Identifying predictors of antispasmodic use following robotic assisted simple prostatectomy.

INTRODUCTION: Anticholinergic or ß-3 agonist use following robotic simple prostatectomy (RASP) is not well described. We describe rates of antispasmodic use following RASP and identify potential predictors of medication use. MATERIALS AND METHODS: A retrospective review of all RASP patients from 2/2016 - 1/2020 was conducted. Patients with no preoperative International Prostate Symptom Score (IPSS) were excluded. Demographics, clinical data, and postoperative medication use were collected by electronic medical record review. Multivariable logistic regression analysis using a priori variables was performed to identify independent factors associated with antispasmodic use. RESULTS: A total of 255 patients underwent RASP at a mean age of 70.0 years ± 7.3 and mean body mass index (BMI) of 28.6 kg/m2 ± 5.0. Median preoperative prostate volume was 132.3 cc ± 45.0. Rates of preoperative diabetes, obstructive sleep apnea (OSA), smoking and alcohol use were 19.6%, 6.3%, 3.1%, and 11.8% respectively; 8.6% of patients (n = 22) initiated antispasmodics at a median of 2.5 months (IQR 1.3-4.2) postoperatively. Median duration of antispasmodic use was 6.5 months (IQR 1.7-14.7). Mirabegron was most commonly prescribed (31.8%). On multivariable logistic regression analysis, OSA was independently associated with postoperative antispasmodic use (OR 8.13, 95% CI 2.02-32.67, p = 0.003); 68.8% of OSA patients were treated with continuous positive airway pressure (CPAP). Treatment was not significantly associated with postoperative antispasmodic use (p = 0.61). CONCLUSION: Patients with OSA are over 8 times more likely to require antispasmodic medications following RASP in the short term. These patients may benefit from more tailored preoperative counseling.

Mapping causal circuit dynamics in stroke using simultaneous electroencephalography and transcranial magnetic stimulation.

BACKGROUND: Motor impairment after stroke is due not only to direct tissue loss but also to disrupted connectivity within the motor network. Mixed results from studies attempting to enhance motor recovery with Transcranial Magnetic Stimulation (TMS) highlight the need for a better understanding of both connectivity after stroke and the impact of TMS on this connectivity. This study used TMS-EEG to map the causal information flow in the motor network of healthy adult subjects and define how stroke alters these circuits. METHODS: Fourteen stroke patients and 12 controls received TMS to two sites (bilateral primary motor cortices) during two motor tasks (paretic/dominant hand movement vs. rest) while EEG measured the cortical response to TMS pulses. TMS-EEG based connectivity measurements were derived for each hemisphere and the change in connectivity (ΔC) between the two motor tasks was calculated. We analyzed if ΔC for each hemisphere differed between the stroke and control groups or across TMS sites, and whether ΔC correlated with arm function in stroke patients. RESULTS: Right hand movement increased connectivity in the left compared to the right hemisphere in controls, while hand movement did not significantly change connectivity in either hemisphere in stroke. Stroke patients with the largest increase in healthy hemisphere connectivity during paretic hand movement had the best arm function. CONCLUSIONS: TMS-EEG measurements are sensitive to movement-induced changes in brain connectivity. These measurements may characterize clinically meaningful changes in circuit dynamics after stroke, thus providing specific targets for trials of TMS in post-stroke rehabilitation.

DNA methylation and expression of KCNQ3 in bipolar disorder.

OBJECTIVES: Accumulating evidence implicates the potassium voltage-gated channel, KQT-like subfamily, member 2 and 3 (KCNQ2 and KCNQ3) genes in the etiology of bipolar disorder (BPD). Reduced KCNQ2 or KCNQ3 gene expression might lead to a loss of inhibitory M-current and an increase in neuronal hyperexcitability in disease. The goal of the present study was to evaluate epigenetic and gene expression associations of the KCNQ2 and KCNQ3 genes with BPD. METHODS: DNA methylation and gene expression levels of alternative transcripts of KCNQ2 and KCNQ3 capable of binding the ankyrin G (ANK3) gene were evaluated using bisulfite pyrosequencing and the quantitative real-time polymerase chain reaction in the postmortem prefrontal cortex of subjects with BPD and matched controls from the McLean Hospital. Replication analyses of DNA methylation findings were performed using prefrontal cortical DNA obtained from the Stanley Medical Research Institute. RESULTS: Significantly lower expression was observed in KCNQ3, but not KCNQ2. DNA methylation analysis of CpGs within an alternative exonic region of KCNQ3 exon 11 demonstrated significantly lower methylation in BPD, and correlated significantly with KCNQ3 mRNA levels. Lower KCNQ3 exon 11 DNA methylation was observed in the Stanley Medical Research Institute replication cohort, although only after correcting for mood stabilizer status. Mood stabilizer treatment in rats resulted in a slight DNA methylation increase at the syntenic KCNQ3 exon 11 region, which subsequent analyses suggested could be the result of alterations in neuronal proportion. CONCLUSION: The results of the present study suggest that epigenetic alterations in the KCNQ3 gene may be important in the etiopathogenesis of BPD and highlight the importance of controlling for medication and cellular composition-induced heterogeneity in psychiatric studies of the brain.

Scheduled intravenous ketorolac is safe and reduces narcotic use after robotic-assisted simple prostatectomy.

We sought to examine whether scheduled intravenous (IV) ketorolac decreased post-operative narcotic utilization and changed peri-operative outcomes (including complications) in patients undergoing robotic-assisted simple prostatectomy (RASP). An IRB-approved, retrospective chart review was performed of all patients undergoing RASP at a single institution from November 2017 to July 2019. Patient demographic, peri-operative, and post-operative data, including morphine equivalent use (MEU), were collected. Scheduled ketorolac use was implemented at the surgeon's discretion for up to 5 days post-operatively. The primary outcome was MEU in the post-operative stay. Two hundred seven men underwent RASP during the study period, of which 143 (69%) received scheduled ketorolac. No differences in patient demographics, prostate size, prior opioid utilization, or operative characteristics were identified between groups. Median MEU was significant less (5 vs 15, p < 0.001) in patients receiving scheduled ketorolac. Significantly more patients receiving scheduled ketorolac did not require the use of any narcotic during hospitalization (30% vs 11%, p = 0.005). On multivariable linear regression adjusted for age, BMI, prior opioid use, and length of stay, ketorolac use independently associated with decreased narcotic use (p = 0.003). No significant difference in transfusion rates were identified (3.5% vs. 1.6%, p = 0.44). Scheduled ketorolac is effective in reducing post-operative, in-hospital opioid utilization without increasing morbidity after RASP. Almost a third of patients on scheduled ketorolac did not require any opioids post-operatively.

A larval zebrafish model of cardiac physiological recovery following cardiac arrest and myocardial hypoxic damage.

Contemporary cardiac injury models in zebrafish larvae include cryoinjury, laser ablation, pharmacological treatment and cardiac dysfunction mutations. Although effective in damaging cardiomyocytes, these models lack the important element of myocardial hypoxia, which induces critical molecular cascades within cardiac muscle. We have developed a novel, tractable, high throughput in vivo model of hypoxia-induced cardiac damage that can subsequently be used in screening cardioactive drugs and testing recovery therapies. Our potentially more realistic model for studying cardiac arrest and recovery involves larval zebrafish (Danio rerio) acutely exposed to severe hypoxia (PO2=5-7 mmHg). Such exposure induces loss of mobility quickly followed by cardiac arrest occurring within 120 min in 5 days post fertilization (dpf) and within 40 min at 10 dpf. Approximately 90% of 5 dpf larvae survive acute hypoxic exposure, but survival fell to 30% by 10 dpf. Upon return to air-saturated water, only a subset of larvae resumed heartbeat, occurring within 4 min (5 dpf) and 6-8 min (8-10 dpf). Heart rate, stroke volume and cardiac output in control larvae before hypoxic exposure were 188±5 bpm, 0.20±0.001 nL and 35.5±2.2 nL/min (n=35), respectively. After briefly falling to zero upon severe hypoxic exposure, heart rate returned to control values by 24 h of recovery. However, reflecting the severe cardiac damage induced by the hypoxic episode, stroke volume and cardiac output remained depressed by ∼50% from control values at 24 h of recovery, and full restoration of cardiac function ultimately required 72 h post-cardiac arrest. Immunohistological staining showed co-localization of Troponin C (identifying cardiomyocytes) and Capase-3 (identifying cellular apoptosis). As an alternative to models employing mechanical or pharmacological damage to the developing myocardium, the highly reproducible cardiac effects of acute hypoxia-induced cardiac arrest in the larval zebrafish represent an alternative, potentially more realistic model that mimics the cellular and molecular consequences of an infarction for studying cardiac tissue hypoxia injury and recovery of function.

Quality over quantity: How qualitative research informs and improves quantitative research.

We highlight five recent, high-quality, representative, qualitative articles about Spina Bifida and DSD care that contextualize their findings within the scope of a larger envisioned clinical project. Qualitative research is uniquely poised to address issues such as how to define treatment success and optimize fertility-related education and surgical experiences in DSD care. This approach is also well-suited to explore caregiver burden and financial toxicity in spina bifida care and identify areas for improvement. We encourage researchers to add a qualitative approach to their quantitative research to provide a more holistic, patient-centered view of their subject matter.

Evaluating Surgical Outcomes of Robot Assisted Simple Prostatectomy in the Retreatment Setting.

OBJECTIVE: To report perioperative and postoperative outcomes in men who undergo salvage RASP (sRASP) following some other endoscopic outlet procedure for benign prostate enlargement (BPE) compared to those undergoing RASP for primary treatment (pRASP). METHODS: A prospectively maintained database consisting of all RASP surgeries (December 2014-October 2019) performed at our institution by 3 different urologists was used. Patients who had received an endoscopic procedure for BPE prior to their RASP (sRASP) were compared to those who had not had a prior outlet procedure (pRASP). RESULTS: In total, 310 men underwent RASP during the study period. Of those, 30 (9.7%) had undergone an endoscopic procedure prior to surgery. There were no significant differences in age, race, ASA, BMI, prostate volume, PSA or rates of preoperative retention (P> .05 for all). Men who were treatment-naive had significantly higher preoperative International Prostate Symptom Scores (IPSS) than men who had a prior procedure (18.3 ± 7.7 vs 13.6 ± 6.2, P = .008). However, there were no significant differences in functional or quality of life outcomes between the 2 groups (P > .05 for all). There were no significant differences in perioperative or post-operative outcomes between the 2 groups. Furthermore, rates of post-operative complications and incontinence were similar between groups (11% vs 10%, P = .9 and 2% vs 0%, P = 1 respectively). CONCLUSION: Performing a RASP after prior endoscopic procedure for BPE was found to be safe and effective. Success and complication rates were similar to patients with no prior procedures.

Single-port robotic-assisted simple prostatectomy is associated with decreased post-operative narcotic use in a propensity score matched analysis.

Robotic-assisted simple prostatectomy (RASP) has proven to be an effective minimally invasive option for benign prostatic enlargement (BPE) in recent years. Single-site surgery is theorized to reduce post-operative pain beyond traditional minimally invasive approaches. We sought to assess whether use of a single-port robotic platform decreases post-operative opioid use in patients undergoing robotic-assisted simple prostatectomy (RASP). A retrospective review was performed of all patients undergoing RASP our institution from November 2017 to July 2019. Demographic, intraoperative, and post-operative data, including morphine equivalent (ME) use, were collected. Patients were stratified by robotic platform utilized. Propensity score matching using nearest neighbor method was performed using prostate volume, Charlson comorbidity index (CCI), and post-op ketorolac use in 4:1 fashion. Chi-squared analysis and Kruskal-Wallis analyses were utilized. Two-hundred-and-seven men underwent RASP. After matching, 80 patients (64 multi-port, 16 single-port) were included in the analysis. Groups were comparable for age, body mass index, CCI, prostate volume, prior opioid use, and use of scheduled ketorolac post op. The single-port approach was associated with a reduction in MEs once admitted to the floor (5 vs. 11 mg, p = 0.025) and an increase in the proportion of patients who did not require any narcotics post-operatively (44 vs. 19%, p = 0.036). In a propensity matched cohort of patients undergoing RASP at a single institution, use of the single-port robotic system conferred a significant decrease in post-operative narcotic use by approximately 50%.

Inguinal prolapse of a retroperitoneal lymphovascular malformation.

Abdominal lymphovascular malformations (ALMs) are rare cystic masses that can present with nonspecific symptoms. We present a case of a 7-month-old boy who, during an uncomplicated communicating hydrocele repair, was found to have an incidental large, prolapsed mesenteric abdominal lymphovascular malformation. The case serves to highlight the variability in presentation and natural history of ALMs, and the ease with which they can be disguised by more common pathology. We further underscore the importance of individualized therapy with regards to ALMs, emphasized by our course of active surveillance allowing our patient to avoid ionizing radiation and additional surgical intervention.

Transcranial magnetic stimulation demonstrates a role for the ventrolateral prefrontal cortex in emotion perception.

The lateral prefrontal cortex, a region with both structural and functional connectivity to the amygdala, has been consistently implicated in the downregulation of subcortical-generated emotional responses. Although previous work has demonstrated that the ventral lateral prefrontal cortex (vlPFC) is important to emotion processing, no study has interrupted vlPFC function in order to test is role in emotion perception. In the current study, we acutely disrupted vlPFC function in twenty healthy adult participants by administering sham stimulation and transcranial magnetic stimulation (TMS), in randomized order, during performance of an emotional perception task. During sham stimulation, participants demonstrated increased perceptual sensitivity for happy faces compared to angry faces. Disruption of the vlPFC eliminated this difference: in this condition, perceptual sensitivity did not differ between happy and angry faces. Reaction times and response bias did not differ between emotions or TMS conditions. This pattern of perceptual bias is consistent with effects observed in a wide range of affective disorders, in which vlPFC dysfunction has also been reported. This study provides insight into a possible mechanism through which the vlPFC may contribute to emotion perception.

First Do No Harm: A Cautious, Risk-adapted Approach to Testicular Cancer Patients.

Current guidelines regarding treatment for germ-cell tumors (GCTs) emphasizes cautious progression focusing on stage-specific treatments. Presented herein is the case of a 30-year-old man who, through monitoring of serum alpha-fetoprotein (AFP) levels and surveillance imaging, avoided excessive treatment. This case demonstrates how an experienced clinician, familiar with natural history of GCTs, can appropriately classify level of risk and allow a patient to preserve natural fertility. Furthermore, we highlight the potential for miRNA analysis in staging and management of GCTs. This case serves to underscore the importance of acting with caution in the pursuit of the best outcome for our patients.

An electroencephalographic signature predicts antidepressant response in major depression.

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309). Symptom improvement was robustly predicted in a manner both specific for the antidepressant sertraline (versus placebo) and generalizable across different study sites and EEG equipment. This sertraline-predictive EEG signature generalized to two depression samples, wherein it reflected general antidepressant medication responsivity and related differentially to a repetitive transcranial magnetic stimulation treatment outcome. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Our findings advance the neurobiological understanding of antidepressant treatment through an EEG-tailored computational model and provide a clinical avenue for personalized treatment of depression.