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1.
Can J Anaesth ; 70(7): 1194-1201, 2023 07.
Article in English | MEDLINE | ID: mdl-37280454

ABSTRACT

PURPOSE: Protocol-driven oxytocin regimens can reduce oxytocin administration compared with a nonprotocol free-flow continuous infusion. Our aim was to compare secondary uterotonic use between a modified "rule of threes" oxytocin protocol and a free-flow continuous oxytocin infusion after Cesarean delivery. METHODS: We conducted a retrospective before-and-after study to compare patients who underwent Cesarean delivery between 1 January 2010 and 31 December 2013 (preprotocol) with patients who underwent Cesarean delivery between 1 January 2015 and 31 August 2017 (postprotocol). The preprotocol group received free-flow oxytocin administration and the postprotocol group received oxytocin according to a modified rule of threes algorithm. The primary outcome was secondary uterotonic use and the secondary outcomes included blood transfusion, hemoglobin value < 8 g·dL-1, and estimated blood loss. RESULTS: In total, 4,010 Cesarean deliveries were performed in 3,637 patients (2,262 preprotocol and 1,748 postprotocol). The odds of receiving secondary uterotonic drugs were increased in the postprotocol group (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.04 to 1.70; P = 0.02). Patients in the postprotocol group were less likely to receive a blood transfusion. Nevertheless, the two groups were similar for the composite end point of transfusion or hemoglobin < 8 g·dL-1 (OR, 0.86; 95% CI, 0.66 to 1.11; P = 0.25). The odds of an estimated blood loss greater than 1,000 mL were reduced in the postprotocol group (OR, 0.64; 95% CI, 0.50 to 0.84; P = 0.001). CONCLUSIONS: Patients in the modified rule of threes oxytocin protocol group were more likely to receive a secondary uterotonic than those in the preprotocol group. Estimated blood loss and transfusion outcomes were similar.


RéSUMé: OBJECTIF: Les schémas thérapeutiques d'ocytocine basés sur un protocole peuvent réduire l'administration d'ocytocine par rapport à une perfusion continue en débit libre hors protocole. Notre objectif était de comparer l'utilisation secondaires d'agents utérotoniques entre un protocole modifié d'ocytocine en « règle de trois ¼ et une perfusion continue d'ocytocine à débit libre après un accouchement par césarienne. MéTHODE: Nous avons mené une étude rétrospective avant-après pour comparer les personnes ayant bénéficié d'une césarienne entre le 1er janvier 2010 et le 31 décembre 2013 (pré-protocole) avec les personnes ayant subi une césarienne entre le 1er janvier 2015 et le 31 août 2017 (post-protocole). Le groupe pré-protocole a reçu une administration d'ocytocine en débit libre et le groupe post-protocole a reçu de l'ocytocine selon un algorithme de règle de trois modifié. Le critère d'évaluation principal était l'utilisation secondaire d'agents utérotoniques et les critères d'évaluation secondaires incluaient la transfusion sanguine, un indice d'hémoglobine < 8 g·dL­1 et les pertes de sang estimées. RéSULTATS: Au total, 4010 accouchements par césarienne ont été réalisés chez 3637 patient·es (2262 pré-protocole et 1748 post-protocole). Les chances de recevoir des médicaments utérotoniques secondaires étaient plus élevées dans le groupe post-protocole (rapport de cotes [RC], 1,33; intervalle de confiance [IC] à 95 %, 1,04 à 1,70; P = 0,02). Les patient·es du groupe post-protocole étaient moins susceptibles de recevoir une transfusion sanguine. Néanmoins, les deux groupes étaient similaires en ce qui touchait au critère d'évaluation composite de transfusion ou d'hémoglobine < 8 g·dL­1 (RC, 0,86; IC 95, 0,66 à 1,11; P = 0,25). Les risques d'une perte de sang estimée supérieure à 1000 mL ont été réduits dans le groupe post-protocole (RC, 0,64; IC 95 %, 0,50 à 0,84; P = 0,001). CONCLUSION: Les patient·es du groupe du protocole d'ocytocine en règle de trois modifiée étaient plus susceptibles de recevoir un utérotonique secondaire que les personnes du groupe pré-protocole. Les pertes sanguines estimées et les résultats transfusionnels étaient similaires.


Subject(s)
Oxytocics , Postpartum Hemorrhage , Pregnancy , Female , Humans , Oxytocin , Retrospective Studies , Cesarean Section/methods , Blood Transfusion , Postpartum Hemorrhage/prevention & control
2.
Cult Health Sex ; 24(4): 499-516, 2022 04.
Article in English | MEDLINE | ID: mdl-33530887

ABSTRACT

Intimate partner violence and HIV remain significant health challenges among women living with HIV. Intimate partner violence has been linked to negative health outcomes and poorer HIV care engagement. This study examined intimate partner violence among Ugandan women living with HIV, their experiences disclosing such violence and how culturally normative factors affected disclosure-related outcomes. In a mixed-methods study conducted in Uganda in 2018, 168 women participated in interviewer-administered surveys; a sub-set who reported experiencing intimate partner violence participated in in-depth interviews (IDIs). Intimate partner violence was prevalent among women in the sample (68.0%); almost half experienced emotional violence (45.2%), while a smaller proportion had experienced physical (32.1%) and/or sexual violence (19.6%). Most women living with HIV (61.8%) had disclosed their experience of intimate partner violence to someone. Women who experienced intimate partner violence had higher odds of disclosure if they feared their partner and perpetrated violence against their partner. Thematic analysis of IDIs revealed enduring violence and blaming alcohol for men's perpetration of violence. Traditional cultural and gender norms, especially concerning motherhood and partnership, influenced women's experiences of intimate partner violence and disclosure. Multi-sectoral responses to challenge and reform cultural norms that perpetuate violence are needed, including mobilising key stakeholders (e.g. family, community, policy-makers) to serve as catalysts for change and encourage resource- and safety-seeking for women living with HIV to escape violence.


Subject(s)
HIV Infections , Intimate Partner Violence , Disclosure , Female , HIV Infections/psychology , Humans , Intimate Partner Violence/psychology , Male , Men , Sexual Partners/psychology , Uganda
3.
Br J Neurosurg ; 32(3): 291-294, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29430977

ABSTRACT

BACKGROUND: Endocrine abnormalities are well-recognized consequences of intracranial pathology such as pituitary tumours. Less commonly, hydrocephalus may lead to dysfunction of the endocrine system, presenting as amenorrhoea or precocious puberty. We present a case report and literature review of hydrocephalus causing endocrine abnormalities including reversible infertility. CASE DESCRIPTION: A 34 year-old female presented with amenorrhoea and infertility. MRI showed a third ventricular mass and hydrocephalus. The amenorrhoea resolved within weeks of endoscopic third ventriculostomy and tumour biopsy; pregnancy ensued within 6 months. Thirty-two cases of hydrocephalus-related amenorrhoea were reported between 1915 and 2007. All patients who underwent modern hydrocephalus treatment experienced partial or complete resolution of endocrine dysfunction. Successful pregnancy was reported in three patients, as in our case presentation. While mechanisms of dysfunction have not been completely elucidated, studies point toward loss of GnRH pulsatility due to compression of the medio-basal hypothalamic structures. CONCLUSION: Hydrocephalus can cause endocrine dysfunction, including amenorrhoea, which may reverse with CSF diversion. Therefore, cranial imaging is an important component in the evaluation of such endocrine abnormalities.


Subject(s)
Amenorrhea/etiology , Hydrocephalus/complications , Infertility, Female/etiology , Adult , Amenorrhea/pathology , Amenorrhea/surgery , Biopsy , Cerebral Aqueduct/pathology , Cerebral Aqueduct/surgery , Cerebral Ventricle Neoplasms/complications , Cerebral Ventricle Neoplasms/diagnosis , Cerebral Ventricle Neoplasms/pathology , Cerebral Ventricle Neoplasms/surgery , Female , Humans , Hydrocephalus/pathology , Hydrocephalus/surgery , Infertility, Female/pathology , Infertility, Female/surgery , Magnetic Resonance Imaging , Neurocytoma/complications , Neurocytoma/diagnosis , Neurocytoma/pathology , Neurocytoma/surgery , Neuroendoscopy , Neuronavigation , Pregnancy , Ventriculostomy/methods
4.
WMJ ; 116(4): 201-205, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29323806

ABSTRACT

BACKGROUND: Deer hunting is popular in much of the United States. In Wisconsin, use of tree stands for hunting is common. Spine surgeons at a Level 1 Trauma Center observed a high incidence of spine and spinal cord injury due to falls from tree stands while hunting. This study's purpose is to systematically characterize and classify those injuries. METHODS: We reviewed the University of Wisconsin Hospital and Clinics' trauma database for tree stand-related injuries from 1999 to 2013. We collected and analyzed data pertaining to hunters' demographics, comorbidities, type and mechanism of injury, injury severity, and management. RESULTS: We identified 117 patients evaluated after a tree stand fall. Sixty-five (ages 16-76) suffered spine fractures that occurred at all levels, from occipital condyle to sacrum, with thoracolumbar compression and burst fractures being most common. Fractures occurred in the following locations: cranio-cervical junction (8.7%), cervical spine (7.6%), cervical-thoracic junction (6.5%), thoracic spine (32.6%), thoracolumbar junction (33.7%), and lumbar spine (10.9%). Twenty-one patients (32%) experienced a single spinal fracture; 44 patients (68%) suffered multiple spinal fractures. Twenty-five patients (38%) required surgical fixation; 19 patients experienced loss of neurologic function: 5 complete spinal cord injuries (SCI), 5 incomplete SCI, 2 central cord syndromes, and 8 radiculopathies. Two mortalities, both of cardiopulmonary etiology, were noted-one in a patient without a spine fracture and the other in a patient with a complete spinal cord injury at T4. CONCLUSIONS: The majority of spine fractures are treated nonoperatively. However, enough patients require surgical intervention that consultation with a neurosurgical or orthopedic spine surgeon is prudent. It is more common to have multiple spine fractures from a tree stand fall, therefore, it is recommended that if 1 fracture is identified the entire spine be evaluated for additional fractures. For safety, it is recommended that hunters wear and use safety harnesses appropriately. Additionally, keeping the height of the tree stand at 10 feet or less is associated with a lower likelihood of spinal cord injury. Further study is needed to determine additional interventions such as education that might reduce the injury frequency in this population.


Subject(s)
Accidental Falls/statistics & numerical data , Spinal Cord Injuries/epidemiology , Spinal Injuries/epidemiology , Trees , Adolescent , Adult , Aged , Animals , Deer , Female , Humans , Male , Middle Aged , Retrospective Studies , Seasons , Spinal Cord Injuries/etiology , Spinal Injuries/etiology , Trauma Centers , Wisconsin/epidemiology , Young Adult
5.
J Emerg Med ; 48(3): 366-70.e3, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25497842

ABSTRACT

BACKGROUND: The Centers for Disease Control reports that motor vehicle crashes (MVCs) are the leading cause of injury and death among U.S. teenagers, and disproportionately affect males. Among preventable causes of MVCs involving teenage drivers, distracted driving continues to be a serious public health problem. OBJECTIVES: To describe gender differences in teenage drivers' self-perceptions of safe driving behaviors, and self-reported risk behaviors and distractions while driving. METHODS: We prospectively surveyed teenage drivers from four high schools in Pennsylvania and New Jersey. Gender comparisons were made between self-reported perceptions and self-reported driving behaviors. Descriptive statistics and chi-squared testing were used in data analyses; significance was set at p < 0.05. RESULTS: Seven hundred fifty-six high school teenage drivers completed surveys. Males (52%) and females (48%) were equally distributed; 32% of males reported that they were extremely safe drivers, whereas only 18% of females reported that they were extremely safe drivers (p < 0.001). Significantly more females (91%) compared to males (77%) reported always wearing their seatbelts (p < 0.001). Female drivers were more likely than male drivers to self-report that they always make their passengers wear a seat belt (76% vs. 63%, p < 0.001). A higher proportion of males reported using their cell phones while driving, compared to females (68% vs. 56%, p = 0.004), and 42% of males reported texting while driving, compared to 34% of females (p = 0.037). CONCLUSION: Teenage male drivers perceive themselves to be safe drivers, but report engaging in more distracted driving and risky behaviors compared to females. These results suggest that there is an opportunity for gender-specific educational and injury prevention programs for teen drivers.


Subject(s)
Adolescent Behavior/psychology , Automobile Driving/psychology , Dangerous Behavior , Risk-Taking , Sex Factors , Adolescent , Cell Phone/statistics & numerical data , Female , Humans , Male , New Jersey , Pennsylvania , Perception , Prospective Studies , Seat Belts/statistics & numerical data , Self Report , Text Messaging/statistics & numerical data
6.
Am J Hematol ; 89(4): 349-54, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24273135

ABSTRACT

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Salvage Therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Disease-Free Survival , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Hematologic Diseases/chemically induced , Humans , Infection Control , Kaplan-Meier Estimate , Karyotyping , Lenalidomide , Maintenance Chemotherapy , Male , Middle Aged , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Peripheral Nervous System Diseases/chemically induced , Proportional Hazards Models , Remission Induction , Thalidomide/administration & dosage , Thalidomide/adverse effects , Thalidomide/analogs & derivatives , Thrombosis/prevention & control , Treatment Outcome , Vincristine/administration & dosage , Vincristine/adverse effects
7.
World Neurosurg ; 189: 174-180, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878895

ABSTRACT

OBJECTIVE: This report describes the procedural nuances for use of an irrigating external ventricular drain (EVD) in an infant patient. Intraventricular hemorrhage (IVH) and other intraventricular pathologies, such as infection, can occur in a variety of situations and patient populations, with few interventions available for immediate resolution. While manual endoscopic surgical irrigation has been trialed in both adult and pediatric patient populations to clear blood products or debris, this concept has recently been further extrapolated to the use of a continuous irrigating EVD over a more extended period. While this technique has been more commonly used for subarachnoid hemorrhage in adults, study of its use in pediatric patients, particularly in infants, is lacking. METHODS: In this single case technical note of proof of feasibility, a continuous irrigating EVD was used in an infant to help clear an iatrogenic IVH. RESULTS: Utilization of an irrigating EVD was successfully completed in a 9 kg infant without associated complications. Clearance of IVH was noted after 9 days of irrigation. CONCLUSIONS: Use of irrigating EVD catheters should not be limited to the adult population. Indications for use are broad in the pediatric population and warrant further exploration.

8.
Med Sci Law ; : 258024231212878, 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37960837

ABSTRACT

This is a case of a patient who underwent an esophageal dilatation for benign esophageal strictures. As a consequence of the procedure, she developed an esophageal rupture and multiple cerebral and cerebellar air emboli resulting in infarction. The patient died after being placed on comfort care measures. The postmortem examination revealed focal breach of the esophageal mucosa but no sites of cardiac or vascular shunting that could account for the transit of air from the esophagus to the central nervous system. The phenomenon of vascular air entry as a consequence of upper gastrointestinal endoscopic intervention is an uncommon but very serious complication of balloon dilatation therapy. Instances of progression to intracranial arterial gas embolism are even less common, but are well described in a small number of case reports. We present a fatal case of central nervous system air embolism post-balloon dilatation therapy with associated antemortem imaging, autopsy, and microscopic images followed by a discussion of potential mechanisms of entry of air into the brain.

9.
J Emerg Med ; 43(1): 166-71, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22178506

ABSTRACT

BACKGROUND: The American Heart Association wants to increase the number of citizens who know how to perform cardiopulmonary resuscitation (CPR). It is unknown whether giving patients a prescription (Rx) to learn CPR is effective. We sought to determine if patients with, or at risk for, heart disease and their families were more likely to follow prescriptive advice to buy a CPR Anytime™ kit (American Heart Association, Dallas, TX) or to take a CPR class. METHODS: This was a prospective randomized pilot study of a convenience sample of 162 patients who presented to one of three recruiting sites: a suburban community emergency department (ED), an office-based primary care (IM), or cardiology (CD) setting. After consent was obtained, CPR-naïve participants aged>44 years were randomized to one of two study arms. One group received a Rx for a CPR Anytime™ self-learning kit, consisting of a CPR mannequin and a 22-minute DVD. The comparator group was prescribed a CPR class. RESULTS: At the IM office, 7/29 (24%), at the CD office 3/25 (12%), and at the ED 2/23 (9%) patients purchased the CPR kit. Across both investigational arms, 4 were lost to follow-up, yielding approximately 15% (12/77) who followed Rx advice to purchase the CPR kit and 0% (0/79) who took a CPR class. Cumulatively, a participant was significantly more likely to purchase a kit than to take a class (p=0.0004). CONCLUSION: Patients can be motivated to purchase CPR Anytime™ kits but not to take a CPR class from prescribed advice.


Subject(s)
Cardiopulmonary Resuscitation/education , Computer-Assisted Instruction , Patient Education as Topic/methods , Prescriptions , Aged , Cardiology , Emergency Service, Hospital , Female , Humans , Male , Middle Aged , Motivation , Pilot Projects , Primary Health Care
10.
Oper Neurosurg (Hagerstown) ; 22(4): 187-191, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35147577

ABSTRACT

BACKGROUND: The mainstay of treatment for cerebellar pilocytic astrocytomas in the pediatric population is surgery. The use of intraoperative magnetic resonance imaging (iMRI) as a surgical adjunct may lower the likelihood of reoperation. Studies have examined iMRI in heterogenous tumor populations, but few have looked at single pathologies. OBJECTIVE: To compare iMRI vs non-iMRI for hemispheric cerebellar pilocystic astrocytomas, specifically looking at revision surgeries and residual disease in follow-up. METHODS: Retrospective review of medical records for 60 sequential patients with cerebellar hemispheric pilocytic astrocytoma at a single institution was conducted. Thirty-two patients with cerebellar pilocytic astrocytoma underwent surgery without iMRI, whereas 28 patients underwent surgical resection with iMRI. All patients had at least 3-year follow-up. RESULTS: There were no significant differences between the patient populations in age, tumor size, or need for cerebrospinal fluid diversion between groups. Operative time was shorter without iMRI (without iMRI 4.4 ± 1.3 hours, iMRI 6.1 ± 1.5, P = .0001). There was no significant difference in the patients who had repeat surgery within 30 days (9% without iMRI, 0% iMRI, P = .25), residual disease at 3 months (19% without iMRI, 14% iMRI, P = .78), or underwent a second resection beyond 30 days (9% without iMRI, 4% iMRI, P = .61). There were more total reoperations in the group without iMRI, although this did not reach significance (19% vs 4%, P = .11). CONCLUSION: For hemispheric cerebellar pilocytic astrocytomas, iMRI tended to leave less residual and fewer reoperations; however, neither of these outcomes achieved statistical significance leaving utilization to be determined by the surgeon.


Subject(s)
Astrocytoma , Cerebellar Neoplasms , Astrocytoma/diagnostic imaging , Astrocytoma/surgery , Cerebellar Neoplasms/diagnostic imaging , Cerebellar Neoplasms/surgery , Child , Cohort Studies , Follow-Up Studies , Humans , Magnetic Resonance Imaging/methods , Neoplasm, Residual/diagnostic imaging , Neoplasm, Residual/surgery
11.
Oper Neurosurg (Hagerstown) ; 20(5): 469-476, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33428751

ABSTRACT

BACKGROUND: It is expected that the incidence of cerebrospinal fluid (CSF) shunt malfunctions would remain unchanged during the shelter-in-place period related to the COVID-19 pandemic. OBJECTIVE: To examine the number of shunt surgeries performed in a single institution during this time interval in comparison to equivalent periods in past years. METHODS: The numbers of elective and emergent/urgent shunt surgeries performed at a single institution were queried for a 28-d period starting on the third Monday of March, between years 2015 and 2020. These were further stratified by how they presented as well as the type of surgery performed. RESULTS: During the 28-d period of interest, in the years between 2015 and 2020, there was a steady increase in the number of shunt surgeries performed, with a maximum of 64 shunt surgeries performed in 2019. Of these, approximately 50% presented in urgent fashion in any given year. In the 4-wk period starting March 16, 2020, a total of 32 shunt surgeries were performed, with 15 of those cases presenting from the outpatient setting in emergent/urgent fashion. For the surgeries performed, there was a statistically significant decrease in the number of revision shunt surgeries performed. CONCLUSION: During the 2020 COVID-19 pandemic, there was an unexpected decrease in the number of shunt surgeries performed, and particularly in the number of revision surgeries performed. This suggests that an environmental factor related to the pandemic is altering the presentation rate of shunt malfunctions.


Subject(s)
COVID-19 , Cerebrospinal Fluid Shunts/statistics & numerical data , Neurosurgical Procedures/statistics & numerical data , Pandemics , Child , Communicable Disease Control , Georgia , Humans
12.
CNS Oncol ; 10(3): CNS75, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34469205

ABSTRACT

Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Histone H3 mutations have been identified in pediatric and adult gliomas, with H3K27M mutations typically associated with a posterior fossa midline tumor location and poor prognosis. Leptomeningeal disease is a known complication of histone-mutant glioma, but uncommon at the time of initial diagnosis. We describe a case of glioblastoma with H3K27M mutation that initially presented with progressive vision loss due to diffuse leptomeningeal disease in the absence of a mass lesion other than a small cerebellar area of enhancement and with cerebrospinal fluid cytology negative for malignant cells on two occasions, highlighting the importance of including primary CNS malignancies in the differential of diffuse radiographic leptomeningeal enhancement.


Lay abstract Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Histones are molecules around which DNA winds. GBM and other gliomas sometimes have genetic alterations called mutations in histone genes. Of these, a specific alteration in histone 3 called H3K27M has been described in a variety of primary brain tumors. In adult gliomas, the H3K27M mutation is typically associated with tumors located within the brainstem or other structures in the midline of the central nervous system and a poor prognosis. Although previously reported, involvement of the leptomeninges (the thin membranes covering the brain and spinal cord) is uncommon at the time of initial diagnosis of gliomas harboring H3K27M mutations. We describe a case of GBM that initially presented with vision loss due to diffuse leptomeningeal involvement. Imaging and laboratory studies, including two cerebrospinal fluid analyses by lumbar puncture, did not establish a diagnosis. Brain biopsy confirmed the presence of a tumor, and genetic testing performed on the tumor tissue identified the histone mutation. This case highlights the importance of including primary central nervous system malignancies as a possible diagnosis when there is diffuse radiographic leptomeningeal enhancement.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Meningeal Neoplasms , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Child , Glioma/diagnostic imaging , Glioma/genetics , Histones/genetics , Humans , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/genetics , Mutation/genetics
13.
Semin Hematol ; 58(1): 45-55, 2021 01.
Article in English | MEDLINE | ID: mdl-33509443

ABSTRACT

The DNA methyltransferase inhibitor azacytidine (aza) may reactivate pathways associated with plasma cell differentiation, cell cycle control, apoptosis, and immune recognition and thereby restore sensitivity to lenalidomide (len) and dexamethasone (dex) in relapsed and/or refractory multiple myeloma (RRMM). We aimed to develop an aza regimen that reaches epigenetically active levels 8 times in 28 days with less bone marrow toxicity than the myeloid malignancy standard of 7 consecutive doses to enable safe combination with len. Aza was escalated from 30 mg/m2 once a week up to a predefined maximum of 50 mg/m2 twice a week in combination with GFR-adjusted len (≥ 60 mL/min: 25 mg, 3059 mL/min: 10 mg) day 1 to 21 every 28 days and dex 40 mg once a week followed by a limited expansion study to a total N of 23 at the highest tolerated dose. Fifty-one patients (pts) with RRMM were screened, 42 were treated and 41 were evaluable for response based on at least 1 response assessment or progression after treatment start. The median number of prior lines of therapy was 5 (1-11) and 81% (34) were refractory to len and/or pomalidomide (pom). Two DLTs occurred in different cohorts, 1 neutropenic fever in 1/6 pts on the aza 40 mg/m2 twice a week GFR ≥ 60 mL/min cohort and 1 GGT elevation in 1/6 pts on the aza 50 mg/m2 GFR 30-59 mL/min cohort. An MTD was not reached and aza 50 mg/m2 SC twice a week was chosen for the expansion study. At least possibly related Grade 3/4 AEs occurred in 28 pts (67%) with the following in > 1 pt: neutropenia (N = 16, 38%), anemia (N = 6, 14%), lymphopenia (N = 5, 12%), thrombocytopenia (N = 4, 10%), leukopenia (N = 4, 10%), febrile neutropenia (N = 4, 10%), fatigue (N = 3, 7%), fever (N = 2, 5%), and infection (N = 2, 5%). At a median follow up time for alive pts of 60.2 months (range: 36.1-82.5 months), the overall response rate (≥ partial response) and clinical benefit response rate (≥ minor response) was 22 and 32%, respectively, with 4 very good partial responses (10%), 5 partial responses (12%), and 4 minor responses (10%). The median PFS was 3.1 months (95% confidence interval [CI]: 2.1-5.1 months), median TTP 2.7 months (95% CI: 2.1-7.5 months), and median OS 18.6 months (95% CI: 12.9-33.0 months). Achieving at least minor response and reaching TTP > 6 months was associated with approximately 35% lower median plasma levels of the enzyme that inactivates aza, plasma cytidine deaminase (CDA, P< .0001). Two of the len refractory pts achieved longer disease control than with any prior regimen and 1 responded immediately after progression on len, bortezomib, and prednisone. Analyses of the methylation state of over 480,000 CpG sites in purified myeloma cells at screening were possible in 11 pts and on day 28 in 8 of them. As in other studies, the majority of differentially methylated CpGs compared to normal plasma cells were hypomethylated in myeloma. Treatment decreased the number of CpGs that were differentially methylated in normal plasma cells by > 0.5% in 6 and by > 5% in 3 of the 8 pts, most pronounced in 2 pts with clinically convincing aza contribution who achieved a reduction in overall differentially methylated CpGs by 23 and 68%, respectively, associated with increased expression of immunoglobulin genes. The study demonstrated tolerability of twice a week SC aza at 50 mg/m2 with len and dex in RRMM and suggested aza may help overcome the len/pom refractory state, possibly by activating differentiation pathways. Relatively low response rates and association of clinical benefit with low plasma levels of the aza inactivating enzyme CDA suggest the aza regimen will need to be optimized further and pt selection may be required to maximize benefit.


Subject(s)
Multiple Myeloma , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Azacitidine/adverse effects , DNA Methylation , Dexamethasone/adverse effects , Humans , Lenalidomide/pharmacology , Lenalidomide/therapeutic use , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Treatment Outcome
14.
World Neurosurg ; 126: 134-138, 2019 06.
Article in English | MEDLINE | ID: mdl-30831286

ABSTRACT

BACKGROUND: Slit-ventricle syndrome (SVS) is a recognized complication of ventricular shunt malfunction, resulting in cyclical symptoms without ventricular dilatation. We present a case of SVS with transient, repetitive, and progressive signs of brainstem herniation evidenced by pupillary dilatation, posturing, and unresponsiveness, with diffuse voltage attenuation on electroencephalogram (EEG). CASE DESCRIPTION: A 32-year-old female presented with a history of hydrocephalus and ventriculoperitoneal shunt placement at 9 months of age. She began experiencing significant headaches in college, later accompanied by stereotypical 5- to 25-minute episodes of unresponsiveness, posturing and pupillary dilatation, and failing anticonvulsant therapy. No neurosurgical evaluation was sought because of small ventricles on brain imaging. Episodes became progressively more frequent over a 10-year period, eventually occurring daily. On presentation, 5 clinical events were captured on EEG over 12 hours of monitoring. With each episode, she became unresponsive and hypertensive, with fixed, dilated pupils and flexor posturing. Between events, she was awake and alert, without confusion or postictal state. She had papilledema and limited extraocular movements, with normal pupils and vital signs. Computed tomography scanning showed small ventricles. A shunt tap revealed no flow. With each episode onset, an EEG revealed an abrupt background rhythm slowing to 2-3 Hz delta range without epileptiform discharges. Between events, EEGs displayed normal waveform activity. Emergent ventriculoperitoneal shunt revision resulted in no further episodes in a 4-year follow-up period. CONCLUSIONS: SVS can lead to severe intermittent brainstem herniation syndrome in the setting of shunt malfunction. Seizure diagnosis should be reserved for cases with proven functional shunt and EEG confirmation of epileptiform activity.


Subject(s)
Hernia/diagnosis , Seizures/diagnosis , Slit Ventricle Syndrome/surgery , Ventriculoperitoneal Shunt/adverse effects , Adult , Diagnosis, Differential , Electroencephalography , Female , Hernia/diagnostic imaging , Hernia/etiology , Humans , Hydrocephalus/surgery , Reoperation , Seizures/diagnostic imaging , Seizures/etiology , Slit Ventricle Syndrome/complications , Tomography, X-Ray Computed
15.
Oper Neurosurg (Hagerstown) ; 17(3): E113, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-30690494

ABSTRACT

The superficial temporal artery (STA) to the middle cerebral artery (MCA) bypass is the most common bypass type for revascularization to treat cerebral ischemia. If the ipsilateral STA is not available for anastomosis, various options for bypass conduits can be exercised. When the entire ipsilateral external carotid and its branches are not available, the contralateral STA may be used as a donor artery through an interposition graft. This technique is known as a "bonnet bypass." In this video, we demonstrate the utilization of a bonnet bypass in a 48-yr-old man with protein S deficiency, and right carotid artery occlusion with recurrent strokes and transient ischemic attacks (TIA). After exhausting nonsurgical options by treating with 2 antiplatelet drugs and supportive lifestyle changes, the patient continued to experience TIAs and watershed strokes in the right hemisphere. Angiography showed that the right anterior artery and the MCA were filled through the Circle of Willis, but the ipsilateral STA and entire external and common carotid arteries were not patent for potential use as a bypass donor. Since the ipsilateral bypass options were not available, we elected to perform a bypass from the contralateral STA trunk to the ipsilateral M2 with a saphenous vein interposition graft, for a so-called bonnet bypass. The patient did well after surgery and has remained symptom-free for 19 mo post bypass. The surgical technique and each step in performing this bonnet bypass are demonstrated in this 3-dimensional video. The patient consented to the publication of his operative video.

16.
J Neurosurg Pediatr ; : 1-6, 2019 Feb 22.
Article in English | MEDLINE | ID: mdl-30797212

ABSTRACT

An extraosseous intradural presentation for a sacral chordoma in the pediatric age group has not been reported to date. This is a report on an 11-year-old boy who presented with an extraosseous, intradural sacral chordoma. He underwent gross-total resection and received adjuvant proton beam therapy. Neoplastic transformation of the notochord is reviewed to illustrate the developmental basis for the surgical anatomy and pathogenesis of the classic chordoma variant. Clinical and pathological features are reviewed to differentiate this chordoma presentation from classic osseous chordomas and ecchordosis physaliphora, a related benign developmental notochordal lesion. Finally, the role of developmental signaling in the pathogenesis of chordomas from postembryonic notochordal tissue is discussed.

17.
World Neurosurg ; 127: e101-e107, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30851463

ABSTRACT

OBJECTIVES: Spine surgeons at a Level 1 Trauma Center have observed a high incidence of spine and spinal cord injuries owing to falls from tree stands. These injuries have been retrospectively reviewed in the context of the Thoracolumbar Injury Classification and Severity (TLICS) and the Subaxial Cervical Injury Classification and Severity (SLICS) classification systems to assess inter-user reliability and validity. We hypothesize that the inter-rater reliability will be similar between neuroradiology and neurosurgery raters and validity of the scoring system will be maintained at our institution. METHODS: The University of Wisconsin Hospital and Clinics' trauma database was reviewed for tree stand-related injuries from 1999 to 2013, with a focus on patients suffering from spine and spinal cord injuries. The TLICS and SLICS scores were then independently determined for these injuries by a neurosurgeon and a neuroradiologist. RESULTS: When cases were grouped by management recommendation (operative, equivocal, and nonoperative) reviewer agreement was 12/15 (80%) of SLICS and 38/52 (73%) of TLICS scores. Operative SLICS positive predictive value reached 100%, however, with a wide confidence interval. Conversely, the SLICS negative predictive value was poor at 54%-60%, with frequent operative treatment for patients assigned nonoperative scores. TLICS scores reached 77.8% and 93.3% positive predictive value per reviewer, whereas negative predictive values reached 93.9% and 89.2%, respectively. CONCLUSIONS: The TLICS and SLICS systems provide good-to-excellent inter-rater reliability. SLICS validity was poor, whereas TLICS was reasonable for nonoperative cases and moderate for operative cases. Systems such as the TLICS and the SLICS may be best applied in the educational setting to confirm the fracture morphology and presence or absence of ligamentous injury between surgeons and radiologists.


Subject(s)
Cervical Vertebrae/injuries , Lumbar Vertebrae/injuries , Spinal Cord Injuries/surgery , Spinal Fractures/surgery , Thoracic Vertebrae/injuries , Trauma Severity Indices , Accidental Falls/statistics & numerical data , Cervical Vertebrae/surgery , Conservative Treatment , Female , Humans , Lumbar Vertebrae/surgery , Male , Neck Injuries/classification , Observer Variation , Predictive Value of Tests , Registries , Retrospective Studies , Spinal Cord Injuries/classification , Spinal Cord Injuries/etiology , Spinal Cord Injuries/therapy , Spinal Fractures/classification , Spinal Fractures/etiology , Spinal Fractures/therapy , Thoracic Vertebrae/surgery , Wisconsin/epidemiology
18.
Cleve Clin J Med ; 86(1): 39-46, 2019 01.
Article in English | MEDLINE | ID: mdl-30624183

ABSTRACT

Monoclonal gammopathy of undetermined significance (MGUS) is commonly diagnosed in outpatients being worked up for an array of clinical concerns. It carries a risk of progression to myeloma and other lymphoproliferative disorders that, albeit low (1% per year), warrants regular follow-up. Patients with MGUS can be risk-stratified on the basis of the amount and type of their monoclonal protein as well as whether they have an abnormal light-chain ratio. Here, we provide a guide to the diagnosis, workup, and management of MGUS.


Subject(s)
Paraproteinemias/therapy , Humans , Paraproteinemias/diagnosis
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