Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

A Randomized Controlled Trial of Intrathecal versus Caudal Morphine-Bupivacaine on Postoperative Analgesia and Cortisol Levels in Pediatric Patients.

BACKGROUND: Morphine is commonly used in pediatric caudal blocks. We compared the analgesic efficacy and effect on cortisol levels of intrathecal morphine and bupivacaine with caudal morphine and bupivacaine in children undergoing lower abdominal surgeries. METHODS: Forty children undergoing lower abdominal surgeries were randomized to receive 4 µg/kg of intrathecal morphine and 0.5% hyperbaric bupivacaine (n = 20), or caudal morphine 40 µg/kg and 0.25% bupivacaine (n = 20). Postoperative analgesia was provided with intravenous (IV) paracetamol (PCM). The primary outcome was time to reach Face, Legs, Activity, Cry, and Consolability (FLACC) score ≥4 postoperatively. Secondary outcomes were perioperative serum cortisol levels, analgesic requirement, and parent satisfaction. RESULTS: Since seventy 5% of patients receiving intrathecal morphine and bupivacaine did not reach a FLACC score ≥4 within 24 hours, the primary outcome was presented as the Kaplan-Meier curve. The probability of FLACC score <4 was significantly higher with intrathecal morphine and bupivacaine than with caudal morphine and bupivacaine (P < .001). The unadjusted and adjusted (for gender) hazard ratio (95% confidence interval [CI]) of occurrence of pain (FLACC score ≥4) was 0.07 (0.03-0.15, P < .001) and 0.06 (0.03-0.14, P < .001), respectively. The difference in means (95% CI) of cortisol levels between caudal morphine (with bupivacaine) and intrathecal morphine (with bupivacaine) groups were after intubation -0.667 (-4.99 to 3.65, P = .76), at 2 hours intraoperatively 7.88 (3.55-12.2, P < .001), 6 hours postoperatively 16.8 (12.5-21.1, P < .001), and 24 hours postoperatively 15.4 (11.1-19.7, P < .001) µg/dL. Intraoperatively, rescue fentanyl was required by 60% of patients on caudal morphine and bupivacaine against 20% of patients receiving intrathecal morphine and bupivacaine (absolute risk-reduction [95% CI] of 40% [12%-68%]; P = .010). Postoperative rescue fentanyl was required in 45% of patients on caudal morphine and bupivacaine and 5% of patients on intrathecal morphine and bupivacaine. All (100%) patients on caudal morphine and bupivacaine required postoperative PCM against 6 (30%) patients on intrathecal morphine and bupivacaine (absolute risk-reduction [95% CI] of 70% [50%-90%]; P < .001).The median (interquartile range [IQR]) parent satisfaction score for patients on caudal morphine (with bupivacaine) and intrathecal morphine (with bupivacaine) was 0(0-0) and 2(2-2) at 12 hours postoperatively (P < .001) and 0(0-1) and 2(1.5-2) at 24 hours postoperatively (P < .001). One patient in each group developed nausea and vomiting, and 1 patient in the intrathecal group developed pruritus. There was no incidence of respiratory depression. CONCLUSIONS: Intrathecal morphine and bupivacaine results in longer duration of analgesia, lower analgesic consumption, prevents surgical-stress-related elevation of serum cortisol, and improves parent satisfaction compared to caudal morphine with bupivacaine in children undergoing lower abdominal surgeries.

Utility of an in-house real-time PCR in whole blood samples as a minimally invasive method for early and accurate diagnosis of invasive mould infections.

INTRODUCTION: Invasive mould infections (IMIs) are a leading cause of death in patients with compromised immune systems. Proven invasive mould infection requires detection of a fungus by histopathological analysis of a biopsied specimen, sterile culture, or fungal DNA amplification by PCR in tissue. However, the clinical performance of a PCR assay on blood samples taken from patients suspected of invasive mould disease has not been fully evaluated, particularly for the differential diagnosis of invasive aspergillosis (IA) and invasive Mucormycosis (IM). OBJECTIVES: To assess the diagnostic utility of our previously validated in-house real-time PCR in blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection. METHODS: All patients with suspected invasive mould infection were prospectively enrolled from May 2021 to July 2021. Conventional fungal diagnosis was performed using tissue and respiratory samples. In-house PCR was performed on blood samples and its diagnostic performance evaluated. RESULTS: A total of 158 cases of suspected invasive mould infection were enrolled in the study. The sensitivity and specificity of in-house PCR performed on blood samples was found to be 92.5% and 81.4% respectively for diagnosis of probable IA, and 65% and 84.62% respectively for diagnosis of proven and probable IM. It was also able to detect 3 out of 5 cases of possible IM where no other microbiological evidence of IM was obtained. CONCLUSIONS: This assay could be helpful in minimally invasive diagnosis of IMIs for patients in whom invasive sampling is not feasible, especially as a preliminary or screening test. It can help in early diagnosis, anticipating conventional laboratory confirmation by days or weeks. Possible correlation between fungal load and mortality can help in initiating aggressive treatment for patients with high initial fungal load.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Utility of in-house and commercial PCR assay in diagnosis of Covid-19 associated mucormycoss in an emergency setting in a tertiary care center.

Introduction. Invasive mucormycosis (IM) is a potentially fatal infection caused by fungi of the order Mucorales. Histopathology, culture, and radiology are the mainstays of diagnosis, but they are not sufficiently sensitive, resulting in delayed diagnosis and intervention. Recent studies have shown that PCR-based techniques can be a promising way to diagnose IM.Hypothesis/Gap Statement. Early diagnosis of fungal infections using molecular diagnostic techniques can improve patient outcomes, especially in invasive mucormycosis.Aim. The aim of this study was to evaluate the utility of our in-house mould-specific real time PCR assay (qPCR) in comparison with the commercially available real time PCR (MucorGenius PCR), for the early diagnosis of mucormycosis in tissue samples from patients with suspicion of invasive mucormycosis (IM). This in-house assay can detect and distinguish three clinically relevant mould species, e.g. Aspergillus spp., Mucorales and Fusarium spp. in a single reaction with only one pair of primers, without the need for sequencing.Methodology. We enrolled 313 tissue samples from 193 patients with suspected IM in this prospective study. All cases were classified using EORTC/MSGERC guidelines. All samples were tested using traditional methods, in-house qPCR, and MucorGenius PCR.Results. Using direct microscopy as a gold standard, the overall sensitivity and specificity of in-house qPCR for detection of IM was 92.46% and 80% respectively, while that of the MucorGenius PCR was 66.67% and 90% respectively. However, co-infection of IM and IA adversely affected the performance of MucorGenius PCR in detection of IM.The in-house PCR detected Aspergillus spp. in 14 cases and Fusarium spp. in 4 cases which showed clinical and radiological features of fungal sinusitis. The in-house qPCR also performed better in detecting possible cases of IM. This aids early diagnosis and appropriate treatment to improve patient outcomes.Conclusion. Because the in-house PCR is not only sensitive and specific, but also entirely based on SYBR Green for detection of targets, it is less expensive than probe-based assays and can be used on a regular basis for the diagnosis of IM in resource-constrained settings. It can be used to distinguish between mucormycosis and fungal sinusitis caused by Aspergillus and Fusarium in high-risk patients, as well as to accurately detect Mucorales in fungal co-infection cases.

Clinical profile and treatment outcomes among patients with sporadic and multiple endocrine neoplasia syndrome-related primary hyperparathyroidism.

OBJECTIVE: Accurate demarcation between multiple endocrine neoplasia, type 1 (MEN1)- related primary hyperparathyroidism (MPHPT) and sporadic PHPT (SPHPT) is important to plan the management of primary parathyroid disease and surveillance for other endocrine and nonendocrine tumours. The objective of this study is to compare the clinical, biochemical and radiological features and surgical outcomes in patients with MPHPT versus SPHPT and to identify the predictors of MEN1 syndrome in PHPT. DESIGN, PATIENTS AND MEASUREMENTS: This was an ambispective observationalstudy involving 251 patients with SPHPT and 23 patients with MPHPT evaluated at the endocrine clinic of All India Institute of Medical Sciences, New Delhi, India between January 2015 and December 2021. RESULTS: The prevalence of MEN1 syndrome among patients with PHPT was 8.2% and a genetic mutation was identified by Sanger sequencing in 26.1% of patients with MPHPT. Patients with MPHPT were younger (p < .001), had lower mean serum calcium (p = .01) and alkaline phosphatase (ALP; p = .03) levels and lower bone mineral density (BMD) Z score at lumbar spine (p < .001) and femoral neck (p = .007). The prevalence of renal stones (p = .03) and their complications (p = .006) was significantly higher in MPHPT group. On multivariable analysis, factors predictive of MPHPT were hyperplasia on histopathology [OR 40.1, p < .001], ALP levels within reference range [OR 5.6, p = .02] and lumbar spine BMD [OR 0.39 per unit increase in Z score, p < .001]. CONCLUSIONS: Patients with MPHPT have more severe, frequent and early onset of bone and renal involvement despite milder biochemical features. A normal serum ALP, low BMD for age and gender at lumbar spine and histopathology evidence of hyperplasia are predictive factors for MEN1 syndrome in PHPT.

Prevalence and Predictors of Osteoporosis/BMD Below Expected Range for Age in Pheochromocytoma/Paraganglioma and BMD, TBS Change Post-Operatively: A Prospective Cohort Study.

Context: Pheochromocytomas/paragangliomas (PPGLs) have recently been shown to be associated with lower bone mineral density (BMD) and trabecular bone score as compared to healthy controls suggesting low bone mineral concentration and disrupted bone microarchitecture. There is paucity of data on prevalence and clinical predictors of low BMD/osteoporosis in PPGL from India and the extent of change in BMD post-operatively. Aims: This study aimed to find prevalence of low BMD/osteoporosis and trabecular bone score (TBS)-adjusted FRAX score in subjects with PPGL and to see the post-operative change in BMD and TBS at follow-up. Material and Methods: 32 consecutively diagnosed adult cases with PPGL were enrolled. Although the provisional diagnosis of PPGL was made based on imaging consistent with PPGL supported by biochemical evidence of catecholamine excess, its confirmation was made histopathologically before final analysis. Results: We found significantly low average BMD T-score/Z-score at spine, hip or wrist. Osteoporosis was evident in 87.5% of subjects (nine of 11 post-menopausal women or men >50 years of age) and BMD below the expected range for age in 42.9% of subjects (nine of 21 pre-menopausal women or men <50 years of age) by International Society for Clinical Densitometry criteria. Conclusions: 87% of older subjects with PPGL had osteoporosis while 43% of younger subjects had BMD below expected range for age (Z-score ≤-2.0), more at lumbar spine than at hip. Decreased body weight was associated with osteoporosis in older or Z-score ≤-2.0 in younger subjects. There was no significant change in BMD and TBS scores at a median of four months post-operatively.

Late-night salivary cortisol cut-offs for diagnosis of Cushing syndrome using second-generation electrochemiluminescence immunoassay kits.

CONTEXT: Late-night salivary cortisol (LNSC) is a simple and reliable screening test for Cushing syndrome (CS). With improved analytical performance of the current second-generation electrochemiluminescence immunoassay (ECLIA; Elecsys Cortisol-II; Roche Diagnostics), there is a need to revisit the LNSC cut-offs, especially in a South-Asian population. OBJECTIVE: To derive LNSC cut-offs for diagnosis of CS using second-generation ECLIA kits. DESIGN: Diagnostic accuracy study. METHODS: We prospectively recruited 155 controls aged 18-60 years, including, normal-weight (body mass index [BMI] < 25 kg/m2 and no hypertension or diabetes [n = 53]) and overweight/obese (BMI 25-30 kg/m2 and hypertension and/or diabetes [n = 52] or BMI ≥ 30 kg/m2 with/without comorbidities [n = 50]) participants. All participants submitted LNSC samples collected at home; overweight/obese controls additionally underwent dexamethasone suppression test to exclude CS. We also reviewed records of adults with endogenous CS (cases, n = 92) and a valid LNSC result using the same method. RESULTS: The 95th percentile for LNSC in controls was 6.76 nmol/L. The mean ± SD LNSC levels were 40.47 ± 49.63 nmol/L in cases and 3.37 ± 1.18 nmol/L in controls (p < 0.001). Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of LNSC for CS, with area under curves (AUCs) of 0.994 (cases vs. all controls) and 0.993 (cases vs. overweight/obese controls), respectively. The best diagnostic performance was achieved at cut-offs ≥6.73 nmol/L (sensitivity: 97.8%, specificity: 94.8%) and ≥7.26 nmol/L (sensitivity: 97.8%, specificity: 95.1%), respectively. CONCLUSIONS: LNSC measured using second-generation ECLIA demonstrated high diagnostic accuracy for CS. Based on this study, we propose a LNSC cutoff ≥6.73 nmol/L to diagnose CS.

Clinical profile and treatment outcomes of patients with ectopic ACTH syndrome compared to Cushing disease: a single-center experience.

PURPOSE: We aimed to evaluate and compare the clinical, biochemical and radiological profile and outcomes of patients with ectopic ACTH syndrome (EAS) and Cushing disease (CD) treated over a period of 10 years (2013-2022). METHODS: In this ambispective observational study, we collected data for 146 patients with ACTH-dependent CS (EAS, n = 23; CD, n = 94; occult ACTH source, n = 29). Relevant details were filled in a predesigned proforma and outcomes were ascertained at the most recent visit. RESULTS: EAS was more common in males (65.2 vs. 27.6%, p < 0.001). Patients with EAS had a shorter duration of symptoms [12 (6-12) vs. 31.5 (15-48) months, p < 0.001] and were more likely to have hypokalemia (82.6 vs. 21.0%, p = 0.001), pedal edema (65.2 vs. 34.2%, p = 0.015), weight loss (34.8 vs. 4.0%, p < 0.001) and systemic infection (30.4 vs. 6.5%, p = 0.006). They also had significantly higher 8 a.m. serum cortisol, midnight serum and salivary cortisol and 8 a.m. plasma ACTH levels. Bronchial carcinoid (n = 10, 43.5%) was the most common etiology of EAS. Bilateral adrenalectomy was performed in 11 (47.8%) patients with EAS. Eight patients (34.8%) with EAS died at the last follow-up, of whom 7 (87.5%) had metastatic disease. In CD group, overall remission rate was 69.4% (56.1%, early and 13.3%, delayed) and 26.3% of patients with an initial remission had recurrence. CONCLUSIONS: Bronchial carcinoid was the most common cause of EAS in our cohort. Bilateral adrenalectomy was performed in approximately every 1 in 2 patients with EAS and approximately every 1 in 3 patients expired till the last follow-up.

Correlation of Levator-Muller's Complex Thickness on Ultrasound Biomicroscopy to Botulinum Toxin A Injection in Thyroid-Related Upper Eyelid Retraction.

OBJECTIVES: To study the thickness of levator palpebra superioris-Muller's muscle complex (LMC) on ultrasound biomicroscopy (UBM) and to correlate with the clinical response to botulinum toxin A (BTA) injection in patients with inactive-stage of thyroid-related upper eyelid retraction (UER). We also studied the correlation of clinical parameters, preinjection with postinjection values. METHODS: This was a prospective, interventional study. Patients with thyroid-related UER who underwent subconjunctival injection of BTA were recruited. Demographic data and clinical details were evaluated. UBM (50 MHz) was done to measure the thickness of LMC. Patient's satisfaction was graded at each follow-up. Follow-up was done at 1 week, 1 month, and 3 months' time intervals. RESULTS: A total of 13 patients were recruited and 26 eyes were divided into two groups; group 1 included eyes with UER (n = 17), and group 2 included eyes without UER (n = 9). There was a statistically significant reduction in margin reflex distance 1 (MRD1) after BTA injection at 1-week, 1-month, and 3-months follow-up with maximum reduction at 1 month. The mean LMC thickness of 26 eyes was 0.96 mm which was found to be significantly more than normal controls. On comparison of mean LMC thickness with the amount of UER and reduction in MRD1, we did not find a significant difference. CONCLUSIONS: Patients with TED have significantly thicker LMC on UBM than controls. Further studies are needed with a larger sample size on the correlation of UBM features of levator aponeurosis with response to BTA injection.

Spontaneous Remission of Acromegaly After Pituitary Apoplexy in a Middle-Aged Male.

Background: Pituitary apoplexy results from hemorrhage, infarction, or hemorrhagic infarction within a pituitary tumor. Subclinical or clinical apoplexy is not uncommon in acromegaly, owing to the large size of the tumor at initial detection. Growth hormone excess in acromegaly often persists following surgery. However, in rare instances, pituitary apoplexy may present a spontaneous cure to growth hormone excess. Case Report: A 40-year-old male presented with holocranial headache for the past 16 years that had worsened in severity during the prior year. Two months before presentation, he experienced a severe headache that he described as the worst headache of his life. The patient had prominent acromegaloid features that he ignored, as they seemed to cause no harm. The patient had no signs of clinically active disease. Magnetic resonance imaging of the brain revealed a pituitary macroadenoma with evidence of hemorrhage. Serum insulin-like growth factor 1 and oral glucose-suppressed serum growth hormone levels were normal, suggestive of inactive or silent disease. Pituitary apoplexy causing spontaneous remission of acromegaly was diagnosed, and close follow-up was planned for the evolution of hypopituitarism. Conclusion: This case highlights a rare presentation of acromegaly in which an episode of symptomatic pituitary apoplexy revealed the diagnosis of pituitary adenoma and led to the cure of growth hormone hypersecretion.

Association of cognitive impairment with sleep quality, depression and cardiometabolic risk factors in individuals with type 2 diabetes mellitus: A cross sectional study.

AIM: The aim of this study was to evaluate the association of cognitive impairment with sleep quality, depression, and cardiometabolic risk factors among participants with type 2 diabetes mellitus. METHODS: Subjects underwent clinical interview to capture socio-demographic details, medical history, sleep quality, presence of depression, along with anthropometric and biochemical measurements. A detailed neuropsychological assessment [Montreal cognitive assessment scale (MoCA), Trail making A and B, Digit span, Spatial span, Letter Number Sequencing] was done. Cognitive impairment was defined as MoCA score of <23. RESULTS: Participants (n=250, 50% women, 63.6% middle-age) had a mean (±SD) age of 53.6 (±9.1) years and HbA1c of 55.1±6.8mmol/mol (7.2±0.6%). Cognitive impairment was present in 57 (22.8%) participants. In the middle-age subgroup, cognitive impairment was higher (23.9%) than those in the fourth decade (6.3%), but comparable (24.0%) to the older age (60-70years) individuals. Diabetes-related vascular complications [Odds ratio (95% CI) 2.03 (1.05, 3.94)]; hypertension [2.00 (1.04, 3.84)], depression [2.37 (1.24, 4.55)] and lower education [2.73 (1.42, 5.23)] had a significant association with cognitive impairment on multivariate logistic regression analysis. CONCLUSION: The high burden of cognitive impairment calls for an urgent need to establish longitudinal cohorts in midlife to understand this population's cognitive trajectories and see the influence of various bio-psychosocial variables.

Conventional PCR as a reliable method for diagnosing invasive mucormycosis in resource-limited settings.

Introduction. Invasive mucormycosis (IM) is a life-threatening infection caused by fungi belonging to the order Mucorales. Histopathology, culture and radiology are the mainstay of diagnosis but lack sensitivity, leading to a delay in timely diagnosis and intervention. Recently, PCR-based approaches have been shown to be a promising method in diagnosing IM.Hypothesis/Gap Statement. Molecular-based approaches may be a valuable adjunct to standard conventional methods for diagnosing IM, especially among culture negatives and patients on antifungal therapy.Aim. In the present study we aimed to evaluate the clinical utility of panfungal and Mucorales-specific PCR for diagnosing IM from various clinical specimens.Methodology. This was a prospective study in which 239 clinically suspected cases of IM attending our tertiary care hospital from August 2015 to March 2018 were enrolled. All the cases were defined as 'proven', 'probable' or 'possible' based on EORTC/MSGERC guidelines. In addition to conventional diagnostics (KOH-calcofluor stain and culture), panfungal and Mucorales-specific PCR assays were also performed. The amplified products were sequenced for species identification. In vitro antifungal susceptibility was performed on all the culture-positive isolates.Results. Among 239 clinically suspected cases of IM, only 140 cases were diagnosed by the demonstration of aseptate ribbon-like hyphae on direct microscopy. Culture was positive in 35.7 % (54/140) of direct microscopy-positive samples. Among the proven cases (n=11), the sensitivity for both Mucorales-specific nested PCR and panfungal PCR was 100 %, but specificity was 91.9 and 73.7% respectively. In probable cases (n=129), the sensitivity of both the PCRs was 98.5 % and specificity for panfungal PCR was 73.7 and 91.9 % for Mucorales-specific PCR.Conclusion. Pan fungal PCR in combination with Mucorales-specific PCR, followed by sequencing, may play a significant role in IM diagnosis especially among those negative for both direct microscopy and culture.

Development of a Sensitive and Specific Novel qPCR Assay for Simultaneous Detection and Differentiation of Mucormycosis and Aspergillosis by Melting Curve Analysis.

Molecular diagnostic assays can expedite the diagnosis of fungal infections, and subsequently help in early interventions and appropriate management of patients. The aim of this study was to develop a single set of primers for a real-time quantitative polymerase chain reaction (qPCR) assay to detect and identify commonly reported, clinically relevant molds i.e., Aspergillus spp, Mucorales and Fusarium spp., up to genus level by melting curve analysis. This assay was evaluated in whole blood from patients with suspected invasive aspergillosis (IA), and in tissue biopsy, bronchoalveolar lavage (BAL) fluid and other site-specific samples from patients with suspected invasive mucormycosis (IM). The limit of detection (LoD) was determined as 10 copies/µl for all three molds. The mean coefficient of variation (CV) across all sets of intra- and inter-assay data was 0.63% (ranging from 0.42 to 1.56%), showing high reproducibility of the assay. Sensitivity and specificity of the assay were 93.3 and 97.1% respectively for diagnosis of IA, and 99.29 and 83.84% respectively for diagnosis of IM. Fusarium was not detected in any of the clinical samples included and the few laboratory confirmed cases of fusariosis did not meet the inclusion criteria of the study. Hence no ROC curve or cutoff value could be generated for the same. This newly developed qPCR assay therefore appears to be a promising tool in detection of IA and IM.

Epidemiology and Antifungal Susceptibility Patterns of Invasive Fungal Infections (IFIs) in India: A Prospective Observational Study.

The epidemiology of invasive fungal infections (IFI) is ever evolving. The aim of the present study was to analyze the clinical, microbiological, susceptibility, and outcome data of IFI in Indian patients to identify determinants of infection and 30-day mortality. Proven and probable/putative IFI (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group and AspICU criteria) from April 2017 to December 2018 were evaluated in a prospective observational study. All recruited patients were antifungal naïve (n = 3300). There were 253 episodes of IFI (7.6%) with 134 (52.9%) proven and 119 (47%) probable/putative infections. There were four major clusters of infection: invasive candidiasis (IC) (n = 53, 20.9%), cryptococcosis (n = 34, 13.4%), invasive aspergillosis (IA) (n = 103, 40.7%), and mucormycosis (n = 62, 24.5%). The significant risk factors were high particulate efficiency air (HEPA) room admission, ICU admission, prolonged exposure to corticosteroids, diabetes mellitus, chronic liver disease (CLD), acquired immunodeficiency syndrome (AIDS), coronary arterial disease (CAD), trauma, and multiorgan involvement (p < 0.5; odds ratio: >1). The all-cause 30-day mortality was 43.4% (n = 110). It varied by fungal group: 52.8% (28/53) in IC, 58.8% (20/34) in cryptococcosis, 39.8% (41/103) in IA, and 33.9% (21/62) in mucormycosis. HEPA room, ICU admission for IC; HEPA rooms, diabetes mellitus for cryptococcosis; hematological malignancies, chronic kidney disease (CKD), sepsis, galactomannan antigen index value ≥1 for IA and nodules; and ground glass opacities on radiology for mucormycosis were significant predictors of death (odds ratio >1). High minimum inhibitory concentration (MIC) values for azoles were observed in C. albicans, C. parapsilosis, C. glabrata, A. fumigatus, A. flavus, R. arrhizus, R. microsporus, and M. circinelloides. For echinocandin, high MIC values were seen in C. tropicalis, C. guillermondii, C. glabrata, and A. fumigatus. This study highlights the shift in epidemiology and also raises concern of high MICs to azoles among our isolates. It warrants regular surveillance, which can provide the local clinically correlated microbiological data to clinicians and which might aid in guiding patient treatment.

Effectiveness of Yoga-based Exercise Program Compared to Usual Care, in Improving HbA1c in Individuals with Type 2 Diabetes: A Randomized Control Trial.

BACKGROUND: This study was designed to evaluate the effectiveness of a yoga-based exercise program (YBEP) in improving glycemic control in people with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients on stable oral glucose-lowering agents for at least 3 months and HbA1c 7.5%-10% were randomized in 1:1 ratio. The primary outcome measure was the difference of change in mean HbA1c between groups. RESULTS: The participants (n = 81) had mean (±standard deviation) age of 50.6 (±8.5) years and HbA1c of 8.5 ± 0.7% (68.97 ± 7.42 mmol/mol). The follow-up data were available in 96% (78/81) of participants. Of 40 participants, 25 (62.5%) attended ≥75% (≥10 out of 13) of the sessions in YBEP. On the intention to treat analysis, a favorable reduction (0.21% 95% confidence interval [-0.34, 0.75], P = 0.454) in HbA1c was seen in YBEP group as compared to usual care. The reduction in HbA1c by ≥0.5% was observed in 44.7% of participants in YBEP as compared to 37.5% in usual care arm, respectively. Those who attended ≥75% of the sessions had better HbA1c reduction of 0.3% in comparison to 0.1% reduction seen in those who attended <75% of the sessions. CONCLUSIONS: YBEP demonstrated a clinically relevant HbA1c reduction compared to usual care in participants who had attended at least 75% of the yoga sessions. The reduction in HbA1c by >0.5% in 44.7% in the yoga group, suggests, that it can be prescribed as an exercise to individuals who are unable to walk either due to limited joint mobility, adverse weather conditions, lack of space for walking, cultural or religious prohibitions for women for outdoor physical activity, and so on.CTRI registration no: CTRI/2017/05/008564.

Impact of parental origin of X-chromosome on clinical and biochemical profile in Turner syndrome.

Objectives To evaluate if the parental origin of X-chromosome has an impact on the phenotype and biochemical profile in Turner syndrome (TS). Result of the previous studies have been equivocal and could be attributable to the multicentric study design with different experts examining heterogeneous TS population of various ethnic background. Methods A cross-sectional single center study from Northern India. Fifty nine diagnosed subjects of TS and their parents participated in the study. Parental origin of intact X-chromosome was determined using 12 highly polymorphic short tandem repeats (STR) on X-chromosome. For the evaluation of parent-of-origin effects, typical phenotypic traits including congenital malformations, anthropometry, body composition by dual energy X-ray absorptiometry (DXA) and biochemical profile were compared. Clinical stigmata of TS in all subjects were examined by a single expert. Results The intact X-chromosome was of maternal origin (Xm) in 49.1% subjects while 50.9% had paternal origin (Xp). Skeletal anomalies were more common in Xm group, out of which prevalence of short neck and short fourth metatarsal reached statistical significance (p=0.04 and 0.01 respectively). A strong correlation was observed between subject's baseline height standard deviation score (Ht SDS) and paternal height (r=0.593, p<0.001), maternal height (r=0.564, p<0.001) and mid-parental height (MPH) (r=0.372, p=0.047) in Xp group. This effect was not seen in Xm subjects whose baseline Ht SDS showed no significant correlation with maternal height, paternal height or MPH. No differences were detected between the groups with regard to biochemical profile or body composition. Conclusions We speculate that the differences in skeletal anomalies and height correlations between Xm and Xp groups could be due to the modifying effect of epigenetic signature on short stature homeobox (SHOX) gene of Xm. SHOX gene is not modified on Xp thereby explaining the paucity of skeletal changes and height correlations in Xp subjects.

Evaluation of eating disorders and their association with glycemic control and metabolic parameters in adult patients with type 2 diabetes mellitus.

BACKGROUND: There is little data on the prevalence and effects of eating disorders in patients with T2DM. AIMS: To evaluate the presence of eating disorders (ED) and their association with glycemic control and metabolic parameters in adult patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted in the endocrinology outpatient unit of our tertiary care centre between January 2017 to December 2018. Eating Attitudes Test (EAT-26) and Binge Eating Scale (BES) questionnaires were used to screen for ED in adults with T2DM (group 1) and controls without T2DM (group 2). Cut off scores ≥18 on BES was considered as a positive screen for Binge eating disorder in participants with and without T2DM. A score of ≥30 on EAT-26 was defined as abnormal for participants with T2DM and ≥20 for those without T2DM. Formal psychiatric assessment was done to diagnose ED in those who screened positive on the basis of scores on BES or EAT-26 or both. Demographic, anthropometric and relevant medical details like duration of treatment, glycemic control, complications were recorded. RESULTS: A total of 512 individuals (256 in each group) participated in this study. Out of these, 10.9% of individuals with T2DM and 14.1% of those without T2DM screened positive for ED, with no significant difference in the two groups. After a detailed psychiatric assessment, two patients (0.8%) in each group were confirmed to have ED. Participants with T2DM who were on thiazolidinediones had higher odds (2.2) of screening positive for an ED.(p = 0.03). CONCLUSIONS: Our study reveals that eating disorders are not very common in our clinical population of T2DM, and the prevalence is comparable to BMI matched individuals without T2DM. The prevalence rates of eating disorders are lower (in both controls and patients with T2DM) than those reported from developed western countries.

Improvement in Angiotensin 1-7 precedes and correlates with improvement in Arterial stiffness and endothelial function following Renin-Angiotensin system inhibition in type 2 diabetes with newly diagnosed hypertension.

BACKGROUND AND AIM: Studies in cell cultures and animal models have revealed the possible pathophysiological factors associated with vascular endothelial dysfunction. However, the same in human subjects has not been clearly established. The current study uses a novel approach to identify the factors associated with endothelial function and arterial function by altering these vascular parameters using Angiotensin-Converting-Enzyme (ACE) inhibition. METHODS: Diabetic patients with newly diagnosed hypertension (n = 60) were recruited for the study. Flow-mediated-dilation (FMD), carotid-femoral (cf), carotid-radial (cr) Pulse-wave-velocity (PWV), Augmentation-Index, Carotid-Intima-Media-Thickness (CIMT), serum levels of Renin, Angiotensin II (AngII), Angiotensin-Converting-Enzyme2 (ACE2), Angiotensin1-7 (Ang1-7), E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), Highly-sensitive-C-Reactive-Protein (hsCRP) and Interleukin-10 were measured at baseline (V1), after 1 week (V2) and 3 months (V3) of ACE inhibition in patients of diabetes with newly diagnosed hypertension. The amplitude of change after 1 week (V2-V1) and 3 months (V3-V1) for the clinical and various parameters were correlated with the change in endothelial function and arterial stiffness. RESULTS: Carotid radial-PWVV2-V1 (p = 0.001) and Ang1-7V2-V1 (p = 0.01) emerged as independent predictors of FMDV2-V1. ReninV2-V1 and VCAM-1V2-V1 independently predicted E-selectinV2-V1 [(p = 0.01) and (p = 0.001), respectively]. ACE 2V2-V1 was the only independent predictor of cf-PWVV2-V1. The same parameters remained as independent predictors of the respective vascular factors after 3 months of ACE inhibition. CONCLUSION: The study highlights the role of AngII/Ang1-7 balance in alteration of endothelial function and central arterial stiffness in humans in addition to identifying the interrelationship between the renin-angiotensin-aldosterone-system components and clinically ascertainable parameters.