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Introduction: Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. Methods: HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. Results: We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. Conclusions: Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.

Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated.Report the results of the first years (2017-2019) of the Mexican FH registry.There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations.To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033).The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

Objective: To examine the relationships between diabetes care measures and HbA1c levels through analyzing the National Health and Nutrition Examination Survey (NHANES) data between 2007 and 2016. Methods: This cross-sectional study involved subjective and objective data obtained from the CDC NHANES website. Data was then analyzed by STATA14 with ordered logistic regression models, controlling for age, race, gender, health insurance coverage. Subjective data included participants’ answers to the general and diabetes-related questionnaires, and the objective data was their HbA1c levels at the time of the interview/standardized clinical examination. Results: Three of the eight regression analysis models showed statistically significant associations between HbA1c levels and identified diabetes care questions. Conclusion: The levels of HbA1c in people with diabetes were associated with how long ago the participant checked-in with a diabetes specialist, whether having a doctor for diabetes care or not, and how often the participant saw a doctor within a year before the NHANES interview/examination. These findings suggest that connecting with healthcare professionals (Questions 1 - 3) showed significant relationships with HbA1c levels, but the same relationships were not observed between receiving or performing the actual diabetes care measures (Questions 4 - 8) and HbA1c levels. Disclosure C.F. Young: None. H.E. Velasco: None.

The asthma-obesity syndrome represents a major public health concern that disproportionately contributes to asthma severity and induces insensitivity to therapy. To date, no study has shown an intrinsic difference between human airway smooth muscle (HASM) cells derived from nonobese subjects and those derived from obese subjects. The objective of this study was to address whether there is a greater response to agonist-induced calcium mobilization, phosphorylation of myosin light chain (MLC), and greater shortening in HASM cells derived from obese subjects. HASM cells derived from nonobese and obese subjects were age and sex matched. Phosphorylation of MLC was measured after having been stimulated by carbachol. Carbachol- or histamine-induced mobilization of calcium and cell shortening were assessed in HASM cells derived from nonobese and obese donors. Agonist-induced MLC phosphorylation, mobilization of calcium, and cell shortening were greater in obese compared with non-obese-derived HASM cells. The MLC response was comparable in HASM cells derived from obese nonasthma and nonobese fatal asthma subjects. HASM cells derived from obese female subjects were more responsive to carbachol than HASM cells derived from obese male subjects. Insulin pretreatment had little effect on these responses. Our results show an increase in agonist-induced calcium mobilization associated with an increase in MLC phosphorylation and an increase in ASM cell shortening in favor of agonist-induced hyperresponsiveness in HASM cells derived from obese subjects. Our studies suggest that obesity induces a retained phenotype of hyperresponsiveness in cultured human airway smooth muscle cells.

Background: Scabies is a contagious dermatosis caused by human mites, (Sarcoptes scabei, variant hominis). In crusted (Norwegian) scabies, the burden of mite infestation is higher and up to 2 million per person, facilitating easy skin-to-skin transmission and nosocomial transmission. We describe a case of undiagnosed crusted scabies and subsequent transmission to employees in our hospital. Methods: A 90-year-old female was admitted to our 636-bed, nonprofit, academic hospital for 22 days prior to diagnosis of crusted scabies by skin scraping. The patient was admitted to 2 different medical-surgical wards and the medical intensive care unit. We collected healthcare worker (HCW) demographics, including department of service, age, sex, pregnancy, and breastfeeding status in those who were at risk of exposure. We interviewed HCWs at 2 time points and collected information related to infestation, allergies to treatment, acceptance of empiric treatment, and whether employee was furloughed. Results: On initial screening, 20 of 124 at-risk HCWs had symptoms (Fig.). Most had a “new onset raised red rash or new pimple like rash (not on face), or linear rash” and 4 had “new onset uncontrollable itching.” All 124 HCWs were contacted 28 days later. One HCW that had not been compliant with prophylaxis became symptomatic and was diagnosed with scabies by dermatology. Of the remaining 20 HCWs, 3 were still having symptoms (2 had itching and 1 had a rash and a scrape performed by dermatology with confirmation of mites). All 3 were retreated with ivermectin. Overall, 21 of 124 exposed HCWs were ultimately symptomatic. Conclusions: During a 22-day admission of an undiagnosed and unisolated elderly patient with crusted scabies, the scabies mite was transmitted to 21 HCWs for an acquisition rate of 17%. Persistence of symptoms after treatment with permethrin occurred in 14%. The infectivity of this disease necessitates early recognition and infection control measures.Funding: NoneDisclosures: None

Background Tracking of disinfection of portable medical equipment (PME) and demonstration of compliance with PME disinfection policies can be difficult to demonstrate. A Disinfection Tracking System (DTS) was implemented in our hospital to assess the impact of such a system on the disinfection events of PME and its ability to capture disinfection events. The DTS system improved the total disinfection events as well as disinfection events on commonly used items such as Computer-on-wheels (COWs) and vitals machine (VM) (Figures 1 & 2). Here we present a summary of healthcare workers’ (HCWs) opinions about the implementation of the DTS system in their routine work flow. Image of DTS Mounted on a Computer-on-Wheel Image of a DTS Mounted on a Vitals Machine Methods The study was conducted on two medical-surgical acute care units in Temple, TX Veterans Affairs hospital. The DTS devices were equipped with sensors to detect moisture events corresponding to disinfection. A display on the device indicated the last time the PME was disinfected. Opinions were obtained after the 10-week study period through a survey and facilitated group discussions between frontline HCWs and managers who had encountered the DTS during their daily work routine. The survey measured level of agreement with 13 items on a Likert-type scale system ranging from one (least agreement) to ten (most agreement). Disinfection Tracking System with Screen Displaying Time Since Last Disinfection Results A total of 17 surveys were completed. The lowest mean agreement score was 5.1 for the statement - the DTS system display corresponds to a real disinfection of the equipment and the highest mean agreement scores included - the DTS system was easy to understand and follow and the DTS system can easily be adopted in my routine workflow. Lastly, - the DTS system helped improve the disinfection of my COW and the DTS system will improve patient outcomes corresponded to agreement score means of 8.1 and 7.9, respectively. In the group discussions, all the involved groups of healthcare workers expressed agreement in the ease of use of the system and minimal disruption in workflow. Conclusion Our survey and interview results indicate that most of the HCWs who interacted with the device had a positive interaction with the device. They stated the DTS system helped serve as an indicator about the last disinfection event. They also noted the system integrated well into their workflow without any disruption or additional workload. Disclosures Sarah Simmons, DrPH, Xenex Disinfection Services (Employee, Shareholder) Mark Stibich, PhD MHS, Xenex Disinfection Services, Inc (Board Member, Employee) Chetan Jinadatha, MD, MPH, AHRQ (Research Grant or Support)Department of Veterans Affairs (Other Financial or Material Support, Owner: Department of Veterans Affairs. Licensed to: Xenex Disinfection System, San Antonio, TX)Inventor (Other Financial or Material Support, Methods for organizing the disinfection of one or more items contaminated with biological agents)NiH/NINR (Research Grant or Support)NSF (Research Grant or Support)Xenex Healthcare Services (Research Grant or Support)

Introduction Analysis of sleep breathing sounds has been employed to screen obstructive sleep apnea (OSA). However, most current methods rely on specialized equipment (e.g., tracheal microphones), require additional physiological data (e.g., oxygen saturation), are rule-based, or are trained on data collected in-lab, making them less suitable for home use. In this study, deep learning methods were leveraged to explore the hypothesis that sleep audio recordings collected via smartphones can be used alone to screen for OSA by exploiting the temporal pattern of respiration sounds. Methods Adult participants with suspected sleep-disordered breathing of varying degrees of severity were recruited from the general population and from GP referrals to sleep clinic. Audio recordings were collected via smartphones during home sleep apnea testing (HSAT). HSAT data were scored by a registered polysomnographic technologist in accordance with current international guidelines (AASM V2.5, 2018) and used as reference. To exploit acoustic respiration temporal pattern, time interval histograms were computed for sequences of audio-words that were automatically learned from spectral features with a deep neural network. Means and standard deviations of the time intervals for each audio-word were employed by a Gaussian mixture model to classify 2-minute audio recording segments as either containing OSA events or not. Results Preliminary data from 4 valid nights’ recordings obtained from 2 consented participants was analysed. 550 segments were used for training, with 180 segments used for evaluation. Audio recording demonstrated a sensitivity of 0.71 and specificity of 0.66 when compared with manually-scored HSAT. Conclusion Preliminary results suggest that an approach to OSA screening based on deep learning with inter-audio-word intervals to capture information about respiration temporal pattern may be a useful tool in diagnosis of OSA. Further model development is underway using data collected from up to 200 patients and full study data will be presented. Support The project is supported by an Innovate UK grant (project number 157358). HR is supported by a joint scholarship from Passion for Life Healthcare Ltd and University of Sheffield. LH acknowledges the financial support of NHS Research Scotland (NRS), through NHS Lothian.

Mutations in KRAS, NRAS, and BRAF (RAS/BRAF) genes are the main predictive biomarkers for the response to anti-EGFR monoclonal antibodies (MAbs) targeted therapy in metastatic colorectal cancer (mCRC). This retrospective study aimed to report the mutational status prevalence of these genes, explore their possible associations with clinicopathological features, and build and validate a predictive model. To achieve these objectives, 500 mCRC Mexican patients were screened for clinically relevant mutations in RAS/BRAF genes. Fifty-two percent of these specimens harbored clinically relevant mutations in at least one screened gene. Among these, 86% had a mutation in KRAS, 7% in NRAS, 6% in BRAF, and 2% in both NRAS and BRAF. Only tumor location in the proximal colon exhibited a significant correlation with KRAS and BRAF mutational status (p-value = 0.0414 and 0.0065, respectively). Further t-SNE analyses were made to 191 specimens to reveal patterns among patients with clinical parameters and KRAS mutational status. Then, directed by the results from classical statistical tests and t-SNE analysis, neural network models utilized entity embeddings to learn patterns and build predictive models using a minimal number of trainable parameters. This study could be the first step in the prediction for RAS/BRAF mutational status from tumoral features and could lead the way to a more detailed and more diverse dataset that could benefit from machine learning methods.

BackgroundRecent surveys have failed to examine cerebrovascular aneurysm treatment practices among US physicians.ObjectiveTo survey physicians who are actively involved in the care of patients with cerebrovascular aneurysms to determine current aneurysm treatment preferences.MethodsA 25-question SurveyMonkey online survey was designed and distributed electronically to members of the Society of NeuroInterventional Surgery, Society of Vascular and Interventional Neurology, and the American Association of Neurological Surgeons/Congress of Neurological Surgeons Combined Cerebrovascular Section.Results211 physicians completed the survey. Most respondents recommend endovascular treatment as the first-line management strategy for most ruptured (78%) and unruptured (71%) aneurysms. Thirty-eight per cent of respondents indicate that they routinely treat all patients with subarachnoid hemorrhage regardless of grade. Most physicians use the International Study of Unruptured Intracranial Aneurysms data for counseling patients on natural history risk (80%); a small minority (11%) always or usually recommend treatment of anterior circulation aneurysms of ConclusionsThis survey demonstrates considerable variability in patient selection for intracranial aneurysm treatment, preferred treatment strategies, and follow-up imaging schedules among US physicians.

Background Portable Medical Equipment (PME) can play a vital role in transmission of multidrug-resistant organisms. Cleaning PME is challenging and protocols vary by institution. Tracking of PME cleaning events is usually performed manually and demonstration of compliance with protocols is difficult. We studied a Disinfection Tracking Systems (DTS) to understand its potential role in tracking disinfection events of PME and whether its implementation led to improvement in the number of cleaning events. The DTS device was designed to automatically register several types of disinfection events and could be set to display time since last disinfected on the screen. Methods For a 25-day period, a single acute care unit received a DTS device with the display screen off but with the ability to detect and log disinfection events in a database from a disinfectant wipe. After the 25-day screen-off period the DTS units screen was turned on to display the number of hours since the last recorded disinfection event (Figure 1) for a 42-day period. DTS devices were placed on 10 computer-on-wheels (COW) and 5 vitals machine (VM). An interrupted time series analysis, using a Bayesian model compared the number of events in the display screen-off to the screen-on period. Disinfection Tracking System with Screen-off and Screen-on Results During the 25-day screen-off period, there were a total of 345 events captured with 61 events on VM and 284 on COWs averaging 0.49 and 1.26 cleaning events for VM and COWs respectively per day. During the 42-day screen-on period, there were 845 total disinfection events with 104 events on VM and 741 events on COWs with 0.50 and 1.76 mean events for VM and COWs respectively per day. The mean events per device per day in the screen-on period for COW’s were 1.32 (1.10 – 1.57) times greater than those in the screen-off Period. The mean events per device per day in the screen-on period for VM devices was 1.37 (0.89 – 2.01) times greater than those in the screen-off period. Conclusion Disinfection events for COWs and VMs were found to be above the local policy requirements. Implementation of a DTS device was able to increase the rate of disinfection events for COWs potentially due to the prompt on the screen. Additionally, it captured disinfection events successfully on the database demonstrating its effective to be a tool for demonstration of compliance. Disclosures Mark Stibich, PhD MHS, Xenex Disinfection Services, Inc (Board Member, Employee) Sarah Simmons, DrPH, Xenex Disinfection Services (Employee, Shareholder) Chetan Jinadatha, MD, MPH, AHRQ (Research Grant or Support)Department of Veterans Affairs (Other Financial or Material Support, Owner: Department of Veterans Affairs. Licensed to: Xenex Disinfection System, San Antonio, TX)Inventor (Other Financial or Material Support, Methods for organizing the disinfection of one or more items contaminated with biological agents)NiH/NINR (Research Grant or Support)NSF (Research Grant or Support)Xenex Healthcare Services (Research Grant or Support)

Introduction Comorbidities including pulmonary disease are common in patients undergoing LVAD implantation. The impact of pre-implant pulmonary function on post-implant LVAD outcomes has not been comprehensively explored. In this study, we examined the association between pre-implant pulmonary function on post-implant outcomes. Methods A retrospective review of 415 primary LVAD implants at our center between 2008 and 2019 identified 251 patients with pre-implant pulmonary function tests (PFT), of which 248 had pre-implant chest CT scans. PFT results were classified as obstructive or restrictive and were sub-stratified by severity. Chest CT scan findings were assessed for presence of fibrosis or emphysema. Our primary outcome was 1-year mortality. Secondary outcomes included reintubation, days on mechanical ventilation, post-operative pneumonia, ICU length of stay (LOS), hospital LOS and 30-day mortality. Continuous variables were evaluated using two-sample Student's t-test or Wilcoxon test. Categorical variables were evaluated using χ2 test or Fisher's exact test. The group comparison in outcomes were assessed using logistics regression and linear regression. Results PFTs and chest CT scans were completed at a median of 42 days (IQR 18-127 days) and 26 days (IQR 10-63 days), respectively, prior to LVAD implantation. 84 patients (35%) had obstructive lung disease (52% moderately severe or severe) and 132 patients (55%) had restrictive lung disease (23% moderately severe or severe). Lung diffusing capacity for carbon monoxide (DLCO) was normal in 23% of patients and reduced in others by mild (29%), moderate (41%) or severe (7%) degrees. Presence or severity of either obstructive or restrictive lung disease on PFTs were not associated with primary or secondary outcomes. Severe reduction in DLCO and presence of fibrosis on chest CT scan were both strongly predictive of mortality at 30 days (OR 10.0, CI 1.52-65.63, p Conclusions Pulmonary disease is common in patients undergoing LVAD implantation. The presence and severity of obstructive or restrictive lung disease on pre-implant PFTs were not predictive of post LVAD outcomes. However, a severe reduction of DLCO and pulmonary fibrosis on pre-implant chest CT scan were associated with 30-day and 1-year mortality.

Background Portable Medical Equipment (PME) are routinely used by healthcare workers (HCWs). Transmission of healthcare-acquired infections has been attributed to PME. Our institution policy requires at least once daily PME disinfection. Automated tracking of disinfection events by Disinfection Tracking System (DTS) makes routine monitoring possible. We tested the device to see if it could provide accurate information about disinfection practices and patterns, as well as be used to accurately monitor compliance with policy. Methods Data obtained from DTS devices on PME from 2 acute care wards over a 25-day period was obtained. DTS devices record disinfection events and are automatically stored for monitoring. DTS was placed on 10 computer-on-wheels (COWs) and 5 vitals machine (VMs) on both the wards. One ward received DTS with “Screen-on” feedback displaying the time since last disinfection event, and one unit had no display on the screen (screen-off). The number of recorded events was summed over the 25-day period and sorted by time of day to determine the pattern of events over a typical 24-hour period. Minute “0” indicates start of each monitoring period in a 24-hour cycle and corresponds to 12 midnight (Figure 1). Results A total of 421 moisture events were recorded for the screen-on and 345 for the screen-off, during the 25-day implementation period. The highest number of events occurred between 6am and 7am, with 69 moisture events recorded in the screen-on group and 75 events were recorded for the screen-off group. Further, 37 events were recorded in the screen-on group and 43 events in the screen-off group between 2pm and 3pm. Between 6pm and 7pm the screen-on group showed 52 moisture events and 32 events for the screen-off group. Figures 1 shows the three peaks corresponding with a spike in disinfection events. Conclusion The pattern of disinfection events over 24 hours demonstrate that most events occurred regularly at certain times in the day. These time points correspond with higher volumes of disinfection happening at the beginning of shift changes for nursing. It also demonstrated that disinfection rates were higher than the policy recommended once a day PME disinfection. DTS has the potential to continuously record & report data related of disinfection events on PME in healthcare settings. Disclosures Chetan Jinadatha, MD, MPH, AHRQ (Research Grant or Support)Department of Veterans Affairs (Other Financial or Material Support, Owner: Department of Veterans Affairs. Licensed to: Xenex Disinfection System, San Antonio, TX)Inventor (Other Financial or Material Support, Methods for organizing the disinfection of one or more items contaminated with biological agents)NiH/NINR (Research Grant or Support)NSF (Research Grant or Support)Xenex Healthcare Services (Research Grant or Support) Mark Stibich, PhD MHS, Xenex Disinfection Services, Inc (Board Member, Employee) Sarah Simmons, DrPH, Xenex Disinfection Services (Employee, Shareholder)

Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n = 42) patients included in the analysis had Child B (n = 35) or C (n = 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n = 7) or without (n = 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End-Stage Liver Disease score was 12 (range, 6-25). Treatment was well tolerated overall with more than one-half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n = 6), insomnia (n = 4), headache (n = 5), nausea (n = 4), and grade 1 rash (n = 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12; 100% of patients with genotype 1b decompensated cirrhosis achieved SVR12.

OBJECT The transition of the young adult with spina bifida (YASB) from pediatric to adult health care is considered a priority by organized pediatrics. There is a paucity of transition programs and related studies. Jacksonville Health and Transition Services (JaxHATS) is one such transition program in Jacksonville, Florida. This study’s purpose was to evaluate the health care access, utilization, and quality of life (QOL) of a group of YASBs who have transitioned from pediatric care. METHODS A survey tool addressing access to health care and quality of health and life was developed based on an established survey. Records of the Spinal Defects Clinic held at Wolfson Children’s Hospital and JaxHATS Clinic were reviewed and YASBs (> 18 and < 30 years old) were identified. RESULTS Ten of the 12 invited YASBs in the Jacksonville area completed the surveys. The mean age of respondents was 25.1 years. All reported regular medical home visits, 8 with JaxHATS and 2 with other family care groups. All reported easy access to medical care and routine visits to spina bifida (SB) specialists; none reported difficulty or delays in obtaining health care. Only 2 patients required emergent care in the last year for an SB-related medical problem. Seven respondents reported very good to excellent QOL. Family, lifestyle, and environmental factors were also examined. CONCLUSIONS In this small group of YASBs with a medical home, easy access to care for medical conditions was the norm, with few individuals having recent emergency visits and almost all reporting at least a good overall QOL. Larger studies of YASBs are needed to evaluate the positive effects of medical homes on health and QOL in this population.

Background & Aims Treating chronic hepatitis C (CHC) in patients with end-stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC-infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR)

Background Non-human primate (NHP) diabetic models using chemical ablation of β-cells with STZ have been achieved by several research groups. Chemotherapeutic STZ could lead to serious adverse events including nephrotoxicity, hepatotoxicity, and mortality. Methods We implemented a comprehensive therapeutic strategy that included the tether system, permanent indwelling catheter implants, an aggressive hydration protocol, management for pain with IV nubain and anxiety with IV midazolam, moment-by-moment monitoring of glucose levels post-STZ administration, and continuous intravenous insulin therapy. Results A triphasic response in blood glucose after STZ administration was fully characterized. A dangerous hypoglycemic phase was also detected in all baboons. Other significant findings were hyperglycemia associated with low levels of plasma leptin, insulin and C-peptide concentrations, hyperglucagonemia, and elevated non-esterified fatty acids (NEFA) concentrations. Conclusions We successfully induced frank diabetes by IV administering a single dose of pharmaceutical-grade STZ safely and without adverse events in conscious tethered baboons.

The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients’ response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments.

We describe the initiation and development of a comprehensive multidisciplinary and multi-institutional program for the evaluation and management of youth with spasticity. A descriptive step-by-step process of the administrative and organizational sequence of the development of the program is delineated. The Spasticity Clinic now meets regularly, and multiple diagnostic and treatment modalities are performed. This experience may assist those that wish to initiate a similar venue for youth with spasticity.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the “royal disease”. Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers’ attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this “royal disease”.

OBJECTIVE Parental diabetes history is a well-known risk factor for type 2 diabetes and considered strong evidence for a genetic basis of type 2 diabetes. Whether this relationship is affected by other known risk factors, specifically obesity, remains unclear, possibly due to a relative paucity of lean diabetic patients. RESEARCH DESIGN AND METHODS This issue was investigated using data from a high-risk population from Mexico (National Health Survey 2000, n = 27,349), with observations replicated using U.S. citizens of Mexican descent from the National Health and Nutrition Examination Survey 2001–2002 and 2003–2004 (n = 1,568). RESULTS As expected, positive parental diabetes was a significant risk factor for type 2 diabetes, regardless of age, sex, or adiposity level. However, positive parental diabetes conferred greater risk in leaner individuals than in their overweight peers (P = 0.001). In other words, the effect of BMI on type 2 diabetes risk was smaller in the presence of parental diabetes history. CONCLUSIONS These findings suggest that parental diabetes is a stronger risk factor for type 2 diabetes in the absence of obesity. Thus, studies in lean diabetic patients could help identify type 2 diabetes susceptibility genes. This study reinforces the concept that parental diabetes and BMI are independent type 2 diabetes risk factors and suggests that glycemic screening may be helpful in assessing type 2 diabetes risk in individuals with parental diabetes history, regardless of their overweight status.

Obesity has been associated with an increased risk for colonic adenomatous polyps (APs) and colorectal cancers, but the influence of obesity on the development of advanced APs is not clear. The purpose of this study is to determine the influence of obesity on the prevalence of advanced APs in a male veteran population. We performed a retrospective study of patients (n = 2,903) with histologically confirmed APs on an index colonoscopy. APs were evaluated for advanced features (sizeor = 1 cm in diameter and/or a villous component and/or high grade dysplasia). Patients were categorized as: normal weight (BMI18.5 and25), overweight (BMIor = 25 and30), and obese (BMIor = 30). An association between clinical factors and advanced APs was sought by Kruskal-Wallis test and Pearson Chi-square. Multiple logistic regression analysis was used to determine independent predictors for advanced APs. We identified 2,903 male patients with APs (mean age 64 + 1.1(SE) years; 770 (27%) normal weight, 1,029 (35%) overweight, 1,104 (38%) obese. By univariate analysis, obese patients had a greater prevalence of advanced APs than the overweight and normal weight patients (28 vs. 23 vs. 24%, p = 0.025). Multiple logistic regression analysis confirmed the association of obesity and advanced APs (OR = 1.01, CI = 1-1.02, p = 0.04). For every one-unit increase in BMI above 30, there was a corresponding 1% increase in the frequency of finding advanced APs. Obesity in male veteran patients is associated with the finding of advanced APs on colonoscopy. We speculate that obesity may increase the risk for CRC by promoting the development of advanced APs.

Background: To treat with minimally invasive surgery, recurrent spinal arachnoid cysts, progressive syringomyelia, cranial and spinal cerebrospinal fluid fistulas. Patients andMethods: This is a clinical report that describes the management of recurrent spinal arachnoid cysts (2 patients), progressive syringomyelia (11 patients), postoperative spinal cerebrospinal fluid fistulas (15 patients) and postoperative cranial cerebrospinal fluid fistulas (2 patients) that were treated with spinal peritoneal shunts. The spinal arachnoid cyst and syringomyelia patients promptly resolved the signs and symptoms. The cranial and spinal cerebrospinal fluid fistula patients had a resolution of the fistulas. The shunts placed for spinal arachnoid cysts and syringomyelia required permanent implantation. The shunts placed for cerebrospinal fluid fistulas were temporary. All were removed, except for 2 patients whose parents did not want further operative interventions. Conclusion: Spinal peritoneal shunts have a variety of clinical applications and should be considered by neurological surgeons for disease processes other than communicating hydrocephalus and pseudotumor cerebri.

We have evaluated the efficacy of dapagliflozin in patients with type 1 diabetes mellitus (DM1) without adequate control. We expected that adding dapagliflozin to this population on top of their base treatment would lower their HbA1c levels.We conducted a pragmatic, open, 24-week study of treatment with 10 mg of oral dapagliflozin in patients with DM1 and chronic hyperglycemia. We evaluated glycemic control, lipid profile, weight, and insulin dose. Safety was assessed by adverse event reporting.Fasting glucose levels decreased from 176.42 ± 45.33 mg/dL to 139.67 ± 44.42 mg/dL (p = 0.05); although no significant valued was reached, postprandial glucose showed a decreased tendency from 230.25 ± 52.06 mg/dL to 193.83 ± 45.43 mg/dL (p = 0.08). The hemoglobin A1C (HbA1C) level decreased from 9.18 ± 1.02 (77 ± 11.1 mmol/mol) to 8.05 ± 1.09 % (64 ± 11.9 mmol/mol) (p = 0.0156); total cholesterol decreased from 299 ± 12 to 199 ± 7 mg/dL (p = 0.02); triglycerides decreased from 184 ± 15 to 160 ± 11 mg/dL (p = 0.0002), HDL-C decreased from 40 ± 17 to 42 ± 9 mg/dL (p = 0.54); and LDL-C decreased from 187 ± 19 to 170 ± 21 mg/dL (p = 0.049). No adverse events were reported.The beneficial effects of SGLT2 inhibitors on metabolic control and their safety after a 24-week open study demonstrate their potential indication as an adjunctive treatment with insulin in patients with DM1; however, long-term clinical trials should be considered.

We have previously reported on the initiation, development, and preliminary results of a comprehensive multidisciplinary team for the long-term management of children with neurosurgical conditions other than spina bifida. This report addresses the follow-up of the care of these patients and identifies limitations in the care sequence including, but not limited to, lack of parental/caregiver compliance, unmet educational needs, and medical insurance issues.

Myelomeningoceles are routinely diagnosed prenatally by using ultrasonography. Because the level of the neural defect has been shown to correlate with functional and cognitive outcome in infants with myelomeningocele, it is of prognostic importance to identify the level prenatally. The authors report on a case in which the postnatal vertebral level of the myelomeningocele was more rostral than expected based on prenatal imaging.

Cranial asymmetry may be present at birth or may develop during the first few months of life. Over the past several years, pediatricians have seen an increase in the number of children with cranial asymmetry, particularly unilateral flattening of the occiput. This increase likely is attributable to parents following the American Academy of Pediatrics “Back to Sleep” positioning recommendations aimed at decreasing the risk of sudden infant death syndrome. Although associated with some risk of deformational plagiocephaly, healthy young infants should be placed down for sleep on their backs. This practice has been associated with a dramatic decrease in the incidence of sudden infant death syndrome. Pediatricians need to be able to properly diagnose skull deformities, educate parents on methods to proactively decrease the likelihood of the development of occipital flattening, initiate appropriate management, and make referrals when necessary. This report provides guidelines for the prevention, diagnosis, and management of positional skull deformity in an otherwise normal infant without evidence of associated anomalies, syndromes, or spinal disease.

The authors describe 3 children who presented with progressively enlarging skin-covered solid masses over the shunt catheter in the neck/clavicular region. The authors reviewed the clinical, laboratory, pathological, radiographic, and follow-up data for all 3 patients and reviewed the literature on the subject. The patients had no clinical evidence of an infectious process. Surgical exploration revealed that masses were surrounding and encasing the shunt tubing to which they were strongly attached. Pathological studies of the tissues demonstrated varying degrees of exuberant chronically inflamed granulation tissues, interstitial fibrosis, and dystrophic calcification. One patient had associated thinning of the skin overlying the mass and subsequently developed ulceration. No infectious organisms were observed. The cerebrospinal fluid aspirates from the shunts did not yield any organisms. There has been no recurrence of the masses. The presence of a growing mass over the shunt tube in the neck or the chest region without clinical evidence of infection does not indicate that the mass should be treated with antibiotics and complete shunt removal. Rather, the mass can be cured by extirpation and with “bypass” new shunt tubing locally.

Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists’ scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist’s score had a quadratic weighted Cohen’s kappa of 0.64.

Recent studies provide strong evidence implicating Peptostreptococcus micros in the pathogenesis of various oral infections, including oropharyngeal abscesses and periodontal disease. To date, very little is known regarding the role of P. micros in periodontal disease. Therefore, a genetic analysis was initiated to differentiate among strains of P. micros infecting periodontal patients.Sixty DNA samples of P. micros isolated from 15 patients with periodontal disease were evaluated. Arbitrarily primed polymerase chain reactions (AP-PCR) were performed using primer 3 (AGTCAGCCAC) and primer 13 (CAGCACCCAC). The PCR products were analyzed by gel electrophoresis.The primers produced several unique patterns among the strains tested. Primer 3 resulted in 30 different patterns, whereas primer 13 resulted in 31 different patterns, which were distinct from those seen with primer 3. In 8 of 15 patients, the PCR profile was identical for all isolates cultured from that patient, indicating a clonal infection. In 4 of 15 patients, 2 different genotypes were identified. In the remaining 3 patients, all isolates cultured from these patients exhibited a unique genotype.While P. micros appears to be heterogeneous throughout a population of periodontal patients, each patient is, for the most part, infected with a limited number of genotypes. These results demonstrate the genetic diversity of P. micros and the usefulness of AP-PCR for future epidemiological studies in understanding the role P. micros plays in periodontal disease pathogenesis.

Object. Congenital spinal hamartomas are defined as tumors of well-differentiated mature elements situated in an abnormal location. In this report, the authors document the clinical and pathological features of spinal hamartomas in 10 patients. Methods. Ten patients presented with midline dorsal malformations at birth, initially diagnosed as teratomas or myelomeningoceles. The locations of the masses were variable: two were located in the thoracic region, four at the thoracolumbar junction, two in the lumbar region, one at the lumbosacral junction, and one in the sacral region. The results of the neurological examination were normal in nine patients. All but one mass had intact skin and seven had palpable bone components. Neuroimaging studies revealed widening of the spinal canal, heterotopic bone located dorsally in some patients, and varying degrees of involvement of the intraspinal contents. During surgery, six patients were found to have involvement of the spinal cord or cauda equina. The pathological characteristics of the masses included three or more of the following: bone, cartilage, synovial membrane, urinary tract tissue, cyst wall, yellow or brown fat, and nerves. The well-differentiated cellular elements, which formed mature structures, along with the absence of primitive cellular components and neoplastic characteristics are more consistent with a diagnosis of hamartoma than teratoma. Conclusions. In this series, the authors describe a lesion that is overt on physical examination, yet can have occult spinal canal involvement. Complete neurosurgical evaluation is essential to provide appropriate treatment and prognosis.

Agricultural production in general, and specifically the output of food products, has consistently grown ahead of population in recent decades, thus increasing food output per capita. But food products may be used also for non-food purposes (seed, animal feed, non-food industries) or may be lost or wasted after being produced. There are also people unable to get the food they need, for economic or social reasons, and people who suffer malnutrition due to lack of food or as a consequence of poor health and sanitation. This paper analyses trends in the prevalence of undernourishment (insufficient dietary energy) and malnutrition (stunting, wasting, underweight and overweight) across the developing world. Using existing projections and scenarios the paper also discusses the likely future prospects of hunger and its major cause, extreme poverty. A Technical Appendix explains sources and methods used. Undernourishment and malnutrition in the developing world are rapidly decreasing, though the pace of decrease is very slow in Africa (especially in anthropometric measures of child malnutrition) relative to Asia and Latin America. The world as a whole is on track to meet the Millennium Development Goal of halving by 2015 the prevalence of undernourishment estimated for 1990-92, but this would not yet be achieved until a much later time in regions like Sub-Saharan Africa or South Asia. However, projections suggest that by 2050 and at world level both undernourishment and malnutrition would reach non-significant levels of prevalence (roughly around or below 5%); even in the poorer regions these levels would be achieved at some point between 2050 and 2080, even under very conservative assumptions. The world is thus expected to be on the verge of eradicating chronic hunger for the first time in history. On the other hand, overweight and obesity are on the rise in all continents, amongst children and adults, male and female. The 'food problem' is now including an epidemic of overweight whereas famines are rarer and chronic hunger appears to be on the wane in most countries. Just a few countries report increasing levels of undernourishment or malnutrition, and they are mostly countries afflicted by prolonged violence or facing a collapse of the State apparatus. On the other hand, projections suggest that by 2050, though at the world scale there would be a low prevalence of these problems, some areas or countries may still be suffering from higher levels of both, albeit lower than they suffer now.

Osteophytes, a common degenerative change in the spine, are found in 90 % of the population over 60 years of age. We have developed an automated system to detect and assess spinal osteophytes on \(^{18}\)F-sodium fluoride (\(^{18}\)F-NaF) PET/CT studies. We first segment the cortical shell of the vertebral body and unwrap it to a 2D map. Multiple characteristic features derived from PET/CT images are then projected onto the map. Finally, we adopt a three-tier learning based scheme to compute a confidence map and detect osteophyte sites and clusters. The system was tested on 20 studies (10 training and 10 testing) and achieved 84 % sensitivity at 3.8 false positives per case for the training set, and 82 % sensitivity at a 4.7 false positive rate for the testing set.

This paper explores changes in the level and composition of per capita food consumption across the world; it does not discuss intra-country inequalities in food access, nor the prevalence of hunger resulting from those inequalities. The world's food output has more than trebled since 1961 whilst population only doubled, causing a marked increase in per capita food supply. By 2011 the average human was consuming nearly 2900 daily kilocalories per person, up from less than 2200 in 1961; per capita protein intake had also increased significantly from 61 to 80 grams per day. Besides these overall increases in food consumption, the composition of the average diet also changed. One major finding in this regard is that per capita consumption of cereals reached a plateau (or slightly declined) in recent decades, whilst consumption of other foods increased significantly. All the increase in per capita dietary energy supply since 1990 reflects higher consumption of non-cereal food; per capita cereal food consumption stabilised or declined. The saturation level at which cereal food consumption stabilises seems to vary across regions, probably due to local culture and custom. Due to changing dietary patterns, some regions of the world have enormously increased their consumption of fats, especially vegetable oil, contributing to a growing obesity epidemic. In some regions, chiefly North America, this has been compounded by a significant increase in per capita consumption of sugar. But humans have also changed their diets in beneficial ways, consuming more pulses, fruit, vegetables, meat, fish, milk and eggs. These trends are present in all major regions, albeit varying across regions. Most of these trends imply greater intake of micronutrients. More diversified diets, with increased presence of fruits, vegetables and foods of animal origin, suggest that the micronutrient content of per capita food supply is increasing, at the world level and for all major regions.

The Division of Pediatric Neurosurgery of the University of Florida College of Medicine Jacksonville initiated and developed a multidisciplinary comprehensive team for the management of patients with a neurosurgical condition other than spina bifida. This report relates the rationale and stages of development of a multidisciplinary team to facilitate the health care and special needs of these children.

World food prices surged strongly in recent years, with two waves of rising prices in 2007-08 and 2010-11. For food-importing countries affected at the same time by significant levels of undernourishment and malnutrition, sudden rises in the international price of food may have a strong impact on domestic prices and greatly affect access to food. Such is the case of two South American countries: Bolivia and Peru, which pursued quite different policies affecting the transmission of international commodity price changes into domestic consumer prices for major food items. This paper examines policies enacted in both countries at the macroeconomic and sectoral level, and the outcome in terms of domestic prices.

Purpose: To assess the frequency of persistent infection after injection of intravitreal antimicrobials as therapy for endophthalmitis and to determine if persistent infection influences the final visual outcome after treatment. Methods: In a series of 42 eyes with culture-positive endophthalmitis of various types, the authors performed a second vitreous culture and injection of antimicrobial agents in 22 eyes. Repeat cultures were obtained 3 to 8 days after initial therapy in 20 of the 22 eyes. Results: Twelve of the 22 eyes were persistently culture-positive. Organisms identified in the persistently culture-positive eyes included staphylococcal species (n = 4), Streptococcus (n = 4), Serratia (n = 1), Propionibacterium acnes (n = 1), and fungi (n = 2). Eyes in which the initial antimicrobial therapy failed to eradicate a bacterial infection had a worse outcome than those that were culture-negative on repeat sampling. Final visual acuity of 20/200 or better after repeat injection was attained in 4 of the 12 culture-positive eyes. Conclusion: A single injection of intravitreal antimicrobial agents may be insufficient to cure some cases of endophthalmitis, and a second injection should be considered in some circumstances.

Sonographic and clinical features of 26 fetal cephaloceles were reviewed retrospectively. The most frequent reason for referral was elevated maternal serum α-fetoprotein levels. The smallest lesion identified was 0.4 × 0.5 cm (frontal, at 20 weeks); the largest was 9.0 × 10.0 cm (frontal, at 27 weeks). Twenty-four of 26 cephaloceles were detected on prenatal ultrasound examination; in 13 of these, more than 50% of the intracranial contents were exteriorized. Fifteen of 24 cephaloceles detected prenatally had a sulcal pattern (identified between 16 and 36 weeks' gestation); five were solid without a sulcal pattern (identified between 13 and 21 weeks' gestation), three were cystic, and one underwent a change in appearance from solid at 21 weeks to cystic at 26 weeks. Other cranial features were evaluated and included visible skull defect, seen in 23/24 (96%), ventriculomegaly, in 6/26 (23%); microcephaly, in 12/24 (50%); beaked tectal plate, in 6/16 (38%); and flattened basiocciput, in 9/24 (38%). Of the 26 cases, 14 had normal amniotic fluid volume, five had oligohydramnios and seven had polyhydramnios. Fetuses with oligohydramnios had the highest incidence of concurrent fetal abnormalities; four of five fetuses (80%) with oligohydramnios had additional structural abnormalities. In the overall population, a very high incidence of other abnormalities was found; 17/26 (65%) cases showed additional abnormalities, some of which were not detected by ultrasound. Five fetuses had Meckel-Gruber syndrome and three had amniotic band syndrome. Only one of the 18 karyotypes obtained was abnormal (trisomy 18). Survival was very poor; only two of the eight who survived until birth are currently living. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology

Eight infants with choroid plexus carcinomas were treated with surgery, prolonged postoperative chemotherapy and delayed radiation. The results suggest that some infants with choroid plexus carcinomas can be successfully treated with multimodality therapy, even allowing children with less than a gross total resection to have prolonged disease-free intervals.

Objective: To evaluate clinical characteristics of these patients, with otosclerosis, complications,and observations of the benefits of implants to medium and long term.Method: Thirty two adult patients, age 50 years old, 22 women and 10 men, with profound sensorineural hearing loss, and otosclerosis far advanced, were treated with multi-channel cochlear implants. All had otological examination, psychological, audiometry, and 0% of speech discriminations with-well-fitted hearing aid, CTS (4 with RMI) to determine hypodensity or morphologic changes.Results: CTS with morphologic changes in the cochlea in 24/32 patients (Rottevel’s grading): 9 had type 2 (localized retrofenestral disease), 6 type 3 (retrofenestral diffuse). Full insertion inside the cochlea in 28/32 cases, where in 6 patients it was necessary to drill the bone in 4 to 6 mm in the tympanic basal turn. four patients had partial insertion of electrodes, 1 of them with 2 electrodes in IAC and leakage of CSF, 1 with stimulation of the facial nerv...

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide and accounts for 20% of all liver transplants (Wigg, 2010). Its incidence has increased two fold in the last decade and it is the fifth leading cause of cancer in males. The availability of liver transplantation as a cure for chronic liver disease and the demonstration of outcomes exceeding 70% at 5 years after transplantation for HCC have pushed the field to refine this therapy in order to utilize this precious resource in the most effective, fair and safe manner. The combination of a rising incidence of HCC and a flat donor procurement rates has resulted in longer waiting times in many areas. The complex decision making and management issues of patients with HCC, cirrhosis and possibly undergoing oncological therapies while waiting for an organ transplant poses challenges to the management team, not encountered in any other clinical or surgical field.

Purpose: The authors report their experience with the surgical removal of subfoveal choroidal neovascularization. Correlations between preoperative characteristics and final postoperative visual acuity are explored. Methods: A retrospective study of 159 consecutive patients was performed between February 1990 and August 1993. Follow-up of 2 or more months was available for 147 eyes: presumed ocular histoplasmosis syndrome, 67 eyes; age-related macular degeneration, 41 eyes; myopia, 10 eyes; multifocal choroiditis, 9 eyes; idiopathic, 8 eyes; angioid streaks, 4 eyes; and miscellaneous, 8 eyes. Results: Sixty-seven eyes had presumed ocular histoplasmosis syndrome: mean follow-up was 10.5 months. Visual acuity was stable or improved in 56 (83%) eyes and 20/40 or greater in 21 (31 %) eyes. Mean interval to best visual acuity was 3 months. A recurrence rate of 37% had no significant effect on final visual outcome ( P = 0.952). Forty-one eyes had age-related macular degeneration: mean follow-up was 15 months. Visual acuity was improved in only five (12%) eyes and was 20/40 or greater in only two (5%) eyes. The interval to best visual acuity was 5 months. A recurrence rate of 27% had no significant effect on final visual outcome ( P = 0.31). The visual results and recurrence rates for eyes with less common disorders are presented. Conclusion: The surgical excision of subfoveal choroidal neovascularization may stabilize or improve visual acuity in selected cases. Patients with focal disorders of the retinal pigment epithelium—Bruch's membrane complex appear to have a better surgical outcome than those with diffuse disease.

BACKGROUND Vogt-Koyanagi-Harada Syndrome (VKHS) is a systemic disorder consisting of bilateral panuveitis with associated cutaneous and neurologic findings. In the absence of extraocular manifestations, diagnosis of VKHS may be difficult. METHODS The results of magnetic resonance imaging (MRI) in two patients with VKHS and of computed tomography (CT) in a third patient with VKHS are described. RESULTS Bilateral, diffuse choroidal thickening with scleral sparing was the norm. Choroidal thickening was demonstrable, despite the normal fundus appearance and fluorescein angiogram, in one eye. Intense enhancement after administration of gadopentetate was seen in the acute stages, but not after corticosteroid treatment. High-intensity periventricular lesions were seen in one patient. CONCLUSION MRI superbly discriminates the fibrous sclera from the choroid and allows for the detection of subclinical ocular and central nervous system disease. It is therefore a useful adjunct in the diagnosis and follow-up of VKHS.

Purpose: Bioresorbable implant systems have been used for the rigid fixation of cranial and facial bones. A relatively recent advancement has been the fixation of these implants using an ultrasonic device. Published reports with such a device in pediatric craniofacial surgery have been limited. We report our experience with ultrasound-aided fixation of bioresorbable implants in the craniofacial surgery of children. Methods: We retrospectively examined the clinical information, complications and outcome following the use of a commercially available ultrasound-aided bioresorbable implant system (SonicWeld Rx™, KLS Martin, Jacksonville, Fla., USA) during craniofacial surgery by University of Florida College of Medicine Jacksonville surgeons. Follow-up was obtained via clinical examination or telephone interview. Results: Over a period of 3 years, 37 pediatric patients (age range: 2 months to 16 years) had placement of these implants for immediate bony fixation during craniofacial procedures. Pathology consisted mainly of craniosynostosis (n = 19), and trauma (n = 16). Twenty-eight had combined craniofacial procedures; 9 patients had facial procedures. Reoperation was performed for: wound infection (n = 1), plate extrusion (n = 1). Delayed subcutaneous plate-related swelling was seen in 5 patients (4 were infants) and had a benign clinical course. Good cosmetic outcomes were seen in all patients. Conclusions: The use of a bioresorbable implant system with ultrasound-aided pin fixation in pediatric craniofacial surgery achieves rapid fixation with minimal morbidity and good cosmetic outcome. This system is easy to use and provides reliable stability in the setting of pediatric trauma and craniosynostosis.

Purpose: Infants and children with microcrania are referred to pediatric neurosurgeons for evaluation and treatment of possible craniosynostosis and other disorders. We present an approach to these children to facilitate the appropriate clinical evaluation and management. Methods: We reviewed our experience and the literature on infants and children with microcephaly, and developed a management strategy for these children when seen in the University of Florida Division of Pediatric Neurosurgery. Results: We request the same sex parent to accompany the child for their consultation. If the head circumference of the child matches that of the same sex parent in percentiles, and there are no other abnormalities, no further assessment or studies are performed. If there is a disproportionate head size to that of the same sex parent and/or other structural abnormalities are present, the child is referred to clinical genetics for further assessment. Conclusions: When patients are referred to pediatric neurosurgery for microcrania, their head size should be compared to that of the same sex parent. This will facilitate the diagnosis of familial microcephaly, and if no other abnormalities are noted, no further studies or surgical interventions are necessary.

We prospectively evaluated the effect of interferon alfa-2a on subfoveal choroidal neovascularization. Eight patients with recurrent subfoveal choroidal neovascularization after surgical excision and 12 patients with subfoveal choroidal neovascularization without previous surgical excision received interferon alfa-2a (3.0 to 6.0 million U/m 2 of body surface area), every other night for an average of 12 weeks. Mean follow-up was nine months. Visual acuity improved in two of 20 (10%), remained stable in seven of 20 (35%), and worsened in 11 of 20 (55%) patients. The fluorescein angiogram improved in two of 20 (10%), remained stable in three of 20 (15%), and deteriorated in 15 of 20 (75%) patients. All patients had side effects, which led to the discontinuation of therapy in five of 20 (25%) patients. Side effects included flulike symptoms, leukopenia, thrombocytopenia, increased liver enzymes, alopecia, fever, nausea, and suicidal depression. Interferon alfa-2a failed to improve visual acuity or the fluorescein angiographic appearance of subfoveal neovascular membranes in 90% of cases and was associated with marked side effects. We discourage the widespread use of interferon alfa-2a in the treatment of choroidal neovascularization.

Objectives: Fiducial markers (FM) have been used to enhance the accuracy of radiation therapy in central nervous system (CNS) tumors. Recently, image-guided radiotherapy utilizing FM has been used in proton therapy of CNS tumors. We describe our surgical technique of placement of titanium screws as cranial FM in children undergoing proton therapy for CNS tumors. Methods: Records of children undergoing cranial fiducial placement for proton therapy were reviewed. Details of the adjuvant treatment of their CNS tumors were examined. Indications for placement of the FM, the technique of placement as well as the operative data and complications were reviewed. Results: Twelve children, aged 10 months to 16 years (mean: 7.6 years), underwent FM placement. When available, the patients had their proton irradiation as part of or according to Children’s Oncology Group protocols. All patients had implantations of FM onto bilateral frontal and parietal bone sites, using commercial titanium screws, in a noncollinear fashion. Ten operations were performed on an outpatient basis. There were no surgery-related complications. FM facilitated the cranial alignment for targeting of proton irradiation in all patients. Conclusions: Commercially available titanium screws can be used as FM for cranial proton radiotherapy. The procedure can be done quickly and safely on an outpatient basis. Pediatric neurosurgeons can perform this procedure on their patients at their home institutions to facilitate treatment at regional proton therapy centers.