scholarly journals Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort

2021 ◽  
Author(s):  
Marloes A. H. M. Michels ◽  
Kioa L. Wijnsma ◽  
Roel A. J. Kurvers ◽  
Dineke Westra ◽  
Michiel F. Schreuder ◽  
...  
Keyword(s):  
Mixed Model ◽  
Linear Mixed Model ◽  
Immunosuppressive Treatment ◽  
Complement C3 ◽  
C3 Glomerulopathy ◽  
Laboratory Findings ◽  
Mixed Model Analysis ◽  
Long Term Follow Up

Abstract Background C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G. Methods Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood. Results DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m2 at last follow-up. Conclusions We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics. Graphical abstract

Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

2019 ◽  
Vol 24 (2) ◽  
pp. 200-208
Author(s):  
Ravindra Arya ◽  
Francesco T. Mangano ◽  
Paul S. Horn ◽  
Sabrina K. Kaul ◽  
Serena K. Kaul ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Hippocampal Sclerosis ◽  
Brain Mri ◽  
Temporal Lobectomy ◽  
Seizure Freedom ◽  
Seizure Onset

OBJECTIVEThere is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.METHODSChildren who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.RESULTSOne hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.CONCLUSIONSA lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

scholarly journals Improved cephalic index following early cranial vault remodeling in patients with isolated nonsyndromic sagittal synostosis

2021 ◽  
Vol 50 (4) ◽  
pp. E7
Author(s):  
Arvid Frostell ◽  
Maryam Haghighi ◽  
Jiri Bartek ◽  
Ulrika Sandvik ◽  
Bengt Gustavsson ◽  
...  
Keyword(s):  
Mixed Model ◽  
Linear Mixed Model ◽  
Cranial Vault ◽  
Hospital Length Of Stay ◽  
Cephalic Index ◽  
Sagittal Synostosis ◽  
The Mean ◽  
Cranial Vault Remodeling

OBJECTIVE Isolated nonsyndromic sagittal synostosis (SS) is the most common form of craniosynostosis in children, accounting for approximately 60% of all craniosynostoses. The typical cranial measurement used to define and follow SS is the cephalic index (CI). Several surgical techniques have been suggested, but agreement on type and timing of surgery is lacking. This study aimed to evaluate the authors’ institutional experience of surgically treating SS using a modified subtotal cranial vault remodeling technique in a population-based cohort. Special attention was directed toward the effect of patient age at time of surgery on long-term CI outcome. METHODS A retrospective analysis was conducted on all patients with isolated nonsyndromic SS who were surgically treated from 2003 to 2011. Data from electronic medical records were gathered. Eighty-two patients with SS were identified, 77 fulfilled inclusion criteria, and 72 had sufficient follow-up data and were included. CI during follow-up after surgery was investigated with ANOVA and a linear mixed model. RESULTS In total, 72 patients were analyzed, consisting of 16 females (22%) and 56 males (78%). The mean ± SD age at surgery was 4.1 ± 3.1 months. Blood transfusions were received by 81% of patients (26% intraoperatively, 64% postoperatively, 9% both). The mean ± SD time in the pediatric ICU was 1.1 ± 0.25 days, and the mean ± SD total hospital length of stay was 4.6 ± 2.0 days. No patient required reoperation. The mean ± SD CI increased from 69 ± 3 to 87 ± 5 for patients who underwent surgery before 45 days of age. Surgery resulted in a larger increase in CI for patients who underwent surgery at a younger age compared with older patients (p < 0.05, Tukey’s HSD test). In the comparison of patients who underwent surgery before 45 days of age with patients who underwent surgery at 45–90, 90–180, and more than 180 days of age, the linear mixed model estimated a long-term loss of CI of 3.0, 5.5, and 7.4 points, respectively. CONCLUSIONS The modified subtotal cranial vault remodeling technique used in this study significantly improved CI in patients with SS. The best results were achieved when surgery was performed early in life.

scholarly journals Tissue is the issue: when a second biopsy reveals the true diagnosis

2019 ◽  
Author(s):  
Anne-Marie Bogaert ◽  
Anne Hoorens ◽  
Marleen Praet ◽  
Jo Van Dorpe ◽  
Bruce Poppe ◽  
...  
Keyword(s):  
Kidney Biopsy ◽  
Late Onset ◽  
Immunosuppressive Treatment ◽  
Treatment Strategies ◽  
Nephrotic Proteinuria ◽  
Long Term Follow Up ◽  
Generation Sequencing ◽  
Genetic Form

Abstract We describe the case of a woman with minimal glomerular changes on initial kidney biopsy. On long-term follow-up, the patient developed nephrotic proteinuria and a second kidney biopsy was performed, which revealed focal segmental glomerulosclerosis (FSGS). Findings from electron microscopy (EM) examination suggested a genetic form of FSGS. Next-generation sequencing showed heterozygosity for a mutation in COL4A3. Collagen IV nephropathies can be linked to late-onset FSGS. By establishing a genetic cause of FSGS, immunosuppressive treatment can be avoided. This case emphasizes the importance of re-biopsy in cases of a non-explained rise in proteinuria. EM can be helpful in differentiating between primary and secondary FSGS and informing treatment strategies. In cases of adult-onset FSGS that cannot be categorized by clinical–pathological assessment, genetic testing should be considered.

Arterial stiffness to predict hypertensive response to antiangiogenic drugs.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13589-e13589
Author(s):  
Julie Giroux ◽  
Maureen Alivon ◽  
Marie Briet ◽  
Pascaline Boudou-Rouquette ◽  
Stanislas Ropert ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Common Side Effect ◽  
Large Artery ◽  
Mixed Model Analysis ◽  
Large Arteries ◽  
Antiangiogenic Drugs ◽  
Carotid Distensibility

e13589 Background: Targeting angiogenesis with anti-VEGF receptors is a new approach for cancer treatment. The most common side effect is arterial hypertension. We hypothesize that pre-existing large artery remodeling with increased arterial stiffness is a determinant of blood pressure (BP) increase under antiangiogenic (AAD) and that AAD may alter mechanical properties of large arteries independently of BP increase. Methods: 49 patients (mean age=57[15] years, mean bSBP=128[22] mmHg and mean DBP=75[11] mmHg; treated for a cancer with an indication to start AAD (Sorafenib, Sunitinib or Bevacizumab) were included in this longitudinal study. Arterial evaluation was assessed at baseline (BL) before the introduction of AAD and every two weeks for 2 months (V1 to V4) with aortic stiffness (PWV) and central BP measurements by aplanation tonometry (SphygmoCor), carotid distensibility with high resolution echotracking system (ArtLab). Results: 43% of the patients developed hypertension between BL and V1. Using linear mixed model analysis with random effects, PWV significantly increased between BL and V1 (BL-V1, adjusted slope 0.89 m/s, F value=6.8, p=0.04) after adjustment to age and mean BP, carotid distensibility decreased significantly during follow-up (BL-V1, adjusted slope= -4.4, p=0.04; BL-V2, adjusted slope= -5.23, p=0.001) after adjustment to age and mean BP. The determinants of BP increase were studied between BL and V1 since anti-hypertensive drugs were introduced after V1. Using multivariate analysis, BL PWV was an independent determinant of the delta brachial SBP (β= -1.36 [-2.61; 0.11], p=0.034) with age (β=0.25 [0.04; 0.47], p=0.02). Conclusions: AAD induce functional alterations of large arteries, increasing arterial stiffness, independently of BP increase. In addition, pre-AAD administration arterial properties influence the hypertensive response to AAD.

Clinical findings and effect of sodium hydrogen carbonate in patients with glutathione synthetase deficiency

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Mehmet Gündüz ◽  
Özlem Ünal ◽  
Sumru Kavurt ◽  
Emrecan Türk ◽  
Neslihan Önenli Mungan
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Hydrogen Carbonate ◽  
Enzyme Analysis ◽  
Glutathione Synthetase ◽  
Laboratory Findings ◽  
Sodium Hydrogen ◽  
Hydrogen Carbonate ◽  
Long Term Follow Up

AbstractGlutathione synthetase (GS) deficiency is a rare inborn error of glutathione (GSH) metabolism manifested by severe metabolic acidosis, hemolytic anemia, neurological problems and massive excretion of pyroglutamic acid (5-oxoproline) in the urine. The disorder has mild, moderate, and severe clinical variants. We aimed to report clinical and laboratory findings of four patients, effect of sodium hydrogen carbonate treatment and long-term follow up of three patients.Urine organic acid analysis was performed with gas chromatography-mass spectrometry. Molecular genetic analysis was performed in three patients, mutation was found in two of them. Enzyme analysis was performed in one patient. Clinical and laboratory findings of four patients were evaluated.One patient died at 4 months old, one patient’s growth and development are normal, two patients have developed intellectual disability and seizures in the long term follow up period. Three patients benefited from sodium hydrogen carbonate treatment.The clinical picture varies from patient to patient, so it is difficult to predict the prognosis and the effectiveness of treatment protocols. We reported long term follow up of four patients and demonstrated that sodium hydrogen carbonate is effective for treatment of chronic metabolic acidosis in GS deficieny.

Temporalis muscle thickness as an indicator of sarcopenia is associated with long-term motor outcomes in Parkinson’s disease

2021 ◽  
Author(s):  
Seok Jong Chung ◽  
Yun Joong Kim ◽  
Han Soo Yoo ◽  
Jin Ho Jung ◽  
KyoungWon Baik ◽  
...  
Keyword(s):  
Regression Models ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Cox Regression ◽  
Muscle Thickness ◽  
Temporalis Muscle ◽  
Wearing Off ◽  
Motor Outcomes

Abstract Background To investigate the relationship between temporalis muscle thickness (TMT) at baseline as a surrogate marker for sarcopenia and long-term motor outcomes in patients with Parkinson’s disease (PD). Methods We enrolled 249 patients with drug-naïve early-stage PD (119 males and 130 females, follow-up &gt; 3 years). Baseline TMT of each patient was measured on the axial plane of T1-weighted images. The association between baseline TMT and long-term motor outcomes in PD was assessed using Cox regression models for levodopa-induced dyskinesia (LID), wearing-off, and freezing of gait (FOG) and a linear mixed model for the longitudinal increases in levodopa-equivalent dose (LED) per body weight over time. Statistical analyses were performed separately for sex if an interaction effect between TMT and sex was assumed. Results TMT differed substantially between the sexes, and male PD patients had higher TMT (6.69 ± 1.39 mm) than female PD patients (5.64 ± 1.34 mm, p &lt; 0.001). Cox regression models demonstrated that baseline TMT was not associated with the risk of developing LID, wearing-off, or FOG during the follow-up period. The linear mixed model was applied separately for sex and demonstrated that higher TMT at baseline was associated with slower increases in LED per body weight in male PD patients, but not in female PD patients. Conclusions This study demonstrated that baseline TMT could be an indicator of the longitudinal requirement for dopaminergic medications in male patients with PD, suggesting that sarcopenia may have a detrimental effect on disease progression in PD in a sex-specific manner.

scholarly journals Weight Development Between Age 5 And 10 Years And Its Associations With Dietary Patterns At Age 5 In The Abcd Cohort 

2020 ◽  
Author(s):  
Viyan Rashid ◽  
Martinette T Streppel ◽  
Marielle F. Engberink ◽  
Peter J.M. Weijs ◽  
Mary Nicolaou ◽  
...  
Keyword(s):  
Dietary Patterns ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Social Inequalities ◽  
Important Determinant ◽  
Normal Weight ◽  
Mixed Model Analysis ◽  
Valid Data ◽  
Unexpected Findings

Abstract Background: Social inequalities in bodyweight start early in life and track into adulthood. Dietary patterns are an important determinant of weight development in children, towards both overweight and underweight. T herefore, w e aimed to examine weight development between age 5 and 10 years by ethnicity, SES and thereafter by BMI category at age 5, to explore its association with dietary patterns at age 5. Methods: Participants were 1 765 children from the Amsterdam Born Children and their Development (ABCD) cohort that had valid data on BMI at age 5 and 10 and diet at age 5. Linear mixed model analysis was used to examine weight development between age 5 and 10 years and to assess if four previously identified dietary patterns at age 5 (snacking, full-fat, meat and healthy) were associated with weight development. Analyses were adjusted for relevant confounders, stratified by ethnicity and SES and thereafter stratified per BMI category at age 5. Results: Overall, weight decreased in Dutch and high SES children and increased in non-Dutch and low/middle SES children. Across the range of bodyweight categories at age 5, we observed a conversion to normal weight, which was stronger in Dutch and high SES children but less pronounced in non-Dutch and low/middle SES children. Overall, the observed associations between weight development and dietary patterns were mixed with some unexpected findings: a healthy dietary pattern was positively associated with weight development in most groups, regardless of ethnicity and SES (e.g. Dutch B 0.084, 95% CI 0.038;0.130 and high SES B 0.096, 95% CI 0.047;0.143) whereas the full-fat pattern was negatively associated with weight development (e.g. Dutch B -0.069, 95% CI -0.114;-0.024 and high SES B -0.072, 95% CI -0.119;-0.026). Conclusions: We observed differential weight development per ethnic and SES group. Our results indicate that each ethnic and SES group follows its own path of weight development. Associations between dietary patterns and weight development showed some unexpected findings; follow-up research is needed to understand the association between dietary patterns and weight development. Keywords: BMI, body mass index, thinness, normal weight, overweight, obesity, socio-economic position, ethnicity, children, young children.

Long term follow-up and effect of immunosuppression in acute zonal occult outer retinopathy

2020 ◽  
pp. 112067212098187
Author(s):  
Andrea Guijarro ◽  
Nelida Muñoz ◽  
Nicolas Alejandre ◽  
Sheila Recuero ◽  
Olga Sanchez-Pernaute ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Visual Field ◽  
Young Women ◽  
Immunosuppressive Treatment ◽  
Intravenous Immunoglobulins ◽  
Sudden Onset ◽  
Electrophysiological Tests ◽  
Long Term Follow Up

Acute zonal occult outer retinopathy (AZOOR) is a rare syndrome characterized by sudden onset of photopsia, scotomas, and abnormal electrophysiological tests, predominantly affecting young women. Although its pathogenesis remains unknown, auto-reactivity to retinal components is thought to mediate tissue damage. A 42-year-old woman presented with symptoms and examination consistent with the diagnosis of AZOOR. She was treated with azathioprine for 5 years. In spite of the immunosuppressive treatment, clear progression in the visual field, autofluorescence, electrophysiological tests and optical coherence tomography was observed. Treatment with intravenous immunoglobulins (IVIg) and subcutaneous Abatacept was subsequently started with little efficacy. Hereby, we present a case of progressive AZOOR despite aggressive immunosuppression with 10-year follow up. Currently, there is no consensus regarding management of AZOOR, and the convenience of administering aggressive immunosuppression remains uncertain.

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