Despite advances in systemic therapy for metastatic renal cell carcinoma, durable responses remain rare and surgical management remains a mainstay of treatment for many patients with metastatic ...disease. Management of the primary tumor in metastatic patients can occur as 1) palliative nephrectomy for symptomatic patients in whom cure is not achievable, 2) cytoreductive nephrectomy before systemic therapy, or 3) consolidative nephrectomy after systemic therapy. Palliative nephrectomy is rarely performed in centers where angioembolization is available. The evidence for cytoreductive nephrectomy is based on randomized trials in the cytokine era and retrospective studies in the more recent targeted therapy era. Consolidative nephrectomy is utilized after systemic therapy for intermediate- and poor-risk patients or in patients with potentially unresectable disease based on retrospective evidence. Resection of metastatic lesions, or metastasectomy, is utilized in select patients, with efficacy predicated on the organs involved and the extent of resection that is achievable, based on retrospective data. Herein, the evidence for surgical management of both the primary tumor and metastatic lesions in patients with metastatic renal cell carcinoma is reviewed.
•GPT-4 accurately detected postoperative complications from renal surgeries.•GPT-4 performed worse for Clavien-Dindo classification and institutional categories.•GPT-4 may struggle with more complex ...reasoning tasks.•GPT-4 can be used with human oversight to help identify postoperative complications.
Large language models, a subset of artificial intelligence, have immense potential to support human tasks. The role of these models in science and medicine is unclear, requiring strong critical thinking and analysis skills. The objective of our study was to evaluate GPT-4's abilities to assess postoperative complications after renal surgeries.
Discharge summaries were compiled, and patient information was deidentified in a Python-based program. Prompts were engineered in GPT-4 to assess for the presence of postoperative complications. GPT-4 was further asked to interpret each complication's Clavien-Dindo classification and institutional-specific category. GPT-4's database was compared to a human-curated database. Discrepancies were manually reviewed to calculate match and accuracy rates.
Approximately 944 renal surgeries were conducted from August 2005 to March 2022. There was a 79.6% match rate between GPT-4 and human-curated data in detecting postoperative complications. Accuracy rates were 86.7% for GPT-4 and 92.9% for human-curated. A subgroup of 139 patients had a complication detected by both GPT-4 and human with available Clavien-Dindo classification and category information. There was a 37.4% overall match rate for Clavien-Dindo grade and 55.4% match rate for category.
GPT-4 was able to accurately detect if there were any postoperative complications. It struggled with the complex task of further analyzing complications, especially with Clavien-Dindo classification, which requires more critical thinking and interpretation. While GPT-4 is not yet ready for advanced postoperative complication analysis, it can still be used to support clinicians in this endeavor.
There is evidence that a natural control system influences global atmospheric surface temperature (Leggett and Ball
2020
). The present paper sets up and tests a hypothesis concerning the physical ...makeup of the sequential elements of the control system and its outcomes. The final outcome that the control system influences is defined as global atmospheric surface temperature. The terms used for the control system element types in the hypothesis are, in sequence: leading element, controller and actuator. Actuators are hypothesised to affect, in turn, the final outcome - either directly, or via penultimate outcomes. The existence of the control system is evidenced by demonstration of statistically significant one-way Granger causality across each step of the hypothesised control system sequence. Evidence is presented that the leading element of the control system, represented by the Normalized Difference Vegetation Index, is the global biosphere. The biosphere as a control system has previously been referred to as Gaia (Lovelock and Margulis
1974
). A fourth, second-derivative, term is found to enhance the Proportional, Integral and Derivative process terms of the control system shown in Leggett and Ball (
2020
). The main actuators of the control system found are shown to be wind speed and cloud cover. Cloud cover is shown to influence the final outcome, global surface temperature, directly. It and wind speed also influence the penultimate outcomes found, those of enhanced ocean heat uptake and enhanced outgoing longwave radiation. These together lead to control system output to the final outcome, global atmospheric temperature. Overall, evidence for the activity of the control system is shown to be present across many major physical dimensions of the Earth's atmosphere.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Parent smartphone use has been associated with decreased responsiveness to children,1 fewer verbal and nonverbal interactions,2 and higher ratings of child externalizing behavior.3 However, existing ...studies are limited by use of brief (10–15 min) observations of parents using smartphones1,4 or rely on parent self-report,3 which may be biased by social desirability. In addition, self-report of smartphone use may be inaccurate due to the brief, intermittent ways users interact with mobile devices,5 which makes recall difficult.6
Purpose We evaluated the early oncological end point of recurrence-free survival in patients with renal cell carcinoma up-staged from cT1 to pT3a after partial nephrectomy. We also aimed to establish ...preoperative factors associated with pathological tumor up-staging. Materials and Methods A prospective database of robotic partial nephrectomy cases performed at 5 academic centers was queried for patients who underwent surgery for a solitary cT1 renal mass. Patients with pT1-2 renal cell carcinoma were compared to those with pT3a tumors to determine the difference in recurrence-free survival. Preoperative factors associated with cT1 to pT3a up-staging were studied using multivariate logistic regression analysis. Results A total of 1,096 patients underwent robotic partial nephrectomy for a cT1 renal mass. At final pathological evaluation 855 tumors (78.0%) were found to be renal cell carcinoma, of which 41 (4.8%) were up-staged to pT3a. The 24-month recurrence-free survival estimates for pT1-2 and pT3a tumors were 99.2% and 91.8%, respectively (p = 0.003). Multivariate analysis revealed that a high vs low R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score was associated with tumor up-staging (OR 2.97, 95% CI 1.20–7.35, p = 0.02). On separate multivariate analysis increasing tumor diameter (OR 1.66, 95% CI 1.32–2.08, p <0.001) and hilar location (OR 2.83, 95% CI 1.43–5.61, p = 0.003) were also associated with up-staging. Conclusions At short-term followup patients with renal cell carcinoma up-staged from cT1 to pT3a have reasonable oncological outcomes after partial nephrectomy. Factors associated with tumor up-staging include high tumor complexity, increasing tumor diameter and hilar location. Further studies are needed to determine the comparative efficacy of partial vs radical nephrectomy for small pT3a tumors.
Renal cell carcinoma is a term that represents multiple different disease processes, each driven by different genetic alterations, with distinct histology, and biological potential which necessitates ...divergent management strategies. This review discusses the genetic alterations seen in several forms of hereditary kidney cancer and how that knowledge can dictate when and how to intervene with a focus on the surgical management of these tumors.
Birt‐Hogg‐Dubé (BHD) syndrome is an inherited familial cancer syndrome characterized by the development of cutaneous lesions, pulmonary cysts, renal tumors and cysts and caused by loss‐of‐function ...pathogenic variants in the gene encoding the tumor‐suppressor protein folliculin (FLCN). FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We have previously shown that deletion of Tfeb rescued the renal cystic phenotype of kidney‐specific Flcn KO mice. Using Flcn/Tfeb/Tfe3 double and triple KO mice, we now show that both Tfeb and Tfe3 contribute, in a differential and cooperative manner, to kidney cystogenesis. Remarkably, the analysis of BHD patient‐derived tumor samples revealed increased activation of TFEB/TFE3‐mediated transcriptional program and silencing either of the two genes rescued tumorigenesis in human BHD renal tumor cell line‐derived xenografts (CDXs). Our findings demonstrate in disease‐relevant models that both TFEB and TFE3 are key drivers of renal tumorigenesis and suggest novel therapeutic strategies based on the inhibition of these transcription factors.
Synopsis
TFEB and TFE3 transcription factors are master regulators of cell metabolism. This study shows that in Birt‐Hogg‐Dubé (BHD) hereditary cancer syndrome, these factors concomitantly activate cellular catabolic and anabolic pathways, playing a key role in kidney cystogenesis and tumorigenesis.
Genetic interaction studies revealed that TFEB and TFE3 have a differential and cooperative role in the kidney phenotype of a mouse model of BHD syndrome.
Transcriptomic and proteomic analyses of tumor samples from BHD patients showed upregulation of the TFEB/TFE3 transcriptional program and induction of both lysosomal and mTORC1 pathways.
Depletion of TFEB or TFE3 fully abrogated the growth of BHD renal tumor cells in xenograft experiments, indicating that both genes are key drivers of tumorigenesis.
TFEB and TFE3 transcription factors are master regulators of cell metabolism. This study shows that in Birt‐Hogg‐Dubé (BHD) hereditary cancer syndrome, these factors concomitantly activate cellular catabolic and anabolic pathways, playing a key role in kidney cystogenesis and tumorigenesis.
To evaluate the recurrence and functional outcomes in a primarily hereditary cohort of patients undergoing partial adrenalectomy for pheochromocytoma.
A retrospective review from a prospectively ...managed database of patients undergoing partial adrenalectomy from 1995 to 2018 at the National Cancer Institute was performed. Local recurrence was defined as imaging evidence of a recurrent or de novo lesion on the operative side. Steroid dependency was defined as requiring daily steroid replacement at time of last follow-up.
One hundred and twenty-four partial adrenalectomies, removing 162 tumors, were performed in 107 patients. Most patients had a known hereditary predisposition to develop bilateral, multifocal, and recurrent pheochromocytoma. Median tumor size was 2 cm (interquartile range (IQR) 1.5-2.8). Median follow-up was 60 months (IQR 13-131). Local recurrence occurred in 17 patients (15.8%) and were managed with active surveillance or surgery. A single patient (1/106, 0.9%) developed metastatic spread of pheochromocytoma approximately 14 years after his first of 2 partial adrenalectomies and remains alive under active surveillance. Median time to recurrence was 71 months (IQR 26-127) with 10 patients (9.3%) requiring daily steroid replacement at time of last follow-up.
Partial adrenalectomy offers excellent oncologic and functional outcomes, sparing most patients from lifelong steroid replacement therapy. Recurrences can be easily managed with repeat surgery or active surveillance via functional work-up and imaging. Partial adrenalectomy remains the recommended surgical management for patients pre-disposed to development of bilateral, multifocal and recurrent pheochromocytoma.
Objective We evaluated the effects of three cognitive training interventions on depressive symptoms at 1 and 5 years. Methods Advanced Cognitive Training for Independent and Vital Elderly is a ...multisite randomized controlled trial (age ≥ 65 years), with four groups (memory, reasoning, speed-of-processing, and no-contact control). Complete data were available for 2,014 (72%) and 1,516 (54%) of 2,802 participants at 1 and 5 years. Separate propensity score models adjusted for potential attrition bias. Clinically important increases in depressive symptoms were defined as: (a) Center for Epidemiological Studies–Depression scale (CES-D)-12 score increases ≥0.5 SD and (b) CES-D-12 score increases ≥1.0 SD. Multivariable logistic regression was used. Results The speed-of-processing group (vs the no-contact control group) was 30% less likely to experience clinically important increases in depressive symptoms at 1-year (adjusted odds ratio AOR = 0.700, p = .012) and 5-year (AOR = 0.698, p = .023) posttraining for the ≥0.5 SD threshold. Similar results (AOR = .669 with p = .039 at 1 year; AOR = 0.651 with p = .059 at 5 years) were obtained for the ≥1.0 SD threshold. No differences were observed among the control, memory, or reasoning groups at either time period or at either threshold. Conclusion The speed-of-processing intervention reduced the risk of clinically important increases in depressive symptoms at 1- and 5-years postbaseline.
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