Citations

Introduction: Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs. Methods: We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled. Results: Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197–2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027–2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1). Conclusions: Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.

The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor–related diarrhea/colitis and cardiovascular irAEs.

AbstractBackgroundPeripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to‐date.MethodsThis multicenter IRB‐approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow‐up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature.ResultsThe study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time‐to‐repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50–70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit.ConclusionsThese findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.

Abstract BACKGROUND Aneurysm recurrence after coiling has been associated with aneurysm growth, (re)hemorrhage, and a greater need for follow-up. The second-generation HydroCoil Embolic System (HES; MicroVention, Inc) consists of a platinum core with integrated hydrogel and was developed to reduce recurrence through enhancing packing density and healing within the aneurysm. OBJECTIVE To compare recurrence between the second-generation HES and bare platinum coil (BPC) in the new-generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT). METHODS HEAT is a randomized, controlled trial that enrolled subjects with ruptured or unruptured 3- to 14-mm intracranial aneurysms amenable to coiling. The primary endpoint was aneurysm recurrence using the Raymond-Roy scale. Secondary endpoints included minor and major recurrence, packing density, adverse events related to the procedure and/or device, mortality, initial complete occlusion, aneurysm retreatment, hemorrhage from target aneurysm during follow-up, aneurysm occlusion stability, and clinical outcome at final follow-up. RESULTS A total of 600 patients were randomized (HES, n = 297 and BPC, n = 303), including 28% with ruptured aneurysms. Recurrence occurred in 11 (4.4%) subjects in the HES arm and 44 (15.4%) subjects in the BPC arm ( P = .002). While the initial occlusion rate was higher with BPC, the packing density and both major and minor recurrence rates were in favor of HES. Secondary endpoints including adverse events, retreatment, hemorrhage, mortality, and clinical outcome did not differ between arms. CONCLUSION Coiling of small-to-medium aneurysms with second-generation HES resulted in less recurrence when compared to BPC, without increased harm. These data further support the use of the second-generation HES for the embolization of intracranial aneurysms. Video Abstract

BACKGROUND: Restorative total proctocolectomy with IPAA may not be feasible in some patients because of technical intraoperative limitations. OBJECTIVE: This study aimed to assess preoperative predictors for intraoperative IPAA and review management. DESIGN: This is a retrospective review. SETTING: This study was conducted at Cleveland Clinic between January 2010 and May 2018. PATIENTS: Patients ≥18 years of age who underwent ileoanal pouch surgery were included. Patients with successful pouch creation as planned were grouped as “successful IPAA creation.” Operative reports of patients who underwent alternative procedures were reviewed to identify cases when the pouch was preoperatively planned but intraoperatively abandoned (IPAA-abandoned group). Multivariate logistic regression models were developed to determine predictors of intraoperative pouch abandonment. We also reviewed the management of patients in whom the initial pouch creation failed. MAIN OUTCOME MEASURES: The primary outcomes measured were preoperative predictors for intraoperative ileoanal pouch abandonment. RESULTS: A total of 1438 patients were offered an ileoanal pouch; 21 (1.5%) experienced pouch abandonment due to inadequate reach (n = 17) and other technical reasons (n = 4). These patients underwent alternative procedures such as end or loop ileostomy with/without proctectomy. Multivariate logistic regression analysis indicated male sex (OR, 6.021; 95% CI, 1.540–23.534), BMI (OR, 1.217; 95% CI, 1.114–1.329), and a 2-stage procedure (OR, 14.510; 95% CI, 4.123–51.064) as independent factors associated with intraoperative abandonment of pouch creation. Alternative procedures were total proctocolectomy with end ileostomy (n = 14) and total abdominal colectomy with end ileostomy without proctectomy (n = 7). Ultimately, pouch creation was achieved in 6 of 21 patients after a median interval of 8.8 (range, 4.1–34.8) months. All patients had intentional weight loss before a reattempt and total abdominal colectomy with end ileostomy without proctectomy as their initial procedure. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Ileoanal pouch abandonment is rare and can be mitigated by initial total abdominal colectomy and weight loss. Male, obese patients are at a higher risk of failure. Intraoperative assessment of ileoanal pouch feasibility should occur before rectal dissection. See Video Abstract at http://links.lww.com/DCR/B156. PREDICCIÓN MULTIVARIANTE DEL ABANDONO INTRAOPERATORIO DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL ANTECEDENTES: La proctocolectomía total restaurativa con anastomosis de bolsa ileoanal puede no ser posible en algunos pacientes debido a limitaciones técnicas intraoperatorias. OBJETIVO: Evaluar los predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal y revisar el manejo. DISEÑO: Revisión retrospectiva. MARCO: Cleveland Clinic entre Enero de 2010 y mayo de 2018. PACIENTES: Pacientes > 18 años que se sometieron a cirugía de bolsa ileoanal. Los pacientes con una creación exitosa de la bolsa según lo planeado se agruparon como “creación exitosa de anastomosis de bolsa ileoanal”. Se revisaron los informes operativos de los pacientes que se sometieron a procedimientos alternativos para identificar los casos en que la bolsa se planificó preoperatoriamente pero se abandonó intraoperatoriamente (grupo de “anastomosis anal de bolsa ileoanal abandonada”). Se desarrollaron modelos de regresión logística multivariante para determinar los predictores del abandono intraoperatorio de la bolsa. También revisamos el manejo de pacientes que fallaron en la creación inicial de la bolsa. MEDIDAS DE RESULTADOS PRINCIPALES: Predictores preoperatorios para el abandono intraoperatorio de la bolsa ileoanal. RESULTADOS: A un total de 1438 pacientes se les ofreció una bolsa ileoanal; 21 (1.5%) experimentaron abandono de la bolsa debido a un alcance inadecuado (n = 17) y otras razones técnicas (n = 4). Estos pacientes se sometieron a procedimientos alternativos como ileostomía final o de asa con / sin proctectomía. El análisis de regresión logística multivariante indicó género masculino (OR, 6.021; IC 95%, 1.540–23.534), índice de masa corporal (OR, 1.217; IC 95%, 1.114–1.329) y procedimiento en 2 etapas (OR, 14.510; IC 95%, 4.123–51.064) como factores independientes asociados con el abandono intraoperatorio de la creación de la bolsa. Los procedimientos alternativos fueron la proctocolectomía total con ileostomía final (n = 14) y la colectomía abdominal total con ileostomía final sin proctectomía (n = 7). Finalmente, la creación de la bolsa se logró en 6/21 pacientes después de un intervalo medio de 8.8 (rango, 4.1–34.8) meses. Todos los pacientes tuvieron pérdida de peso intencional antes de la reintenta y colectomía abdominal total con ileostomía final sin proctectomía como procedimiento inicial. LIMITACIONES: Naturaleza retrospectiva. CONCLUSIONES: El abandono de la bolsa ileoanal es raro y puede mitigarse mediante la colectomía abdominal total inicial y la pérdida de peso. Los pacientes masculinos y obesos tienen un mayor riesgo de fracaso. La evaluación intraoperatoria de la viabilidad de la bolsa ileoanal debe ocurrir antes de la disección rectal. Consulte Video Resumen en http://links.lww.com/DCR/B156. (Traducción—Dr. Yesenia Rojas-Kahlil)

746 Background: Pelareorep is a proprietary formulation of live, replication-competent, naturally occurring Reovirus Type 3 Dearing strain. A randomized phase II trial of pelareorep in combination with carboplatin and paclitaxel in first-line treatment of metastatic PDAC (NCT01280058) was performed. Although pelareorep did not improve the primary endpoint of progression-free survival compared to carboplatin and paclitaxel alone, impressive durable responses were seen in the pelareorep arm in some patients (pts). Further, prior studies have noted the immunomodulatory carcinoembryonic antigen-related cell adhesion molecule (CEACAM6/CD66c) as a receptor for specific viral subtypes. We thus speculated that altered CEACAM6 levels may be predictive for pelareorep sensitivity. Methods: Pre-treatment tissue biopsies were collected prior enrolment for all 73 pts on study. Evaluable pts with transcriptomic data was available for only 31 pts. RNA was purified from FFPE tissue and gene expression analysis was performed using SensationPlus FFPE Amplification and WT labelling kit and the Human Transcriptome Array 2.0. CEACAM6 protein expression was determined by immunohistochemistry. Differential gene expression and survival analysis using were performed in R/Bioconductor. Appropriate corrections for multiplicity were performed. Results: When comparing extraordinary responders in the pelareorep treated arm to those with poor outcomes, low levels of CEACAM6 mRNA expression were associated with prolonged PFS in pelareorep-treated pts (adjusted p = 0.05). This effect was not seen in non-pelareorep treated pts. The luminal, but not the cytoplasmic immunohistochemistry score, was highly correlated with mRNA expression levels of CEACAM6, p = 0.001. Modulation of CEACAM6 in vitro and in vivo are underway. Conclusions: CEACAM6 may be a candidate biomarker of sensitivity to pelareorep and, in theory, could improve viral trafficking of this compound in tumor cells. Clinical trial information: NCT01280058 . [Table: see text]

40 Background: Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. Methods: US HIPEC Collaborative (2000-17) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. Analysis was stratified by non-invasive appendiceal neoplasm vs invasive appendiceal/colorectal adenocarcinoma. POCs were grouped into infectious, cardiopulmonary, thromboembolic and intestinal dysmotility. Primary outcomes were 3-yr overall survival (OS) and recurrence-free survival (RFS). Results: Of 1304 pts, median age was 55 yrs, 41% were male (n = 537), 33% had non-invasive appendiceal (n = 426) and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the non-invasive appendiceal cohort, POCs were identified in 55% (n = 233) and OS and RFS did not differ between patients who experienced a complication and those who did not (OS 94 vs 94% p = 0.26; RFS 68 vs 60% p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased OS (59 vs 74% p < 0.001) and RFS (32 vs 42% p < 0.001). Infectious POCs were most common (35%; n = 196). On MV analysis accounting for gender, PCI and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared to no complication (HR 2.08 95%CI 1.48-2.93 p < 0.01) or other types of complications (HR 1.7 95%CI 1.28-2.25 p < 0.01). This association persisted for infectious POCs and reduced RFS (HR 1.61 95%CI 1.23-2.10 p < 0.01). Conclusions: Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease like non-invasive appendiceal neoplasm. Of all complication types, infectious complications are the main driver for this association. The exact mechanism is not known, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious POCs.

Objective: Ringer’s lactate may improve early systemic inflammation during critical illnesses like severe acute pancreatitis, which are associated with hypocalcemia. Ringer’s lactate is buffered and contains lactate and calcium. We, thus analyzed extracellular calcium or lactate’s effects on the mechanisms, intermediary markers, and organ failure in models mimicking human disease with nonesterified fatty acid (NEFA) elevation. Methods: Meta-analyses and experimental studies were performed. Experimentally, extracellular calcium and lactate were compared in their interaction with linoleic acid (LA; a NEFA increased in human severe pancreatitis), and its subsequent effects on mitochondrial depolarization and cytosolic calcium signaling resulting in cell injury. In vivo, the effect of LA was studied on organ failure, along with the effect of calcium or lactate (pH 7.4) on severe acute pancreatitis-associated organ failure. A meta-analysis of human randomized control trials comparing Ringer’s lactate to normal saline was done, focusing on necrosis and organ failure. Results: Calcium reacted ionically with LA and reduced lipotoxic necrosis. In vivo, LA induced organ failure and hypocalcemia. During severe pancreatitis, calcium supplementation in saline pH 7.4, unlike lactate, prevented hypocalcemia, increased NEFA saponification, reduced circulating NEFA and C-reactive protein, reduced pancreatic necrosis adjacent to fat necrosis, and normalized shock (carotid pulse distension) and blood urea nitrogen elevation on day 1. This, however, did not prevent the later increase in serum NEFA which caused delayed organ failure. Meta-analysis showed Ringer’s lactate reduced necrosis, but not organ failure, compared with normal saline. Conclusion: Hypocalcemia occurs due to excess NEFA binding calcium during a critical illness. Ringer’s lactate’s early benefits in systemic inflammation are by the calcium it provides reacting ionically with NEFA. This, however, does not prevent later organ failure from sustained NEFA generation. Future studies comparing calcium supplemented saline resuscitation to Ringer’s lactate may provide insights to this pathophysiology.