Stereoelectroencephalography-guided radiofrequency ablation of the epileptogenic zone as a treatment and predictor of future success of further surgical intervention.

OBJECTIVE: Stereoelectroencephalography (SEEG)-guided radiofrequency ablation (RFA) is increasingly being used as a treatment for drug-resistant localization-related epilepsy. The aim of this study is to analyze the successes and failures using RFA and how response correlates with surgical epilepsy treatment outcomes. METHODS: We retrospectively reviewed 62 patients who underwent RFA via SEEG electrodes. After excluding five, the remaining 57 were classified into subgroups based on procedures and outcomes. Forty patients (70%) underwent a secondary surgical procedure, of whom 32 were delayed: 26 laser interstitial thermal therapy (LITT), five resection, one neuromodulation. We determined the predictive value of RFA outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the transient time of seizure freedom after RFA were calculated for each patient. RESULTS: Twelve of 49 patients (24.5%) who had RFA alone and delayed follow-up achieved Engel class I. Of the 32 patients who underwent a delayed secondary surgical procedure, 15 achieved Engel class I and nine Engel class II (24 successes), and eight were considered failures (Engel class III/IV). The transient time of seizure freedom after RFA was significantly longer in the success group (4 months, SD = 2.6) as compared to the failure group (.75 months, SD = 1.16; p < .001). Additionally, there was a higher portion of preoperative lesional findings in patients in the RFA alone and delayed surgical success group (p = .03) and a longer time to seizure recurrence in the presence of lesions (p < .05). Side effects occurred in 1% of patients. SIGNIFICANCE: In this series, RFA provided a treatment during SEEG-guided intracranial monitoring that led to seizure freedom in ~25% of patients. Of the 70% who underwent delayed surgery, longer transient time of seizure freedom after RFA was predictive of the results of the secondary surgeries, 74% of which were LITT.

Growing pains: strategies for improving ergonomics in minimally invasive gynecologic surgery.

PURPOSE OF REVIEW: To evaluate factors contributing to the development of work-related musculoskeletal disorders (WMSDs) and review strategies for mitigating ergonomic strain in minimally invasive gynecologic surgery. RECENT FINDINGS: Factors associated with increased ergonomic strain and the development of WMSDs include increasing patient body mass index (BMI), smaller surgeon hand size, noninclusive design of instruments and energy devices and improper positioning of surgical equipment. Each type of minimally invasive surgery (laparoscopic, robotic, vaginal) confers its own ergonomic risk to the surgeon. Recommendations have been published regarding optimal ergonomic surgeon and equipment positioning. Intraoperative breaks and stretching are effective in reducing surgeon discomfort. Formal training in ergonomics has not yet been widely implemented, but educational interventions have been effective in reducing surgeon discomfort and can improve surgeon recognition of suboptimal ergonomics. SUMMARY: Considering the serious downstream effects of WMSDs on surgeons, it is imperative to implement strategies for WMSD prevention. Optimal positioning of the surgeons and operative equipment should be routine. Intraoperative breaks and stretching should be incorporated during procedures and between every case. Formal education in ergonomics should be provided to surgeons and trainees. Additionally, more inclusive instrument design by industry partners should be prioritized.

Ice-POP: Ice Packs for Postoperative Pain: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate the benefit of ice packs as a supplement to standard pain management following laparoscopic hysterectomy (LH). DESIGN: This Institutional Review Board-approved randomized controlled trial involved patients undergoing LH for benign conditions. Subjects were randomized to receive standard enhanced recovery after surgery pain management or standard enhanced recovery after surgery plus ice packs. SETTING: Two academic tertiary care centers PATIENTS: Patients undergoing planned outpatient LH with the minimally invasive gynecologic surgery team between February 2019 and November 2020 were considered. Patients with chronic pain, current opioid use ≥1 week, or planned overnight hospitalizations were excluded. Primary outcome data were available for 51 subjects (24 control, 27 intervention). INTERVENTIONS: Ice packs were placed on the abdomen in the operating room. MEASUREMENTS AND MAIN RESULTS: Pain was assessed at multiple time points throughout the study using a visual analogue scale (VAS). Opioid requirement was assessed using morphine milligram equivalent. There was no difference between the groups on any demographic variables. Morphine milligram equivalent requirements were also not different between the groups (p = .63). Postoperative day 1 (POD#1) VAS scores were not different (p = .89). Eighty-five percent of subjects reported feeling that their pain was controlled. Subjects who reported that they did not feel their pain was controlled did not use more opioids on POD#1 (p = .37), nor did they have higher POD#1 VAS scores (p = .55). Eighty-seven percent of the intervention subjects said they would use ice again, and 82.6% of them said they would recommend ice to others. There were no adverse events related to ice. All subjects were prescribed 20 tablets oxycodone and averaged 2.9 (SD 3.4) tablets used after discharge. CONCLUSION: Ice packs are an acceptable supplement for postoperative pain control, but they do not reduce postoperative pain or opioid usage compared to standard pain management without ice packs.

Tuning heterologous glucan biosynthesis in yeast to understand and exploit plant starch diversity.

BACKGROUND: Starch, a vital plant-derived polysaccharide comprised of branched glucans, is essential in nutrition and many industrial applications. Starch is often modified post-extraction to alter its structure and enhance its functionality. Targeted metabolic engineering of crops to produce valuable and versatile starches requires knowledge of the relationships between starch biosynthesis, structure, and properties, but systematic studies to obtain this knowledge are difficult to conduct in plants. Here we used Saccharomyces cerevisiae as a testbed to dissect the functions of plant starch biosynthetic enzymes and create diverse starch-like polymers. RESULTS: We explored yeast promoters and terminators to tune the expression levels of the starch-biosynthesis machinery from Arabidopsis thaliana. We systematically modulated the expression of each starch synthase (SS) together with a branching enzyme (BE) in yeast. Protein quantification by parallel reaction monitoring (targeted proteomics) revealed unexpected effects of glucan biosynthesis on protein abundances but showed that the anticipated broad range of SS/BE enzyme ratios was maintained during the biosynthetic process. The different SS/BE ratios clearly influenced glucan structure and solubility: The higher the SS/BE ratio, the longer the glucan chains and the more glucans were partitioned into the insoluble fraction. This effect was irrespective of the SS isoform, demonstrating that the elongation/branching ratio controls glucan properties separate from enzyme specificity. CONCLUSIONS: Our results provide a quantitative framework for the in silico design of improved starch biosynthetic processes in plants. Our study also exemplifies a workflow for the rational tuning of a complex pathway in yeast, starting from the selection and evaluation of expression modules to multi-gene assembly and targeted protein monitoring during the biosynthetic process.

Rupture of a superficial temporal artery pseudoaneurysm following craniotomy.

Pseudoaneurysm of the superficial temporal artery (STA) is a rare entity that has been reported in the literature after trauma or iatrogenic injuries. We describe a unique case of STA pseudoaneurysm rupture and the clinical sequelae associated with its rupture. We report a case of pseudoaneurysm rupture of the STA that occurred 14 days after craniotomy for cerebrospinal fluid leak repair. We also review the literature, diagnosis and treatment of external carotid artery aneurysms. Rupture of a STA pseudoaneurysm is a previously unreported and serious complication that must be quickly recognized in order to control hemorrhage that may have life threatening complications.

Management of cerebrospinal fluid leak from cervical gunshot wounds with external ventricular drainage: a small case series.

Historically, the surgical management of gunshot wounds to the spine has been controversial. Repair of a persistent cerebrospinal fluid (CSF) leak is a generally agreed upon indication. The management of such CSF leaks typically involves lumbar drainage or direct surgical repair. Here, the authors report two cases of CSF diversion with an external ventricular drain (EVD) in patients with cervical gunshot wounds. Both patients had spinal canal obliteration or physiologic myelographic block at or below the level of injury. To the best of the author's knowledge, these are the first two reports of successful EVD treatment of persistent CSF leaks related cervical gunshot wounds. The authors also propose a CSF treatment algorithm for cervical gunshot wounds that includes EVD.

Minimally invasive lateral corpectomy for thoracolumbar traumatic burst fractures.

OBJECTIVE: The need for anterior column reconstruction after thoracolumbar burst fractures remains controversial. Here, the authors present their experience with minimally invasive lateral thoracolumbar corpectomies for traumatic fractures. METHODS: Between 2012 and 2019, 59 patients with 65 thoracolumbar fractures underwent 65 minimally invasive lateral corpectomies (MIS group). This group was compared to 16 patients with single-level thoracolumbar fractures who had undergone open lateral corpectomies with the assistance of general surgery between 2007 and 2011 (open control group). Comparisons of the two groups were made with regard to operative time, estimated blood loss, time to ambulation, and fusion rates at 1 year postoperatively. The authors further analyzed the MIS group with regard to injury mechanism, fracture characteristics, neurological outcome, and complications. RESULTS: Patients in the MIS group had a significantly shorter mean operative time (228.3 ± 27.9 vs 255.6 ± 34.1 minutes, p = 0.001) and significantly shorter mean time to ambulation after surgery (1.8 ± 1.1 vs 5.0 ± 0.8 days, p < 0.001) than the open corpectomy group. Mean estimated blood loss did not differ significantly between the two groups, though the MIS group did trend toward a lower mean blood loss. There was no significant difference in fusion status at 1 year between the MIS and open groups; however, this comparison was limited by poor follow-up, with only 32 of 59 patients (54.2%) in the MIS group and 8 of 16 (50%) in the open group having available imaging at 1 year. Complications in the MIS group included 1 screw misplacement requiring revision, 2 postoperative femoral neuropathies (one of which improved), 1 return to surgery for inadequate posterior decompression, 4 pneumothoraces requiring chest tube placement, and 1 posterior wound infection. The rate of revision surgery for the failure of fusion in the MIS group was 1.7% (1 of 59 patients). CONCLUSIONS: The minimally invasive lateral thoracolumbar corpectomy approach for traumatic fractures appears to be relatively safe and may result in shorter operative times and quicker mobilization as compared to those with open techniques. This should be considered as a treatment option for thoracolumbar spine fractures.

Task-specific interhemispheric hypoconnectivity in writer's cramp - An EEG study.

OBJECTIVE: Writer's cramp (WC) is a focal task-specific dystonia characterized by abnormal posturing of the hand muscles during handwriting, but not during other tasks that involve the same set of muscles and objects such as sharpening a pencil. Our objective was to investigate the pathophysiology underlying the task specificity of this disorder using EEG. We hypothesized that premotor-parietal connectivity will be lower in WC patients specifically during handwriting and motor imagery of handwriting. METHODS: We recruited 15 WC patients and 15 healthy controls. EEG was recorded while participants performed 4 tasks - writing with a pencil, sharpening a pencil, imagining writing and imagining sharpening. We determined the connectivity changes between relevant brain regions during these tasks. RESULTS: We found reduced interhemispheric alpha coherence in the sensorimotor areas in WC patients exclusively during handwriting. WC patients also showed less reduction of task-related beta spectral power and a trend for reduced premotor-parietal coherence during motor tasks. CONCLUSION: We could not confirm an abnormality in premotor-parietal connectivity specific to handwriting by this method. However, there was a task-specific reduction in interhemispheric alpha connectivity in WC patients, whose behavioral correlate remains unknown. SIGNIFICANCE: Interhemispheric alpha connectivity can be a potential interventional target in WC.

Minimally Invasive Management of Civilian Gunshot Wounds to the Lumbar Spine: A Case Series and Technical Report.

BACKGROUND: Treatment of penetrating gunshot wounds (GSW) to the spine remains controversial. The decision to operate is often based on surgeon preference and experience. We present a case series of 7 patients who underwent minimally invasive thoracolumbar/sacral decompression and bullet removal at a level 1 trauma center. OBJECTIVE: To describe the use of minimally invasive techniques to achieve decompression and bullet removal for GSW to the spine. METHODS: From 2010 to 2017, 7 patients with spinal GSW underwent minimally invasive decompression and bullet removal at an academic level 1 trauma center. RESULTS: Patient ages ranged from 20 to 55 yr (mean: 31 yr). The mechanisms of injury were GSW to the abdomen/pelvis (n = 6) and direct GSW to the spine (n = 1). Based on the neurological examination, the injuries were characterized as complete (n = 1) or incomplete (n = 6). Decompression and bullet removal were performed using a tubular retractor system. All patients with incomplete injuries who had postdischarge follow-up demonstrated some neurologic recovery. There were no postoperative wound infections, cerebrospinal fluid (CSF) fistulas, or other complications related to the procedure. CONCLUSION: Minimally invasive decompression and bullet removal is a safe technique that may help reduce the risk of postoperative infections and CSF fistulas in patients with GSW to the lumbar spine compared to the standard open technique. This approach appears to be particularly beneficial in patients with incomplete injuries and neuropathic pain refractory to medical treatment.

Primary pain generator identification by CT-SPECT in patients with degenerative spinal disease.

OBJECTIVE: Axial spinal pain generators are difficult to identify using current diagnostic modalities. Merging CT with SPECT (CT-SPECT) scans allows for accurate identification of areas with increased osteoblastic activity, which may reflect pain generators. In this study, the authors aimed to evaluate the degree of pain improvement in patients who underwent surgery, addressing primary pain generators identified by CT-SPECT. METHODS: The authors retrospectively reviewed all patients with chronic axial spine pain who underwent diagnostic CT-SPECT at their institution and analyzed pain improvement in those who underwent surgical treatment in order to determine whether CT-SPECT correctly identified the primary pain generator. RESULTS: A total of 315 patients underwent diagnostic CT-SPECT between January 2014 and August 2018. Forty-eight patients underwent either cervical or lumbar fusion; there were 26 women (16 cervical, 10 lumbar) and 22 men (9 cervical, 13 lumbar). The overall axial spinal pain, as assessed through self-reporting of visual analog scale scores at 6 months postoperatively, improved from 9.04 ± 1.4 to 4.34 ± 2.3 (p = 0.026), with cervical fusion patients improving from 8.8 ± 1.8 to 3.92 ± 2.2 (p = 0.019) and lumbar fusion patients improving from 9.35 ± 0.7 to 4.87 ± 2.3 (p = 0.008). CONCLUSIONS: CT-SPECT may offer a diagnostic advantage over current imaging modalities in identifying the primary pain generator in patients with axial spinal pain.

Preoperative Evaluation for Minimally Invasive Gynecologic Surgery: What Is the Best Evidence and Recommendations for Clinical Practice.

Preoperative evaluation for elective benign gynecologic procedures is a necessary step in reducing perioperative complications. Although a thorough history and physical examination are the foundation of this assessment, much evidence exists that physicians rely on unnecessary laboratory and diagnostic testing. Our goal was to perform a systematic review of the available literature regarding preoperative evaluation to better inform preoperative test selection and to identify deficiencies in the current literature. There is very limited data specific to preoperative testing for patients undergoing gynecologic surgeries. Abnormal test results are common when routine, unselected testing is applied. Using a protocol to guide preoperative testing improves patient care by eliminating unnecessary tests without compromising the efficacy of predicting adverse perioperative events or case cancellation and modifications.

Preoperative evaluation for gynecologic surgery: a guide to judicious, evidence-based testing.

PURPOSE OF REVIEW: Preoperative testing is a routine component of surgical planning, however, the majority of literature agree that laboratory and diagnostic studies are over utilized. We aim to summarize the available literature and provide gynecologists performing elective surgery for benign indications guidance to determine when, in whom, and in what time frame preoperative studies should be collected. RECENT FINDINGS: Current literature supports previous publications indicating routine laboratory and diagnostic testing for elective surgery is unnecessary and continues to be excessive. The frequency of abnormal results is high, whereas the impact on surgical planning and outcomes is negligible. SUMMARY: The preoperative evaluation including thorough history and physical examination should be the cornerstones for eliciting underlying disease, which may alter a surgical strategy. Devising a protocol to direct preoperative testing has been shown to decrease unnecessary tests without compromising prediction of perioperative morbidity/mortality or case cancellation and changes. Avoidance of 'routine preoperative testing' and instead, thoughtful risk stratification of individual patients, should be a goal of providing value-based care.

Unilateral repetitive transcranial magnetic stimulation differentially affects younger and older adults completing a verbal working memory task.

Functional neuroimaging studies have found that lateralization of activity in the dorsolateral prefrontal cortex (dlPFC) is reduced with aging. In the present study, repetitive transcranial magnetic stimulation (rTMS) was used to disrupt dlPFC activity in order to test the relationship of dlPFC laterality and age in verbal working memory (WM). Young (n=36) and older (n=35) subjects received 1Hz-rTMS (sham or active) to left or right dlPFC and WM performance was assessed pre- and post-stimulation via the n-back task. Significant increases in WM accuracy were observed following rTMS in the right dlPFC and sham conditions, but not with the left dlPFC stimulation. This was accompanied by a decrease in left P1 latency was also observed following left dlPFC stimulation. In contrast, older adults did not show a disruption in WM performance following rTMS in any of the stimulation conditions and exhibited increased left P3 amplitude following left stimulation. Our results show that changes in prefrontal laterality are evident with increasing age (left stimulation affects younger adults while older adults are not affected by stimulation) and this change is associated with specific neurophysiologic measures.

HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015.

BACKGROUND: In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures. METHODS: We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner. HIV polymerase (pol) sequences from case patients were phylogenetically analyzed, and potential risk factors associated with HIV infection were ascertained. RESULTS: From November 18, 2014, to November 1, 2015, HIV infection was diagnosed in 181 case patients. Most of these patients (87.8%) reported having injected the extended-release formulation of the prescription opioid oxymorphone, and 92.3% were coinfected with hepatitis C virus. Among 159 case patients who had an HIV type 1 pol gene sequence, 157 (98.7%) had sequences that were highly related, as determined by phylogenetic analyses. Contact tracing investigations led to the identification of 536 persons who were named as contacts of case patients; 468 of these contacts (87.3%) were located, assessed for risk, tested for HIV, and, if infected, linked to care. The number of times a contact was named as a syringe-sharing partner by a case patient was significantly associated with the risk of HIV infection (adjusted risk ratio for each time named, 1.9; P<0.001). In response to this outbreak, a public health emergency was declared on March 26, 2015, and a syringe-service program in Indiana was established for the first time. CONCLUSIONS: Injection-drug use of extended-release oxymorphone within a network of persons who inject drugs in Indiana led to the introduction and rapid transmission of HIV. (Funded by the state government of Indiana and others.).

Probing the interaction of the ipsilateral posterior parietal cortex with the premotor cortex using a novel transcranial magnetic stimulation technique.

OBJECTIVE: Functional imaging studies have shown that control of planned movement involves a distributed network that involves the premotor (PMv) and posterior parietal cortices (PPC). Similarly, anatomical studies show that these regions are densely interconnected via white matter tracts. We therefore hypothesized that the PPC influence over the motor cortex is partly via a connection with the PMv. METHODS: Using a novel three-pulse ipsilateral transcranial magnetic stimulation technique, we preconditioned the PPC (80% RMT) at ISIs from 4-15 ms prior to stimulating the PMv and M1 at ISIs of 4 and 6 ms. RESULTS: As previously shown, PMv-M1 paired-pulse stimulation resulted in inhibition of the MEP (90% RMT, 4-6 ms) and PPC-M1 paired-pulse stimulation resulted in facilitation of the MEP (90% RMT, 4-8 ms). PPC-M1 paired-pulse stimulation at 80% RMT preconditioning had no effect on M1. PPC-PMv-M1 stimulation resulted in reversal of inhibition observed with PMv-M1 stimulation at ISIs ranging from 6 to 15 ms. CONCLUSIONS: The reversal of inhibition observed with PPC-PMv-M1 stimulation suggests that the parietal connection to the PMv plays a role in the modulation of M1. SIGNIFICANCE: This is the first study to stimulate three intrahemispheric regions in order to test a disynaptic connection with M1. The described network may be important in a variety of movement disorders.

Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone--Indiana, 2015.

On January 23, 2015, the Indiana State Department of Health (ISDH) began an ongoing investigation of an outbreak of human immunodeficiency virus (HIV) infection, after Indiana disease intervention specialists reported 11 confirmed HIV cases traced to a rural county in southeastern Indiana. Historically, fewer than five cases of HIV infection have been reported annually in this county. The majority of cases were in residents of the same community and were linked to syringe-sharing partners injecting the prescription opioid oxymorphone (a powerful oral semi-synthetic opioid analgesic). As of April 21, ISDH had diagnosed HIV infection in 135 persons (129 with confirmed HIV infection and six with preliminarily positive results from rapid HIV testing that were pending confirmatory testing) in a community of 4,200 persons.

High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI.

Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1ß (IL-1ß) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1ß expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.