Malignant pheochromocytoma. Chromaffin granule transmitters and response to treatment

Chromaffin granule transmitters such as chromogranin A and catecholamines have been used in the diagnosis of pheochromocytoma, but the diagnostic and prognostic value of chromogranin A have not been explored in malignant pheochromocytoma. We evaluated these transmitters in patients with pheochromocytoma (n=27), both benign (n=13) and malignant (n=14). Patients with benign pheochromocytoma were studied before and after surgical excision (n=6), whereas patients with malignant pheochromocytoma were evaluated before and after combination chemotherapy with regular cycles of cyclophosphamide/dacarbazine/vincristine (nonrandomized trial in n=9). During treatment, patient responses to chemotherapy were divided according to anatomic and clinical criteria: responders (n=5) versus nonresponders (n=4). Plasma chromogranin A rose progressively (P<0.0001) from control subjects (48.0+/-3.0 ng/mL) to benign pheochromocytoma (188+/-40.5 ng/mL) to malignant pheochromocytoma (2932+/-960 ng/mL). Parallel changes were seen for plasma norepinephrine (P<0.0001), though plasma epinephrine was actually lower in malignant than benign pheochromocytoma (P=0.0182). In bivariate analyses, chromogranin A, norepinephrine, and epinephrine discriminated between pheochromocytoma and control subjects (all P<0.0001), whereas in a multivariate analyses, norepinephrine was the best discriminator (P:=0.011). Chromogranin A was significantly different in benign versus malignant pheochromocytoma on both bivariate (P=0.0003) and multivariate (P:=0.011) analyses. After excision of benign pheochromocytoma, chromogranin A (P=0.028), norepinephrine (P=0.047), and epinephrine (P=0.037) all fell to values near normal. During chemotherapy of malignant pheochromocytoma (n=9), plasma chromogranin A (P=0.047) and norepinephrine (P=0.02) fell but not epinephrine. In 5 responders to chemotherapy, there were significant declines in chromogranin A (P=0.03) and norepinephrine (P=0.03) but not epinephrine; in 4 nonresponders, none of the transmitters changed. Plasma chromogranin A varied longitudinally with tumor response and relapse. We conclude that plasma chromogranin A is an effective tool in the diagnosis of pheochromocytoma, and markedly elevated chromogranin A may point to malignant pheochromocytoma. During chemotherapy of malignant pheochromocytoma, chromogranin A can be used to gauge tumor response and relapse.     

Validation of fitness tracker for sleep measures in women with asthma

Objective: Nighttime wakening with asthma symptoms is a key to assessment and therapy decisions, with no gold standard objective measure. The study aims were to (1) determine the feasibility, (2) explore equivalence, and (3) test concordance of a consumer-based accelerometer with standard actigraphy for measurement of sleep patterns in women with asthma as an adjunct to self-report. Methods: Panel study design of women with poorly controlled asthma from a university-affiliated primary care clinic system was used. We assessed sensitivity and specificity, equivalence and concordance of sleep time, sleep efficiency, and wake counts between the consumer-based accelerometer Fitbit Charge? and Actigraph wGT3X+. We linked data between devices for comparison both automatically by 24-hour period and manually by sleep segment. Results: Analysis included 424 938?minutes, 738 nights, and 833 unique sleep segments from 47 women. The fitness tracker demonstrated 97% sensitivity and 40% specificity to identify sleep. Between device equivalence for total sleep time (15 and 42-minute threshold) was demonstrated by sleep segment. Concordance improved for wake counts and sleep efficiency when adjusting for a linear trend. Conclusions: There were important differences in total sleep time, efficiency, and wake count measures when comparing individual sleep segments versus 24-hour measures of sleep. Fitbit overestimates sleep efficiency and underestimates wake counts in this population compared to actigraphy. Low levels of systematic bias indicate the potential for raw measurements from the devices to achieve equivalence and concordance with additional processing, algorithm modification, and modeling. Fitness trackers offer an accessible and inexpensive method to quantify sleep patterns in the home environment as an adjunct to subjective reports, and require further informatics development.     

Preparedness Planning for Emergencies Among Postpartum Women in Arkansas During 2009

PurposeHaving an emergency plan may reduce negative effects of disaster on the health of postpartum women and their infants. However, little is known about the prevalence of emergency plans among postpartum women. In 2009, Arkansas added a question to the Pregnancy Risk Assessment Monitoring System surveillance system about whether women who gave birth that year had an emergency plan. In this study, we first describe the sociodemographic characteristics, disaster experience, and region of residence of postpartum women in Arkansas who indicated that they had an emergency plan for their families in 2009, and second, examine associations between sociodemographic characteristics and disaster experience and the presence of an emergency plan.MethodsMultivariable logistic regression (n = 1,173) was conducted to examine associations between maternal race/ethnicity, sociodemographic characteristics, region of residence, disaster experience, and having a disaster plan. We adjusted for maternal education, federal poverty level, and family size in our final model.FindingsForty-eight percent (n = 559) of women reported having an emergency plan. Hispanic women were less likely to report having a plan compared with non-Hispanic White women (n = 102 [10%]; adjusted prevalence ratio [aPR], 0.6; 95% confidence interval [CI], 0.4–0.9). Families with five or more members were more likely to have a plan compared with smaller families (n = 123 [11%]; aPR, 1.3; 95% CI, 1.1–1.6).ConclusionsPolicymakers and public health practitioners can use these results to promote emergency planning among postpartum women in Arkansas, with special outreach to postpartum women who are Hispanic or have smaller families.     

Identification of Possible Virulence Marker from Campylobacter jejuni Isolates

A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.     

Coffee,caffeine, and risk of completed suicide: Results from three prospective cohorts of American adults

Objective.To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of US men and women. Methods. We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988–2008), 73,820 women in the Nurses’ Health Study (NHS, 1992–2008), and 91,005 women in the NHS II (1993–2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every 4 years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. Results. We documented 277 deaths from suicide. Compared to those consuming ≤ 1 cup/week of caffeinated coffee (< 8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38–0.78) for those consuming 2–3 cups/day and 0.47 (0.27–0.81) for those consuming ≥ 4 cups/day (P trend < 0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63–0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63–0.93) for each increment of 300 mg/day of caffeine. Conclusions. These results from three large cohorts support an association between caffeine consumption and lower risk of suicide.     

Skin pigmentation and genetic variants in an admixed Brazilian population of primarily European ancestry

International Journal of Legal Medicine - Although many genes have been shown to be associated with human pigmentary traits and forensic prediction assays exist (e.g. HIrisPlex-S), the genetic...     

Levels of satisfaction with rheumatoid arthritis treatment and associated alignment between physicians and patients across Latin America

Clinical Rheumatology - Discordance (misalignment) regarding treatment satisfaction may exist in real-life clinical practice between patients and their physicians. We aimed to assess physician and...     

Immunization with genetically attenuated P. falciparum parasites induces long-lived antibodies that efficiently block hepatocyte invasion by sporozoites

Whole-parasite malaria vaccines have shown promise in clinical trials. We recently reported the first human trial of a malaria vaccine based on Plasmodium falciparum genetically attenuated parasites (PfGAP). Herein we report for the first time that PfGAP induces prolonged functional humoral responses in humans. Six volunteers were exposed to 5 bites of PfGAP-infected mosquitoes followed by approximately 200 bites. Plasma collected from all volunteers 3 months after the last exposure efficiently inhibits invasion of hepatocytes by P. falciparum sporozoites. The level of inhibition observed is comparable to that attained using plasma collected after 4–5 intravenously administrations of high numbers of irradiated sporozoites, validating the potential of PfGAP malaria vaccines. Our data highlight the role of antibody responses in pre-erythrocytic stages of human malaria, and suggests that to be protective, malaria vaccines might need to elicit long-lasting functional antibodies in addition to cellular responses.     

Specialized Inpatient Psychiatry for Serious Behavioral Disturbance in Autism and Intellectual Disability

Psychiatric hospitalization of children with autism spectrum disorder and/or intellectual disability is common, however, the effectiveness of this intervention is largely unknown. Thirty-eight clinically-referred children 8–19 years old admitted to a specialized inpatient psychiatry unit were assessed by a consistent caregiver on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale at admission, discharge and 2 months post discharge. There was a decrease in the mean ABC-I score from admission (27.3, SD 7.4) to discharge (11.9, SD 8.8), which was sustained at 2 months post discharge (14.8, SD 9.3) (p < 0.001). Seventy-eight percent of the subjects were rated as “Improved” on the clinician Clinical Global Impressions Improvement scale at discharge. The study is limited by lack of a control group, but offers preliminary evidence for specialized inpatient psychiatry as an intervention for serious behavioral disturbance in this population.     

Clinical significance of isolated v lesions in paediatric renal transplant biopsies: muscular arteries required to refute the diagnosis of acute rejection

Intimal vascular lesions are considered features of acute T‐cell‐mediated rejection yet can occur in the absence of tubulointerstitial inflammation, termed isolated ‘v’ lesions. The clinical significance of these lesions is unclear. The diagnosis requires a biopsy with the presence of arteries. The frequency of adequate biopsies was analysed in 89 renal transplant biopsies from 57 paediatric renal allograft recipients, and the incidence of isolated endarteritis was determined. 60 (67%) biopsies contained an artery and of these, isolated ‘v’ lesions occurred in 6 (10%). 5 (83%) biopsies with isolated ‘v’ lesions were associated with positive DSA, suggesting that these lesions may represent acute antibody‐mediated rejection. Patients with vessel‐negative biopsies had an increased decline in eGFR (median ?20.5, IQR ?24.4 to 1.2 ml/min/1.73 m² vs. ?9.6, IQR ?78.7 to ?6.8 ml/min/1.73 m²; P = 0.01). Patients with vessel‐negative biopsies were more likely to have repeat biopsy for ongoing allograft dysfunction, (25.0% vs. 2.4%; P < 0.01). The data suggest that isolated ‘v’ lesions are more common than previously thought. A significant proportion of biopsies classified as ‘normal’ or ‘borderline change’ in the absence of a large vessel may represent undiagnosed acute rejection. This may result in suboptimal therapy with possible adverse effects on renal outcome.