The Impact of Treatment Delay on Hepatitis C Liver Transplant Outcomes.

Background: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) have improved outcomes in liver transplant recipients (LTRs). However, the timing of HCV treatment and approach to treating rejection have not been well described. Additionally, pharmacists' roles in these comprehensive areas have not been investigated. Methods: This single-center, retrospective, cohort review compared 1-year graft and patient survival between HCV-positive and HCV-negative LTRs. Secondary endpoints included 1-year rejection rates, HCV sustained virologic response and time to HCV treatment. Results: Ninety-two HCV Nucleic Acid Amplification Test (NAT)-positive LTRs were matched 1:1 to HCV-seronegative LTRs. One-year graft and patient survival were similar between groups. HCV-positive LTRs were more likely to experience biopsy-proven acute rejection (BPAR), and despite treatment with pulse steroids, there was no impact on graft survival or occurrence of fibrosing cholestatic hepatitis (FCH). Time to HCV treatment was 5.4-6.4 months post-transplant, with no treatment failures or impact on graft or patient survival. Conclusions: No difference was seen in graft survival at 1 year between HCV-positive and HCV-seronegative LTRs. Delayed time to treatment of HCV and treatment of rejections in the HCV-positive cohort did not impact outcomes. However, pharmacist-driven protocols could ensure more efficient initiation of HCV treatment in the future.

Impact of high MELD scores on CMV viremia following liver transplantation.

INTRODUCTION: Advanced liver disease or cirrhosis is associated with an increased risk of infections; however, the impact of high pretransplant model for end-stage liver disease (MELD) score on cytomegalovirus (CMV) viremia after liver transplantation is unknown. METHODS: This single-center, retrospective, cohort study evaluated CMV high-risk (CMV immunoglobulin G D+/R-) liver transplant recipients who received valganciclovir prophylaxis for 3 months between 2009 and 2019. Patients were stratified by pretransplant MELD score of <35 (low MELD) and ≥35 (high MELD). The primary outcome was 12-month CMV viremia, and secondary outcomes included CMV resistance and tissue invasive disease, mortality, biopsy-proven acute rejection (BPAR), leukopenia, and thrombocytopenia. Multivariable Cox proportional-hazards modeling was used to assess the association of MELD score with the time to CMV viremia. RESULTS: There were 162 and 79 patients in the low and high MELD groups, respectively. Pretransplant MELD score ≥35 was associated with an increased risk of CMV viremia (hazard ratio [HR] 1.73; confidence interval 1.06-2.82, p = .03). CMV viremia occurred at 162 ± 61 days in the low MELD group and 139 ± 62 days in the high MELD group. Although BPAR occurred early at 30 days (13-59) in the low-MELD group and at 18 days (11-66) in the high-MELD group (p = .56), BPAR was not associated with an increased risk of CMV viremia (HR 1.55 [0.93-2.60], p = .1). DISCUSSION: MELD scores ≥35 were associated with an increased hazards of CMV viremia. In liver transplant recipients with MELD scores ≥35 who are CMV high-risk, additional CMV intervention may be warranted.

Comparison of coronally advanced versus semilunar coronally repositioned flap in the management of maxillary gingival recessions.

OBJECTIVES: Maxillary gingival recessions can be managed by both semilunar coronally repositioned flap (SLCRF) and coronally advanced flap (CAF). The objective of this study was to compare SLRCF and CAF in terms of wound healing and periodontal parameters in the presence of magnification. MATERIALS AND METHODS: Thirty patients with Miller's class I gingival recession in maxillary anteriors and premolars were assigned to 2 groups including SLCRF and CAF. All procedures were performed using 2.5× magnifying loupes. Wound healing and periodontal clinical parameters were assessed at baseline and at 2nd, 4th, 8th and 12th week. RESULTS: No significant difference was observed in wound healing and mean percentage root coverage in both the groups at 12th week (p > 0.05). However, SLCRF showed a statistically significant reduction in percentage of root coverage (PRC) at 12th week compared to 2nd week (p < 0.05). A significant gain in Clinical attachment level, width of keratinised tissue and a significant reduction in Recession Depth and Probing Depth were seen in both the groups at 12th week. CONCLUSION: Within the limitation of this study, both techniques resulted in similar wound healing at 12th week with the use of magnification. CAF provided more root coverage compared to SLCRF technique in the maxillary class I gingival recession defects.

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation.

INTRODUCTION: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. RESEARCH QUESTION: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. DESIGN: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. RESULTS: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. DISCUSSION: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Survival benefit of renal transplantation in octogenarians.

BACKGROUND: Elderly patients are the fastest growing population requiring renal replacement therapy. As previous studies have shown a survival benefit of kidney transplantation compared to dialysis for end-stage renal disease, we sought to evaluate if this survival benefit extends to octogenarians. METHODS: This was a single-center retrospective cohort study of renal allograft recipients ≥80 years transplanted from 1999 to 2014 who were compared to patients listed during the same period that did not proceed to transplantation. A secondary matched group was selected from the UNOS transplant waitlist database. The primary outcome was patient survival. Secondary outcomes included graft survival and rejection incidence. RESULTS: Thirty-three transplanted patients were compared to 71 patients waitlisted at our center and 66 patients from the UNOS database. Patients in the study group were transplanted 20.8 ± 16.1 months after listing. Patient survival was 87.8% at 6 months and 1 year and 71.4% at 3 years. Kidney transplantation was associated with a significant decrease in the risk of death after listing (HR: 0.22, CI: 0.11-0.45, P < .001). CONCLUSION: With escalating life expectancy, kidney transplantation is a suitable treatment option in eligible octogenarians.

The Correlation of Endothelial Nitric Oxide Synthase (eNOS) Polymorphism and Other Risk Factors with Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study.

OBJECTIVE: Endothelial nitric oxide synthase gene (eNOS) polymorphism is an association with cerebral aneurysm formation, rupture, and vasospasm and plays a role in the a functional outcome. PATIENTS AND METHODS: The aim of the study was to evaluate the role of eNOS gene polymorphism and further assess the predictors of outcome in the aneurysmal subarachnoid hemorrhage (aSAH). A prospective case-control study was conducted from 2009 to 2012 among those who presented with aSAH. A serum sample was collected from aSAH patients along with age and sex-matched healthy controls. The frequency of polymorphism of eNOS gene and other factors (demographic and aneurysmal) were correlated with functional outcome at six month of follow-up. RESULTS: 100 patients with aSAH and 100 healthy controls were enrolled in the cohort. The mean age of the patient group was 51.61 years and control group was 45.81 years with a male:female ratio of 1:1.38 and 1:1.08 for patients and controls, respectively. Among all eNOS polymorphisms, 4BB (65%) 24-VNTR, TT (71%) of T-786C, and GG (71%) of G947T were the most common and frequency was similar in the control group. The occurrences of hypertension, smoking, diabetes were 32%, 37%, and 7% respectively in the patient group. Maximum patients were in WFNS grade 1 (53%) followed by 23% grade 2 and only 10% in grade 4. Fisher grade 3 (57%) was the most common followed by Fisher grade 4 (28%). Most aneurysms (97%) were in anterior circulation. 83% of the aneurysms were clipped and 10% underwent coiling. Size-wise most of the aneurysms were in the middle group (6-9 mm) followed by bigger group (>10 mm) (37%); only 6% aneurysms were in the small aneurysm (<6 mm) group. 33% of the patients had evidence of vasospasm. TT of G894T polymorphism (60%) had the highest incidence of vasospasm. Univariate analysis showed smoking (OR: 3.19, CI: 1.19-8.84, P = 0.01), 4AA (OR: 12.15, CI: 1.13-624.9, P = 0.03) variety of 24-VNTR polymorphism, CC (OR: 15.39, CI: 1.60-762.8, P = 0.01) variety of T786C polymorphism, Fisher grade 4 (OR: 3.43, CI: 1.24-9.68, P = 0.01), WFNS grade (poor vs. good) (OR: 3.42, CI: 1.17-10.12, P = 0.02), vasospasm (OR: 3.84, CI: 1.42-10.75, P = 0.006), intraoperative rupture (OR: 4.77, CI: 1.55-15.27, P = 0.004) were significantly related with unfavorable outcome at 6 months follow-up. In regression analysis, smoking (CI: 0.06-0.69, P = 0.01), Fisher grade 4 (CI: 0.09-1.00, P = 0.05), and intraoperative rupture (CI: 0.05-0.89, P = 0.03) were correlated with an unfavorable outcome at 6 months follow-up. CONCLUSION: The eNOS gene polymorphism, smoking, clinical grade (WFNS), Fisher grade, intraoperative rupture, and vasospasm play a role in functional outcome after the treatment of cerebral aneurysms.

Clinical outcomes of valganciclovir prophylaxis in high-risk (D+/R-) renal transplant recipients experiencing delayed graft function.

BACKGROUND: Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear. METHODS: This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66). RESULTS: Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively. CONCLUSION: Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.

Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma.

PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.

Compact and Programmable Ultrasound Front-End Processing Module for Research Activities.

Ultrasound signal processing involves diversified requirements in terms of processing, power, hardware etc. Ultrasound signal processing is continuously evolving area, and hence researchers who need to evaluate the novel algorithms in real time need to have the complete hardware setup. Commercially available ultrasound scanners are based on Application Specific Integrated Circuit (ASIC) and hence it does not have any provision to test the novel algorithms. In this paper, we propose a compact and programmable module, equipped with required hardware support for implementing complete front-end processing. The board is supported with an external interface that can be connected to other computing platforms like Field-Programmable Gate Arrays (FPGA's), and Digital Signal Processors (DSP's), etc, for implementing the mid-end and back-end algorithms. Provision is provided for acquiring the raw RF data, which will be beneficial for developing computer-aided diagnostics, and also to develop signal processing algorithms in offline. The proposed front-end hardware module will be very beneficial for rapid testing of the novel ultrasound signal processing algorithms.

Collaborative practice agreement in solid organ transplantation.

Background Given the complexity of solid organ transplant recipients, a multidisciplinary approach is required. To promote medication safety and enable providers to focus on the medical and surgical needs of these patients, our department of pharmacy created a collaborative practice agreement between physicians and pharmacists. Through this agreement, credentialed pharmacists are empowered to provide inpatient services including initiation and adjustment of medications through independent review of laboratory results after multidisciplinary rounds. Objective To evaluate the effect of our collaborative practice agreement on clinical care and institutional finances. Setting An inpatient setting at a large academic medical center. Methods Three transplant pharmacists entered all clinical interventions made on abdominal transplant recipients between September and October 2013 into Quantifi®, a software application that categorizes and assigns a cost savings value based on impact and type of intervention. Main outcome measure The main outcome measures in this study were number and categorization of interventions, as well as estimated cost savings to the institution. Results There were 1060 interventions recorded, an average of 20 interventions per pharmacist per day. The most common interventions were pharmacokinetic evaluations (36%) and dose adjustments (19%). Over the time period, these interventions translated into an estimated savings of $107,634.00, or an annual cost savings of $373,131.20 per pharmacist, or a cost-benefit ratio of 2.65 to the institution. Conclusions Based on our study, implementation of a collaborative practice agreement enables credentialed pharmacists to make clinically and financially meaningful interventions in a complex patient population.

Predictors of Surgical Outcomes of Traumatic Peripheral Nerve Injuries in Children: An Institutional Experience.

AIM: This study was undertaken to address the epidemiological characteristics, operative details, and surgical outcome of peripheral nerve injuries in children treated in a tertiary hospital in India (NIMHANS, Bangalore). MATERIALS AND METHODS: This is a retrospective study of epidemiology, operative findings, and surgical outcomes over the period of 2000-2016. Our series includes 102 children with peripheral nerve injuries of various causes. RESULTS: Intramuscular injections were the most common cause (52.9%), followed by entrapment (15.6%). The most common nerve involved was the sciatic nerve (54.9%), followed by the common peroneal nerve (13.7%), the ulnar nerve (10.8%), and the radial nerve (10.8%). Perineural adhesion was the most common intraoperative finding (74.5%), followed by a neuroma in continuity (14.7%) and gap (10.8%). Most of the children with peripheral adhesion underwent external and internal neurolysis (75.5%). Follow-up was available for 67 children. The median follow-up period was 7 months (range 3-36). The outcome was assessed according to MRC grading. Favorable functional improvement was noted in 76.1% of the children. Age less than 10 years (p = 0. 06), injury before 6 months (p = 0.03), and MRC motor grade (<3) (p = 0. 01) were positive predictive factors related to the final outcome. CONCLUSION: Early surgical intervention, age less than 10 years, and incomplete motor palsy were the best predictors of a superior functional outcome. This study can serve as a guide to determine the epidemiology, duration of intervention, and surgical outcome of traumatic peripheral nerve injuries in the pediatric population.

Deep scattering convolution network based features for ultrasonic fatty liver tissue characterization.

Accumulation of excess fat in the liver tissue is the leading cause for dysfunction of liver, which can lead to the diseases from fibrosis to end stage cirrhosis. Hence, early detection of fatty liver becomes crucial in avoiding the liver from permanent failure. Depending on the concentration of fat in the tissue, the liver is classified as Normal, Grade 1, Grade 2 and Grade 3 respectively. The texture of liver tissue in ultrasound image is so specific to the concentration of fat, hence classifying the fatty liver is formulated as a texture discrimination problem. In this paper, we present an automated algorithm for grading the tissue of a fatty liver based on the features obtained from the invariant scattering convolution network (ISCN). ISCN, which involves cascade of modulus complex wavelet transforms and averaging operations results in scattering coefficients (SC), these coefficients will give stable invariant representations and also maps the texture of fatty liver image to a discriminative manifold giving good features for classification. SC are of high dimension and hence a compact representation feature is obtained by summing all the SC coefficients. Summed SC features along with cubic SVM classifier gave an accuracy of 96.6% in automatically categorizing the fatty content present in the tissue of a liver.

Smartphone based automatic organ validation in ultrasound video.

Telesonography involves transmission of ultrasound video from remote areas to the doctors for getting diagnosis. Due to the lack of trained sonographers in remote areas, the ultrasound videos scanned by these untrained persons do not contain the proper information that is required by a physician. As compared to standard methods for video transmission, mHealth driven systems need to be developed for transmitting valid medical videos. To overcome this problem, we are proposing an organ validation algorithm to evaluate the ultrasound video based on the content present. This will guide the semi skilled person to acquire the representative data from patient. Advancement in smartphone technology allows us to perform high medical image processing on smartphone. In this paper we have developed an Application (APP) for a smartphone which can automatically detect the valid frames (which consist of clear organ visibility) in an ultrasound video and ignores the invalid frames (which consist of no-organ visibility), and produces a compressed sized video. This is done by extracting the GIST features from the Region of Interest (ROI) of the frame and then classifying the frame using SVM classifier with quadratic kernel. The developed application resulted with the accuracy of 94.93% in classifying valid and invalid images.

Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer.

BACKGROUND: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. METHODS AND MATERIAL: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. RESULTS: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months).

A rare case of multiple brain abscess and probably disseminated phaeohyphomycosis due to Cladophialophora bantiana in an immunosuppressed individual from India.

Cladophialophora bantiana, a dematiaceous neurotropic mold causes rare and lethal brain abscess, commonly in immunocompetent hosts. We report a rare and probably a case of disseminated infection with this black mold in an immunosuppressed individual from India. A 55-year-old diabetic male presented with severe headache, blurred-vision, behavioural abnormalities, eye-pain and ear-discharge. He was undergoing treatment for hypertension, prostatomegaly and obstructive pulmonary disease. He was on steroids for the past six years for uveitis. Haematology reports indicated elevated WBC and platelet count. He was negative for HIV, hepatitis, autoimmune antibodies and tumour markers. CD4 count was within normal limits. Brain magnetic resonance imaging revealed multiple ring-enhancing lesions and oedema in the left tempero-parietal region. Chest X-ray showed irregular consolidations in right paracardiac region and confluence in both lungs. Positron Emission Tomography of whole body revealed multiple lesions in brain, lungs, lymph nodes and C3-vertebrae. Histopathology of the lung lesion showed non-tuberculous infectious pathology and brain lesions showed necrosis with occurrence of pigmented hyphal fungi. The pus aspirated during surgical excision of brain lesions grew black mold, identified as C. bantiana. Although patient was started on intravenous Voriconazole, he succumbed to the infection after 7 days. The lesion was initially suspected to be of tuberculous etiology, and the lesions in lungs were also suggestive of malignancy, which was however ruled out by histopathological examination. Such diagnostic dilemmas are common in the infection caused by Cladophialophora, which can cause treatment delay and death. Early diagnosis is therefore mandatory for the rapid treatment and survival of patients.

Successful treatment of primary cerebral mucormycosis: Role of microbiologist.

Fungal brain abscess is rare with a rapidly progressive disease with fulminant course and invariably fatal outcome, unless diagnosed early and treated rapidly. We report a 56-year-old woman diagnosed to have fungal abscess who recovered completely following amphotericin B treatment. She presented with weakness of the right hand, deviation of mouth to left and aphasia for 2 days. Computed tomography of the brain revealed a left frontal capsuloganglionic hypodense lesion. Stereotactic biopsy was performed, and microbiological confirmation of non-septate fungal hyphae from pus from aspirate within 2 h helped initiate timely and appropriate treatment leading to cure. Histopathology and culture later confirmed mucormycosis.

Reduced small world brain connectivity in probands with a family history of epilepsy.

BACKGROUND AND PURPOSE: The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). METHODS: Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE-, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. RESULTS: A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE- (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. CONCLUSION: Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations.