0 at 30°C for 72 h in a 5 l fermenter. Aeration rate and agitator speed had no effect on the pigment production. Thin layer chromatogram of the pigment extracted from the fermented broth with chloroform on silica gel GF254 using ethyl acetate and hexane (1 : 1) as solvent showed three fractions. The major fraction (C3 ) was separated out and identified as 9-methyl-1, 4, 5, 8-tetra-azaphenanthrene. Acute toxicity test revealed the nontoxic nature upto a dose of 2000 mg kg(-1) , b.wt., of mice. MTT assay showed the cytotoxic nature in HL60 cells having an IC50 of 2.47 mmol. So, this biopigment may have application in food, textile colorant and pharmaceutical industry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the optimum production of a biopigment (9-methyl-1, 4, 5, 8-tetra-azaphenanthrene) by fermentation of a complex medium with Bacillus cereus M(1) 16 (MTCC 5521) in submerged fermentation. This is the first investigation of toxicity and cytotoxicity activities of this biopigment. The study showed that the purified pigment had no toxicity to healthy albino mice but a high cytotoxicity activity in HL60 cancer cell line in vitro. The biopigment had further displayed dyeing capability to both solidified agar and cotton cloth. Therefore, it may represent a nontoxic and natural alternative to chemical dyes and pigments.

'Reverse' scarf osteotomy for bunionette correction: Initial results of a new surgical technique.

BACKGROUND: The bunionette or tailor's bunion is a lateral prominence of the fifth metatarsal head. It is usually characterised by a wide intermetatarsal angle (IMA) between the 4th and 5th metatarsals, varus of the metatarsophalangeal (MTP) joint, pain and callus formation. Various distal, shaft and basal osteotomies have been described in the literature. We have described a reverse scarf osteotomy for bunionette correction. PATIENTS AND METHODS: We have used a 'reverse' scarf osteotomy in 12 cases (10F: 2M) with a mean follow-up of 12 months (range 5-22 months) with radiographs and clinical scoring. RESULTS: Post operatively, mean IMA improved from 13.1° to 7.27° (range 2.0-11.5°); mean 5th MTP angle improved from 19.9° to 6.36° (range 2.8-9.0°) and postoperative mean AOFAS improved from 54.25 to 89.58 (range 70-100). CONCLUSION: 'Reverse' scarf osteotomy in the correction of bunionette deformity offers promising results in the short term.

Malreduction of syndesmosis--are we considering the anatomical variation?

Previous studies have demonstrated the need for accurate reduction of ankle syndesmosis. Measurement of syndesmosis is difficult on plain radiographs. A computed tomography (CT) scan allows better visualisation of the transverse relationship between the fibula and incisura fibularis. The difference ('G' a term we coined for ease of description) between the fibula and the anterior and posterior facets of the incisura fibularis was compared between normal and injured ankles following syndesmotic fixation in 19 patients. The mean diastasis (MD) was also calculated, representing the average measurement between the fibula and the anterior and posterior incisura. When compared with the normal side, eight out of 19 (42%) cases were found to have a residual diastasis even after fixation across the syndesmosis. However, if a standard value of G (2mm) was used for the injured leg only, all of the 19 cases would have abnormal values of 'G' following reduction. Our study has clearly demonstrated the need for individualising the assessment method to guide surgeons and radiologists prior to revision surgery. A standard value of 'G' of 2mm as the normal limit cannot be applied universally, as apparent from the data presented in this study.

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system.

The GATA transcription factors consist of six family members, which bind to the consensus DNA-binding element, W-GATA-R, and are poorly characterized in the central nervous system (CNS). Using retroviral gene trapping on transgenic mouse glioma models, we identified GATA6 to be a novel tumor suppressor gene in glioblastoma multiforme. We now show GATA4, a family member of GATA6, to be expressed in the neurons and glia of normal murine and human embryonic and adult CNS. Silencing GATA4 in normal astrocytes did not alter their growth properties. In contrast, knockdown of Gata4 in p53 null non-transformed murine astrocytes induced transformation, with increased proliferation and resistance to chemotherapy or radiation-induced apoptosis. Furthermore, GATA4 expression was lost in a panel of human malignant astrocytoma cell lines. GATA4 overexpression in normal human and murine astrocytes resulted in a cell cycle block in G1 phase, with increased apoptosis. Mechanistically, GATA4 was a transcriptional inducer of the cyclin-dependent kinase inhibitor, p15INK4B, leading to the attenuation of cyclin D1. GATA4 expression was also induced by transforming growth factor-beta, leading to the inhibition of astrocyte proliferation. Collectively, we show that GATA4 is expressed in the embryonic and adult CNS and acts as a negative regulator of astrocyte proliferation and growth.

Percutaneous fusion of the sacroiliac joint with hollow modular anchorage screws: clinical and radiological outcome.

We reviewed 15 consecutive patients, 11 women and four men, with a mean age of 48.7 years (37.3 to 62.6), who between July 2004 and August 2007 had undergone percutaneous sacroiliac fusion using hollow modular anchorage screws filled with demineralised bone matrix. Each patient was carefully assessed to exclude other conditions and underwent pre-operative CT and MR scans. The diagnosis of symptomatic sacroiliac disease was confirmed by an injection of local anaesthetic and steroid under image intensifier control. The short form-36 questionnaire and Majeed's scoring system were used for pre- and post-operative functional evaluation. Post-operative radiological evaluation was performed using plain radiographs. Intra-operative blood loss was minimal and there were no post-operative clinical or radiological complications. The mean follow-up was for 17 months (9 to 39). The mean short form-36 scores improved from 37 (23 to 51) to 80 (67 to 92) for physical function and from 53 (34 to 73) to 86 (70 to 98) for general health (p = 0.037). The mean Majeed's score improved from 37 (18 to 54) pre-operatively to 79 (63 to 96) post-operatively (p = 0.014). There were 13 good to excellent results. The remaining two patients improved in short form-36 from a mean of 29 (26 to 35) to 48 (44 to 52). Their persistent pain was probably due to concurrent lumbar pathology. We conclude that percutaneous hollow modular anchorage screws are a satisfactory method of achieving sacroiliac fusion.

Conservative management of vestibular schwannomas: third review of a 10-year prospective study.

Seventy-two patients with a unilateral vestibular schwannoma have been treated conservatively for a median of 121 months. They have been followed prospectively by serial clinical examination, MRI scans and audiometry. Twenty-five patients (35%, 95% CI: 24-47) failed conservative management and required active intervention during the study. No factors predictive of tumour growth or failure of conservative management could be identified. Seventy-five per cent of failures occurred in the first half of the 10-year study. The median growth rate for all tumours at 10 years was 1 mm/year (range -0.53-7.84). Cerebellopontine angle tumours grew faster (1.4 mm/year) than intracanalicular tumours (0 mm/year, P < 0.01); 92% had growth rates under 2 mm/year. Hearing deteriorated substantially even in tumours that did not grow, but did so faster in tumours that grew significantly (mean deterioration in pure tone average at 0.5, 1, 2 and 3 kHz was 36 dB; speech discrimination scores deteriorated by 40%). Patients who failed conservative management had clinical outcomes that were not different from those who underwent primary treatment without a period of conservative management.

Mucinous, gland predominant synovial sarcoma of a large peripheral nerve: a rare case closely mimicking metastatic mucinous carcinoma.

Synovial sarcoma is a distinctive soft tissue neoplasm with monophasic and biphasic forms. It is typically a deep-seated soft tissue tumour of the extremities of young adults and occasional cases have been described in large peripheral nerves. A rare example has a predominance of the glandular component and may mimic metastatic carcinoma. Here, a unique synovial sarcoma with <1% spindle cell component involving the posterior tibial nerve is decribed. In addition to having only small bands or islands of stroma, there was also mucin dissection of the surrounding soft tissue. Isolated glands were seen "floating" in pools of mucin. There was abundant intracellular mucin present as well. These latter two findings have not been described in synovial sarcoma thus far, to our knowledge. The diagnosis was confirmed by molecular detection of the t(X;18) by reverse transcription-PCR and confirmed by dual colour break apart fluorescence in situ hybridisation, in a second laboratory. Mucinous, gland predominant synovial sarcoma must be recognised to avoid misdiagnosis of metastatic carcinoma or a glandular malignant peripheral nerve sheath tumour when occurring in a peripheral nerve.