An investigation of the shelf life of cold brew coffee and the influence of extraction temperature using chemical, microbial, and sensory analysis.

The shelf-life of cold and hot water extraction coffees based on sensory and chemical profiles and microbial growth was examined, which also allowed the study of the influence of extraction temperature on the chemical and sensorial profiles of coffee. The shelf life of refrigerated cold- and hot-brewed coffee was limited not by microbial stability but rather by deterioration in sensory attributes. Further work is recommended to elucidate the mechanisms of coffee staling in a refrigerated environment, with particular interest in the degradation products of chlorogenic acid, as a significant decline in chlorogenic acid concentration was found over the storage period. Cold-extracted coffees were found to be chemically and sensorially different beverages from coffees extracted at high temperatures. Additionally, the cold-brewed coffees had greater sensory flavor stability over the storage time than the hot-brewed treatment. Practical application: This study advances the industry's understanding of the shelf life of ready-to-drink bottled cold coffees and demonstrates that lower brewing temperatures lead to greater flavor stability over shelf life. The findings also provide brewing parameters that can help guide product developers in modulating the flavor of commercial cold coffees.

Carole A. Miller, MD: Matriarch of the Ohio State University's Department of Neurosurgery.

Carole A. Miller, M.D., was born (May 7, 1939) and raised in Kalamazoo, Michigan. She obtained her undergraduate and medical degrees at the Ohio State University. She went on to complete her neurosurgical training at the Ohio State University Medical Center. After her first faculty role at the University of Michigan (1971), she returned to the Ohio State University Medical Center (1975) where she spent nearly 4 decades. She thrived in the specialty, achieving in every facet of academic practice including scientific contributions, graduate medical education, clinical care, and leadership roles within her academic department, locally, and at the national level of organized neurosurgery. Dr. Miller passed away peacefully, on October 28, 2015, after a courageous battle with cancer. Based on her essential programmatic and specialty-related contributions, she is remembered as the 'founding mother' of neurosurgery at the Ohio State University.

Current Indications for Management Options in Pseudotumor Cerebri.

There are surgical options available for those patients with idiopathic intracranial hypertension (IIH) who have significant visual threat or visual deterioration despite best medical management or whose visual deterioration is rapid enough to warrant urgent intervention. Optic nerve sheath fenestrations, venous sinus stenting, and cerebrospinal fluid diversion via ventriculoperitoneal and lumboperitoneal shunting are useful adjuncts in the management of this condition. Significant resources are used in the care of patients with IIH. Further understanding of the pathophysiology of IIH will likely direct future treatment options to more targeted therapeutics including surgery for IIH in the future.

Biographies of international women leaders in neurosurgery.

We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as "first" of their country or color or other achievement. All of them are included as outstanding-in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life's work, they chose service, often of the most neglected-those with pain, trauma, and disability. These women inspire and point the way to a time when the term "women leaders" as an exception is unnecessary.-Katharine J. Drummond, MD, on behalf of this month's topic editors.

Optimizing Medical Care Via Practice Guidelines and Quality Improvement Initiatives.

In an effort, to curtail rising health care costs, government and private payers have begun to focus on measuring quality of care. Along with quality improvement initiatives, clinical practice guidelines may also be utilized to provide better care. Clinical practice guidelines are recommendations for clinicians about the care of patients with specific conditions. This review provides an overview of clinical practice guidelines and quality improvement initiatives to highlight strategies to optimize patient outcomes.

An institutional review of hospital resource utilization and patient radiation exposure in shunted idiopathic intracranial hypertension.

Patients with idiopathic intracranial hypertension (IIH) frequently utilize healthcare services and undergo radiological studies to assess refractory headache symptoms despite cerebrospinal fluid diversion. To delineate the clinical utility of different imaging modalities and to estimate cumulative patient radiation exposure in shunted patients with IIH, we retrospectively reviewed 100 randomly selected patients with IIH and a prior cerebrospinal fluid diversion procedure treated at our institution between July 2010 and August 2018. Patients had an average of 16.3 office (SD ± 13.8), 12.4 emergency department (± 21.0), and 4.6 inpatient (± 5.1) encounters over an average 4.8 years of follow-up. Patients underwent an average of 9.0 head CTs (± 8.1), 10.3 shunt series x-rays (± 11.2), and 4.3 MRIs (± 3.7). Approximated radiation exposure per patient was 21.4 mSv (± 18.7). Radiological studies performed for acute symptoms usually demonstrated no actionable findings (82.5% CTs, 97.5% shunt series x-rays, and 79.6% MRIs). Shunted IIH patients undergo numerous radiological studies and are subject to considerable levels of radiation, yet imaging shows actionable findings in less than 10% percent of radiographic studies. IIH patients may benefit from radiation-reducing protocols and the use of alternative imaging to assess symptoms.

Unilateral Nerve Root Ligation for Multilevel Vertebral Column Resection After Fixed Post-infectious Deformity.

Kyphotic deformity is a well-recognized complication of thoracic vertebral osteomyelitis, often requiring multi-level vertebral column resection for mobilization of the spine and reduction of the deformity. We present a case of severe post-infectious kyphosis treated with multi-level vertebral column resection via a unilateral approach. We obtained excellent decompression and deformity correction without neurologic decline. We review relevant literature regarding spinal cord blood supply and known potential complication of nerve root ligations.

Linear accelerator-based radiosurgery is associated with lower incidence of radionecrosis compared with gamma knife for treatment of multiple brain metastases.

BACKGROUND: Gamma knife (GK) and linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) both offer excellent local control in the management of multiple brain metastases. The efficacy and toxicity of LINAC and GK SRS have not been directly compared in the modern era. We studied outcomes in patients treated with LINAC SRS and GK at two separate institutions. METHODS: We identified patients treated with either LINAC or GK who were treated to ≥2 lesions and had available follow up. LINAC patients were treated using single-isocenter multitarget technique. We used Cox regression, Fine and Gray competing risks regression, and nearest neighbor propensity score matching to account for confounders and imbalance between cohorts. Kaplan-Meier curves were used to estimate overall survival and rates of radionecrosis. RESULTS: We identified 391 patients who were treated in 537 courses to a total 2699 lesions (LINAC: 1014, GK: 1685). After propensity score matching, GK was associated with similar overall survival (HR = 0.86; 95% CI 0.59-1.24; p = 0.41) and higher rate of radionecrosis (HR = 3.83; 95% CI 1.66-8.84; p = 0.002) compared to LINAC. In a secondary propensity score matched analysis comparing radionecrosis in single-fraction LINAC and GK, GK remained associated with higher incidence of radionecrosis (HR = 4.42; 95% CI 1.28-15.29; p = 0.019). CONCLUSIONS: In this multi-institutional study, we found similar overall survival with lower incidence of radionecrosis in patients treated with LINAC compared to GK SRS. These findings are hypothesis generating and should be validated in an independent cohort.

Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases.

PURPOSE: Multiple studies have reported favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique. METHODS AND MATERIALS: We reviewed the records of patients with intact or resected brain metastases treated with SRS in 1 to 5 fractions using SIMT technique at our institution, with at least 1 available follow-up brain magnetic resonance imaging. Survival, disease control, and toxicity were evaluated using Cox regression, logistic regression, and Kaplan-Meier analysis. RESULTS: We identified 173 patients with 1014 brain metastases. Median follow up was 12.7 months. Median beam-on time was 4.1 minutes. The median dose to the brain was 219.4 cGy. Median overall survival and freedom from intracranial progression were 13.2 and 6.3 months, respectively. Overall survival did not differ between patients treated with greater than or less than 4 lesions (hazard ratio, 1.03; 95% confidence interval 0.66-1.61; P = .91). Actuarial 1- and 2-year local control were 99.0% and 95.1%, respectively. Rates of grade 2 and grade 3 or higher radionecrosis were 1.4% and 0.9%, respectively. CONCLUSIONS: SIMT radiosurgery delivered in 1 to 5 fractions offers excellent local control and acceptable toxicity in the treatment of multiple intact and postoperative brain metastases. This technique should be evaluated prospectively.

Characteristics of the cerebrospinal fluid pressure waveform and craniospinal compliance in idiopathic intracranial hypertension subjects.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of abnormally high intracranial pressure with an unknown etiology. The objective of this study is to characterize craniospinal compliance and measure the cerebrospinal fluid (CSF) pressure waveform as CSF is passively drained during a diagnostic and therapeutic lumbar puncture (LP) in IIH. METHODS: Eighteen subjects who met the Modified Dandy Criteria, including papilledema and visual field loss, received an ultrasound guided LP where CSF pressure (CSFP) was recorded at each increment of CSF removal. Joinpoint regression models were used to calculate compliance from CSF pressure and the corresponding volume removed at each increment for each subject. Twelve subjects had their CSFP waveform recorded with an electronic transducer. Body mass index, mean CSFP, and cerebral perfusion pressure (CPP) were also calculated. T-tests were used to compare measurements, and correlations were performed between parameters. RESULTS: Cerebrospinal fluid pressure, CSFP pulse amplitude (CPA), and CPP were found to be significantly different (p < 0.05) before and after the LP. CSFP and CPA decreased after the LP, while CPP increased. The craniospinal compliance significantly increased (p < 0.05) post-LP. CPA and CSFP were significantly positively correlated. CONCLUSIONS: Both low craniospinal compliance (at high CSFP) and high craniospinal compliance (at low CSFP) regions were determined. The CSFP waveform morphology in IIH was characterized and CPA was found to be positively correlated to the magnitude of CSFP. Future studies will investigate how craniospinal compliance may correlate to symptoms and/or response to therapy in IIH subjects.

Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial.

OBJECTIVES: A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. DESIGN: Randomized prospective clinical trial. SETTING: Ten ICUs in the United States. PATIENTS: One hundred nineteen severe traumatic brain injury patients. INTERVENTIONS: Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended. MEASUREMENTS AND MAIN RESULTS: A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p < 0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy. CONCLUSIONS: Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.

Analysis of lesion localisation at colonoscopy: outcomes from a multi-centre U.K. study.

BACKGROUND: Colonoscopy is currently the gold standard for detection of colorectal lesions, but may be limited in anatomically localising lesions. This audit aimed to determine the accuracy of colonoscopy lesion localisation, any subsequent changes in surgical management and any potentially influencing factors. METHODS: Patients undergoing colonoscopy prior to elective curative surgery for colorectal lesion/s were included from 8 registered U.K. sites (2012-2014). Three sets of data were recorded: patient factors (age, sex, BMI, screener vs. symptomatic, previous abdominal surgery); colonoscopy factors (caecal intubation, scope guide used, colonoscopist accreditation) and imaging modality. Lesion localisation was standardised with intra-operative location taken as the gold standard. Changes to surgical management were recorded. RESULTS: 364 cases were included; majority of lesions were colonic, solitary, malignant and in symptomatic referrals. 82% patients had their lesion/s correctly located at colonoscopy. Pre-operative CT visualised lesion/s in only 73% of cases with a reduction in screening patients (64 vs. 77%; p = 0.008). 5.2% incorrectly located cases at colonoscopy underwent altered surgical management, including conversion to open. Univariate analysis found colonoscopy accreditation, scope guide use, incomplete colonoscopy and previous abdominal surgery significantly influenced lesion localisation. On multi-variate analysis, caecal intubation and scope guide use remained significant (HR 0.35, 0.20-0.60 95% CI and 0.47; 0.25-0.88, respectively). CONCLUSION: Lesion localisation at colonoscopy is incorrect in 18% of cases leading to potentially significant surgical management alterations. As part of accreditation, colonoscopists need lesion localisation training and awareness of when inaccuracies can occur.

Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.

BACKGROUND: Despite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This Phase II, prospective, matched controlled, multicenter trial was conducted to assess the safety and efficacy of aglatimagene besadenovec (AdV-tk) plus valacyclovir (gene-mediated cytotoxic immunotherapy [GMCI]) in combination with SOC for newly diagnosed malignant glioma patients. METHODS: Treatment cohort patients received SOC + GMCI and were enrolled at 4 institutions from 2006 to 2010. The preplanned, matched-control cohort included all concurrent patients meeting protocol criteria and SOC at a fifth institution. AdV-tk was administered at surgery followed by SOC radiation and temozolomide. Subset analyses were preplanned, based on prognostic factors: pathological diagnosis (glioblastoma vs others) and extent of resection. RESULTS: Forty-eight patients completed SOC + GMCI, and 134 met control cohort criteria. Median overall survival (OS) was 17.1 months for GMCI + SOC versus 13.5 months for SOC alone (P = .0417). Survival at 1, 2, and 3 years was 67%, 35%, and 19% versus 57%, 22%, and 8%, respectively. The greatest benefit was observed in gross total resection patients: median OS of 25 versus 16.9 months (P = .0492); 1, 2, and 3-year survival of 90%, 53%, and 32% versus 64%, 28% and 6%, respectively. There were no dose-limiting toxicities; fever, fatigue, and headache were the most common GMCI-related symptoms. CONCLUSIONS: GMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival outcomes were most notably improved in patients with minimal residual disease after gross total resection. These data should help guide future immunotherapy studies and strongly support further evaluation of GMCI for malignant gliomas. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov NCT00589875.

Neuromodulation as a last resort option in the treatment of chronic daily headaches in patients with idiopathic intracranial hypertension.

OBJECTIVE: To determine the feasibility and efficacy of occipital nerve stimulation (ONS) in patients with refractory headaches secondary to idiopathic intracranial hypertension (IIH). BACKGROUND: IIH is a syndrome characterized by elevated intracranial pressures in the absence of a mass lesion. These patients typically present with chronic and intractable headaches. Cerebrospinal fluid (CSF) diversion fails in relieving the headache in a significant proportion of this population. ONS has been shown to be effective in medically refractory headaches and to our knowledge, has not been attempted as a therapeutic modality in this population. METHODS: Four patients with occipital predominant chronic daily headaches and IIH who failed medical management underwent bilateral ONSs. Octopolar percutaneous electrodes were implanted in the defined area of pain. Visual Analog Scale (VAS) was used as an outcome measure. Patient demographics and surgical complications were also reviewed in this retrospective study. Following the trial period, all patients had >50% pain reduction resulting in permanent implantation. RESULTS: All 4 patients had an average improvement of their VAS scores by 75%, with 85% spatial coverage and the remainder of the uncovered region being frontal. Sustained benefits were seen up to 3 years of follow-up. One patient had a lead erosion requiring removal followed by delayed re-implantation and another lost treatment efficacy at 2 years resulting in explantation. One patient required CSF diversion due to visual threat during the follow-up period but maintained sustained benefit from her ONS. CONCLUSIONS: Bilateral ONS may be a useful treatment option in the management of selected patients with IIH, after standard surgical interventions have been attempted. Bilateral ONS may provide therapeutic option for management of residual headaches in these complicated patients.

A survey of morbidity and mortality review meetings in the general surgical units of the West of Scotland.

BACKGROUND AND AIMS: There is little consensus as to the conduct of surgical morbidity and mortality review meetings. The aim of this survey was to determine how surgical morbidity and mortality meetings in the surgical units in the West of Scotland are carried out and to explore possible areas for improvement. METHODS AND RESULTS: Forty six surgical trainees distributed between the 15 general surgery units of the West of Scotland were asked to provide details of their surgical morbidity and mortality meetings for the training year 2012-2013. Twenty-five of 46 (54%) specialty trainees responded with all units being represented. All had designated time for surgical morbidity and mortality review. Meeting frequency varied as follows: weekly (3 units), fortnightly (1 unit), monthly (10 units), three monthly (1 unit). Fewer than half the units (6) included Foundation Trainees, and only one meeting was attended by nursing staff. Five units had clear criteria for morbidity, but only three included morbidity collected from outpatient follow-up. A standardised proforma was used to present the cases in only 2 units. CONCLUSIONS: All 15 surgical units in the West of Scotland have a regular surgical morbidity and mortality meeting but significant variations were observed as to frequency and participating personnel. A more robust system for reporting morbidities should be considered.

A multiscale model for the study of cardiac biomechanics in single-ventricle surgeries: a clinical case.

Complex congenital heart disease characterized by the underdevelopment of one ventricular chamber (single ventricle (SV) circulation) is normally treated with a three-stage surgical repair. This study aims at developing a multiscale computational framework able to couple a patient-specific three-dimensional finite-element model of the SV to a patient-specific lumped parameter (LP) model of the whole circulation, in a closed-loop fashion. A sequential approach was carried out: (i) cardiocirculatory parameters were estimated by using a fully LP model; (ii) ventricular material parameters and unloaded geometry were identified by means of the stand-alone, three-dimensional model of the SV; and (iii) the three-dimensional model of SV was coupled to the LP model of the circulation, thus closing the loop and creating a multiscale model. Once the patient-specific multiscale model was set using pre-operative clinical data, the virtual surgery was performed, and the post-operative conditions were simulated. This approach allows the analysis of local information on ventricular function as well as global parameters of the cardiovascular system. This methodology is generally applicable to patients suffering from SV disease for surgical planning at different stages of treatment. As an example, a clinical case from stage 1 to stage 2 is considered here.

Unsanctifying the sanctuary: challenges and opportunities with brain metastases.

While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present.

Development and validation of sensitive liquid chromatography/tandem mass spectrometry method for quantification of bendamustine in mouse brain tissue.

A liquid chromatography-tandem mass spectrometry method for quantification of bendamustine in mouse brain tissue was developed and fully validated. Methanol was used to precipitate proteins in brain tissue. Bendamustine and internal standard (chlorambucil) were separated with reverse-phase chromatography on a C-18 column with a gradient of water and 95% methanol in 0.1% formic acid. Positive mode electrospray ionization was applied with selected reaction monitoring to achieve 5 ng/ml lower limits of quantitation in mouse brain tissue. The calibration curve for bendamustine in mouse brain was linear between 5 and 2000 ng/ml. The within- and between-batch accuracy and precision of the assay were within 15% at 10, 100 and 1000 ng/ml. The recovery and matrix effect of bendamustine in mouse brain tissue ranged from 41.1% to 51.6% and 107.4% to 110.3%, respectively. The validated method was then applied to quantitate bendamustine in an animal study. Results indicate the assay can be applied to evaluate bendamustine disposition in mouse brain tissue. This assay will be applied in the future to detect and quantify bendamustine in human brain tissue samples.