Dorsal Root Ganglion Stimulation as a Salvage Therapy Following Failed Spinal Cord Stimulation.

INTRODUCTION: Spinal cord stimulation (SCS) can provide long-term pain relief for various chronic pain conditions, but some patients have no relief with trial stimulation or lose efficacy over time. To "salvage" relief in patients who do not respond or have lost efficacy, alternative stimulation paradigms or anatomical targets can be considered. Dorsal root ganglion stimulation (DRG-S) has a different mechanism of action and anatomical target than SCS. OBJECTIVES: We assessed DRG-S salvage therapy outcomes in patients who did not respond to SCS or had lost SCS efficacy. MATERIALS AND METHODS: We retrospectively included consecutive patients from 2016 to 2020 who were salvaged with DRG-S after failed SCS trials (<50% pain reduction) or who had lost efficacy after permanent SCS. We compared numerical rating scale (NRS) pain, Oswestry disability index (ODI), health-related quality of life (EuroQol five-dimensions five-level), and oral morphine equivalent (OME) opioid requirements before DRG-S salvage and at patients' last follow-up. RESULTS: A total of 60 patients who had failed SCS were salvaged with DRG-S. The mean age was 56 ± 12 years, and the most common diagnoses were complex regional pain syndrome (n = 24) and failed back surgery syndrome (n = 24). The most common failed modalities included tonic (n = 32), Burst (n = 18), and high-frequency (n = 10) SCS. The median follow-up duration of salvage DRG-S was 34 months. With DRG-S, NRS decreased (8.7 ± 1.2 to 3.8 ± 2.1), and OME declined (median 23 mg to median 15 mg), whereas EuroQol 5D scores increased (0.40 ± 0.15 to 0.71 ± 0.15), and ODI improved (64 ± 14% to 31 ± 18%) (all p < 0.05). CONCLUSIONS: DRG-S can be used in patients with chronic pain who have previously failed to receive persistent benefit from SCS.

All or nothing? Partial business shutdowns and COVID-19 fatality growth.

Incomplete vaccine uptake and limited vaccine availability for some segments of the population could lead policymakers to consider re-imposing restrictions to help reduce fatalities. Early in the pandemic, full business shutdowns were commonplace. Given this response, much of the literature on policy effectiveness has focused on full closures and their impact. But were complete closures necessary? Using a hand-collected database of partial business closures for all U.S. counties from March through December 2020, we examine the impact of capacity restrictions on COVID-19 fatality growth. For the restaurant and bar sector, we find that several combinations of partial capacity restrictions are as effective as full shutdowns. For example, point estimates indicate that, for the average county, limiting restaurants and bars to 25% of capacity reduces the fatality growth rate six weeks ahead by approximately 43%, while completely closing them reduces fatality growth by about 16%. The evidence is more mixed for the other sectors that we study. We find that full gym closures reduce the COVID-19 fatality growth rate, while partial closures may be counterproductive relative to leaving capacity unrestricted. Retail closures are ineffective, but 50% capacity limits reduce fatality growth. We find that restricting salons, other personal services and movie theaters is either ineffective or counterproductive.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

BACKGROUND: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known. METHODS: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly. RESULTS: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss. CONCLUSION: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

A paramedian approach for dorsal root ganglion stimulation placement developed to limit lead migration and fracture.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S), has demonstrated superiority in the treatment of complex regional pain syndrome and causalgia. Lead migration and fracture impact DRG-S therapeutic stability. Lead anchoring reduces DRG-S lead migration without increasing lead fracture. Lead fracture may be related to lead entrapment in the superficial fascial plane. A novel medialized approach for lead placement and anchoring is presented to address these issues. METHODS: We suggest an alternative technique for implanting percutaneous DRG-S leads at the T10-L5 levels. RESULTS: A novel medialized ipsilateral technique for lead placement and anchoring for single, bilateral, and adjacent segment placement is presented. The Tuohy needle puncture site is medial to the pedicle and adjacent to the spinous process, two vertebral levels caudad to the target foramen. Trajectory is maintained in the sagittal plane, to access the caudad interlaminar space near the midline. This technique allows for ipsilateral or contralateral lead placement. After epidural access, the introducer sheath is rotated toward the targeted foramen and advanced. The guidewire followed by the lead is passed, and once lead position is confirmed, tension "S" loops are created, followed by anchoring to the deep fascia. CONCLUSION: We describe a new paramedian technique for DRG-S lead placement. We propose it will decrease DRG-S complication rates through anchoring to reduce migration and by avoiding the fascial planes thought to be responsible for fracture. Long-term outcomes applying our proposed techniques are required for determining the true impact, however, early anecdotal results suggest that these new techniques are favorable.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Incidence of Dementia in Patients With Open-angle Glaucoma: A Population-based Study.

PRECIS: In this population-based study of 509 open-angle glaucoma (OAG) patients over a 36-year period, we identified a decreased rate of developing dementia compared with the rate in the general population. PURPOSE: The aim was to determine the incidence of dementia and Alzheimer disease (AD) among patients with OAG. PATIENTS AND METHODS: Retrospective, population-based cohort study. All residents of Olmsted County, Minnesota (≥40 y) who were diagnosed with OAG between January 1, 1965 and December 31, 2000, were eligible for inclusion in this study. A total of 509 patients were included over the 36-year period. The cumulative probability of developing dementia was calculated and compared with the population risk of dementia. RESULTS: Of the 509 patients included, 300 (58.9%) were female, the median age was 67.5 years, and 278 patients (54.6%) had primary OAG. Other subgroups were pseudoexfoliation in 15.1%, treated ocular hypertension in 14.1%, normal tension glaucoma in 10.6%, and pigmentary glaucoma in 5.5% of the patients. Respectively, 118 (23.0%) and 99 (19.4%) patients developed dementia and AD. The 10-year cumulative probability of developing dementia and AD was 12.0% and 9.9%, with a 95% confidence interval of 9.3%-15.3% and 7.5%-13%, respectively. The observed 10-year incidence of dementia and AD were significantly lower than the expected population incidence (19.0% and 19.0%; P<0.001). Older age at diagnosis of glaucoma was a strong predictor for the development of dementia by multivariate analysis (hazard ratio: 3.31, 95% confidence interval: 2.61-4.20, P<0.001). CONCLUSION: The risk of developing dementia or AD was decreased in OAG patients compared with the general population. OAG with onset at a later age may present as a different etiopathogenetic entity compared with onset at a younger age, and represent the optic nerve findings of generalized neurodegenerative processes.

Evaluation of an Intrathecal Drug Delivery Protocol Leads to Rapid Reduction of Systemic Opioids in the Oncological Population.

Objective: The article that follows is purposed at demonstrating how IT opioid plus bupivacaine achieves sustained acceptable pain relief while simultaneously rapidly reducing oral morphine equivalents (OME). Background: Cancer patients represent a population with significant morbidity, pain, and limited life expectancy. It is, therefore, vital to achieve satisfactory analgesia quickly and safely. To date, there is limited data in the literature that discusses efficacy of combined intrathecal (IT) medication therapy in reducing systemic opioids in the oncological population. Methods: This was a retrospective analysis that reviewed cancer pain patients from day of IT pump implantation through the six-month postoperative time point. A cohort of 50 oncological patients who had intrathecal drug delivery systems (IDDSs) implanted at Memorial Sloan Kettering Cancer Center between 2017 and 2019 were studied. Median OMEs were the primary modality of analysis for this review. Mean visual analogue scale scores were secondarily reviewed. Results: Median OMEs decreased from 503 preoperative to 105 at six months postoperative time point. Median time to discharge was 6.5 days. Unfortunately, due to malignant mortality, 27 patients did not make it to the 6-month postoperative time point. Discussion: IDDSs with opioid plus bupivacaine represent a safe and efficient route toward expeditious pain relief and decreased OMEs in the cancer pain population.

Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

Proton-pump-inhibitor use associated with lower short-term rebleeding and mortality in patients receiving esophageal variceal band ligation: a retrospective cohort study.

BACKGROUND: The impact of proton-pump inhibitor (PPI) therapy on subsequent hemorrhage and mortality after variceal hemorrhage is unclear. AIM: Evaluate the associations of PPI use with upper gastrointestinal bleeding (UGIB) and death within 30 days of undergoing esophageal variceal band ligation (EBL) separately in inpatient and outpatient settings. METHODS: Retrospective review of cirrhotic patients with variceal hemorrhage who underwent EBL between 2005 and 2018. Endoscopic findings, PPI use at admission (inpatients only), PPI use at discharge (inpatients and outpatients), and adverse outcomes data (liver transplant, UGIB, transjugular intrahepatic portosystemic shunt, and death within 30 days of discharge or death during hospitalization) were reviewed. RESULTS: A total of 446 patients (164 inpatients, 282 outpatients) were included. The most commonly observed outcomes were death within 30 days of discharge in inpatients (12.8%), UGIB within 30 days of discharge in inpatients (21.3%), and UGIB within 30 days of discharge in outpatients (8.5%). For inpatients, prescription of PPI at discharge was associated with a lower risk of bleeding within 30 days (odds ratio: 0.30, P = 0.025) and death within 30 days (odds ratio = 0.16, P = 0.002). No other significant associations of PPI with death or UGIB were reported. CONCLUSION: Post-EBL PPI therapy is associated with reduced risk of bleeding and death within 30 days after variceal hemorrhage in hospitalized patients.

Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients.

OBJECTIVE: To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients. PATIENTS AND METHODS: From April 3 to June 2, 2020, the US Food and Drug Administration Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma. RESULTS: The incidence of all serious adverse events was low; these included transfusion reactions (n=78; <1%), thromboembolic or thrombotic events (n=113; <1%), and cardiac events (n=677, ~3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=75) and cardiac events (n=597) were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate was 13.0% (12.5%, 13.4%), and was higher among more critically ill patients relative to less ill counterparts, including patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%). CONCLUSION: These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.

Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia.

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

Mandibular slope: a reproducible and simple measure of horizontal gaze.

STUDY DESIGN: This study is a single-center retrospective radiographic review. OBJECTIVES: The objective of this study is to evaluate a novel measurement parameter, mandibular slope (MS), as a measure of horizontal gaze. INTRODUCTION: Assessment of sagittal spinal alignment is essential in the evaluation of spinal deformity patients. Ability to achieve a horizontal gaze, a parameter of sagittal alignment, is needed for the performance of daily activities. Standard measures of horizontal gaze, including the gold-standard chin-brow to vertical angle (CBVA) and the surrogate measures McGregor's line (McGS) and Chamberlain's line (CS), require high-quality imaging, precise head positioning, and reliance on difficult to view visual landmarks. A novel measurement parameter, MS, utilizing the caudal margin of the mandible on standard lateral spine radiographs is proposed. METHODS: 90 radiographs from spine deformity patients with or without spinal implants from a single center were evaluated. Three spine surgery fellows independently measured CBVA, McGS, CS, and MS at two timepoints at least one week apart to assess accuracy and reliability. MS was measured as the angle created by the inferior edge of the mandibular body and the horizontal. Formulas for calculating CBVA based on the above parameters were derived and compared to the actual CBVA. RESULTS: Mean age was 49.7 years, 76 females and 14 males. CBVA correlated with CS, McGS, and MS, r = 0.85, 0.81, and 0.80, respectively (p < 0.001). Standard error between real CBVA and calculated CBVA using CS (0.4 ± 4.79) and McGS (0.4 ± 3.9) was higher than that calculated using MS (- 0.2 ± 4.3). ICC demonstrated the highest inter-observer reliability with MS (0.999). MS had the highest intra-observer reliabilities 0.975, 0.981, and 0.988 (p < 0.001); CS and McGS also demonstrated high intra-observer reliability. CONCLUSIONS: MS is a promising measure of horizontal gaze that correlates highly with CBVA, has excellent intra- and inter-observer reliability with CBVA, and is easily measured using standard lateral spine radiographs.

Etiology of Papilledema in Patients in the Eye Clinic Setting.

Importance: The study of health conditions associated with papilledema will augment the clinical judgment of eye care professionals treating patients with optic disc edema in determining the urgency of additional evaluation and counseling patients accordingly. Objectives: To determine the incidence, demographic characteristics, and etiologies of papilledema based on a unique records-linkage research platform; and to describe the demographic and clinical differences between patients with idiopathic intracranial hypertension (IIH) and other causes of papilledema. Design, Setting, and Participants: Retrospective population-based cross-sectional study of patients treated for papilledema at outpatient eye clinics in Olmsted County, Minnesota, using the Rochester Epidemiology Project. Data were collected from January 1990 to December 2014 and analyzed from September 2018 to April 2019. Main Outcomes and Measures: Etiologies of papilledema, body mass index, incidence of headache, or localizing neurologic signs. Results: Eighty-six patients were diagnosed with papilledema during the 24-year period, providing an age- and sex-adjusted incidence of 2.5 individuals per 100 000 per year; 68 patients (79%) were women, 73 (85%) were white patients, and the median (range) age was 27.7 (6.2-64.2) years. Nineteen patients (22%) presented with a previously diagnosed attributable cause (eg, trauma or intracranial tumor). Among patients presenting with papilledema without a previously diagnosed attributable cause, 58 patients (87%) had IIH, and 9 patients (13%) were found to have a secondary cause of raised intracranial pressure, such as intracranial tumor, cerebral venous sinus thrombosis, or granulomatous meningitis. Patients with IIH had a higher median (range) body mass index (37.5 [20.4-55.7] vs 27.4 [16.6-40.1]; P = .003) and headache prevalence (54 of 58 patients [93%] vs 6 of 9 patients [67%]; P = .004) than patients with other causes of papilledema. Of 9 patients with papilledema but no IIH, 2 (22%) had localizing neurologic signs, such as gait abnormalities, hearing loss, focal weakness or numbness, visual field defects, or aphasia. Among 42 patients with demographic characteristics typically associated with IIH (female sex, with obesity, aged 15 to 45 years, and absent localizing neurologic signs or symptoms), 40 (95%) had papilledema that was associated with IIH. Conversely, among the 19 patients without these demographic characteristics, 7 (37%) had an alternative cause. Conclusions and Relevance: In this study, most patients who presented to the eye clinic with papilledema without a previously known cause were found to have IIH. These patients were more likely to present with headaches and had statistically higher body mass index. Clinicians should take these findings into account when determining the pretest probability of a patient having IIH or an alternative cause of papilledema.

Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients.

BACKGROUND: Convalescent plasma is the only antibody based therapy currently available for COVID-19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. METHODS: Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. RESULTS: The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n=4), transfusion-associated circulatory overload (TACO; n=7), transfusion-related acute lung injury (TRALI; n=11), and severe allergic transfusion reactions (n=3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. CONCLUSION: Given the deadly nature of COVID-19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.

Early safety indicators of COVID-19 convalescent plasma in 5000 patients.

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Evaluation of Fixed Intrathecal Bupivacaine Infusion Doses in the Oncologic Population.

OBJECTIVES: Intrathecal drug delivery systems (IDDS) are an important method of pain control for patients with refractory oncologic pain. Local anesthetics such as bupivacaine have been infused either alone or with opioids. While effective, bupivacaine can cause adverse effects such as numbness, weakness, and urinary retention. This study looks to establish a safe and efficacious fixed bupivacaine dosing algorithm in intrathecal pumps for cancer patients. MATERIALS AND METHODS: A bupivacaine dosing algorithm was developed using data from 120 previous patients who underwent IDDS placement at Memorial Sloan Kettering Cancer Center. The outcomes were then evaluated for 43 subsequent patients who were treated with bupivacaine IDDS according to our aforementioned algorithm. RESULTS: Our data show that in patients treated with our bupivacaine guideline, visual analog pain scale scores decreased by 59% and oral morphine equivalence decreased by 70% from the period between IDDS implantation until discharge from the MSKCC hospital. However, 16.3% of our patients had bupivacaine-related side effects. CONCLUSIONS: For oncological patients, our data and experience support the initiation of intrathecal bupivacaine at the following doses: 5 mg/day for catheter tips in the cervical spine, 8 mg/day for catheter tips at T1-4, and 10 mg/day for catheter tips at T5-8. Given the higher likelihood of adverse effects in catheters at T9-12 and the lumbar spine, we start at 8 mg/day with close follow-up of the patient. Initiating these doses allow our patients to safely reach adequate analgesia faster, with a shorter hospitalization and quicker return to anti-cancer therapy.

Trends in glioblastoma: outcomes over time and type of intervention: a systematic evidence based analysis.

INTRODUCTION: Despite aggressive treatment with chemoradiotherapy and maximum surgical resection, survival in patients with glioblastoma (GBM) remains poor. Ongoing efforts are aiming to prolong the lifespan of these patients; however, disparities exist in reported survival values with lack of clear evidence that objectively examines GBM survival trends. We aim to describe the current status and advances in the survival of patients with GBM, by analyzing median overall survival through time and between treatment modalities. METHODS: A systematic review was conducted according to PRISMA guidelines to identify articles of newly diagnosed glioblastoma from 1978 to 2018. Full-text glioblastoma papers with human subjects, ≥ 18 years old, and n ≥ 25, were included for evaluation. RESULTS: The central tendency of median overall survival (MOS) was 13.5 months (2.3-29.6) and cumulative 5-year survival was 5.8% (0.01%-29.1%), with a significant difference in survival between studies that predate versus postdate the implementation of temozolomide and radiation, [12.5 (2.3-28) vs 15.6 (3.8-29.6) months, P < 0.001]. In clinical trials, bevacizumab [18.2 (10.6-23.0) months], tumor treating fields (TTF) [20.7 (20.5-20.9) months], and vaccines [19.2 (15.3-26.0) months] reported the highest central measure of median survival. CONCLUSION: Coadministration with radiotherapy and temozolomide provided a statistically significant increase in survival for patients suffering from glioblastoma. However, the natural history for GBM remains poor. Therapies including TTF pooled values of MOS and provide means of prolonging the survival of GBM patients.

Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome.

Background Patients with Eisenmenger syndrome are known to have a high incidence of sudden cardiac death (SCD), yet the underlying causes are not well understood. We sought to define the predictors of SCD in this population. Methods and Results A retrospective analysis of all patients with Eisenmenger syndrome from 2 large tertiary referral centers was performed. ECGs, prolonged ambulatory recordings, echocardiograms, and clinical histories were reviewed; and the cause of death was identified. A total of 246 patients (85 [34.6%] men) with a mean age of 37.3 (±14.2) years were followed up for a median of 7 years. Over the study period, 136 patients died, with 40 experiencing SCD and 74 experiencing cardiac death (sudden and nonsudden). Age, atrial fibrillation, prolonged QRS duration, complete heart block, right atrial enlargement, right bundle branch block, increased right atrial pressure, impaired biventricular function, and the presence of a pacemaker were associated with increased risk of SCD, whereas advanced pulmonary hypertension therapies were protective. Atrial fibrillation (11.45-fold increased risk; P<0.001) and QRS duration ≥120 ms (2.06-fold increased risk; P=0.034) remained significant predictors of SCD in the multivariate analysis, whereas advanced pulmonary hypertension therapies were strongly protective against SCD (P<0.001). Conclusions Atrial arrhythmias, impaired ventricular function, and conduction system disease were associated with increased risk of SCD in this cohort of patients with Eisenmenger syndrome, providing an opportunity for early risk stratification and potential intervention. Clinical heart failure symptoms (New York Heart Association class ≥II) were predictive of increased mortality but not of SCD, suggesting a potential arrhythmic cause behind SCD.