An in-frame deletion affecting the critical acid loop of PPP2R5D is associated with a neonatal lethal form of PPP2R5D-related neurodevelopmental disorder.

Heterozygous pathogenic variants in PPP2R5D gene are associated with PPP2R5D-related neurodevelopmental disorder, a rare autosomal dominant condition, characterized by neurodevelopmental impairment in childhood, macrocephaly/megalencephaly, hypotonia, epilepsy, and dysmorphic features. Up-to-date, only approximately 100 cases have been published in the literature and the full phenotypic and genotypic spectrum have not yet been fully described. PPP2R5D gene encodes the B56δ subunit of the PP2A enzyme complex. We describe a neonatal form of PPP2R5D-related disorder with early infantile death, caused by a novel in-frame deletion causing loss of 8 amino acids and insertion of serine at position 201 (p.Phe194_Pro201delinsSer) of the B56δ subunit. This deletion is predicted to disrupt a critical acidic loop of amino acids important for binding other subunits of the PP2A enzyme complex, and harbors many of the residues previously reported to cause a mild-moderate form of this condition. This report describes a neonatal lethal presentation of the PPP2R5D-related neurodevelopmental disorder and provides additional evidence that disruption of the acidic loop is an important pathomechanism underlying PPP2R5D-related disorder.

How can we measure the renal pelvic anteroposterior diameter in postnatal isolated hydronephrosis?

INTRODUCTION: The anteroposterior diameter (APD) of the renal pelvis is a commonly used ultrasound parameter in the evaluation and management of hydronephrosis. It has been established that an APD value associated with pyeloplasty is around 25 mm. Some believe the APD should be measured at the innermost part of the renal pelvis while others suggest that it should be done at the renal contour. However, there is no consensus on the optimal APD measurement technique including whether it should be measured supine or prone. This study compared six different techniques of APD measurements, in both supine and prone positions, and further evaluated their association with pyeloplasty. METHODS: Data was obtained by retrospectively reviewing patients' charts that had initial high-grade hydronephrosis (HGH) from 2008 to 2014. We recorded the patients' demographics, ultrasound data and management choice. In the mid-renal transverse plane, the APD was measured by 2 blinded investigators, at the intra-renal, renal contour and extra-renal regions of the renal pelvis in supine and prone positions (Figure A). We compared the six APD measurements based on the outcome of management (pyeloplasty vs. conservative management). The ROC curve obtained was then used to assess the ability of various APD measurements in predicting surgical intervention. The cutoff value chosen that predicts pyeloplasty was the lowest diameter with 100% specificity. RESULTS: We included 129 patients (134 renal units). Forty-four renal units (42 patients) underwent pyeloplasty whereas 90 renal units (87 patients) were managed conservatively. Patients' demographics were grouped by both SFU grade and clinical outcome. Regardless of grade, the APD measurements were different in all 6 techniques. All APD measurement techniques showed good inter-rater reliability. Based on the ROC curve, all APD measurements were associated with pyeloplasty with an AUC from 0.89 to 0.91. The supine extra-renal APD measurement of 24 mm was the most sensitive cutoff value. The cutoff values ranged from 18 to 27 mm when including patients from all grades of hydronephrosis. The median APD measurements were significantly less for SFU grade 3 than grade 4 hydronephrosis in all positions (P < 0.001 for all measurements), yet the predictive cutoff value of 24 mm for the supine extra-renal was similar for both grades. CONCLUSION: APD measurements differ based on the technique, but they are all equally associated with the clinical outcome of pyeloplasty. The inter-rater reliability of all techniques were excellent. Though the median APD measurements are smaller in SFU grade 3, it appears that the cutoff for a predictive renal pelvic APD does not differ between SFU grades 3 and 4 for the supine extra-renal technique. We conclude that the technique for measuring the APD needs to be specified in studies of hydronephrosis and in any grading systems.

Bilateral Parietal Skull Fractures in Infants Attributable to Accidental Falls.

INTRODUCTION: Multiple skull fractures, including bilateral parietal skull fractures (BPSFs) in infants are considered to be suspicious for abusive head trauma (AHT). The aim of this report is to describe a series of BPSF cases in infants which occurred due to accidental falls. METHODS: We searched our neuroradiology database for BPSF in infants (<1 year old) diagnosed between 2006 and 2019; we reviewed initial presentation, mechanisms of injury, clinical course, head imaging, skeletal survey X-rays, ophthalmology, social work and child abuse physicians (CAP) assessments, and long-term follow-up. "Confirmed accidental BPSF" were strictly defined as having negative skeletal survey and ophthalmology evaluation and a CAP conclusion of accidental injury. RESULTS: Twelve cases of BPSF were found; 3 were confirmed to be accidental, with a mean age at presentation of 3 months. Two infants had single-impact falls, and 1 had a compression injury; all 3 had small intracranial hemorrhages. None had bruises or other injuries, and all remained clinically well. A literature search found 10 similar cases and further biomechanical evidence that these fractures can occur from accidental falls. CONCLUSION: While AHT should be kept in the differential diagnosis whenever BPSFs are seen, these injuries can occur as a result of accidental falls.

Megalencephaly-Capillary Malformation-Polymicrogyria with Cerebral Venous Thrombosis.

Megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome (OMIM #602501) is characterized by megalencephaly, midline capillary malformations, and cortical malformations. This genetic overgrowth syndrome is associated with mosaic gain-of-function pathogenic PIK3CA variants (OMIM #171834).

Emergence of and risk factors for ciprofloxacin-gentamicin-resistant Escherichia coli urinary tract infections in a region of Quebec.

BACKGROUND: An increased incidence of urinary tract infections (UTIs) caused by ciprofloxacin-gentamicin-resistant Escherichia coli (CiGREC) has been observed in a tertiary care centre in Sherbrooke, Quebec. The risk factors for such infections remained unclear. METHODS: To determine risk factors for, and outcomes of, CiGREC UTIs, a case control study was conducted. Between 2000 and 2007, 93 cases and 186 controls were identified using laboratory records of patients with greater than 10(7) colony-forming units/L of E coli in a urinary specimen. Cases had E coli with minimum inhibitory concentration to ciprofloxacin of 4 mg/L or greater and minimum inhibitory concentration to gentamicin of 8 mg/L or greater (CiGREC), and controls had E coli with any other susceptibility pattern to ciprofloxacin and gentamicin. Clinical and laboratory data were collected. Adjusted odds ratios (AOR) and their 95% CIs were calculated by logistic regression. RESULTS: The prevalence of CiGREC increased sixfold during the study period. Risk factors associated with CiGREC UTI were advanced age, male sex, urological abnormality, domicile outside Sherbrooke, living in a nursing home (AOR 11.73; 95% CI 3.70 to 37.15), use of fluoroquinolones (AOR 15.24; 95% CI 5.42 to 42.83) or aminoglycosides (AOR 6.59; 95% CI 1.22 to 35.61) within the previous month, and use of fluoroquinolones during the preceding one to 12 months (AOR 2.45; 95% CI 1.06 to 5.62). Compared with controls, cases were more likely not to receive an active antibiotic as empirical or definitive treatment, and were more likely to relapse. INTERPRETATION: In the future, it may become necessary to avoid selecting as empirical therapy of urinary tract infection an antibiotic to which the patient has been recently exposed.

The delay in diagnosis of tuberculosis in the Monteregie region of Quebec, Canada.

INTRODUCTION: Despite being more prevalent in developing countries, tuberculosis (TB) remains an important health problem in Canada. Long diagnosis delays of respiratory tuberculosis are associated with adverse consequences for the patient but also for the community. From a public health perspective, identification of factors associated with long delays of diagnosis could help reduce these delays. OBJECTIVES: 1)To describe diagnosis delays of respiratory tuberculosis in Monteregie 2)To identify the characteristics of patients and factors associated with longer diagnosis delays 3)To identify consequences of these delays. METHODS: The study is descriptive and transversal. Data were obtained from notifiable diseases files of the Public Health Department of the Health and Social Services Agency of Monteregie. The diagnosis delay was calculated using the first symptomatic date and the date of diagnosis. For continued variable analyses, Student t tests and an ANOVA test were done. For categorical variables, Pearson's chi squared test and a Mann-Whitney test were done. RESULTS: The average delay of diagnosis for the 115 cases studied was 92.2 days (CI 80.6-103.8). Weight loss and/or non specific general malaise were associated with a longer diagnosis delay. No association was found between the diagnosis delay and possible consequences of longer delays. DISCUSSION AND CONCLUSION: Most patients had a diagnosis delay longer than two months. A larger study that would divide the total diagnosis delay into a patient delay and a suspicion delay (health care system delay) could permit a better identification of factors that favour long delays.