STEMI associated with SARS-CoV-2 infection and the use of ECMO as a potential therapeutic approach in addition to the PCI.

A 55-year-old male presented to the emergency department with the complaints of chest pain that started 4 h before presentation. Pain was located over the anterior chest, 5 out of 10 intensity, with radiation to the left arm. Chest x-ray on admission showed severe diffuse bilateral pulmonary infiltrates concerning for COVID-19 pneumonia. Electrocardiogram showed inferior and lateral ST-segment elevation compatible with acute inferolateral myocardial infarction. Successful percutaneous coronary intervention (PCI) of the proximal and mid-right coronary artery using the balloon angioplasty and drug-eluting stent was performed. Post-PCI stenosis was 0% with a thrombolysis in myocardial infarction (TIMI) flow of 3. Five-day course of azithromycin and hydroxychloroquine was completed with no improvement overall. Patient received two doses of 400 mg of tocilizumab intravenously on hospital days 5 (HD#5) and #6. The patient was proned, on FiO2 100%, PEEP 15 cm H2O, on epoprostenol sodium and paralytics and eventually received venovenous ECMO, which improved outcome.

Coronary Artery Fistula-Associated Endocarditis: Report of Two Cases and a Review of the Literature.

Coronary artery fistulae (CAF) are rare congenital anomalies and reported to have an incidence of 0.1-0.2% of all coronary angiograms. An association between fistulae and nonatherosclerotic coronary artery aneurysms is even more rare. In childhood, patients are mostly asymptomatic; however, patients older than 20 years old may present with signs of infective endocarditis, myocardial ischemia, congestive heart failure, and aneurysm rupture. CAF are typically identified by coronary angiography; however, there are some limited studies showing that transesophageal echocardiography (TEE) can also be useful in identifying CAF. Here we report two cases of endocarditis secondary to congenital coronary artery fistulae draining into either a cardiac cavity or a coronary sinus, which were detected by TEE. Vegetations were found at the site of the fistulae drainage. Management for young patients is either percutaneous or surgical intervention. For elderly patients with multiple comorbidities, conservative treatment is another option. In these two cases, treating endocarditis with proper antibiotics and supportive treatment, the patients' conditions improved significantly.

Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis.

BACKGROUND: Hypoxia leads to the stabilisation of the hypoxia-inducible factor (HIF) transcription factor that drives the expression of target genes including microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs (HRMs) in bladder cancer and investigate their functional significance. METHODS: Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and interrogated for the expression of 384 miRNAs by qPCR. Functional studies were carried out using siRNA-mediated gene knockdown and chromatin immunoprecipitations. Apoptosis was quantified by annexin V staining and flow cytometry. RESULTS: The HRM signature for NMI bladder cancer lines includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia-upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1α and two hypoxia response elements were identified within the promoter region of the gene. Finally, the hypoxic upregulation of miR-145 contributed to increased apoptosis in RT4 cells. CONCLUSIONS: We have demonstrated the hypoxic regulation of a number of miRNAs in bladder cancer. We have shown that miR-145 is a novel, robust and direct HIF target gene that in turn leads to increased cell death in NMI bladder cancer cell lines.

The importance of intraoperative transoesophageal monitoring when operating on renal cancers that involve the right atrium.

The surgical treatment of advanced renal cancers is challenging. Renal cell carcinoma is interesting in that it invades the vasculature and can extend up as far as the right atrium. Extension of tumour thrombus into the right atrium represents level IV disease, according to Robson staging. Transoesophageal echocardiography is useful for diagnostic purposes. It is also of great value for intraoperative cardiac monitoring and to confirm the extent of vascular involvement.

Benefits of thrombolytics in prolonged cardiac arrest and hypothermia over its bleeding risk.

A 52-year-old non-smoking Caucasian male, who was admitted to our emergency room after he was found unconscious in the bathroom, went into cardiac arrest requiring prolonged cardiopulmonary resuscitation (CPR) and hypothermia therapy. Cardiac catheterization showed non-obstructive coronary arteries and further bedside echocardiogram suggested probable pulmonary embolism (PE) as an underlying cause of cardiac arrest. Although thrombolytic therapy is an effective therapy for PE, it is not routinely given during prolonged CPR for its life- threatening bleeding complications. Many reported cases have suggested a beneficial effect of empiric thrombolytic in cardiac arrest, but unrelated to duration of resuscitation and adjuvant treatments that imposes bleeding risk. We suspect that tissue plasminogen activator (tPA) should be promptly given to prolonged cardiac arrest patients, even when bleeding risk is high with the concurrent hypothermia treatment, keeping the benefits over risk strategy. Our patient received thrombolytic, tPA and showed remarkable clinical, physiological and radiographical improvement.

Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia. METHODS: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3 by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in two-dimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively. RESULTS: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1α-dependent manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells. CONCLUSION: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an important role in maintaining cell viability under conditions of stress.

High-intensity focused ultrasound treatment of liver tumours: post-treatment MRI correlates well with intra-operative estimates of treatment volume.

OBJECTIVES: To assess the safety and feasibility of high-intensity focused ultrasound (HIFU) ablation of liver tumours and to determine whether post-operative MRI correlates with intra-operative imaging. METHODS: 31 patients were recruited into two ethically approved clinical trials (median age 64; mean BMI 26 kg m(-2)). Patients with liver tumours (primary or metastatic) underwent a single HIFU treatment monitored using intra-operative B-mode ultrasound. Follow-up consisted of radiology and histology (surgical trial) or radiology alone (radiology trial). Radiological follow-up was digital subtraction contrast-enhanced MRI. RESULTS: Treatment according to protocol was possible in 30 of 31 patients. One treatment was abandoned because of equipment failure. Transient pain and superficial skin burns were seen in 81% (25/31) and 39% (12/31) of patients, respectively. One moderate skin burn occurred. One patient died prior to radiological follow-up. Radiological evidence of ablation was seen in 93% (27/29) of patients. Ablation accuracy was good in 89% (24/27) of patients. In three patients the zone of ablation lay ≤2 mm outside the tumour. The median cross-sectional area (CSA) of the zone of ablation was 5.0 and 5.1 cm(2) using intra-operative and post-operative imaging, respectively. The mean MRI:B-mode CSA ratio was 1.57 [95% confidence interval (CI)=0.57-2.71]. There was positive correlation between MRI and B-mode CSA (Spearman's r=0.48; 95% CI 0.11-0.73; p=0.011) and the slope of linear regression was significantly non-zero (1.23; 95% CI=0.68-1.77; p<0.0001). CONCLUSIONS: HIFU ablation of liver tumours is safe and feasible. HIFU treatment is accurate, and intra-operative assessment of treatment provides an accurate measure of the zone of ablation and correlates well with MRI follow-up.

A lucky fall? Case report.

Renal cell carcinomas (RCCs) account for 3% of all solid neoplasms, with an increased incidence after renal transplantation. In transplant recipients, RCCs predominantly occur in the patient's native kidneys. Herein is reported a case of a localized RCC of recipient origin that developed in the donor allograft and was detected 8 years after renal transplantation. Treatment with high-intensity focussed ultrasound followed by partial nephrectomy was successful, averting the need for dialysis therapy.

High-intensity focused ultrasound ablation of liver tumours: can radiological assessment predict the histological response?

Cancer therapies usually depend on cross-sectional imaging for the assessment of treatment response. This study was designed to evaluate the ability of MRI to predict zones of necrosis following the use of high-intensity focused ultrasound (HIFU) to treat liver metastases. Patients with liver metastases, who had been scheduled for elective surgical resection of their tumours, were recruited to this non-randomized Phase II study. In each case, a proportion of an index liver tumour target was ablated. The response to HIFU was assessed after 12 days using contrast-enhanced MRI and compared directly with histological analysis at the time of surgery. Eight patients were treated, of whom six were subsequently assessed with both MRI and histology. There were no major complications. MRI predicted complete ablation in three cases. In each case, histological analysis confirmed complete ablation. In one case, the region of ablation observed on MRI appeared smaller than predicted at the time of HIFU, but histology revealed complete ablation of the target region. The predominant characteristic of HIFU-ablated tissue was coagulative necrosis but heat fixation was evident in some areas. Heat-fixed cells appeared normal under haematoxylin and eosin staining, indicating that this is unreliable as an indicator of HIFU-induced cell death. This study demonstrates that HIFU is capable of achieving selective ablation of pre-defined regions of liver tumour targets, and that MRI evidence of complete ablation of the target region can be taken to infer histological success.

The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population.

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.

Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer.

Hypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. We investigated the hypoxia transcriptome in primary human bladder cancer using cDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated in 39 bladder tumour specimens (27 superficial and 12 invasive). We correlated array mRNA fold changes with carbonic anhydrase 9 (CA IX) staining of tumours as a surrogate marker of hypoxia. Of 6000 genes, 32 were hypoxia inducible in vitro more than two-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor mRNA was upregulated two-fold by hypoxia and 2-18-fold in 31 out of 39 tumours. Glucose transporter 1 was also upregulated on both arrays mRNA, and fold changes on the in vivo array significantly correlated with CA IX staining of tumours (P=0.008). However, insulin-like growth factor binding protein 3 mRNA was the most strongly differentially expressed gene in both arrays and this confirmed its upregulation in urine of bladder cancer patients (n=157, P<0.01). This study defines genes suitable for an in vivo hypoxia 'profile', shows the heterogeneity of the hypoxia response and describes new hypoxia-regulated genes.

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma.

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, non-randomized dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10-150 mg ml(-1) in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml(-1). Urinary VEGF was affected by Suramin at doses above 50 mg ml(-1), corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml(-1) intravesically.

High-intensity focused ultrasound for the treatment of liver tumours.

High-intensity focused ultrasound (HIFU) has been investigated as a tool for the treatment of cancer for many decades, but is only now beginning to emerge as a potential alternative to conventional therapies. In recent years, clinical trials have evaluated the clinical efficacy of a number of devices worldwide. In Oxford, UK, we have been using the JC HIFU system (HAIFU Technology Company, Chongqing, PR China) in clinical trials since November 2002. This is the first report of its clinical use outside mainland China. The device is non-invasive, and employs an extracorporeal transducer operating at 0.8-1.6 MHz (aperture 12-15 cm, focal length 9-15 cm), operating clinically at Isp (free field) of 5-15 KWcm(-2). The aims of the trials are to evaluate the safety and performance of the device. Performance is being evaluated through two parallel protocols. One employs radiological assessment of response with the use of follow-up magnetic resonance imaging and microbubble-contrast ultrasound. In the other, histological assessment will be made following elective surgical resection of the HIFU treated tumours. Eleven patients with liver tumours have been treated with HIFU to date. Adverse events include transient pain and minor skin burns. Observed response from the various assessment modalities is discussed.

Polymorphisms in tumour necrosis factor (TNF) are associated with risk of bladder cancer and grade of tumour at presentation.

The purpose of this study is to assess the role of tumour necrosis factor (TNF) polymorphisms in the risk of developing bladder cancer and effect on tumour stage, grade and progression. In all, seven single-nucleotide polymorphisms in TNF were studied in 196 bladder cancer patients and 208 controls using a PCR-SSP genotyping technique. It was seen that there was a significant association of two polymorphisms in TNF with bladder cancer: the TNF+488A allele was found in 28.1% of patients compared with 14.9% of controls (P=0.0012). In addition, TNF-859T was found in 26.0% of patients compared with 14.4% of the controls (P=0.0036). The two loci were in tight linkage disequilibrium, that is, almost all the individuals having TNF+488A also had TNF-859T. Patients with the TNF+488A or TNF-859T were more likely to present with a moderately differentiated tumour than those patients without the uncommon allele. In all, 16.7% of patients with TNF+488A and 29.9% of patients without TNF+488A presented with a G1 tumour (P=0.015). A total of 14% of patients with TNF-859T and 30.5% of patients without TNF-859T presented with a G1 tumour (P=0.0043). There was no significant effect on time to first recurrence, stage progression or grade progression. In conclusion, a significant association between TNF polymorphisms TNF+488A and TNF-859T and risk of bladder cancer was detected in this study. Both these polymorphisms were associated with grade of tumour at presentation although there was no significant effect on subsequent tumour behaviour.

High intensity focused ultrasound: surgery of the future?

For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords "HIFU" and "high intensity focused ultrasound". Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice.

The urological complications of renal transplantation: a series of 1535 patients.

OBJECTIVE: To determine the incidence of urological complications of renal transplantation at one institution, and relate this to donor and recipient factors. PATIENTS AND METHODS: A consecutive series of 1535 renal transplants were audited, and a database of donor and recipient characteristics created for risk-factor analysis. An unstented Leadbetter-Politano anastomosis was the preferred method of ureteric reimplantation. RESULTS: There were 45 urinary leaks, 54 primary ureteric obstructions, nine cases of ureteric calculi, three bladder stones and 19 cases of bladder outlet obstruction at some time after transplantation. The overall incidence of urological complications was 9.2%, with that for urinary leak or primary ureteric obstruction being 6.5%. One graft was lost because of complications, and there were three deaths associated directly or indirectly with urological complications. There was no association with recipient age, cadaveric vs living-donor transplants, or cold ischaemic times before organ reimplantation, although the donor age was slightly higher in cases of urinary leak. There was no association with kidneys imported via the UK national organ-sharing scheme vs the use of local kidneys. The management of these complications is discussed. CONCLUSION: The incidence of urological complications in this series has remained essentially unchanged for 20 years. The causes of these complications and techniques for their prevention are discussed.