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Objective: To evaluate the potential savings to health plans when the Pigmented Lesion Assay(PLA) is incorporated into the assessment of pigmented lesions clinically suspicious formelanoma.Methods: A Return on Investment (ROI) model was developed from a US payor perspective todetermine the per member per month (PMPM) net savings impact of incorporating PLA into thevisual assessment/histopathology (VAH) pathway. Using 2019 claims data for patients withlesions suspicious for melanoma (N=239,854), use of PLA in year 1 was modeled and followedthrough subsequent years. Costs were assessed through the pathway of initial visual assessment,surgical procedure(s), histopathology, and subsequent management.Results: The ROI model predicted annual net savings of $0.54 PMPM for commercial healthplans over a three-year period. In this analysis, 95.7% of surgically assessed lesions clinicallysuspicious for melanoma were diagnosed as benign, with 30.4% of patients with benign lesionsundergoing a more advanced procedure (e.g., excision). Melanoma diagnosis rates associatedwith biopsy only, excision only, and biopsy followed by excision procedures in the VAHpathway were 0.7%, 1.1%, and 18.0%, respectively.Conclusion: Incorporation of the PLA into the VAH pathway for assessingsuspicious pigmented lesions results in savings for commercial health insurance plans. Use of thePLA improves patient care by using genomic assessments to minimize avoidable surgicalprocedures on benign lesions, enrich the population of melanomas diagnosed, and decreasedownstream costs of late-stage melanoma diagnoses.

Calcium ions (Ca2+) play a fundamental role in membrane-associated physiological processes. Ca2+ can also significantly modulate the physicochemical properties of phospholipid bilayers, but whether this occurs at physiologically relevant concentrations is difficult to determine because of the uncertainty in the reported affinity of Ca2+ for phospholipid bilayers. In this article, we determine the apparent affinity of Ca2+ for zwitterionic phospholipid bilayers using tethered bilayer lipid membranes (tBLMs) used in conjunction with swept-frequency electrical impedance spectroscopy (EIS). We report that Ca2+ binds to phospholipid bilayers at physiologically relevant concentrations and modulates membrane permeability. We present direct experimental evidence that this effect is governed by specific interactions with select lipid headgroup moieties, which is supported by data from molecular dynamics (MD) simulations. This is the first reported use of tBLM/EIS to estimate cation-membrane affinity. Combined with MD simulations, this technique provides a novel methodology to elucidate the molecular details of cation-membrane interactions at the water-phospholipid interface.

Study Design Retrospective cohort study. Objectives Intraoperative neurophysiological monitoring (IONM) is widely used in spinal neurosurgery, particularly for intramedullary tumours. However, its validity in intradural extramedullary (IDEM) spinal tumours is less clearly defined, this being the focus of this study. Methods We compared outcomes for patients that underwent resection of IDEM tumours with and without IONM between 2010 and 2020. Primary outcomes were postoperative American Spinal Injury Association (ASIA) scores. Other factors assessed were use of intraoperative ultrasound, drain placement, postoperative complications, postoperative Eastern Cooperative Oncology Group (ECOG) score, extent of resection, length of hospital stay, discharge location and recurrence. Results 163 patients were included, 71 patients in the IONM group and 92 in the non-IONM group. No significant differences were noted in baseline demographics. For preoperative ASIA D patients, 44.0% remained ASIA D and 49.9% improved to ASIA E in the IONM group, compared to 39.7% and 30.2% respectively in the non-IONM group. For preoperative ASIA E patients, 50.3% remained ASIA E and 44.0% deteriorated to ASIA D in the IONM group, compared to 30.2% and 39.7% respectively in the non-IONM group (all other patients deteriorated further). Length of inpatient stay was significantly shorter in the IONM group ( P = .043). There were no significant differences in extent of resection, postoperative complications, discharge location or tumour recurrence. Conclusions Research focusing on the use of IONM in IDEM tumour surgery remains scarce. Our study supports the use of IONM during surgical excision of IDEM tumours.

Objective: To compare valveless insufflation (AirSeal®) with a conventional insufflation system (CIS) during robotic prostatectomy (RP) and the ability to use ultralow pneumoperitoneum at 6 mm Hg w...

BACKGROUND Enlarged median lobes (ML) can be technically challenging, particularly during bladder-neck dissection, and may affect urinary functional outcomes of robotic radical prostatectomy (RARP). If known, the impact of potentially larger bladder necks on continence and chronic obstruction on postoperative urinary symptoms might aid patient counseling. We assessed the impact of intraoperatively identified median lobes (ML) on urinary function. METHODS We reviewed our prospective RP database from 2013 to 2020. AUA symptoms scores (AUA-SS) were assessed preoperatively and at 1, 3, and 6 months. We compared patients with and without ML (NoML). Bladder-neck sparing was routine to avoid reconstruction. RESULTS Of 663 patients who completed AUA-SS questionnaires at all time points, 202 (30%) had ML. There were no significant differences in demographics, PSA, or clinical stage. Only two patients in ML and one in NoML group required bladder-neck reconstruction (1.2% and 0.2%). There was no immediate or long-term difference in continence rates between groups. Baseline mean AUA-SS was higher in ML patients and showed more improvement postoperatively (-5.5 vs. -3.6, p

International audience; Phospholipase-A (PLA) enzymes catalyze the hydrolysis of ester bonds in select glycerophospholipids. Sensors for rapidly measuring the PLA activity in biological samples have relevance in the study of venom compositions and in medical diagnostics for the diagnosis of diseases such as acute pancreatitis. Current PLA sensor technologies are often restricted by the time it takes to prepare an assay, the necessity of using fluorescent labels, or the fact they might require strict pH control of the buffer vehicles used. Here we present a tethered bilayer lipid membrane (tBLM) impedance sensor array for the rapid and real-time detection of PLA, which includes the ability to selectively detect phospholipase-A(2)(PLA(2)) from phospholipase-A(1) (PLA(1)) isoforms. Comparing the activity of PLA(1) and PLA(2) in an array of tBLMs composed of ether phospholipids, ester phospholipids or ether-ester phospholipids allows for the rapid and reliable distinction between the isoforms, as measured using swept-frequency electrical impedance spectroscopy. After testing the assay using pure enzymes, we demonstrate the capacity of the sensor to identify specific PLA(2)-type, calcium-dependent activity from the venom of the South American bullet ant, Paraponera clavata, at a concentration of 1 mu g/mL. The specificity of the phospholipase activity was corroborated using matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. As further validation, we tested the activities of a PLA(1) isoform in the presence of different buffers commonly used in biology and biochemistry experiments. Sensitivity testing shows that PLA(1) can be detected at an activity as low as 0.06 U/mL. The rapid and reliable detection of phospholipases presented in this study has potential applications in the study of animal venoms as well as in lipase bioreactors and point-of-care devices.

Purpose of review Robotic nephrectomy for complex renal masses and in the setting of inferior vena cava (IVC) tumor thrombus has been shown to be a well tolerated and reproducible surgical option. Recent developments in such procedures will be discussed as they continue to evolve. Recent findings Multiple case series have demonstrated the application of robotic surgery in the management of the most complex renal tumors and for IVC thrombi with acceptable oncologic and perioperative outcomes. Prior to the advent of robotic surgery, massive tumors, contiguous organ invasion, need for lymphadenectomy, and IVC tumor thrombus were thought by many to require open surgery. Since 2011, several studies have reported robotic nephrectomy for complex tumors with recent comparisons of robotic and open approaches finding similar oncologic and survival outcomes but with shorter length of stay (LOS) and less blood loss with robotic surgery. Summary Robotic surgery is a feasible and well tolerated alternative to open surgery for the management of complex renal tumors and IVC thrombi. The potential benefits of shorter LOS, less blood loss, and earlier convalescence suggest this approach should continue to be evaluated. Patient selection and surgeon experience are of paramount importance.

As formal crisis responders, police are trained in de-escalation tactics that are expected to mitigate intimate partner violence and promote survivor safety. However, the alignment between expected and actual practice of police intervention varies, especially when the survivor does not initiate the call, police treat the survivor poorly, or provide an undesirable arrest outcome. At best, unsuccessful interventions do not change survivors’ risk level, and at worse, elevate their risk of experiencing harm. The purpose of this qualitative study was to explore survivors’ perspectives on the process of police intervention, specifically how variations in initiation, quality of engagement, and arrest influence survivors’ safety. Twenty-four women whose partners were in a relationship violence intervention program were recruited to participate in the study. Results showed that many survivors described a range of ongoing, strategic violence perpetrated by their partners that required intervention; yet the complex nature of the violence often extended beyond police capacity. Either survivors called the police, or they were initiated externally by neighbors or strangers; some survivors had dual initiations. Whether survivors reported that police used safety practices during the intervention was related to who initiated the police. Arrests of abusive partners were inconsistent, and they varied based on number of previous calls to the police and visible signs of injury. Survivors of color, specifically Black women, self-initiated at higher rates, experienced fewer safety strategies used by police, and had fewer arrests. No matter the outcomes of police intervention, survivors actively engaged in strategies outside of formal systems to protect themselves and their families. Study results imply that police intervention may be ill-suited to support survivors’ safety goals and highlight a need for alternative interventions focused on de-escalation and prevention.

Cauda equina syndrome (CES) can have devastating neurological sequelae if surgical treatment is delayed. However, out-of-hours surgery (weekdays from 6:00 pm to 8:00 am and all weekend operations) can potentially result in higher rates of intraoperative complications, resulting in worse outcomes. In the present study, we have described our outcomes for patients with CES during an 8-year period (December 2011 to October 2019) with the aim of assessing the risk of out-of-hours surgery.We performed a retrospective analysis of inpatient events and outcomes at 6 months of follow-up. Patient demographics, symptoms, and management data were extracted, and a risk factor analysis was performed using logistic regression. The outcome measures were the incidence of complications and symptom changes at follow-up. Symptom outcome changes between 2 time points were analyzed using repeated measures.A total of 278 patients were included in the present study. Surgery out-of-hours (P = 0.018) and prolonged operations (P = 0.018) were significant risk factors for intraoperative complications. Improved outcomes at 6 months of follow-up were found for lower back pain, sciatica, altered saddle sensation, and urinary sphincter disturbance, with no significant changes for the remaining symptoms. Out-of-hours surgeries did not significantly affect individual symptom outcomes.Our analysis has suggested that emergency decompressive surgery for patients with CES does not result in worsening of outcomes with out-of-hours surgery compared with in-hours. However, our findings also showed that no clear benefit exists to expediting surgery for those with severe presentations. Thus, decompressive surgery should be undertaken at the earliest possible time to safely do so.

The terminal ventricle (TV) of Krause is a rare cystic dilation of the conus’ central canal. Due to limited understanding surrounding its pathophysiology, optimal management remains controversial. We report a 25-year-old female presenting with acute paraparesis. Magnetic resonance imaging spine revealed a cystic conus medullaris lesion in keeping with an incidental TV cyst. However, the patient experienced a rapid resolution of symptoms. We hypothesize that the TV cyst spontaneously ruptured and auto-decompressed. To our knowledge, this is the first reported case of an enlarging symptomatic TV cyst with spontaneous rupture and resolution of symptoms, highlighting the variable natural history of this condition.

In this dataset, we provide the averaged functional connectivity spectra and the functional connectivity matrices of frequency-band averages for all pairs of recording sites of the manuscript "Brain rhythms define distinct interaction networks with differential dependence on anatomy".

The benefits of using 5-aminolevulinic acid (5-ALA) in resection of grade IV tumors have been extensively researched. However, few studies have investigated the use of 5-ALA in grade III gliomas.To discover whether 5-ALA provides significant benefit in assisting resection of grade III gliomas.A single-center, retrospective cohort study between January 2013 and January 2019 of adult patients with grade III gliomas. Patients were separated into a 5-ALA-guided surgery group (5-ALA-GS) and non-5-ALA-guided surgery group (non-5-ALA-GS). Primary outcome was overall survival (OS); secondary outcomes were both postoperative and 6-month performance status (PS6m), and extent of resection (EoR).Sixty-nine patients with grade III gliomas were included (39 and 30 patients in the 5-ALA-GS group and non-5-ALA-GS group, respectively). There was no significant difference in tumor characteristics between the groups. No significant difference was observed in OS (P = .072) and EoR (P = .609) between both the groups. In a subgroup of the 5-ALA-GS where gross total resection (GTR) was achieved, there was a better OS (P = .043). Significantly worse outcomes were seen postoperatively (P = .044) and at PS6m (P = .041) in the 5-ALA-GS group, mainly because of the poorer outcome in the subtotal resection subgroup.Despite the benefits of 5-ALA in grade IV glioma surgery, these benefits are limited to a smaller group of patients with grade III tumors where there is sufficient fluorescence to allow GTR. In this cohort of patients, 5-ALA use may result in worse neurological outcomes particularly when GTR is not feasible and therefore caution is warranted.

Abdominal drain use is a common practice after urologic procedures involving urinary tract violation with the intention of externalizing potential urine leaks and preventing urinomas. Drains may alternatively be placed to detect bleeding or bowel injury, prevent hematomas or lymphoceles, or for other reasons equally lacking any evidence showing benefits. In general, the practice of placing abdominal drains in urology is based on dogma and learned habits.

Background: Suction during robotic surgery has traditionally been performed by a bedside assistant. Adequately skilled assistants are not always available. We assessed a purpose-designed robotic su...

BACKGROUND Recurrent glioblastoma (rGBM) has poor response rate and survival. Laser Interstitial Thermotherapy (LITT), a minimally invasive approach, improves survival but is not curative alone. Previous studies of LITT suggested the possibility of an abscopal effect. Indeed, GBM are known to harbor elevated levels of immunosuppressive cells such as Treg, M2 macrophages and MDSC both in the tumor microenvironment as well as in the systemic circulation. Checkpoint inhibition (CPI) immunotherapy has proven highly effective for some solid tumors. CPI in newly diagnosed GBM demonstrated safety in phase I trials (NRG BN-002). Further, preclinical studies targeting PD-1 with concurrent RT appears to be synergistic and improve survival. We hypothesized that LITT would block tumor-induced immunosuppression and introduce tumor neoantigens. However, there was no data regarding safety of pembrolizumab combined with LITT. We thus conducted a phase I/II study of LITT + pembrolizumab starting at three times relative to LITT. METHODS This is a three armed Phase I/II study based on timing of pembrolizumab (200 mg q 21 days) relative to LITT at 35d or 14d post-op, or 7d pre-op, with an expansion cohort phase II arm conducted at the earliest tolerated time of CPI administration. Adults with proven supratentorial rGBM with KPS >=70 and RESULTS Arm 1-2 of the phase I trial demonstrated no SAEs grade II or greater, but limited evidence of response. Arm 3 (neoadjuvant) pembrolizumab appears to be equally safe and has been expanded to phase II, demonstrating at least two CR among the first 3 patients (66.6%) with >= 9 month follow-up and patients remain clinically stable at 10 and 15 months post-op. CONCLUSIONS Neoadjuvant pembrolizumab combined with LITT for rGBM appears to be safe in this phase I trial, and demonstrates early evidence of response. The phase II trial is ongoing.

Originally the only option available for transfusion therapy, whole blood transfusions fell out of widespread usage in civilian practice the United States towards the conclusion of World War II, as modern blood banking techniques emerged. With the emergence of blood banks, came the rise of component therapy, which allowed for more efficient utilization of blood products, with one unit of donated blood being able to serve several patients. However, the practice of whole blood transfusion in the military has continued, with forward surgical teams relying on it for massive transfusion scenarios in settings of limited supplies. Recent success with whole blood transfusion in the military has prompted new discussions about implication in a civilian setting, particularly in the treatment of traumatic hemorrhage. Current treatment guidelines for resuscitation of traumatic hemorrhage call for blood products to be administered in a 1:1:1 ratio of packed red blood cells, fresh frozen plasma, and platelets. The aim of this is to re-create whole blood as closely as possible. However, this mixture has been shown to be have a lower than anticipated hematocrit, as well as sub-optimal function of platelets and plasma coagulation factors. Whole blood delivers a product that most closely resembles what is being lost, with a higher hematocrit and better function of platelets and plasma coagulation factors. With clinical trials beginning at several major trauma centers across the United States, whole blood transfusion is poised to have a tremendous impact on the management of hemorrhage in the civilian setting that should be watched closely by anesthesiologists going forward.

INTRODUCTION GBM has median survival of 12 months despite current SOC therapy. The most important mechanism of TMZ resistance is the O6-methylguanine-DNA methyltransferase (MGMT) gene. The MGMT inhibitor O6-benzylguanine (BG) demonstrated efficacy in depleting MGMT but approach led to unacceptable bone marrow toxicity and has thus been abandoned. We hypothesized that chemoprotection of hematopoietic HPC with an MGMT mutant (MGMT-P140K) characterized by normal methyltransferase activity, coupled with low affinity for BG would maximize anti-tumor response while enabling patients to tolerate TMZ & BG dose escalation with minimal toxicity. A phase I trial was performed to test this hypothesis. METHODS 10 adults with newly diagnosed MGMT unmethylated, IDH-1 WT, GBM underwent standard surgery and radiation, followed by transplantation with autologous CD34+ HPC transfected with MGMT-P140K using a lentiviral vector. We tested tolerance and efficacy of three different paradigms for conditioning bone marrow and re-infusion of HPC. RESULTS Treatment was moderately toxic with 3/10 patients suffering grade 3–4 hematologic toxicity; no high grade non-hematologic toxicity was observed. Viral transduction rates ranged from 3–75% and were clearly improved in Arm III utilizing BCNU conditioning and intra-patient dose escalation of TMZ/O6GB. In patients tolerating 3 cycles or more, P140K-MGMT gene markings in peripheral blood and bone marrow cells increased 3-26-fold with only mild (Grade 2–3) myelosuppression consistent with chemo-protection as hypothesized. Median PFS and OS was 24 and 33 months respectfully, and three patients in Arm III were progression free at 36 months with one progression free at 48 months. OS exceeded RPA & Nomogram predicted survival by 3.6-fold, suggesting clinical benefit. Viral insertion site analysis demonstrate no clonal dominance. CONCLUSIONS P140K-MGMT transfected HPC enables TMZ/ BG dose escalation with acceptable toxicity and increased survival in a small cohort of selected patients. A U-01 funded phase II study is ongoing at UH and NIH.

Objective: To demonstrate two distinct methods for adopting the single-port (SP) robotic surgery system for robotic-assisted laparoscopic prostatectomy (RALP) by two experienced robotic surgeons (J...

Purpose To evaluate overall survival for atypical teratoid rhabdoid tumors (ATRTs) in relation to extent of surgical resection. Methods The neurosurgical tumor databases from three UK Pediatric centers (University Hospital of Wales, Alder Hey and Royal Manchester Children’s Hospital) were analyzed. Patients with a diagnosis of ATRT were identified between 2000 and 2018. Data was collected regarding demographics, extent of resection, complications, and overall survival. Results Twenty-four patients diagnosed with ATRT underwent thirty-eight operations. The age range was 20 days to 147 months (median 17.5 months). The most common location for the tumor was the posterior fossa (nine patients; 38%). Six patients (25%) underwent a complete total resection (CTR), seven (29%) underwent a near total resection (NTR), eight (33.3%) underwent a subtotal resection (STR), and three patients (12.5%) had biopsy only. Two-thirds of patients who underwent a CTR are still alive, as of March 2019, compared to 29% in the NTR and 12.5% in the STR groups. Out of the thirty-eight operations, there were a total of twenty-two complications, of which the most common was pseudomeningocele (27%). The extent of surgical resection (p = 0.021), age at surgery (p = 0.00015), and the presence of metastases at diagnosis (0.015) significantly affected overall survival. Conclusions Although these patients are a highly vulnerable group, maximal resection is recommended where possible, for the best chance of long-term survival. However, near total resections are likely beneficial when compared with subtotal resections and biopsy alone. Maximal surgical resection should be combined with adjuvant therapies for the best long-term outcomes.