Publications

We studied mice with or without heterozygous deletion of the Casr in the parathyroid gland (PTG) [(PTG) CaSR(+/-)] to delineate effects of age and sex on manifestations of hyperparathyroidism (HPT). In control mice, aging induced a left-shift in the Ca(2+) /parathyroid hormone (PTH) set point accompanied by increased PTG CaSR expression along with lowered serum Ca(2+) and mildly increased PTH levels, suggesting adaptive responses of PTGs to aging-induced changes in mineral homeostasis. The aging effects on Ca(2+) /PTH set point and CaSR expression were significantly blunted in (PTG) CaSR(+/-) mice, who showed instead progressively elevated PTH levels with age, especially in 12-month-old females. These 12-month-old knockout mice demonstrated resistance to their high PTH levels in that serum 1,25-dihydroxyvitamin D (1,25-D) levels and RNA expression of renal Cyp27b1 and expression of genes involved in Ca(2+) transport in kidney and intestine were unresponsive to the rising PTH levels. Such changes may promote negative Ca(2+) balance, which further exacerbate the HPT. Skeletal responses to HPT were age-, sex-, and site-dependent. In control mice of either sex, trabecular bone in the distal femur decreased whereas cortical bone in the tibiofibular junction increased with age. In male (PTG) CaSR(+/-) mice, anabolic actions of the elevated PTH levels seemed to protect against trabecular bone loss at ≥ 3 months of age at the expense of cortical bone loss. In contrast, HPT produced catabolic effects on trabecular bone and anabolic effects on cortical bone in 3-month-old females; but these effects reversed by 12 months, preserving trabecular bone in aging mice. We demonstrate that the CaSR plays a central role in the adaptive responses of parathyroid function to age-induced changes in mineral metabolism and in target organ responses to calciotropic hormones. Restraining the ability of the PTG to upregulate CaSRs by heterozygous gene deletion contributes to biochemical and skeletal manifestations of HPT, especially in aging females.

OBJECTIVE

We describe a young woman with previously undiagnosed thyrotoxicosis who presented with acute liver failure (ALF).

METHODS

We present a case report and review the relevant literature.

RESULTS

An extensive evaluation excluded possible causes of ALF other than thyrotoxicosis. The management of thyrotoxicosis posed several unique challenges in the setting of ALF, particularly because we did not want to use potentially hepatotoxic thionamides. The patient was treated with prednisone and propranolol and was started on potassium iodide when she was listed for liver transplantation. She underwent an uncomplicated liver transplant and subsequent thyroidectomy and is doing well.

CONCLUSION

This well-characterized case describes thyrotoxicosis as a possible cause of ALF after thoroughly excluding other possible causes and illustrates the challenges of simultaneously managing both disorders. To our knowledge, this is the first report of ALF possibly resulting from untreated thyrotoxicosis that was successfully treated with liver transplantation.

Transient low-level viremia (TLLV) of 50-400 HIV RNA copies per milliliter is common during antiretroviral therapy, but its pathogenesis, consequences, and optimal management are unclear. Heightened immune activation is associated with detrimental outcomes, including impaired CD4 T-cell reconstitution. Using CD38/HLA-DR expression on CD8 T cells measured in 2 large studies, we determined associations between TLLV and immune activation levels before, during, and after TLLV. We found that TLLV does not significantly change CD8 T-cell activation and that higher CD8 T-cell activation during viral suppression <50 copies per milliliter is associated with a modest increase in the risk of a subsequent TLLV.

OBJECT

The authors evaluated the rates of ventriculostomy-related infections (VRIs) after antibiotic-coated extraventricular drains (ac-EVDs) were introduced as the standard of care.

METHODS

A retrospective chart review was conducted of adult patients admitted to NewYork-Presbyterian Hospital neurological intensive care unit in whom an EVD was placed between February 2007 and November 2009, excluding individuals receiving EVDs due to an infection of a primary device. Three time periods were defined depending on type of EVD in use: Period 1, conventional EVDs; Period 2, either ac-EVDs or conventional EVDs; and Period 3, ac-EVDs. Definite/probable VRIs that occurred during the 3 periods were evaluated and established as determinants of VRIs by using a Cox proportional hazards model. Prolonged systemic antibiotics were given for the duration of EVD placement in each of the 3 periods per institutional policy.

RESULTS

Data from 141 individuals were evaluated; mean patient age was 53.8 ± 17.2 years and 54% were female. There were 2 definite and 19 probable VRIs. The incidence of definite/probable VRI (per 1000 person-catheter days) decreased from Period 1 to 3 (24.5, 16.2, and 4.4 in Periods 1, 2, and 3, respectively; p < 0.0001). Patients with VRIs were more likely to be female than male (23.7% vs 3.1%, p < 0.003) and have had an EVD in place for a longer duration, although there was no significant difference among the 3 periods (7.9 ± 6.7 [Period 1], 8.1 ± 7.1 [Period 2], and 8.6 ± 5.8 [Period 3] mean days; p = 0.87, ANOVA). Analysis of effect modification in a stepwise model showed that period, age, and age and female interaction were significant predictors of VRIs. The period was the strongest predictor of VRI (p = 0.0075). After adjustment for age and age and sex interaction, the survival rate was 53% at the end of Period 2 and 91% at the end of Period 3.

CONCLUSIONS

Rates of VRIs have decreased with the addition of ac-EVDs to the routine use of prolonged systemic antibiotics at the authors' institution.

Transgender patients have particular needs with respect to demographic information and health records; specifically, transgender patients may have a chosen name and gender identity that differs from their current legally designated name and sex. Additionally, sex-specific health information, for example, a man with a cervix or a woman with a prostate, requires special attention in electronic health record (EHR) systems. The World Professional Association for Transgender Health (WPATH) is an international multidisciplinary professional association that publishes recognized standards for the care of transgender and gender variant persons. In September 2011, the WPATH Executive Committee convened an Electronic Medical Records Working Group comprised of both expert clinicians and medical information technology specialists, to make recommendations for developers, vendors, and users of EHR systems with respect to transgender patients. These recommendations and supporting rationale are presented here.