Evaluating the impact of accessible low-cost pediatric genetic testing on underserved communities in the United States.

BACKGROUND: Genetic testing is at the forefront of medical diagnosis, management, and preventative care particularly within the field of nephrology, but such testing can be prohibitively expensive for patients from disadvantaged backgrounds. This study is aimed at exploring how use of a low-cost, comprehensive commercial panel could increase availability of genetic testing to patients served by an inner-city American hospital and overcome many of the obstacles faced by these patients, including lack of availability of pediatric geneticist and genetic counselors, leading to delay in care and management, cost of genetic testing, and inaccessibility of genetic testing to underserved populations. METHODS: Single-center retrospective analysis patients who underwent genetic testing with NATERA Renasight Kidney Gene Panels run between November 2020 and October 2021. RESULTS: Genetic testing was offered to 208 patients, with 193 tests performed, 10 pending, and 4 deferred. Seventy-six patients were found to have results of clinical significance; 117 patients were found to have a negative result, of which 79 were found to have a variant of unknown significance (VUS); and 8 of these 79 VUS were later determined to be clinically significant leading to a change in management. Patient payment data breakdown showed that of 173, 68% used public insurance coverage, 27% used commercial or private insurance, and 5% were unknown. CONCLUSIONS: Genetic testing with the NATERA Renasight Panel provided a high positivity rate for genetic testing using next generation sequencing. It also allowed us to provide access to genetic testing to a larger population, specifically underserved and underrepresented patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats.

The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min(-1)·100 g body wt(-1) in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min(-1)·100 g body wt(-1), which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min(-1)·100 g body wt(-1)). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

Prenatal programming of rat cortical collecting tubule sodium transport.

Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 µmol/24 h) compared with the 20% group (279.1 ± 137.0 µmol/24 h), consistent with greater ENaC activity in vivo (P < 0.05). In this study, we also directly studied cortical collecting tubule function from adult rats using in vitro microperfusion. There was no difference in basal or vasopressin-stimulated osmotic water permeability. However, while cortical collecting ducts of adult offspring whose mothers ate a 20% protein diet had no sodium transport (-1.9 ± 3.1 pmol·mm(-1)·min(-1)), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm(-1)·min(-1) (P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.

Epileptic seizures in the pediatric intensive care unit setting.

PURPOSE: The clinical features of seizures occurring in the pediatric intensive care unit (PICU) setting are not well characterized. Adult ICU studies reveal an incidence of seizures ranging from 0.8% to 3.3%, with vascular, metabolic abnormalities, and drug withdrawal being the most common etiologies. The objective of this study is to investigate the clinical characteristics of seizures in children admitted to the PICU at our institution. METHODS: We performed a retrospective review of all patients with diagnoses of seizures or epilepsy, admitted to our PICU from 2002 to 2004. Of 6,820 admissions, 32 patients, aged one month to 19 years had seizures in the PICU. RESULTS: The incidence of seizures was 0.5%. Developmental delay or mental retardation was present in 37% of patients. Seizures were generalized in 26 (81%), and focal in 6 (19%); 34% had status epilepticus. The etiology of seizures was epilepsy in 11 (34%). Seizures that do not meet the diagnosis of epilepsy were diagnosed in 21 (66%) including post-craniotomy in five (23%), febrile seizures in three (14%), encephalitis in three (14%), and hydrocephalus in three (14%). Thirty-one patients (97%) were initially treated with either lorazepam or fosphenytoin. CONCLUSIONS: Seizures in PICU have different clinical characteristics from those in adults. Recognizing the common seizure etiologies in PICU is likely to lead to a more prompt and effective treatment. Antiepileptic drug prophylaxis may be useful in post-craniotomy patients. A neurological consultation and EEG evaluation are of the utmost importance to help rule in or out epileptic disorders in the PICU.

Enalapril attenuates the exaggerated sympathetic response to physical stress in prenatally programmed hypertensive rats.

Adulthood hypertension can be prenatally programmed by maternal dietary protein deprivation. We have shown that the sympathetically mediated pressor response to physical stress is exaggerated in prenatally programmed hypertensive (PPH) rats. The mechanisms underlying this abnormal responsiveness remain undetermined. The renin-angiotensin system is known to affect sympathetic nerve activity. Therefore, the purpose of this study was to determine whether inhibition of the renin-angiotensin system attenuates the enhanced sympathetic and pressor responses to physical stress in PPH rats. Changes in renal sympathetic nerve activity and blood pressure in response to hindlimb contraction, hindlimb stretch, and hindlimb intra-arterial capsaicin administration were assessed in control and PPH rats treated (from age 3 weeks) with either vehicle or the angiotensin-converting enzyme inhibitor enalapril. Conscious resting systolic arterial pressure was significantly greater in PPH rats (142±5 mm Hg) than in control (128±2 mm Hg) after vehicle treatment (P<0.05). Resting systolic pressure was reduced by enalapril treatment in PPH rats (125±2 mm Hg) but had no effect in control (128±2 mm Hg). The pressor and renal sympathetic responses to muscle contraction and stretch were significantly higher in decerebrate PPH rats than in decerebrate control in vehicle-treated groups. Responses to capsaicin were variable. Enalapril significantly attenuated the enhanced contraction-induced elevations in mean pressure (vehicle, 45±6 mm Hg; enalapril, 21±3 mm Hg) and renal sympathetic activity (vehicle, 175±22%; enalapril, 89±23%) in PPH rats. Its effects were similar on responses to stretch in PPH rats but were equivocal during capsaicin administration. The results suggest that the renin-angiotensin system contributes to the enhancement of the renal sympathetic and pressor responses to physical stress in PPH rats.

Cáncer del ano: tratamento quirúrgico / Anal neoplasm: surgical treatment

Se presentan 21 pacientes portadores de cáncer del canal anal, se analizan métodos diagnósticos y conducta quirúrgica