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1.  Intraoral and Oropharyngeal Lesions: Role of Fine Needle Aspiration Cytology in the Diagnosis 
The oral cavity is affected by a wide range of pathologic lesions, for which a morphologic diagnosis is required for proper management. Fine needle aspiration (FNA) is being increasingly used for preliminary diagnoses of such lesions. This is retrospective analysis of intraoral and oropharyngeal lesions diagnosed with FNAC over a period of 7 years. Out of total 55 cases, a definite diagnosis could be made on cytology in 50 cases (90.9 %). These 50 cases were further included in the study. Thirty cases were reported as non-neoplastic and 20 as neoplastic (11 benign and nine malignant). The diagnoses were made taking into account the background material (blood, mucin) and the predominant cells present (neutrophils, lymphoid cells, macrophages, hemosiderin laden macrophages, squamous cells, basaloid cells, spindle cells, giant cells). Histopathological diagnosis was available in 17 cases and corresponded with FNA diagnosis in 16 cases (94.12 %). No significant complications were seen in patients undergoing these FNAs. It can be concluded that FNA is a simple and rapid diagnostic test that can be useful for preliminary assessment of oral and oropharyngeal lesions.
PMCID: PMC4678267  PMID: 26693456
Oral cavity; Pharyngeal masses; Tongue swelling; Cheek; Fine needle aspiration
2.  Hematopoietic cell transplantation as curative therapy for patients with myelofibrosis: Long-term success in all age groups 
Myeloproliferative neoplasms (MPN) are chronic marrow disorders with variable prognosis. Most patients with Polycythemia Vera, Essential Thrombocythemia or even Primary Myelofibrosis (PMF) are successfully managed by conservative strategies for years or even decades, and recent data suggest that even in patients with high-risk disease, in particular those with PMF, life expectancy can be extended by treatment with JAK2 inhibitors. However, none of those modalities are curative, and once marrow failure develops, the disease “accelerates” or transforms to acute leukemia, the only treatment option able to effectively treat and, in fact, cure MPN is allogeneic hematopoietic cell transplantation (HCT). Outcome is superior if HCT is performed before leukemic transformation occurs. Several reports document survival in unmaintained remission beyond 10 years. The most recent analyses show reduced regimen-related mortality (less than 10% or even 5% at day 100), and progressively improved survival with both HLA-identical sibling and unrelated donors. The development of low/reduced intensity conditioning regimens has contributed to the improved success rate and has allowed to successfully carry out HCT in patients in the 7th and even 8th decade of life. We propose, therefore, that HCT should be offered to fit patients in these age groups and should be covered by their respective insurance carriers.
PMCID: PMC4604067  PMID: 26371371
3.  High-Definition and Non-Invasive Brain Modulation of Pain and Motor Dysfunction in Chronic TMD 
Brain stimulation  2015;8(6):1085-1092.
Temporomandibular disorders (TMD) have a relatively high prevalence and in many patients pain and masticatory dysfunction persist despite a range of treatments. Non-invasive brain neuromodulatory methods, namely transcranial direct current stimulation (tDCS), can provide relatively long-lasting pain relief in chronic pain patients.
To define the neuromodulatory effect of five daily 2×2 motor cortex high-definition tDCS (HD-tDCS) sessions on clinical pain and motor measures in chronic TMD patients. It is predicted that M1 HD-tDCS will selectively modulate clinical measures, by showing greater analgesic after-effects compared to placebo, and active treatment will increase pain free jaw movement more than placebo.
Twenty-four females with chronic myofascial TMD pain underwent five daily, 20-minute sessions of active or sham 2 milliamps (mA) HD-tDCS. Measurable outcomes included pain-free mouth opening, visual analog scale (VAS), sectional sensory-discriminative pain measures tracked by a mobile application, short form of the McGill Pain Questionnaire, and the Positive and Negative Affect Schedule. Follow-up occurred at one-week and four-weeks post treatment.
There were significant improvements for clinical pain and motor measurements in the active HD-tDCS group compared to the placebo group for: responders with pain relief above 50% in the VAS at four-week follow-up (p=0.04); pain-free mouth opening at one-week follow-up (p<0.01); and sectional pain area, intensity and their sum measures contralateral to putative M1 stimulation during the treatment week (p<0.01). No changes in emotional values were shown between groups.
Putative M1 stimulation by HD-tDCS selectively improved meaningful clinical sensory-discriminative pain and motor measures during stimulation, and up to four weeks post-treatment in chronic myofascial TMD pain patients.
PMCID: PMC4656049  PMID: 26226938
transcranial direct current stimulation; temporomandibular disorder; pain; PainTrek; clinical trial
4.  A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia 
Cancer Medicine  2016;5(11):3031-3040.
Acute myeloid leukemia (AML) cells meet the higher energy, metabolic, and signaling demands of the cell by increasing mitochondrial biogenesis and mitochondrial protein translation. Blocking mitochondrial protein synthesis through genetic and chemical approaches kills human AML cells at all stages of development in vitro and in vivo. Tigecycline is an antimicrobial that we found inhibits mitochondrial protein synthesis in AML cells. Therefore, we conducted a phase 1 dose‐escalation study of tigecycline administered intravenously daily 5 of 7 days for 2 weeks to patients with AML. A total of 27 adult patients with relapsed and refractory AML were enrolled in this study with 42 cycles being administered over seven dose levels (50–350 mg/day). Two patients experienced DLTs related to tigecycline at the 350 mg/day level resulting in a maximal tolerated dose of tigecycline of 300 mg as a once daily infusion. Pharmacokinetic experiments showed that tigecycline had a markedly shorter half‐life in these patients than reported for noncancer patients. No significant pharmacodynamic changes or clinical responses were observed. Thus, we have defined the safety of once daily tigecycline in patients with refractory AML. Future studies should focus on schedules of the drug that permit more sustained target inhibition.
PMCID: PMC5119957  PMID: 27734609
Cox‐1; Cox‐4; mitochondrial protein synthesis; pharmacodynamics; pharmacokinetics
5.  Tacrolimus versus cyclosporine after hematopoietic cell transplantation for acquired aplastic anemia 
Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD and mortality. TAC+MTX was used more frequently in older patients and in recent years in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier ANC recovery in SIB recipients. Other outcomes did not differ statistically between the two regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after HCT for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia.
PMCID: PMC4568149  PMID: 26033280
aplastic anemia; hematopoietic cell transplantation; graft-versus-host disease; immunosuppression; cyclosporine; tacrolimus
6.  Comparison of Characteristics and Outcomes of Trial Participants and Non-participants: Example of Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial 
Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) transplantation from unrelated donors (URD), conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN).
We compared characteristics and outcomes of study participants (n=494) and non-participants (n=1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time-period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the two groups using Cox proportional hazards regression models.
No significant differences in age, sex and disease distribution, race/ ethnicity, HLA matching, comorbidities and interval from diagnosis to HCT were seen between the participants and non-participants. Non-participants were more likely to have lower performance status, lower-risk disease, and older donors, and to receive myeloablative conditioning and anti-thymocyte globulin. Non-participants were also more likely to receive PB grafts, the intervention tested in the trial (66% vs. 50% p<0.001). Overall survival, transplant-related mortality, and incidences of acute or chronic GVHD were comparable between the two groups though relapse was higher (HR 1.22, 95% CI 1.02–1.46, p=0.028) in non-participants.
Despite differences in certain baseline characteristics, survival was comparable between study participants and non-participants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients.
PMCID: PMC4568172  PMID: 26071866
7.  A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia 
Leukemia & lymphoma  2015;56(10):2793-2802.
This phase I trial evaluated two schedules of escalating vorinostat in combination with decitabine every 28 days: (i) sequential or (ii) concurrent. There were three dose-limiting toxicities: grade 3 fatigue and generalized muscle weakness on the sequential schedule (n = 1) and grade 3 fatigue on the concurrent schedule (n = 2). The maximum tolerated dose was not reached on both planned schedules. The overall response rate (ORR) was 23% (three complete response [CR], two CR with incomplete incomplete blood count recovery [CRi], one partial response [PR] and two morphological leukemic free state [MLFS]). The ORR for all and previously untreated patients in the sequential arm was 13% (one CRi; one MLFS) and 0% compared to 30% (three CR; one CRi; one PR; one MLFS) and 36% in the concurrent arm (p = 0.26 for both), respectively. Decitabine plus vorinostat was safe and has clinical activity in patients with previously untreated acute myeloid leukemia. Responses appear higher with the concurrent dose schedule. Cumulative toxicities may limit long-term usage on the current dose/schedules.
PMCID: PMC4688006  PMID: 25682963
Decitabine; vorinostat; hypomethylating agent; histone deacetylase inhibitor; acute myeloid leukemia
8.  Isolation and characterization of quinine from Polygonatum verticillatum: A new marker approach to identify substitution and adulteration 
Polygonatum verticillatum (Mahameda) is an important ingredient of Ashtawarga and Ayurvedic formulations. Nowadays, it comes under the category of endangered plants due to large scale and indiscriminate collection of wild material. To overcome the scarcity, substitutes of Mahameda are also commonly used in market. These additives are different from the authentic plant by Ayurvedic and pharmacological theory of drug action, thereby resulting in substitution/adulteration. Substitution is a critical issue in isolation and quantification of the therapeutically active ingredients that can be used as markers in the identification of substitution/adulteration. Methanolic extract of the rhizomes of P. verticillatum was subjected to preliminary phytochemical screening for the detection of phytoconstituents, followed by column chromatography for isolation of the marker. The column was first eluted with pure hexane, and polarity of the solvent was gradually increased. A total of 1180 fractions were collected and pooled on the basis of thin-layer chromatography profile. The single compound was isolated and confirmed by chemical test, melting point, spectral analysis, and comparison with literature. Phytochemical screening of the extract shows the presence of alkaloids, flavonoids, carbohydrates, terpenoids, and phenolics. A pure white crystalline powder was isolated by column chromatography which was characterized as (6-methoxyquinolin-4-yl-8-vinylquinuclidin-2-yl) methanol, i.e. Quinine. The isolated compound, Quinine, was identified as a novel compound in Mahameda as it has not been reported in the genus Polygonatum, till now. It can be used as a marker for the identification of substitution/adulteration and standardization of P. verticillatum.
PMCID: PMC5052943  PMID: 27833896
Adulterants; column chromatography; marker compound; Polygonatum verticillatum; substituents
9.  Pre-Clinical Testing of a Novel Thin Film Nitinol Flow Diversion Stent in a Rabbit Elastase Aneurysm Model 
Thin Film Nitinol (TFN) can be processed to produce a thin microporous sheet with low percent metal coverage (<20%) and high pore density (~70 pores/mm2) for flow diversion. We present in vivo results from treatment of experimental rabbit aneurysms using a TFN-based flow diversion device.
Materials and Methods
Nineteen aneurysms in the rabbit elastase aneurysm model were treated with a single TFN flow diverter. Devices were also placed over 17 lumbar arteries to model peri-aneurysmal branch arteries of the intracranial circulation. Angiography was performed at 2 weeks (n=7), 1 month (n=8) and 3 months (n=4) immediately before sacrifice. Aneurysm occlusion was graded on a 3-point scale (Grade 1, complete occlusion; Grade 2, near-complete occlusion; Grade 3, incomplete occlusion). Toluidine blue staining was used for histologic evaluation. En face CD31 immunofluorescent staining was performed to quantify neck endothelialization.
Markedly reduced intra-aneurysmal flow was observed on angiography immediately after device placement in all aneurysms. Grade 1 or 2 occlusion was noted in four (57%) aneurysms at 2-week, in six (75%) aneurysms at 4-week and in three (75%) aneurysms at 12-week follow-up. All 17 lumbar arteries were patent. CD31 staining showed that 75 ± 16% of the aneurysm neck region was endothelialized. Histopathology demonstrated incorporation of the TFN flow diverter into the vessel wall and no evidence of excessive neointimal hyperplasia.
In this rabbit model, the TFN flow diverter achieved high rates of aneurysm occlusion and promoted tissue in-growth and aneurysm neck healing, even early after implantation.
PMCID: PMC4792643  PMID: 26494695
10.  Identification of pre-leukemic hematopoietic stem cells in acute leukemia 
Nature  2014;506(7488):328-333.
In acute myeloid leukemia (AML), the cell of origin, nature and biological consequences of initiating lesions and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukemic phase. Here, highly purified hematopoietic stem cells (HSC), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3a mutations (DNMT3amut) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3amut-bearing HSC exhibited multilineage repopulation advantage over non-mutated HSC in xenografts, establishing their identity as pre-leukemic-HSC (preL-HSC). preL-HSC were found in remission samples indicating that they survive chemotherapy. Thus DNMT3amut arises early in AML evolution, likely in HSC, leading to a clonally expanded pool of preL-HSC from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.
PMCID: PMC4991939  PMID: 24522528 CAMSID: cams3940
11.  Emerging role of bioinformatics tools and software in evolution of clinical research 
Clinical research is making toiling efforts for promotion and wellbeing of the health status of the people. There is a rapid increase in number and severity of diseases like cancer, hepatitis, HIV etc, resulting in high morbidity and mortality. Clinical research involves drug discovery and development whereas clinical trials are performed to establish safety and efficacy of drugs. Drug discovery is a long process starting with the target identification, validation and lead optimization. This is followed by the preclinical trials, intensive clinical trials and eventually post marketing vigilance for drug safety. Softwares and the bioinformatics tools play a great role not only in the drug discovery but also in drug development. It involves the use of informatics in the development of new knowledge pertaining to health and disease, data management during clinical trials and to use clinical data for secondary research. In addition, new technology likes molecular docking, molecular dynamics simulation, proteomics and quantitative structure activity relationship in clinical research results in faster and easier drug discovery process. During the preclinical trials, the software is used for randomization to remove bias and to plan study design. In clinical trials software like electronic data capture, Remote data capture and electronic case report form (eCRF) is used to store the data. eClinical, Oracle clinical are software used for clinical data management and for statistical analysis of the data. After the drug is marketed the safety of a drug could be monitored by drug safety software like Oracle Argus or ARISg. Therefore, softwares are used from the very early stages of drug designing, to drug development, clinical trials and during pharmacovigilance. This review describes different aspects related to application of computers and bioinformatics in drug designing, discovery and development, formulation designing and clinical research.
PMCID: PMC4936069  PMID: 27453827
Argus; ARISg; bioinformatics; clinical research; eClinical
12.  Thumb ultrasound: Technique and pathologies 
Ultrasound is ideally suited for the assessment of complex anatomy and pathologies of the thumb. Focused and dynamic thumb ultrasound can provide a rapid real-time diagnosis and can be used for guided treatment in certain clinical situations. We present a simplified approach to scanning technique for thumb-related pathologies and illustrate a spectrum of common and uncommon pathologies encountered.
PMCID: PMC5036340  PMID: 27857468
Pathology; technique; thumb; ultrasound
13.  Dexamethasone treatment promotes Bcl-2-dependence in multiple myeloma resulting in sensitivity to Venetoclax 
Leukemia  2015;30(5):1086-1093.
Venetoclax (ABT-199), a specific inhibitor of the anti-apoptotic protein Bcl-2, is currently in phase I clinical trials for multiple myeloma. Results suggest that venetoclax is only active in a small cohort of patients therefore we wanted to determine its efficacy when used in combination. Combining venetoclax with melphalan or carfilzomib produced additive or better cell death in 4 of the 5 cell lines tested. The most striking results were seen with dexamethasone. Co-treatment of human myeloma cell lines and primary patient samples, with dexamethasone and venetoclax significantly increased cell death over venetoclax alone in 4 of the 5 cell lines, and in all patient samples tested. The mechanism by which this occurs is an increase in the expression of both Bcl-2 and Bim upon addition of dexamethasone. This results in alterations in Bim binding to anti-apoptotic proteins. Dexamethasone shifts Bim binding towards Bcl-2 resulting in increased sensitivity to venetoclax. These data suggest that knowledge of drug-induced alterations of Bim binding patterns may help inform better combination drug regimens. Furthermore, the data indicate combining this novel therapeutic with dexamethasone could be an effective therapy for a broader range of patients than would be predicted by single agent activity.
PMCID: PMC4874660  PMID: 26707935
Bcl-2; apoptosis; plasma cell dyscrasia
14.  A Double-Blind Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis 
The New England journal of medicine  2012;366(9):799-807.
Ruxolitinib, a selective JAK1 and JAK2 inhibitor, has clinically significant activity in myelofibrosis.
In a double-blind trial, patients with intermediate-2 or high-risk myelofibrosis were randomized to twice-daily oral ruxolitinib (n=155) or placebo (n=154). The primary endpoint was the proportion of patients with ≥35% spleen volume reduction at 24 weeks assessed by magnetic resonance imaging. Secondary endpoints included durability of response, changes in symptom burden (assessed by Total Symptom Score [TSS]), and overall survival.
In the ruxolitinib group, 41.9% achieved the primary endpoint versus 0.7% in the placebo group (P<0.001). Spleen response was maintained while taking ruxolitinib: 67% of responding patients maintained response for ≥48 weeks. A ≥50% improvement in TSS at 24 weeks was achieved by 45.9% of ruxolitinib-treated versus 5.3% of placebo-treated patients (P<0.001). Thirteen deaths occurred in the ruxolitinib and 24 in the placebo group (hazard ratio, 0.50; 95% CI, 0.25–0.98; P=0.04). Discontinuations for adverse events were similar between groups (11% each). Among ruxolitinib-treated patients, anemia and thrombocytopenia were the most common adverse events, but rarely led to discontinuation (1 patient for each event). Two patients underwent transformation to acute myeloid leukemia (AML), both in the ruxolitinib group.
Ruxolitinib provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, improving debilitating myelofibrosis-related symptoms, and improving overall survival. Improvement came at a cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. The imbalance in AML transformation requires attention in further studies. (Funded by Incyte Corporation;, NCT00952289)
PMCID: PMC4822164  PMID: 22375971
15.  Effects of Ruxolitinib Treatment on Metabolic and Nutritional Parameters in Patients With Myelofibrosis From COMFORT-I 
Clinical lymphoma, myeloma & leukemia  2014;15(4):214-221.e1.
In the COMFORT-I study, the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib provided significant reductions in splenomegaly, improvements in myelofibrosis (MF)-related symptoms, and a survival advantage relative to placebo in patients with intermediate-2 or high-risk MF. This post-hoc analysis assessed the effects of ruxolitinib treatment on measures of metabolic and nutritional status.
Patients and Methods
Patients were randomized to receive ruxolitinib (n = 155; 15 or 20 mg twice a day for patients with baseline platelet counts of 100–200 × 109/L or > 200 × 109/L, respectively) or placebo (n = 154). The primary endpoint was the proportion of patients with a ≥ 35% spleen volume reduction from baseline to week 24. A secondary endpoint was the proportion of patients with ≥ 50% improvement in Total Symptom Score (TSS) from baseline to week 24, measured by the modified Myelofibrosis Symptom Assessment Form v2.0. Weight, cholesterol, and albumin were measured at specified time points throughout the study.
Compared with placebo, ruxolitinib treatment was associated with increased weight (mean change: +3.9 kg vs. −1.9 kg), total cholesterol (mean percentage change: +26.4% vs. −3.3%), and albumin levels (mean percentage change: +5.8% vs. −1.7%) at week 24; sustained improvements were observed with longer-term ruxolitinib therapy. Relative to placebo, increases in mean weight, total cholesterol, and albumin levels were observed with ruxolitinib treatment regardless of the degree of spleen volume and TSS reductions at 24 weeks.
Treatment with ruxolitinib improved measures of metabolic and nutritional status of patients with intermediate-2 or high-risk MF.
PMCID: PMC4418454  PMID: 25682576
Myelofibrosis; JAK Inhibitor; Weight; Cholesterol; Albumin
16.  MicroRNA therapeutics: Discovering novel targets and developing specific therapy 
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological process. They act as intracellular mediators that are necessary for various biological processes. MicroRNAs targeting pathways of human disease provide a new and potential powerful candidate for therapeutic intervention against various pathological conditions. Even though, the information about miRNA biology has significantly enriched but we still do not completely understand the mechanism of miRNA gene regulation. Various groups across the globe and pharmaceutical companies are conducting research and developments to explore miRNA based therapy and build a whole new area of miroRNA therapeutics. Consequently, few miRNAs have entered the preclinical and clinical stage and soon might be available in the market for use in humans.
PMCID: PMC4840794  PMID: 27141472
Clinical stage; gene expression; microRNA; therapeutics
17.  Quantifying the Amount of Bleeding and Associated Changes in Intra-Abdominal Pressure and Mean Airway Pressure in Patients Undergoing Lumbar Fixation Surgeries: A Comparison of Three Positioning Systems 
Asian Spine Journal  2016;10(2):199-204.
Study Design
Prospective, randomised controlled, single centre study of 45 patients posted for two level lumbar fixation surgery in the prone position.
To compare intra-abdominal pressure (IAP), mean airway pressure mean airway pressure and blood loss during the spine surgery in prone position using three different positioning systems.
Overview of Literature
Studies have correlated IAP with the amount of perioperative bleeding. However, IAP and airway pressures while assessing the bleeding comparing two or more prone positioning systems are unclear.
This prospective study was conducted on a cohort of 45 patients scheduled for two-level lumbar fixation. Patients were randomly allocated to a spine table, Wilson's frame, and thermomodulated pads. Bladder pressure as an indicator of IAP, mean and peak airway pressures, and blood loss were monitored.
IAP increased whenever patient position was changed to prone .The increase in pressure was more in the Wilson's frame group but was statistically significant only on prolonged positioning. Adopting the prone position always increased the mean airway pressure, but the increased was significant only in the Wilson's frame group. Mean airway pressure decreased in the spine table group and was statistically significant. The blood loss in the spine table group was significantly less as compared to the other groups.
Positioning on a spine table results in less blood loss and low mean airway pressure. The Wilson's frame results in high IAP, increased mean airway pressure, and more blood loss. The thermomodulated frame increases mean airway pressure and produces a moderate increase in IAP and airway pressure.
PMCID: PMC4843053  PMID: 27114757
Intra-abdominal pressure; Prone position; Mean airway pressure
18.  ‘O’ Configuration of Biliary-Enteric Drainage: a Preventable Surgical Error 
The Indian Journal of Surgery  2015;77(Suppl 1):156-158.
Surgical errors in Roux limb reconstruction are not reported widely. A young male who underwent hepaticojejunostomy after biliary injury developed acute obstruction of the proximal jejunum. Barium study revealed the O configuration of alimentary limb—‘O’ sign. At laparotomy, he was found to have the alimentary limb joining on to itself and without any connection with the biliary limb. The O loop complex was resected, and Roux-en-Y construction was refashioned. He made an uneventful recovery and is well at one year follow-up. We have reviewed the literature and propose a classification system for such type of errors. Every effort should be made to prevent this complication.
PMCID: PMC4425795  PMID: 25972680
Roux-en-Y; Roux-en-O; O loop; Hepaticojejunostomy; Biliary; Injury; Stricture; Reconstruction; Surgery; Error
19.  Isolated Lichen Planus of Lower Lip: A Case Report 
Lichen planus is an idiopathic inflammatory condition, which may involve mucosa of the oral cavity, gastrointestinal tract, larynx or the cutaneous surface either in isolation or in combinations. Mucosal lichen planus is more common than the cutaneous variant. Isolated lip involvement is very rare and should be differentiated from other similar leukoplakic lesions. We are reporting a rare case of oral lichen planus in an elderly male that was exclusively localised to the lower lip.
PMCID: PMC4298609  PMID: 25621274
Oral lichen planus (OLP); Lip; Plaque; Leukoplakia
20.  Dengue vaccine: Come let's fight the menace 
Although dengue has a global distribution, the World Health Organization (WHO) South-East Asia region together with Western Pacific region bears nearly 75% of the current global disease burden. Globally, the societal burden has been estimated to be approximately 528 to 1300 disability-adjusted life years (DALY) per million to populations in endemic regions Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization, resulting in approximately 12,500 to 25,000 deaths. Despite being known for decades and nearly half the world's population is at risk for infection with as many as 100 million cases occurring annually, the pitiable state is that we still have no antiviral drugs to treat it and no vaccines to prevent it. In recent years, however, the development of dengue vaccines has accelerated dramatically in tandem with the burgeoning dengue problem with a rejuvenated vigour. However, recent progress in molecular-based vaccine strategies, as well as a renewed commitment by the World Health Organization (WHO) to co-ordinate global efforts on vaccine development, finally provides hope that control of this serious disease may be at hand. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on 5 candidate vaccines. Trials in the most advanced stages are showing encouraging preliminary data, and the leading candidate could be licensed as early as 2015.
PMCID: PMC4514274  PMID: 25695523
Dengue; endemic; tetravalent; trials; vaccine
21.  Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies 
Leukemia  2015;29(8):1754-1762.
Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells.
PMCID: PMC4527886  PMID: 25772027
Allogeneic hematopoietic cell transplantation; primary graft failure; myeloablative; leukemia; myelodysplastic syndrome; myeloproliferative disorders
22.  Spontaneous Trans-Abdominal Expulsion of a Foreign Body: A Rare Occurrence 
Large and sharp foreign bodies invariably need surgical removal. A 55-year-old male, had epigastric pain, two weeks after accidental ingestion of wooden tooth brush. Later he developed pain, fever and indurations in left iliac fossa followed by spontaneous expulsion of foreign body through indurated area on the anterior abdominal wall. Contrast enhanced computed tomography revealed an inflammatory tract along the posterior wall of stomach communicating with the anterior abdominal wall. Patient was managed conservatively and made an uneventful recovery.
PMCID: PMC4668465  PMID: 26675621
Abscess; Ingestion; Perforation; Sharp
23.  Clinical features of patients with Philadelphia-negative myeloproliferative neoplasms complicated by portal hypertension 
Portal hypertension (PHTN) has been reported to afflict 7-18% of patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), with complications of variceal bleeding and ascites. The clinical features and outcomes of these patients are unclear.
Patients and Methods
In this multi-centre retrospective study, we evaluated the clinical features of 51 patients with MPNs complicated by PHTN.
The diagnosis of underlying MPN was most frequently polycythemia vera (PV) (39%) and primary myelofibrosis (MF) (35%), followed by post-PV myelofibrosis (18%), essential thrombocythemia (ET) (4%) and post-ET myelofibrosis (4%). Frequency of JAK2 V617F mutation appears as expected in the underlying MPN. Thrombosis within the splanchnic circulation was prevalent in patients with polycythemia compared to other MPNs (76% vs. 26%, p=0.0007).
PV and MF patients have a higher incidence of PHTN in our population, with thrombosis contributing to PHTN development in PV patients. Patients with splanchnic circulation thrombosis are potential candidates for screening for portal hypertension. These data may be useful for developing screening strategies for early detection of PHTN in patients with MPN.
PMCID: PMC4361182  PMID: 25027569
Essential thromobocythemia; Polycythemia vera; Myelofibrosis; Thrombosis; portal hypertension
24.  Is There Any Scientific Basis of Hawan to be used in Epilepsy-Prevention/Cure? 
Journal of Epilepsy Research  2015;5(2):33-45.
Epilepsy is a neuropsychiatric disorder associated with religiosity and spirituality. Nasal drug delivery systems are the best for diseases related to brain. In older times RishiMuni, ancient scholars and physicians used to recommend Hawan for mental peace and well being. Gayatri Mantra also tells that sughandhim (aroma, fragrance) puushtivardhanam (gives rise to good health). Om triambkum yajamahe, sughandhim puushtivardhanam, urvarukmev vandhanaat, mrityu mokshay mamritaat! Hawan is a scientific experiment in which special herbs (Hawan Samagri) are offered in the fire of medicinal woods ignited in a specially designed fire pit called agnikuñda. Hawan seems to be designed by the ancient scholars to fight with the diseases of the brain. Our metadata analysis demonstrates that the components of Hawan are having a number of volatile oils that are specifically useful for epilepsy through one or the other mechanism of action. Due to high temperature of fire the vapors of these oils enter into the central nervous system through nasal route. The routine of performing Hawan might keep the threshold value of the therapeutic components in the body and help in preventing epilepsy. In the present manuscript authors have tried to highlight and integrate the modern and ancient concepts for treatment and prevention of epilepsy.
PMCID: PMC4724851  PMID: 26819935
Epilepsy; Hawan; Traditional therapies; Volatile oil
25.  Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease 
World Journal of Gastroenterology : WJG  2015;21(37):10621-10635.
Rates of non-alcoholic fatty liver disease (NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, non-alcoholic steatohepatitis (NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/ fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research.
PMCID: PMC4588084  PMID: 26457022
Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Diet; Coffee; Tea; Olive oil; Nuts; Walnuts; Fish; Fish oils; Red wine

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