Angiotensin converting enzyme genotype affects development and course of sarcoidosis in Asian Indians

BACKGROUND AND OBJECTIVES: Studies of serum angiotensin converting enzyme (SACE) activity and its association with ACE gene insertion/deletion (I/D) polymorphism in relation to sarcoidosis have yielded variable results. This has been attributed to possible ethnic differences. Present study was designed to evaluate the relationship between I/D polymorphism and susceptibility to develop sarcoidosis and its effect on SACE activity and disease course in Asian Indian patients with sarcoidosis. METHODS: ACE genotyping was performed in 72 consecutive patients with sarcoidosis and 199 controls (96 normal healthy individuals and 103 tuberculosis patients taken as disease controls). SACE activity was determined in all patients with sarcoidosis. Various parameters were compared amongst patients with different genotypes as well as between sarcoidosis and control groups. RESULTS: Gene frequency of I and D in control group was 0.6 and 0.4, whereas in patients with sarcoidosis it was 0.35 and 0.65 respectively (p < 0.001). For individuals with D allele (DD&ID genotypes), odds ratios for developing sarcoidosis were 9.0 (95% CI: 3.4; 23.7) and 5.5 (95% CI: 2.2; 13.6) respectively considering individuals with II genotype as reference. Mean SACE activity was highest in patients with DD genotype and followed an order of DD > ID > II. Good response to initial corticosteroids was seen in 6 of 6 (100%) patients with II genotype whereas in only 32 of 37 (84%) with ID and 16 of 25 (64%) with DD (p = 0.013). INTERPRETATION AND CONCLUSION: In Asian Indian population 'D' allele is associated with an increased risk for development of sarcoidosis and patients with 'D' allele show poor response to corticosteroids.     

Perinatal outcome of twin pregnancies according to chorionicity: an observational study from tertiary care hospital

Objective: To assess the perinatal outcome in twin pregnancies according to chorionicity.

Methods: This was a retrospective cohort study of twin pregnancies from January 2001 to December 2012. Maternal and perinatal outcomes of monochorionic (MC) and dichorionic (DC) twins were compared by using chi-square and t-test. Perinatal complications were compared by adjusted odds ratio using logistic regression at 5% level of significance.

Results: Among 391 twin pregnancies, 116 (29.6%) were MC and 275 (72.95%) were DC. In MC twins, the rate of miscarriage was three fold higher than DC (12.6% versus 4.4%; p-value?p value?p value?=?0.042] more likely to be delivered preterm. Likewise, neonatal intensive care admission for MC was 2.23 times [CI (1.08–4.06), p-value?=?0.03], congenital anomalies were 4.75 times [CI (1.22–18.4), p value?=?0.024]. Fetal growth restriction was 1.86 times more common in the MC twin pair [CI (1.07–3.21), p-value?=?0.026].

Conclusions: MC twins were more at risk for adverse outcomes than DC twins. Determining chorionicity at early pregnancy will help the Obstetricians to plan the care of these patients. This will help not only in managing twin pregnancies but also help in counseling according to the local perinatal outcome.     

Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

Background:

Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review.

Methods:

In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software.

Results:

Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists'' masks (κ=0.91), this had little impact on computed IHC scores (Allred; =0.91, Quickscore; =0.92).

Conclusions:

The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials.     

Intraoperative hypercyanosis in a patient with pulmonary artery band: case report and review of the literature

A case of intraoperative cyanosis in a patient with a common atrioventricular canal palliated with a pulmonary artery (PA) band is presented. The patient's physiology was consistent with cyanosis due to inadequate pulmonary blood flow, and responded quickly to typical interventions used for a hypercyanotic episode in a patient with unrepaired Tetralogy of Fallot. Differences and similarities in the physiology of PA banding compared with Tetralogy of Fallot are presented, including a rationale for treatment options for hemodynamic decompensation occurring in the setting of anesthesia and surgery.