Mutations in STAT3 underlie sporadic and dominant forms of the hyper-IgE syndrome, an immunodeficiency syndrome involving increased innate immune response, recurrent infections, and complex somatic features.

Objective To describe the genotypes, phenotypes, immunophenotypes, and treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), a rare autoinflammatory disease, in 5 patients. Methods Clinical information was gathered from medical records and through interviews with 5 patients from 4 kindreds. PSTPIP1 (CD2BP1) exon 10 and exon 11 sequencing was performed in each patient. Neutrophil granule content and cytokine levels were determined in plasma and stimulated peripheral blood mononuclear cells (PBMCs) from patients and controls. Results We identified 2 previously described PAPA syndrome–associated PSTPIP1 mutations, A230T and E250Q, and a novel change, E250K. Disease penetrance was incomplete, with variable expressivity. The cutaneous manifestations included pathergy, cystic acne, and pyoderma gangrenosum. Interleukin-1 (IL-1β) and circulating neutrophil granule enzyme levels were markedly elevated in patients compared to those in controls. PBMC stimulation studies demonstrated impaired production of IL-10 and enhanced production of granulocyte–macrophage colony-stimulating factor. Good resolution of pyoderma gangrenosum was achieved in 3 patients with tumor necrosis factor (TNFα) blockade treatment. Conclusion This analysis of 5 patients demonstrates that mutations in PSTPIP1 are incompletely penetrant and variably expressed in the PAPA syndrome. Neutrophil granule proteins are markedly elevated ex vivo and in the plasma, and elevated levels might be compatible with a diagnosis of PAPA syndrome. TNFα blockade appears to be effective in treating the cutaneous manifestations of PAPA syndrome.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5 , ATP1A1 , ATP2B3 , and CACNA1D . Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population. In the present study, we investigated genetic characteristics of APAs in blacks using a CYP11B2 (aldosterone synthase) immunohistochemistry-guided next-generation sequencing approach. The adrenal glands with adrenocortical adenomas from 79 black patients with primary aldosteronism were studied. Seventy-three tumors from 69 adrenal glands were confirmed to be APAs by CYP11B2 immunohistochemistry. Sixty-five of 73 APAs (89%) had somatic mutations in aldosterone-driver genes. Somatic CACNA1D mutations were the most prevalent genetic alteration (42%), followed by KCNJ5 (34%), ATP1A1 (8%), and ATP2B3 mutations (4%). CACNA1D mutations were more often observed in APAs from males than those from females (55% versus 29%, P =0.033), whereas KCNJ5 mutations were more prevalent in APAs from females compared with those from males (57% versus 13%, P <0.001). No somatic mutations in aldosterone-driver genes were identified in tumors without CYP11B2 expression. In conclusion, 89% of APAs in blacks harbor aldosterone-driving mutations, and unlike Europeans and East Asians, the most frequently mutated aldosterone-driver gene was CACNA1D . Determination of racial differences in the prevalence of aldosterone-driver gene mutations may facilitate the development of personalized medicines for patients with primary aldosteronism.

We reviewed diabetes apps for Android smartphones. We compiled a list of free and paid apps in April 2011 by searching the Android Market for apps which could track self-monitoring of blood glucose (SMBG), diabetes medications or calculate prandial insulin dosages. Two reviewers independently evaluated six features per app, using a five-point Likert scale. The sum of the six ratings was the composite usability score, and the mean score of an app's features was the average usability score. Of the 80 Android diabetes apps identified, 42 unique apps were eligible for the study. SMBG recording was present in 36 (86%) of the apps, a tool to track insulin or oral diabetic medications was found in 19 (45%) apps, and a prandial insulin dose calculator existed for 11 (26%) apps. Eighteen apps were free of charge and the other 24 apps had a mean purchase price of $2.86 (range 0.99-6.99). The mean composite usability score was 11.3 out of a possible 30. The mean average usability score was 3.0 out of a possible 5.0. Only four of the 42 apps had a composite usability score above 20 and none offered direct data input from glucometers, suggesting that few provided a comprehensive method of diabetes management. The apps Glucool Diabetes, OnTrack Diabetes, Dbees and Track3 Diabetes Planner were the highest rated. Clinicians may find it useful to recommend these apps.