A Pilot Study of Ultrasound-Guided Cryoablation of Invasive Ductal Carcinomas up to 15 mm With MRI Follow-Up and Subsequent Surgical Resection.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of ultrasound-guided cryoablation in treating small invasive ductal carcinoma and to assess the role of contrast-enhanced (CE) MRI in determining the outcome of cryoablation. SUBJECTS AND METHODS: Twenty consecutive participants with invasive ductal carcinomas up to 15 mm, with limited or no ductal carcinoma in situ (DCIS), underwent ultrasound-guided cryoablation. Preablation mammography, ultrasound, and CE-MRI were performed to assess eligibility. Clinical status was evaluated at 1 day, 7-10 days, and 2 weeks after ablation. CE-MRI was performed 25-40 days after ablation, followed by surgical resection within 5 days. RESULTS: Ultrasound-guided cryoablation was uniformly technically successful, and postablation clinical status was good to excellent in all participants. Cryoablation was not clinically successful in 15% (three of 20 patients). Three participants had residual cancer at the periphery of the cryoablation site. Two participants had viable nonmalignant tissue within the central zone of cryoablation-induced necrosis. Postablation CE-MRI had a sensitivity of 0% (0/3) and specificity of 88% (15/17). The predictive value of negative findings on CE-MRI was 83% (15/18). Correlations between cancer characteristics, cryoablation procedural variables, postablation CE-MRI findings, and surgical specimen features were not statistically significant. There were also no significant differences in participants with or without residual cancer. CONCLUSION: In our pilot experience, ultrasound-guided cryoablation of invasive ductal carcinomas up to 15 mm has a clinical failure rate of 15% but is technically feasible and well tolerated by patients. The majority of cryoablation failures are manifest as DCIS outside the cryoablation field. Postablation CE-MRI does not reliably predict cryoablation outcome.

Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations.

Congenital hyperinsulinism is a condition of dysregulated insulin secretion often caused by inactivating mutations of the ATP-sensitive K+ (KATP) channel in the pancreatic beta cell. Though most disease-causing mutations of the 2 genes encoding KATP subunits, ABCC8 (SUR1) and KCNJ11 (Kir6.2), are recessively inherited, some cases of dominantly inherited inactivating mutations have been reported. To better understand the differences between dominantly and recessively inherited inactivating KATP mutations, we have identified and characterized 16 families with 14 different dominantly inherited KATP mutations, including a total of 33 affected individuals. The 16 probands presented with hypoglycemia at ages from birth to 3.3 years, and 15 of 16 were well controlled on diazoxide, a KATP channel agonist. Of 29 adults with mutations, 14 were asymptomatic. In contrast to a previous report of increased diabetes risk in dominant KATP hyperinsulinism, only 4 of 29 adults had diabetes. Unlike recessive mutations, dominantly inherited KATP mutant subunits trafficked normally to the plasma membrane when expressed in COSm6 cells. Dominant mutations also resulted in different channel-gating defects, as dominant ABCC8 mutations diminished channel responses to magnesium adenosine diphosphate or diazoxide, while dominant KCNJ11 mutations impaired channel opening, even in the absence of nucleotides. These data highlight distinctive features of dominant KATP hyperinsulinism relative to the more common and more severe recessive form, including retention of normal subunit trafficking, impaired channel activity, and a milder hypoglycemia phenotype that may escape detection in infancy and is often responsive to diazoxide medical therapy, without the need for surgical pancreatectomy.

Detecting Congenital Central Hypothyroidism by Newborn Screening: Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency.

BACKGROUND/AIMS: Congenital central hypothyroidism (CH-C) can be detected on newborn screening (NBS) by programs using thyroxine (T4)-reflex thyroid-stimulating hormone (TSH) test approach. CH-C must be distinguished from T4-binding globulin (TBG) deficiency. We sought to determine whether thyroid function tests reliably separate CH-C from TBG deficiency. METHODS: We analyzed NBS and serum free and total T4, T3 resin uptake (T3RU) or TBG, and TSH for infants in the Northwest Regional NBS Program (NWRSP) between the years 2008 and 2015 with either CH-C or TBG deficiency. RESULTS: We discovered a significant overlap in T3RU and TBG levels amongst 21 cases of CH-C and 250 cases of TBG deficiency. Mean serum TBG levels were lower in CH-C cases (20.3 µg/mL, range 14.2-33.3) than what is reported in healthy infants (28.6 µg/mL, range 19.1-44.6). Serum free T4 was lower in CH-C cases than TBG deficiency but did not always differentiate between the two conditions. CONCLUSION: CH-C benefits from detection on NBS but must be distinguished from TBG deficiency. The diagnosis of CH-C rests solely on subnormal serum free T4, but is supported by the demonstration of other pituitary hormone deficiencies. As an overlap exists, serum TBG (or T3RU) levels do not play a role in the diagnosis of CH-C.

Androgen replacement in adolescents and young women with hypopituitarism.

The aim of this study was to test the hypothesis that young women with androgen deficiency due to hypopituitarism would benefit from androgen replacement in the form of dehydroepiandrosterone (DHEA). Five young women, age 15.2-23.1 years, with panhypopituitarism were studied in a 12-month double blind placebo-controlled crossover trial of DHEA replacement in a dose 50 mg/day (Belmar Pharmacy, Lakewood, CO). All had growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and antidiuretic hormone deficiencies. Gonadotropin deficiency was complete in three and partial in two. The patients were evaluated at baseline, 6 months and 12 months. Serum hormone levels, body composition, lumbar bone mineral density (BMD), exercise capacity and tests of psychological function were performed. DHEA replacement restored serum DHEA levels to normal, 359.8+/-337 ng/dl (12.5+/-11.7 nmol/l). The Life Situation Survey showed significantly better life satisfaction on DHEA than placebo (110 vs 102, p = 0.05). Trends for improved maximal oxygen uptake (VO2), and decreased percent body fat did not reach statistical significance. In conclusion, androgen replacement with DHEA should be considered in young women with panhypopituitarism. Further studies over longer periods in larger groups of patients are necessary to better evaluate the effects of DHEA replacement on BMD, muscle strength and body composition.

The paradox of progress: translating Evan Stark's Coercive Control into legal doctrine for abused women.

This article examines Evan Stark's model of coercive control and what this paradigm shift might mean for the law. Coercive control can help redefine both criminal offenses involving domestic violence and defenses available to women who kill their abusers. This redefinition would shift the law away from incident-based violence and toward a more comprehensive and accurate paradigm that accounts for the deprivation of a woman's autonomy within the context of an abusive relationship. Such a change would likely provide more effective state intervention into what were once considered private relationships. Yet, this approach may also have some unintended consequences, including refocusing the law on a victim's mental state and complicity in her own abuse rather than on the harm caused by abusive men. Thus, although the law should more fully account for coercive control, lawyers must be cautiously optimistic in implementing Stark's proposed reforms.

Adolescent thyroid disorders.

Thyroid disorders are common in adolescence. Thyroid nodules can present in this age group, and although most are benign, malignancy is not unheard of. Chronic lymphocytic thyroiditis can present as hypothyroidism, while the adolescent with a goiter due to autoimmune thyroid disease is frequently euthyroid. Graves disease is a common etiology of hyperthyroid presentation in this age group. While there are known genetic and iatrogenic conditions that may predispose thyroid problems, they may also happen randomly in the general population. Thyroid problems may present as a goiter, a nodule, or a general cluster of abnormal symptoms and physical findings. The unique challenge to the provider of adolescent health care is that thyroid problems can adversely affect growth and development during puberty, a crucial period of hormonal interaction. This chapter addresses the diagnosis, treatment alternatives, and prognosis for a variety of common and uncommon thyroid abnormalities in adolescents. Many are readily treatable if recognized promptly, and even thyroid cancer often can be effectively treated and managed. Physicians treating the adolescent population have to be aware of the various thyroid problems that their patients can face.

The use and effectiveness of electrocardiographic telemetry monitoring in a community hospital general care setting.

UNLABELLED: The purpose of this study was to determine if rates of telemetry events differ between patients whose monitoring is appropriately "indicated" versus "not indicated" by systematically applying rigorous criteria for appropriateness of electrocardiogram (ECG) telemetry usage. We performed a retrospective cohort study on 1097 telemetry admissions between January 1, 2000 and March 31, 2000. A convenience sample of 218 patients generated 236 telemetry admissions. One-hundred-sixty-two arrhythmic events were detected during 400 "indicated" telemetry days. Nine arrhythmic events were detected during 345 "not indicated" telemetry days. The relative rate for arrhythmic events was significantly different, at P < 0.0001, with the incidence rate ratio of 15 indicating a very large effect size. Consequently, current use of ECG telemetry may not be optimal, and a prospective analysis of the application of rigorous indications for ECG telemetry needs to be undertaken. IMPLICATIONS: The application of standard criteria to electrocardiogram telemetry admissions found that the majority of abnormal heart rhythms were found when patients met appropriate criteria.