Utilization of immediate extubation in a multidisciplinary pathway for pediatric liver transplantation associated with improved postoperative outcomes.

BACKGROUND: Immediate extubation is becoming more common in liver transplantation. However, limited data exist on how to identify pediatric patients with potential for successful immediate extubation and how this intervention may affect recovery. METHODS: This retrospective review evaluated patients who underwent liver transplantation from 2015 to 2021 at Children's Healthcare of Atlanta. Preoperative status and intraoperative management were evaluated and compared. Outcomes comprised thrombosis, surgical reexploration, retransplantation, as well as reintubation, high flow nasal cannula (HFNC) usage, postoperative infection, the length of stay (LOS), and mortality. RESULTS: A total of 173 patients were analyzed, with 121 patients (69.9%) extubated immediately. The extubation group had older age (median 4.0 vs 1.25 years, p = .048), lower PELD/MELD (28 vs. 34, p = .03), decreased transfusion (10.2 vs. 41.7 mL/kg, p < .001), shorter surgical time (332 vs. 392 min, p < .001), and primary abdominal closure (81% vs. 40.4%, p < .001). Immediate extubation was associated with decreased HFNC (0.21 vs. 0.71 days, p = .02), postoperative infection (9.9% vs. 26.9%, p = .007), mortality (0% vs. 5.8%, p = .036), and pediatric intensive care unit LOS (4.7 vs. 11.4 days, p < .001). The complication rate was lower in the extubation group (24.8% vs. 36.5%), but not statistically significant. CONCLUSIONS: Approximately 70% of patients were able to be successfully extubated immediately, with only 2.5% requiring reintubation. Those immediately extubated had decreased need for HFNC, lower infection rates, shorter LOS, and decreased mortality. Our results show that with proper patient selection and a multidisciplinary approach, immediate extubation allows for improved recovery without increased respiratory complications after pediatric liver transplantation.

Trends in sedation-analgesia practices in pediatric liver transplant patients admitted postoperatively to the pediatric intensive care unit: An analysis of data from the pediatric health information system (PHIS) database.

BACKGROUND: Children admitted to the pediatric intensive care unit (PICU), after liver transplantation, frequently require analgesia and sedation in the immediate postoperative period. Our objective was to assess trends and variations in sedation and analgesia used in this cohort. METHODS: Multicenter retrospective cohort study using the Pediatric Health Information System from 2012 to 2022. RESULTS: During the study period, 3963 patients with liver transplantation were admitted to the PICU from 32 US children's hospitals with a median age of 2 years [IQR: 0.00, 10.00]. 54 percent of patients received mechanical ventilation (MV). Compared with patients without MV, those with MV were more likely to receive morphine (57% vs 49%, p < .001), fentanyl (57% vs 44%), midazolam (45% vs 31%), lorazepam (39% vs. 24%), dexmedetomidine (38% vs 30%), and ketamine (25% vs 12%), all p < .001. Vasopressor usage was also higher in MV patients (22% vs. 35%, p < .001). During the study period, there was an increasing trend in the utilization of dexmedetomidine and ketamine, but the use of benzodiazepine decreased (p < .001). CONCLUSION: About 50% of patients who undergo liver transplant are placed on MV in the PICU postoperatively and receive a greater amount of benzodiazepines in comparison with those without MV. The overall utilization of dexmedetomidine and ketamine was more frequent, whereas the administration of benzodiazepines was less during the study period. Pediatric intensivists have a distinctive opportunity to collaborate with the liver transplant team to develop comprehensive guidelines for sedation and analgesia, aimed at enhancing the quality of care provided to these patients.

Femoral nerve neuromonitoring for lateral lumbar interbody fusion surgery.

BACKGROUND CONTEXT: The transpsoas lateral lumbar interbody fusion (LLIF) technique is an effective alternative to traditional anterior and posterior approaches to the lumbar spine; however, nerve injuries are the most reported postoperative complication. Commonly used strategies to avoid nerve injury (eg, limiting retraction duration) have not been effective in detecting or preventing femoral nerve injuries. PURPOSE: To evaluate the efficacy of emerging intraoperative femoral nerve monitoring techniques and the importance of employing prompt surgical countermeasures when degraded femoral nerve function is detected. STUDY DESIGN/SETTING: We present the results from a retrospective analysis of a multi-center study conducted over the course of 3 years. PATIENT SAMPLE: One hundred and seventy-two lateral lumbar interbody fusion procedures were reviewed. OUTCOME MEASURES: Intraoperative femoral nerve monitoring data was correlated to immediate postoperative neurologic examinations. METHODS: Femoral nerve evoked potentials (FNEP) including saphenous nerve somatosensory evoked potentials (snSSEP) and motor evoked potentials with quadriceps recordings were used to detect evidence of degraded femoral nerve function during the time of surgical retraction. RESULTS: In 89% (n=153) of the surgeries, there were no surgeon alerts as the FNEP response amplitudes remained relatively unchanged throughout the surgery (negative group). The positive group included 11% of the cases (n=19) where the surgeon was alerted to a deterioration of the FNEP amplitudes during surgical retraction. Prompt surgical countermeasures to an FNEP alert included loosening, adjusting, or removing surgical retraction, and/or requesting an increase in blood pressure from the anesthesiologist. All the cases where prompt surgical countermeasures were employed resulted in recovery of the degraded FNEP amplitudes and no postoperative femoral nerve injuries. In two cases, the surgeons were given verbal alerts of degraded FNEPs but did not employ prompt surgical countermeasures. In both cases, the degraded FNEP amplitudes did not recover by the time of surgical closure, and both patients exhibited postoperative signs of sensorimotor femoral nerve injury including anterior thigh numbness and weakened knee extension. CONCLUSIONS: Multimodal femoral nerve monitoring can provide surgeons with a timely alert to hyperacute femoral nerve conduction failure, enabling prompt surgical countermeasures to be employed that can mitigate or avoid femoral nerve injury. Our data also suggests that the common strategy of limiting retraction duration may not be effective in preventing iatrogenic femoral nerve injuries.

Intralesional cryotherapy with triamcinolone and onabotulinumtoxinA injections for umbilical keloid: A case report.

INTRODUCTION: Keloid scars are therapeutically challenging and although many treatment options exist, there are no specific guidelines, and few reports have discussed keloids in the umbilical region. METHODS: Here, we present a successful treatment of a 31-year-old female with a history of a recurrent keloid in the umbilical region. The keloid was treated using intralesional cryotherapy followed by intralesional onabotulinumtoxinA and triamcinolone acetonide injections. DISCUSSION: The patient expressed high satisfaction, minimal side effects, and no recurrence. CONCLUSION: Overall, due to the low rate of side effects, high patient satisfaction, and absence of recurrence, this treatment modality should be considered as an option for umbilical keloids. LAY SUMMARY: Background to subject: Keloids are a type of scar that are difficult to treat. There are many treatment options available, but there is no single best treatment for keloids that form around the belly button region. Question being asked: Is intralesional cryotherapy with intralesional onabotulinumtoxinA and triamcinolone acetonide injections effective at treating keloids in the belly button region? How the work was conducted: We treated a 31-year-old female with a keloid around the belly button region that returned after prior treatment. The keloid was treated using combination therapy of freezing the keloid from the inside out, which is called intralesional cryotherapy. This was followed by two types of injections, called onabotulinumtoxinA and triamcinolone acetonide, directly into the keloid. What we learned: Overall, due to the low rate of side effects, high patient satisfaction and the keloid not returning, this treatment plan should be considered as an option for keloids in the belly button region. What we did not learn: This treatment may or may not be effective and safe for all patients of all skin types and demographics as this treatment was performed for only one patient.

Optimizing the Therapeutic Window of Targeted Drugs in Oncology: Potency-Guided First-in-Human Studies.

Many targeted therapies are administered at or near the maximum tolerated dose (MTD). With the advent of precision medicine, a larger therapeutic window is expected. Therefore, dose optimization will require a new approach to early clinical trial design. We analyzed publicly available data for 21 therapies targeting six kinases, and four poly (ADP-ribose) polymerase inhibitors, focusing on potency and exposure to gain insight into dose selection. The free average steady-state concentration (Css ) at the approved dose was compared to the in vitro cell potency (half-maximal inhibitory concentration (IC50 )). Average steady-state area under the plasma concentration-time curve, the fraction unbound drug in plasma, and the cell potency were taken from the US drug labels, US and European regulatory reviews, and peer-reviewed journal articles. The Css was remarkably similar to the IC50 . The median Css /IC50 value was 1.2, and 76% of the values were within 3-fold of unity. However, three drugs (encorafenib, erlotinib, and ribociclib) had a Css /IC50 value > 25. Seven other therapies targeting the same 3 kinases had much lower Css /IC50 values ranging from 0.5 to 4. These data suggest that these kinase inhibitors have a large therapeutic window that is not fully exploited; lower doses may be similarly efficacious with improved tolerability. We propose a revised first-in-human trial design in which dose cohort expansion is initiated at doses less than the MTD when there is evidence of clinical activity and Css exceeds a potency threshold. This potency-guided approach is expected to maximize the therapeutic window thereby improving patient outcomes.

Improved resolution of mixed STR profiles using a fully automated differential cell lysis/DNA extraction method.

Sexual assault evidence often contains sperm cells, which are typically separated from nonsperm cells using manual differential lysis procedures. The goal of this study was to evaluate the automated QIAGEN QIAcube for this purpose and to compare it to manual QIAGEN and manual organic differential methods using DNA yields and STR profile data for assessment. DNA yields were determined by qPCR, followed by multiplex STR amplification, CE analysis, and mixture interpretation. The automated method was capable of effective cell separation, producing DNA yields sufficient for STR amplification. Further, sperm fraction human:male DNA ratios from the QIAcube samples were consistently closer to the desired 1:1 and STR profiles were less likely to result in mixtures, with 6-8× fewer female alleles detected (median 1.5 alleles). Ultimately, using the QIAcube for automated differential processing of semen-containing mixtures reduces the need for downstream mixture interpretation and improves STR profile quality with substantially less hands-on time.

PKC induces release of a functional ectodomain of the guidance cue semaphorin6A.

Semaphorins (Semas) are a family of secreted and transmembrane proteins that play critical roles in development. Interestingly, several vertebrate transmembrane Sema classes are capable of producing functional soluble ectodomains. However, little is known of soluble Sema6 ectodomains in the nervous system. Herein, we show that the soluble Sema6A ectodomain, sSema6A, exhibits natural and protein kinase C (PKC)-induced release. We show that PKC mediates Sema6A phosphorylation at specific sites and while this phosphorylation is not the primary mechanism regulating sSema6A production, we found that the intracellular domain confers resistance to ectodomain release. Finally, sSema6A is functional as it promotes the cohesion of zebrafish early eye field explants. This suggests that in addition to its canonical contact-mediated functions, Sema6A may have regulated, long-range, forward-signaling capacity.

Does Metformin Have an Effect on Stent Patency Rates.

BACKGROUND: Metformin is the most commonly used drug for type 2 diabetes. Research has shown that metformin also has a protective effect on endothelium by decreasing endothelial vascular reactivity. We hypothesize that metformin will decrease restenosis/reintervention rates in patients receiving lower extremity non-drug-eluting stents (nDESs) in the superficial femoral artery(SFA) and/or popliteal artery. MATERIALS/METHODS: Retrospective study was performed on 187 patients from October 2012 to December 2015 who received an nDES in the SFA and/or popliteal artery. Patients were divided into 3 groups (Table 1) and compared against for duplex based restenosis (>60%) rates, limb loss rates, and reintervention rates. Each patient's Trans-Atlantic-Inter-Society-Consensus II (TASC-II) class was collected. Postoperative duplex was performed 1 week after the procedure, then every 3 months for the first year, then, every 6 months to check for patency. IBM-SPSS-22 was used for all analyses. RESULTS: Average age of the patients was 64.65 ± 73.4 years. 101 patients had 101 procedures performed on the left lower extremity; 86 patients had 86 procedures performed on the right lower extremity; 123 patients were male and 64 were female. Average length of follow-up was 13.1±9.7 months. Most common indication for intervention was claudication, followed by critical limb threatening ischemia. Restenosis and reintervention by groups can be seen in Table 1. No patients experienced limb loss. There were no statistically significant differences between any of the 3 groups and their limb loss, restenosis, or reintervention rates. CONCLUSIONS: Despite having multiple proven effects in improving certain clinical outcomes and a proven protective effect on endothelium by decreasing endothelial vascular reactivity, metformin does not appear to reduce restenosis or reintervention rates in patients receiving lower extremity nDESs in the SFA and/or popliteal artery.

Quantifying Anesthesia Exposure in Growing Rod Treatment for Early Onset Scoliosis.

BACKGROUND: Growing rod (GR) treatment for early-onset scoliosis requires repeated anesthesia exposure (AE). At a minimum, GR treatment requires AE for diagnostic imaging, index GR surgery, periodic lengthenings, and final fusion. Adjunct procedures and complication-related procedures also increase AE. To our knowledge, this is the first study to quantify AE in GR treatment and to establish preoperative expectations. METHODS: A single-center retrospective review of 16 patients who completed GR treatment and underwent final fusion. Duration of all AE related to GR treatment for "standard" care procedures (ie, advanced imaging, index surgery, lengthenings, final fusion) and "associated" care procedures (ie, revisions, adjunctive surgical procedures, wound-related complications) were reviewed. Etiologies were classified per the classification of early-onset scoliosis. Mean total anesthesia time (TAT) was tallied and analyzed for standard care and associated care procedures. RESULTS: There were 5 syndromic, 8 neuromuscular, and 3 idiopathic patients. The mean age at the first AE event related to GR treatment was 7.4 years (range, 3.8 to 11 y). Mean age at the index GR surgery and final fusion was 8.1 years (range, 3.9 to 14.4 y) and 12.8 years (range, 9.7 to 19 y), respectively. The percentage of TAT for each procedural category was 7% for advanced imaging, 14% for index GR, 14% for lengthenings, 21% for final fusion, 27% for revisions, 9% for adjunct surgery, and 9% for wound complications. Standard care procedures accounted for 55% of TAT, whereas associated care procedures accounted for 45%. CONCLUSIONS: This study quantified expected duration of AE in GR treatment. Revisions and final fusion contributed most to TAT. Given the recent controversy of repeated AE in young children, efficiency measures should be implemented to reduce AE and avoid duplication without compromising the goals of surgical treatment. Associated care procedures accounted for 45% of the total AE. LEVEL OF EVIDENCE: Level IV.

Randomized phase 2 trial of a coordinated breast cancer follow-up care program.

BACKGROUND: Previous research has demonstrated that cancer survivors often fail to receive recommended care and also undergo unnecessary care; this reduces care quality and increases costs. METHODS: This phase 2 trial randomized 100 stage 0 to IIIa breast cancer patients who had primary care providers within a large Massachusetts-based hospital network (with accessible online records) to either coordinated follow-up care (CC), which entailed a tailored survivorship care plan (SCP) and patient navigator calls every 3 months, or standard care (SC), which did not include an SCP or patient navigation, for 1 year after the completion of their last chemotherapy, surgery, or radiation treatment. The primary endpoint was the frequency of redundant examinations (>1 breast/chest wall examination per patient within any 30-day period in the absence of a new breast or chest wall complaint) over the year of follow-up. The total number of non-plastic surgery visits in the year of follow-up was a secondary endpoint. RESULTS: Two patients (both on CC) were ineligible, and 2 patients (1 per arm) had a recurrence or died during follow-up; this left 96 for analysis (47 in the CC arm and 49 in the SC arm). Twenty-two of the 47 CC patients (47%; 95% confidence interval, 32%-62%) and 19 of the 49 SC patients (39%; 95% confidence interval, 25%-54%) had 1 or more redundant breast/chest wall examinations during the year. The median number of non-plastic surgery visits was 12 for CC patients and 8 for SC patients. CONCLUSIONS: Early-stage breast cancer patients visit health care providers very frequently during their first year of follow-up and often receive unnecessary breast/chest wall examinations. An SCP and patient navigator calls did not reduce this surrogate for redundant care. Cancer 2016;122:3546-3554. © 2016 American Cancer Society.

New Minimally Invasive Technique for Direct Pars Interarticularis Osteosynthesis Using Cortical Screws and Spinous-Process Modular Link.

STUDY DESIGN: Case report. OBJECTIVE: To report a case of direct pars osteosynthesis using computed topography (CT) navigation, image guided cortically placed screws with curvilinear subspinous modular link. SUMMARY OF BACKGROUND DATA: Spondylolysis fracture is commonly encountered in athletes who subject their spines to repetitive hyperextension stress. Initial treatment is nonoperative, consisting of rest, activity modification, physical therapy, and/or bracing. When nonoperative treatment is deemed unsuccessful, surgery may be recommended. METHODS: A 17-year-old male, competitive rower, presented with 3 months of a traumatic low-back pain without radicular symptoms. After a 9-month period of nonoperative management, the patient was submitted to surgery. Using navigation, cortical screws were placed in the standard inferomedial to superolateral trajectory crossing the fracture lines. A rod was contoured in a curvilinear fashion and passed through the L4-5 interspinous ligament and connected to the screw tulip heads. RESULTS: Patient did well postoperatively and remained neurologically intact throughout his course. CT performed at 1 year demonstrated healed fracture sites without signs of fixation loosening or failure. Patient underwent removal of retained fixation approximately 16 months after surgery. Patient has returned to rowing and all sports activities with no restrictions and no reported lower back pain. CONCLUSION: This technique offers a novel solution for the treatment of pars fractures through a minimally invasive, relative muscle-sparing approach by not compromising healing potential and preserving the native facet joint. LEVEL OF EVIDENCE: 4.

Motor evoked potentials for femoral nerve protection in transpsoas lateral access surgery of the spine.

Detecting potential intraoperative injuries to the femoral nerve should be the main goal of neuromonitoring of lateral lumber interbody fusion (LLIF) procedures. We propose a theory and technique to utilize motor evoked potentials (MEPs) to protect the femoral nerve (a peripheral nerve), which is at risk in LLIF procedures. MEPs have been advocated and widely used for monitoring spinal cord function during surgical correction of spinal deformity and surgery of the cervical and thoracic spine, but have had limited acceptance for use in lumbar procedures. This is due to the theoretical possibility that MEP recordings may not be sensitive in detecting an injury to a single nerve root considering there is overlapping muscle innervation of adjacent root levels. However, in LLIF procedures, the surgeon is more likely to encounter lumbar plexus elements than nerve roots. Within the substance of the psoas muscle, the L2, L3, and L4 nerve roots combine in the lumbar plexus to form the trunk of the femoral nerve. At the point where the nerve roots become the trunk of the femoral nerve, there is no longer any alternative overlapping innervation to the quadriceps muscles. Insult to the fully formed femoral nerve, which completely blocks conduction in motor axons, should theoretically abolish all MEP responses to the quadriceps muscles. On multiple occasions over the past year, our neuro-monitoring groups have observed significantly degraded amplitudes of the femoral motor and/or sensory evoked potentials limited to only the surgical side. Most of these degraded response amplitudes rapidly returned to baseline values with a surgical intervention (i.e., prompt removal of surgical retraction).

What makes a top research medical school? A call for a new model to evaluate academic physicians and medical school performance.

Since the publication of the Flexner Report in 1910, the medical education enterprise has undergone many changes to ensure that medical schools meet a minimum standard for the curricula and clinical training they offer students. Although the efforts of the licensing and accrediting bodies have raised the quality of medical education, the educational processes that produce the physicians who provide the best patient care and conduct the best biomedical research have not been identified. Comparative analyses are powerful tools to understand the differences between institutions, but they are challenging to carry out. As a result, the analysis performed by U.S. News & World Report (USN&WR) has become the default tool to compare U.S. medical schools. Medical educators must explore more rigorous and equitable approaches to analyze and understand the performance of medical schools. In particular, a better understanding and more thorough evaluation of the most successful institutions in producing academic physicians with biomedical research careers are needed. In this Perspective, the authors present a new model to evaluate medical schools' production of academic physicians who advance medicine through basic, clinical, translational, and implementation science research. This model is based on relevant and accessible objective criteria that should replace the subjective criteria used in the current USN&WR rankings system. By fostering a national discussion about the most meaningful criteria that should be measured and reported, the authors hope to increase transparency of assessment standards and ultimately improve educational quality.

Mexiletine Prevents Recurrent Torsades de Pointes in Acquired Long QT Syndrome Refractory to Conventional Measures.

OBJECTIVES: The purpose of this study was to examine the role of mexiletine, a late sodium current (INa-L) blocker, in acute termination of torsades de pointes (TdP) refractory to conventional therapy in acquired long QT syndromes (LQTS). BACKGROUND: Long QT interval can predispose to TdP and is therefore associated with significant mortality. Currently, there is no available pharmacotherapy to target directly the ionic basis of most LQTS for the acute termination of TdP. Earlier evidence highlighted the role of INa-L in the pathophysiology of long QT and TdP, particularly in patients with congenital LQTS. METHODS: Twelve patients with TdP caused by acquired LQTS were treated with mexiletine after failure of conventional treatment including discontinuation of QT-prolonging drugs, intravenous administration of magnesium, and correction of serum electrolyte abnormalities. RESULTS: No recurrence of TdP occurred within 2 h after initiation of treatment with mexiletine in all 12 patients. Macro T-wave alternans accompanied by QT prolongation, an electrocardiographic precursor of TdP that was seen in 3 patients, was also abolished by mexiletine. Treatment with mexiletine shortened the QTc interval from 599 ± 27 ms to 514 ± 16 ms (p = 0.001). The interval from the peak to the end of the T-wave (Tp-e interval) decreased from 145 ± 18 ms to 106 ± 9 ms (p = 0.005). The Tp-e/QT ratio decreased from 0.27 ± 0.02 to 0.23 ± 0.018 (p = 0.01). Mexiletine had no significant effect on QRS complex duration. CONCLUSIONS: INa-L blockade with mexiletine may be an effective treatment approach to terminate refractory TdP from several acquired causes of LQTS.

Targeting CD137 enhances the efficacy of cetuximab.

Treatment with cetuximab, an EGFR-targeting IgG1 mAb, results in beneficial, yet limited, clinical improvement for patients with head and neck (HN) cancer as well as colorectal cancer (CRC) patients with WT KRAS tumors. Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells contributes to the efficacy of cetuximab. The costimulatory molecule CD137 (4-1BB) is expressed following NK and memory T cell activation. We found that isolated human NK cells substantially increased expression of CD137 when exposed to cetuximab-coated, EGFR-expressing HN and CRC cell lines. Furthermore, activation of CD137 with an agonistic mAb enhanced NK cell degranulation and cytotoxicity. In multiple murine xenograft models, including EGFR-expressing cancer cells, HN cells, and KRAS-WT and KRAS-mutant CRC, combined cetuximab and anti-CD137 mAb administration was synergistic and led to complete tumor resolution and prolonged survival, which was dependent on the presence of NK cells. In patients receiving cetuximab, the level of CD137 on circulating and intratumoral NK cells was dependent on postcetuximab time and host FcyRIIIa polymorphism. Interestingly, the increase in CD137-expressing NK cells directly correlated to an increase in EGFR-specific CD8+ T cells. These results support development of a sequential antibody approach against EGFR-expressing malignancies that first targets the tumor and then the host immune system.

Electrical failure of an ICD lead due to a presumed insulation defect only diagnosed by a maximum output shock.

A 55-year-old male patient presented after a single shock caused by oversensing of isolated nonphysiologic signals on both the distal HV and pace-sense channels. No other abnormalities were found. He subsequently returned complaining of device "vibration" and his St. Jude implantable defibrillator (ICD; St. Jude Medical, St. Paul, MN, USA) was found to be in VVI backup mode and could not be interrogated. Direct testing in the electrophysiology lab showed normal lead impedances and thresholds with an inability to reproduce the abnormal signals. Detailed cine fluoroscopy of the leads found no abnormalities. A new ICD was connected and successfully delivered a 20-joule shock but failed to deliver a maximum output (39-joule) shock. The new ICD was again found to be in backup mode. A new Endotak Reliance G lead (Boston Scientific, Natick, MA, USA) was implanted and a maximum-output shock was successful using a new Fortify DR ICD. This case likely represents a Durata lead insulation defect in the form of an inside-out abrasion under the distal HV coil. Increased awareness of this defect is warranted, particularly since routine interrogation and submaximum-output shocks may fail to detect the problem.