Accuracy of Early Neuroprognostication in Pediatric Severe Traumatic Brain Injury.

BACKGROUND: Children with severe traumatic brain injury (sTBI) are at risk for neurological sequelae impacting function. Clinicians are tasked with neuroprognostication to assist in decision-making. We describe a single-center study assessing clinicians' neuroprognostication accuracy. METHODS: Clinicians of various specialties caring for children with sTBI were asked to predict their patients' functioning three to six months postinjury. Clinicians were asked to participate in the study if their patient had survived but not returned to baseline between day 4 and 7 postinjury. The outcome tool utilized was the functional status scale (FSS), ranging from 6 to 30 (best-worst function). Predicted scores were compared with actual scores three to six months postinjury. Lin concordance correlation coefficients were used to estimate agreement between predicted and actual FSS. Outcome was dichotomized as good (FSS 6 to 8) or poor (FSS ≥9). Positive and negative predictive values for poor outcome were calculated. Pessimistic prognostic prediction was defined as predicted worse outcome by ≥3 FSS points. Demographic and clinical variables were collected. RESULTS: A total of 107 surveys were collected on 24 patients. Two children died. Fifteen children had complete (FSS = 6) or near-complete (FSS = 7) recovery. Mean predicted and actual FSS scores were 10.8 (S.D. 5.6) and 8.6 (S.D. 4.1), respectively. Predicted FSS scores were higher than actual scores (P < 0.001). Eight children had collective pessimistic prognostic prediction. CONCLUSIONS: Clinicians predicted worse functional outcomes, despite high percentage of patients with near-normal function at follow-up clinic. Certain patient and provider factors were noted to impact accuracy and need to be studied in larger cohorts.

Implications of drug intoxication on donor utilization and outcomes in liver transplantation.

INTRODUCTION: This study evaluates the implications of drug intoxication (DI) on donor utilization and outcomes in liver transplantation (LT). METHODS: The UNOS STAR database was evaluated for all potential donors and adult, first-time, whole LT between 2005 and 2019. Logistic regression analyses evaluated liver utilization; proportional hazards modeling assessed risk of 1-year graft loss. RESULTS: A total of 132 783 potential donors (10 205, 7.7% from DI), and 90 612 adult LT were identified (7490, 8.3% from DI). DI donors had median age 32 years (IQR 26-40 years, p < .001), were 42.6% female (n = 4346), and 15.5% were DCD donors (n = 1583). Utilization of DI donors changed over time, such that by 2015-2019 they were the most likely donor cause of death (COD) to be utilized. Among LT recipients, there were insignificant differences (<2% variance) in age, gender, ethnicity, and etiology of liver disease according to donor COD. Recipients with MELD scores >30 more frequently received grafts from donors with trauma (23.8%) and DI (21.8%) versus cardiovascular (20.0%) and CVA/stroke (19.9%, p < .001). Among DBD donors, DI-COD was associated with superior 1-year graft survival compared to donors from trauma (HR 1.172, 95% CI 1.057-1.300) and CVA/stroke (HR 1.404, 95% CI 1.264-1.561, p < .001). Donor COD was not significantly associated with 1-year graft loss among DCD donors. CONCLUSIONS: There is an increased likelihood of donor utilization when COD is drug overdose and an increased likelihood of 1-year graft survival compared to donors from trauma, CVA/stroke, and other COD.

Total Synthesis of (-)-Amovillosumin A and Structure Correction of (-)-Amovillosumin C Using Chemical Synthesis.

Norlignans are a rare class of natural products isolated from a diverse range of plant species, many of which have interesting biological activities including antibacterial, antioxidant, phytotoxic, platelet aggregation inhibitory effects, and more. Isolated from Amomum villosum (Amomi Fructus), amovillosumins A (1) and C (3) are norlignans which were of interest to synthesize, due to their interesting bioactivities, specifically their ability to increase stimulation of glucagon-like peptide-1 (GLP-1) secretion. In this research, key intermediate 15 was used to stereoselectively synthesize (7R,8R)-amovillosumins A (1) and C (3). The developed method includes a Mitsunobu coupling, a modified rhodium-catalyzed Miyaura arylation, and an acid-catalyzed cyclization in key bond-forming steps. After synthesis, the structure of 1 was confirmed, but it was revealed that the benzodioxane-containing structure of amovillosumin C (3) that had been proposed in the literature was incorrect. Thus, with further investigation a structure correction of 3 was achieved by synthesis, the correct structure being 8-O-4'-oxynorlignan.

Incidence and Outcomes of Simultaneous Thoracoabdominal Triple Organ Transplantation in the United States.

BACKGROUND: This study aims to evaluate patient outcomes of simultaneous triple organ transplants, which may provide insight into optimal donor allocation while maximizing recipient benefit. METHODS: Triple organ transplants and their corollary dual organ transplants were identified using the United Network for Organ Sharing database. Triple organ transplants evaluated included heart-lung-kidney (n = 12) and heart-liver-kidney (n = 37). Heart-lung-kidney recipients were compared with heart-lung (n = 325), lung-kidney (n = 91), and heart-kidney (n = 2022) groups. Heart-liver-kidney recipients were compared with heart-liver (n = 451), liver-kidney (n = 10422), and heart-kidney (n = 2517) recipients. Patient survival outcomes were calculated using the Kaplan-Meier method and compared using log-rank tests. RESULTS: Patients undergoing triple organ transplants showed similar 10-year survival as their corresponding dual organ transplant cohorts. Patient survival estimate at 10 years for the heart-lung-kidney group was 45%, with no statistically significant difference in survival when compared with dual organ groups (P = .16). Survival estimates at 10 years for the heart-liver-kidney group was 49%, with no statistically significant difference in survival when compared with dual organ groups (P = .06). CONCLUSION: Despite the surgical burden of adding a third organ transplant, heart-liver-kidney and heart-lung-kidney have similar survival outcomes to dual organ equivalents and represent a reasonable allocation option in well-selected patients.

NCBI GEO: archive for gene expression and epigenomics data sets: 23-year update.

The Gene Expression Omnibus (GEO) is an international public repository that archives gene expression and epigenomics data sets generated by next-generation sequencing and microarray technologies. Data are typically submitted to GEO by researchers in compliance with widespread journal and funder mandates to make generated data publicly accessible. The resource handles raw data files, processed data files and descriptive metadata for over 200 000 studies and 6.5 million samples, all of which are indexed, searchable and downloadable. Additionally, GEO offers web-based tools that facilitate analysis and visualization of differential gene expression. This article presents the current status and recent advancements in GEO, including the generation of consistently computed gene expression count matrices for thousands of RNA-seq studies, and new interactive graphical plots in GEO2R that help users identify differentially expressed genes and assess data set quality. The GEO repository is built and maintained by the National Center for Biotechnology Information (NCBI), a division of the National Library of Medicine (NLM), and is publicly accessible at https://www.ncbi.nlm.nih.gov/geo/.

Awake craniotomy for supratentorial tumors or epileptogenic lesions in pediatric patients: a 16-year retrospective cohort study.

OBJECTIVE: Awake craniotomy with intraoperative mapping is the widely accepted procedure for adult patients undergoing supratentorial tumor or epileptogenic focus resection near eloquent cortex. In children, awake craniotomies are notably less common due to concerns for compliance and emotional or psychological repercussions. Despite this, successfully tolerated awake craniotomies have been reported in patients as young as 8 years of age, with success rates comparable to those of adults. The authors sought to describe their experience with pediatric awake craniotomies, including insight regarding feasibility and outcomes. METHODS: A retrospective review was completed for all pediatric (age < 18 years) patients at Children's Wisconsin for whom an awake craniotomy was attempted from January 2004 until March 2020. Institutional review board approval was granted. RESULTS: Candidate patients had intact verbal ability, cognitive profile, and no considerable anxiety concerns during neuropsychology assessment. Nine patients presented with seizure. Five patients were diagnosed with tumor and secondary epilepsy, 3 with tumor only, and 3 with epilepsy only. All patients who underwent preoperative functional MRI successfully completed and tolerated testing paradigms. A total of 12 awake craniotomies were attempted in 11 patients, with 1 procedure aborted due to intraoperative bleeding. One patient had a repeat procedure. The mean patient age was 15.5 years (range 11.5-17.9 years). All patients returned to or maintained baseline motor and speech functions by the latest follow-up (range 14-130 months). Temporary deficits included transient speech errors, mild decline in visuospatial reasoning, leg numbness, and expected hemiparesis. Of the 8 patients with a diagnosis of epilepsy prior to surgery, 7 patients achieved Engel class I designation at the 1-year follow-up, 6 of whom remained in class I at the latest follow-up. CONCLUSIONS: This study analyzes one of the largest cohorts of pediatric patients who underwent awake craniotomy for maximal safe resection of tumor or epileptogenic lesions. For candidate patients, awake craniotomy is safe, feasible, and effective in carefully selected children.

Robotic bilateral nephrectomy for large polycystic kidney disease.

Objective: This study aims to describe our technique and review our experience with synchronous robotic bilateral nephrectomy for large kidneys in ADPKD with the da Vinci XI and da Vinci Single Port platforms (Intuitive Surgical, Sunnyvale, CA). Materials and Methods: We performed a retrospective review of all robotic bilateral nephrectomy cases from January 2020 to present at a high-volume robotic single centre. Demographic data and perioperative details including preoperative CT scans, indication for nephrectomy and renal function were collected. We also collected post-op course data and final specimen data details. Results: Fourteen cases were included. Patient demographics, indications for surgery and specimen data are outlined in Table 1. The largest kidney removed has a measurement of 32 cm in the largest dimension on preoperative imaging. Median operating time from incision to closure was 299 min (IQR 260, 339). Median estimated blood loss was 75 cc (IQR 50, 187.5). Two patients were transfused intraoperatively. Median pre- and post-operative Hgb was 11.0 and 9.6, respectively. Median length of stay was 3 days (IQR 2, 3.5). There were no intraoperative complications and no open conversions. Post-operative complications included one incisional hematoma and one superficial wound infection. One patient was admitted to the surgical ICU post operatively for ventilatory support. Two patients were readmitted within 30 days of surgery. Conclusion: The robotic approach to bilateral native nephrectomy for ADPKD should be considered when native nephrectomies are indicated. The operative times and outcomes are favourable compared with prior series, and this technique works even for very large kidneys.

Preserved 2-y Liver Transplant Outcomes Following Simultaneous Thoracoabdominal DCD Organ Procurement Despite Effects on Liver Utilization Rate.

Background: Current techniques for donation after circulatory determination of death (DCD) heart procurement, through either direct procurement and machine perfusion or thoracoabdominal normothermic regional perfusion (NRP), have demonstrated excellent heart transplant outcomes. However, the impact of thoracoabdominal DCD (TA-DCD) heart procurement on liver allograft outcomes and utilization is poorly understood. Methods: One hundred sixty simultaneous heart and liver DCD donors were identified using the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between December 2019 and July 2021. Liver outcomes from TA-DCD donors were stratified by heart procurement technique and evaluated for organ utilization, graft survival, and patient survival. Results were compared with abdominal-only DCD (A-DCD; n = 1332) and donation after brain death (DBD; n = 12 891) liver transplants during the study interval. Kaplan-Meier methods with log-rank testing were used to evaluate patient and graft survival. Results: One hundred thirty-three of 160 livers procured from TA-DCD donors proceeded to transplant. TA-DCD donors were younger (mean 28.26 y; P < 0.0001) with lower body mass index (mean 26.61; P < 0.0001) than A-DCD and DBD donors. TA-DCD livers had equivalent patient survival ( P = 0.893) and superior graft survival (P = 0.009) compared with A-DCD. TA-DCD livers had higher rates of organ discard for long warm ischemia time (37.0%) than A-DCD (20.5%) and DBD (0.5%; P < 0.0001), with direct procurement and machine perfusion procurements leading to a higher discard rate (18.5%) than NRP procurements (7.4%). Conclusions: Liver transplants after TA-DCD donation demonstrated equivalent patient outcomes and excellent graft outcomes. NRP procurements resulted in the lowest rate of organ discard after DCD donation and may represent an optimal strategy to maximize organ utilization.

Rationale for the Development of a Novel Clinical Grading Scale for Postoperative Facial Nerve Function: Results of a Multidisciplinary International Working Group.

OBJECTIVE: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. STUDY DESIGN: Survey. SETTING: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. RESULTS: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. CONCLUSIONS: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.

A Female Patient Recently Diagnosed with Sjogren Syndrome Presents to the Dental Office Seeking Upper and Lower Complete Dentures.

Sjogren syndrome (SS) is a common autoimmune disease associated with the immune-mediated destruction of exocrine glands, primarily the salivary and lacrimal glands. As a result, patients have xerophthalmia and xerostomia (Sicca syndrome). The diagnosis of SS can be difficult due to its multifactorial nature and often insidious symptoms, and there is no one test for its diagnosis. The many oral manifestations in SS stemming from the xerostomia present challenges to the treating dentist. Dentists should be knowledgeable about SS and its palliative care to help improve their patients' quality of life.

A Patient with a History of Multiple Myeloma Presents for the Evaluation of Oral Lesion and Burning Sensation of the Mouth.

Multiple myeloma (MM) is a hematologic malignancy belonging to a class of disorders known as plasma cell dyscrasias. Common oral manifestations of MM include osteolytic lesions in the mandible and maxilla that can present as painful bony swellings, epulis formation, or sudden teeth movement. MM treatment is coordinated by a multidisciplinary team and is dependent upon the age and physical fitness of the patient, as well as the staging of the disease. A large proportion will be treated with intravenous bisphosphonates, such as pamidronate and zoledronic acid, which places the patients at high risk for developing medication-related osteonecrosis of the jaw (MRONJ).

A Patient Presenting for Dental Extraction After Completion of Chemotherapy.

Acute myeloid leukemia (AML) presents several oral manifestations, including gingival hyperplasia, pale mucosa, poor wound healing, petechiae, ecchymoses, candidiasis, recurrent herpes infection, and ulcerations in the oral mucosa. Chemotherapy is the first-line treatment of AML. Common dental complications of chemotherapy include mucositis, infections secondary to profound bone marrow aplasia, and gingival bleeding. When treating patients with AML, preparing a comprehensive treatment plan is essential to help minimize their risks for developing these oral complications.

A Patient Presents for Dental Extraction and Goes into Sickle Cell Crisis in the Dental Chair.

Sickle Cell Disease is an inherited autosomal recessive hemoglobinopathy associated with multiorgan damage. This single gene disorder involves one DNA base pair alteration, producing HbS. The sickle-shaped cells form when deoxygenated in the capillaries. The resulting RBC stasis leads to ischemia and pain, and acute and chronic organ damage. Patients with SCD presenting to a dental office need careful examination to rule out any current infections, neurologic deficits, or other organ involvement before formulating a dental treatment plan to avoid prolonged and complicated procedures. Early intervention and dental anxiety management are key to the dental treatment of patients with SCD.

A Patient with Herpes Zoster of the Maxillary Division of Trigeminal Nerve Presents for Oral Evaluation and Toothache.

Herpes zoster (HZ) is an acute and painful neurocutaneous infection caused by the reactivation of a latent varicella-zoster virus in the dorsal root or cranial nerve ganglia. It is characterized by 3 stages: prodromal, acute, and chronic. During the prodromal stage, reactivation in the maxillary branch of the trigeminal nerve closely mimics odontalgia, and HZ should be in the differential diagnosis. Patients with HZ develop painful lesions following the affected dermatome. Laboratory testing confirms the diagnosis; treatment is with antiviral agents. Early detection and treatment shorten the course of the infection and lessen the severity of the associated postherpetic neuralgia.

A Patient Diagnosed with Bulimia Reports to the Dental Office Seeking Cosmetic Dental Work.

Bulimia nervosa (BN) is a serious psychiatric illness that typically occurs in adolescents and young adults. It is characterized by recurring episodes of consuming large amounts of food with an inappropriate compensatory behavior of purging to prevent weight gain. The purging behavior results in oral manifestations such as dental erosion, dental caries, sialadenosis, and oral mucosal trauma. Medical complications include electrolyte imbalances, esophageal rupture, and renal and cardiovascular failure. Treatment of BN involves psychosocial and psychopharmacologic approaches. Dentists are in a unique position to recognize patients with BN and help patients with BN and other eating disorders.

Drug Overdose and Cardiovascular Deaths Among Deceased Organ Donors: Implications for Donor Utilization and Data Reporting.

BACKGROUND The present study evaluated expanded cause of death (COD) definitions and its implications on donor utilization for solid organ transplantation. MATERIAL AND METHODS The OPTN Standard Transplant and Research file was queried for potential donors between 2005 and 2019. Donor- and organ-specific utilization were evaluated. Expanded donor COD were identified: trauma, cardiovascular (CV), cerebrovascular accident (CVA) or stroke, drug intoxication (DI), anoxia not otherwise specified (NOS), and other. Descriptive analyses and multivariable logistic regression analyses for donor utilization were performed. RESULTS Among 132 783 potential donors identified, the most common COD was CVA/Stroke (n=44 707, 33.7%), followed by trauma (n=43 356, 32.7%), CV (n=20 053, 15.1%), anoxia-NOS (n=12 261, 9.2%), DI (n=10 205, 7.7%), and other causes (n=2201, 1.7%). Significant differences between CV, DI, and anoxia-NOS groups existed for donor age, sex, ethnicity, body mass index, and comorbidities. Donors from trauma had the highest unadjusted utilization rate (97.2%) while CV donors had the lowest (90.1%). Multivariable analysis of brain-dead donors (DBD) showed that compared to trauma, donors from DI had higher likelihood of utilization (odds ratio 1.217, 95% 1.025-1.446) while CV donors were lower (OR 0.717, 95% CI 0.642-0.800, P<0.001). Among donation after circulatory death (DCD) donors, there was decreased utilization compared to trauma for both CV (OR 0.607, 95% CI 0.523-0.705) and DI (OR 0.754, 95% CI 0.603-0.914, P<0.001). CONCLUSIONS Current COD definitions should be expanded to capture significant differences in the donor population. DI donors are the fastest growing cohort and the most likely utilized DBD donors, while trauma donors remain the most likely utilized DCD donors.

Neural representations of self-perception of voice: An intracortical evoked potential analysis based on an adolescent with right temporal lobe epilepsy.

INTRODUCTION: The neural bases for language perception have been studied elsewhere using Transcranial Magnetic Stimulation, functional Magnetic Resonance Imaging and Direct Cortical Stimulation. However, to our knowledge, there is no previous report about a patient identifying the change in his voice tone, speed, and prosody because of right temporal cortical stimulation. Nor has there been a cortico-cortical evoked potential (CCEP) assessment of the network underlying this process. CASE REPORT: We present CCEP from a patient with right focal refractory temporal lobe epilepsy of tumoral etiology who reported changes in the perception of his own speech prosody during stimulation. This report will serve as a complement to the understanding of the neural networks of language and prosody. CONCLUSION: The present report shows that right superior temporal gyrus, transverse temporal gyrus, right amygdala, hippocampus, and fusiform gyrus (FG) are part of the neural network subjacent to own human voice perception.

Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs.

INTRODUCTION: The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. METHODS: Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. RESULTS: The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p = 0.045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0.0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0.05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p = 0.24 and 0.79 respectively). CONCLUSIONS: Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes.

Total Synthesis of Linear Coumarniolignoids (+) and (-)-Sapiumin C, (-)-Moluccanin, and (-)-Hemidesminine.

Coumarinolignoids (CLs) are a class of natural products isolated from a diverse range of plant species. Due to their unique structural scaffold, they exhibit a wide range of interesting biological activities including hepatoprotective, antitumor, anti-inflammatory, and antioxidant activities among others. In this research, key intermediate 10 was used to stereoselectively synthesize CLs (7'S,8'S)- and (7'R,8'R)-sapiumin C 1 and 2, (7'S,8'S)-moluccanin 3, and (7'S,8'S) hemidesminine 4 for the first time, establishing a versatile synthetic method for the stereoselective synthesis of linear CLs. The developed method includes a Mitsunobu coupling, a modified Miyaura arylation via a rhodium catalyst, and an acid-catalyzed cyclization in key bond-forming steps. The developed synthetic route allows the synthesis of both enantiomers of a given natural product from the same chiral pool reagent (S)-solketal while allowing easy variation of aromatic substitution and hydroxymethyl/allylhydroxymethyl moieties that are common in this class of natural products.