Heavy-element production in a compact object merger observed by JWST.

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GWs)2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process)3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7-12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe.

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

A kilonova following a long-duration gamma-ray burst at 350 Mpc.

Gamma-ray bursts (GRBs) are divided into two populations1,2; long GRBs that derive from the core collapse of massive stars (for example, ref. 3) and short GRBs that form in the merger of two compact objects4,5. Although it is common to divide the two populations at a gamma-ray duration of 2 s, classification based on duration does not always map to the progenitor. Notably, GRBs with short (≲2 s) spikes of prompt gamma-ray emission followed by prolonged, spectrally softer extended emission (EE-SGRBs) have been suggested to arise from compact object mergers6-8. Compact object mergers are of great astrophysical importance as the only confirmed site of rapid neutron capture (r-process) nucleosynthesis, observed in the form of so-called kilonovae9-14. Here we report the discovery of a possible kilonova associated with the nearby (350 Mpc), minute-duration GRB 211211A. The kilonova implies that the progenitor is a compact object merger, suggesting that GRBs with long, complex light curves can be spawned from merger events. The kilonova of GRB 211211A has a similar luminosity, duration and colour to that which accompanied the gravitational wave (GW)-detected binary neutron star (BNS) merger GW170817 (ref. 4). Further searches for GW signals coincident with long GRBs are a promising route for future multi-messenger astronomy.

Reference intervals for selected serum biochemistry analytes in cheetahs Acinonyx jubatus.

Published haematologic and serum biochemistry reference intervals are very scarce for captive cheetahs and even more for free-ranging cheetahs. The current study was performed to establish reference intervals for selected serum biochemistry analytes in cheetahs. Baseline serum biochemistry analytes were analysed from 66 healthy Namibian cheetahs. Samples were collected from 30 captive cheetahs at the AfriCat Foundation and 36 free-ranging cheetahs from central Namibia. The effects of captivity-status, age, sex and haemolysis score on the tested serum analytes were investigated. The biochemistry analytes that were measured were sodium, potassium, magnesium, chloride, urea and creatinine. The 90% confidence interval of the reference limits was obtained using the non-parametric bootstrap method. Reference intervals were preferentially determined by the non-parametric method and were as follows: sodium (128 mmol/L - 166 mmol/L), potassium (3.9 mmol/L - 5.2 mmol/L), magnesium (0.8 mmol/L - 1.2 mmol/L), chloride (97 mmol/L - 130 mmol/L), urea (8.2 mmol/L - 25.1 mmol/L) and creatinine (88 µmol/L - 288 µmol/L). Reference intervals from the current study were compared with International Species Information System values for cheetahs and found to be narrower. Moreover, age, sex and haemolysis score had no significant effect on the serum analytes in this study. Separate reference intervals for captive and free-ranging cheetahs were also determined. Captive cheetahs had higher urea values, most likely due to dietary factors. This study is the first to establish reference intervals for serum biochemistry analytes in cheetahs according to international guidelines. These results can be used for future health and disease assessments in both captive and free-ranging cheetahs.

Translational research will fail without surgical leadership: SCOTRRCC a successful surgeon-led Nationwide translational research infrastructure in renal cancer.

BACKGROUND: High quality human biosamples with associated high quality clinical data are essential for successful translational research. Despite this, the traditional approach is for the surgeon to act as a technician in the tissue collection act. Biomarker research presents multiple challenges and the field is littered with failures. Tissue quality, poor clinical information, small sample numbers and lack of validation cohorts are just a few reasons for failure. It is clear that the surgeon involved in tissue acquisition must be fully engaged in the process of biosampling for a specific condition, as this will negate many of the issues for translational research failure due to an inadequate bioresource. APPROACH: In this Matter for Debate paper, the Scottish Collaboration On Translational Research into Renal Cell Cancer (SCOTRRCC) is discussed as an example of a urological surgery lead bioresource which has resulted in a National collection of renal cancer tissue and blood (from over 900 patients to date), negating all of the traditional issues with biobanks because of close enagagement and acknowledgement of urologists and uropathologists from seven centres around Scotland. SCOTRRCC has leveraged renal cancer research in Scotland resulting in several high impact publications and providing a springboard for future research in this disease in Scotland and beyond. CONCLUSIONS: The SCOTRRCC model presented here can be transferred to other surgical disciplines for success in translational research.

Contralateral renal cell carcinoma ureteric metastases can arise on tyrosine kinase adjuvant therapy and be effectively treated by endoscopic laser excision and ablation.

Renal cell carcinoma (RCC) uncommonly metastasizes to the ureter and rarely to the contralateral ureter. We describe the presentation of 2 successive contralateral ureteric metastases from RCC in our institution. The first represents the only reported metachronous ureteric deposit on adjuvant sorafenib after laparoscopic radical nephrectomy for RCC. The other presented with a synchronous lesion after radiological work-up. Both lesions were treated with endoscopic excision and laser ablation with preservation of the renal unit and no local recurrence. We report these cases and discuss the literature.

The relationship between the local and systemic inflammatory responses and survival in patients undergoing resection for localized renal cancer.

OBJECTIVE: To examine the relationship between the systemic inflammatory response (C-reactive protein, CRP), tumour interleukin-6 receptor and cyclooxygenase (COX)-2 expression, tumour T-lymphocytic (CD4+, CD8+) infiltration and cancer survival in patients undergoing resection for renal cell carcinoma (RCC), as both the local and systemic inflammatory responses appear to predict the outcome in these patients. PATIENTS AND METHODS: The study included 60 patients undergoing nephrectomy for localized RCC. Pre-operative circulating CRP levels were measured and tumour interleukin-6 receptor and COX-2 expression, tumour CD4+ and CD8+ T lymphocytes were assessed using immunohistochemical analysis. RESULTS: The median follow-up was 78 months, with 14 patients relapsing from their disease and nine cancer-specific deaths. On univariate and multivariate survival analysis, tumour stage and grade and CRP levels were identified as significant factors associated with relapse-free and cancer-specific survival. There was a significant direct relationship between Fuhrman grade and CD4+ T-lymphocytic infiltrate (P < 0.05). An increase in tumour expression of interleukin-6 receptor was weakly associated with an increase in tumour CD8+ T-lymphocytic infiltration (P = 0.057). An increase in tumour CD4+ T-lymphocytic infiltration was associated with an increase in CD8+ T-lymphocytic infiltration (P < 0.01). CONCLUSIONS: The present results suggest that tumour-based factors such as interleukin-6 receptor and COX-2 expression or T-lymphocytic subset infiltration are subordinate to systemic factors such as CRP level in determining survival in patients with localized RCC.

Prospective study of the relationship between the systemic inflammatory response, prognostic scoring systems and relapse-free and cancer-specific survival in patients undergoing potentially curative resection for renal cancer.

OBJECTIVE: To examine the prognostic value of markers of systemic inflammatory response, together with established scoring systems, in predicting relapse-free and cancer-specific survival in patients with primary operable renal cancer, as there is increasing evidence that such markers provide prognostic information, in addition to scoring systems, in patients with metastatic renal cancer. PATIENTS AND METHODS: In all, 83 patients undergoing potentially curative nephrectomy for localized renal cancer were recruited. The University of California Los Angeles Integrated Staging System (UISS), 'Stage Size Grade Necrosis' (SSIGN) and Kattan scores were constructed. The systemic inflammatory response was assessed by counting white cells, neutrophils, lymphocytes and platelets, and measuring albumin and C-reactive protein (CRP) concentrations. RESULTS: On multivariate analysis of the significant individual covariates, T stage (hazard ratio 2.38, 95% confidence interval 1.06- 5.36, P = 0.037), necrosis (3.73, 1.26-11.05, P = 0.018) and CRP (4.31, 1.20-15.49, P = 0.025) were significant independent predictors of relapse-free survival. On multivariate analysis of significant scoring systems and CRP, only UISS (3.50, 1.66-7.40, P = 0.001), SSIGN (2.83, 1.19-6.72, P = 0.018) and CRP (4.14, 1.16-14.73, P = 0.028) were significant independent predictors of relapse-free survival. CONCLUSION: Elevated circulating CRP levels appear to be better than other markers of the systemic inflammatory response, and independent of established scoring systems, in predicting relapse-free and cancer-specific survival in patients undergoing potentially curative nephrectomy for renal cancer.

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

BACKGROUND: Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. METHODS: One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. RESULTS: On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. CONCLUSIONS: An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

Case report: octreotide as an adjunct to embolisation in the management of recurrent bleeding upper gastrointestinal metastases from primary renal cell cancer.

The recommended treatment for patients with severe bleeding from upper gastrointestinal (GI) metastases is embolisation. We report a case in which despite adequate embolisation major haemorrhage from renal cell carcinoma (RCC) gastric metastases continually recurred. During a severe bleed refractory to embolisation octreotide was used to control and prevent further bleeding. No further episodes of severe haemorrhage occurred over the following 23 months since starting treatment. Octreotide has been observed to be effective both in the acute management of persistent haemorrhage and in prevention of subsequent haematemesis from GI metastatic RCC.

Management of renal masses in patients medically unsuitable for nephrectomy--natural history, complications, and outcome.

OBJECTIVES: To examine a group of elderly patients with much larger tumors who were deemed unlikely to survive surgery or who would require dialysis postoperatively to establish the natural history of larger renal tumors if left untreated. Little is known of the growth rate and natural history of renal cancer progression because the tumor is usually removed in those patients who can tolerate surgery. The only published data have been in relation to unfit patients with small, homogeneous, well-circumscribed tumors less than 4 cm. METHODS: We identified 36 patients whose tumor had not been removed, without evidence of metastasis at diagnosis, from a database of 421 patients with renal cancer. The data were examined retrospectively for symptoms, survival, and size change. RESULTS: The mean age of the patients treated conservatively was 76.1 years (range 56 to 91), with median tumor size of 6.0 cm (range 3.5 to 20.0) at diagnosis. The median follow-up period was 24 months (range 3 to 136). Of the 36 patients, 13 had died at follow-up, 8 of an unrelated illness and 5 of an unknown cause with no radiologic evidence of progression but severe comorbidity. The median time to death was 9 months (range 3 to 24) after diagnosis. One patient developed metastasis at 132 months and was still alive at 136 months of follow-up. Significant hematuria occurred in 11% of the patients and was successfully managed either conservatively or by embolization. The tumor size was unchanged in most patients during the follow-up period. CONCLUSIONS: In elderly patients, or those with severe comorbidity, conservative management of larger renal masses is a reasonable and safe option.