Publications

BACKGROUND

Heterozygous mutations in melanocortin-4 receptor (MC4R) are the most frequent genetic cause of obesity. Bariatric surgery is a successful treatment for severe obesity. The mechanisms of weight loss after bariatric surgery are not well understood.

METHODS

Ninety-two patients who had Roux-en-Y gastric bypass (RYGB) surgery were screened for MC4R mutations. We compared percent excess weight loss (%EWL) in the four MC4R mutation carriers with that of two control groups: 8 matched controls and with the remaining 80 patients who underwent RYGB.

RESULTS

Four patients were heterozygous for functionally significant MC4R mutations. In patients with MC4R mutations, the %EWL after RYGB (66% EWL) was not significantly different compared to matched controls (70% EWL) and non-matched controls (60% EWL) after 1 year of follow-up.

CONCLUSIONS

This study suggests that patients with heterozygous MC4R mutations also benefit from RYGB and that weight loss may be independent of the presence of such mutations.

PURPOSE OF REVIEW

To provide a narrative synthesis of evidence on interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in individuals with immune-mediated inflammatory disorders (IMIDs).

RECENT FINDINGS

Only a few studies have evaluated IGRAs in IMIDs, and most were small and varied considerably with respect to the use of immunosuppressive medications and types of IMIDs. Current evidence does not clearly suggest that IGRAs are better than tuberculin skin test (TST) in identifying individuals with IMID who could benefit from LTBI treatment. To date, no studies have been done on the predictive value of IGRAs in IMID patients. Important questions remain unanswered as to the impact of immunosuppressive medications and the impact of type of IMID on IGRA performance.

SUMMARY

Despite the lack of clear evidence, there is an increasing tendency for guidelines to prefer IGRA over TST in IMIDs or to recommend both TST and IGRA to enhance sensitivity. We believe the use of either test is acceptable for LTBI screening. Clinicians could consider starting with IGRAs in individuals with a history of Bacille Calmette-Guérin (BCG) vaccination after infancy or with repeated BCG vaccinations. When the index of suspicion for LTBI is high, both IGRA and TST could be performed, especially prior to initiating TNF-α inhibitor therapy. Regardless of the test used, it is important to remember that in the face of immune-suppression, both IGRA and TST can be falsely negative and are thus only diagnostic aids - they will need to be interpreted with other clinical and risk factor data.

BACKGROUND AND OBJECTIVE

The frequency, aetiologies and outcomes of normal chest radiographs (CXRs) among HIV-seropositive patients with suspected pulmonary tuberculosis (TB) have been infrequently described.

METHODS

Consecutive HIV-seropositive adults hospitalized for cough of ≥2 weeks duration at Mulago Hospital (Kampala, Uganda), between September 2007 and July 2008, were enrolled. Baseline CXRs were obtained on admission. Patients with sputum smears that were negative for acid-fast bacilli (AFB) were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii and other fungi. Patients were followed for 2 months after enrolment.

RESULTS

Of the 334 patients, 54 (16%) had normal CXRs. These patients were younger (median age 30 vs 34 years, P = 0.002), had lower counts of CD4+ T lymphocytes (median 13 vs 57 cells/µL, P < 0.001), and were less likely to be smear positive for AFB (17% vs 39%, P = 0.002) than those with abnormal CXRs. Pulmonary TB was the most frequent diagnosis (44%) among those with normal CXRs, followed by unknown diagnoses, pulmonary aspergillosis and pulmonary cryptococcosis. The frequency of normal CXRs was 12% among pulmonary TB patients. There was a trend towards increased 2-month mortality among patients with normal CXRs compared to those with abnormal CXRs (40% vs 29%, P = 0.15).

CONCLUSIONS

Normal CXR findings were common among HIV-seropositive patients with suspected TB, especially those who were young, those with low CD4+ T cell counts and those with sputum smears that were negative for AFB. Mortality was high among those with normal CXRs. Normal CXR findings should not preclude further diagnostic evaluation in this population.

PURPOSE OF REVIEW

To present an updated summary of the relationship between inflammation and localized and generalized bone loss in the rheumatic diseases.

RECENT FINDINGS

In addition to the well established role of inflammatory cytokines in promoting enhanced osteoclast function and bone loss, recent work has discovered the cytokine milieu may also inhibit osteoblast function and bone repair. The WNT and bone morphogenetic protein pathways provide molecular links between inflammation and altered bone homeostasis in chronic inflammatory states. These pathways and others have been the targets of emerging therapies for the management of inflammatory bone loss.

SUMMARY

Inflammation and bone loss are linked through a number of molecular pathways. Both of these processes need to be addressed when designing an effective treatment strategy for the rheumatic diseases.

OBJECTIVE

While inflammatory pain is well described in skeletal muscle, neuropathic muscle pain remains to be clarified. We used 3 well-established rodent models of peripheral neuropathy to evaluate for muscle pain.

METHODS

In rats exposed to either of 2 neurotoxic cancer chemotherapies, paclitaxel or oxaliplatin, or to alcohol consumption, we assessed the evolution of mechanical hyperalgesia in skeletal muscle and skin, in the same animal. To explore the involvement of protein kinase C epsilon (PKCε), a second messenger implicated in some forms of neuropathic pain, antisense oligodeoxynucleotides (AS-ODNs) or mismatch ODNs (MM-ODNs) for PKCε were administered intrathecally.

RESULTS

Rats submitted to models of chemotherapy-induced and alcohol-induced neuropathy developed persistent muscle hyperalgesia, which evolved in parallel in muscle and skin. The administration of PKCε AS, which has been shown to mediate cutaneous hyperalgesia in paclitaxel and ethanol models of neuropathic pain, also inhibited muscle hyperalgesia induced by these agents. Stopping AS-ODN was associated with the reappearance of hyperalgesia at both sites. The AS-ODN to PKCε treatment was devoid of effect in both muscle and skin in the oxaliplatin neuropathy model.

INTERPRETATION

Our results support the suggestion that neuropathic muscle pain may be a greater clinical problem than generally appreciated.

BACKGROUND

Intrauterine devices are cost-effective if used for 2 or more years. Early discontinuation may lead to reduced cost-effectiveness of this method and unintended pregnancy if other contraceptives are not used. This study sought to examine rates and reasons for discontinuation of IUS use in adolescents versus older women and nulliparous versus parous women, as these groups may be more likely to discontinue use.

STUDY DESIGN

Retrospective cohort study of women receiving a levonorgestrel IUS between June 2005 and April 2008 was conducted. Medical records were reviewed for all visits following placement of the IUS; rates and reasons for IUS discontinuation were calculated and categorized. Data were examined under two scenarios: (1) assuming that all women not seen for follow-up continued IUS use and (2) only including women with follow-up visits. Cox regression was used to control for age, parity, race and marital status in comparing rates of IUS discontinuation and expulsion in nulliparous versus parous women and adolescents versus older women.

RESULTS

Of the 828 women included in this analysis, 104 (12.6%) were nulliparous, and 131 (15.8%) were ≤20 years of age. Nulliparous women were not more likely than parous women to have expelled their IUS [hazard ratio (95% confidence interval), 1.40 (0.57, 3.43)]. Adolescent women were more likely to experience expulsion than older women, although this did not reach statistical significance [hazard ratio, 1.49 (0.76, 2.92)]. When we looked at reasons for IUS removal, we found that nulliparous women were not more likely than parous women to have their IUS removed because of dissatisfaction with the contraceptive method (6.7% vs. 11.5%, p=.15) or desire to become pregnant (1.9% vs. 2.6%, p=.50). Similarly, adolescents were not more likely than older women to have their IUS removed because of dissatisfaction with the contraceptive method (10.7% vs. 10.9%, p=.94) or desire to become pregnant (3.1% vs. 2.4%, p=.43).

CONCLUSIONS

Adolescents and nulliparous women are not more likely to prematurely discontinue use of their IUS than adult or parous women.

Women gain visceral fat during pregnancy. Studies examining the impact of breastfeeding on maternal body composition are inconclusive. We examined the extent to which breastfeeding was associated with visceral adiposity in a sample of US women. This was a cross-sectional analysis of 351 women aged 45-58 years, who were free of clinical cardiovascular disease and had not used oral contraceptives or hormone replacement therapy in the 3 months prior to enrollment in the Study of Women's Health Across the Nation (SWAN)-Heart Study (2001-2003). History of breastfeeding was self-reported. Computed tomography was used to assess abdominal adiposity. Among premenopausal/early-peri-menopausal mothers, those who never breastfed had 28% greater visceral adiposity (95% confidence interval (CI): 11-49, P = 0.001), 4.7% greater waist-hip ratio (95% CI: 1.9-7.4, P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71-9.26, P < 0.001) than mothers who breastfed all of their children for ≥3 months in models adjusting for study site; age; parity; years since last birth; socioeconomic, lifestyle, and family history variables; early adult BMI; and current BMI. In comparison to women who were nulliparous, mothers who breastfed all of their children for ≥3 months had similar amounts of visceral fat (P > 0.05). In contrast, premenopausal/early-peri-menopausal mothers who had never breastfed had significantly greater visceral adiposity (42% (95% CI: 17-70), P < 0.001), waist circumference (6.15 cm (95% CI: 2.75-9.56), P < 0.001), and waist-hip ratio (3.7% (95% CI: 0.69-6.8), P = 0.02) than nulliparous women. No significant relationships were observed among late peri-menopausal/postmenopausal women. In conclusion, until menopause, mothers who did not breastfeed all of their children for ≥3 months exhibit significantly greater amounts of metabolically active visceral fat than mothers who had breastfed all of their children for ≥3 months.

BACKGROUND AND PURPOSE

Quality of care delivered in the inpatient and ambulatory settings may be correlated within an integrated health system such as the Veterans Health Administration. We examined the correlation between stroke care quality at hospital discharge and within 6 months postdischarge.

METHODS

We conducted a cross-sectional hospital-level correlation analyses of chart-abstracted data for 3467 veterans discharged alive after an acute ischemic stroke from 108 Veterans Health Administration medical centers and 2380 veterans with postdischarge follow-up within 6 months in fiscal year 2007. Four risk-standardized processes of care represented discharge care quality: prescription of antithrombotic and antilipidmic therapy, anticoagulation for atrial fibrillation, and tobacco cessation counseling along with a composite measure of defect-free care. Five risk-standardized intermediate outcomes represented postdischarge care quality: achievement of blood pressure, low-density lipoprotein, international normalized ratio, and glycosylated hemoglobin target levels, and delivery of appropriate treatment for poststroke depression along with a composite measure of achieved outcomes.

RESULTS

Median risk-standardized composite rate of defect-free care at discharge was 79%. Median risk-standardized postdischarge rates of achieving goal were 56% for blood pressure, 36% for low-density lipoprotein, 41% for international normalized ratio, 40% for glycosylated hemoglobin, and 39% for depression management and the median risk-standardized composite 6-month outcome rate was 44%. The hospital composite rate of defect-free care at discharge was correlated with meeting the low-density lipoprotein goal (r=0.31; P=0.007) and depression management (r=0.27; P=0.03) goal but was not correlated with blood pressure, international normalized ratio, glycosylated hemoglobin goals, nor with the composite measure of achieved postdischarge outcomes (probability values >0.13).

CONCLUSIONS

Hospital discharge care quality was not consistently correlated with ambulatory care quality.