Publications by authors named "Christina Lam"

85 Publications

Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.

Ann Neurol 2021 Oct 15. Epub 2021 Oct 15.

Department of Clinical Genomics, Mayo Clinic, Rochester, MN.

Objective: Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG.

Methods: We performed PMM enzyme measurements, multiplexed proteomics, and glycoproteomics in PMM2-deficient fibroblasts before and after epalrestat treatment. Safety and efficacy of 0.8 mg/kg/day oral epalrestat were studied in a child with PMM2-CDG for 12 months.

Results: PMM enzyme activity increased post-epalrestat treatment. Compared with controls, 24% of glycopeptides had reduced abundance in PMM2-deficient fibroblasts, 46% of which improved upon treatment. Total protein N-glycosylation improved upon epalrestat treatment bringing overall glycosylation toward the control fibroblasts' glycosylation profile. Sorbitol levels were increased in the urine of 74% of patients with PMM2-CDG and correlated with the presence of peripheral neuropathy, and CDG severity rating scale. In the child with PMM2-CDG on epalrestat treatment, ataxia scores improved together with significant growth improvement. Urinary sorbitol levels nearly normalized in 3 months and blood transferrin glycosylation normalized in 6 months.

Interpretation: Epalrestat improved PMM enzyme activity, N-glycosylation, and glycosylation biomarkers in vitro. Leveraging cellular glycoproteome assessment, we provided a systems-level view of treatment efficacy and discovered potential novel biosignatures of therapy response. Epalrestat was well-tolerated and led to significant clinical improvements in the first pediatric patient with PMM2-CDG treated with epalrestat. We also propose urinary sorbitol as a novel biomarker for disease severity and treatment response in future clinical trials in PMM2-CDG. ANN NEUROL 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.26245DOI Listing
October 2021

Range-Adaptive Value Representation in Different Stages of Schizophrenia: A Proof of Concept Study.

Schizophr Bull 2021 Oct;47(6):1524-1533

Neuropsychology and Applied Cognitive Neuroscience Laboratory; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Amotivation is related to value representation. A comprehensive account of amotivation requires a mechanistic understanding of how the brain exploits external information to represent value. To achieve maximal value discriminability, brain valuation system will dynamically adapt its coding sensitivity to the range of values available in any given condition, so-called range adaptive coding. We administered an experimental task to 30 patients with chronic schizophrenia (C-SCZ), 30 first-episode schizophrenia (FE-SCZ), 34 individuals with high social anhedonia (HSoA), and their paired controls to assess range adaptation ability. C-SCZ patients exhibited over-adaptation and their performances were negatively correlated with avolition symptoms and positive symptoms and positively correlated with blunted-affect symptoms and self-reported consummatory interpersonal pleasure scores, though the results were non-significant. FE-SCZ patients exhibited reduced adaptation, which was significantly and negatively correlated with avolition symptoms and positively correlated with the overall proportion of choosing to exert more effort. Although HSoA participants exhibited comparable range adaptation to controls, their performances were significantly and negatively correlated with the proportion of choosing to exert more effort under the lowest value condition. Our results suggest that different stages of schizophrenia spectrum showed distinct range adaptation patterns. Range adaptation impairments may index a possible underlying mechanism for amotivation symptoms in FE-SCZ and more complicated and pervasive effects on clinical symptoms in C-SCZ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbab099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530390PMC
October 2021

Enhancing the Prelicensure Clinical Learning Experience: A Student-Centered Learning Approach.

Nurse Educ 2021 Aug 4. Epub 2021 Aug 4.

Author affiliations: Assistant Professor (Dr Donovan), School of Nursing, Shepherd University, Shepherdstown, WV; Associate Professor (Drs Strunk and Argenbright), Assistant Professor (Drs Robinson and Lam, and Ms Leisen), and Assistant Professor (Ms Puffenbarger), School of Nursing, James Madison University, Harrisonburg, VA.

Background: Studies of the clinical learning environment document the importance of the student's clinical learning process.

Purpose: The aim of this study was to gather information on students' perceptions of their learning in the clinical environment.

Methods: A mixed-method strategy was used to explore nursing students' (N = 194) perceptions of their clinical learning experiences. Data were collected using the Clinical Learning Environment Inventory (CLEI) survey and open-ended questions.

Results: The results showed that significant CLEI factors were affordances and engagement, student-centeredness, valuing nurses' work, and fostering workplace learning and that these factors were important to prelicensure nursing students' learning in the clinical environment. In addition, the thematic concepts that enhanced their learning were clinical faculty who exhibited strong communication, encouraged and challenged learners, and were readily available.

Conclusions: Clinical faculty in the clinical environment must be competent and able to support the prelicensure nursing student learner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NNE.0000000000001085DOI Listing
August 2021

Hair to blood mercury concentration ratios and a retrospective hair segmental mercury analysis in the Northwest Territories, Canada.

Environ Res 2021 Aug 5;203:111800. Epub 2021 Aug 5.

School of Public Health and Health Systems, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada. Electronic address:

Concentrations of total mercury were measured in blood and hair samples collected as part of a human biomonitoring project conducted in First Nations communities of the Mackenzie Valley, Northwest Territories, Canada. Hair (n = 443) and blood (n = 276) samples were obtained from six communities in the Dehcho region and three communities in the Sahtú region of the Mackenzie Valley. The aim of this paper was to calculate hair to blood mercury ratios (for matched samples) and determine if: 1) ratios differed significantly between the two regions; 2) ratios differed from the 250:1 ratio proposed by the WHO; and, 3) point estimates of hair to blood mercury ratios could be used to estimate blood mercury concentrations. In addition, this paper aims to determine if there were seasonal patterns in hair mercury concentrations in these regions and if so, if patterns were related to among-season variability in fish consumption. The majority of mercury levels in hair and blood were below relevant health-based guidance values. The geometric mean hair (most recent segment) to blood mercury ratio (stratified by region) was 619:1 for the Dehcho region and 1220:1 for the Sahtú region. Mean log-transformed hair to blood mercury ratios were statistically significantly different between the two regions. Hair to blood ratios calculated in this study were far higher (2-5 times higher) than those typically reported in the literature and there was a large amount of inter-individual variation in calculated ratios (range: 114:1 to 4290:1). Using the 250:1 ratio derived by the World Health Organisation to estimate blood mercury concentrations from hair mercury concentrations would substantially over-estimate blood mercury concentrations in the studied regions. However, geometric mean site-specific hair to blood mercury ratios can provide estimates of measures of central tendency for blood mercury concentrations from hair mercury concentrations at a population level. Mercury concentrations were determined in segments of long hair samples to examine exposure of participants to mercury over the past year. Hair segments were assigned to six time periods and the highest hair mercury concentrations were generally observed in hair segments that aligned with September/October and November/December, whereas the lowest hair mercury concentrations were aligned with March/April and May/June. Mean log-transformed hair mercury concentrations were statistically significantly different between time periods. Between time periods (e.g., September/October vs. March/April), the geometric mean mercury concentration in hair differed by up to 0.22 μg/g, and the upper margins of mercury exposure (e.g., 95th percentile of hair mercury) varied by up to 0.86 μg/g. Results from self-reported fish consumption frequency questionnaires (subset of participants; n = 170) showed total fish intake peaked in late summer, decreased during the winter, and then increased during the spring. Visual assessment of results indicated that mean hair mercury concentrations followed this same seasonal pattern. Results from mixed effects models, however, indicated that variability in hair mercury concentrations among time periods was not best explained by total fish consumption frequency. Instead, seasonal trends in hair mercury concentrations may be more related to the consumption of specific fish species (rather than total wild-harvested fish in general). Future work should examine whether seasonal changes in the consumption of specific fish species are associated with seasonal changes in hair mercury concentrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2021.111800DOI Listing
August 2021

The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses.

JIMD Rep 2021 Jul 5;60(1):67-74. Epub 2021 Apr 5.

Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.

Background: Glutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical "low-excretor" (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation.

Methods: Samples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated.

Results: Five LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype.

Conclusions: The data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmd2.12217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260482PMC
July 2021

Targeted long-read sequencing identifies missing disease-causing variation.

Am J Hum Genet 2021 08 2;108(8):1436-1449. Epub 2021 Jul 2.

Department of Pediatrics, Division of Genetic Medicine, University of Washington and Seattle Children's Hospital, Seattle, WA 98105, USA; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.

Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate structural differences, candidate variants that do not fully explain the phenotype, single pathogenic variants in recessive disorders, or no variants in genes of interest. Thus, there is a need for better tools to identify a precise genetic diagnosis in individuals when conventional testing approaches have been exhausted. We performed targeted long-read sequencing (T-LRS) using adaptive sampling on the Oxford Nanopore platform on 40 individuals, 10 of whom lacked a complete molecular diagnosis. We computationally targeted up to 151 Mbp of sequence per individual and searched for pathogenic substitutions, structural variants, and methylation differences using a single data source. We detected all genomic aberrations-including single-nucleotide variants, copy number changes, repeat expansions, and methylation differences-identified by prior clinical testing. In 8/8 individuals with complex structural rearrangements, T-LRS enabled more precise resolution of the mutation, leading to changes in clinical management in one case. In ten individuals with suspected Mendelian conditions lacking a precise genetic diagnosis, T-LRS identified pathogenic or likely pathogenic variants in six and variants of uncertain significance in two others. T-LRS accurately identifies pathogenic structural variants, resolves complex rearrangements, and identifies Mendelian variants not detected by other technologies. T-LRS represents an efficient and cost-effective strategy to evaluate high-priority genes and regions or complex clinical testing results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2021.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387463PMC
August 2021

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?

Mol Genet Metab 2021 08 11;133(4):397-399. Epub 2021 Jun 11.

Dept. of Pediatrics - Divisions of Endocrinology and Genetics & Metabolism, Dept. of Experimental & Clinical Pharmacology, University of Minnesota, USA.

PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production. Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multi-center Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 μg/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned. Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgme.2021.06.003DOI Listing
August 2021

Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.

Genet Med 2021 09 26;23(9):1604-1615. Epub 2021 May 26.

Department of Dermatology, University Hospital Münster, Münster, Germany.

Purpose: Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature.

Methods: Nineteen patients were phenotyped per local institutional procedures. A systematic review following PRISMA criteria identified 132 articles describing 161 patients. Main outcome analyses were performed for manifestation frequency, diagnostic delay, overall survival, symptom-free survival, and ulcer-free survival.

Results: Our cohort presented a wide variability of severity. Autoimmune disorders were found in 6/19, including Crohn disease, systemic lupus erythematosus, and arthritis. Another immune finding was hemophagocytic lymphohistiocytosis (HLH). Half of published patients were symptomatic by age 4 and had a delayed diagnosis (mean delay 11.6 years). Ulcers were present initially in only 30% of cases, with a median age of onset at 12 years old.

Conclusion: Prolidase deficiency has a broad range of manifestations. Symptoms at onset may be nonspecific, likely contributing to the diagnostic delay. Testing for this disorder should be considered in any child with unexplained autoimmunity, lower extremity ulcers, splenomegaly, or HLH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-021-01200-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463480PMC
September 2021

Implementing Enhanced Primary Care Registered Nurse Reimbursement in Rural Health Clinics: A Policy Analysis.

Policy Polit Nurs Pract 2021 Aug 27;22(3):201-211. Epub 2021 Apr 27.

School of Nursing, James Madison University, Harrisonburg, Virginia, United States.

Rural Health Clinics (RHCs) were created in 1977 to address the high health care needs, limited provider access, and poor health outcomes of rural Americans. Although innovative at their inception, the provider-centric model of RHC cost-based reimbursement structures has not evolved, leaving limited opportunities for change; many have failed. Comprehensive, proactive change is needed. Registered nurses (RNs) working at the top of their practice scope are a neglected clinical resource that can improve access, quality, value, and satisfaction for rural patient communities. RHC reimbursement policy must evolve to sustain and support this significant RN role. RNs have demonstrated value in care continuity and disease management, but there is little research on the utilization of RNs using their enhanced skill set in RHCs. Using the Bardach and Patashnik's eight steps of policy analysis, the authors will describe the background and regulations of RHCs, identify current barriers to improving the health of America's rural residents, and then provide evidence to support a new policy option according to the Quadruple Aim framework. The result is a sustainable policy recommendation designed to best serve rural communities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15271544211011989DOI Listing
August 2021

Assessment of Structural Competency in Baccalaureate Nursing Students: A Descriptive Study.

Nurs Educ Perspect 2021 Apr 14. Epub 2021 Apr 14.

About the Authors Elle J. Del Gallo, BSN, RN, is nurse at Virginia Commonwealth University, Richmond, VA. Christina K. Lam, PhD, RN, is an Assistant Professor of Nursing at James Madison University School of Nursing, Harrisonburg, VA. For more information, contact Dr. Christina Lam,

Abstract: Structural competency describes the ability to recognize structural factors that affect health disparities, such as inequity and stigma. These structural factors can alter a patient's symptoms and risk for certain diseases. The purpose of this study was to describe baccalaureate nursing students' attributions of the effects of structural factors on health. Participants in this study attributed structural factors as being relevant to adverse health outcomes. Findings demonstrated differences in attribution of structural factors by academic level. Given the shifting demographics in the United States and gaps in health care access, further research is needed on the development of structural competence in nursing students.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.NEP.0000000000000807DOI Listing
April 2021

Nurse Faculty Experiences Teaching Chronic Illness Self-Management Concepts: An Exploratory Study.

Nurs Educ Perspect 2021 Nov-Dec 01;42(6):344-349

About the Authors Christina K. Lam, PhD, RN, is an assistant professor, School of Nursing, James Madison University, Harrisonburg, Virginia. Linda C. Copel, PhD, RN, CNS, BC, CNE, NCC, FAPA, is a professor, M. Louise Fitzpatrick College of Nursing, Villanova University, Villanova, Pennsylvania. Lilianna Deveneau, BA, BS, is a master's student in sociology at George Mason University, Fairfax, Virginia. For more information, contact Dr. Lam at

Aim: The aim of the study was to explore how nurse faculty prepare students to teach chronic disease self-management.

Background: Self-management addresses patient activities in response to a change in baseline health. Evidence suggests nurses may not be educated on how to engage patients in chronic disease self-management.

Method: This qualitative study used semistructured interviews to explore experiences of 13 nurse faculty across three universities in preparing nursing students to address self-management concepts for adults living with chronic disease.

Results: Three themes emerged from 104 identified significant statements: conceptualizing and valuing chronic disease self-management in nursing education, making chronic disease self-management fit, and sharing the impact of health care reform on chronic disease care.

Conclusion: Self-management is regarded as highly complex and evolving. As such, nursing education curricula must also evolve to emphasize successful approaches to preventing chronic disease and incorporating chronic disease self-management and behavior modification in the curriculum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.NEP.0000000000000808DOI Listing
April 2021

Perceptions of peer mental health: impact of race and student-athlete status.

J Am Coll Health 2021 Apr 8:1-13. Epub 2021 Apr 8.

College of Integrated Sciences and Arts, Arizona State University, Tempe, Arizona, USA.

This study used a multi-faceted methodological approach to examine if peer perceptions of stereotyped student groups' mental health needs varied by target race and student-athlete status. In Study 1, 502 university students completed an online experiment. Study 2 data were drawn from the American College Health Association (ACHA)-National College Health Assessment ( = 65,167) and Healthy Minds Study ( = 43,487). Study 1 participants rated the severity of various mental health concerns for Black non-student-athletes, White non-student-athletes, Black student-athletes, or White student-athletes. Study 2 conceptualized peer perceptions vis-à-vis mental health patterns in national data. Study 1 generally revealed lower perceived severity of mental health concerns for Black non-student-athletes. In contrast, Study 2 patterns revealed more variations across student status groups, including that Black non-student-athletes exhibited relatively high prevalence rates of numerous mental health concerns. Results may suggest mental health under-/over-pathologizing, with implications for training and peer-to-peer mental health interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07448481.2021.1903477DOI Listing
April 2021

RNA tape sampling in cutaneous lupus erythematosus discriminates affected from unaffected and healthy volunteer skin.

Lupus Sci Med 2021 03;8(1)

Biogen Inc, Cambridge, Massachusetts, USA

Objective: Punch biopsy, a standard diagnostic procedure for patients with cutaneous lupus erythematosus (CLE) carries an infection risk, is invasive, uncomfortable and potentially scarring, and impedes patient recruitment in clinical trials. Non-invasive tape sampling is an alternative that could enable serial evaluation of specific lesions. This cross-sectional pilot research study evaluated the use of a non-invasive adhesive tape device to collect messenger RNA (mRNA) from the skin surface of participants with CLE and healthy volunteers (HVs) and investigated its feasibility to detect biologically meaningful differences between samples collected from participants with CLE and samples from HVs.

Methods: Affected and unaffected skin tape samples and simultaneous punch biopsies were collected from 10 participants with CLE. Unaffected skin tape and punch biopsies were collected from 10 HVs. Paired samples were tested using quantitative PCR for a candidate immune gene panel and semi-quantitative immunohistochemistry for hallmark CLE proteins.

Results: mRNA collected using the tape device was of sufficient quality for amplification of 94 candidate immune genes. Among these, we found an interferon (IFN)-dominant gene cluster that differentiated CLE-affected from HV (23-fold change; p<0.001) and CLE-unaffected skin (sevenfold change; p=0.002), respectively. We found a CLE-associated gene cluster that differentiated CLE-affected from HV (fourfold change; p=0.005) and CLE-unaffected skin (fourfold change; p=0.012), respectively. Spearman's correlation between per cent area myxovirus 1 protein immunoreactivity and IFN-dominant mRNA gene cluster expression was highly significant (dermis, rho=0.86, p<0.001). In total, skin tape-derived RNA expression comprising both IFN-dominant and CLE-associated gene clusters correlated with per cent area immunoreactivity of some hallmark CLE-associated proteins in punch biopsies from the same lesions.

Conclusions: A non-invasive tape RNA collection technique is a potential tool for repeated skin biomarker measures throughout a clinical trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2020-000428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931768PMC
March 2021

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study.

Orphanet J Rare Dis 2021 02 25;16(1):102. Epub 2021 Feb 25.

Department of Clinical Genomics, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.

A recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study's conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients' lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-021-01751-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908710PMC
February 2021

Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG.

J Inherit Metab Dis 2021 07 1;44(4):987-1000. Epub 2021 Mar 1.

Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.

Congenital disorders of glycosylation (CDGs) are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid biosynthesis that cause multisystem diseases. Individuals with ALG3-CDG frequently exhibit severe neurological involvement (epilepsy, microcephaly, and hypotonia), ocular anomalies, dysmorphic features, skeletal anomalies, and feeding difficulties. We present 10 unreported individuals diagnosed with ALG3-CDG based on molecular and biochemical testing with 11 novel variants in ALG3, bringing the total to 40 reported individuals. In addition to the typical multisystem disease seen in ALG3-CDG, we expand the symptomatology of ALG3-CDG to now include endocrine abnormalities, neural tube defects, mild aortic root dilatation, immunodeficiency, and renal anomalies. N-glycan analyses of these individuals showed combined deficiencies of hybrid glycans and glycan extension beyond Man GlcNAc consistent with their truncated lipid-linked precursor oligosaccharides. This spectrum of N-glycan changes is unique to ALG3-CDG. These expanded features of ALG3-CDG facilitate diagnosis and suggest that optimal management should include baseline endocrine, renal, cardiac, and immunological evaluation at the time of diagnosis and with ongoing monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282734PMC
July 2021

ABO maternal-child discordance: Evidence of variable allelic expression and considerations for investigation.

Transfusion 2021 03 21;61(3):979-985. Epub 2021 Jan 21.

Department of Pathology, University of California San Diego, La Jolla, California, USA.

Background: We report a case of apparent mother-child ABO group noninheritance. A Caucasian mother initially typed as group O and her infant group AB. Investigation ruled out preanalytical causes such as mislabeled samples and in vitro fertilization.

Materials And Methods: Red blood cells were characterized by routine serologic testing. Genomic data were analyzed by targeted polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing. Transferase structures were modeled using PyMOL molecular visualization software.

Results: Serologic testing initially demonstrated the mother was group O, father group AB, and infant group AB. Further testing of the maternal sample with anti-A,B demonstrated weak A expression. Molecular testing revealed the maternal sample had an ABO*O.01.01 allele in trans to an A allele, ABO*AW.29 (c.311T>A, p.Ile104Asn), determined by gene sequencing. The sample from the infant carried the same ABO*AW.29 allele in trans to a B allele, ABO*B.01.

Conclusion: ABO genotyping revealed an A transferase encoded by ABO*AW.29, with apparent variable activity. Although A antigen expression is well known to be weak in newborns, it was robust on the red blood cells (RBCs) of the AB infant and undetectable with anti-A on the mother. Variable expression of weak subgroups may reflect competition or enhancement by a codominant allele, as well as glycan chain maturation on red cells. Previous examples in group AB mothers with A infants suggested that the decreased expression is primarily due to glycan immaturity. To our knowledge, this is the first reported case of the ABO*AW.29 allele presenting with weak A expression in a group A mother and robust A expression in a group AB infant, suggesting the in trans allele is an important factor in determining transferase activity and may override age-related effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16263DOI Listing
March 2021

Methylated and unmethylated epialleles support variegated epigenetic silencing in Friedreich ataxia.

Hum Mol Genet 2021 02;29(23):3818-3829

Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Friedreich ataxia (FRDA) is typically caused by homozygosity for an expanded GAA triplet-repeat in intron 1 of the FXN gene, which results in transcriptional deficiency via epigenetic silencing. Most patients are homozygous for alleles containing > 500 triplets, but a subset (~20%) have at least one expanded allele with < 500 triplets and a distinctly milder phenotype. We show that in FRDA DNA methylation spreads upstream from the expanded repeat, further than previously recognized, and establishes an FRDA-specific region of hypermethylation in intron 1 (~90% in FRDA versus < 10% in non-FRDA) as a novel epigenetic signature. The hypermethylation of this differentially methylated region (FRDA-DMR) was observed in a variety of patient-derived cells; it significantly correlated with FXN transcriptional deficiency and age of onset, and it reverted to the non-disease state in isogenically corrected induced pluripotent stem cell (iPSC)-derived neurons. Bisulfite deep sequencing of the FRDA-DMR in peripheral blood mononuclear cells from 73 FRDA patients revealed considerable intra-individual epiallelic variability, including fully methylated, partially methylated, and unmethylated epialleles. Although unmethylated epialleles were rare (median = 0.33%) in typical patients homozygous for long GAA alleles with > 500 triplets, a significantly higher prevalence of unmethylated epialleles (median = 9.8%) was observed in patients with at least one allele containing < 500 triplets, less severe FXN deficiency (>20%) and later onset (>15 years). The higher prevalence in mild FRDA of somatic FXN epialleles devoid of DNA methylation is consistent with variegated epigenetic silencing mediated by expanded triplet-repeats. The proportion of unsilenced somatic FXN genes is an unrecognized phenotypic determinant in FRDA and has implications for the deployment of effective therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddaa267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861014PMC
February 2021

Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up.

Orphanet J Rare Dis 2021 01 7;16(1):20. Epub 2021 Jan 7.

Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.

Background: The congenital disorders of glycosylation (CDG) are a heterogeneous group of rare metabolic diseases with multi-system involvement. The liver phenotype of CDG varies not only according to the specific disorder, but also from patient to patient. In this study, we sought to identify common patterns of liver injury among patients with a broad spectrum of CDG, and to provide recommendations for follow-up in clinical practice.

Methods: Patients were enrolled in the Frontiers in Congenital Disorders of Glycosylation natural history study. We analyzed clinical history, molecular genetics, serum markers of liver injury, liver ultrasonography and transient elastography, liver histopathology (when available), and clinical scores of 39 patients with 16 different CDG types (PMM2-CDG, n = 19), with a median age of 7 years (range: 10 months to 65 years). For patients with disorders which are treatable by specific interventions, we have added a description of liver parameters on treatment.

Results: Our principal findings are (1) there is a clear pattern in the evolution of the hepatocellular injury markers alanine aminotransferase and aspartate aminotransferase according to age, especially in PMM2-CDG patients but also in other CDG-I, and that the cholangiocellular injury marker gamma-glutamyltransferase is not elevated in most patients, pointing to an exclusive hepatocellular origin of injury; (2) there is a dissociation between liver ultrasound and transient elastography regarding signs of liver fibrosis; (3) histopathological findings in liver tissue of PMM2-CDG patients include cytoplasmic glycogen deposits; and (4) most CDG types show more than one type of liver injury.

Conclusions: Based on these findings, we recommend that all CDG patients have regular systematic, comprehensive screening for liver disease, including physical examination (for hepatomegaly and signs of liver failure), laboratory tests (serum alanine aminotransferase and aspartate aminotransferase), liver ultrasound (for steatosis and liver tumors), and liver elastography (for fibrosis).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-020-01630-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788939PMC
January 2021

Utilizing evidence-based guidelines to develop a language barriers simulation.

Contemp Nurse 2020 Oct-Dec;56(5-6):534-539. Epub 2020 Dec 10.

School of Nursing, James Madison University, 235 Martin Luther King Jr Way, MSC 4305, Harrisonburg, VA 22807, USA.

Background: The United States population is becoming increasingly diverse. Despite this trend, diversity in the nursing profession lags. In order to provide patient-centered care, students must learn the nuances of providing culturally competent care. There are many ways to assess the impact of culture on healthcare behaviors and norms, and can include, but are not limited to, ethnicity, sexual orientation, or religious preference. Clinical experiences offer inconsistent opportunities for students to interact with potentially diverse patients.

Objective: The aim of this project was to develop a simulation that built upon curricular objectives and evidence-based guidelines for healthcare providers communicating across language barriers.

Findings: Regulations and evidence-based guidelines describe how to provide quality patient-centered care to diverse groups of patients. These guidelines can be adapted at the clinician and systems level to facilitate culturally sensitive and linguistically appropriate services to patients. These guidelines were applied in an educational setting, and combined with best practices in simulation, to enhance undergraduate nursing students' experience in caring for diverse patients.

Conclusion: The use of simulation can be optimized when based on evidence-based guidelines encountered in clinical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10376178.2020.1855996DOI Listing
October 2021

Evidence-Based Practice Competence in Nursing Students Preparing to Transition to Practice.

Worldviews Evid Based Nurs 2020 Dec 28;17(6):418-426. Epub 2020 Nov 28.

School of Nursing, James Madison University, Harrisonburg, VA, USA.

Background: Opportunities to embed and evaluate evidence-based practice (EBP) competency in the clinical setting across nursing curricula are not well described in the literature.

Aims: This research aims to describe how clinical learning environments influence senior nursing students' integration of EBP competencies in their practice and perceptions of EBP competence development in a traditional baccalaureate nursing program.

Methods: A sequential, mixed-methods design was used with senior students upon completion of their last two clinical experiences in the nursing program. Students completed the EBP Work Environment Scale (Pryse, McDaniel, & Schafer, 2014) and semi-structured interviews.

Findings: Students appraised EBP Work Environments positively during preceptor-led experiences as opposed to instructor-led, group clinical experiences. Students described the evolution of emerging EBP competence throughout their nursing education and emphasized the importance of coursework in intentionally developing EBP competence.

Linking Evidence To Action: Assessment of clinical experiences and models that contribute to EBP competence is needed. Participants in this study emphasized the importance of coursework that builds on EBP competencies, and the tremendous value of nurse preceptors that encouraged growth in their ability to engage with EBP in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/wvn.12479DOI Listing
December 2020

Beyond Premature Ovarian Insufficiency: Staging Reproductive Aging in Adolescent and Young Adult Cancer Survivors.

J Clin Endocrinol Metab 2021 01;106(2):e1002-e1013

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, California.

Context: Although stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors).

Objective: This work aimed to evaluate applying STRAW + 10 criteria in AYA survivors using bleeding patterns with and without endocrine biomarkers, and to assess how cancer treatment gonadotoxicity is related to reproductive aging stage.

Design: The sample (n = 338) included AYA survivors from the Reproductive Window Study cohort. Menstrual bleeding data and dried-blood spots for antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) measurements (Ansh DBS enzyme-linked immunosorbent assays) were used for reproductive aging stage assessment. Cancer treatment data were abstracted from medical records.

Results: Among participants, mean age 34.0 ± 4.5 years and at a mean of 6.9 ± 4.6 years since cancer treatment, the most common cancers were lymphomas (31%), breast (23%), and thyroid (17%). Twenty-nine percent were unclassifiable by STRAW + 10 criteria, occurring more frequently in the first 2 years from treatment. Most unclassifiable survivors exhibited bleeding patterns consistent with the menopausal transition, but had reproductive phase AMH and/or FSH levels. For classifiable survivors (48% peak reproductive, 30% late reproductive, 12% early transition, 3% late transition, and 7% postmenopause), endocrine biomarkers distinguished among peak, early, and late stages within the reproductive and transition phases. Gonadotoxic treatments were associated with more advanced stages.

Conclusions: We demonstrate a novel association between gonadotoxic treatments and advanced stages of reproductive aging. Without endocrine biomarkers, bleeding pattern alone can misclassify AYA survivors into more or less advanced stages. Moreover, a large proportion of AYA survivors exhibited combinations of endocrine biomarkers and bleeding patterns that do not fit the STRAW + 10 criteria, suggesting the need for modified staging for this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823232PMC
January 2021

Tutorial: Triheptanoin and Nutrition Management for Treatment of Long-Chain Fatty Acid Oxidation Disorders.

JPEN J Parenter Enteral Nutr 2021 02 11;45(2):230-238. Epub 2020 Nov 11.

Department of Pediatrics, Biochemical Genetics, University of Washington, Seattle Children's Hospital, Seattle, Washington, USA.

Background: Patients with severe long-chain fatty acid oxidation disorders (LC-FAODs) experience serious morbidity and mortality despite traditional dietary management including medium-chain triglyceride (MCT)-supplemented, low-fat diets. Triheptanoin is a triglyceride oil that is broken down to acetyl-coenzyme A (CoA) and propionyl-CoA, which replenishes deficient tricarboxylic acid cycle intermediates. We report the complex medical and nutrition management of triheptanoin therapy initiated emergently for 3 patients with LC-FAOD.

Methods: Triheptanoin (Ultragenyx Pharmaceutical, Inc, Novato, CA, USA) was administered to 3 patients with LC-FAOD on a compassionate-use basis. Triheptanoin was mixed with non-MCT-containing low-fat formula. Patients were closely followed with regular cardiac and laboratory monitoring.

Results: Cardiac ejection fraction normalized after triheptanoin initiation. Patients experienced fewer hospitalizations related to metabolic crises while on triheptanoin. Patient 1 has tolerated oral administration without difficulty since birth. Patients 2 and 3 experienced increased diarrhea. Recurrent breakdown of the silicone gastrostomy tube occurred in patient 3, whereas the polyurethane nasogastric tube for patient 2 remained intact. Patient 3 experiences recurrent episodes of elevated creatine kinase levels and muscle weakness associated with illness. Patient 3 had chronically elevated C10-acylcarnitines while on MCT supplementation, which normalized after initiation of triheptanoin and discontinuation of MCT oil.

Conclusions: Triheptanoin can ameliorate acute cardiomyopathy and increase survival in patients with severe LC-FAOD. Substituting triheptanoin for traditional MCT-based treatment improves clinical outcomes. MCT oil might be less effective in carnitine-acylcarnitine translocase deficiency patients compared with other FAODs and needs further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.2034DOI Listing
February 2021

Nurse Led Smartphone Electrographic Monitoring for Atrial Fibrillation after Ischemic Stroke: SPOT-AF.

J Stroke 2020 Sep 29;22(3):387-395. Epub 2020 Sep 29.

Heart Research Institute Charles Perkins Centre, and Concord Hospital Cardiology, University of Sydney, Sydney, Australia.

Background And Purpose: Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate.

Methods: We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection.

Results: One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (P<0.001). Median duration from stroke onset to AF detection for iECG was 3 days (interquartile range [IQR], 2 to 6) compared with 7 days (IQR, 6 to 10) for Holter recordings (P=0.02). Of 25 patients with AF detected by iECG, 11 were commenced on oral anticoagulant, compared to 5/8 for Holter. AF was detected in 8.8% (69/785 patients) who underwent iECG recordings only (P=0.8 vs. those who had both iECG and 24-hour Holter).

Conclusions: Nurse-led in-hospital iECG surveillance after stroke is feasible and effective and detects more PAF earlier and more frequently than routine 24-hour Holter recordings. Screening with iECG could be incorporated into routine post-stroke nursing observations to increase diagnosis of PAF, and facilitate institution of guideline-recommended anticoagulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5853/jos.2020.00689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568969PMC
September 2020

Immune dysfunction in MGAT2-CDG: A clinical report and review of the literature.

Am J Med Genet A 2021 01 12;185(1):213-218. Epub 2020 Oct 12.

Department of Pediatrics, School of Medicine, University of Washington, Seattle, Washington, USA.

Glycosylation is a critical post/peri-translational modification required for the appropriate development and function of the immune system. As an example, abnormalities in glycosylation can cause antibody deficiency and reduced lymphocyte signaling, although the phenotype can be complex given the diverse roles of glycosylation. Human MGAT2 encodes N-acetylglucosaminyltransferase II, which is a critical enzyme in the processing of oligomannose to complex N-glycans. Complex N-glycans are essential for immune system functionality, but only one individual with MGAT2-CDG has been described to have an abnormal immunologic evaluation. MGAT2-CDG (CDG-IIa) is a congenital disorder of glycosylation (CDG) associated with profound global developmental disability, hypotonia, early onset epilepsy, and other multisystem manifestations. Here, we report a 4-year old female with MGAT2-CDG due to a novel homozygous pathogenic variant in MGAT2, a 4-base pair deletion, c.1006_1009delGACA. In addition to clinical features previously described in MGAT2-CDG, she experienced episodic asystole, persistent hypogammaglobulinemia, and defective ex vivo mitogen and antigen proliferative responses, but intact specific vaccine antibody titers. Her infection history has been mild despite the testing abnormalities. We compare this patient to the 15 previously reported patients in the literature, thus expanding both the genotypic and phenotypic spectrum for MGAT2-CDG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098812PMC
January 2021

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management.

J Inherit Metab Dis 2021 01 15;44(1):148-163. Epub 2020 Sep 15.

Center for Child and Adolescent Medicine, Department, University of Heidelberg, Heidelberg, Germany.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1-CDG. PGM1-CDG usually manifests as a multisystem disease. Most patients present as infants with cleft palate, liver function abnormalities and hypoglycemia, but some patients present in adulthood with isolated muscle involvement. Some patients develop life-threatening cardiomyopathy. Unlike most other CDG, PGM1-CDG has an effective treatment option, d-galactose, which has been shown to improve many of the patients' symptoms. Therefore, early diagnosis and initiation of treatment for PGM1-CDG patients are crucial decisions. In this article, our group of international experts suggests diagnostic, follow-up, and management guidelines for PGM1-CDG. These guidelines are based on the best available evidence-based data and experts' opinions aiming to provide a practical resource for health care providers to facilitate successful diagnosis and optimal management of PGM1-CDG patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855268PMC
January 2021

The Impact of Rapid Exome Sequencing on Medical Management of Critically Ill Children.

J Pediatr 2020 Jun 15. Epub 2020 Jun 15.

Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA; Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA; Brotman Baty Institute for Precision Medicine, Seattle, WA; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA. Electronic address:

Objectives: To evaluate the clinical usefulness of rapid exome sequencing (rES) in critically ill children with likely genetic disease using a standardized process at a single institution. To provide evidence that rES with should become standard of care for this patient population.

Study Design: We implemented a process to provide clinical-grade rES to eligible children at a single institution. Eligibility included (a) recommendation of rES by a consulting geneticist, (b) monogenic disorder suspected, (c) rapid diagnosis predicted to affect inpatient management, (d) pretest counseling provided by an appropriate provider, and (e) unanimous approval by a committee of 4 geneticists. Trio exome sequencing was sent to a reference laboratory that provided verbal report within 7-10 days. Clinical outcomes related to rES were prospectively collected. Input from geneticists, genetic counselors, pathologists, neonatologists, and critical care pediatricians was collected to identify changes in management related to rES.

Results: There were 54 patients who were eligible for rES over a 34-month study period. Of these patients, 46 underwent rES, 24 of whom (52%) had at least 1 change in management related to rES. In 20 patients (43%), a molecular diagnosis was achieved, demonstrating that nondiagnostic exomes could change medical management in some cases. Overall, 84% of patients were under 1 month old at rES request and the mean turnaround time was 9 days.

Conclusions: rES testing has a significant impact on the management of critically ill children with suspected monogenic disease and should be considered standard of care for tertiary institutions who can provide coordinated genetics expertise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736066PMC
June 2020

Cosmetic treatment in patients with autoimmune connective tissue diseases: Best practices for patients with lupus erythematosus.

J Am Acad Dermatol 2020 Aug 28;83(2):343-363. Epub 2020 Apr 28.

Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts. Electronic address:

The cutaneous manifestations of lupus, especially chronic cutaneous lupus erythematosus, are a source of significant morbidity and can negatively impact patient quality of life. While the active inflammatory component of the disease may be adequately treated, patients are frequently left with residual skin damage and disfiguring aesthetic deficits. Dermatologists lack guidelines regarding the use and safety of various reconstructive and cosmetic interventions in this patient population. Laser treatments are largely avoided in the lupus population because of the possible photodamaging effects of ultraviolet and visible light. Similarly, given the autoimmune nature of this disease, some physicians avoid injectable treatment and grafts because of the concern for disease reactivation via antigenic stimulation. In the second article in this continuing medical education series we compile available data on this topic with the goal of providing evidence-based guidance on the cosmetic treatment of patients with lupus erythematosus with a focus on chronic cutaneous lupus erythematosus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.03.123DOI Listing
August 2020

Cosmetic treatment in patients with autoimmune connective tissue diseases: Best practices for patients with morphea/systemic sclerosis.

J Am Acad Dermatol 2020 Aug 28;83(2):315-341. Epub 2020 Apr 28.

Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts. Electronic address:

Morphea and systemic sclerosis are inflammatory, sclerosing disorders. Morphea primarily affects the dermis and subcutaneous fat, while systemic sclerosis typically involves the skin and internal organs. Functional impairment and cosmetic disfigurement are common in both diseases. Treatment options to mitigate disease progression remain limited. Both functional impairment and cosmetic deficits negatively impact quality of life and psychological well-being in this patient population. While the number of cosmetic procedures performed in the United States continues to rise each year, limited data exist regarding best practices for correcting aesthetic deficits caused by autoimmune conditions. There is scarce information to guide safety decisions regarding laser parameters, soft tissue augmentation, treatment intervals, and the concurrent use of immune-modifying or immune-suppressing medications. Given the fears of disease reactivation and exacerbation from postprocedural inflammation along with limited data, it is difficult for clinicians to provide evidence-based cosmetic treatment with realistic expectations with regard to short- and long-term outcomes. In the first article in this continuing medical education series, we attempt to address this practice gap.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2019.12.081DOI Listing
August 2020

Reproductive intentions in childless female adolescent and young adult cancer survivors.

Fertil Steril 2020 02;113(2):392-399

Department of Obstetrics, Gynecology and Reproductive Science, University of California, San Diego, La Jolla, California; Moores Cancer Center, University of California, San Diego, La Jolla, California. Electronic address:

Objective: To examine the association between prior cancer treatments, medical comorbidities, and voluntary childlessness in reproductive-age women who are survivors of cancers diagnosed as adolescents and young adults (AYA survivors).

Design: Cross-sectional analysis.

Setting: Participants were recruited from California and Texas cancer registries, fertility preservation programs, and cancer advocacy groups.

Patient(s): Women (n = 413) ages 18-40 who were diagnosed with cancer between ages 15 and 35, completed primary cancer treatments, had at least one ovary, and were nulliparous.

Intervention(s): Cancer treatment gonadotoxicity and medical comorbidities.

Main Outcome Measure(s): Voluntary childlessness.

Result(s): The mean age of survivors was 31.8 years (SD, 4.9) with a mean of 6.5 years (SD, 4.4) since cancer diagnosis. Breast (26%), thyroid (19%), and Hodgkin lymphoma (18%) were the most common cancers. Twenty-two percent of the cohort was voluntarily childless. Medical comorbidities, cancer diagnosis, prior surgery, prior chemotherapy, and prior gonadotoxic treatments were not significantly associated with voluntary childlessness. In adjusted analysis, survivors of older reproductive age (adjusted odds ratio = 2.97 [1.71-5.18]) and nonheterosexual participants (adjusted odds ratio = 4.71 [2.15-10.32]) were more likely to report voluntary childlessness.

Conclusion(s): A moderate proportion of AYA cancer survivors are voluntarily childless, but reproductive intentions were not related to cancer type or cancer treatments. AYA survivors of older age and nonheterosexual identification were more likely to be voluntarily childless. These data support assessing reproductive intentions and tailoring reproductive care such as fertility and contraception counseling that is appropriate for a survivor's intentions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2019.09.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112460PMC
February 2020
-->