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To better explore the potential of rice extra-large G (XLG) proteins in future breeding, we characterised the function of OsXLG1, OsXLG2 and OsXLG3 in disease resistance. Loss-of-function Osxlg2 and Osxlg3 mutants showed reduced resistance to the fungal pathogen Magnaporthe oryzae, whereas Osxlg1 mutants were specifically compromised in resistance to the bacterial pathogen Xanthomonas oryzae pv oryzae. Consistent with their effects on rice blast resistance, mutations in OsXLG2 and OsXLG3 caused greater defects than did mutations in OsXLG1 for chitin-induced defence responses. All three OsXLGs interacted with components of a surface immune receptor complex composed of OsCERK1, OsRLCK176 and OsRLCK185. Further characterisation of yield-related traits showed that the Osxlg3 mutants displayed reduced plant height, panicle length and 1000grain weight, whereas Osxlg1 mutants exhibited increased plant height, panicle length and 1000-grain weight. Together the study shows the differential contributions of the three OsXLG proteins to disease resistance to fungal and bacterial pathogens, their yield-related traits and provides insights for future improvement of rice production.

Introduction: Observational studies suggest that low-dose valganciclovir prophylaxis (450 mg daily for normal renal function) is as effective as and perhaps safer than standard-dose valganciclovir (900 mg daily) in preventing CMV infection among kidney transplant recipients. However, this practice is not supported by current guidelines due to concerns for breakthrough infection from resistant CMV, mainly in high-risk CMV donor-seropositive/recipient-seronegative kidney transplant recipients. Standard-dose valganciclovir is costly and possibly associated with higher incidence of neutropenia and BKV DNAemia. Our institution adopted low-dose valganciclovir prophylaxis for intermediate-risk (seropositive) kidney transplant recipients in January 2018. Research Question: To analyze the efficacy (CMV DNAemia), safety (BK virus DNAemia, neutropenia, graft loss, and death), and cost savings associated with this change. Design: We retrospectively compared the above outcomes between CMV-seropositive kidney transplant recipients who received low-dose and standard-dose valganciclovir, transplanted within our institution, between 1/19/2014 and 7/15/2019, using propensity score-adjusted competing risk analyses. We also compared cost estimates between the two dosing regimens, for 3 months of prophylaxis, and for different percentage of patient-weeks with normal renal function, using the current average wholesale price of valganciclovir. Results: We studied 179 CMV-seropositive kidney transplant recipients, of whom 55 received low-dose and 124 standard-dose valganciclovir. The majority received nonlymphocyte depleting induction (basiliximab). Low-dose valganciclovir was at least as effective and safe as, and more cost-saving than standard-dose valganciclovir. Conclusion: This single-center study contributes to mounting evidence for future guidelines to be adjusted in favor of low-dose valganciclovir prophylaxis in CMV-seropositive kidney transplant recipients.

Background Mitochondrial disorders present with high clinical, genetic and neuroimaging heterogeneity. The spectrum of neuroimaging characteristics expanded fast based on the expanding of molecular etiologies. Methods In this study, we retrospectively recruited a cohort of primary pediatric mitochondrial disorder patients with confirmed genetic diagnosis. The clinical presentation, brain CT/MRI data, genetic results and biological dysfunction were collected and reviewed.Results Seventy-seven patients were enrolled, including 54 patients with mtDNA (70.1%) and 23 patients with nDNA mutations (29.9%). The most common MRI findings were deep nuclei lesion (65.1%), brain atrophy (50.0%), cortical and subcortical white matter lesion (36.4%), deep white matter lesion (30.3%), and diffused cerebral atrophy (10.6%). Overall lesion in diffused deep white matter was more common in nDNA-mutated patients (p=0.0365). Deep nuclei lesion was observed most frequently in patients with mutations in MT-ATP6, MT-ND6, and NDUFAF5 genes, while cortical/subcortical white matter lesion was common in patients with MT-TL1 gene, mtDNA large-scale deletion, or NDUFAF5 gene defects. The most common MRI finding in patients with m.3243A>G mutation was simultaneous cortical/subcortical white matter and deep nuclei involvement (9/24, 37.5%), followed by cortical grey/subcortical white matter lesion (7/24, 29.2%), unilateral or bilateral lesion in deep nuclei (5/24, 20.8%), whereas some patients showed normal MRI (3/24, 12.5%). The most common MRI change in POLG-mutated patients was brain atrophy (4/4,100%), lesion in deep nuclei (3/4, 75%), deep white matter (2/4, 50%) and cortical grey/subcortical white matter lesion (1/4,25%). Heatmap showed multi deep nuclei lesion was more common in patients with OXPHOS subunits defects; cortical grey and subcortical white matter lesion was more common in dysfunction of mtDNA maintenance, expression and translation; and lesion in deep white matter was more common in patients with dysfunction of metabolism of cofactors. Discussion Neuroimaging findings in pediatric mitochondrial disorder patients are variable. The most common patterns are deep nuclei lesion, brain atrophy, cortical grey/subcortical white matter lesion, deep white matter lesion, and cerebellar atrophy. There are some correlations between brain MRI results of patients and their genetic defects, as well as biological dysfunction.

Background: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. Methods: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing. Findings: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p

Background:CLCN1-related myotonia congenita (MC) is one of the most common forms of non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. However, there is limited data of clinical and molecular spectrum of MC patients in China.Patients and Methods: Five patients with myotonia congenita due to mutations in CLCN1 gene were enrolled, which were identified through trio-whole-exome sequencing or panel-based next-generation sequencing test. The clinical presentation, laboratory data, electrophysiological tests, muscular pathology feature, and genetic results were collected and reviewed. We also searched all previously reported cases of MC patients with genetic diagnosis in Chinese populations, and their data were reviewed.Results: The median onset age of five patients was 3.0 years old, ranging from 1.0 to 5.0 years old, while the median age of admit was 5.0 years old, ranging from 3.5 to 8.8 years old. Five patients complained of muscle stiffness when rising from chairs or starting to climb stairs (5/5, 100.0%), four patients complained of delayed relaxation of their hands after forceful grip (4/5, 80.0%), all of which improved with exercise (warm-up phenomenon) (5/5, 100%). Electromyogram was conducted in five patients, which all revealed myotonic change (100%). Genetic tests revealed nine potential disease-causing variants in CLCN1 gene, including two novel variants: c.962T>A (p.V321E) and c.1250A>T (p.E417V). Literature review showed that 43 MC Chinese patients with genetic diagnosis have been reported till now (including our five patients). Forty-seven variants in CLCN1 gene were found, which consisted of 33 missense variants, 6 nonsense variants, 5 frame-shift variants, and 3 splicing variants. Variants in exon 8, 15, 12, and 16 were most prevalent, while the most common variants were c.892G>A (p.A298T) (n = 9), c.139C>T (p.R47W) (n = 3), c.1205C>T(p.A402V) (n = 3), c.1657A>T (p.I553F) (n = 3), c.1679T>C (p.M560T) (n = 3), c.350A>G (p.D117G) (n = 2), c.762C>G (p.C254W) (n = 2), c.782A>G (P.Y261C) (n = 2), and c.1277C>A (p.T426N) (n = 2).Conclusion: Our results reported five CLCN1-related MC patients, which expanded the clinical and genetic spectrum of MC patients in China. Based on literature review, 43MC Chinese patients with genetic diagnosis have been reported till now, and variants in exon eight were most prevalent in Chinese MC patients while c.892G>A (p.A298T) was probably a founder mutation.

Background Kidney transplant recipients (KTR) are considered high-risk for morbidity and mortality from coronavirus disease 2019 (COVID-19). However, some studies did not show worse outcomes compared to non-transplant patients and there is little data about immunosuppressant drug levels and secondary infections in KTR with COVID-19. Herein, we describe our single-center experience with COVID-19 in KTR. Methods We captured KTR diagnosed with COVID-19 between March 1, 2020 and May 18, 2020. After exclusion of KTR on hemodialysis and off immunosuppression, we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by age and sex (controls). Results Eleven KTR were hospitalized and matched with 44 controls. One KTR and 4 controls died (case fatality rate: 9.1%). There were no significant differences in length of stay or clinical outcomes between KTR and controls. Tacrolimus or sirolimus levels were >10 ng/mL in 6 out of 9 KTR (67%). Bacterial infections were more frequent in KTR (36.3%), compared with controls (6.8%, P = .02). Conclusions In our small case series, unlike earlier reports from the pandemic epicenters, the clinical outcomes of KTR with COVID-19 were comparable to those of non-transplant patients. Calcineurin or mammalian target of rapamycin inhibitor (mTOR) levels were high. Bacterial infections were more common in KTR, compared with controls.

Background In order for healthcare systems to prepare for future waves of COVID-19, an in-depth understanding of clinical predictors is essential for efficient triage of hospitalized patients. Methods We performed a retrospective cohort study of 259 patients admitted to our hospitals in Rhode Island to examine differences in baseline characteristics (demographics and comorbidities) as well as presenting symptoms, signs, labs, and imaging findings that predicted disease progression and in-hospital mortality. Results Patients with severe COVID-19 were more likely to be older (p = 0.02), Black (47.2% vs. 32.0%, p = 0.04), admitted from a nursing facility (33.0% vs. 17.9%, p = 0.006), have diabetes (53.9% vs. 30.4%, p Conclusions Certain patient characteristics and clinical features can help clinicians with early identification and triage of high-risk patients during subsequent waves of COVID-19.

BACKGROUND Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. METHODS We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. RESULTS A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P

Background: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. Methods: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. Results: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. Conclusions: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).

Objective We aimed to externally validate the predictive performance of two recently developed COVID‐19‐specific prognostic tools, the COVID‐GRAM and CALL scores, and prior prognostic scores for community‐acquired pneumonia (CURB‐65), viral pneumonia (MuBLSTA) and H1N1 influenza pneumonia (Influenza risk score) in a contemporary US cohort. Methods We included 257 hospitalised patients with laboratory‐confirmed COVID‐19 pneumonia from three teaching hospitals in Rhode Island. We extracted data from within the first 24 hours of admission. Variables were excluded if values were missing in >20% of cases, otherwise, missing values were imputed. One hundred and fifteen patients with complete data after imputation were used for the primary analysis. Sensitivity analysis was performed after the exclusion of one variable (LDH) in the complete dataset (n = 257). Primary and secondary outcomes were in‐hospital mortality and critical illness (mechanical ventilation or death), respectively. Results Only the areas under the receiver‐operating characteristic curves (RO‐AUC) of COVID‐GRAM (RO‐AUC = 0.775, 95% CI 0.525‐0.915) for in‐hospital death, and CURB65 for in‐hospital death (RO‐AUC = 0.842, 95% CI 0.674‐0.932) or critical illness (RO‐AUC = 0.766, 95% CI 0.584‐0.884) were significantly better than random. Sensitivity analysis yielded similar trends. Calibration plots showed better agreement between the estimated and observed probability of in‐hospital death for CURB65, compared with COVID‐GRAM. The negative predictive value (NPV) of CURB65 ≥2 was 97.2% for in‐hospital death and 88.1% for critical illness. Conclusions The COVID‐GRAM score demonstrated acceptable predictive performance for in‐hospital death. The CURB65 score had better prognostic utility for in‐hospital death and critical illness. The high NPV of CURB65 values ≥2 may be useful in triaging and allocation of resources.

Introduction: Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking.Patients and Methods: In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediatric mitochondrial myopathy cases from China.Results: Twenty-four patients suspected with mitochondrial myopathy were enrolled initially and 21 were genetically identified. Fourteen patients were found to harbor mitochondrial DNA point mutations (14/21, 66.7%), including m.3243A>G (9/15, 60%), m.3303C>T (2/15, 13.3%), m.3302A>G (1/15, 6.7%), m.3250T>C (1/15, 6.7%), m.3251A>G (1/15, 6.7%), of whom 12 patients presented with progressive proximal mitochondrial myopathy (12/14, 85.7%). Three patients revealed large-scale deletion in blood or muscle tissue (3/21, 14.3%), presenting with Kearns-Sayer syndrome (1/3, 33.3%) or chronic progressive external ophthalmoplegia (2/3, 66.7%). Four patients were found to harbor pathogenic nuclear gene variants (4/21, 19.0%), including five variants in TK2 gene and two variants in SURF1 gene. During the follow-ups up to 7 years, 10 patients developed cardiomyopathy (10/21, 47.6%), 13 patients occurred at least once hypercapnic respiratory failure (13/21, 61.9%), six experienced recurrent respiratory failure and intubation (6/21, 28.6%), eight patients failed to survive (8/21, 38.1%). With nocturnal non-invasive ventilation of BiPAP, three patients recovered from respiratory failure, and led a relative stable and functional life (3/21, 14.3%).Conclusion: Mitochondrial myopathy in children has great clinical, pathological, and genetical heterogeneity. Progressive proximal myopathy is most prevalent. Mitochondrial DNA point mutations are most common. And respiratory failure is a critical risk factor of poor prognosis.

To carry out genetic and metabolite analysis for an infant with cerebral creatine deficiency syndrome type 2 (CCDS2).Clinical data of the child was collected. Whole-exome sequencing was carried out to identify potential variants by next generation sequencing. Candidate variants were confirmed by Sanger sequencing. Metabolites were determined by tandem mass spectrometry and magnetic resonance spectroscopy. Treatment was carried out following the diagnosis and genetic counseling for the affected family.Two novel heterozygous variants (c.289delC and c.392-1GC) of the GAMT gene were identified in the proband, which were respectively inherited from her father and mother. In silico analysis suggested both variants to be pathogenic. Creatine (Cr) level of the child was very low, and cerebral guanidinoacetate (GAA) level was slightly increased. But both had recovered to normal in two weeks, and cerebral Cr level was significantly improved after two months. Intellectual and motor development of the child were significantly improved.The child was diagnosed with CCDS type 2, for which pathogenic variants of the GAMT gene may be accountable. Treatment has attained a satisfactory effect for the patient.

Background Variants in the SLC25A1 gene are associated with a severe neurometabolic disease, D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA). A report in 2014 presented the first account of congenital myasthenic syndrome (CMS) with mild intellectual disability (ID) caused by SLC25A1. To date, only two missense variants in SLC25A1 have been linked to CMS. Case presentations A Chinese boy presented fatigable muscular weakness, myasthenic crisis, epilepsy and developmental delay along with mild elevation of urinary 2-ketoglutarate (2-KG) and lactic acid levels. He showed a partial response to pyridostigmine. Genetic analysis using trio whole-exome sequencing (WES), Sanger sequencing, and cosegregation analyses revealed two novel pathogenic variants of SLC25A1 (c.628C > T, p.R210X; c.145G > A, p.V49M). Conclusions We report a boy who carries novel compound heterozygous variants of SLC25A1 and presents a phenotype intermediate between CMS and D/L-2-HGA. This case expands the range of known phenotypes and genotypes associated with SLC25A1.

Additional file 1. Muscle biopsy. A–D Skeletal muscle sections from the patient were stained with COX (A), HE(B), MGT2 (C) and SDH (D) to visualize mitochondria. E-F Electron microscopy findings.

Background To better understand patient factors that impact clinical outcomes in COVID-19, we performed a retrospective cohort study of patients hospitalized with COVID-19 in Rhode Island to identify patient and clinical characteristics associated with severe disease. Methods We analyzed 259 patients admitted to our academic medical center during a three month period with confirmed COVID-19. Clinical data was extracted via chart review and lab results within the first 24 hours of admission were extracted directly from electronic medical records. Patients were divided in two groups based upon the highest level of supplemental oxygen (O2) required during hospitalization: severe COVID-19 (high flow O2, non-invasive, or invasive mechanical ventilation) and non-severe COVID-19 (low flow O2 or no supplemental O2). SAS 9.4 (Cary, NC) was used for statistical analyses. Chi-square or Fisher’s exact tests for categorical variables and the Student’s t-test for continuous variables were used to compare demographics, baseline comorbidities, and clinical data between the severe and non-severe groups. Table 1: Demographics Results Of 259 patients, 166 (64%) had non-severe disease, and 93 (36%) severe disease; median age [IQR] was 62 [51,73]. There were 138(53%) males and 75 (29%) Hispanics. Among non-Hispanics,124(48%) were White, 48(19%) African Americans, and 12(5%) other races. Sixty (23%) were admitted from a nursing facility and the in-hospital mortality rate was 15% (38/259). Severe COVID-19 was associated with older age (p=0.02), admission from nursing facility (p=0.009), increased BMI (p=0.03), diabetes mellitus (p=0.0002), and COPD (p=0.03). At the time of presentation, severe COVID-19 was associated with tachypnea, hypoxia, hypotension (all p< 0.0001), elevated BUN (p=0.002) and AST (p=0.001), and acute or chronic kidney injury (p=0.01). Median hospital stay [IQR] was 11 days [7,18] in the severe vs. 6 days [3,11] in the non-severe group. In the severe group, 72% required ICU admission and 39% died. Table 2: Medical comorbidities Table 3: Presenting symptoms and signs in the first 48 hours of admission Table 4: Basic labs in the first 24 hours Conclusion In this cohort of patients with COVID-19, specific comorbidities, and vital signs at presentation were associated with severe COVID-19. These findings help clinicians with early identification and triage of high risk patients. Disclosures All Authors: No reported disclosures

Background Observational studies suggest that half-dose valganciclovir (VGV) prophylaxis (450 mg daily for normal renal function) is as effective as full-dose (900 mg daily) in preventing CMV infection among kidney transplant recipients (KTR). However, this practice is not supported by current guidelines, for fear of selecting resistance, mainly in high-risk, i.e. donor CMV seropositive/recipient negative (D+/R-) KTR. Full-dose VGV is costly, and possibly associated with higher incidence of neutropenia and BK viremia. Our institution adopted half-dose VGV prophylaxis for R+ KTR in January 2018. Methods We included R+ KTR transplanted between 1/1/2014 and 12/31/2018 at our center. Data were censored at 1-year post-transplant, graft loss or death. Primary outcomes were early (< 6 months from transplant) and any CMV viremia. Secondary outcomes were neutropenia, BK viremia, graft loss and death. Categorical variables were compared with χ 2 or Fisher’s exact tests, continuous variables with the Mann-Whitney test. We used log-rank and Gray’s tests to compare cumulative incidence of outcomes, after adjustment by propensity score for differences in baseline characteristics. Results 106 R+ KTR received full-dose and 35 half-dose VGV. Antithymocyte globulin (ATG) induction was associated with significantly higher cumulative incidence of both early (P=0.017) and any (P=0.02) CMV viremia, compared to basiliximab induction (Fig. 1). After adjusting for gender and induction regimen, we noted a signal for higher cumulative incidence of any (P=0.044), but not early (P=0.598) CMV viremia in the full-dose VGV group (Fig. 2). There were no significant differences (P >0.1) in incidence of neutropenia, BK viremia, graft loss or death between the two groups. Cost savings were estimated at $2630 per CMV R+ KTR (Table 1). Table 1. Comparison of outcomes and cost between the two anti-CMV prophylaxis groups. Data are presented as n (%), unless otherwise indicated. Fig 1. Probability of CMV viremia in KTR who received ATG vs. basiliximab induction. Fig 2. Probability of CMV viremia in KTR who received full-dose vs. half-dose VGV prophylaxis. Conclusion In our pilot series, half-dose VGV was at least as effective as full-dose VGV in preventing CMV viremia in R+ RTR, and less costly. If larger scale studies verify generalizability of these results, half-dose VGV may be considered as standard of care for R+ KTR. In KTR, the antimetabolite probably contributes to neutropenia more than VGV prophylaxis. Disclosures All Authors: No reported disclosures

Background Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19. Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses. To our knowledge, no case-control study of COVID-19 in OTR has been published to-date. Methods We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020. After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls). All patients were discharged from the hospital or died. Results 16 KTR had COVID-19. All 3 KTR off IS, who were excluded from further analyses, survived. Median age was 54 (range: 34–65) years; 5/13 KTR (38.4%) were men. Median time from transplant was 41 (range: 1–203) months. Two KTR, both transplanted >10 years ago, were managed as outpatients. IS was reduced in 12/13 (92.3%), most often by discontinuation of the antimetabolite. IL6 levels were >1,000 (normal: < 5) pg/mL in 3 KTR. Tacrolimus or sirolimus levels were >10 ng/mL in 6/9 KTR (67%) (Table 1). Eleven KTR were hospitalized (84.6%) and matched with 44 controls. One KTR, the only one treated with hydroxychloroquine, died (CFR 5.8%; 7.6% in KTR on IS; 9% in hospitalized KTR on IS). Four controls died (CFR: 9%; state CFR: 5.2%; inpatient CFR: 16.6%). There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls. Four KTR (30.7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab. KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2). Table 1 Table 2 Conclusion Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients. Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction. Extremely high IL6 levels were common. The role of IS and potential benefits from investigational treatments remain to be elucidated. A larger multi-institutional study is underway. Disclosures All Authors: No reported disclosures

Mitochondrial disorders (MDs) are genetic ailments affecting all age groups. Epidemiological data and frequencies of gene mutations in pediatric patients in China are scarce. This retrospective study assessed 101 patients with suspected MDs treated at the Neurology Department of Children's Hospital, Fudan University, in 2011–2017. Mitochondrial (mtDNA) and nuclear (nDNA) samples were assessed by long-range polymerase chain reaction (PCR)-based whole mtDNA sequencing and whole exome sequencing (WES) for identifying pathogenic mutations. Muscle samples underwent various staining protocols and immunofluorescence for detecting selected proteins. Seventeen mutations in the MT-TL1, MT-COX2, MT-ND4, MT, tRNA TRNE, MT-TN, MT-TK, MT-ATP6, MT-ND6, MT-ND3 and MT-CO3 genes were identified in 39 patients, of which m.3243A > G, m.3303C > T, m.8993T > C/G, m.9176T > C, and m.10191T > C were most common. Mitochondrial myopathy and MELAS were most common for m.3243A > G mutation. Four novel mutations were detected, including m.9478insT, m.5666T > C, m.8265T > C, and m.8380–13600 deletion mutations related to Leigh syndrome, mitochondrial myopathy and KSS, respectively. Thirty-three mutations in the TK2, POLG, IBA57, HADHB, FBXL4, ALDH5A1, FOXRED1, TPK1, NDUFAF5, NDUFAF7, NDUFV1, CARS2, PDHA1, and HIBCH genes were identified in 19 patients, including 23 currently unknown. Higher rates of TK2, POLG, IBA57, and HADHB mutations were found in nDNA-mutated MD compared with the remaining individuals. Besides, IBA57 c.286T > C (p.Y96H), TK2 c.497A > T (p.D166V) founder mutations critically contributed to MDs. Comprehensive genomic analysis plays a critical role in pediatric MD diagnosis. These data summarize the relative frequencies of different gene mutations in a large Chinese population, and identified 23 novel MD-associated nDNA and 4 novel mtDNA mutations.

A total of 20 normal newborns and 8 brain injured newborns were monitored for 2 hours with domestic digital amplitude integrated cerebral function monitor (CFM 3000) and similar imported products LECTROMED CFM 5330 simultaneously. 32 newborns with seizures or suspected seizures were monitored with CFM 3000 and conventional electroencephalogram (EEG) simultaneously. The tracings of amplitude integrated electroencephalogram (aEEG) monitored by CFM 3000 and LECTROMED CFM 5330 are similar to each other. The continuous electrical activity, sleep-wake cycle, the mean of lower or upper bound voltage and duration of broad and narrow band were no significant statistical difference between different machines; The pattern of aEEG tracing of 8 infants with brain injury monitored by CFM 3000 was the same as monitored by the LECTROMED CFM 5330. The detection rate of seizure with CFM 3000 and conventional EEG were no statistically significant difference, and the consistency with Kappa test was: Kappa = 0.552, P = 0.001. The CFM 3000 can reflect the change of cerebral function and identify infants with brain injury reliably.

Amplitude integrated electroencephalogram (aEEG), also known as cerebral function monitor (CFM), is a non-invasive detection of brain function, having good accuracy in early diagnosis and prognosis evaluation of neonatal brain damage. Today, doctors classify amplitude integrated electroencephalogram mainly based on its waveform and amplitude, then they make correct diagnosis of brain function of neonates. However, in some cases, the amplitude and waveform of aEEG are not very clearly shown, the only way is relying on doctors' experience to give out judgement, which has some subjective factors, so doctors can not present accurate diagnostic information. To solve this problem by the use of non-linear dynamics, we calculate and analyze the correlation dimension, Lyapunov exponent and approximate entropy of the aEEG for neonates with convulsions and for normal neonates; then we take these three characters as a three-dimensional vector; finally, the aEEG of neonates with convulsions and the aEEG of normal neonates are distributed into two parts in threedimensional space, thus the correlation dimension, Lyapunov exponent and approximate entropy of the aEEG can reflect the internal information of neonatal brain function. Therefore, it can be used as a new method for studying neonatal aEEG.

Currently, there is no cure for Duchenne and Becker muscular dystrophies (DMD/BMD). However, clinical trials with new therapeutic strategies are being conducted or considered. A comprehensive database is critical for patient recruitment and efficacy evaluation. China has the largest population, yet, no comprehensive database for DMD/BMD is available. Our study registered the data of the DMD/BMD patients in East China. A modified registry form of Remudy ( http://www.remudy.jp/ ) was applied to Chinese DMD/BMD patients through the outpatient clinic at Children’s Hospital of Fudan University, Shanghai during the period of August 2011 to December 2013. The data included geographic distribution of patients, age at diagnosis, clinical manifestation, genetic analysis and treatment status. 194 DMD and 35 BMD patients were registered. Most patients lived in East China, namely Jiangsu province, Anhui province, Zhejiang province, Jiangxi province, Shanghai, Fujian province and Shandong province. All individuals aged less than 18 years (age limit to a children’s hospital). Diagnosis was made for a majority of patients during the age of 3–4 (16.6%) and 7–8 (14.8%) years old. Exon deletion was the most frequent genetic mutations (65.5% and 74.3%) followed by point mutations (14.4% and 11.4%), duplications (9.8% and 8.6%) and small insertion/deletion (9.3% and 2.9%) for DMD and BMD, respectively. 82.5% of DMD registrants were ambulatory, and all the BMD registrants were able to walk. 26.3% of DMD registrants have been treated with steroids. Cardiac functions were examined for 46.4% DMD boys and 45.7% BMD boys and respiratory functions were examined for 18.6% DMD boys and 14.3% BMD boys. Four boys with abnormal cardiac function were prescribed for treatment with cardiac medicine. 33.2% of DMD patients are eligible for exon skipping therapy, and among them 9.2% and 4.3% patients are eligible for skipping exon 51 and 53, respectively. The database is the first linking accurate genetic diagnosis with clinical manifestation and treatment status of dystrophinopathy patients in East China. It provides comprehensive information essential for further patient management, especially for promotion of international cooperation in developing experimental therapies such as exon skipping and read-through of nonsense mutations targeting a subgroup of DMD patient population.