Mortality and Pulmonary Complications in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection: An International Cohort Study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 82·6% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28-2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65-3·22], p<0·0001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (2·35 [1·57-3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01-2·39], p=0·046), emergency versus elective surgery (1·67 [1·06-2·63], p=0·026), and major versus minor surgery (1·52 [1·01-2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery

Development of a DNA methylation-based diagnostic signature to distinguish benign oncocytoma form renal cell carcinoma

Introduction: A challenge in the diagnosis of renal cell carcinoma (RCC) is to distinguish chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma, as these tumor types are histologically and morphologically similar, yet they require different clinical management. Molecular biomarkers could provide a way of distinguishing oncocytoma from chRCC, which could prevent unnecessary treatment of oncocytoma. Such biomarkers could also be applied to preoperative biopsies such as needle core biopsies, to avoid unnecessary surgery of oncocytoma. Methods: We profiled DNA methylation in fresh-frozen oncocytoma and chRCC tumors and adjacent normal tissue and used machine learning to identify a signature of differentially methylated CpG sites (CpGs) that robustly distinguish oncocytoma from chRCC. Results: Unsupervised clustering of Stanford and pre-existing TCGA RCC data revealed that of all RCC subtypes, oncocytoma is most similar to chRCC. Unexpectedly, however, oncocytoma features more extensive overall abnormal methylation than chRCC. We identified 79 CpGs with large methylation differences between oncocytoma and chRCC. A diagnostic model trained on thirty CpGs could distinguish oncocytoma from chRCC in ten-fold cross validation (area underthe ROC curve (AUC): 0.96 (95% CI: 0.88-1)) and could distinguish TCGA chRCCs from an independent set of oncocytomas from a previous study (AUC=0.87). This signature also separated oncocytoma from other RCC subtypes and normal tissue, revealing it as a standalone diagnostic biomarker for oncocytoma. Conclusions: This CpG signature could be developed as a clinical biomarker to support differential diagnosis of oncocytoma and chRCC in surgical samples. With improved biopsy techniques, this signature could be applied to preoperative biopsies.CRU

DONSON:Slding in 2 the limelight

For over a decade, it has been known that yeast Sld2, Dpb11, GINS and Polε form the pre-loading complex (pre-LC), which is recruited to a CDC45-bound MCM2-7 complex by the Sld3/Sld7 heterodimer in a phospho-dependent manner. Whilst functional orthologs of Dbp11 (TOPBP1), Sld3 (TICRR) and Sld7 (MTBP) have been identified in metazoans, controversy has surrounded the identity of the Sld2 ortholog. It was originally proposed that the RECQ helicase, RECQL4, which is mutated in Rothmund-Thomson syndrome, represented the closest vertebrate ortholog of Sld2 due to a small region of sequence homology at its N-Terminus. However, there is no clear evidence that RECQL4 is required for CMG loading. Recently, new findings suggest that the functional ortholog of Sld2 is actually DONSON, a replication fork stability factor mutated in a range of neurodevelopmental disorders characterised by microcephaly, short stature and limb abnormalities. These studies show that DONSON forms a complex with TOPBP1, GINS and Polε analogous to the pre-LC in yeast, which is required to position the GINS complex on the MCM complex and initiate DNA replication. Taken together with previously published functions for DONSON, these observations indicate that DONSON plays two roles in regulating DNA replication, one in promoting replication initiation and one in stabilising the fork during elongation. Combined, these findings may help to uncover why DONSON mutations are associated with such a wide range of clinical deficits.</p

Aggressive water attack on carbonated cement materials

Aggressive attack on samples was monitored by measuring changes in chemical characteristics of the water exposed to cement concrete samples, inter alia pH, calcium and alkalinity. Over the period of the investigation (100 days) the following observations were found to apply to both brown and white water: (i) Generally uncarbonated OPC experiences significantly higher calcium mineral dissolution rates than both carbonated OPC and 30% fly ash OPC cement concretes. (ii) Once steady dissolution rates were attained, measurements indicated that 30% fly ash OPC and carbonated OPC concrete undergo closely the same calcium mineral dissolution rates. Before these findings are implemented, the following practical considerations need to be addressed: (i) An economic assessment of the benefits of using carbonated OPC, fly ash OPC and carbonated fly ash OPC as a means of resisting aggressive attack. (ii) The investigation should be upgraded from laboratory scale to pilot scale. (iii) The influence of accelerated carbonation on corrosion of steel reinforcing

O Silver Moon : Forgive! Forgive!

https://digitalcommons.library.umaine.edu/mmb-vp/3492/thumbnail.jp

Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

Clear cell renal cell carcinoma is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cancer. We find hotspots of point mutations in the 5’-UTR of TERT, targeting a MYC-MAX-MAD1 repressor, that result in telomere lengthening. The commonest structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This occurs in childhood or adolescence, is generally the initiating event, and precedes emergence of the tumor’s most recent common ancestor by years to decades. Similar genomic changes drive inherited kidney cancers. Modelling differences in age-incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Targeting essential genes in deleted regions of chromosome 3p could represent a potential preventative strategy for renal cancer

Disagreement in risk groups for metastatic renal cancer.

In patients with metastatic renal cell carcinoma, risk stratification according to the Memorial Sloan-Kettering Cancer Center or the International Metastatic Renal Cell Carcinoma Database Consortium classification systems is a crucial part of clinical assessment and essential for guiding management. New research has now demonstrated that disagreement in risk-group classification is common and prognostically relevant