Laura E. Dichtel

Lateral entry compared with medial and lateral entry pin fixation for completely displaced supracondylar humeral fractures in children. A randomized clinical trial.

BACKGROUND Closed reduction and percutaneous pin fixation is the treatment of choice for completely displaced (type-III) extension supracondylar fractures of the humerus in children, although controversy persists regarding the optimal pin-fixation technique. The purpose of this study was to compare the efficacy of lateral entry pin fixation with that of medial and lateral entry pin fixation for the operative treatment of completely displaced extension supracondylar fractures of the humerus in children. METHODS This prospective, randomized clinical trial had sufficient power to detect a 10% difference in the rate of loss of reduction between the two groups. The techniques of lateral entry and medial and lateral entry pin fixation were standardized in terms of the pin location, the pin size, the incision and position of the elbow used for medial pin placement, and the postoperative course. The primary study end points were a major loss of reduction and iatrogenic ulnar nerve injury. Secondary study end points included radiographic measurements, clinical alignment, Flynn grade, elbow range of motion, function, and complications. RESULTS The lateral entry group (twenty-eight patients) and the medial and lateral entry group (twenty-four patients) were similar in terms of mean age, sex distribution, and preoperative displacement, comminution, and associated neurovascular status. No patient in either group had a major loss of reduction. There was no significant difference between the rates of mild loss of reduction, which occurred in six of the twenty-eight patients treated with lateral entry and one of the twenty-four treated with medial and lateral entry (p = 0.107). There were no cases of iatrogenic ulnar nerve injury in either group. There were also no significant differences (p > 0.05) between groups with respect to the Baumann angle, change in the Baumann angle, humerocapitellar angle, change in the humerocapitellar angle, Flynn grade, carrying angle, elbow flexion, elbow extension, total elbow range of motion, return to function, or complications. CONCLUSIONS With use of the specific techniques employed in this study, both lateral entry pin fixation and medial and lateral entry pin fixation are effective in the treatment of completely displaced (type-III) extension supracondylar fractures of the humerus in children. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Chronic recurrent anterior sternoclavicular joint instability: results of surgical management.

Chronic anterior sternoclavicular joint (SCJ) instability may cause pain and persistent functional limitation in active patients. Although SCJ reconstruction and medial clavicular resection have been advocated in these situations, the results of surgical treatment are not well characterized. The purpose of this investigation was to determine the functional outcome of surgical treatment in adolescent and young adult patients with chronic recurrent anterior SCJ instability. Fifteen patients with chronic recurrent anterior SCJ instability refractory to nonoperative therapy who underwent joint reconstruction or medial clavicular resection were evaluated for pain and function using the American Shoulder and Elbow Surgeons (ASES) Standard Shoulder Assessment Form and the Simple Shoulder Test (SST). At average follow-up of 55 months, the mean ASES score was 85 and the mean SST score was 10.9. Sixty percent of patients reported stable, pain-free joints, although 87% (n = 13) reported some limitations of athletic or recreational activity. There were no surgical complications, and no patient underwent subsequent revision procedures. Although subsequent activity modification is often required, surgical treatment of chronic anterior SCJ instability in adolescents and young adults can provide near-complete pain relief and return of shoulder and upper extremity function.

Overweight/Obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency.

CONTEXT Obesity is associated with diminished GH secretion, which may result in the overdiagnosis of adult GH deficiency (GHD) in overweight/obese pituitary patients. However, there are no body mass index (BMI)-specific peak GH cutoffs for the glucagon stimulation test (GST), the favored dynamic test for assessing adult GHD in the United States. OBJECTIVE The objective of the study was to determine a peak GH cutoff level for the diagnosis of adult GHD in overweight/obese individuals using the GST. DESIGN This was a retrospective, cross-sectional study. SETTING The study was conducted at Massachusetts General Hospital and Oregon Health and Science University. METHODS A total of 108 subjects with a BMI ≥ 25 kg/m(2) were studied: healthy controls (n = 47), subjects with total pituitary deficiency (TPD) (n = 20, ≥ 3 non-GH pituitary hormone deficiencies), and subjects with partial pituitary deficiency (PPD) (n = 41, 1-2 non-GH pituitary hormone deficiencies). INTERVENTION The intervention consisted of a standard 4-hour GST. MAIN OUTCOME MEASURES The main outcome measure was peak GH level on GST. RESULTS Using the standard peak GH cutoff of 3 ng/mL, 95% of TPD cases (19 of 20), 80% of PPD (33 of 41), and 45% of controls (21 of 47) were classified as GHD. In receiver-operator characteristic curve analysis (controls vs TPD), a peak GH value of 0.94 ng/mL provided the greatest sensitivity (90%) and specificity (94%). Using a peak GH cutoff of 1 ng/mL, 6% of controls (3 of 47), 59% of PPDs (24 of 41), and 90% of TPDs (18 of 20) were classified as GHD. BMI (R = -0.35, P = .02) and visceral adipose tissue (R = -0.32, P = .03) negatively correlated with peak GH levels in controls. CONCLUSION A large proportion of healthy overweight/obese individuals (45%) failed the GST using the standard 3 ng/mL GH cutoff. Overweight/obese pituitary patients are at risk of being misclassified as GHD using this cutoff level. A 1-ng/mL GH cutoff may reduce the overdiagnosis of adult GHD in overweight/obese patients.

Cortisol Measures Across the Weight Spectrum

CONTEXT There are conflicting reports of increased vs decreased hypothalamic-pituitary-adrenal (HPA) activation in obesity; the most consistent finding is an inverse relationship between body mass index (BMI) and morning cortisol. In anorexia nervosa (AN), a low-BMI state, cortisol measures are elevated. OBJECTIVE This study aimed to investigate cortisol measures across the weight spectrum. DESIGN AND SETTING This was a cross-sectional study at a clinical research center. PARTICIPANTS This study included 60 women, 18-45 years of age: overweight/obese (OB; N = 21); AN (N = 18); and normal-weight controls (HC; N = 21). MEASURES HPA dynamics were assessed by urinary free cortisol, mean overnight serum cortisol obtained by pooled frequent sampling every 20 minutes from 2000-0800 h, 0800 h serum cortisol and cortisol-binding globulin, morning and late-night salivary cortisol, and dexamethasone-CRH testing. Body composition and bone mineral density (BMD) were assessed by dual-energy x-ray absorptiometry. RESULTS Cortisol measures demonstrated a U-shaped relationship with BMI, nadiring in the overweight-class I obese range, and were similarly associated with visceral adipose tissue and total fat mass. Mean cortisol levels were higher in AN than OB. There were weak negative linear relationships between lean mass and some cortisol measures. Most cortisol measures were negatively associated with postero-anterior spine and total hip BMD. CONCLUSIONS Cortisol measures are lowest in overweight-class I obese women-lower than in lean women. With more significant obesity, cortisol levels increase, although not to as high as in AN. Therefore, extreme underweight and overweight states may activate the HPA axis, and hypercortisolemia may contribute to increased adiposity in the setting of caloric excess. Hypercortisolemia may also contribute to decreased BMD and muscle wasting in the setting of both caloric restriction and excess.

Osteogenesis imperfecta misdiagnosed as child abuse.

The differential diagnosis of child abuse includes osteogenesis imperfecta (OI). Mild phenotypes of OI may be misdiagnosed as child abuse. The purpose of this study was to review the experience of families in which OI was misdiagnosed as child abuse. Sixty-one potential cases of misdiagnosis were identified from a lay support organization. Upon review of the medical records, 33 cases were identified with a confirmed diagnosis of OI (skin biopsy or DNA blood test). Questionnaires were given to families to describe their condition and experiences. There were 19 male and 14 female children. Mean age at presentation was 7.1 months (range: 1–23 months). All patients had fractures and the presenting symptoms included pain (n=14), swelling (n=7), decreased limb movement (n=5), or unusual limb position (n=2). Abnormal radiograph findings consistent with OI were found in 19 of 33 patients (58%), clinical findings of OI were present in 23 of 33 patients (70%), and a family history that could be supportive of OI was present in 18 of 33 families (55%). Children were removed from the family in 70% of cases and older siblings were removed from the family in 62% of cases. The mean age at the time of diagnosis of OI was 10.5 months (range: 3–35 months). The consequences of misdiagnosis of OI as child abuse are devastating to the family. OI should be considered in all cases of suspected child abuse. In children with any clinical, radiographic, or family history features of OI, early involvement of a bone specialist and performance of laboratory testing should be considered to establish a timely and accurate diagnosis.

Renal artery revascularization in patients with atherosclerotic renal artery stenosis and impaired renal function: conservative management versus renal artery stenting.

BACKGROUND The impact of percutaneous renal artery angioplasty and stenting (PTRAS) for treatment of atherosclerotic renal artery stenosis (ARAS) is not fully understood, especially in patients with chronic kidney disease (CKD). The goal of this study was to compare renal outcomes in patients treated with PTRAS with those managed conservatively. METHODS Retrospective cohort study of 118 prevalent patients with significant ARAS and moderate-to-severe CKD who were treated medically (n = 71) or with PTRAS (n = 47). The primary endpoint was change in renal function over the first year after diagnosis/treatment. RESULTS Average age was 73 +/- 8 years, baseline glomerular filtration rate was 37 +/- 15 ml/min/1.73 m2, and average follow-up was 34 months. Baseline characteristics were similar between the two groups, with the exception of higher diastolic blood pressure in the PTRAS group (75 versus 70 mmHg, p = 0.028). There were no significant differences between the two groups during follow-up. The decline in glomerular filtration rate was similar in both groups (-1.6 ml/min/1.73 m2 in the medical group versus -1.4 ml/min/1.73 m2 in the PTRAS group, p = 0.938). Multivariate models did not indicate an association between treatment modality and changes in renal function or rates of ESRD or death. CONCLUSION In patients with advanced kidney disease, medical therapy and renal artery stenting appear comparable in stabilizing renal function for ARAS.

The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease.

Objectives:The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies.Methods:A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary’s Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1.Results:Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels.Conclusions:Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets.

Neuroactive Steroids and Affective Symptoms in Women Across the Weight Spectrum

3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABAA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective comorbidities and hypothalamic–pituitary–gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum. We hypothesized that serum allopregnanolone and 3α-androstanediol levels would be decreased in AN compared with healthy controls (HC) and negatively associated with affective symptoms throughout the weight spectrum, independent of body mass index (BMI). Thirty-six women were 1 : 1 age-matched across three groups: AN, HC, and overweight/obese (OW/OB). AN were amenorrheic; HC and OW/OB were studied in the follicular phase. Fasting serum neuroactive steroids were measured by gas chromatography/mass spectrometry. Mean Hamilton depression and anxiety scores were highest in AN (p<0.0001). Mean serum allopregnanolone was lower in AN and OW/OB than HC (AN 95.3±56.4 vs OW/OB 73.8±31.3 vs HC 199.5±167.8 pg/ml, p=0.01), despite comparable mean serum progesterone. Allopregnanolone levels, but not progesterone levels, were negatively associated with depression and anxiety symptom severity, independent of BMI. Serum 3α-androstanediol levels did not differ among groups and were not associated with depression or anxiety scores, despite a significant negative association between free testosterone levels and both anxiety and depression severity. In conclusion, women at both extremes of the weight spectrum have low mean serum allopregnanolone, which is associated with increased depression and anxiety severity, independent of BMI. Neuroactive steroids such as allopregnanolone may be potential therapeutic targets for depression and anxiety in traditionally treatment-resistant groups, including AN.

Preventing and treating maternal hypothyroidism during pregnancy.

Purpose of review Thyroid disease is common during pregnancy. There are multiple alterations in maternal thyroid physiology, leading to an increased demand for thyroid hormone during gestation, that have significant implications for both maternal and fetal health. Importantly, pregnant reference ranges must be used for appropriate diagnosis and treatment of maternal hypothyroidism. There is currently broad interest in the maternal and fetal complications of hypothyroidism during pregnancy, with significant debate regarding the nuances of screening, despite universal agreement regarding the need for treatment. Recent findings Current literature has provided new evidence demonstrating maternal and fetal complications of hypothyroidism during pregnancy. There is evidence for improved outcomes with appropriate treatment of maternal hypothyroidism. Summary Although universal screening for hypothyroidism in pregnancy is currently controversial, it is increasingly apparent that maternal hypothyroidism can significantly affect both maternal and fetal health outcomes. Because of the ease and low risk of treatment, current recommendations emphasize appropriate case recognition and treatment to minimize the risk of unnecessary complications.

Short- and Long-Term Reproducibility of Intrahepatic Lipid Quantification by 1H-MR Spectroscopy and CT in Obesity.

Objective This study aimed to assess short- and long-term reproducibility of intrahepatic lipid (IHL) quantification by proton magnetic resonance spectroscopy (1H-MRS) and computed tomography (CT). Methods Sixteen obese subjects underwent 1H-MRS using a single-voxel point-resolved single-voxel spectroscopy sequence at 3 T and noncontrast single-slice CT of the liver. Measurements were repeated after 6 weeks and 6 months. Clinical parameters (weight, activity, serum lipids) were collected. Short-term (baseline to 6 weeks) and long-term (baseline to 6 months) reproducibility of IHL was assessed by coefficient of variance (CV), SD, and intraclass correlation coefficient (ICC). Results Short-term reproducibility and long-term reproducibility of 1H-MRS were as follows: CV, 5.9% to 18.8%; SD, 0.7 to 1.9; and ICC, 0.998 to 0.995 (95% confidence interval, 0.942–0.999). Short-term reproducibility and long-term reproducibility of CT were as follows: CV, 4.4% to 14.2%; SD, 2.4 to 8.7; and ICC, 0.766 to 0.982 (95% confidence interval, 0.271–0.994). There was no significant change in clinical parameters (P > 0.3). Conclusions Proton magnetic resonance spectroscopy and CT are reproducible methods for short- and long-term quantification of IHL content. Our results can guide sample size calculations for interventional and longitudinal studies.