Does Utilizing IRIS, a Segmented Three-dimensional Model, Increase Surgical Precision During Robotic Partial Nephrectomy?

PURPOSE: Preservation of renal parenchyma is a major goal when performing a partial nephrectomy. IRIS anatomical visualization software generates a segmented 3D model, allowing improved visualization of the tumor and surrounding structures. We hypothesize that using IRIS intraoperatively during partial nephrectomy on complex tumors increases the precision of surgical procedures and therefore may result in more tissue preservation. METHODS: We identified 74 non-IRIS and 19 IRIS patients who underwent partial nephrectomy, with nephrometry scores of 9, 10, and 11. Propensity scores were used to match 18 pairs of patients on nephrometry score, age, and tumor volume. Pre- and postoperative imaging (MRI/CT) was obtained. Volumes of the preoperative tumor and preoperative whole kidney were obtained to calculate predicted postoperative whole kidney volume and then compared to actual postoperative whole kidney volume. RESULTS: Mean differences between predicted and actual postoperative whole kidney volumes were 19.2 cm3 (SD=20.2) and 32 cm3 (SD=16.1, P = .0074) for IRIS and non-IRIS groups, respectively. The mean improvement in precision for the IRIS procedure was 12.8 cm3 (95% confidence interval, 2.5 to Inf; P = .02). There was no significant change in mean glomerular filtration rate from baseline to 6 months postoperatively between IRIS and non-IRIS groups (-6.39, SD=15.8 vs -9.54, SD=13.3; P = .5). No significant differences in complication rates (0 vs 1, P = .2), worsening glomerular filtration rate staging (5 vs 4, P = 1), and >25% decrease in glomerular filtration rate (3 vs 4, P = 1) were found between IRIS and non-IRIS groups. CONCLUSIONS: We demonstrated that using IRIS intraoperatively when performing partial nephrectomy on complex tumors is associated with improved surgical precision.

Enhanced striatopallidal gamma-aminobutyric acid (GABA)A receptor transmission in mouse models of huntington's disease.

BACKGROUND: Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin gene. This mutation leads to progressive dysfunction that is largely attributable to dysfunction of the striatum. The earliest signs of striatal pathology in HD are found in indirect pathway gamma-Aminobutyric acid (GABA)-ergic spiny projection neurons that innervate the external segment of the globus pallidus (GPe). What is less clear is whether the synaptic coupling of spiny projection neurons with GPe neurons changes in HD. OBJECTIVES: The principal goal of this study was to determine whether striatopallidal synaptic transmission was altered in 2 mouse models of HD. METHODS: Striatopallidal synaptic transmission was studied using electrophysiological and optogenetic approaches in ex vivo brain slices from 2 HD models: Q175 heterozygous (het) and R6/2 mice. RESULTS: Striatopallidal synaptic transmission increased in strength with the progression of behavioral deficits in Q175 and R6/2 mice. The alteration in synaptic transmission was evident in both prototypical and arkypallidal GPe neurons. This change did not appear attributable to an increase in the probability of GABA release but, rather, to an enhancement in the postsynaptic response to GABA released at synaptic sites. This alteration significantly increased the ability of striatopallidal axon terminals to pause ongoing GPe activity. CONCLUSIONS: In 2 mouse models of HD, striatopallidal synaptic transmission increased in parallel with the progression of behavioral deficits. This adaptation could compensate in part for the concomitant deficit in the ability of corticostriatal signals to activate spiny projection neurons and pause GPe activity. © 2019 International Parkinson and Movement Disorder Society.

Classic Papers Revisited: My Love Affair with the Venous System.

The Pathophysiology of Aortic Cross-clamping and Unclamping. By Gelman S. ANESTHESIOLOGY 1995; 82:1026-60. Reprinted with permission.Aortic cross-clamping (AoX) and unclamping are associated with severe hemodynamic disturbances in virtually all organs and systems. The main hemodynamic changes induced by AoX result from an increase in impedance to aortic flow, an increase in systemic vascular resistance and afterload, blood volume redistribution caused by collapse and constriction of venous vasculature distal to the aortic clamp, and a subsequent increase in preload. Preload may not increase if the aorta is clamped distal to the celiac artery; in that case, blood volume from distal venous vasculature may be redistributed to the splanchnic vasculature without associated increases in preload. Increases in afterload and preload demand an increase in contractility, which results in an autoregulatory increase in coronary blood flow. Without increases in coronary blood flow and myocardial contractility, decompensation may occur. Aortic cross-clamping is associated with the formation and release of many mediators which constitute a double-edged sword: they may mitigate or aggravate the harmful hemodynamic effects of AoX and unclamping. Injuries to the lungs, kidneys, spinal cord, or abdominal viscera are caused mainly by ischemia and reperfusion of organs distal to aortic cross-clamping. A clear understanding of the pathophysiologic mechanisms involved in these processes should help to promote rational, well-focused, and effective measures to prevent and treat homeostatic disturbances occurring during AoX and unclamping.

The physiologic basis for goal-directed hemodynamic and fluid therapy: the pivotal role of the venous circulation.

PURPOSE: Understanding cardiovascular physiology should help clinicians to understand the purpose of fluid and drug management during the perioperative period. The purpose of this narrative review is to describe the pivotal role of the venous circulation in goal-directed hemodynamic and fluid therapy. SOURCE: We selected relevant literature that examines the appropriateness of fluid therapy and pharmacologic interventions during the perioperative period. PRINCIPAL FINDINGS: The interaction between the stressed and unstressed intravascular volume (Vs and Vu, respectively) regulates the venous return, which is the main determinant of cardiac output. The lack of hemodynamic response to an intravascular fluid challenge likely results from an unpredictable distribution of infused fluid between the Vs and Vu. Other factors affecting hemodynamic responses include the pharmacodynamics of common vasoactive drugs, which further highlight the complexity of the regulation of venous return during infusion of exogenous catecholamines. The response to even a highly selective agent can result in different hemodynamic effects. Low doses of α-adrenergic agonists constrict veins and may often shift blood from the Vu to the Vs, subsequently increasing the venous return and cardiac output, whereas higher drug doses constrict arteries and usually decrease cardiac output. CONCLUSIONS: The physiologic basis of goal-directed hemodynamic therapy is complex and not necessarily reflected in the information received from hemodynamic monitors. Understanding the physiologic basis of such therapy is a logical step towards its optimal use.

Trends in cannabis use in New Jersey: Effects of COVID-19 and cannabis legalization.

Objectives: With the legalization of cannabis in New Jersey on April 21, 2022, including the licensing of cannabis dispensaries, concerns have arisen about potential adverse events related to cannabis use. Here, we explore temporal trends and risk factors for cannabis-related harm in both adult and pediatric cannabis-related visits at a tertiary care academic institution. Methods: We performed a retrospective chart review and temporal trend analysis via the electronic health record from May 1, 2019 to October 31, 2022, covering 2 years before, and 6 months after, cannabis legalization in New Jersey. The pediatric charts identified were analyzed for root causes of adverse events, and changes in the frequency of specific unsafe practices since cannabis legalization were tracked. Results: We found that adult cannabis ED-related visits significantly increased during the COVID-19 pandemic and remained higher than pre-pandemic levels for the remainder of the study periods, without a significant change upon legalization. Pediatric rates of cannabis-related ED visits did not vary significantly during the study period. The vast majority of visits for children aged 0-12 years were related to accidental cannabis exposures-often a household member's edibles-whereas most visits for older children stemmed from intentional cannabis use. Conclusion: This project highlights the unintended consequences of wider cannabis access in New Jersey. Notably, cannabis use increased even before its legalization, presumably in response to the COVID-19 pandemic and its attendant mental health effects. Rates of cannabis use disorder and its highlight of other concurrent psychiatric disorders are important topics for both clinicians and lawmakers to consider.

Improved clinical trial race/ethnicity reporting and updated inclusion profile, 2017-2022: A New Jersey snapshot.

Background: Diverse representation in clinical trials is an important goal in the testing of a medical, diagnostic, or therapeutic intervention. To date, the desired level of trial equity and inclusivity has been unevenly achieved. Methods: Employing the US National Library of Medicine's Clinicaltrials.gov registry, we examined 481 clinical trials conducted - at least in part - in the state of New Jersey. These trials were initiated after the FDA-mandated Common Rule changes, i.e., between January 2017 and October 2022, were enacted, and had their results posted. We analyzed sex/race/ethnicity reporting as well as applicable enrollment. Using meta-analysis, we estimated group participation proportions of a subset of the 481 identified trials; specifically, the 229 studies that were conducted solely within the US (i.e., without international sites) and compared them to US census data. Findings: Within the 481 clinical trials analyzed, over 97% reported on the race and/or ethnicity of their enrollees; all included information on sex. Reporting was not affected by funding source or therapeutic area. Based on the 229 solely US-based studies, the participants overall were 76.7% White; 14.1% Black; 2.7% Asian; and 15% Hispanic. Inclusion of Black participants did not differ from the 2020 US census data; in contrast, the levels of Asian and Hispanic participation were below the corresponding census percentages. Interpretation: The past five years have seen an overall uptick in the equity of race/ethnicity reporting and inclusivity of clinical trials, as compared to previously reported data, presaging the potential acquisition of ever more powerful and meaningful results of such interventional studies going forward. Funding: Support for this study comes from the Hackensack Meridian Health Research Institute and the Hackensack Meridian School of Medicine. Research in context: Evidence before this studyClinical trials are a critical part of determining whether or not a medical (drug/device/biologic) or socio-behavioral intervention is safe and truly effective. Through their use, scientific understanding is advanced and, ideally, human health is improved. To gain the most impactful information from a clinical trial, it should be sufficiently representative, that is, should enroll an adequate number of participants, and include a diverse population. Without such inclusion, the study is of only limited generalizability. Efforts are underway by funders, sites, and other stakeholders, to enhance reporting and promote inclusive enrollment. The extent to which such attempts are yielding results - at least for clinical trials in the state of New Jersey - is the focus of this data-driven analysis. The ClinicalTrials.gov registry database was carefully mined for the information contained in this report.Added value of this studyOur analysis of clinical trials initiated in the state of New Jersey and conducted there or elsewhere in the US reveals several positive trends. Our 5-year snapshot reveals that a very large percentage of trials report on race/ethnicity - and inclusivity is improving. While there is still some way to go to have the demographic numbers in these trials match US census values, our results suggest that recent efforts are having an effect.Implications of all the available evidenceFor myriad reasons, clinical trials have not enjoyed the public's universal trust over the years. In many ways, medicine moves at the speed of trust - without it, the promise of modern healthcare is brought into question. Clinical trials must include a commitment to diverse enrollment pools and equitable reporting under the law. Creating a legacy of trust - through greater inclusivity in clinical trials and more transparent reporting of results - will begin to heal the divide and engender faith in modern medicine and today's healthcare system. It would also allow for the desired far-reaching generalizability of results across patient populations. To better appreciate what needs to be done going forward, we must truly understand the state of clinical trials reporting and demographic inclusion. This report initiates such an analysis, by carefully documenting how New Jersey's clinical trials are performing. By virtue of its location (e.g., proximity to the cities of New York and Philadelphia) the state is part of a large biopharma cluster and healthcare nexus; it is critical that it performs well with respect to adopting/adhering to updated clinical trial guideline mandates. This report provides a glimpse - an important first look - into the state of clinical trials in New Jersey - from 2017 through 2022.

Does Incision Location Matter? Analysis of Single-Port Cosmesis in Urologic Reconstructive Surgery.

Introduction and Objective: One potential advantage of single-port (SP) robotic surgery compared with multiport (MP) robotic surgery is improved cosmesis. The only studies in urology patients to suggest this finding did not assess differences based on incision site. Our study evaluated SP, MP, incision location, age, gender, and prior abdominal surgery as predictors of cosmesis and scar consciousness for reconstructive procedures. Methods: This is a cohort study using an institutional review board-approved prospective genitourinary reconstruction database. Patients at least 3 months from surgery were emailed and called to complete the Consciousness subsection of the Patient Scar Assessment Questionnaire. Bothersome was defined as a score of 11 or greater. Overall consciousness was scored with a single item as "not conscious" or "conscious." Pearson's chi-squared, Wilcoxon rank sum, Fisher's exact test, and logistic regression were performed to assess how age, gender, prior surgery, and incision location affect cosmesis. Results: There were 111 patients (54 MP, 57 SP), of which 27 were SP umbilical, 14 were SP midline nonumbilical, and 16 were SP lower quadrant. On univariate analysis the periumbilical incision had the lowest consciousness. Age was associated with Bother (p = 0.012) and Consciousness (p = 0.002), whereas gender, prior abdominal surgery, and incision site were not significant. On logistic regression, all SP incisions were less likely to be bothered compared with MP, although only SP umbilical was statistically significant (odds ratio [OR] = 0.08, 95% confidence interval [CI]: 0.01,0.38; p = 0.005). Age was also significant on logistic regression for Bother (OR = 0.96, 95% CI: 0.93,0.99; p = 0.005). Gender and prior abdominal surgery were not associated with Bother or Consciousness. Conclusions: SP periumbilical incisions provide the best outcomes for cosmesis compared with other SP incision sites and MP incisions. This finding should be discussed and taken into account when planning surgical approaches for patients undergoing urinary reconstruction, especially in patients younger than 40 years of age.