Osmania General Hospital

BACKGROUND:Patients with diabetes frequently have multivessel disease and are at increased risk of adverse outcomes. The outcomes with a new-generation ultra-thin strut sirolimus-eluting stent (SES) vs everolimus-eluting stent (EES) is unclear as stent-to-stent comparison trials have routinely excluded these patients or included a small proportion of such patients. OBJECTIVES:The purpose of this study was to compare the clinical outcomes of ultra-thin biodegradable polymer (BP) SES vs durable polymer (DP) EES when combined with contemporary optimal medical therapy in patients with diabetes and multivessel disease. METHODS:The TUXEDO-2 is an investigator-initiated prospective, open-label, multicenter, 2 × 2 factorial, randomized (1:1) controlled trial. Patients undergoing percutaneous coronary intervention were randomized to receive either a Supraflex Cruz SES or Xience EES. The participants were also randomized to Ticagrelor or Prasugrel. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction or ischemia-driven target lesion revascularization at 1-year follow up. The trial was designed to test noninferiority of BP-SES vs DP-EES, with a noninferiority margin of 4.5% (1-sided upper 97.5% confidence bound). RESULTS:Among the 1,800 patients randomized, mean age was 60.3 years with 28% of participants being women. At 1 year, the primary endpoint of target lesion failure occurred in 148 patients, including 70 patients (7.92%) in the BP-SES group and 78 patients (8.75%) in the DP-EES group. The risk difference of -0.83 percentage points (1-sided upper 97.5% confidence bound 3.42%) met the prespecified noninferiority margin (PNI = 0.005). There were no significant differences in cardiac death (3.6% vs 3.4%), target vessel myocardial infarction (6.61% vs 7.54%), and ischemia-driven target lesion revascularization (0.8% vs 1.0%) between the 2 groups. Nonfatal myocardial infarction (4.7% vs 6.4%) and stent thrombosis was similar (1.0 % vs 0.7%) between the 2 groups. CONCLUSIONS:In patients with diabetes and multivessel disease undergoing percutaneous coronary intervention, ultra-thin biodegradable polymer SES was noninferior to durable polymer EES at 1 year follow-up. (Trial Registration Number CTRI/2019/11/022088).

Abstract Introduction Pituitary Stalk Interruption Syndrome is a rare disorder with incidence of 0.5 per 100000 births. Ectopic posterior pituitary (EPP) is the cardinal feature. MRI shows a triad of-thin/absent stalk, EPP, Anterior pituitary hypoplasia. GH deficiency is seen in almost 100% cases. Isolated sparing of TSH has also been described. DI is very rare. We describe 12 cases of PSIS that presented to a tertiary care center. Case summary Age/Gender Presenting complaint Height SDS GH(Peak)(ng/ml) T3/T4/TSH LH/FSH Cortisol(mcg/dl) MRI 1 4/m Hypoglycemic seizuresMicropenis cryptorchidism −3.95 2.83 97 ng/dL7.3 mcg/dl1.105 mIU/mL Post Hcg T: 208 ng/dL 21.77 EPP/Thin infundibulum/ Pituitary Hypoplasia 2 18/m Short statureStalled puberty −6 1.01 90 ng/dL8.3 mcg/dl2.1 mIU/mL 1.23/2.25T: 266 ng/dL 21.27 EPP/Thin infundibulum/ Pituitary Hypoplasia 3 16/f Short statureDelayed puberty −4.5 1.8 T4 3.5 mcg/dlTSH 3.5 1.26/2.95E2 13.09 pg/mL On Replacement EPP/Thin infundibulum/Pituitary Hypoplasia 4 15/f Short stature stalled puberty −4 0.4 T4 9.9 mcg/dlTSH 6.72 0.52/1.62E2 < 5 pg/mL 26.7 EPP/Thin infundibulum/Pituitary Hypoplasia 5 4/m Hypoglycemic seizures −3 0.41 T4 8. mcg/dlTSH 2.7 23 EPP/Absent Stalk/ Ant. Pituitary Hypoplasia 6 1 mo/m Hypoglycemic seizuresNeonatal jaundice Random 2.74 T4 2.96 mcg/dlTSH 3.28 2.14/1.43T: 116 ng/ml Critical sample 1.88 EPP/Thin infundibulum/Ant. Pituitary Hypoplasia 7 11/m Short stature micropenis −3.5 0.5 FT4 0.7 ng/mlTSH 2.5 27.80 EPP/Absent Stalk/ Pituitary Hypoplasia 8 11/m Short stature micropenis −5.2 0.19 FT4 0.97 ng/mlTSH 1.47 23.25 EPP/Absent Stalk/ Pituitary Hypoplasia 9 12/m Short stature micropenis −3.21 0.235 T4 6 mcg/dlTSH 1.8 24 EPP/hypoplastic infundibulum 10 8/f Short stature −4.38 0.20 T4 13.1 mcg/dlTSH 3.86 24.86 EPP/Absent Stalk/ Ant. Pituitary Hypoplasia 11 7/f Short stature −3.95 0.5 T4 11.1 mcg/dlTSH 4.86 21 EPP/Absent Stalk/ Ant. Pituitary Hypoplasia 12 4/m Short stature micropenis −3.06 1.03 T4 9.8 mcg/dlTSH 3.4 26 EPP/Absent Stalk/ Ant. Pituitary Hypoplasia 13 1/m Asymptomatic, 3 siblings affected −1.58 1.5 T4 12. mcg/dlTSH 2.4 32 EPP/Absent Stalk/ Ant. Pituitary Hypoplasia Discussion All subjects had GH deficiency, 2 subjects had central hypocortisolism. 3 subjects had central hypothyroidism. The 2nd most common hormonal defect was hypogonadotropic hypogonadism. 4 siblings had isolated GH deficiency. Early childhood and neonatal presentation was with hypoglycemia. Children and adolescents presented with short stature and delayed puberty. Conclusions Our cohort highlights the entire spectrum of PSIS from neonatal hypoglycemia to childhood short stature and delayed puberty.

Abstract Introduction Virilization in a female child is due to androgen exposure during 10-12 weeks of gestation. The most common cause is CAH due to 21 OH deficiency. Placental Aromatase deficiency is a rare disorder that leads to defective conversion of androgens into estrogens by the placenta, thus causing maternal and fetal virilization. The effected infants present with atypical genitalia and no features of CAH like salt wasting crisis or hyperpigmentation and the virilization is characteristically non progressive in the immediate postnatal period. Case Presentation A 2 months old child, reared as a female was brought with history of enlarged phallic structure noted at birth. There was no history of pigmentation or crisis. Antenatally, mother had a severe form of cystic acne. On examination, Genitalia were female looking with an enlarged phallic structure of 15 mm in length. There were no palpable gonads, labioscrotal swellings or inguinal hernias. There was a single urogenital opening, Prader stage 3, with evidence of posterior fusion of labioscrotal folds. No hyperpigmentation or rugosity was seen. EGS was 2.5 with an anogenital ratio of 0.7. Serum potassium- 4.9 meq/l. Stimulated 17 OHP-75 ng/dl, Cortisol-41.8 microgram/dl-Normal. Androstenedione was elevated at 392 ng/dl and testosterone was also elevated, 70 ng/dl. FSH was elevated at 25.34 mIU/mL. MRI pelvis identified the presence of Uterus and Ovaries. In view of elevated androgens, no biochemical features of CAH and history of maternal virilization, Aromatase deficiency was suspected and whole exome sequencing was sent A Homozygous mutation in CYP19A1 gene with a novel c.[1369C>T] variant on exon 10 was identified. The latest follow up was at 12 months of age where the child was well and maternal acne was spontaneously resolving. Treatment The proposed management is usually estrogen supplementation at puberty for development of secondary sexual characters and preserving bone mineral density. Monitoring for Rupture of ovarian cysts. The child was not started on any estrogen. Follow-up The child was last seen at 12 months of age, was thriving well. Acne almost completely resolved in the mother. The child is planned for feminizing genitoplasty. Conslusion We hereby present a case of virilization in mother and neonate due to placental aromatase deficiency. This is a rare disorder can be suspected when there is history of antenatal maternal virilization. The genetic variant in our case is a novel mutation. The identification of this disease has important therapeutic implications for treatment and followup.