Neonatal diabetes, gallbladder agenesis, duodenal atresia, and intestinal malrotation caused by a novel homozygous mutation in RFX6

Recently, bi-allelic mutations in the transcription factor RFX6 were described as the cause of a rare condition characterized by neonatal diabetes with pancreatic and biliary hypoplasia and duodenal/jejunal atresia. A male infant developed severe hyperglycemia (446mg/dL) within 24h of birth. Acute abdominal concerns by day five necessitated exploratory surgery that revealed duodenal atresia, gallbladder agenesis, annular pancreas and intestinal malrotation. He also exhibited chronic diarrhea and feeding intolerance, cholestatic jaundice, and subsequent liver failure. He died of sepsis at four months old while awaiting liver transplantation. The phenotype of neonatal diabetes with intestinal atresia and biliary agenesis clearly pointed to RFX6 as the causative gene; indeed, whole exome sequencing revealed a novel homozygous RFX6 mutation c.779A>C; p.Lys260Thr (K260T). This missense mutation also changes the consensus 5′ splice donor site before intron 7 and is thus predicted to cause disruption in splicing. Both parents, who were not known to be related, were heterozygous carriers. Targeted genetic testing based on consideration of phenotypic features may reveal a cause among the many genes now associated with heterogeneous forms of monogenic neonatal diabetes. Our study demonstrates the feasibility of using modern sequencing technology to identify one such rare cause. Continued research is needed to determine the possible cost-effectiveness of this approach, especially when clear phenotypic clues are absent. Further study of patients with RFX6 mutations should clarify its role in pancreatic, intestinal and enteroendocrine cellular development and explain features such as the diarrhea exhibited in our case

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Coercivity Behavior In Gd (co1-x Cux)5 System As Function Of The Microstructureevolution

Magnetic measurements, X-ray diffraction and scanning electron microscopy (SEM) experiments were carried out in the as-cast Gd(Co1-x Cux)5 samples with different Co/Cu content. Already in the as cast state, this system shows high coercive field for x=0.3 and a magnetization driven by nucleation of reversal domain. SEM micrograph and microanalysis show possible spinodal decomposition in the as-cast state, hence regions with different Co/Cu-content are observed, while the Gd-content almost does not change. High resolution X-ray diffraction patterns show a main CaCu5-type structure with traces of a secondary phase and distorted peak profiles as function of the Cu content. The evolution of the microstructure is discussed in relation with the Cu incorporation into the CaCu 5-type structure. The Cu addition avoids the formation of the 2:7 phase within the 1:5 matrix, favoring the formation of a more homogeneous Gd(Co,Cu)5 phase. The relation between the observed microstructure and the magnetic behavior is also discussed. © 2013 Elsevier B.V. All rights reserved.4146771Nesbitt, E.A., Willens, R.H., Shenvood, R.C., Buehler, E., Wernick, J.H., (1968) Appl. Phys. Lett., 12 (361)Hasegawa, R., Taylor, R.C., (1975) J. Appl. Phys., 46, p. 3606Senno, H., Tawara, Y., (1974) IEEE Trans. Magn., MAG-10 (2), p. 313Strnat, K.J., Rare earth-cobalt permanent magnets (1988) Handbook of Magnetic Materials, 4. , E.P. Wohlfarth, K.H.J. Buschow (Eds.) ElsevierHumar, K., (1988) J. Appl. Phys., 63 (6)Grössinger, R., Tellez-Blanco, J.C., Turtelli, R.S., Hauser, R., Reiterer, K., Sassik, H., Chouteau, G., (2001) Phys. B, 194, p. 294Seixas, T.M., Machado Da Silva, J.M., Braun, H.F., Eska, G., (2008) J. Appl. Phys., 103, pp. 07b720Seixas, T.M., Salgueiro Da Silva, M.A., Braun, H.F., Eska, G., (2009) J. Appl. Phys., 105, pp. 07E102Kuznetsova, Yu.V., Suponev, N.P., Degteva, O.B., Salev, P.S., (2011) J. Surf. Invest., 5-6, p. 1107Grechishkin, R.M., Kustov, M.S., Cugat, O., Delamare, J., Poulin, G., Mavrudieva, D., Dempsey, N.M., (2006) Appl. Phys. Lett., 89, p. 122505De Oliveira, L.A.S., Sinnecker, J.P., Grössinger, R., Pentón- Madrigal, A., Estévez-Rams, E., (2011) J. Magn. Magn. Mater., 323, p. 1890Hubbard, W.M., Adams, E., Gilfrich, J.V., (1960) J. Appl. Phys. Suppl., 31 (5)Uehara, M., (1980) J. Appl. Phys., 51, p. 5495Uehara, M., (1982) J. Appl. Phys., 53, p. 3730Shidlovsky, I., Wallace, W.E., (1970) J. Solid State Chem., 2, p. 193Chuang, Y.C., Wu, C.H., Chen, H.B., (1985) J. Less-Common Mater., 106, p. 41Estévez-Rams, E., Fidler, J., Pentón, A., Valor-Reed, A., Tellez-Blanco, J.C., Turtelli, R.S., Grössinger, R., (1999) J. Magn. Magn. Mater., 195, p. 595Espina-Hernandez, J.H., Lora-Serrano, R., Knobel, M., Sinnecker, E.H.C.P., De Oliveira, L.A.S., Sinnecker, J.P., Grössinger, R., Estévez-Rams, E., (2009) J. Phys. D Appl. Phys., 42, p. 125005Kahn, Y., (1974) Phys. Status Solidi A, 23 K151Pareti, L., Solzi, M., Marusi, G., (1992) J. Appl. Phys., 72 (7), p. 3009Allen, C.W., Lia, K.C., Miller, A.E., (1977) J. Less-Common Met., 52 (109)Pentón, A., Estévez, E., Lora, R., Espina-Hernandez, J.H., Grössinger, R., Valor-Reed, A., Turtelli, R.S., (2007) J. Alloys Compd., 429, p. 343Lectard, E., Allibert, C.H., Valignat, N., (1994) Proceedings of the Eighth International Symposium on Magnetic Anisotropy and Coercivity in RE-TM Alloys, p. 30

Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study.

BACKGROUND No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer. METHOD This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI: 0.54-1.32, p = 0.5), compared to HIC. CONCLUSION Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer