Application of Brain Injury Guidelines at a Pediatric Level 1 Trauma Center predicts reliability, safety, and improved resource utilization.

PURPOSE: Brain Injury Guidelines (BIG) have been established to guide management related to TBI in adults. Here, BIG criteria were applied to pediatric TBI patients to evaluate reliability, safety, and resource utilization. METHODS: A retrospective study was performed on all pediatric TBI patients aged 18 years or younger from January 2012 to July 2023 at a Level 1 Pediatric Trauma Center. The severity of TBI (BIG 1/2/3) was rated by review of initial cranial imaging by two independent observers. Inter-observer reliability was assessed. Predictions based on BIG criteria regarding repeat cranial imaging, ICU admission, and neurosurgical consultation were compared with observations from the cohort. Outcome data was collected, including neurosurgical intervention and mortality rate. RESULTS: Three hundred fifty-nine patients were included with mean age of 5.3 years. Injury severity included 44 BIG 1 (12.2%), 170 BIG 2 (47.4%), and 145 BIG 3 injuries (40.4%). Inter-rater reliability was 96.4%. Neurosurgical consultation was obtained in all patients, though only predicted by guidelines in 40.4%. Repeat imaging was obtained in 166 BIG 1/2 patients, with an average of 1.3 CT scans and 0.8 MRIs/rapid MRIs per patient. ICU was utilized in 104 (77.6%) patients not recommended per BIG criteria. Ultimately, 37 patients, all BIG 3, required neurosurgical intervention; no neurosurgical interventions were required in those classified as BIG 1/2. CONCLUSIONS: BIG criteria can be applied to pediatric TBI with high inter-observer reliability and without formal neurosurgical training. Retrospective application of BIG predicted fewer imaging studies, ICU admissions, and neurosurgical consults without overlooking patients requiring neurosurgical intervention.

Hashimoto's Thyroiditis in Noonan Syndrome: A Case Report.

Noonan syndrome is a genetic, developmental disorder characterized by facial deformities, congenital heart defects, webbed neck, wide space nipples, and growth hormone deficiencies. We report a case of a 15-year-old female patient who presented to the outpatient department with recurrent puffiness of both eyes, easy fatiguability, and dyspnea on exertion. The condition was associated with bilateral proximal muscular weakness of lower limbs with positive Gower's sign. On examination, the patient had a webbed neck, hypertelorism, a shielded chest, short stature, and a high-arched palate. Thyroid function tests revealed hypothyroidism. Chromosomal analysis revealed 46 XX. After excluding Turner syndrome on karyotyping, Noonan syndrome with hypothyroidism was diagnosed. The patient was started on levothyroxine and referred to a pediatric endocrinologist for further growth and development assessment. Autoimmune hypothyroidism in a patient with Noonan Syndrome is rare; it may occur as a separate entity or have some genetic susceptibility. Further research is needed to determine the association of autoimmune hypothyroidism with Noonan syndrome.

Co-design for stroke intervention development: Results of a scoping review.

BACKGROUND: Co-design methodology seeks to actively engage end-users in developing interventions. It is increasingly used to design stroke interventions; however, limited guidance exists, particularly with/for individuals with stroke who have diverse cognitive, physical and functional abilities. Thus, we describe 1) the extent of existing research that has used co-design for stroke intervention development and 2) how co-design has been used to develop stroke interventions among studies that explicitly used co-design, including the rationale, types of co-designed stroke interventions, participants involved, research methodologies/approaches, methods of incorporating end-users in the research, co-design limitations, challenges and potential strategies reported by researchers. MATERIALS AND METHODS: A scoping review informed by Joanna Briggs Institute and Arksey & O'Malley methodology was conducted by searching nine databases on December 21, 2022, to locate English-language literature that used co-design to develop a stroke intervention. Additional data sources were identified through a hand search. Data sources were de-duplicated, and two research team members reviewed their titles, abstracts and full text to ensure they met the inclusion criteria. Data relating to the research objectives were extracted, analyzed, and reported numerically and descriptively. RESULTS: Data sources used co-design for stroke intervention development with (n = 89) and without (n = 139) explicitly using the term 'co-design.' Among studies explicitly using co-design, it was commonly used to understand end-user needs and generate new ideas. Many co-designed interventions were technology-based (65%), and 48% were for physical rehabilitation or activity-based. Co-design was commonly conducted with multiple participants (82%; e.g., individuals with stroke, family members/caregivers and clinicians) and used various methods to engage end-users, including focus groups and workshops. Limitations, challenges and potential strategies for recruitment, participant-engagement, contextual and logistical and ethics of co-designed interventions were described. CONCLUSIONS: Given the increasing popularity of co-design as a methodology for developing stroke interventions internationally, these findings can inform future co-designed studies.

Lipid Mediators and Cytokines/Chemokines Display Differential Profiles in Severe versus Mild/Moderate COVID-19 Patients.

Host immune responses play a key role in COVID-19 pathogenesis. The underlying phenomena are orchestrated by signaling molecules such as cytokines/chemokines and lipid mediators. These immune molecules, including anti-SARS-CoV-2 antibodies, interact with immune cells and regulate host responses, contributing to inflammation that drives the disease. We investigated 48 plasma cytokines/chemokines, 21 lipid mediators, and anti-S protein (RBD) antibodies in COVID-19 patients (n = 56) and non-COVID-19 respiratory disease controls (n = 49), to identify immune-biomarker profiles. Cytokines/chemokines (IL-6, CXCL-10 (IP-10), HGF, MIG, MCP-1, and G-CSF) and lipid mediators (TxB2, 11-HETE, 9-HODE, 13-HODE, 5-HETE, 12-HETE, 15-HETE, 14S-HDHA, 17S-HDHA, and 5-oxo ETE) were significantly elevated in COVID-19 patients compared to controls. In patients exhibiting severe disease, pro-inflammatory cytokines/chemokines (IL-6, CXCL-10, and HGF) and anti-SARS-CoV-2 antibodies were significantly elevated. In contrast, lipid mediators involved in the reduction/resolution of inflammation, in particular, 5-HETE, 11-HETE, and 5-oxoETE, were significantly elevated in mild/moderate disease. Taken together, these immune-biomarker profiles provide insight into immune responses related to COVID-19 pathogenesis. Importantly, our findings suggest that elevation in plasma concentrations of IL-6, CXCL-10, HGF, and anti-SARS-CoV-2 antibodies can predict severe disease, whereas elevation in lipid mediators peaks early (compared to cytokines) and includes induction of mechanisms leading to reduction of inflammation, associated complications, and maintenance of homeostasis.

The demographics of autoimmune hepatitis in human immunodeficiency virus-infected patients: a United States cross-sectional study.

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver with increasing global prevalence. However, no epidemiological data exist for AIH in human immunodeficiency virus (HIV)-infected patients. Aim: To determine the demographics and comorbid conditions associated with AIH among HIV-infected individuals in the United States. Material and methods: The United States National Inpatient Sample database was used to identify HIV hospital encounters in 2012-2014. The encounters were then classified into 2 groups based on a concomitant primary diagnosis of AIH. Primary outcomes included the demographics and comorbid conditions of AIH among HIV-infected patients. Secondary outcomes assessed the independent predictors of AIH. Results: A total of 48,3310 patients with an HIV diagnosis were included. The estimated AIH prevalence was 52.8/100,000 HIV hospital encounters. The female gender was more likely to have AIH with an odds ratio (OR) of 1.82; 95% confidence interval (CI) 1.42-2.32, p < 0.0001. The age intervals of 35-50 and 51-65 years had higher odds of AIH 110 (43.1%) and 115 (45.1%) with OR = 1.30; 95% CI: 1.02-1.67, p = 0.03 and OR = 1.34; 95% CI: 1.05-1.71, p = 0.02, respectively. African American and Hispanic races were more commonly affected. Moreover, HIV-infected patients with AIH had a higher risk of having elevated transaminases, long-term steroid use, rheumatoid arthritis, and ulcerative colitis. Conclusions: This study illustrates that the estimated prevalence of AIH in HIV-infected patients in the United States is 52.8/100,000. AIH in HIV-positive individuals has a predilection for the female gender and African American and Hispanic races, and shows a higher correlation with rheumatoid arthritis and ulcerative colitis.

Non-syndromic Intellectual Disability: An Experimental In-Depth Exploration of Inheritance Pattern, Phenotypic Presentation, and Genomic Composition.

Background Intellectual disability (ID), also termed mental retardation (MR), is a neurodevelopmental disorder characterized by an intelligence quotient (IQ) of 70 or below and a deficit in at least two behaviors associated with adaptive functioning. The condition is further classified into syndromic intellectual disability (S-ID) and non-syndromic intellectual disability (NS-ID). This study highlights the genes associated with NS-ID. Objectives A genetic study was performed on two Pakistani families to know the inheritance patterns, clinical phenotypes, and molecular genetics of affected individuals with NS-ID. Methodology Samples were collected from two families: families A and B. All affected individuals in both families were diagnosed by a neurologist. Written informed consent was taken from the affected individuals and guardians before collecting the data and sample. Family A belongs to the Swabi District of Pakistan having four affected individuals, out of whom three were male and one was female. Family B also belongs to the Swabi District of Pakistan having two affected individuals, out of whom one was male and one was female. A total of 10 candidate genes were selected and were further screened by microarray analysis. Results In family A, this analysis identified a region of 9.6 Mb on chromosome 17q11.2-q12 between the single nucleotide polymorphisms (SNPs) rs953527 and rs2680398. The region was genotyped using microsatellite markers to confirm the haplotypes in all family members. Based on the phenotype-genotype relationship, 10 possible candidate genes were selected out of more than 140 genes in this critical region of 9.6 Mb. In family B, homozygosity mapping through microarray identified four homozygous areas of affected individuals: two (27,324,822-59,122,062 and 96,423,252123,656,241) on chromosome 8, one (14,785,224-19,722,760) on chromosome 9, and one (126173647-126215644) on chromosome 11. Conclusion An autosomal recessive pattern was found in the pedigrees of both families A and B. Phenotypically affected individuals showed IQ levels below 70. Three genes, CDK5R1, OMG, and EV12A, were found on chromosome 17q11.2-q12 region of affected individuals in family A with high expression in the frontal cortex of the brain, hippocampus, and spinal cord, respectively. Other regions on chromosomes 8, 9, and 11 as evident from the affected individuals in family B can also contribute to the non-syndromic autosomal recessive intellectual disability (NS-ARID). Further research is needed to find the association of these genes with intelligence and other neuropsychiatric conditions.

Gastric Electrical Stimulation for the Treatment of Gastroparesis or Gastroparesis-like Symptoms: A Systemic Review and Meta-analysis.

BACKGROUND: The effects of gastric electrical stimulation are not fully understood. We aimed to assess the efficacy of gastric electrical stimulation (GES) for patients with gastroparesis and gastroparesis-like symptoms. MATERIALS AND METHODS: We searched PubMed, Scopus, Cochrane, Web of Science, Embase, and Science Direct to identify controlled trials and cohort studies. We used random effects models to estimate pooled effects. A total of nine studies met the criteria and were included for the final qualitative synthesis and the quantitative analysis. We examined the mean absolute differences (MD) and 95% CIs. RESULTS: Nine studies (n = 730) met the criteria and were included for the final qualitative synthesis and the quantitative analysis. There was significant improvement in gastrointestinal (GI) total symptom score (TSS) with the GES group compared with controls during the randomized blind trials. This effect was sustained at 12 months after treatment compared with before treatment (MD = -6.07; 95% CI, -4.5 to -7.65; p < 0.00001). The pooled effect estimate showed a significant improvement in frequency of weekly vomiting episodes at 12 months compared with before treatment (MD = -15.59; 95% CI, -10.29 to -20.9; p < 0.00001). CONCLUSION: GES appears beneficial, with significant improvement in GI TSS, weekly vomiting frequency, gastric emptying study, and quality of life.

Effectiveness of polyhexamethylene biguanide, chlorhexidine, and calcium hydroxide intracanal medicament against intraradicular mature polymicrobial biofilm: A microbiological study.

Aim: To compare the effectiveness of different intracanal medicaments against polymicrobial biofilm formed by Enterococcus faecalis, Staphylococcus aureus, and Candida albicans. Materials and Methods: Eighty mature human roots with intraradicular polymicrobial biofilm were randomly assigned into four groups (n = 20). Intracanal medicaments 0.2% polyhexamethylene biguanide (PHMB), 2% chlorhexidine (CHX), and calcium hydroxide (CH) were applied into the root canals. Collected dentine samples were tested at 7th, 15th, and 30th day for microbial growth, and the colony-forming units per ml (CFU/ml) were determined. Results: The CFU/ml data were analyzed using unpaired t-test and one-way ANOVA-F comparison test. All medicaments resulted in a significant reduction (P < 0.05) in microbial growth at all time intervals compared to the control group. CHX and PHMB showed a similar reduction in CFU/ml at 7th and 15th day but significantly more than CH at all time intervals. At 30th day, PHMB caused a significantly more reduction in CFU/ml than CHX. Conclusions: All the three tested intracanal medicaments such as CH, CHX, and PHMB Gel were effective in reducing the microbial count. CH has a limited antimicrobial effect against the polymicrobial biofilm found inside the root canal. 2% CHX gel has a time-dependent antimicrobial effect. PHMB has a superior antimicrobial effect in comparison with CHX and CH.

Medicines prescribing for homeless persons: analysis of prescription data from specialist homelessness general practices.

BACKGROUND: Specialist homelessness practices remain the main primary care access point for many persons experiencing homelessness. Prescribing practices are poorly understood in this population. OBJECTIVE: This study aims to investigate prescribing of medicines to homeless persons who present to specialist homelessness primary care practices and compares the data with the general population. SETTING: Analyses of publicly available prescribing and demographics data pertaining to primary care in England. METHODS: Prescribing data from 15 specialist homelessness practices in England were extracted for the period 04/2019-03/2020 and compared with data from (a) general populations, (b) the most deprived populations, and (c) the least deprived populations in England. MAIN OUTCOME MEASURE: Prescribing rates, measured as the number of items/1000 population in key disease areas. RESULTS: Data corresponding to 20,572 homeless persons was included. Marked disparity were observed in regards to prescribing rates of drugs for Central Nervous System disorders. For example, prescribing rates were 83-fold (mean (SD) 1296.7(1447.6) vs. 15.7(9.2) p = 0.033) items), and 12-fold (p = 0.018) higher amongst homeless populations for opioid dependence and psychosis disorders respectively compared to the general populations. Differences with populations in the least deprived populations were even higher. Prescribing medicines for other long-term conditions other than mental health and substance misuse was lower in the homeless than in the general population. CONCLUSIONS: Most of the prescribing activities in the homeless population relate to mental health conditions and substance misuse. It is possible that other long-term conditions that overlap with homelessness are under-diagnosed and under-managed. Wide variations in data across practices needs investigation.

Physical therapy assessment and whole-body magnetic resonance imaging findings in children with glycogen storage disease type IIIa: A clinical study and review of the literature.

INTRODUCTION: Early recognized manifestations of GSD III include hypoglycemia, hepatomegaly, and elevated liver enzymes. Motor symptoms such as fatigue, muscle weakness, functional impairments, and muscle wasting are typically reported in the 3rd to 4th decade of life. OBJECTIVE: In this study, we investigated the early musculoskeletal findings in children with GSD IIIa, compared to a cohort of adults with GSD IIIa. METHODS: We utilized a comprehensive number of physical therapy outcome measures to cross-sectionally assess strength and gross motor function including the modified Medical Research Council (mMRC) scale, grip and lateral/key pinch, Gross Motor Function Measure (GMFM), Gait, Stairs, Gowers, Chair (GSGC) test, 6 Minute Walk Test (6MWT), and Bruininks-Oseretsky Test of Motor Proficiency Ed. 2 (BOT-2). We also assessed laboratory biomarkers (AST, ALT, CK and urine Glc4) and conducted whole-body magnetic resonance imaging (WBMRI) to evaluate for proton density fat fraction (PDFF) in children with GSD IIIa. Nerve Conduction Studies and Electromyography results were analyzed where available and a thorough literature review was conducted. RESULTS: There were a total of 22 individuals with GSD IIIa evaluated in our study, 17 pediatric patients and 5 adult patients. These pediatric patients demonstrated weakness on manual muscle testing, decreased grip and lateral/key pinch strength, and decreased functional ability compared to non-disease peers on the GMFM, 6MWT, BOT-2, and GSGC. Additionally, all laboratory biomarkers analyzed and PDFF obtained from WBMRI were increased in comparison to non-diseased peers. In comparison to the pediatric cohort, adults demonstrated worse overall performance on functional assessments demonstrating the expected progression of disease phenotype with age. CONCLUSION: These results demonstrate the presence of early musculoskeletal involvement in children with GSD IIIa, most evident on physical therapy assessments, in addition to the more commonly reported hepatic symptoms. Muscular weakness in both children and adults was most significant in proximal and trunk musculature, and intrinsic musculature of the hands. These findings indicate the importance of early assessment of patients with GSD IIIa for detection of muscular weakness and development of treatment approaches that target both the liver and muscle.

Past and Future Perspectives for Hepatitis B and C in Pakistan.

Background Hepatitis B and C are viral infections of the liver transmitted by blood contamination. These infections are endemic in Pakistan and put a tremendous burden on its healthcare system. We conducted this study to assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Gujranwala, Pakistan, from 2010 to 2015 and determine the trend of future infections for a prediction of the disease burden by 2030 so policymakers can make informed decisions. Methods We conducted a retrospective cross-sectional study of 66,308 healthy blood donor samples at District Headquarters Teaching Hospital in Gujranwala from January 2010 to December 2015. Samples were screened for HBV and HCV using the kit method, and data were analyzed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY). We applied a least squares regression to our results to predict HBV and HCV incidence in 2030. Results A total of 715 samples (1.08%) were positive for HBV and 1,846 samples (2.78%) were positive for HCV. Our projections indicate that 3.25% of patients in Pakistan will be positive for HBV, and 6.36% will be positive for HBC by 2030. Conclusion We found an unexpectedly greater burden of HBV and HCV in the recent past than at current levels. The predicted percentages of future burden over the next decade were alarmingly high. These data necessitate implementing preventive and therapeutic measures by policymakers to reduce the disease burden and mortality in Pakistan.

Diurnal variability of glucose tetrasaccharide (Glc4) excretion in patients with glycogen storage disease type III.

AIM: The urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc4), is a glycogen limit dextrin that is elevated in patients with glycogen storage disease (GSD) type III. We evaluated the potential of uncooked cornstarch therapy to interfere with Glc4 monitoring, by measuring the diurnal variability of Glc4 excretion in patients with GSD III. METHODS: Voids were collected at home over 24 hours, stored at 4°C and frozen within 48 hours. Glc4 was analyzed using liquid chromatography-tandem mass spectrometry and normalized to creatinine. RESULTS: Subjects with GSD III (median age: 13.5 years, range: 3.7-62; n = 18) completed one or more 24-hour urine collection, and 28/36 collections were accepted for analysis. Glc4 was elevated in 16/18 subjects (median: 13 mmol/mol creatinine, range: 2-75, reference range: <3). In collections with elevated Glc4 (23/28), two-thirds (15/23) had low diurnal variability in Glc4 excretion (coefficient of variation [CV%] <25). The diurnal variability was significantly correlated with the Glc4 concentration (Pearson R = .644, P < .05), but not with the dose of uncooked cornstarch. High intraday variability (>25%) was not consistently observed in repeat collections by the same subject. CONCLUSIONS: The extent and variability of Glc4 excretion relative to creatinine was not correlated with cornstarch dose. A majority of collections showed low variability over 24 hours. These findings support the use of single time-point collections to evaluate Glc4 in patients with GSD III treated with cornstarch. However, repeat sampling over short time-periods will provide the most accurate assessment of Glc4 excretion, as intraday variability may be increased in patients with high Glc4 excretion.

Quantitative whole-body magnetic resonance imaging in children with Pompe disease: Clinical tools to evaluate severity of muscle disease.

OBJECTIVE: Since the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement. METHODS: Eleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7-17 years, received whole-body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4. RESULTS: Patients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = -.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD. CONCLUSION: In the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.

Distal Revascularization And Interval Ligation Procedure For The Treatment Of Dialysis Access Induced Steal Syndrome.

BACKGROUND: We aim to share our experience of the efficacy of Distal Revascularization and Interval Ligation (DRIL) in alleviating ischemic symptoms of dialysis access induced steal syndrome (DAISS) while preserving the original access. METHODS: In this multicentre study, all consecutive patients with DAISS undergoing DRIL over a period of 3 years were included. RESULTS: A total of 25 DRILs were included. Mean age was 37.8±SD 7.8 years and 52% (n=13) were females. Out of 25 patients; 88% (n=22) had more than one of the following ischemic symptoms: coolness (96%), pain (88%), paresthesia (80%), and discoloration (44%). Significant improvement following DRIL was noted in paraesthesia (86%, p-value 0.00), pain (85%, P value 0.00), coolness (83%, p-value 0.00). There was significant improvement in distal blood flow following DRIL, reflected by increase in the Aggregate Peak Systolic Velocities (PSV) in forearm vessels (PSV aggregate pre-op 39cm/s: PSV aggregate post-op 58 cm/s; p-value 0.01). The cumulative patency of DRIL graft was 96% at 3 months, 84% at 6 months and 76% at 1 year. CONCLUSION: Distal Revascularization and Interval Ligation significantly improves circulation to the distal limb and reduce ischemic symptoms thus making it a procedure of choice for treatment of DAISS.

An Unusual Presentation of Bony Outgrowths on the Chest: A Case from Pakistan.

We present a case of hereditary multiple exostoses in a male child, who presented to us with bony outgrowths on the chest and recurrent respiratory infections. On questioning, it was revealed that the child had a family history of bony outgrowths, though those affected in his family were not symptomatic. Other causes of recurrent respiratory infections were systematically ruled out, which led us to our conclusion. The treatment of this condition can be either conservative or surgical, but owing to the seriousness of our patient's condition, the preferred option was surgery in this case.

Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature.

PURPOSE: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease. METHODS: We conducted a retrospective study on infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) patients with onset before age 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation. Long-term follow-up of up to 18 years was obtained. We obtained physical therapy, lingual strength, biochemical, and pulmonary assessments as dose was escalated. RESULTS: Eleven patients with IPD (n = 7) or LOPD (n = 4) were treated with higher doses of up to 40 mg/kg weekly. There were improvements in gross motor function measure in 9/10 patients, in lingual strength in 6/6 patients, and in pulmonary function in 4/11. Significant reductions in urinary glucose tetrasaccharide, creatine kinase, aspartate aminotransferase, and alanine aminotransferase were observed at 40 mg/kg weekly compared with lower doses (p < 0.05). No safety or immunogenicity concerns were observed at higher doses. CONCLUSION: Higher rhGAA doses are safe, improve gross motor outcomes, lingual strength, pulmonary function measures, and biochemical markers in early-onset Pompe disease, and should be considered in patients with clinical and functional decline.

Whole-body magnetic resonance imaging in late-onset Pompe disease: Clinical utility and correlation with functional measures.

Whole-body magnetic resonance imaging (WBMRI) has clinical utility in measuring the amount of fatty infiltration in late-onset Pompe disease (LOPD). Muscle strength and function testing also provide valuable insight to the progression of myopathy seen in these patients. The main purpose of this study was to determine how closely muscle strength and functional testing correlate to the amount of fatty infiltration seen on WBMRI. LOPD patients were followed longitudinally and WBMRI, muscle strength testing using the modified Medical Research Council (mMRC) scale, muscle function testing using the Gait, Stairs, Gowers, Chair (GSGC) score, and labs including urinary glucose tetrasaccharide (Glc4) were performed at each visit. The amount of fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests. Nineteen patients with LOPD aged 10 to 67 years were followed for a 1 to 2 year duration. There was a small increase of 1.26% (±2.57%) in overall PDFF per year in patients on ERT. Muscle strength (mMRC) and functional testing (GSGC) correlated highly with PDFF (r = -.7596, P < .0001 and r = .8267, P < .0001, respectively). Time to carry out individual tasks of the GSGC also correlated highly with PDFF of the muscles involved. Glc4 levels were normal on most visits (27/39) despite varying severity of muscle weakness in patients. Muscle strength and GSGC scores correlate highly with PDFF values from WBMRI. They may be used in assessing severity of muscle disease and to follow LOPD patients over time.

Thyroid Screening During Early Pregnancy and the Need for Trimester Specific Reference Ranges: A Cross-Sectional Study in Lahore, Pakistan.

Background Derangements in thyroid hormone levels can cause multiple complications in the mother and the foetus. Thyroid stimulating hormone (TSH) and free thyroxine (free T4 or FT4) levels are used to screen for maternal thyroid dysfunction; these should be compared with population based trimester-specific reference ranges. Our goal was: to determine the prevalence of various thyroid derangements, in early pregnancy, according to the current reference ranges available; to determine the need for trimester specific reference ranges for the local population. Methods A multi-centric, cross sectional population survey was conducted in Lahore, Pakistan. Serum TSH and FT4 levels were measured at the hormone lab of the Pathology department of Combined Military Hospital (CMH) Lahore. The results were entered and analysed using Statistical Package for the Social Sciences (SPSS) version 23.  Results In the 293 women sampled, mean FT4 and TSH levels were 15.03 (±5.62) pmol/L and 2.53 (±6.82) mIU/L respectively. According to the laboratory specific reference ranges, the prevalence of overt hyperthyroidism was 4.10%, (mean TSH= 0.03mIU/L); subclinical hyperthyroidism was 16.38%, (mean TSH= 0.17mIU/L); normal 70.65%, (mean TSH = 1.29mIU/L); subclinical hypothyroidism 4.44%, (mean TSH= 15.11mIU/L); overt hypothyroidism 4.44%, (mean TSH = 20.60mIU/L). Conclusion Our study showed a significant prevalence of thyroid dysfunction in the first trimester of pregnancy, and therefore highlights the need for more rigorous thyroid screening of women, in early pregnancy. There is a need to monitor these women in order to reduce maternal and foetal complications. Trimester specific reference ranges for thyroid hormones need to be developed in Pakistan.