Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder.

We describe a genetic syndrome due to PGM2L1 deficiency. PGM2 and PGM2L1 make hexose-bisphosphates, like glucose-1,6-bisphosphate, which are indispensable cofactors for sugar phosphomutases. These enzymes form the hexose-1-phosphates crucial for NDP-sugars synthesis and ensuing glycosylation reactions. While PGM2 has a wide tissue distribution, PGM2L1 is highly expressed in the brain, accounting for the elevated concentrations of glucose-1,6-bisphosphate found there. Four individuals (three females and one male aged between 2 and 7.5 years) with bi-allelic inactivating mutations of PGM2L1 were identified by exome sequencing. All four had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. Analysis of the children's fibroblasts showed that glucose-1,6-bisphosphate and other sugar bisphosphates were markedly reduced but still present at concentrations able to stimulate phosphomutases maximally. Hence, the concentrations of NDP-sugars and glycosylation of the heavily glycosylated protein LAMP2 were normal. Consistent with this, serum transferrin was normally glycosylated in affected individuals. PGM2L1 deficiency does not appear to be a glycosylation defect, but the clinical features observed in this neurodevelopmental disorder point toward an important but still unknown role of glucose-1,6-bisphosphate or other sugar bisphosphates in brain metabolism.

Soil Properties and Moisture Synergistically Influence Nontuberculous Mycobacterial Prevalence in Natural Environments of Hawai'i.

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that cause chronic pulmonary disease (PD). NTM infections are thought to be acquired from the environment; however, the basal environmental factors that drive and sustain NTM prevalence are not well understood. The highest prevalence of NTM PD cases in the United States is reported from Hawai'i, which is unique in its climate and soil composition, providing an opportunity to investigate the environmental drivers of NTM prevalence. We used microbiological sampling and spatial logistic regression complemented with fine-scale soil mineralogy to model the probability of NTM presence across the natural landscape of Hawai'i. Over 7 years, we collected and microbiologically cultured 771 samples from 422 geographic sites in natural areas across the Hawaiian Islands for the presence of NTM. NTM were detected in 210 of these samples (27%), with Mycobacterium abscessus being the most frequently isolated species. The probability of NTM presence was highest in expansive soils (those that swell with water) with a high water balance (>1-m difference between rainfall and evapotranspiration) and rich in Fe-oxides/hydroxides. We observed a positive association between NTM presence and iron in wet soils, supporting past studies, but no such association in dry soils. High soil-water balance may facilitate underground movement of NTM into the aquifer system, potentially compounded by expansive capabilities allowing crack formation under drought conditions, representing further possible avenues for aquifer infiltration. These results suggest both precipitation and soil properties are mechanisms by which surface NTM may reach the human water supply. IMPORTANCE Nontuberculous mycobacteria (NTM) are ubiquitous in the environment, being found commonly in soils and natural bodies of freshwater. However, little is known about the environmental niches of NTM and how they relate to NTM prevalence in homes and other human-dominated areas. To characterize NTM environmental associations, we collected and cultured 771 samples from 422 geographic sites in natural areas across Hawai'i, the U.S. state with the highest prevalence of NTM pulmonary disease. We show that the environmental niches of NTM are most associated with highly expansive, moist soils containing high levels of iron oxides/hydroxides. Understanding the factors associated with NTM presence in the natural environment will be crucial for identifying potential mechanisms and risk factors associated with NTM infiltration into water supplies, which are ultimately piped into homes where most exposure risk is thought to occur.

Emergency Department Health Care Utilization and Opioid Administration Among Pediatric Patients With Sickle Cell Vasoocclusive Pain Crisis and Coexisting Mental Health Illness.

OBJECTIVES: To determine whether patients with sickle cell disease (SCD) who present to the emergency department (ED) with vasoocclusive pain crises (VOC), and have coexisting mental health (MH) diagnoses, are more likely to have increased health care utilization and more frequent opioid administration compared with those without coexisting MH conditions. METHODS: This is a retrospective study of patients aged 5 to 18 years with SCD who presented to a tertiary care ED with a primary complaint of VOC between January 1, 2013, and December 31, 2017. We excluded patients with sickle cell trait and without a pain management plan in the electronic medical record. Outcomes included ED length of stay (LOS), admission rate, and opioid administration in the ED. Morphine equivalents were used to standardize opioid dosing. Mann-Whitney U and χ2 tests were used for univariate analysis. Multivariable logistic was performed for categorical and continuous outcomes, respectively, after adjusting for confounding factors. RESULTS: We identified 978 encounters. We excluded 196 without a pain management plan and one with inaccurate ED LOS, resulting in 781 encounters (148 patients) for analysis. Coexisting MH diagnoses were present in 75.0% of encounters, with anxiety (83.0%) and depressive disorders (55.9%) being most common. Compared with SCD patients without coexisting MH diagnoses, those with coexisting MH diagnoses had significantly longer ED LOS (252 ± 139 minutes vs 232 ± 145 minutes, P = 0.03), longer median hospital LOS (1.4 ± 3.2 days vs 0.3 ± 2.4 days, P < 0.001) in univariate analyses, but these differences were no longer significant in adjusted regression models. Patients with coexisting MH diagnoses had higher frequency of opioid administration in the ED (85.6% vs 71.4%, P < 0.0001) and higher odds of receiving opioids (adjusted odds ratio, 2.07; 95% confidence interval, 1.28-3.33). CONCLUSIONS: Patients with SCD and coexisting MH diagnoses presenting with VOC have greater odds of receiving opioids compared with patients with SCD without coexisting MH diagnoses. Our results indicate a need for more MH resources in this vulnerable population and may help guide future management strategies.

Assessment of Soil Features on the Growth of Environmental Nontuberculous Mycobacterial Isolates from Hawai'i.

Environmental nontuberculous mycobacteria (NTM), with the potential to cause opportunistic lung infections, can reside in soil. This might be particularly relevant in Hawai'i, a geographic hot spot for NTM infections and whose soil composition differs from many other areas of the world. Soil components are likely to contribute to NTM prevalence in certain niches as food sources or attachment scaffolds, but the particular types of soils, clays, and minerals that impact NTM growth are not well-defined. Hawai'i soil and chemically weathered rock (saprolite) samples were examined to characterize the microbiome and quantify 11 mineralogical features as well as soil pH. Machine learning methods were applied to identify important soil features influencing the presence of NTM. Next, these features were directly tested in vitro by incubating synthetic clays and minerals in the presence of Mycobacteroides abscessus and Mycobacterium chimaera isolates recovered from the Hawai'i environment, and changes in bacterial growth were determined. Of the components examined, synthetic gibbsite, a mineral form of aluminum hydroxide, inhibited the growth of both M. abscessus and M. chimaera, while other minerals tested showed differential effects on each species. For example, M. abscessus (but not M. chimaera) growth was significantly higher in the presence of hematite, an iron oxide mineral. In contrast, M. chimaera (but not M. abscessus) counts were significantly reduced in the presence of birnessite, a manganese-containing mineral. These studies shed new light on the mineralogic features that promote or inhibit the presence of Hawai'i NTM in Hawai'i soil.IMPORTANCE Globally and in the United States, the prevalence of NTM pulmonary disease-a potentially life-threatening but underdiagnosed chronic illness-is prominently rising. While NTM are ubiquitous in the environment, including in soil, the specific soil components that promote or inhibit NTM growth have not been elucidated. We hypothesized that NTM culture-positive soil contains minerals that promote NTM growth in vitro Because Hawai'i is a hot spot for NTM and a unique geographic archipelago, we examined the composition of Hawai'i soil and identified individual clay, iron, and manganese minerals associated with NTM. Next, individual components were evaluated for their ability to directly modulate NTM growth in culture. In general, gibbsite and some manganese oxides were shown to decrease NTM, whereas iron-containing minerals were associated with higher NTM counts. These data provide new information to guide future analyses of soil-associated factors impacting persistence of these soil bacteria.

How do I incorporate red cell genotyping to improve chronic transfusion therapy?

BACKGROUND: Children with transfusion dependent anemia, such as sickle cell disease (SCD) and thalassemia, are at an increased risk for developing red blood cell (RBC) alloantibodies due to their lifelong need for transfusion therapy. With the advent of genotyping, extended RBC antigen typing can be incorporated into chronic transfusion therapy programs (CTTPs) to improve patient care and provide antigen matched blood for this population of patients. STUDY DESIGN AND METHODS: The hospital, blood center (BC), and hematology clinic caring for children requiring long-term transfusion support developed a CTTP. Genotyping was performed at entry to determine patient RBC antigen type. Limited versus extended antigen matching of transfusions was provided based on known RBC antibodies. RESULTS: Fifty patients with the following disorders were enrolled: 20 with SCD, 23 with thalassemia, and 7 with other disorders. At enrollment, nine (18%) had RBC alloantibodies, including six (30%) of patients with SCD and three (13%) with thalassemia. Two children developed antibodies after enrollment; one warm autoantibody following limited "CEK" matched RBCs and one patient with a hemizygous variant RHD allele developed anti-D. Six (30%) patients with SCD had variant RHCE alleles; two had homozygous variant alleles and four had a variant present along with a wild type allele. CONCLUSION: We demonstrate how a CTTP can be developed in a community hospital through collaboration with the blood supplier, hospital, and clinical care team. A model of incorporating RBC genotyping informs risk for alloimmunization and allows consideration of transfusion strategy for providing prophylactic antigen matched blood.

TRANSCUTANEOUS OXYGEN MONITORING IN LOUISIANA PINE SNAKES (PITUOPHIS RUTHVENI).

Hypoxic physiological states may occur during anesthetic events of snakes but accurate monitoring of oxygenation is challenging. Oxygenation levels of nine Louisiana pine snakes (Pituophis ruthveni) were assessed using transcutaneous regional oxygen saturation (rSO2) at the level of the liver (rSO2Liver) and at the halfway point of the body (rSO2Half ). Reflectance pulse oximetry measured SpO2, with a sensor overlying the heart. Values were compared with the venous partial pressure of oxygen (PvO2). Measurements were taken during four phases, simulating an anesthetic event: phase 1, breathing room air; phase 2, while supplied with supplemental oxygen via face mask; phase 3, during ketamine and dexmedetomidine sedation; and phase 4, after receiving atipamezole. There were no significant changes in any oxygenation parameters between concurrent phases, but respiratory rate significantly decreased (P = 0.02) between phases 1 and 2. Strong positive associations were found between both rSO2Liver and rSO2Half when compared with PvO2 irrespective of phase (r = 0.72, r = 0.63 respectively), but not with SpO2 (r = 0.3). Strength of correlation varied with each phase but was uniformly strongest for rSO2Liver. The measurement of rSO2 appears superior compared with traditional pulse oximetry for assessing oxygenation levels of snakes.

Hydroxyurea use in young infants with sickle cell disease.

BACKGROUND: Hydroxyurea (HU) reduces complications and improves quality and duration of life in sickle cell disease. Evidence supports the use of HU starting after nine months of age. PROCEDURES: We performed a retrospective study of patients starting HU at less than five years of age between January 1, 2008, and December 31, 2016. We evaluated clinical events, laboratory data, and toxicity between three different age groups: cohort 1 (0-1 year), cohort 2 (1-2 years), and cohort 3 (2-5 years). RESULTS: Sixty-five patients were included in the analysis. The mean age was 7.2 months (n = 35), 19.5 months (n = 13), and 35.5 months (n = 17) for cohorts 1, 2, and 3, respectively. Cohort 1 had higher hemoglobin (P = 0.0003) and MCV (P = 0.0199) and lower absolute reticulocyte count (P = 0.0304) at 24 months of age compared with cohort 3. The absolute neutrophil count (ANC) was lower compared with both older cohorts (P = 0.0364, 0.0025). The mean baseline hemoglobin F in cohort 1 was 31.5% compared with 19.7% and 16.5% in cohorts 2 and 3, respectively (P = 0.002, P < 0.0001). The mean duration of therapy was 31.3 months, 57.6 months (P = 0.018), and 29.1 months (P = 0.401), respectively. Mean Hb F levels remained higher in cohort 1 (29.9%) compared with cohorts 2 and 3 (20.4%, P = 0.007; 20.6%, P = 0.003). Cohort 1 experienced fewer hospitalizations (P = 0.0025), pain crises (P = 0.0618), and transfusions (P = 0.0426). There was no difference in toxicity between groups. CONCLUSION: HU is safe and effective in patients 5 to 12 months of age and generated a more robust response compared with initiation in older patients.

Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease.

BACKGROUND: Generalized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are rare complicated lymphatic malformations that occur in multiple body sites and are associated with significant morbidity and mortality. Treatment options have been limited, and conventional medical therapies have been generally ineffective. Emerging data suggest a role for sirolimus as a treatment option for complex lymphatic anomalies. PROCEDURE: Disease response was evaluated by radiologic imaging, quality of life (QOL), and clinical status assessments in children and young adults with GLA and GSD from a multicenter systematic retrospective review of patients treated with oral sirolimus and the prospective phase 2 clinical trial assessing the efficacy and safety of sirolimus in complicated vascular anomalies (NCT00975819). Sirolimus dosing regimens and toxicities were also assessed. RESULTS: Eighteen children and young adults with GLA (n = 13) or GSD (n = 5) received oral sirolimus. Fifteen patients (83%) had improvement in one or more aspects of their disease (QOL 78%, clinical status 72%, imaging 28%). No patients with bone involvement had progression of bone disease, and the majority had symptom or functional improvement on sirolimus. Improvement of pleural and pericardial effusion(s) occurred in 72% and 50% of affected patients; no effusions worsened on treatment. CONCLUSIONS: Sirolimus appears effective at stabilizing or reducing signs/symptoms of disease in patients with GLA and GSD. Functional impairment and/or QOL improved in the majority of individuals with GLA and GSD with sirolimus treatment.

Increasing Public Interest in Stem Cell Injections for Osteoarthritis of the Hip and Knee: A Google Trends Analysis.

BACKGROUND: Stem cell injections are being offered to patients as a nonoperative treatment for osteoarthritis of the hip and knee. To our knowledge, no peer-reviewed data exist to document the usage frequency of these injections nor to quantify the public interest in these injections. We sought to use Google Trends to provide a quantitative analysis of interest in hip and knee stem cell injections at the population level. METHODS: Google Trends search parameters were set to obtain query data from January 2010 through December 2017. 'Arthritis,' 'osteoarthritis,' 'stem cell,' 'injection,' 'knee,' and 'hip' were entered in various combinations to obtain the highest yield search volume. Trend analyses were performed. RESULTS: Six linear models were generated to show trends in the volume of searches for the United States and the World. Model fit was good, and regression analysis showed significant trends over time for all searches. Use of search terms increased significantly over time (all models P < .001). Adjusted R-square values ranged from 54.4% to 78.1%. All trends showed an upward trajectory for the entirety of the study time period. CONCLUSION: There has been a marked and statistically significant rise in search query volume related to stem cells and osteoarthritis of the hip and knee since 2010. Online interest in stem cell injections may suggest increased utilization of these procedures. Well-designed clinical studies are required to keep pace with the rising popularity and public interest in this intervention for hip and knee arthritis.

Ceftriaxone-induced drug reaction mimicking acute splenic sequestration crisis in a child with hemoglobin SC disease.

BACKGROUND: Acute splenic sequestration crisis is a complication of sickle cell disease (SCD) occurring when intrasplenic red blood cell (RBC) sickling prevents blood from leaving the spleen, causing acute splenic enlargement. Although typically seen in young children, it has been reported in older children with hemoglobin (Hb)SC disease, eventually resulting in functional asplenia. Ceftriaxone is a frequently used antibiotic of choice for children with SCD, because of its efficacy against invasive pneumococcal disease. CASE REPORT: We report a case of a 9-year-old female with HbSC disease, who had a fatal reaction after receiving a dose of ceftriaxone in the outpatient clinic for fever. Her Hb level decreased abruptly from 9.3 to 2.3 mg/dL. RBC clumps with no visible hemolysis were observed in the postreaction sample. Autopsy examination revealed marked splenomegaly with acute congestion and sickled cells in the spleen and liver. Serologic testing revealed a positive direct antiglobulin test with polyspecific antibody, anti-C3, and anti-C3d, but negative with anti-immunoglobulin G. Ceftriaxone-dependent RBC antibodies were detected in her serum and RBC eluate when tested in the presence of the drug. CONCLUSION: We report a new presentation of ceftriaxone-induced drug reaction in a patient with SCD mimicking an acute splenic sequestration crisis. Review of the literature for cases of ceftriaxone-induced drug reactions in pediatric patients revealed nine previously reported cases of ceftriaxone-induced immune hemolytic anemia in children with SCD since 1995, but none with an initial presentation suggestive of acute splenic sequestration crisis.

Upfront eltrombopag monotherapy induces stable hematologic remission in pediatric patients with nonsevere idiopathic aplastic anemia.

Aplastic anemia (AA) is characterized by multilineage cytopenias and bone marrow hypocellularity. Severe AA can be treated with immunosuppressive therapy (IST) and/or allogeneic hematopoietic stem cell transplantation. The thrombopoietin agonist eltrombopag has been shown to induce hematopoietic recovery and transfusion independence in adults with refractory and relapsed AA. Recently, upfront eltrombopag therapy in patients with AA in combination with IST has shown efficacy. Data for its use without concurrent IST in pediatric patients with AA remain sparse. Here we report two pediatric patients with AA not meeting severe criteria who achieved hematologic response with upfront eltrombopag monotherapy.

Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era.

Invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) can be devastating. We sought to assess the impact of IPD in children with SCD since licensure of the pneumococcal conjugate vaccines (PCVs). We found 11 cases of IPD giving an incidence of 417 per 100,000 person-years, much higher than that reported in children without SCD. Although all isolates were sensitive to penicillin, 89% of isolates were nonvaccine serotypes. Further study is needed to characterize the incidence of and risk factors for the development of IPD in SCD in the PCV era to help drive better prevention strategies.

Similar 30-Day Complications for Septic Knee Arthritis Treated With Arthrotomy or Arthroscopy: An American College of Surgeons National Surgical Quality Improvement Program Analysis.

PURPOSE: The purpose of the current study was to use the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) to determine whether there were differences in 30-day perioperative complications between open arthrotomy and arthroscopy for the treatment of septic knees in a large national sample. METHODS: Patients who were diagnosed with a septic knee and underwent open arthrotomy or arthroscopy were identified in the 2005-2014 NSQIP data sets. Patient demographics and perioperative complications were characterized and compared between the 2 procedures. RESULTS: In total, 168 patients undergoing knee arthrotomy and 216 patients undergoing knee arthroscopy for septic knee were identified. There were no statistically significant differences in demographic variables between the 2 groups. On univariate analysis, the rate of minor adverse events (MAEs; 15.48% vs 8.80%, P = .043) was higher in the open arthrotomy treatment group, while the rate of serious adverse events (SAEs; 37.50% vs 26.19%, P = .019) was higher in the arthroscopic surgery treatment group. On multivariate analysis, which controlled for patient characteristics/comorbidities and used the Bonferroni correction for multiple comparisons, there were no statistically significant differences in risk of any adverse events (relative risk [RR] = 0.851; 99% confidence interval [CI], 0.598-1.211; P = .240), MAE (RR = 1.653; 99% CI, 0.818-3.341; P = .066), SAE (RR = 0.706; 99% CI, 0.471-1.058; P = .027), return to the operating room (RR = 0.810; 99% CI, 0.433-1.516; P = .387), or readmission (RR = 1.022; 99% CI, 0.456-2.294; P = .944) between open compared with arthroscopic surgery. CONCLUSIONS: Univariate analysis revealed a lower rate of MAE but a higher rate of SAE in the arthroscopic surgery treatment group. However, on multivariate analysis, similar perioperative complications, rate of return to the operating room, and rate of readmission were found after open and arthroscopic debridement for septic knees. Based on the lack of demonstrated superiority of either of these 2 treatment modalities for this given diagnosis, and the expectation that most differences in perioperative complications for this diagnosis would have declared themselves within the first 30 days, deciding between the studied treatment modalities may be based more on other factors not included in this study. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health.

ALG13-CDG in a male with seizures, normal cognitive development, and normal transferrin isoelectric focusing.

ALG13-CDG has been recently discovered as a disorder of severe developmental, intellectual and speech disability, microcephaly, visual abnormalities, seizures, hepatomegaly, coagulation abnormalities, and abnormal serumtransferrin isoelectric focusing in serum. A male with seizures, delayed motor, and speech development, but normal cognition carried a hemizygous, predicted pathogenic ALG13 variant (p.E463G). N-glycosylation studies in plasma were normal. ICAM-1 expression was decreased in patient fibroblasts, supporting the variant's pathogenicity. Adding D-galactose to the patient's fibroblast culture increased ICAM-1 expression in vitro, offering a potential treatment option in ALG13-CDG. The present report is a new example for an N-glycosylation disorder, that may present with normal transferrin isoform analysis, and also demonstrates, that CDG type I patients can have normal cognitive development.

Outpatient and Inpatient Unicompartmental Knee Arthroplasty Procedures Have Similar Short-Term Complication Profiles.

BACKGROUND: Advances in surgical techniques and anesthesia have made performing unicompartmental knee arthroplasty (UKA) in the outpatient setting a possibility. The touted benefits of outpatient surgery include higher patient satisfaction and reduced costs. However, detailed information on the perioperative outcomes of outpatient compared with inpatient UKA in a large, national patient population in the United States has never been reported. The present study compares perioperative complications between outpatient and inpatient UKAs in the National Surgical Quality Improvement Program database. METHODS: Patients who underwent UKA were identified in the 2005-2015 National Surgical Quality Improvement Program database. Outpatient procedures were defined as those with length of hospital stay = 0 days, whereas inpatient procedures were defined as those with length of hospital stay = 1-4 days. Patients' characteristics and comorbidities were compared between the two groups. Propensity score matched comparisons were performed for 30-day perioperative complications and readmissions between the two cohorts. RESULTS: This study included 568 outpatient and 5312 inpatient UKA cases. After propensity matching to control potential confounding factors, statistical analysis revealed no significant difference in any perioperative complications or any postdischarge complications between the outpatient and inpatient cohorts. Notably, the rate of 30-day readmissions between the two cohorts was not statistically different. CONCLUSION: Based on the perioperative outcome measures assessed in this study, outpatient UKA can be appropriately considered in carefully selected patients based on the lack of differences in rates of 30-day perioperative complications and readmissions between the outpatient and matched inpatient groups.

Is Outpatient Total Hip Arthroplasty Safe?

BACKGROUND: Safety data for outpatient total hip arthroplasty (THA) remains scarce. METHODS: The present study retrospectively reviews prospectively collected data from the 2005-2014 American College of Surgeons National Surgical Quality Improvement Program Database. Patients who underwent THA were categorized by day of hospital discharge to be outpatient (length of stay [LOS] 0 days) or inpatient (LOS 1-5 days). Those with extended LOS beyond 5 days were excluded. To account for baseline nonrandom assignment between the study groups, propensity score matching was used. The propensity matched populations were then compared with multivariate Poisson regression to compare the relative risks of adverse events during the initial 30 postoperative days including readmission. RESULTS: A total of 63,844 THA patients were identified. Of these, 420 (0.66%) were performed as outpatients and 63,424 (99.34%) had LOS 1-5 days. Outpatients tended to be younger, male, and to have fewer comorbidities. After propensity score matching, outpatients had no difference in any of 18 adverse events evaluated other than blood transfusion, which was less for outpatients than those with a LOS of 1-5 days (3.69% vs 9.06%, P < .001). CONCLUSION: After adjusting for potential confounders using propensity score matching and multivariate logistic regression, patients undergoing outpatient THA were not at greater risk of 30 days adverse events or readmission than those that were performed as inpatient procedures. Based on the general health outcome measures assessed, this data supports the notion that outpatient THA can appropriately be considered in appropriately selected patients.

Comparison of Outpatient vs Inpatient Total Knee Arthroplasty: An ACS-NSQIP Analysis.

BACKGROUND: There has been a recent surge of interest in performing primary total knee arthroplasty (TKA) in the outpatient setting to reduce cost and increase patient satisfaction. Detailed information on the safety of outpatient TKA in large sample sizes is scarce. METHODS: Patients who underwent primary, elective TKA were identified in the 2005-2014 American College of Surgeons National Surgical Quality Improvement Program database. Outpatient procedure was defined as having a hospital length of stay of 0 days, whereas inpatient procedure was defined as having a length of stay ≥1 days. To reduce the effect of confounding factors and nonrandom assignment of treatment, propensity score matching was used. Multivariate analyses on the matched samples were used to compare the rates of adverse events that happened any time during the 30-day postoperative period, postdischarge adverse events, and readmissions between the outpatient and inpatient cohorts. RESULTS: A total of 112,922 TKA patients met the inclusion criteria. Of these, only 642 (0.57%) were outpatient procedures. Outpatients tended to be men, slightly younger, and have less comorbidity. After propensity matching, multivariate analysis revealed a higher rate of postdischarge blood transfusions (P < .001) in the outpatient cohort. There were no other significant differences in 30-day postoperative individual adverse events or readmissions. CONCLUSION: Based on the perioperative outcome measures studied here, outpatient TKA can be appropriately considered in select patients based on rates of overall perioperative adverse events and readmissions. However, higher surveillance of these patients postdischarge may be warranted.

Partial Denervation and Anterior Release of the Hip Joint Capsule to Relieve Pain and Improve Function at Five Years Follow-up.

Traditionally, patients with significant hip pain due to degenerative hip disease, who are not surgical candidates for a total hip arthroplasty (THA), or are wary of the procedure, have been managed with various modalities with variable effectiveness. OBJECTIVES: We have recently developed an anterior release of the contracted hip capsule along with par- tial denervation ofthe hip joint performed on an out- patient basis to relieve pain and improve function. STUDY DESIGN: A case series of 24 patients. METHODS: From November 2007 to April 2009, 24 partial,denervation procedures through an anterior approach were performed by a single surgeon. A clinical survey was conducted five years following the intervention. RESULTS: Eighteen ofthe 24 patients were alive at the time of follow-up. Four of the six patients who were deceased at the time of follow-up had not undergone aTHA while two had. Fifteen ofthe 18 patients who were still living received a THA while three did not. Ihe interval time to arthroplasty was 19 months.

Effects of hydroxyurea treatment for patients with hemoglobin SC disease.

Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/ß(0) -thalassemia genotypes, many patients with HbSC experience severe disease complications, including vaso-occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, and poor quality of life. Fully 20 years after the clinical and laboratory efficacy of hydroxyurea was proven in adult SCA patients, the safety and utility of hydroxyurea treatment for HbSC patients remain unclear. Recent NHLBI evidence-based guidelines highlight this as a critical knowledge gap, noting HbSC accounts for ∼30% of sickle cell patients within the United States. To date, only 5 publications have reported short-term, incomplete, or conflicting laboratory and clinical outcomes of hydroxyurea treatment in a total of 71 adults and children with HbSC. We now report on a cohort of 133 adult and pediatric HbSC patients who received hydroxyurea, typically for recurrent vaso-occlusive pain. Hydroxyurea treatment was associated with a stable hemoglobin concentration; increased fetal hemoglobin (HbF) and mean corpuscular volume (MCV); and reduced white blood cell count (WBC), absolute neutrophil count (ANC), and absolute reticulocyte count (ARC). Reversible cytopenias occurred in 22% of patients, primarily neutropenia and thrombocytopenia. Painful events were reduced with hydroxyurea, more in patients >15 years old. These multicenter data support the safety and potentially salutary effects of hydroxyurea treatment for HbSC disease; however, a multicenter, placebo-controlled, Phase 3 clinical trial is needed to determine if hydroxyurea therapy has efficacy for patients with HbSC disease.