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Cardiology in the Young Oct 2015Recent efforts have focused on optimising interstage outcomes, including growth, for infants following the Norwood operation. The impact of the site of interstage care...
BACKGROUND
Recent efforts have focused on optimising interstage outcomes, including growth, for infants following the Norwood operation. The impact of the site of interstage care remains unclear, and it has been hypothesised that care at the surgical site may be beneficial due to greater access to resources such as nutritional support. This study evaluated the relationship between site of interstage care and weight gain in a large multicentre cohort.
METHODS
Infants enrolled in the National Paediatric Cardiology Quality Improvement Collaborative (2008-2013) surviving up to Stage 2 were included. Change in weight-for-age z-score between Norwood discharge and Stage 2 admission was compared in those receiving care at the surgical versus non-surgical site.
RESULTS
Of the 487 interstage survivors, 60% received all care at the surgical site, and 40% received care at a non-surgical site. There was no significant difference between groups in change in weight-for-age z-score: +0.36±0.96 for the surgical site group versus +0.46±1.02 for the non-surgical site group, p=0.3. Results were unchanged in multivariable analysis adjusting for differences in important baseline characteristics, duration of interstage, and home surveillance strategy. The proportion of all patients with weight-for-age z-score <-2 decreased from 40% at Norwood discharge to 29% at Stage 2, with no significant difference in change between the two groups (p=0.1).
CONCLUSIONS
The site of interstage care was not associated with weight gain during the interstage period. Nearly one-third of patients overall had a weight-for-age z-score <-2 at Stage 2. Further study is required to identify methods to optimise weight gain in these patients.
Topics: Ambulatory Care; Female; Heart Ventricles; Humans; Hypoplastic Left Heart Syndrome; Infant; Infant, Newborn; Linear Models; Male; Multivariate Analysis; Norwood Procedures; Nutritional Support; Patient Discharge; Quality Improvement; Retrospective Studies; Weight Gain
PubMed: 25554859
DOI: 10.1017/S1047951114002480 -
HIV Medicine Feb 2013The objective of the study was to conduct a within-cohort assessment of risk factors for incident AIDS-defining cancers (ADCs) and non-ADCs (NADCs) within the Australian...
OBJECTIVES
The objective of the study was to conduct a within-cohort assessment of risk factors for incident AIDS-defining cancers (ADCs) and non-ADCs (NADCs) within the Australian HIV Observational Database (AHOD).
METHODS
A total of 2181 AHOD registrants were linked to the National AIDS Registry/National HIV Database (NAR/NHD) and the Australian Cancer Registry to identify those with a notified cancer diagnosis. Included in the current analyses were cancers diagnosed after HIV infection. Risk factors for cancers were also assessed using logistic regression methods.
RESULTS
One hundred and thirty-nine cancer cases were diagnosed after HIV infection among 129 patients. More than half the diagnoses (n = 68; 60%) were ADCs, of which 69% were Kaposi's sarcoma and 31% non-Hodgkin's lymphoma. Among the NADCs, the most common cancers were melanoma (n = 10), lung cancer (n = 6), Hodgkin's lymphoma (n = 5) and anal cancer (n = 5). Over a total of 21021 person-years (PY) of follow-up since HIV diagnosis, the overall crude cancer incidence rate for any cancer was 5.09/1000 PY. The overall rate of cancers decreased from 15.9/1000 PY [95% confidence interval (CI) 9.25-25.40/1000 PY] for CD4 counts < 100 cells/μL to 2.4/1000 PY (95% CI 1.62-3.39/1000 PY) for CD4 counts > 350 cells/μL. Lower CD4 cell count and prior AIDS diagnoses were significant predictors for both ADCs and NADCs.
CONCLUSIONS
ADCs remain the predominant cancers in this population, although NADC rates have increased in the more recent time period. Immune deficiency is a risk factor for both ADCs and NADCs.
Topics: Acquired Immunodeficiency Syndrome; Adult; Aging; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Anus Neoplasms; Australia; CD4 Lymphocyte Count; Databases, Factual; Female; Follow-Up Studies; Hodgkin Disease; Humans; Logistic Models; Lung Neoplasms; Lymphoma, AIDS-Related; Male; Melanoma; Middle Aged; Prospective Studies; Risk Factors
PubMed: 22934689
DOI: 10.1111/j.1468-1293.2012.01038.x -
Radiology Case Reports Jul 2021The extent, severity, and radiological findings of ovarian growth in infants with genetic syndromes of insulin resistance have not been fully described. We report a rare...
The extent, severity, and radiological findings of ovarian growth in infants with genetic syndromes of insulin resistance have not been fully described. We report a rare case of reversible massive ovarian enlargement in a female infant with a congenital insulin resistance syndrome, likely Rabson-Mendenhall syndrome given the less clinically severe course. The patient presented with neonatal diabetes with hyperinsulinemia and hyperglycemia due to congenital insulin resistance. She developed increasing severe bilateral ovarian enlargement which peaked at 4 months of age, followed by gradual decrease in size of the ovaries following treatment with insulin-sensitizing drugs and improved hyperinsulinemia. The ovarian enlargement is postulated to be secondary to the trophic effects of insulin acting in a gonadotropin-independent mechanism. Hyperinsulinemia in congenital insulin resistance can also result in hypertrophy of other organs. Understanding the pathophysiology behind massive ovarian enlargement in the setting of congenital insulin resistance syndromes can help guide appropriate therapy.
PubMed: 34007398
DOI: 10.1016/j.radcr.2021.03.067 -
Biology of Blood and Marrow... Jul 2005Engraftment syndrome (ES) encompasses a constellation of symptoms that occur during neutrophil recovery after both autologous and allogeneic hematopoietic stem cell... (Clinical Trial)
Clinical Trial
Engraftment syndrome (ES) encompasses a constellation of symptoms that occur during neutrophil recovery after both autologous and allogeneic hematopoietic stem cell transplantation (HCT). Although it is well characterized after conventional myeloablative procedures, limited data exist on this complication after nonmyeloablative allogeneic HCT. The clinical manifestations, incidence, and risk factors associated with ES were investigated in a consecutive series of patients undergoing cyclophosphamide/fludarabine-based nonmyeloablative allogeneic HCT from a related HLA-compatible donor. Fifteen (10%) of 149 patients (median age, 53 years; range, 27-66 years) developed ES; the onset of symptoms occurred at a median of 10 days (range, 3-14 days), and they consisted of fever (100%), cough (53%), diffuse pulmonary infiltrates (100%), rash (13%), and room air hypoxia (87%). ES was more likely to develop in patients who received empiric amphotericin formulations after transplant conditioning (Fisher exact test; P=.007). In a multivariate analysis, older patient age, female sex, and treatment with amphotericin were predictors for the development of ES. Intravenous methylprednisolone led to the rapid resolution of ES; however, transplant-related mortality was significantly higher (cumulative incidence, 49% versus 16%; P=.0005), and median survival was significantly shorter (168 versus 418 days; P=.005) in patients with ES compared with non-ES patients. In conclusion, ES occurs commonly after cyclophosphamide/fludarabine-based nonmyeloablative transplantation and responds rapidly to corticosteroid treatment, but it is associated with a higher risk of nonrelapse mortality and with shorter overall survival.
Topics: Adult; Age Factors; Aged; Cyclophosphamide; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Myelopoiesis; Neoplasms; Neutrophils; Risk Factors; Sex Factors; Syndrome; Transplantation Conditioning; Vidarabine
PubMed: 15983554
DOI: 10.1016/j.bbmt.2005.04.009 -
The Journal of Clinical Endocrinology... Apr 2011In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway.
OBJECTIVE
This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women.
DESIGN
We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women.
SETTING
The study was conducted in a General Clinical Research Center in an academic medical center.
PARTICIPANTS
Women with PCOS (age, 18-37 yr; n = 10) and normal ovulatory controls (age, 18-37 yr; n = 11) were recruited.
INTERVENTIONS
For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 μg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 μg of recombinant hCG.
MAIN OUTCOME MEASURE(S)
We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration.
RESULTS
In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women.
CONCLUSION
In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.
Topics: Adolescent; Adult; Body Mass Index; Chorionic Gonadotropin; Dehydroepiandrosterone; Dose-Response Relationship, Drug; Estradiol; Female; Humans; Hyperandrogenism; Injections, Intravenous; Oligomenorrhea; Polycystic Ovary Syndrome; Recombinant Proteins; Steroids; Up-Regulation; Young Adult
PubMed: 21270326
DOI: 10.1210/jc.2010-2200 -
CPT: Pharmacometrics & Systems... Jun 2024Zavegepant is a novel gepant administered as a nasal spray approved in the United States at a 10 mg dose for the acute treatment of migraine with or without aura in... (Randomized Controlled Trial)
Randomized Controlled Trial
Zavegepant is a novel gepant administered as a nasal spray approved in the United States at a 10 mg dose for the acute treatment of migraine with or without aura in adults. The cardiovascular safety of zavegepant nasal spray was assessed in both single-ascending dose (SAD) and multiple-ascending dose (MAD) studies in healthy participants. The SAD study included 72 participants (54 active/18 placebo) who received 0.1-40 mg zavegepant or placebo. The MAD study included 72 participants (56 active/16 placebo) who received 5-40 mg zavegepant or placebo for 1-14 days. Plasma zavegepant pharmacokinetics and electrocardiographic (ECG) parameters (Fridericia-corrected QT interval [QTcF], heart rate, PR interval, ventricular depolarization [QRS], T-wave morphology, and U-wave presence) were analyzed pre- and post-zavegepant administration. Using pooled data from the SAD and MAD studies, the relationship between time-matched plasma zavegepant concentrations and QTc interval was assessed using a linear mixed-effects model to evaluate the potential for QTc interval prolongation. Results showed that single and multiple doses of zavegepant had no significant impact on ECG parameters versus placebo, and there was no concentration-dependent effect on QTcF interval. The estimated slope of the plasma zavegepant concentration-QTcF model was -0.053 ms per ng/mL with a 90% confidence interval of -0.0955 to -0.0110 (p = 0.0415), which is not considered clinically meaningful. At doses up to four times the recommended daily dose, zavegepant does not prolong the QT interval to any clinically relevant extent.
Topics: Humans; Male; Electrocardiography; Adult; Female; Healthy Volunteers; Nasal Sprays; Heart Rate; Double-Blind Method; Young Adult; Dose-Response Relationship, Drug; Middle Aged; Azepines; Administration, Intranasal; Long QT Syndrome; Adolescent
PubMed: 38812357
DOI: 10.1002/psp4.13140 -
Journal of Clinical Research in... Jun 2018Mutations in the insulin receptor () gene are responsible for Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). Insulin resistance is a feature of both...
Mutations in the insulin receptor () gene are responsible for Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). Insulin resistance is a feature of both diseases. Our patient was a Chinese neonate suffering from abnormal glucose homeostasis, hyperinsulinemia, dry skin, heavy hair, growth retardation and an elevated testosterone level. To search for candidate point mutations, small insertions or deletions and copy number variants, 2742 inherited disease-gene panel sequencing was performed. One pathogenic mutation (c.3355C>T, p.Arg1119Trp) and a novel 2.43Kb deletion (chr19:7150507-7152938) in were found. The patient was diagnosed as RMS. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) confirmed the missense variant and microdeletion, respectively. We therefore supposed that these variants were candidate mutations in this case. We report a novel 2.43Kb deletion in gene and provide further proof of the power of next generation sequencing in rare disease diagnosis.
Topics: Antigens, CD; China; Donohue Syndrome; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Mutation; Receptor, Insulin
PubMed: 29082893
DOI: 10.4274/jcrpe.5080 -
Experimental and Clinical... Oct 2020Wiskott-Aldrich syndrome is a rare primary immuno-deficiency disorder that is characterized by a triad of microthrombocytopenia, eczema, and recurrent infections....
Wiskott-Aldrich syndrome is a rare primary immuno-deficiency disorder that is characterized by a triad of microthrombocytopenia, eczema, and recurrent infections. Progression to end-stage renal failure is common in survivors due to immunoglobulin A nephropathy. We describe the case of a 24-year-old male with Wiskott-Aldrich syndrome. The patient had previous hematopoietic stem cell transplant and was on hemodialysis due to end-stage renal failure. He subsequently underwent living-donor renal transplant from his mother as the donor. This is only the fifth case of renal transplant in a patient with Wiskott-Aldrich syndrome in the world. In all cases, the perioperative management of hemostatic function has been crucial. We used thromboelastography to guide our hemostatic decisions rather than platelet count, thus reducing exposure to unnecessary platelet transfusions and without increased bleeding risk. Our patient had an uneventful course after living-donor kidney transplant.
Topics: Clinical Decision-Making; Glomerulonephritis, IGA; Humans; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Platelet Transfusion; Point-of-Care Testing; Predictive Value of Tests; Risk Factors; Thrombelastography; Treatment Outcome; Wiskott-Aldrich Syndrome; Young Adult
PubMed: 32281533
DOI: 10.6002/ect.2019.0347 -
Clinical Pediatric Endocrinology : Case... Apr 2013Leprechaunism is a rare autosomal recessive disease that is characterized by severe insulin resistance. This disease is caused by a defective insulin receptor and...
Leprechaunism is a rare autosomal recessive disease that is characterized by severe insulin resistance. This disease is caused by a defective insulin receptor and features abnormal glucose metabolism and retarded intrauterine and postnatal growth. However, there are few reports on the long-term course of leprechaunism. We reported the long-term clinical course and rh-IGF-1 treatment in a patient with leprechaunism. During follow-up her diabetes gradually deteriorated despite of treatment of rh-IGF-1. Furthermore, she developed endometrioid adenocarcinoma at the age of 24 yr. The development of endometrial disease must be carefully followed up in this disease.
PubMed: 23990696
DOI: 10.1292/cpe.22.33 -
International Journal of Molecular... Mar 2024Rabson-Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report...
Rabson-Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report the first case of RMS in a Paraguayan patient. The patient is a 6-year-old girl who presented with hypertrichosis, acanthosis nigricans, nephrocalcinosis, and elevated levels of glucose and insulin that served as diagnostic indicators for RMS. Genetic testing by next-generation sequencing (NGS) revealed two pathogenic variants in exons 2 and 19 of the gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software programs predicted it as pathogenic. The c.3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and RMS. The management of RMS is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of RMS to the Paraguayan population and adds a novel pathogenic variant to the existing literature.
Topics: Child; Female; Humans; Donohue Syndrome; Insulin Resistance; Receptor, Insulin; Mutation; Valine; Antigens, CD
PubMed: 38542117
DOI: 10.3390/ijms25063143