Placental DNA methylation changes in detection of tetralogy of Fallot.

OBJECTIVES: To determine whether the methylation level of cytosine nucleotides in placental DNA can be used to predict tetralogy of Fallot (TOF) and provide insights into the developmental mechanism of this condition. METHODS: Tissue sections were obtained from formalin-fixed paraffin-embedded specimens of placental tissue obtained at birth from eight cases with non-chromosomal, non-syndromic TOF and 10 unaffected newborns. The Illumina Infinium HumanMethylation450 BeadChip assay was used to measure cytosine ('CpG' or 'cg') methylation levels at loci throughout the placental genome. Differential methylation was assessed by comparing the ß-values (a measure of the extent of cytosine methylation) for individual CpG loci in fetuses with TOF vs in controls. The most discriminating CpG sites were determined based on a preset cut-off of ≥ 2.0-fold change in the methylation level. The predictive accuracy of CpG loci with significant methylation changes for TOF was determined by the area under the receiver-operating-characteristics curve (AUC). A false-discovery-rate (FDR) P-value < 0.05 was used to define a statistically significant difference in the methylation level. Ingenuity Pathway Analysis (IPA) (Qiagen) was used to identify gene pathways that were significantly overexpressed, and thus altered, in TOF cases compared with controls. RESULTS: We found a total of 165 significantly differentially methylated CpG loci in TOF cases compared with controls, in 165 separate genes. These biomarkers demonstrated from fair to excellent individual predictive accuracy for TOF detection, with AUCs ≥ 0.75 (FDR P-value < 0.001 for all). The following CpG loci (gene) had the highest predictive accuracy: cg05273049 (ARHGAP22; AUC = 1.00; 95% CI, 1.00-1.00), cg02540011 (CDK5; AUC = 0.96; 95% CI, 0.87-1.00), cg08404201 (TRIM27; AUC = 0.95; 95% CI, 0.84-1.00) and cg00687252 (IER3; AUC = 0.95; 95% CI, 0.84-1.00). IPA revealed over-representation (dysregulation) of 14 gene pathways involved in normal cardiac development, including cardiomyocyte differentiation via bone morphogenetic protein receptors, cardiac hypertrophy signaling and role of nuclear factor of activated T cells in cardiac hypertrophy. Cardiac hypertrophy is an important feature of TOF. CONCLUSIONS: Analysis of placental DNA cytosine methylation changes yielded accurate markers for TOF detection and provided mechanistic information on TOF development. Our work appears to confirm the central role of epigenetic changes and of the placenta in the development of TOF. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Thresholding methods for lesion segmentation of basal cell carcinoma in dermoscopy images.

PURPOSE: Algorithms employed for pigmented lesion segmentation perform poorly on dermoscopy images of basal cell carcinoma (BCC), the most common skin cancer. The main objective was to develop better methods for BCC segmentation. METHODS: Fifteen thresholding methods were implemented for BCC lesion segmentation. We propose two error metrics that better measure the type II error: Relative XOR Error and Lesion Capture Ratio. RESULTS: On training/test sets of 305 and 34 BCC images, respectively, five new techniques outperform two state-of-the-art methods used in segmentation of melanomas, based on the new error metrics. CONCLUSION: The proposed algorithms, which include solutions for image vignetting correction and border expansion to achieve dermatologist-like borders, provide more inclusive and feature-preserving border detection, favoring better BCC classification accuracy, in future work.

Role and Relevance of Blood Pressure Variability in Hypertension Related Co-morbidities.

Despite maintaining mean blood pressure at optimal levels, cardiovascular complications still occur in hypertensive patients. Blood pressure variability (BPV) has been implicated as a prominent factor responsible for incurring this additional risk. In this review we attempted to generate a consensus on the importance of BPV in the hypertension management and to evaluate different therapeutic options available to reduce BPV. Panel comprising of 11 leading experts from India in different areas of clinical practice (including nephrology, diabetes and endocrinology, cardiology, and critical care medicine) was convened. The board reviewed up to date literature on BPV, shared personal experiences from their clinical practice, and debated their opinions on the significance of BPV in hypertension management and also on various therapeutic options available to control it. The reviewers agreed that BPV is frequently observed in hypertensive individuals and it is a critical factor in hypertension management. Blood pressure variability can be measured by ambulatory blood pressure monitoring, home blood pressure monitoring, and office blood pressure monitoring. Members concurred that variations in blood pressure that are 10 standard deviations above the mean blood pressure should be considered as pathologically significant and such variations should be reduced using pharmacological therapies. The board opined that Angiotensin II Receptor Blockers,Calcium Channel Blockers etc such as Olmesartan, Nifedipine can be used to reduce BPV. As a way forward, the panel recommends to bridge the evidence gap that establishes a possible direct relationship between BPV and cardiovascular complications. Blood pressure variability has paramount role in the current hypertension management scenario. To reduce disease burden and increase quality of life of hypertensive individuals, physicians should consider lowering BPV along with physiological BP levels.

Adaptable texture-based segmentation by variance and intensity for automatic detection of semitranslucent and pink blush areas in basal cell carcinoma.

BACKGROUND: Pink blush is a common feature in basal cell carcinoma (BCC). A related feature, semitranslucency, appears as smooth pink or orange regions resembling skin color. We introduce an automatic method for detection of these features based on smoothness and brightness. We also introduce a neighborhood correction method for texture area correction. METHODS: Smoothness and brightness were analyzed over four bands: luminance, red, green, and blue, then merged using variance-based dynamic thresholding. Dermoscopic images of 100 biopsy-proven BCCs and 254 competitive benign mimics were used to train the algorithm. Sixteen color and texture features were extracted from the automatically detected areas. The confusion matrix for the algorithm showed 15 classification errors in the training set for the 354 images: three errors in the BCC set and 12 errors in the benign set. RESULTS: Logistic regression analysis on a separate 1024-image test set was able to achieve good separation of BCC from benign lesions with an area under the receiver operating characteristic curve (ROC) of 0.878 and 0.877 using manually-created and automatically-generated BCC border masks, respectively. CONCLUSION: This pilot study indicates that automatic detection of semitranslucent and pink blush areas in BCC is feasible using colors and first-order texture statistics.

Monitored gradual occlusion of the internal carotid artery followed by ligation for giant internal carotid artery aneurysms.

OBJECTIVE: To demonstrate a technique of gradual monitored occlusion of the internal carotid artery (ICA) followed by ligation for giant aneurysms as an option for balloon test occlusion followed by permanent ligation of ICA. MATERIALS AND METHODS: Authors retrospectively analyzed 27 patients with giant and complex ICA aneurysms who underwent carotid artery ligation between January 2001 and December 2010. Clinical presentation included headache, vision loss and diplopia. There were 19 patients with cavernous aneurysm, 5 supraclinoid, 1 ophthalmic, 1 petrous segment and 1 cervical segment aneurysm located extracranially. All demonstrated good cross-circulation. Selverstone clamp was used for gradual occlusion of the ICA over 72 h under closed observation in the intensive care unit. RESULTS: Six patients developed hemiparesis in the postoperative period. Improvement occurred in one patient over two to three weeks while the remaining five patients had residual hemiparesis. One patient developed malignant MCA infarct for which decompressive craniectomy had to be done. There was no mortality in the present series. CONCLUSIONS: Gradual monitored occlusion and ICA ligation may be a simple, safe alternative procedure to clipping in surgically inaccessible and complex aneurysms, especially for surgeons with limited experience. Cross circulation study is an absolute requisite for carotid ligation.

A Comparative Study of Osteoarthritis Knee Arthroscopy versus Intra-Articular Platelet Rich Plasma Injection: A Randomised Study.

Introduction: Osteoarthritis (OA) is estimated to be the fourth leading cause of disability in the general population. It probably is the most common disease of joints in adults throughout the world. Knee OA accounts for more than 80% of the disease's total burden and as per an estimate in US population, it affects at least 19% of adults aged 45 years and older. This was a randomised study aimed to evaluate the efficacy of platelet rich plasma (PRP) as a treatment modality for osteoarthritis knee in comparison to arthroscopic management. Materials and methods: This study was conducted from 2018 to 2020 at a tertiary care teaching hospital, under reference number ELMC&H/RCELL2019/39. A total of 70 patients of osteoarthritis knee with grade 2-3 according to the Kellgren-Lawrence classification were selected using computer generated random number among them 35 patients were subjected to arthroscopy (Group II) and 35 were administered platelet rich plasma injection (Group I) and evaluated at 3, 6 and 9 months of follow-up. Both the groups were assessed and scored with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analog Pain Scale (VAS) to compare pre-treatment and post-treatment values. As all the patients in the sample was followed-up, resulting into no loss of subjects. Result: Overall, percentage reduction in VAS score at 3 months, 6 months, and 9 months was 24.45±9.09, 18.45±11.60 and 8.29±14.19%, respectively in Group I and 18.96±5.85, 7.33±8.60 and 3.20±7.39%, respectively in Group II. A statistically significant difference between two groups was observed at 3- and 6-months' time intervals only (p<0.05). Overall, percentage reduction in WOMAC score at 3 months, 6 months and 9 months was 24.03±11.41, 17.45±9.24, and 9.49±9.80%, respectively in Group I and 11.27±5.73, 5.70±4.78, and -0.13±5.06%, respectively in Group II. At all the three-time intervals, the difference between two groups was significant statistically (p<0.001). Conclusion: This study suggested that both PRP as well as arthroscopy provide a reduction in WOMAC and VAS scores for pain among cases of knee osteoarthritis. Most effective reduction is observed at three months follow-up which thereafter tends to diminish. Of the two modalities, PRP seemed to have an edge over arthroscopic debridement, however, this efficacy was more pronounced for Kellgren-Lawrence Grade 2 as compared to Grade 3.

Cerebral miliary micro aneurysms in polyarteritis nodosa: report of two cases.

Cerebral involvement is rare in polyarteritis nodosa (PAN) and is mostly characterized by ischemic events and intracranial hemorrhages secondary to cerebral aneurysms is extremely rare. We report two patients of PAN with multiple intracranial aneurysms. One patient presented with intracerebral hemorrhage and in the other patient multiple intracranial aneurysms were incidental findings and were asymptomatic. Both our cases suggest that multiple intracranial aneurysms are not very uncommon in PAN and cerebral angiography should be considered while doing abdominal angiogram in these patients.

Intra-arterial thrombolysis in basilar artery occlusions combination of intra-arterial thrombolytics and Gp IIb/IIIa inhibitors in basilar artery thrombosis.

Basilar artery thrombosis has high morbidity and mortality. Though intra-arterial thrombolytics have proven efficacy in the treatment of acute basilar artery occlusion, the elevation of procoagulant factors in the blood after intra-arterial thrombolysis could result in subsequent thrombus formation and clinical deterioration. Glycoprotein IIb/IIIa inhibitors have been shown to reduce this elevation in procoagulants. We present a pilot study of three cases of acute basilar artery occlusion treated with a combination of intra-arterial thrombolytics and Gp IIb/IIIa inhibitor with remarkable clinical recovery seen in all the patients.

Heparin-induced thrombocytopenia in a case of endovascular aneurysm coiling.

We report a case of 46-year-old man who underwent endovascular coil embolization for left anterior inferior cerebellar and posterior inferior cerebellar aneurysms. During embolization of both aneurysms, thrombotic complications were observed along with a relative lack of response to heparin. Intra-arterial abciximab was used to recanalize an almost completely occluded posterior inferior cerebellar artery. A marked decrease in platelet counts was found soon after embolization, which normalized within a few days. Serologic tests confirmed heparin-induced thrombocytopenia. This syndrome should be considered in cases with thromboembolic complications during endovascular procedures, particularly in patients undergoing repeated heparin exposure. A sudden decrease in platelet counts and lack of response to heparin, manifested as a relative lack of increasing activated clotting time, should make one suspect this syndrome.

Isolation and characterization of viruses from natural outbreaks of reticuloendotheliosis in turkeys.

We have described the in vitro isolation of type-C RNA viruses from two outbreaks of a fatal neoplastic disease in turkeys we diagnosed as reticuloendotheliosis. The virus had a density of 1.16 g/ml in sucrose gradients, had a DNA polymerase capable of using both endogenous and exogenous (synthetic) templates, and was infectious in vitro for turkey and chick cells. The culture-propagated virus was oncogenic for turkeys. The virus isolates were unrelated to avian leukosis virus and antigenically identical to reticuloendotheliosis virus (REV) strain T. Thus our studies suggested that REV is a causative agent of naturally occurring, fatal leukosis in turkeys.

Comprehensive stroke care: an overview.

Stroke is a global epidemic and an important cause of morbidity and mortality. It ranks next to cardiovascular disease and cancer as a cause of death. "India is likely to suffer huge social and economic burden in the rehabilitation of stroke patients owing to increased life expectancy" and urbanization. Though, there are national programs in malaria eradication and tuberculosis control, there is hardly any governmental support in stroke management and rehabilitation. We propose to formulate stroke-prevention strategies specific to our national needs and covering all the age groups. Allocation of resources towards the stroke management and research is needed. Emphasis on stroke awareness in community should be stressed and should be inclusive of means of primordial and primary prevention apart from management of stroke and its recurrence. Recent international experience in stroke management has suggested the need of specialized stroke units (comprehensive stroke care under one roof). We wish to establish the need of creating awareness regarding the urgency of specialized care in acute stroke. We also wish to motivate our national health institutions to offer affordable, evidence based management of stroke and offer opportunities in stroke training and research.

Antithrombotic agents in cerebral ischaemia.

The current evidence suggests that aspirin is treatment of choice when compared to anticoagulants for patients with non-cardioembolic stroke. The usefulness of combination therapy (aspirin vs. with or without warfarin) is still debated. Likewise the combination of Aspirin with clopidogrel has no added advantage (MATCH Trial). However anticoagulant therapy significantly benefits high-risk patients with atrial fibrillation in the elderly subjects whereas aspirin may still be the drug of choice in stroke prevention in low risk group in the younger age. There is dire need for well planned randomized double blind controlled studies to define the role of Antithrombotic agents in "cryptogenic stroke" (PFO/ASD related) antiphospholipid antibody syndrome, arterial dissections and intraluminal clot syndromes. Evaluation and treatment of associated risk factors in all categories needs greater emphasis.

Seasonal effect and long-term nutritional status following exit from a Community-Based Management of Severe Acute Malnutrition program in Bihar, India.

BACKGROUND/OBJECTIVES: Children aged 6 months to 5 years completing treatment for severe acute malnutrition (SAM) in a Médecins Sans Frontières Community Management of Acute Malnutrition (CMAM) program in Bihar, India, showed high cure rates; however, the program suffered default rates of 38%. This report describes the nutritional status of 1956 children followed up between 3 and 18 months after exiting the program. SUBJECTS/METHODS: All children aged 6-59 months discharged as cured with mid-upper arm circumference (MUAC) ⩾120 mm or who defaulted from the program with MUAC <115 mm were traced at 3, 6, 9, 12 and 18 months (±10 days) before three exit reference dates: first at the end of the food insecure period, second after the 2-month food security and third after the 4-month food security. RESULTS: Overall, 68.7% (n=692) of defaulters and 76.2% (n=1264) of children discharged as cured were traced. Combined rates of non-recovery in children who defaulted with MUAC <115 mm were 41%, 30.1%, 9.9%, 6.1% and 3.6% at 3, 6, 9, 12 and 18 months following exit, respectively. Combined rates of relapse among cured cases (MUAC ⩾120 mm) were 9.1%, 2.9%, 2.1%, 2.8% and 0% at 3, 6, 9, 12 and 18 months following discharge, respectively. Prevalence of undernutrition increased substantially for both groups traced during low food security periods. Odds of death were much higher for children defaulting with MUAC <110 mm when compared with children discharged as cured, who shared the same mortality risk as those defaulting with MUAC 110-<115 mm. CONCLUSIONS: Seasonal food security predicted short-term nutritional status after exit, with relapse rates and non-recovery from SAM much higher during food insecurity. Mortality outcomes suggest that a MUAC of 110 mm may be considered an appropriate admission point for SAM treatment programs in this context.

Postangiographic thrombosis of a spinal arteriovenous malformation: case report.

The authors report the case of a 30-year-old man who presented with progressive neurological deficits due to a spinal arteriovenous malformation (AVM). There was sudden increase in his neurological deficits after diagnostic angiography was performed. Repeated magnetic resonance imaging and angiography revealed complete thrombosis of the malformation. Stenosis in the draining vein was the most probable cause of this postangiographic occlusion of the AVM. Contrast injection during angiography may have precipitated the thrombosis.

Fusiform aneurysm of a persistent trigeminal artery.

OBJECTIVE: Fusiform aneurysms of the persistent trigeminal artery are rare and endovascular treatment of these aneurysms has not been attempted previously. We describe a case of persistent trigeminal artery with a fusiform aneurysm in its middle third, managed using Guglielmi detachable coils (GDC). CLINICAL PRESENTATION: A 50-year-old, diabetic and hypertensive patient presented with sudden onset headache and neck stiffness. On examination, she was conscious but disoriented, without cranial nerve or sensorimotor deficits. Four-vessel cerebral digital subtraction angiography revealed a fusiform aneurysm of the middle third of a persistent trigeminal artery on the left side with adult type posterior cerebral arteries. INTERVENTION: Guglielmi detachable coils were used for occlusion of the persistent trigeminal artery. RESULTS: The procedure was well tolerated but delayed ischemic neurological deficits developed due to vasospasm. CONCLUSIONS: (1) In spite of angiographically documented independence of the anterior and posterior cerebral circulation, occlusion of a persistent trigeminal artery using endovascular techniques may result in posterior circulation stroke due to a number of factors, including occlusion of brainstem perforators taking origin from the persistent trigeminal artery or vasospasm. (2) The timing for endovascular intervention following aneurysmal rupture remains poorly defined.

Abulia: no will, no way.

Abulia refers to impaired ability to perform voluntary actions, show initiative, make decisions along with decrease in movements, speech, thought and emotional reactions. We describe here two patients who developed this condition following bilateral insult to different sites in the centromedial core of the brain, the first following the cerebral venous thrombosis and the second after the right ACA and MCA infarct. Both these patients improved following treatment with Bromocriptine. These cases are described for proper identification and management by the clinicians.

Recurrent lymphocytic hypophysitis in a woman 27 years after subtotal adrenalectomy for hypercortisolism possibly of autoimmune origin.

Lymphocytic hypophysitis commonly occurs in females in peripartum period but several unusual presentations have been reported. Here we report a rare case of recurrent lymphocytic hypophysitis in a woman who had subtotal adrenalectomy for hypercortisolism 27 years back. Polyglandular autoimmune endocrinopathy with an uncommon combination of Cushing's syndrome and recurrent hypophysitis is a strong possibility in this case. Treatment with steroids has been found to have beneficial effect.

Cytologic screening for the detection of cancer in the uterine cervix--a survey in Patna (India).

Cytologic screening of the uterine cervix of 10,012 married women of Patna (India) was conducted to find out precancerous and cancerous lesions in different age and parity groups. Of the "pap" smears, 80.1% were normal, 11.1% were inflammatory, 5.8% showed dyskaryosis and 2.8% had cellular profiles suggestive of malignancy. In higher age groups i.e., in 40-49 and 50-59 years, the percentage of inflammatory smears were increased to 15 and 35.8; and invasive carcinoma to 8.28 and 14.19, respectively. Higher parity groups (four and above) had greater incidence of invasive carcinoma (6.7%) than those of lower parity groups (1.88%).

Pure motor hemiparesis due to non-hypertensive putaminal haemorrhage.

The syndrome of pure motor hemiplegia (PMH) has been traditionally regarded to be due to lacunar infarcts at various places in the brain. Recently, attention has been drawn towards various other aetiological factors which have been responsible for this clinical presentation. PMH as a result of hypertensive putaminal haemorrhage is extremely uncommon. A case of PMH as a result of non-hypertensive putaminal haemorrhage is described.