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Importance Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, setting, and participants Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main outcomes and measures The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and relevance Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial registration ClinicalTrials.gov Identifier: NCT03509350.

Christos Theophanous,1 Bobeck S Modjtahedi,2,3 Michael Batech,4 David S Marlin,1 Tiffany Q Luong,4 Donald S Fong2–4 1Department of Ophthalmology, Southern California Medical Group, Los Angeles, CA, USA; 2Department of Ophthalmology, Southern California Permanente Medical Group, Baldwin Park, CA, USA; 3Eye Monitoring Center, Kaiser Permanente Southern California, Baldwin Park, CA, USA; 4Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA, USA Purpose: To evaluate the prevalence and risk factors for pediatric myopia in a contemporary American cohort. Methods: A cross-sectional study of pediatric patients enrolled in the Kaiser Permanente Southern California health plan was done. Eligible patients were 5- to 19-years old between January 1, 2008, through December 31, 2013, and received an ophthalmologic or optometric refraction. Electronic medical records were reviewed for demographic data, refraction results, and exercise data. Prevalence and relative risks of myopia (defined as ≤-1.0 diopter) were characterized. Age, sex, race/ethnicity, median neighborhood income, and minutes of exercise per day were examined as risk factors. Results: There were 60,789 patients who met the inclusion criteria, of which 41.9% had myopia. Myopia was more common in older children (14.8% in 5- to 7-year olds, 59.0% in 17- to 19-year olds). Asian/Pacific Islander patients (OR 1.64, CI 1.58–1.70) had an increased rate of myopia compared to White patients as did African Americans to a lesser extent (OR 1.08, CI 1.03–1.13). Median neighborhood household income of $25,000–40,000 was associated with lower rates of myopia (OR 0.90, CI 0.83–0.97) compared to median neighborhood household incomes less than $25,000. Having at least 60 min of daily exercise was associated with lower prevalence of myopia (OR 0.87, CI 0.85–0.89). Discussion: Myopia was common in this large and diverse Southern Californian pediatric cohort. The prevalence of myopia increases with age. Asian children are at highest risk for myopia. Exercise is associated with a lower rate of myopia and represents an important potentially modifiable risk factor that may be a target for future public health efforts. Keywords: children, epidemiology, exercise, refractive error, myopia, pediatrics, prevalence, public health

Developing a laboratory scale or pilot scale chemical process into industrial scale is not trivial. The direct conversion of CO2 to methanol, and concomitant production of hydrogen from water electrolysis on large scale, are no exception. However, when successful, there are certain benefits to this process over the conventional process for producing methanol, both economic and environmental. In this article, we highlight some aspects that are unique to the process of converting pure CO2 to methanol. Starting from pure CO2 and a separate pure source of H2, rather than a mixture of CO, CO2, and H2 as is the case with syngas, simplifies the chemistry, and therefore also changes the reaction and purification processes from conventional methanol producing industrial plants. At the core of the advantages is that the reaction impurities are essentially limited to only water and dissolved CO2 in the crude methanol. In this paper we focus on several aspects of the process that direct conversion of CO2 to methanol enjoys over existing methods from conventional syngas. In particular, we discuss processes for removing CO2 from a methanol synthesis intermediate product stream by way of a stripper unit in an overhead stream of a distillation column, as well as aspects of a split tower design for the distillation column with an integrated vapo-condenser and optionally also featuring mechanical vapor re-compression. Lastly, we highlight some differences in reactor design for the present system over those used in conventional plants.

We report a 56-year-old woman who had an unruptured posterior communicating artery aneurysm. Given the size and location of the aneurysm, as well as her history of smoking and age, she received endovascular treatment with the pipeline embolization device (PED; ev3 Endovascular, Plymouth, MN, USA), complicated by intraoperative rupture (IOR). Flow diversion therapy with the PED has become an increasingly popular method of aneurysmal embolization and parent vessel remodeling. While its on-label approval is for large unruptured aneurysms of the internal carotid artery, success in off-label scenarios has been reported, including ruptured aneurysms. IOR complicates endovascular aneurysm treatment and can cause devastating morbidity or mortality, necessitating acute embolization of the hemorrhaging aneurysm. This patient illustrates the feasibility of treating an IOR with a stand-alone flow diversion device by using PED.

Introduction: The emergence of mechanical thrombectomy has extended the time window for treatment of acute ischemic stroke and improved patient outcomes. Our institution developed a patient selection protocol aimed to improve patient outcomes following the procedure. Hypothesis: Implementation of a patient selection protocol based on evidence-based best practices improves patient outcomes following endovascular intervention in acute ischemic stroke. Methods: In January 2015, our institution developed a patient selection protocol for anterior circulation stroke, including patients with a documented large vessel occlusion, an NIH stroke scale ≥6, a pre-morbid modified Rankin Scale (mRS) ≤2, and with the initial groin puncture within 6 hours of stroke onset. Patients were excluded if pre-morbid life expectancy was ≤90 days, CT perfusion demonstrated 2 test, unpaired t test, and multivariable logistic regression analysis where appropriate. Results: Forty patients underwent endovascular treatment prior to protocol implementation with 65 patients treated under the protocol. Protocol implementation resulted in improved rates of TICI 2B/3 revascularization (87.7% protocol, 57.5% pre-protocol; p Conclusions: The development and implementation of a patient selection protocol for endovascular treatment of large vessel occlusion improves revascularization rates and functional outcomes.

Intracranial aneurysms of the pediatric population are rare, but giant fusiform aneurysms (GFAs) of the middle cerebral artery (MCA) are common within this cohort of patients. These aneurysms are difficult to treat and often require advanced microsurgical skills, as they are usually not amenable to direct clipping. Here, we report the successful treatment of a recurrent GFA of the MCA with three telescoping Pipeline Embolization Devices 6 months after attempted clip reconstruction in a pediatric patient.

Background Diffuse intracranial aneurysmal vasculopathy is a rare condition, previously described in patients with human immunodeficiency virus infection. IgG4-related disease (IgG4-RD) is a recognized inflammatory disease of systemic organs, leading to fibrosis of connective tissues. It also has been linked to inflammatory dilating aortic aneurysms, coronary vascular disease, hypophysitis, orbital pseudotumor, and pachymeningitis. It has not yet been described as a cause of diffuse intracranial dilating vasculopathy. Histologically, this disease is characterized by IgG4-plasma cell infiltration, fibrosis, and phlebitis. Case Description A 40-year-old woman presented with acute heart failure, valvular insufficiency, and mycotic coronary aneurysms, concerning for endocarditis. Infectious workup was negative. Concurrent neurovascular workup revealed intracranial aneurysms, appearing mycotic in origin. Despite aggressive treatment for more than 5 years, she suffered multiple episodes of subarachnoid hemorrhage from a progressive dilating intracranial vasculopathy. Serum IgG levels and aneurysm wall pathology were consistent with IgG4-RD. Conclusions This is the first reported case of a diffuse intracranial dilating vasculopathy secondary to IgG4-RD. Recognition of similar pathologic findings in clinical presentation and radiologic workup should prompt further rheumatologic workup and possible immunosuppressive therapies.

Spinal vascular malformations are rare vascular lesions that most frequently present with back pain, radiculopathy, and/or myelopathy. Neurological decline is typically secondary to progressive radiculopathy, myelopathy, venous thrombosis, and stroke. Few case reports have described thoracolumbar spinal vascular malformations that present with both subarachnoid and intraventricular hemorrhage. This is the first reported case of a thoracolumbar spinal vascular malformation presenting with isolated intraventricular hemorrhage on initial imaging followed by acute and fatal rehemorrhage.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 42 - N° 2 - p. 151-158

Auditory neuropathy (AN) is defined as a sensorineural hearing impairment (HI) characterized by preserved cochlear outer hair cell function with normal otoacoustic emissions but abnormal or absent brainstem evoked potentials. The prevalence of AN in HIs remains to be established and its pathophysiology has not been determined. Several environmental and genetic causes have been identified, but the majority of cases remain unexplained. In the last 10 years, many genes have been identified in isolated and/or syndromic HI. Some of them (OTOF, PJVK, DIAPH3, OPA1, FXN, PMP22, ERCC6, ERCC8, SLC19A2 and TIMM8A, for example) are responsible for phenotypes corresponding to the AN definition. This review will focus on isolated and syndromic forms of AN for which the causative genes have been identified.

To report on the outcomes of sequential bilateral cochlear implantation (CI) in children with inner ear malformation. The study design is a retrospective case study. The setting is a tertiary reference center. Two children presenting a profound bilateral congenital hearing loss with bilateral hypoplasia of the cochleovestibular nerves and hypoplasic external semicircular canal had a cochlear implant at respectively 16 months and 33 months. A second implant was proposed at respectively 17 and 20 months after the first implant. The main outcome measures are audiometry, perceptive results in closed and open set words (CSW and OSW) and oral production at follow-up. The first cochlear implant gave respectively mean thresholds at 60 dB and 70 dB. Bilateral CI showed mean threshold at respectively 40 dB and 55 dB. In case 1, perceptive assessment was 83% and 70% in respectively CSW and OSW with oral production and comprehension of sentences after 1 year follow-up. In case 2, the perceptive assessment showed no perceptive or linguistic evolution at 6 months follow-up. In cochleovestibular nerve hypoplasia, bilateral implantation could be discussed in cases of limited result after unilateral implant.

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.

Basilar artery aneurysms account for a small percentage of intracranial aneurysms; however, they are a diverse group of lesions necessitating different treatment techniques for those that are ruptured and unruptured. Basilar apex aneurysms are the most common type and are frequently wide-necked, necessitating stent-assisted coiling or balloon remodeling. Other techniques have evolved to forego stenting in acutely ruptured wide-necked aneurysms. The prevention of delayed thromboembolic complications with dual antiplatelet therapy in patients with stents is critical. After treatment, basilar aneurysms require close follow-up to ensure complete occlusion. Basilar apex aneurysms often require delayed re-treatment, especially when previously ruptured.

The management of intracranial aneurysms has evolved significantly over the past 2 decades. Anterior communicating artery aneurysms (AComAAs) represent a common and often challenging problem for physicians and patients. Experience and technological advances have broadened the indications for endovascular treatment of all aneurysms. Balloon-mounted catheters and intracranial stents are 2 technological advancements that have made the treatment of previously uncoilable aneurysms feasible. As with all intracranial aneurysms, complete angiographic occlusion remains the goal of care. Balancing the risks of thromboembolic complications with decreasing the risk of hemorrhage, especially in acutely ruptured aneurysms, represents an objective for vascular neurosurgeons.

Optimal medical therapy for symptomatic intracranial stenosis includes antiplatelet therapy and aggressive management of atherosclerotic medical conditions such as diabetes, hypertension, hyperlipidemia, and cigarette smoking. Systemic anticoagulation is not indicated. Two ongoing clinical trials are currently comparing angioplasty and stenting to medical management; the first report of one of these trials, SAMMPRIS, indicated that medical treatment may be superior to angioplasty and stenting. Angioplasty and stenting should be used with caution and be reserved for patients who remain actively symptomatic despite medical therapy.

Shunt infections are most common within the first 6 months following implantation. A shunt infection 19 years after implantation secondary to uterine ablation has not been reported to our knowledge. Office hysteroscopic procedures have become commonplace in gynecologic practice. Infectious complication rates are low, but peritonitis has been described. We present a patient with a ventriculoperitoneal shunt infection following a uterine ablation for dysfunctional uterine bleeding. Three days following the ablation she developed abdominal pain. CT scan of the abdomen 5 months after the procedure revealed a pseudocyst. She then underwent removal of her shunt with intra-operative cultures revealing Streptococcus agalactiae. Definitive treatment consisted of shunt explantation and antibiotic treatment with complete resolution of her pain and pseudocyst. Consideration for prophylactic antibiotics should be made when a patient with a ventriculoperitoneal shunt undergoes any transvaginal procedure.

Materials and methods Retrospective chart review was conducted on normal pressure hydrocephalus patients who received prospective evaluation at an adult hydrocephalus center and underwent ventriculoperitoneal or ventriculoatrial shunting with either Delta 1 (n = 140) or Orbis Sigma (n = 55) valves between September 1999 and June 2007. All patients received treatment and follow-up from a single surgeon. Time until first revision, time until first subdural hematoma requiring intervention, death – confirmed by the social security death index – and clinical outcome were assessed.

We report a new case of Say-Meyer syndrome, a rare X-linked disorder characterized by metopic suture synostosis, a high-arched palate, short stature and delayed development. Proband was a nine-month-old boy admitted to our hospital for evaluation of failure to thrive and global developmental delay. Genetics evaluation revealed: marked growth failure; microcephaly; a closed anterior fontanelle; hypotelorism; esotropia; long eyelashes; a high, narrow palate; distal hypospadias. Neurologic examination demonstrated diffuse hypotonia, diminished deep tendon reflexes, and excessive head lag. A search of the London Dysmorphology and POSSUM databases suggested Say-Meyer syndrome as the unifying diagnosis. This infant's medical history was complicated by prematurity at 32 weeks gestation, postnatal supplemental oxygen requirement and abnormal heart sounds. Cardiac evaluation identified Ebstein anomaly of the tricuspid valve as the etiology of his cardiac problems requiring ongoing medical surveillance. Magnetic resonance imaging (MRI) of the brain revealed a decreased volume of white matter with associated atrophy. The brain stem was small. The corpus callosum was thin and the genu and rostrum were not visualized. Increased signal intensity in the periventricular regions suggested periventricular leukomalacia. The ventricles were enlarged. Skull radiographs showed a decreased interorbital distance and a sclerotic metopic suture. X-linked recessive inheritance has been described. The infant's mother attended special education classes. She had marked hypotelorism, a long face, a high-arched palate, and a thin body habitus. This case of Say-Meyer syndrome includes the first report of brain MRI findings and a previously unreported cardiac defect. Clinical features noted in the mother of this infant that suggest that Say-Meyer syndrome may be an X-linked dominant disorder with variable penetrance rather than an X-linked recessive disorder.

To investigate the relation between common acid-base parameters and blood lactate concentrations and their prognostic importance in sick, ventilated neonates.Two hundred and seventy eight serial simultaneous measurements of arterial acid-base status and blood lactate concentrations were carried out in 75 mechanically ventilated neonates with indwelling arterial catheters (gestational age and birthweight, median (range) -29 (23-40) weeks, and 1340 (550-4080) g, respectively).There were no correlations between arterial blood lactate and pH and base excess within subjects (r = 0.07 and r = -0.06, respectively) and only weakly positive but clinically irrelevant positive correlations between subjects (r = 0.28 and r = 0.27) in this group. Even in those infants who had not received any bicarbonate before their initial measurements (n = 48), there were no correlations between initial blood lactate concentrations and pH (r = 0.27), base excess (r = 0.17), or serum bicarbonate concentrations (r = -0.18). There was no relation between peak lactate concentration (PLC) and base excess (r = 0.16), and only a weak correlation between peak lactate concentration (PLC) and pH (r = 0.28). Negative base excess was an insensitive indicator of raised lactate concentrations. Only two out of 33 (6%) instances of hyperlactataemia (lactate2.5 mmol/l) would have been identified with a base excess-10 mmol/l as a cutoff. Lower cutoff values of base excess or pH performed no better. Raised lactate concentrations were associated with increased mortality at all levels. While six of 53 (11%) infants with a PLC2.5 mmol/l died, this proportion increased to four of 15 (27%) with a PLC between 2.5-5.0 mmol/l, and four of seven (57%) with a PLC5.0 mmol/l. Infants showing little rise or a substantial fall in blood lactate fared better than those with persistently raised values. A clinically important increase in blood lactate preceded the development of clinical markers of deterioration and complications in six infants.Contrary to popular belief, pH or base excess cannot be used as proxy measures for blood lactate concentration, and independent measurement of the latter are needed. Blood lactate concentrations may provide an early warning signal and important prognostic information in ill, ventilated neonates. In this regard, serial measurements of blood lactate are more useful than a single value.