Targeted phasing of 2-200 kilobase DNA fragments with a short-read sequencer and a single-tube linked-read library method.

In the human genome, heterozygous sites refer to genomic positions with a different allele or nucleotide variant on the maternal and paternal chromosomes. Resolving these allelic differences by chromosomal copy, also known as phasing, is achievable on a short-read sequencer when using a library preparation method that captures long-range genomic information. TELL-Seq is a library preparation that captures long-range genomic information with the aid of molecular identifiers (barcodes). The same barcode is used to tag the reads derived from the same long DNA fragment within a range of up to 200 kilobases (kb), generating linked-reads. This strategy can be used to phase an entire genome. Here, we introduce a TELL-Seq protocol developed for targeted applications, enabling the phasing of enriched loci of varying sizes, purity levels, and heterozygosity. To validate this protocol, we phased 2-200 kb loci enriched with different methods: CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis for the longest fragments, CRISPR/Cas9-mediated protection from exonuclease digestion for mid-size fragments, and long PCR for the shortest fragments. All selected loci have known clinical relevance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA. Collectively, the analyses show that TELL-Seq can accurately phase 2-200 kb targets using a short-read sequencer.

Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors.

BACKGROUND AND OBJECTIVE: Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an antibody with affinity for Trop-2 coupled to SN-38 via hydrolyzable linker. SG is approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior chemotherapies (at least one in a metastatic setting) and for patients with pretreated hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. METHODS: In these analyses, the pharmacokinetics of SG, free SN-38, and total antibody (tAB) were characterized using data from 529 patients with mTNBC or other solid tumors across two large clinical trials (NCT01631552; ASCENT, NCT02574455). Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG. RESULTS: Pharmacokinetics of the three analytes were each described by a two-compartment model with estimated body weight-based scaling exponents for clearance and volume. Typical parameter estimates for clearance and steady-state volume of distribution were 0.133 L/h and 3.68 L for SG and 0.0164 L/h and 4.26 L for tAB, respectively. Mild-to-moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, tumor type, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on exposure for any of the three analytes. CONCLUSIONS: These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016.

BACKGROUND: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. METHODS: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. RESULTS: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. CONCLUSIONS: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

The Association of a Peritoneal Interposition Flap With Lymphocele Formation After Pelvic Lymph Node Dissection During Robotic-assisted Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the association of a peritoneal interposition flap (PIF) with lymphocele formation following robotic-assisted laparoscopic radical prostatectomy (RALP) with pelvic lymph node dissection. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 30, 2023, to identify randomized and nonrandomized studies comparing RALP with pelvic lymph node dissection with and without PIF. A random effects meta-analysis was then performed to evaluate the associations of PIF with 90-day postoperative outcomes. RESULTS: Five randomized controlled trials (RCTs) and four observational studies, including a total of 2941 patients, were included. The use of PIF was associated with a reduced risk of 90-day symptomatic lymphocele formation after RALP when examining only RCTs (pooled odds ratios [OR] 0.44, 95% CI 0.28-0.69; I2 =3%) and both RCTs and observational studies (OR 0.35, 95% CI 0.22-0.56; I2 =17%). Similarly, use of PIF was associated with a reduced risk of 90-day any lymphocele formation (OR 0.40, 95% CI 0.28-0.56, I2 =39%). There were no statistically significant differences in postoperative complications between the two groups (OR 0.89; 95% CI 0.69-1.14; I2 =20%). CONCLUSION: Use of the PIF is associated with an approximately 50% reduced risk of symptomatic and any lymphocele formation within 90-days of surgery, and it is not associated with an increase in postoperative complications.

How Can We Identify Extraprostatic Extension (EPE) Before Surgery? The Use of a Preoperative Prostate MRI EPE Scoring System to Assess Postprostatectomy Locally Advanced Prostate Cancer.

Background: Distinguishing between organ-confined disease and extraprostatic extension (EPE) is crucial for the treatment of patients with prostate cancer. EPE is associated with an increased risk of biochemical recurrence, positive surgical margins, and metastatic disease. An MRI-based EPE scoring system was developed by Mehralivand in 2019; however, it has not been adopted in the Urology community. The purpose of this study is to evaluate the association of MRI-based EPE scoring with the pathologic EPE (pEPE) after radical prostatectomy. Methods: We conducted a retrospective review on a prospectively collected database of male patients who underwent a prostate MRI with EPE scoring by a trained genitourinary radiologist and subsequent robotic radical prostatectomy at our institution from September 2020 to December 2022. The associations between MRI EPE (mEPE) score and the presence of EPE on surgical pathology (pEPE) were examined using multivariable logistic regression. Results: A total of 194 patients met inclusion criteria with a median age of 63 years and prostate specific antigen (PSA) 7 ng/mL. Among those with mEPE score 3, 96% had pEPE. Those patients with an mEPE score ≥2 had an increased risk of pEPE compared with those with mEPE score 0 (odds ratio 3.79; 95% confidence interval 1.28-11.3) Furthermore, those with an mEPE score 3 were significantly more likely to have pEPE compared with those with mEPE score 0, 1 and 2 independently. Conclusion: MRI EPE is a straightforward tool that strongly correlates with the presence of pEPE. If validated prospectively, this scoring system could assist in counseling patients regarding nerve-sparing approach.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Practical Use of Self-Adjusted Nitrous Oxide During Transrectal Prostate Biopsy: A Double-Blind Randomized Controlled Trial.

PURPOSE: Transrectal prostate biopsy is a common ambulatory procedure that can result in pain and anxiety for some men. Low-dose, adjustable nitrous oxide is increasingly being used to improve experience of care for patients undergoing painful procedures. This study seeks to evaluate the efficacy and safety of low-dose (<45%) nitrous oxide, which has not been previously established for transrectal prostate biopsies. MATERIALS AND METHODS: A single-institution, prospective, double-blind, randomized, controlled trial was conducted on patients undergoing transrectal prostate biopsies. Patients were randomized to receive either self-adjusted nitrous oxide or oxygen, in addition to routine periprostatic bupivacaine block. Nitrous oxide at levels between 20% and 45% were adjusted to patients' desired effect. Patients completed a visual analog scale for anxiety, State Trait Anxiety Inventory, and a visual analog scale for pain immediately before and after biopsy. The blinded operating urologist evaluated ease of procedure. Periprocedural vitals and complications were assessed. Patients were allowed to drive home independently. RESULTS: A total of 133 patients received either nitrous oxide (66) or oxygen (67). There was no statistically significant difference in the primary anxiety end point of State Trait Anxiety Inventory or the visual analog scale for anxiety scores between the nitrous oxide and oxygen groups. However, patients in the nitrous oxide group reported significantly lower visual analog scale for pain scores compared to the oxygen group (P = .026). The operating urologists' rating of tolerance of the procedure was better in the nitrous oxide group (P = .03). There were no differences in biopsy performance time. Complications were similarly low between the 2 groups. CONCLUSIONS: Patient-adjusted nitrous oxide at levels of 20% to 45% is a safe adjunct during transrectal prostate biopsy. Although there was not an observed difference in the primary end point of anxiety, nitrous oxide was associated with lower patient-reported pain scores.

Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice.

The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP3) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs. PTENOE white adipose tissue (WAT) has increased UCP1, a protein linked to increased thermogenesis. WAT of PTENOE mice also shows a change in polarization of fat-associated macrophages, with elevated levels of arginase 1 (Arg1, characteristic of M2 macrophages) and decreased production of inducible nitric oxide synthase (iNOS, characteristic of M1 macrophages). Muscle and hippocampus showed increased expression of the myokine FNDC5, and higher levels of its cleavage product irisin in plasma, which has been linked to increased conversion of WAT to more thermogenic beige/brown adipose tissue. PTENOE mice also have an increase, in plasma and liver, of GPLD1, which is known to improve cognition in mice. Hippocampus of the PTENOE mice has elevation of both BDNF and DCX, indices of brain resilience and neurogenesis. These changes in fat, macrophages, liver, muscle, hippocampus, and plasma may be considered "aging rate indicators" in that they seem to be consistently changed across many of the long-lived mouse models and may help to extend lifespan by delaying many forms of late-life illness. Our new findings show that PTENOE mice can be added to the group of long-lived mice that share this multi-tissue suite of biochemical characteristics.

Quantum pBac: An effective, high-capacity piggyBac-based gene integration vector system for unlocking gene therapy potential.

Recent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, including piggyBac, have the potential to obviate these shortcomings. In this study, we improved a previously modified piggyBac system with superior transposition efficiency. We demonstrated that the internal domain sequences (IDS) within the 3' terminal repeat domain of hyperactive piggyBac (hyPB) donor vector contain dominant enhancer elements. Plasmid-free donor vector devoid of IDS was used in conjunction with a helper plasmid expressing Quantum PBase™ v2 to generate an optimal piggyBac system, Quantum pBac™ (qPB), for use in T cells. qPB outperformed hyPB in CD20/CD19 CAR-T production in terms of performance as well as yield of the CAR-T cells produced. Furthermore, qPB also produced CAR-T cells with lower donor-associated variabilities compared to lentiviral vector. Importantly, qPB yielded mainly CD8+ CAR-TSCM cells, and the qPB-produced CAR-T cells effectively eliminated CD20/CD19-expressing tumor cells both in vitro and in vivo. Our findings confirm qPB as a promising virus-free vector system with an enhanced payload capacity to incorporate multiple genes. This highly efficient and potentially safe system will be expected to further advance gene therapy applications.

Conditional survival following radical cystectomy for urothelial carcinoma of the bladder.

INTRODUCTION: Traditional surveillance protocols do not adequately account for the decreasing risk of mortality over time in aggressive malignancies, such as bladder cancer. Rather, the risk of death depends on both the baseline risk of mortality and the time survived since treatment. We therefore evaluated the conditional survival of patients diagnosed with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). PATIENTS AND METHODS: We identified patients aged 18 to 75 with Charlson 0-1 and pTany pN0-3 cM0 UCB diagnosed from 2006 to 2015 in the National Cancer Database and treated with RC. The 2- and 5-year conditional overall survival (COS)-i.e., the probability of surviving an additional 2- or 5-years given a specified time survived since treatment-was estimated using the Kaplan-Meier method. Multivariable Cox regression models with landmark time analysis were used to evaluate the associations of baseline characteristics with OS over time. RESULTS: A total of 15,594 patients were included in the study. Median follow-up was 27.8 months. The 2- and 5-year COS for the overall cohort increased through 36 months follow-up and then plateaued. When stratified by pT and pN stage, the COS gain increased with higher pT and pN stage, demonstrating the greatest increase over time for patients with pTany N1-3 disease (5-year COS of 23% at baseline, 58% at 36-months, and 71% at 60-months). In multivariable Cox regression modeling, pT and pN stage were significantly associated with higher all-cause mortality at baseline (HR 3.27 for pT4, HR 2.57 for pT3 vs. ≤pT2; HR 2.26 for pN2-3, HR 1.77 for pN1 vs. pN0), but these associations were attenuated in magnitude with increasing landmark times of 36- and 60-months (HR 1.63 for pT4, HR 1.35 for pT3 vs. ≤pT2; HR 1.34 for pN2-3, HR 1.27 for pN1 vs. pN0). Our study is limited by the retrospective design and the lack of cancer-specific survival data. CONCLUSIONS: Risk of death after RC varies with time elapsed since treatment and disease stage. Accordingly, stage-specific COS may be used to improve prognostication and surveillance protocols.

MicroRNA26a Overexpression Hastens Osteoblast Differentiation Capacity in Dental Stem Cells.

Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are a source of mesenchymal stem cells with the potential to differentiate into several cell types. We initially isolated SHED cells and compared their osteogenic capacity with commercially available DPSCs. Both cells exhibited similar capacities of growth and osteogenic differentiation. A fourfold to sixfold increase in endogenous microRNA26a (miR26a) expression during osteogenic differentiation of preosteoblasts and a similar but attenuated increase (twofold to fourfold) in differentiating SHED was observed, suggesting a role in the process. We, therefore, overexpressed miR26a in SHED to determine if the osteogenic differentiation capacity can be potentiated in vitro. SHED with a threefold increase in miR26a expression showed increased growth rate when compared with parent cells. When exposed to an osteogenic differentiating promoting medium, the miR26a overexpressing cells showed 100-fold increases in the expression of bone marker genes such as type 1 collagen, alkaline phosphatase, and Runx2. The mineralization capacity of these cells was also increased 15-fold. As miR26a targets regulate several bone-specific genes, we evaluated the effect of miR26a overexpression on established targets. We found a moderate decrease in SMAD1 and a profound decrease in PTEN expression. miR26a could potentiate its effect on osteoblast differentiation by its ability to inhibit PTEN and increase the viability of cells and their numbers, a process essential in osteoblast differentiation. Our studies suggest that the upregulation of miR26a can increase bone formation and may serve as an important target to further investigate its potential in tissue engineering applications.

Identifying essential genes in genome-scale metabolic models of consensus molecular subtypes of colorectal cancer.

Identifying essential targets in the genome-scale metabolic networks of cancer cells is a time-consuming process. The present study proposed a fuzzy hierarchical optimization framework for identifying essential genes, metabolites and reactions. On the basis of four objectives, the present study developed a framework for identifying essential targets that lead to cancer cell death and evaluating metabolic flux perturbations in normal cells that have been caused by cancer treatment. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. We applied nested hybrid differential evolution to solve the trilevel MDM problem to identify essential targets in genome-scale metabolic models for five consensus molecular subtypes (CMSs) of colorectal cancer. We used various media to identify essential targets for each CMS and discovered that most targets affected all five CMSs and that some genes were CMS-specific. We obtained experimental data on the lethality of cancer cell lines from the DepMap database to validate the identified essential genes. The results reveal that most of the identified essential genes were compatible with the colorectal cancer cell lines obtained from DepMap and that these genes, with the exception of EBP, LSS, and SLC7A6, could generate a high level of cell death when knocked out. The identified essential genes were mostly involved in cholesterol biosynthesis, nucleotide metabolisms, and the glycerophospholipid biosynthetic pathway. The genes involved in the cholesterol biosynthetic pathway were also revealed to be determinable, if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in the cholesterol biosynthetic pathway became non-essential if such a reaction was induced. Furthermore, the essential gene CRLS1 was revealed as a medium-independent target for all CMSs.

Evaluation of Growth Rates for Small Renal Masses in Elderly Patients Undergoing Active Surveillance.

Background: As the adoption of active surveillance (AS) for small renal masses (SRMs) grows, the number of elderly patients enrolled for a prolonged period of time will increase. However, our understanding of comparative growth rates (GRs) in aging patients with SRMs remains poor. Objective: To examine whether particular age cutoffs are associated with an increased GR for patients undergoing AS for SRMs. Design setting and participants: We identified all patients with SRMs enrolled in the multi-institutional, prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry since 2009 who elected for AS. Outcome measurements and statistical analysis: Two definitions of GR were examined: GR from the initial image (GRi) and GR from the prior image (GRp). Image measurements were dichotomized based on patient age at the time of imaging. Multiple age cutoffs were examined: 65, 70, 75, and 80 yr. Mixed-effect linear regression examined the associations between age and GR, with controlling to account for multiple measurements from the same individual. Results and limitations: We examined 2542 measurements from 571 patients. The median age at enrollment was 70.9 yr (interquartile range [IQR] 63.2-77.4) with a median tumor diameter of 1.8 cm (IQR 1.4-2.5). As a continuous variable, age was not associated with GRi (-0.0001 cm/yr, 95% confidence interval [CI] -0.007 to 0.007, p = 0.97) or GRp (0.008 cm/yr, 95% CI -0.004 to 0.020, p = 0.17) after adjustment. The only age thresholds associated with an increased GR were 65 yr for GRi and 70 yr for GRp. Limitations include the one-dimensional nature of the measurements used. Conclusions: Increased age for patients on AS for SRMs is not associated with increased GRs. Patient summary: We examined whether patients undergoing active surveillance (AS) exhibited accelerated growth of their small renal masses (SRMs) after a certain age. No demonstrable change was seen, suggesting that AS is a safe and durable management option for aging patients with SRMs.

First use of large-bore suction thrombectomy for acute pulmonary embolism in Asia-Pacific: feasibility and short-term clinical outcomes.

Clinical outcomes for intermediate or high-risk pulmonary emboli (PE) remain sub-optimal, with limited improvements in survival for the past 15 years. Anticoagulation alone results in slow thrombus resolution, persistent right ventricular (RV) dysfunction, patients remaining at risk of haemodynamic decompensation and increased likelihood of incomplete recovery. Thrombolysis elevates risk of major bleeding and is thus reserved for high-risk PE. Thus, a huge clinical need exists for an effective technique to restore pulmonary perfusion with minimal risk and avoidance of lytic therapy. In 2021, large bore suction thrombectomy (ST) was introduced in Asia for the first time and this study assessed the feasibility and short-term outcomes of Asian patients undergoing ST for acute PE. 40 consecutive patients (58% male, mean age of 58.3 ± 16.6 years) with intermediate (87.5%) or high-risk PE (12.5%) were enrolled in this prospective registry. 20% had prior VTE, 42.5% had contraindications to thrombolysis, and 10% failed to respond to thrombolysis. PE was idiopathic in 40%, associated with active cancer in 15% and post-operative status in 12.5%. Procedural time was 124 ± 30 min. Emboli were aspirated in all patients without the need for thrombolytics, resulting in a 21.4% reduction in mean pulmonary arterial pressures and 123% increase TASPE-PASP ratio, a prognostic measure of RV-arterial coupling. (both p < 0.001) Procedural complications were 5% and 87.5% patients survived to discharge without symptomatic VTE recurrence during 184 days of mean follow-up. ST affords an effective reperfusion option for PE without thrombolytics, normalises RV overload and provides excellent short-term clinical outcomes.