Musculoskeletal deformities in children with congenital thoracic malformations: a population-based cohort study.

PURPOSE: It is unclear if musculoskeletal deformities observed in patients with congenital diaphragmatic hernia (CDH), congenital lung lesion (CLL) and esophageal atresia/tracheoesophageal fistula (EA/TEF) are associated with the anomaly or are a result of the surgery required to treat the anomaly. This study compared the prevalence of musculoskeletal deformities for: (1) children with congenital thoracic anomalies to controls; (2) CLL to EA/TEF both repaired via thoracotomy; and (3) CLL and EA/TEF to CDH repaired via laparotomy. METHODS: We performed a retrospective study of children with CLL, CDH or EA/TEF between 1990 and 2016. Date-of-birth-matched control groups were generated from a population-based dataset. International Classification of Disease codes were used to identify scoliosis and pectus anomalies. We determined Hazard ratios (HR) for cases versus controls. RESULTS: We included 167 cases (CDH n = 82; CLL n = 29; EA/TEF n = 56) and 1670 controls. EA/TEF had a greater risk of scoliosis (HR 5.52, 95%CI 1.49,13.73) and pectus deformities (HR 4.07, 95%CI 1.96,8.45). CDH showed more scoliosis (HR 5.03, 95%CI 1.99,12.74) but not pectus anomalies. Musculoskeletal deformities were not more common in CLL. CONCLUSION: Children born with CDH or EA/TEF, but not CLL, had more musculoskeletal deformities than controls. The inconsistent association between musculoskeletal deformities and the surgical approach suggested a congenital predisposition.

Cystic fibrosis-related diabetes onset can be predicted using biomarkers measured at birth.

PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms.

BACKGROUND: The apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome. RESULTS: The re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized. CONCLUSIONS: The process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translational modification in apicomplexan parasites.

Bilateral traumatic testicular dislocation after motorbike accident: A case report with literature review.

The occurrence of testicular dislocation resulting from blunt trauma to the scrotum or abdominopelvic region is infrequent. Due to the presence of significant associated injuries, the diagnosis of this condition can often be missed. This case study presents a case of an adult male who experienced bilateral testicular dislocation following a motorbike accident. Additionally, a concise review of relevant literature is included.

Sleep-disordered breathing in children with craniosynostosis.

BACKGROUND: Syndromic craniosynostosis (SC) is associated with a high prevalence of sleep-disordered breathing (SDB). However, it remains unclear whether non-syndromic craniosynostosis (NSC) is associated with an increased risk for SDB. SETTING: This study was conducted at a tertiary referral pediatric medical center. METHODS: A prospective polysomnographic (PSG) evaluation was conducted of all children diagnosed with craniosynostosis over a 3-year period and who had not undergone previous PSG for SDB-related symptoms. RESULTS: Among 14 children fulfilling inclusion criteria, 10 had NSC and 4 were diagnosed with SC (Crouzon syndrome). SDB was present in 50 % of the NSC and in 75 % of SC. No associations emerged between the number of sutures affected and the presence of SDB. CONCLUSIONS: SDB is highly prevalent not only in SC but also among asymptomatic children with NSC. The diagnosis of NSC should prompt a diagnostic PSG as a routine component of the clinical evaluation, and PSG findings may aid in the formulation of decisions regarding timing and need for surgical interventions.

Manganese Neurotoxicity as a Stroke Mimic: A Case Report.

Manganese (Mn)-induced cerebral toxicity is a rare neurological condition that can present as a stroke mimic in high-risk populations. We present a case of a 40-year-old male with no known comorbidities who was brought to the emergency department with complaints of nonprogressive slurred speech and left facial weakness for eight days. Further history revealed that he had been working as a welder in a steel factory for the past seven years without using proper personal protective equipment (PPE). On physical examination, an upper motor neuron (UMN) type weakness on the left side of his face and spastic dysarthria could be appreciated. Following a brain computed tomography (CT) scan that showed ill-defined hypodensities in the basal ganglia without any signs of a hemorrhage, he was admitted to the stroke unit for conservative management and further investigations. A magnetic resonance imaging (MRI) scan of the brain done later showed features of manganese deposition and absorption in the globus pallidus and corticospinal tracts, indicating a diagnosis of manganese-induced cerebral toxicity. His serum manganese levels obtained during admission were normal. He was managed conservatively with intravenous rehydration and was discharged after symptomatic improvement. He was counseled and educated regarding the importance of wearing protective equipment while at work to reduce further exposure to the metal. During his follow-up visit, his symptoms had considerably improved with proper adherence to workplace safety measures.

Pancoast Tumor With Cardiac Metastases and Intracardiac Thrombosis.

Pancoast tumor is a rare and aggressive form of lung cancer; cardiac metastasis is very uncommon. We present a case of advanced Pancoast tumor, with extensive cardiac metastases and intracardiac thrombosis in a woman presenting with dyspnea, shoulder pain, and weight loss. A contrast-enhanced chest computed tomographic scan revealed an apical mass, metastatic thoracic nodes, and filling defects within both ventricles. Further imaging with cardiac magnetic resonance imaging revealed 2 left ventricular masses infiltrating into the myocardium suggestive of metastatic disease, and a multilobulated mass within the right ventricle suggestive of intracardiac thrombus. She was initiated on anticoagulation for intracardiac thrombosis. Surgical pathology of biopsied tissue samples was consistent with advanced metastatic lung adenocarcinoma. She was a poor candidate for surgical intervention. Given the patient's goals of care, she was ultimately transitioned to comfort care.

Multi-modality management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited condition defined by left ventricular wall thickness greater than 15 mm in the absence of other conditions that could explain that degree of hypertrophy. Obstructive HCM associated with left ventricular outflow tract obstruction is defined by an intraventricular systolic pressure gradient greater than or equal to 30 mm Hg. Over the past couple of decades, there has been an expansion of both invasive and pharmacotherapeutic options for patients with HCM, with recent guidelines calling for a melody of invasive and non-invasive treatment strategies. There are several invasive therapies including proven therapies such as alcohol septal ablation and septal myectomy. Novel invasive therapies such as MitraClip, radiofrequency septal ablation and SESAME procedure have more recently been promoted. Pharmacological therapy has also dramatically evolved and includes conventional medications such as beta-blockers, calcium channel blockers, and disopyramide. Mavacamten, a novel cardiac myosin inhibitor, may significantly change management. Other myosin inhibitors and modulators are also being developed and tested in large clinical trials. Given significant phenotypical variability in patients with HCM, clinical management can be challenging, and often requires an individualized approach with a combination of invasive and non-invasive options.

Traumatic Spinal Epidural Hematoma With Significant Neurologic Findings: A Case Report.

Traumatic spinal epidural hematoma (TSEH) is a rare neurosurgical emergency. Our case report centers around a young 34-year-old female brought into our emergency department after a front and rear motor vehicle collision. Clinical deterioration and imaging studies revealed a large spinal epidural hematoma extending from levels C5 to T2. The patient was subsequently transferred to a different hospital for further management. This case involved a multidisciplinary approach by the combined effort of emergency medicine physicians, neurosurgeons, orthopedic trauma surgeons, general surgeons, radiologists, intensive care specialists, anesthesiologists, paramedics and nurses.

Acute inferior ST-elevation myocardial infarction mimicked by direct lightning strike: a case report.

Background: Direct lightning strikes are rare, and multiple organ systems can be involved. Prognosis is dependent on the severity of the injury. Severe myocardial injury associated with transient electrocardiogram changes, which have been previously described, is a hazardous complication. Case summary: A 35-year-old man with no known past medical history presented unresponsive following a direct lightning strike while sitting in a portable toilet. High-quality cardiopulmonary resuscitation was started in the field, with return of spontaneous circulation (ROSC) after 1 h. Following ROSC, he received volume resuscitation and was maintained on multiple vasopressors. Electrocardiogram showed significant ST-elevations in inferior leads with elevated troponin I, consistent with inferior ST-elevation myocardial infarction. Labs revealed lactic acidosis, hyperkalaemia, acute kidney, and liver injury. Due to concern for plaque rupture, coronary angiography was performed and revealed no obstructive coronary artery disease. Vasopressor support and volume resuscitation were continued for extensive burns covering greater than 30% body surface area. The patient became progressively hypotensive, eventually precipitating pulseless electrical activity arrest. Emergent labs were notable for severe acidaemia. Despite aggressive interventions, he expired due to severe multi-organ failure. Discussion: Direct lightning injuries are rare with serious potential complications. Myocardial damage, either from direct electrical insult or from induced coronary vasospasm, can lead to multi-organ system failure.

Sleep-disordered breathing in children with Chiari malformation type II and myelomeningocele.

BACKGROUND: The prevalence of sleep-disordered breathing (SDB) in children with Chiari malformation type II (CM-II), a known association of neural tube defects (NTD), has not been well documented. The aim of the present study was to assess the prevalence and possible predictive factors of SDB in patients with CM-II. METHODS: The study included all patients with documented CM-II who were routinely referred from the Neurosurgery Clinic to the University Sleep Disorders Centre at King Khalid University Hospital, Riyadh, Saudi Arabia, between January 2002 and July 2009. Overnight full polysomnography (PSG) was performed in all patients. Polysomnographic data were analyzed using descriptive statistics. RESULTS: Sixteen children (11 boys, five girls) were included in the study; their mean age was 4.7 years (range, 0.8-10 years) and their mean body mass index was 18.05 kg/m(2) (range, 15.4-25.4 kg/m(2) ). For the whole group, the mean apnea-hypopnea index (AHI) was 6.3/h (range, 0.2-24.5/h), with AHI recorded as >5/h in five patients (31.3%) and ≥ 10/h in three patients (18.8%). The mean central apnea-hypopnea index was 5.9/h (range, 0-24.5/h) and the mean obstructive apnea-hypopnea index was 0.4/h (range, 0-2.9/h). The mean arousal index was 15.1/h (range, 5-34/h). CONCLUSION: The major assumption linking CM-II and NTD with potential brainstem compression and respiratory dysfunction during sleep was confirmed. Indeed, SDB is highly prevalent, and clearly underreported and undertreated in patients with CM-II associated with NTD.

A Case of Chest Jolts: Pulmonary Vein Thrombus Extending into the Left Atrium.

Pulmonary vein thrombosis (PVT) is a rare but life-threatening clinical condition, often found incidentally on imaging. In this report, we present an interesting case of PVT of the left inferior pulmonary vein with extension into the left atrium in a 78-year-old woman presenting with "jolts" in the chest. Initial imaging with plain chest film radiograph showed findings consistent with COPD and no acute intrathoracic process. A CT angiogram of the chest revealed a filling defect consistent with thrombus within the left inferior pulmonary vein extending into the left atrium. A transthoracic echocardiogram was remarkable for a severely enlarged right ventricular cavity with moderately reduced right ventricular systolic function and normal left ventricular size with preserved systolic function. She was not a candidate for any surgical interventions, and she was managed with systemic anticoagulation. Management of PVT mostly depends on the underlying cause as there are no well-defined treatment guidelines. The consensus recommends systemic anticoagulation until thrombus resolution. When anticoagulation is contraindicated, thrombectomy is indicated to restore blood flow. In patients with similar presentation and clinical history it is important to consider PVT, and to focus on prompt diagnosis and early initiation of appropriate treatment.

Unruptured bilateral supra-clinoid internal carotid artery aneurysms: A case report.

Unruptured supra-clinoid carotid aneurysms are rare aneurysmal dilatation of the supra-clinoid segment of internal carotid artery. Most cases are asymptomatic and discovered incidentally, while others may present with compressive symptoms on cranial nerve II, the optic nerve. We present a case of a 44-year-old female who presented with chronic headache and gradual decreased visual acuity. The patient's imaging workup revealed bilateral supra-clinoid carotid aneurysms.

Spontaneous splenic rupture from indeterminate dendritic cell proliferation: a case report.

Spontaneous splenic rupture is a rare and life-threatening phenomenon, usually associated with an underlying infectious, inflammatory, hematological, neoplastic or rheumatologic condition. Indeterminate cell tumor is a rare neoplastic dendritic cell disorder that is poorly understood but shares immunophenotypic markers for Langerhans cells without Birbeck granules. A 73-year-old man presented with upper abdominal pain after an unwitnessed fall. Computed tomography angiography showed splenomegaly and a large ruptured splenic subcapsular hematoma. Intraoperative findings from an emergency laparotomy revealed a large hemoperitoneum and a ruptured spleen. Microscopic sections identified numerous, mostly poorly formed, small nodules classified as a proliferation of indeterminate dendritic cell tumors.

Congenital lung malformation patients experience respiratory infections after resection: A population-based cohort study.

PURPOSE: The benefit of elective resection of congenital lung malformations continues to be debated. Proponents of resection endorse a decreased risk of respiratory complications as one indication for surgery. Our study aimed to compare the prevalence of respiratory infections in cases, before and after resection of congenital lung malformations, to controls without a history of congenital lung malformation. METHODS: We performed a retrospective cohort study of children born from 1991 to 2007 who underwent congenital lung malformation resection. Patients were identified from Winnipeg´s Surgical Database of Outcomes and Management (WiSDOM), and a 10:1 date-of-birth matched control group was generated from a population-based administrative data repository. International Classification of Disease codes were used to assess pulmonary infection outcomes. Relative rates (RR) were calculated to compare the frequency of pneumonia, respiratory infections and influenza between cases and controls. RESULTS: We included 31 congenital lung malformation cases and 310 controls. Cases consisted of 14 (45.16%) congenital pulmonary airway malformations, 9 (29.03%) bronchopulmonary sequestrations and 8 (25.81%) hybrid lesions. Before resection, pneumonia was more common in cases than controls (RR 6.85; 95%CI 3.89, 11.9), while the risk of acute respiratory infections (RR 1.21; 95%CI 0.79, 1.79) and influenza (RR 0.46; 95%CI 0.01, 3.22) were similar to controls. Post-resection, the risk of pneumonia (RR 9.75; 5.06, 18.50) was still higher in cases than controls, and respiratory infections (RR 1.77; 95%CI 1.20, 2.53) and influenza (RR 3.98; 95%CI 1.48, 9.36) were more common in cases than controls. CONCLUSION: Our study demonstrated that after resection of congenital lung malformations, children experience more frequent respiratory infections compared to the general population. Resection does not eliminate the increased risk of pneumonia.

Intrahepatic gallbladder mimicking a cystic liver lesion: A case report & literature review.

Intrahepatic gallbladder is a rare congenital variant that occurs due to migration arrest of the gallbladder from reaching its normal position. We present a case of a 60year-old gentleman presenting with chronic abdominal pain and impaired liver enzymes. Abdominal ultrasonography showed a hepatic cystic lesion which later was identified as an ectopic gallbladder within the liver parenchyma through magnetic resonance imaging study of the liver. Although ectopic gallbladder is a rare anomaly, awareness and correct identification of the abnormality prevents misdiagnosis with other liver pathologies as it may mimic other pathologies as presented in this case. It also allows better operative planning when indicated.

Respiratory outcomes in the first 10 years of life in children with gastroschisis: A retrospective cohort study.

BACKGROUND: Little attention has been given to the long-term respiratory outcomes of children with gastroschisis. The purpose of this study was to determine if gastroschisis survivors have more respiratory illnesses in their first 10 years of life compared with age-matched controls. METHODS: We performed a retrospective cohort study of all gastroschisis children born in Manitoba between 1991 and 2017. Gastroschisis cases were identified from a clinical database, and a date of birth-matched control cohort was constructed from a population-based data repository. International Classification of Disease codes were used to compare the risk and frequency of respiratory diagnoses for children with gastroschisis to date of birth-matched controls from 0-5 years of age and 5-10 years of age. RESULTS: The 0-5 years of age analysis included 117 gastroschisis cases and 1205 date of birth-matched controls; children with gastroschisis had a higher risk of asthma (relative risk [RR] = 1.46; 95% confidence interval [CI]: 1.03, 2.55; p = .029), acute bronchitis/bronchiolitis (RR = 1.61; 95% CI: 1.27, 2.03; p < .001), pneumonia (RR = 1.99; 95% CI: 1.45, 2.72; p < .001), viral pneumonia (RR = 5.15; 95% CI: 1.79, 14.81; p = .007), and pneumonia due to unspecified organism (RR = 2.06; 95% CI: 1.45, 2.92; p < .001). Gastroschisis children 0-5 years of age were also diagnosed more frequently with bronchitis/bronchiolitis (RR = 2.14; 95% CI: 1.79, 2.57; p < .001) and viral pneumonia (RR = 8.10; 95% CI: 3.79, 17.31; p < .001). The 5-10 years of age analysis included 73 cases and 738 controls; no difference in the risk of respiratory illness was found for gastroschisis cases and controls in this age group. However, gastroschisis cases were more frequently diagnosed with bacterial pneumonia (RR = 3.03; 95% CI: 1.67, 5.51; p < .001) and influenza (RR = 3.03; 95% CI: 1.67, 5.51; p < .001). CONCLUSION: Our study shows that children with gastroschisis have an increased risk of asthma and respiratory infections compared with children without gastroschisis, most noticeably in the first 5 years of life.

Outcomes of Cystic Fibrosis Screening-Positive Infants With Inconclusive Diagnosis at School Age.

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children. METHODS: Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes. RESULTS: The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls. CONCLUSIONS: Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.