Fibroscan as a non-invasive predictor of hepatic steatosis in women with polycystic ovary syndrome.

Background & objectives: There is limited data on non-alcoholic fatty liver disease (NAFLD) among Indian women with polycystic ovary syndrome (PCOS), and there are no data on the utility of fibroscan in its assessment. The objective of this study was thus to investigate the frequency of hepatic steatosis in young women with PCOS and evaluate the utility of transient elastography (TE) in its assessment. Methods: Seventy women diagnosed with PCOS and 60 apparently healthy women (controls) were enrolled in this pilot study. These women were evaluated for clinical, biochemical and hormonal parameters, transabdominal ultrasonography, dual-energy X-ray absorptiometry and fibroscan assessing liver stiffness measure (LSM) and controlled attenuation parameter (CAP). Other indices such as liver fat score (LFS), lipid accumulation product (LAP), fibrosis-4 (FIB-4) and aspartate aminotransferase to platelet ratio index, hepatic steatosis index (HIS) scores were also calculated. The main outcome measures were the presence of NAFLD in women with PCOS and its correlation with CAP and LSM on TE. Results: Women with PCOS had higher frequency (38.57 vs. 6.67%) of hepatic steatosis than control women as determined by abdominal sonography. The aminotransferases were higher in PCOS group (14.28 vs. 1.7%, P=0.03) even after adjusting for body mass index implying higher non-alcoholic steatohepatitis among young PCOS patients. PCOS women had significantly higher CAP on TE compared to controls (210 vs. 196). CAP had a significant correlation with LFS, LAP and HIS. Interpretation & conclusions: NAFLD is common in young women with PCOS, and fibroscan using TE may be considered as a promising non-invasive diagnostic modality in its early detection.

Pattern of Lipid Abnormalities Among South Asian Indians With Cushing's Syndrome and the Short Term Impact of Surgical Correction of Hypercortisolism.

Atherosclerotic cardiovascular events are one of the common causes of mortality in patients with Cushing's syndrome (CS). Atherogenic dyslipidemia is more common among South Asian Indians as compared to other ethnicities and is likely to worsen among patients with CS. This retrospective study was done over 5 years at a single institute to evaluate the pattern of lipid abnormalities in subjects with CS and the changes in lipid parameters after surgical control of hypercortisolemia. The study was done in two parts. In the first part, records of patients with CS diagnosed over 3 years were retrospectively reviewed. Hormonal and metabolic parameters including fasting plasma glucose (FPG), post prandial plasma glucose (PPPG), HbA1c, serum lipids, serum cortisol and plasma ACTH were recorded. In the second part, lipid parameters were rechecked among patients who underwent surgery and a median follow up of 4±2 months after remission. Out of the 126 patients diagnosed with endogenous CS over 3 years, 100 patients were eligible for inclusion in the study. At baseline, sixty five (65%) patients had dyslipidemia as defined by the NCEP-ATPIII criteria. 47 out of 63 (74.6%) subjects achieved remission after surgical management of CS. 32 (68.1%) of these patients had dyslipidemia prior to surgery. After excluding 1 death, 26 of 46 (56.5%) subjects had dyslipidemia after the follow up period. Lipid abnormalities are common among South Asian Indian subjects with endogenous CS and the pattern persists in most of them, 3 months after surgical correction of hypercortisolism.

Bone Mineral Density is Unaltered in Women with Polycystic Ovary Syndrome.

CONTEXT: The effects of endocrine aberrations associated with polycystic ovary syndrome (PCOS) on bone mineral density (BMD) in young women is a matter of debate. OBJECTIVES: To compare BMD in young women with PCOS to age and body mass index (BMI) matched controls and to elucidate its correlation to BMI, insulin resistance and serum testosterone. DESIGN AND METHODS: We recruited 60 women with PCOS aged 14-24 years, diagnosed based on Rotterdam 2003 criteria, and 58 age matched controls. BMD was measured by dual energy X-ray absorptiometry. In addition, these subjects underwent biochemical and hormonal analysis including oral glucose tolerance test, calculation of Homeostatic Model Assessment-Insulin Resistance Index, measurement of serum thyroxine, thyrotropin, prolactin, total testosterone, dehydroepiandrosterone sulfate, follicular phase luteinizing hormone and follicle stimulating hormone. RESULTS: There was no difference of BMD between women with PCOS and control women (1.103±0.08 vs 1.126±0.083 g/cm2; p=0.122). In subgroup analysis based on BMI, BMD in obese women with PCOS was significantly higher than their overweight and lean counterparts at lumbar spine (p<0.001), neck of femur (p=0.005) and total hip (p<0.001). BMD was not different at any site between oligomenorrheic and non-oligomenorrheic women with PCOS. It positively correlated with BMI, waist and hip circumference in women with PCOS. No correlation was found with HOMA-IR or Testosterone. CONCLUSIONS: BMI is the most important determinant of BMD in women with PCOS. BMD is not different between healthy young women and those with PCOS.

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.

Early loss of endogenous NAD+ following rotenone treatment leads to mitochondrial dysfunction and Sarm1 induction that is ameliorated by PARP inhibition.

Sarm1 is an evolutionary conserved innate immune adaptor protein that has emerged as a primary regulator of programmed axonal degeneration over the past decade. In vitro structural insights have revealed that although Sarm1 induces energy depletion by breaking down nicotinamide adenine dinucleotide+ (NAD+ ), it is also allosterically inhibited by NAD+ . However, how NAD+ levels modulate the activation of intracellular Sarm1 has not been elucidated so far. This study focuses on understanding the events leading to Sarm1 activation in both neuronal and non-neuronal cells using the mitochondrial complex I inhibitor rotenone. Here, we report the regulation of rotenone-induced cell death by loss of NAD+ that may act as a 'biological trigger' of Sarm1 activation. Our study revealed that early loss of endogenous NAD+ levels arising due to PARP1 hyperactivation preceded Sarm1 induction following rotenone treatment. Interestingly, replenishing NAD+ levels by the PARP inhibitor, PJ34 restored mitochondrial complex I activity and also prevented subsequent Sarm1 activation in rotenone-treated cells. These cellular data were further validated in Drosophila melanogaster where a significant reduction in rotenone-mediated loss of locomotor abilities, and reduced dSarm expression was observed in the flies following PARP inhibition. Taken together, these observations not only uncover a novel regulation of Sarm1 induction by endogenous NAD+ levels but also point towards an important understanding on how PARP inhibitors could be repurposed in the treatment of mitochondrial complex I deficiency disorders.

Measurement of all orthogonal components of displacement in the volume of scattering materials using wavelength scanning interferometry.

A wavelength scanning interferometry system is proposed that provides displacement fields inside the volume of semitransparent scattering materials with high spatial resolution and three-dimensional (3D) displacement sensitivity. This effectively extends digital speckle pattern interferometry into three dimensions. The sample is illuminated by three noncoplanar collimated beams around the observation direction. Sequences of two-dimensional interferograms are recorded while tuning the laser frequency at a constant rate. Different optical paths along each illumination direction ensure that the signals corresponding to each sensitivity vector do not overlap in the frequency domain. All the information required to reconstruct the location and the 3D displacement vector of scattering points within the material is thus recorded simultaneously. A controlled validation experiment is performed, which confirms the ability of the technique to provide 3D displacement distributions inside semitransparent scattering materials.

Peptide Receptor Radionuclide and Octreotide: A Novel Approach for Metastatic Tumor-Induced Osteomalacia.

KEY MESSAGES: Octreotide can be used as an adjunctive therapy to increase phosphorus levels in patients with tumor-induced osteomalacia. Malignant phosphaturic mesenchymal tumor (PMT) may benefit from treatment with peptide receptor radionucleotide therapy. CONTEXT: The success of treatment modalities for malignant PMT is limited. Octreotide has been used to treat hypophosphatemia in patients with tumor-induced osteomalacia with equivocal results. To our knowledge, there are no reports of octreotide or peptide receptor radionuclide therapy use for malignant PMT. CASE DESCRIPTION: We report a 40-year-old man having hypophosphatemia, phosphaturia (tubular maximum of phosphorus corrected for glomerular filtration rate of <2.5 mg/dL), and somatostatin avid lesions in the right foot region with metastasis to both lungs. The patient had been subjected to resection of the primary tumor from the foot with thoracoscopic removal of the lung secondaries. Histology from all three lesions showed a spindle cell soft tissue tumor with a high mitotic index and somatostatin receptor 2 and 5 positivity. A trial of subcutaneous octreotide therapy at a dose of 100 µg thrice daily resulted in an increase in serum phosphorus levels from an average of 1.44 mg/dL to an average of 2.3 mg/dL. Finally, the affected limb was amputated, and the hypophosphatemia persisted postoperatively. In view of persistent hypophosphatemia and transient response to octreotide, the patient was administered four cycles of peptide receptor radionuclide therapy using 177Lutetium, which showed moderate improvement of serum phosphorus levels. CONCLUSION: Although octreotide use has been reported in four patients with benign PMT, to our knowledge, this is the first case of malignant PMT that has used peptide receptor radionuclide therapy in the treatment of malignant PMT. This moderately beneficial evidence is likely to guide the future use of radionuclide treatments in such tumors.

Usefulness of induced sputum eosinophil count to assess severity and treatment outcome in asthma patients.

CONTEXT: Currently treatment decisions in asthma are governed by clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients. AIMS: To establish correlation between change in sputum eosinophil count and forced expiratory volume in one second (FEV1)% predicted value of asthma patients in response to treatment. In this study, we also predicted prognosis and treatment outcome of asthma patients from baseline sputum eosinophil count. SETTINGS AND DESIGN: A longitudinal study was conducted to determine the treatment outcome among newly diagnosed asthma patients who were classified into A (n = 80) and B (n = 80) groups on the basis of initial sputum eosinophil count (A ≥ 3% and B < 3%). MATERIALS AND METHODS: After starting treatment according to Global Initiative for Asthma Guideline, both A and B groups were evaluated every 15 days interval for the 1(st) month and monthly thereafter for a total duration of 12 months. In each follow-up visit detailed history, induced sputum eosinophil count and spirometry were done to evaluate severity and treatment outcome. RESULTS: FEV1% predicted of group A asthma patients gradually increased and sputum eosinophil count gradually decreased on treatment. Longer time was required to achieve satisfactory improvement (FEV1% predicted) in asthma patients with sputum eosinophil count ≥3%. There was statistically significant negative correlation between FEV1% predicted and sputum eosinophil count (%) in of group A patients in each follow-up visit, with most significant negative correlation found in 8(th) visit (r = -0.9237 and P = < 0.001). Change in mean FEV1% (predicted) from baseline showed strong positive correlation (r = 0.976) with change in reduction of mean sputum eosinophil count at each follow-up visits in group A patients. CONCLUSIONS: Sputum eosinophil count, being an excellent biomarker of airway inflammation, can serve as a useful marker to assess disease severity, treatment outcome, and prognosis in asthma patients.

CHARGE Association.

We present here a case of 17-year-old boy from Kolkata presenting with obesity, bilateral gynecomastia, mental retardation, and hypogonadotrophic hypogonadism. The patient weighed 70 kg and was of 153 cm height. Facial asymmetry (unilateral facial palsy), gynecomastia, decreased pubic and axillary hair, small penis, decreased right testicular volume, non-palpable left testis, and right-sided congenital inguinal hernia was present. The patient also had disc coloboma, convergent squint, microcornea, microphthalmia, pseudohypertelorism, low set ears, short neck, and choanalatresia. He had h/o VSD repaired with patch. Laboratory examination revealed haemoglobin 9.9 mg/dl, urea 24 mg/dl, creatinine 0.68 mg/dl. IGF1 77.80 ng/ml (decreased for age), GH <0.05 ng/ml, testosterone 0.25 ng/ml, FSH-0.95 µIU/ml, LH 0.60 ΅IU/ml. ACTH, 8:00 A.M cortisol, FT3, FT4, TSH, estradiol, DHEA-S, lipid profile, and LFT was within normal limits. Prolactin was elevated at 38.50 ng/ml. The patient's karyotype was 46XY. Echocardiography revealed ventricularseptal defect closed with patch, grade 1 aortic regurgitation, and ejection fraction 67%. Ultrasound testis showed small right testis within scrotal sac and undescended left testis within left inguinal canal. CT scan paranasal sinuses revealed choanalatresia and deviation of nasal septum to the right. Sonomammography revealed bilateral proliferation of fibroglandular elements predominantly in subareoalar region of breasts. MRI of brain and pituitary region revealed markedly atrophic pituitary gland parenchyma with preserved infundibulum and hypothalamus and widened suprasellar cistern. The CHARGE association is an increasingly recognized non-random pattern of congenital anomalies comprising of coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities, and/or deafness.[1] These anomalies have a higher probability of occurring together. In this report, we have described a boy with CHARGE association.