Citations

BACKGROUND: There has recently been increasing interest in the use of spinal anesthesia (SA) for spine surgery. The literature that compared spine surgery under SA vs general anesthesia (GA) focused on safety, perioperative outcomes, and costs. OBJECTIVE: To test if SA is associated with less postoperative fatigue, cognitive dysfunction, and better quality of life in patients undergoing lumbar spine surgery compared with GA. METHODS: We conducted a prospective nonrandomized study in patients undergoing elective lumbar spine surgery under SA or GA by a single surgeon. Fatigue was assessed with the fatigue visual analog scale scale (0-10) and Chalder Fatigue Scale, quality of life with Medical Outcomes Study 12-item Short Form (SF-12), and differences in cognition with Mini-Mental State Examination. Patients were baselined before surgery and assessed again 1 mo after surgery. RESULTS: Fifty patients completed the study, 25 underwent surgery under SA and 25 under GA. The groups were homogeneous for baseline clinical characteristics, with no differences in preoperative fatigue, quality of life, and cognition. At 1 mo after surgery, SA compared with GA had better fatigue scores: fatigue visual analog scale (2.9 ± 1.5 vs 5.9 ± 2.3 [ P < .0001]) and Chalder Fatigue Scale (11.2 ± 3.1 vs 16.9 ± 3.9 [ P < .0001]). One month postoperatively, we observed a significant difference in the SF-12 physical component, with SA having 38.8 ± 8.9 vs 29.4 ± 10.3 ( P = .002). We did not observe significant postoperative differences in the SF-12 mental component or Mini-Mental State Examination. CONCLUSION: Our study demonstrates that SA offers unique patient-centered advantages to GA for elective spine surgery. One month after surgery, patients who received SA had less postoperative fatigue and better quality of life.

OBJECTIVE There has been increasing interest in the use of spinal anesthesia (SA) for spine surgery, especially within Enhanced Recovery After Surgery (ERAS) protocols. Despite the wide adoption of SA by the orthopedic practices, it has not gained wide acceptance in lumbar spine surgery. Studies investigating SA versus general anesthesia (GA) in lumbar laminectomy and discectomy have found that SA reduces perioperative costs and leads to a reduction in analgesic use, as well as to shorter anesthesia and surgery time. The aim of this retrospective, case-control study was to compare the perioperative outcomes of patients who underwent minimally invasive surgery (MIS)–transforaminal lumbar interbody fusion (TLIF) after administration of SA with those who underwent MIS-TLIF under GA. METHODS Overall, 40 consecutive patients who underwent MIS-TLIF by a single surgeon were analyzed; 20 patients received SA and 20 patients received GA. Procedure time, intraoperative adverse events, postoperative adverse events, postoperative length of stay, 3-hour postanesthesia care unit (PACU) numeric rating scale (NRS) pain score, opioid medication, and time to first ambulation were collected for each patient. RESULTS The two groups were homogeneous for clinical characteristics. A decrease in total operating room (OR) time was found for patients who underwent MIS-TLIF after administration of SA, with a mean OR time of 156.5 ± 18.9 minutes versus 213.6 ± 47.4 minutes for patients who underwent MIS-TLIF under GA (p < 0.0001), a reduction of 27%. A decrease in total procedure time was also observed for SA versus GA (122 ± 16.7 minutes vs 175.2 ± 10 minutes; p < 0.0001). No significant differences were found in intraoperative and postoperative adverse events. There was a difference in the mean maximum NRS pain score during the first 3 hours in the PACU as patients who received SA reported a lower pain score compared with those who received GA (4.8 ± 3.5 vs 7.3 ± 2.7; p = 0.018). No significant difference was observed in morphine equivalents received by the two groups. A difference was also observed in the mean overall NRS pain score, with 2.4 ± 2.1 for the SA group versus 4.9 ± 2.3 for the GA group (p = 0.001). Patients who received SA had a shorter time to first ambulation compared with those who received GA (385.8 ± 353.8 minutes vs 855.9 ± 337.4 minutes; p < 0.0001). CONCLUSIONS The results of this study have pointed to some important observations in this patient population. SA offers unique advantages in comparison with GA for performing MIS-TLIF, including reduced OR time and postoperative pain, and faster postoperative mobilization.

Abstract Background Niemann-Pick Disease Type C (NPC) is an autosomal recessive rare disease characterised by progressive neurovisceral manifestations. The collection of on-going large-scale NPC clinical data may generate better understandings of the natural history of the disease. Here we report NPC patient data from the International Niemann-Pick Disease Registry (INPDR). Method The INPDR is a web-based, patient-led independent registry for the collection of prospective and retrospective clinical data from Niemann-Pick Disease patients. Baseline data from NPC patients enrolled into the INPDR from September 2014 to December 2019 was extracted to analyse the demographic, genetic and clinical features. Results A total of 203 NPC patients from six European countries were included in this study. The mean age (SD) at diagnosis was 11.2 years (14.2). Among enrolled patients, 168 had known neurological manifestations; 43 (24.2%) had early-infantile onset, 47 (26.4%) had late-infantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. 10 (5.6%) patients had the neonatal rapidly fatal systemic form. Among the 97 patients with identified NPC1 variants, the most common variant was the c. 3182T > C variant responsible for the p.lle1061Thr protein change, reported in 35.1% (N = 34) of patients. The frequencies of hepatomegaly and neonatal jaundice were greatest in patients with early-infantile and late-infantile onset. Splenomegaly was the most commonly reported observation, including 80% of adult-onset patients. The most commonly reported neurological manifestations were cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (VSGP) (70.9%), dysphagia (69.6%). A 6-domain composite disability scale was used to calculate the overall disability score according to neurological-onset. Across all with neurological onset, the majority of patients showed moderate to severe impairments in all domains, excluding ‘swallowing’ and ‘seizure’. The age at diagnosis and death increased with increased age of neurological symptom onset. Miglustat use was recorded in 62.43% of patients and the most common symptomatic therapies used by patients were antiepileptics (32.94%), antidepressants (11.76%) and antacids (9.41%). Conclusion The proportion of participants at each age of neurological onset was relatively consistent across the cohort. Neurological manifestations, such as ataxia, dysphagia, and dysarthria, were frequently observed across all age categories.

Neutral lipids are a critical source for cellular energy and are stored within specialized organelles known as lipid droplets (LD). Degradation of LDs for energy utilization is accomplished by two principal pathways: lipolysis that is activated by cAMP to recruit adipose triglyceride lipase (ATGL) to the LD surface, and lipophagy that utilizes the autophagic machinery to target and traffic LDs for degradation by lysosomal acid lipase (LAL). However, the mechanisms underlying synergy between these seemingly distinct pathways are not well understood. Previous studies show that autpohagic membrane cannot effectively engulf large organelles, but is size‐restricted to small cargo. Based on this, we HYPOTHESIZE that lipolysis and lipophagy are sequential pathways whereby lipolysis first reduces the size of large LDs to allow for subsequent autophagic engulfment of small LDs for lipophagy. Methods Using light and electron microscopy combined with biochemical approaches, we explored LD size and the sequential nature of lipolysis and lipophagy in primary rat and AML12 hepatocytes. Live‐cell microscopy was used for the first time to monitor LDs transitioning from lipolysis in the cytoplasm to lipophagy within endolysosomal vesicles. Results Confocal microscopy of endogenous ATGL revealed a preferential association with large LDs with an average size of 4.0 μm 2 , seven‐fold larger than LDs not associated with ATGL. In striking comparison, LDs associated with components of the autophagic machinery (LC3, Lamp3) were 50% smaller in size (0.39 μm 2 ). Consistent with this observation, siRNA knockdown of ATGL resulted in the persistence of large LDs (2.8 μm 2 ), whereas knockdown of LAL left cells filled with numerous small LDs (1.5 μm 2 ). These observations were mimicked by inhibitors of ATGL (atglistatin) and LAL (lalistat). In support of these findings, differential centrifugation of AML12 homogenates allowed for separation of two distinct populations of LDs: a buoyant fraction of large LDs enriched in the cytosolic lipase ATGL, and a second collection of smaller, less buoyant LDs enriched in lysosomal enzymes such as Lamp2A, the autophagosome marker LC3‐II, and the endosomal marker Tsg101. Most interesting are time lapse movies of live cells showing engulfment of small LDs by a Lamp3‐positive late endosomal compartment, suggesting that these organelles play an important role in the direct targeting and engulfment of LDs for lipophagy. Conclusion Hepatocytes appear to catabolize LDs in a tandem stepwise process that first utilizes cytosolic lipases to substantially reduce LD size, thereby allowing for subsequent engulfment of small LDs by autophagosomes as well as late endosomes and lysosomes. Support or Funding Information Supported by NIAAA RO1AA020735 to MAM; NIDDK award T32DK007352 to MBS and RJS, and the Mayo Clinic Kogod Aging Fellowship to MBS. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Fatty liver disease affects 80–100 million Americans and is a precursor to irreversible and sometimes fatal liver damage. The initial stages of fatty liver disease are marked by the hepatocellular accumulation of fat‐storage organelles known as lipid droplets (LDs) that are degraded by two pathways: lipolysis that involves the recruitment of cytosolic lipases (ATGL, HSL) to the LD surface, and lipophagy that relies on autophagic membranes to target and traffic LDs for lysosomal degradation. Importantly, the mechanisms underlying a cooperation between these seemingly distinct pathways are not well understood. Previous studies have shown that the autophagic engulfment of cytosolic cargo is size‐restricted. Because of this, we HYPOTHESIZE that lipolysis and lipophagy occur as sequential processes initiated by cytosolic lipases to reduce LD size and allow for subsequent engulfment by autophagic membranes. Methods In AML12 hepatocytes, immunofluorescence microscopy and biochemical approaches were used to determine the enrichment of lipolysis vs lipophagy machinery on large vs. small LDs. Live‐cell microscopy was used for the first time to monitor LDs transitioning from lipolysis to lipophagic engulfment. Results Confocal microscopy of AML12 cells immunolabeled for adipose triglyceride lipase (ATGL) revealed a preferential association with large LDs with an average area of 4.0 μm 2 , seven‐fold larger than LDs not associated with ATGL. In striking comparison, LDs associated with components of the autophagic machinery (LC3) were two‐fold smaller in area (0.39 μm 2 ). Consistent with this observation was the finding that siRNA knockdown of ATGL resulted in the persistence of large LDs (2.8 μm 2 ), whereas knockdown of lysosomal acid lipase (LAL) left cells filled with many LDs of a smaller size (1.5 μm 2 ). These observations were mimicked by inhibitors of ATGL (atglistatin) and lysosomal acidification (chloroquine). In support of these findings, differential centrifugation of AML12 homogenates allowed for separation of two distinct populations of LDs: a buoyant fraction of large LDs enriched in the cytosolic lipase ATGL, and a second collection of smaller, less buoyant LDs enriched in lysosomal enzymes such as Lamp2A and the autophagosome marker LC3‐II. Most interesting are time lapse movies of live cells showing engulfment of small LDs by a LAMP3‐positive late endosomal/lysosomal compartment, suggesting that these organelles play an important role in the direct targeting and engulfment of LDs for lipophagy. Conclusion Hepatocytes appear to catabolize LDs in a tandem stepwise process that first utilizes cytosolic lipases to substantially reduce LD size, thereby allowing for subsequent engulfment by autophagosomes as well as late endosomes and lysosomes. Support or Funding Information This study was generously supported by funding from NIAAA R01AA020735, NIDDK T32DK007352, and the Mayo Clinic Robert and Arlene Kogod Center on Aging. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

AbstractAbsence seizures (AS), presenting as short losses of consciousness with staring spells, are a common manifestation of childhood epilepsy that is associated with behavioral, emotional, and social impairments. It has also been suggested that patients with AS are more likely to suffer from mood disorders such as depression and anxiety. This systematic review and meta‐analysis synthesizes human and animal models that investigated mood disorders and AS. Of the 1019 scientific publications identified, 35 articles met the inclusion criteria for this review. We found that patients with AS had greater odds of developing depression and anxiety when compared to controls (odds ratio = 4.93, 95% confidence interval = 2.91–8.35, p < .01). The included studies further suggest a strong correlation between AS and depression and anxiety in the form of a bidirectional relationship. The current literature emphasizes that these conditions likely share underlying mechanisms, such as genetic predisposition, neurophysiology, and anatomical pathways. Further research will clarify this relationship and ensure more effective treatment for AS and mood disorders.

Abstract The brain vital signs framework is a portable, objective, neurophysiological evaluation of brain function at point-of-care. We investigated brain vital signs at pre- and post-season for age 14 or under (Bantam) and age 16–20 (Junior-A) male ice hockey players to (i) further investigate previously published brain vital sign results showing subconcussive cognitive deficits and (ii) validate these findings through comparison with head-impact data obtained from instrumented accelerometers. With a longitudinal study design, 23 male ice hockey players in Bantam (n = 13; age 13.63 ± 0.62) and Tier II Junior-A (n = 10; age 18.62 ± 0.86) divisions were assessed at pre- and post-season. None were diagnosed with a concussion during the season. Cognitive evoked potential measures of Auditory sensation (N100), Basic attention (P300) and Cognitive processing (N400) were analysed as changes in peak amplitudes and latencies (six standard scores total). A regression analysis examined the relationship between brain vital signs and the number of head impacts received during the study season. Significant pre/post differences in brain vital signs were detected for both groups. Bantam and Junior-A players also differed in number of head impacts (Bantam: 32.92 ± 17.68; Junior-A: 195.00 ± 61.08; P &lt; 0.001). Importantly, the regression model demonstrated a significant linear relationship between changes in brain vital signs and total head impacts received (R = 0.799, P = 0.007), with clear differences between the Bantam and Junior-A groups. In the absence of a clinically diagnosed concussion, the brain vital sign changes appear to have demonstrated the compounding effects of repetitive subconcussive impacts. The findings underscored the importance of an objective physiological measure of brain function along the spectrum of concussive impacts.

A growing number of patients undergoing percutaneous coronary intervention (PCI) with stent implantation also have atrial fibrillation. This poses challenges for their optimal antithrombotic management because patients with atrial fibrillation undergoing PCI require oral anticoagulation for the prevention of cardiac thromboembolism and dual antiplatelet therapy for the prevention of coronary thrombotic complications. The combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding. Over the last decade, a series of North American Consensus Statements on the Management of Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention have been reported. Since the last update in 2018, several pivotal clinical trials in the field have been published. This document provides a focused updated of the 2018 recommendations. The group recommends that in patients with atrial fibrillation undergoing PCI, a non–vitamin K antagonist oral anticoagulant is the oral anticoagulation of choice. Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor should be given to all patients during the peri-PCI period (during inpatient stay, until time of discharge, up to 1 week after PCI, at the discretion of the treating physician), after which the default strategy is to stop aspirin and continue treatment with a P2Y 12 inhibitor, preferably clopidogrel, in combination with a non–vitamin K antagonist oral anticoagulant (ie, double therapy). In patients at increased thrombotic risk who have an acceptable risk of bleeding, it is reasonable to continue aspirin (ie, triple therapy) for up to 1 month. Double therapy should be given for 6 to 12 months with the actual duration depending on the ischemic and bleeding risk profile of the patient, after which patients should discontinue antiplatelet therapy and receive oral anticoagulation alone.