Integrating Discussions on Racism and Health Equity into Clinical Reasoning Conference.

OBJECTIVE: Intentionally discussing racism and health equity in clinical reasoning conference may provide an opportunity to reinforce antiracist praxis. We aimed to understand 1) whether these discussions provide a meaningful opportunity to practice applying an antiracist lens in patient care, 2) the feasibility of implementing these discussions in a clinical reasoning format, and 3) the acceptability to Black, Indigenous, and People of Color (BIPOC) and white residents. METHODS: In 2021, 4 clinical reasoning conference pilot sessions were implemented in a pediatrics residency program. Trained faculty facilitated discussions on mitigating inequity in clinical cases. Residents who attended at least 1 session were invited to participate in focus groups, which were analyzed using grounded theory. RESULTS: Thirty residents attended each pilot session out of the 30 to 35 who had the opportunity to attend. The focus groups included 6 BIPOC and 6 white residents. The discussions offered a meaningful opportunity to practice recognizing and naming racism. Having faculty facilitators made the discussions more feasible. Both groups experienced benefits and wanted the discussions to continue, but BIPOC residents want more engagement from their white peers. CONCLUSIONS: Discussing racism and health equity in clinical reasoning conference was a meaningful, feasible, and acceptable opportunity for antiracist praxis.

Tilting the Scale: Current Provider Perspectives and Practices on Breastfeeding with HIV in the United States.

The risk of vertical transmission from breastfeeding with HIV (BFHIV) has been found to be very low in optimal scenarios with sustained maternal viral suppression during pregnancy and postpartum. Medical providers must account for the risk of this serious adverse event alongside parental autonomy, breastfeeding benefits, and patient values. To assess provider practices, comfort, and challenges with BFHIV, an online mixed-method survey was sent to breastfeeding and HIV provider listservs from June to July 2021. The target population was US medical professionals from diverse practice settings with experience in clinical issues associated with BFHIV, including physicians, advanced practice providers, nurses, and lactation consultants. Data analysis utilized nonparametric hypothesis testing, ordinal regression, and reflexive thematic analysis. Most providers reported counseling pregnant people with HIV on infant feeding choices, but fewer specifically endorsed counseling about breastfeeding. Of 84 unique institutions identified by 100 included respondents, 10% had an institutional protocol supporting BFHIV. Institutional protocols were associated with higher degrees of provider comfort with BFHIV in optimal scenario clinical vignettes. Providers perceived that White patients faced fewer BFHIV barriers than patients with other racial identities. Discomfort balancing the goals to protect infants from infection risk and support the parent's role in infant feeding decisions was a key theme in free text responses; this manifested in a spectrum of management styles ranging from patient's informed choice to paternalism. This study highlights the tension providers navigate regarding BFHIV discussions, calling for patient care guidelines and protocols grounded in risk reduction and respect of patient autonomy.

Discovery of a new biomarker for the mucopolysaccharidoses (MPS), dipeptidyl peptidase IV (DPP-IV; CD26), by SELDI-TOF mass spectrometry.

Surface enhanced laser desorption/ionisation time of flight (SELDI-TOF) mass spectrometry has been used to search for new protein biomarkers in the plasma of patients with mucopolysacharidoses (MPS). Differences in the levels of some plasma proteins, particularly the apolipoprotein ApoCI, were observed between MPS patients and normal controls, using the different chromatographic surfaces (ProteinChips). ApoCI was identified by both its mass and by immunological techniques. In plasma, it exists in two forms, ApoCI and a truncated form which lacks two N-terminal amino acids, ApoCI'. In controls, the ratio of ApoCI':ApoCI observed using the cation-exchange surface (CM10) was approximately 1:2 whereas in most MPS patients it varied from 1:1 to 1:0.8. The ratio of ApoCI':ApoCI in plasma is determined by the activity of dipeptidyl peptidase IV, DPP-IV (also known as the leucocyte antigen CD26), which was found to be elevated up to 3-fold in MPS patients. The DPP-IV activity decreased in MPS I patients undergoing enzyme replacement therapy, indicating that it could be a useful biomarker for monitoring the efficacy of treatment in MPS disease. As DPP-IV has an important regulatory role in metabolism, it is possible that its elevation could cause some of the secondary pathology in MPS, and inhibition of DPP-IV might have a role in MPS therapy.

Treatment of Fabry disease with different dosing regimens of agalsidase: effects on antibody formation and GL-3.

Two different enzyme preparations are used for the treatment of Fabry disease patients, agalsidase alpha (Replagal, Shire) and agalsidase beta (Fabrazyme, Genzyme). Therapeutic efficacy of both products has been variable probably due to differences in gender, severity, age and other patient characteristics. We studied the occurrence of alpha-Gal A antibodies and their effect on urinary and plasma globotriaosylceramide (GL-3), plasma chitotriosidase and clinical outcome in 52 patients after 12 months of treatment with either 0.2mg/kg agalsidase alppha (10 males, 8 females) or beta (8 males, 5 females) or 1.0mg/kg agalsidase beta (10 males, 11 females). Antibodies were detected in 18/28 male patients after 6 months. None of the females developed antibodies. Following 12 months of 0.2mg/kg treatment, urinary GL-3 decreased in antibody negative (AB-) but increased in antibody positive (AB+) patients. Treatment with 1.0mg/kg gave a reduction in urinary GL-3 in both AB- and AB+ patients. Levels of plasma GL-3 and chitotriosidase decreased in all patient groups. Twelve months of 0.2mg/kg treatment did not change renal function or left ventricular mass. Further, no change in renal function was seen following 1.0mg/kg treatment and left ventricular mass decreased in both AB- and AB+ patients. In summary, alpha-Gal A antibodies frequently develop in male Fabry disease patients and interfere with urinary GL-3 excretion. Infusion of a dose of 1.0mg/kg results in a more robust decline in GL-3, less impact, if any of antibodies, stable renal function and reduction of LVMass.

Lead in Air in Bangladesh: Exposure in a Rural Community with Elevated Blood Lead Concentrations among Young Children.

Previous evaluations of a birth cohort in the Munshiganj District of Bangladesh had found that over 85% of 397 children aged 2⁻3 years had blood lead concentrations above the United States Centers for Disease Control and Prevention's reference level of 5 µg/dL. Studies in urban areas of Bangladesh have found elevated levels of lead in the air due to industries and remaining contamination from the historic use of leaded gasoline. Sources of lead in rural areas of Bangladesh remain unknown. We conducted air sampling in both residential and industrial sites in Munshiganj to determine whether children are exposed to elevated lead concentrations in the air and study the association between the children's blood lead levels and sampled air lead concentrations. Residential and industrial air samples in Munshiganj were found to have elevated lead concentrations (mean 1.22 µg/m³) but were not found to be associated with the observed blood lead concentrations. Lead in air is an important environmental health exposure risk to the for children in Munshiganj, and further research may shed light on specific sources to inform exposure prevention and mitigation programs.

Assessment of Osteoporosis in Injured Older Women Admitted to a Safety-Net Level One Trauma Center: A Unique Opportunity to Fulfill an Unmet Need.

BACKGROUND: Older trauma patients often undergo computed tomography (CT) as part of the initial work-up. CT imaging can also be used opportunistically to measure bone density and assess osteoporosis. METHODS: In this retrospective cohort study, osteoporosis was ascertained from admission CT scans in women aged ≥65 admitted to the ICU for traumatic injury during a 3-year period at a single, safety-net, level 1 trauma center. Osteoporosis was defined by established CT-based criteria of average L1 vertebral body Hounsfield units <110. Evidence of diagnosis and/or treatment of osteoporosis was the primary outcome. RESULTS: The study cohort consisted of 215 women over a 3-year study period, of which 101 (47%) had evidence of osteoporosis by CT scan criteria. There were no differences in injury severity score, hospital length of stay, cost, or discharge disposition between groups with and without evidence of osteoporosis. Only 55 (59%) of the 94 patients with osteoporosis who survived to discharge had a documented osteoporosis diagnosis and/or corresponding evaluation/treatment plan. CONCLUSION: Nearly half of older women admitted with traumatic injuries had underlying osteoporosis, but 41% had neither clinical recognition of this finding nor a treatment plan for osteoporosis. Admission for traumatic injury is an opportunity to assess osteoporosis, initiate appropriate intervention, and coordinate follow-up care. Trauma and acute care teams should consider assessment of osteoporosis in women who undergo CT imaging and provide a bridge to outpatient services.

Survivorship of penstemon grandiflorus in an oak woodland: combined effects of fire and pocket gophers.

The effects of fire and pocket gophers, Geomys bursarius, on the survivorship of Penstemon grandiflorus growing in an oak woodland in Minnesota were studied from 1986 to 1990. Plants growing in sparse vegetation experienced mortality rates twice that of plants growing in dense vegetation. This difference was due partly to pocket gophers whose earth moving activities reduce the density of vegetation and bury and kill individual Penstemon plants. Laboratory feeding trials showed that gophers readily eat Penstemon, particularly the fleshy roots. An experiment involving the removal of 25-75% of the root tissue in 90 plants showed that root loss significantly reduced survivorship, suggesting that gopher herbivory might also kill plants. When gophers were experimentally excluded, plants growing in sparse vegetation exhibited significantly lower mortality rates than those growing in dense vegetation. Plants in the smallest size class exhibited reduced survivorship following a late spring burn; however, overall patterns of survivorship of plants in burned areas did not differ markedly from those in the unburned areas. A longitudenal analysis of plants with different reproductive histories revealed no survivorship cost to reproduction. Mortality rates decreased with increasing plant size. Small plants were more likely to be killed by fire and by being buried under gopher mounds. Differences in underground energy reserves of small and large plants can account for most of the survivorship patterns observed in this study. The study shows that within openings of the oak woodland, fire and gophers reduce the survival of individual Penstemon plants. Nevertheless, since both gophers and fire also serve to perpetuate suitable habitat in the woodland, Penstemon is ultimately dependent on both for its long term persistence in the landscape.

Prenatal diagnosis of cystinosis by quantitative measurement of cystine in chorionic villi and cultured cells.

OBJECTIVE: Prenatal diagnosis of cystinosis has been available for over 30 years by the incubation of cultured amniotic cells, intact chorionic villi and cultured chorionic cells with [35S]-cystine followed by thin layer chromatography and visual inspection of autoradiographs of the chromatograms for cystine. This method has proved highly reliable but because of the short half-life of [35S]-cystine, its cost and the length of the assay procedure, an alternative method of diagnosis was investigated. METHOD: Cystine was quantitatively measured in chorionic villi directly, in cultured chorionic villi and cultured amniotic cells using a cystine-binding protein from Escherichia coli. RESULTS: Twelve pregnancies at risk for cystinosis were monitored by both the [35S]-cystine uptake method and the new quantitative method in uncultured chorionic villi. There was no discrepancy between the results obtained with the two methods and subsequently 15 pregnancies have been monitored by the quantitative assay only--13 in chorionic villi directly, 1 in cultured chorionic villi cells and 1 in cultured amniotic cells. Grossly elevated levels of cystine were found in seven pregnancies. CONCLUSION: An unequivocal diagnosis of cystinosis can be made within 24 h of sampling by the quantitative measurement of cystine in uncultured chorionic villi.

The synthesis of internal standards for the quantitative determination of sphingolipids by tandem mass spectrometry.

Novel internal standards have been synthesised for the quantitative determination by tandem mass spectrometry (MS/MS) of the sphingolipids that accumulate in lysosomal storage diseases. The [d4]C16- and [d47]C24-isoforms of galactosylceramide (CMH), lactosylceramide (CDH), globotriaosylceramide (CTH), cerebroside sulphate, sphingomyelin and G(M1)-, G(M2)- and G(M3)-gangliosides were synthesised by the reaction of their lyso-forms with the acid chlorides of hexadecanoic 5,5,6,6-d4 acid ([d4]-palmitic acid) and tetracosanoic-d47 acid ([d47]-lignoceric acid), respectively. The acid chlorides were formed using oxalyl chloride. The structures of the internal standards were confirmed by MS/MS. The fragmentation pattern of each novel compound was similar to that of the corresponding natural form of the sphingolipid, making it a good internal standard for the quantitative determination of the natural sphingolipid by ESI-MS/MS. Characteristic product ions were identified for each compound.

Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease.

UNLABELLED: Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A. This leads to the progressive accumulation of glycosphingolipids in lysosomes of most visceral tissues and in body fluids. Following successful clinical trials in adults, two recombinant enzyme preparations of alpha-galactosidase have recently been licensed in Europe for the treatment of Fabry disease and treatment in children has commenced. We now report the clinical findings and the levels of globotriaosylceramide in plasma and urine in three boys who have been treated with enzyme replacement therapy (agalsidase beta, Fabrazyme), 1 mg/kg for 2 years. In one boy there was a rapid improvement in all the clinical and biochemical parameters measured. This has been maintained. In the other two boys, who are siblings, there was no measurable clinical improvement after 1 year and the levels of globotriaosylceramide in plasma and urine, although lower than before treatment, were still considerably elevated. There was no evidence of blocking or neutralising antibodies so the dose of enzyme was increased to 2 mg/kg at 74 weeks of therapy. At 2 years their pain scores had improved but this was not accompanied by any reduction in the plasma or urine globotriaosylceramide levels. CONCLUSION: Measurement of globotriaosylceramide in plasma and urine may not be the most appropriate marker to monitor the progression of treatment by enzyme replacement therapy in all patients. Certainly the subjective clinical improvement in the two brothers in this report outweighed the objective biochemical findings.

A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity.

We identified a novel mutation in the glycogen phosphorylase gene (PGYL) in a Chinese patient with glycogen storage disease (GSD) type VI. The patient presented with gross hepatomegaly since the age of two without history of any hypoglycemic attack. Otherwise, he was largely asymptomatic. Liver tissue enzyme assays revealed a mild deficiency of total glycogen phosphorylase. Both PGYL and PHKA2 genes were sequenced. The patient was homozygous of a missense mutation G233D in PGYL. This location forms a hairpin turn secondary structure and the small glycine residue is completely conserved in all the orthologous proteins from Escherichia coli to mammals. This is the sixth reported mutation of this form of GSD.