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The most fundamental aspect of a contact lens is its optics; the manner in which the refraction of light is managed to optimise vision to the clinical benefit of the lens wearer. This report presents contemporary information on the optical structure of the eye and the optical models employed to understand the correction of refractive error. The design, measurement and clinical assessment of spherical, aspheric, toric, multifocal and myopia control contact lenses are described. The complexity and variety of multifocal lenses is recognised and detailed information is provided for alternating, simultaneous, diffractive, annular, aspheric and extended depth of field lens designs. In terms of clinical assessment, a contemporary review is provided for the measurement of: visual acuity, contrast sensitivity, through focus curves, reading performance, peripheral refraction, toric displacement realignment and patient reported outcomes. Overall, the paper aims to serve as a resource for the prescribing clinician, who can optimise contact lens corrections for patients by building on the optical rationale of these devices; and also highlights future opportunities for research innovation.

End-stage liver disease (ESLD) patients undergoing liver transplant (LT) surgery are often multiply alloimmunized and pose significant challenges to the transfusion services in terms of red cell cross-match incompatibility, unpredictable blood requirements, and often lead to significant delays in availing compatible red cell units. We report a case of a 64-year-old female from Bahrain, a known case of hepatitis C-related ESLD referred for LT surgery. She had a history of multiple uneventful transfusions in the preceding year. Her blood group was A-positive, direct antiglobulin test, and cold antibodies were negative. Indirect antiglobulin test was positive, and antibody identification confirmed the presence of anti-C, anti-e, and anti-K. Her red cell phenotype was R2R2 and Kell negative (C-c+E+e-K-). The patient was started on erythropoietin. Requests for R2R2 and Kell negative units were sent to various blood banks across the country. After >800 A/O group units phenotyping and a waiting period of 6 weeks, two compatible R2R2 phenotypes and Kell negative could be arranged in-house and three units were received from Gurgaon, North India. Intraoperative management included blood preservation techniques including cell salvage, antifibrinolytic drug, and monitoring using thromboelastography. The estimated blood loss was 350 ml with pre- and postoperative Hb 10.4 gm% and 9.2 gm%, respectively. She received intraoperatively two units of single-donor platelet and four units of fresh frozen plasma and postoperatively one unit of leukocyte-depleted-packed red cells and doing well at 12-month follow-up. This case highlights the importance of advance immunohematology for timely detection of alloimmunization and providing antigen-negative compatible units, proper communication between the transfusion specialists, and the clinical team for proper patient blood management as well as the need for central rare donor registry program to avoid delays in providing compatible blood in such inevitable cases.

Survival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 as selectively cytotoxic to high-risk neuroblastoma and synergistic with low picomolar concentrations of topoisomerase I inhibitors in improving survival in vivo in orthotopic patient-derived xenograft neuroblastoma mouse models. CX-5461 recently progressed through phase I clinical trial as a first-in-human inhibitor of RNA-POL I. However, we also use a comprehensive panel of in vitro and in vivo assays to demonstrate that CX-5461 has been mischaracterized and that its primary target at pharmacologically relevant concentrations, is in fact topoisomerase II beta (TOP2B), not RNA-POL I. This is important because existing clinically approved chemotherapeutics have well-documented off-target interactions with TOP2B, which have previously been shown to cause both therapy-induced leukemia and cardiotoxicity—often-fatal adverse events, which can emerge several years after treatment. Thus, while we show that combination therapies involving CX-5461 have promising anti-tumor activity in vivo in neuroblastoma, our identification of TOP2B as the primary target of CX-5461 indicates unexpected safety concerns that should be examined in ongoing phase II clinical trials in adult patients before pursuing clinical studies in children., CX-5461 recently progressed through phase I clinical trial as a first-inhuman inhibitor of RNA-POL I. Here, the authors demonstrate that CX-5461 synergizes with topoisomerase I inhibitors to inhibit neuroblastoma cells and that its primary target in this disease is topoisomerase II beta and not RNA-POL I.

Sudden cardiac death (SCD) is the sudden, unexpected death due to abrupt loss of heart function secondary to cardiovascular disease. In certain populations living with cardiovascular disease, SCD follows a distinct 24-hour pattern in occurrence, suggesting day/night rhythms in behavior, the environment, and endogenous circadian rhythms result in daily spans of increased vulnerability. The National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death to identify fundamental questions regarding the role of the circadian rhythms in SCD. Part 2 summarizes research gaps and opportunities in the areas of population and clinical research identified in the workshop. Established research supports a complex interaction between circadian rhythms and physiological responses that increase the risk for SCD. Moreover, these physiological responses themselves are influenced by several biological variables, including the type of cardiovascular disease, sex, age, and genetics, as well as environmental factors. The emergence of new noninvasive biotechnological tools that continuously measure key cardiovascular variables, as well as the identification of biomarkers to assess circadian rhythms, hold promise for generating large-scale human data sets that will delineate which subsets of individuals are most vulnerable to SCD. Additionally, these data will improve our understanding of how people who suffer from circadian disruptions develop cardiovascular diseases that increase the risk for SCD. Emerging strategies to identify new biomarkers that can quantify circadian health (eg, environmental, behavioral, and internal misalignment) may lead to new interventions and therapeutic targets to prevent the progression of cardiovascular diseases that cause SCD.

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period.

These data demonstrate that binocular vision disorders (BVDs) contribute to contact lens (CL) dissatisfaction independently of CL discomfort (CLD) in myopic, pre-presbyopic, adult, single-vision CL wearers.This study aimed to determine whether BVDs contribute to CL dissatisfaction and whether this contribution is independent of CLD.Participants attended one clinical visit while wearing their habitual CLs. Symptoms from CLD and BVDs were measured with the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and Convergence Insufficiency Syndrome Survey (CISS), respectively. A comprehensive binocular vision (BV) assessment was performed. The Ocular Surface Disease Index (OSDI) was used to measure CL dissatisfaction from CLD and BVDs based on reported correlations between the CLDEQ-8 and the CISS with the OSDI. Participants were categorized according to their CL comfort status (CLD [≥12 on CLDEQ-8] or non-CLD [12 on CLDEQ-8]) and BV status (BVD or non-BVD).Seventy-six participants completed the trial, and 19 (25%) were diagnosed with BVD. Those diagnosed with BVD scored higher than did those diagnosed with non-BVD for the OSDI (25.1 ± 12.7 vs. 10.7 ± 7.3, P.001) and CISS (18.7 ± 7.7 vs. 11.9 ± 5.9, P = .001), but not the CLDEQ-8 (P = .25). Those categorized as having CLD scored higher than did those categorized as having non-CLD for the OSDI (19.0 ± 12.3 vs. 9.3 ± 5.9, P = .003) and CISS (16.1 ± 6.8 vs. 11.0 ± 6.2, P = .001). There were no significant interactions between BV status and CL comfort status for any questionnaire (P.08).Higher scores for OSDI in those with CLD or BVD indicate that both conditions contribute to CL dissatisfaction. Higher scores for the CISS in those with CLD suggest a degree of overlap for some BVD symptoms. Nonsignificant differences between BVD and non-BVD for the CLDEQ-8 suggest that BVDs contribute to CL dissatisfaction independently of CLD.

Purpose To ascertain the impact of altering cylinder (cyl) power and axis on vision in astigmatism. Methods In a prospective, randomized, participant-masked, crossover clinical trial, 28 astigmatic participants were tested for the following conditions on different days: full sphero-cyl correction and undercorrection by 0.25, 0.50, and 0.75 DC while maintaining spherical equivalence. Axis was also misaligned between -30° and +30°, in 10° steps. For each configuration, monocular high- and low-contrast visual acuities (HCVA, LCVA) were measured at 6 m, and participants rated vision clarity (1-10), vision satisfaction (1-10), and vision acceptability (yes/no). Linear mixed models were used to compare visual performance in the overall group and in low, medium, and high cyl subgroups. Results Undercorrecting cyl power affected all groups equally (P≥0.073). Undercorrection by 0.75 DC was significantly different to full cyl power for all variables (P≤0.007), while 0.25 DC undercorrection did not cause any significant decreases (P>0.05). Undercorrection by 0.50 DC was significantly different to full cyl power for HCVA (P=0.006, however not clinically significant) and vision acceptability (P=0.034). Axis misalignment affected the cyl groups differently (P

Residual thyroid tissue after total thyroidectomy in differentiated thyroid cancers is considered an independent risk factor for recurrence. Guidelines recommend following up patients after surgery with thyroglobulin (Tg), neck ultrasonography, and occasionally whole-body radioactive scan. However, the results of serum thyroglobulin and whole-body radioiodine scan are often discordant. The present study was undertaken to determine the levels of serum-stimulated thyroglobulin to complement the findings of residual thyroid tissue in the radioactive whole-body scan. One hundred twenty-six patients had undergone a radioiodine ((131) I) whole-body scan (WBS) during the study duration, and 121 were available for analysis. The thyroglobulin level (measured by the CLIA method) was recorded at the time of these scans. The data was analysed to determine the level of stimulated thyroglobulin correlating with residual thyroid tissue, locoregional, and distant metastasis as assessed by WBS. The presence of residual thyroid tissue was noted in an overwhelmingly high 94% of cases. Twenty-four of the 28 patients with stimulated Tg

Facial swelling has several etiologies. In patients with head and neck malignancies, this can include primary disease progression or iatrogenic causes. A 66-year-old man presented with increased facial swelling and erythema for 18 months. He had a history of baseline postoperative facial lymphedema following head and neck surgery and radiotherapy for desmoplastic melanoma approximately 20 years ago. However, his facial edema acutely worsened 18 months prior to presentation. A medication review revealed that he was regularly taking melatonin for the past two years. Approximately two weeks after cessation of melatonin therapy, the patient's facial appearance returned to baseline. In conclusion, it is important for clinicians to perform a thorough medication review for patients with facial swelling and erythema.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has had a major impact on the behavior of patients, as well as on the delivery of healthcare services. With older and more medically vulnerable people tending to stay at home to avoid contracting the virus, it is unclear how the behavior of people with acute myocardial infarction (AMI) has changed. The aim of this study was to determine if delays in presentation and healthcare service delivery for AMI exist during the COVID-19 pandemic compared to the same period a year prior. Methods: In this single-center, retrospective study, we evaluated patients admitted with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) during early months of the COVID-19 pandemic (March 11, 2020 to April 20, 2020) compared to patients admitted with same diagnosis during the same period a year prior. Results: There were 30 and 62 patients who presented with NSTEMI in the pandemic and pre-pandemic eras, respectively. The median pain-to-door time was significantly larger during the pandemic compared to pre-pandemic era (1,885 (880, 5,732) vs. 606 (388, 944) min, P < 0.0001). There was a significant delay in door-to-reperfusion time during the pandemic with a median time of 332 (182, 581) vs. 194 (92, 329) min (P = 0.0371). There were 24 (80%) and 25 (42%) patients who presented after 12 h of pain onset in pandemic and pre-pandemic eras, respectively (P = 0.0006). There were 47 and 60 patients who presented with STEMI during the pandemic timeframe of study and pre-pandemic timeframe, respectively. The median pain-to-door time during the pandemic was significantly larger than that of the pre-pandemic (620 (255, 1,500) vs. 349 (146, 659) min, P = 0.0141). There were 22 (47%) and 14 (24%) patients who presented after 12 h of pain onset in the pandemic and pre-pandemic eras, respectively (P = 0.0127). There was not a significant delay in door-to-reperfusion time (P = 0.9833). There were no differences in in-hospital death, stroke, or length of hospitalization between early and late presenters, as well as between pandemic and pre-pandemic eras. Conclusions: In conclusion, this study found that patients waited significantly longer during the pandemic to seek medical treatment for AMI compared to before the pandemic, and that pandemic-specific protocols may delay revascularization for NSTEMI patients. These findings resulted in more than a threefold increase from the onset of symptoms to revascularization increasing the risks for future complications such as left ventricular dysfunction and cardiovascular death. Efforts should be made to increase patients’ awareness regarding consequences of delayed presentation, and to find a balance between hospital evaluation strategies and goals of minimizing total ischemic time. Cardiol Res. 2020;11(6):386-391 doi: https://doi.org/10.14740/cr1175

Background Surgical scars are not a well-known risk factor for the development of dermatofibrosarcoma protuberans (DFSP). However, DFSP can arise within a surgical scar. Objective This study determined the number of DFSP found within scars from prior surgical procedures at a tertiary academic cancer center. Methods A retrospective data analysis was performed of all patients with biopsy-proven DFSP from January 2000 to April 2018 at MD Anderson Cancer Center (MDACC), a tertiary referral cancer center. Chart review was performed, and data were recorded for gender, race, and age of patients. We also recorded the site, location, and size of the DFSP and whether the patients had a history of prior surgery at the DFSP site. All patients had a pathologic diagnosis of DFSP at MDACC. Patients were selected from the pathology database at MDACC using the keywords "DFSP" or "dermatofibrosarcoma protuberans". A total of 458 patients were identified; however, 94 patients were excluded from the study because they were only referred to MDACC with a confirmed diagnosis of DFSP and were not seen as patients by a MDACC physician. Results Of the remaining 364 patients, 37 patients (10.1%) had either a history of a benign neoplasm or an inflammatory disease that had been evaluated or treated by either punch biopsy, shave biopsy, or minor excision at the site of DFSP (8.5%, 31 patients) or a DFSP arising within a major surgical procedural scar (1.6%, six patients). The surgical sites identified were the abdomen (four patients) and the groin (two patients). Three of the patients with a major surgical scar DFSP had prior laparoscopic surgery at the site. Conclusions DFSPs occur at surgical scars. The development of surgical scar DFSP in 10% of our patients prompts us to postulate that the neoplasm may be associated with the malignant transformation of these scars.

BACKGROUND Fractional flow reserve(FFR) is a validated tool for evaluating functional severity and guiding the revascularization of angiographically moderate coronary artery lesions. OBJECTIVE To study if there is a higher frequency of positive FFR measurements in the left anterior descending(LAD) versus other major coronary arteries and also evaluate the differences in the total length of the stent placed. METHODS A retrospective cohort study including all subjects (January 2011 to December 2015) who had fractional flow reserve (FFR) measured during coronary catheterization was conducted. Coronary catheterizations with FFR at a single tertiary care center were reviewed and FFR ≤ 0.80 post adenosine was deemed positive. The differences in the baseline characteristics and the degree of stenosis were compared between the different vessel groups. RESULTS Of the 758 vessels included in the analysis, the majority were LAD(51.3%) followed by right coronary artery(RCA)(22.8%), Circumflex(22.2%), Left main(2.2%), and Ramus intermedius(1.5%). 25.1% of 758 vessels were FFR positive. The proportion of positive FFR were higher among LAD versus other vessels(33.2%vs.16.5%,p

Key points Mutations in the caveolae scaffolding protein, caveolin-3 (Cav3), have been linked to the long QT type 9 inherited arrhythmia syndrome (LQT9) and the cause of underlying action potential duration prolongation is incompletely understood. In the present study, we show that LQT9 Cav3 mutations, F97C and S141R, cause mutation-specific gain of function effects on Cav 1.2-encoded L-type Ca2+ channels responsible for ICa,L and also cause loss of function effects on heterologously expressed Kv 4.2 and Kv 4.3 channels responsible for Ito . A computational model of the human ventricular myocyte action potential suggests that the major ionic current change causing action potential duration prolongation in the presence of Cav3-F97C is the slowly inactivating ICa,L but, for Cav3-S141R, both increased ICa,L and increased late Na+ current contribute equally to action potential duration prolongation. Overall, the LQT9 Cav3-F97C and Cav3-S141R mutations differentially impact multiple ionic currents, highlighting the complexity of Cav3 regulation of cardiac excitability and suggesting mutation-specific therapeutic approaches. Abstract Mutations in the CAV3 gene encoding caveolin-3 (Cav3), a scaffolding protein integral to caveolae in cardiomyocytes, have been associated with the congenital long-QT syndrome (LQT9). Initial studies demonstrated that LQT9-associated Cav3 mutations, F97C and S141R, increase late sodium current as a potential mechanism to prolong action potential duration (APD) and cause LQT9. Whether these Cav3 LQT9 mutations impact other caveolae related ion channels remains unknown. We used the whole-cell, patch clamp technique to characterize the effect of Cav3-F97C and Cav3-S141R mutations on heterologously expressed Cav 1.2+Cav β2cN4 channels, as well as Kv 4.2 and Kv 4.3 channels, in HEK 293 cells. Expression of Cav3-S141R increased ICa,L density without changes in gating properties, whereas expression of Cav3-F97C reduced Ca2+ -dependent inactivation of ICa,L without changing current density. The Cav3-F97C mutation reduced current density and altered the kinetics of IKv4.2 and IKv4.3 and also slowed recovery from inactivation. Cav3-S141R decreased current density and also slowed activation kinetics and recovery from inactivation of IKv4.2 but had no effect on IKv4.3 . Using the O'Hara-Rudy computational model of the human ventricular myocyte action potential, the Cav3 mutation-induced changes in Ito are predicted to have negligible effect on APD, whereas blunted Ca2+ -dependent inactivation of ICa,L by Cav3-F97C is predicted to be primarily responsible for APD prolongation, although increased ICa,L and late INa by Cav3-S141R contribute equally to APD prolongation. Thus, LQT9 Cav3-associated mutations, F97C and S141R, produce mutation-specific changes in multiple ionic currents leading to different primary causes of APD prolongation, which suggests the use of mutation-specific therapeutic approaches in the future.

Introduction: Serological tests for syphilis contributed greatly to the detection of Treponema pallidum infection in blood donors and especially in those who were missed during the medical selection. Although several different treponemal assays have been evaluated in India, the debate that which treponemal test-formats would be suitable for a particular blood transfusion service is far from settled. Aims and Objectives: The study was undertaken with an objective of comparing conventional immunochromatographic assay (ICA) with new automated T. pallidum hemagglutination assay (a-TPHA) in over 10,000 consecutive blood donor samples with fluorescent treponemal antibody-absorption assay (FTA-Abs) as the gold standard to resolve the discordant samples. Materials and Methods: The study was conducted in the Department of Transfusion Medicine in a large tertiary care hospital in India. Consecutive blood donors from July 2014 to January 2015 were evaluated simultaneously for antitreponemal antibodies by solid-phase ICA (SD BIOLINE Syphilis 3.0, Alere Medical Pvt. Ltd., USA), a-TPHA (Immucor Diagnostics, USA) and FTA-Abs (Biocientifica SA, FTA-Abs, Argentina). Performances of both the assays were evaluated using statistical tools. Results: A total of 10,129 donor samples were evaluated. A total of 113 (1.1%) donor samples were reactive for syphilis; either on ICA or a-TPHA or both. Ninety-one of these 113 reactive samples were reactive on FTA-Abs, giving seroprevalance of syphilis as 0.9%. a-TPHA was superior to ICA in terms of sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index. Conclusion: The new “a-TPHA” is a superior assay to ICA as the screening assay for syphilis in blood donors.

Introduction Post-donation counselling informs donors of unusual test results. Timely notification and counselling regarding their Transfusion Transmitted Infection (TTI) status is necessary for early clinical intervention in the donor and reducing risk of transmission. We share our experience with respect to Hepatitis B (HBV) and Hepatitis C (HCV) positive donors who were counselled and followed-up for clinical outcome. Materials and methods It was prospective 2-year study in TTI positive blood donors. Confirmed positive HBV/ HCV donors were notified to attend the donor-clinic or to visit local hepatologist for further management. At donor clinic, donor’s immediate emotional response was observed; donors were offered contact-testing, associated risk factors were noted, counselled, referred to hepatologist, treated and followed-up for clinical outcome. Results Of 481 donors (0.91%) confirmed positives, 351 were contacted telephonically; 280 promised to attend donor clinic and 71 were referred to their local hepatologist. 145 donors attended the donor clinic, eventually. Most common immediate emotional response noted were ‘feeling of fear’ (55.2%) and ‘disbelief’ (35.2%). Most common associated risk factor was history of medical treatment/ injections without knowledge of sterilisation. Five donors availed contact testing and four (spouses in all four cases) came out positive. Of 98 donors contacted post-counselling; 89 went to hepatologist. No medication was advised to seven donors (low viral load), 59 donors completed treatment course and 23 donors were undergoing treatment at time of follow-up. Nine donors opted for alternative treatment or “no treatment”. Conclusion Donor-clinic proved beneficial to substantial number of donors and their families.

Introduction: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opinion: Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.

Patients of β-thalassemia major are dependent on regular blood transfusions for their entire lifetime. Development of antibodies against red blood cell (RBC) antigen which may be alloantibody or autoantibody, several times as a result of frequent red cell component transfusions, further complicates the subsequent transfusion therapy. Among the autoantibodies, warm-reactive autoantibodies are commoner and interfere in the pretransfusion testing. These RBC autoantibodies present in patient's serum potentially react with all the cells of antibody identification panel giving “pan-reactive” picture and making alloantibody identification complex. In this report, we present our approach in a thalassemia patient who presented with warm-type autoimmune hemolytic anemia, low hemoglobin of 5.8 g/dl, and three significant alloantibodies (anti-D, anti-S, and anti-Jk b) which were masked by pan-reactive warm autoantibody(s). Differential adsorption was used to unmask underlying alloantibodies. We suggest that differential adsorption procedure is an effective and efficient method for autoantibody adsorption, detection, and identification of masked alloantibody(s), especially in patients with low hemoglobin and history of recent blood transfusion.

Background and Objectives: The US Food and Drug Administration and American Association of Blood Banks approved the type and screen approach in 1980s, long after antibody screen (AS) was introduced in 1950s. The present study omits conventional anti-human globulin (AHG) crossmatch and replaces it with immediate-spin (IS) crossmatch as part of pretransfusion testing in AS-negative patients to study the safety and effectiveness of IS crossmatch in recipients. Materials and Methods: This prospective longitudinal study was conducted on over 5000 red cell units transfused to AS-negative patients admitted to the hospital. Pretransfusion testing comprised blood grouping and AS followed by IS crossmatch, at the time of issue of red cell unit. The patients were transfused IS compatible red cell units. AHG crossmatch was performed posttransfusion for all red cell units. Any incompatible AHG crossmatch was followed up as suspected transfusion reaction. Results: A total of 5023 red cell units were transfused to 2402 patients with negative AS. 99.7% IS compatible red cell units were also compatible on posttransfusion AHG crossmatch. Anti-P1 alloantibody was identified in one patient who was transfused two IS crossmatch compatible units but later both units were incompatible on AHG crossmatch. There was no clinical or serological sign of hemolysis in the patient. Conclusion: In AS-negative patients, IS crossmatch is as safe as conventional AHG crossmatch and can, therefore, replace conventional AHG crossmatch protocol.

Introduction: Serological tests for syphilis (STS) contributed greatly to the detection of Treponema pallidum infection in blood donors and especially in those who were not identified during the medical selection. Most of the blood centers use nontreponemal tests due to lesser cost, ease of performance, and their ability to pick up early primary stage infection, despite reported high false positivity. However, increasingly large number of blood centers have begun testing with the treponemal tests such as immuno-chromatographic assay (ICA) which is possibly easier and more objective than rapid plasma reagin (RPR), albeit slightly expensive. It is with this background that we undertook a head-to-head comparison of nontreponemal test RPR with treponemal test ICA in over 10,000 consecutive blood donor samples with confirmation of all reactive and discordant samples by fluorescent treponemal antibody absorption assay (FTA-ABS) as the gold standard. Materials and Methods: The study was conducted in the department of transfusion medicine in a large tertiary care hospital in India. Consecutive blood donors from July 2014 to January 2015 were evaluated simultaneously for antitreponemal antibodies by solid phase ICA (SD BIOLINE Syphilis 3.0, Alere Medical Pvt. Ltd., USA), RPR (Immutrep RPR, Omega Diagnostics, Scotland, UK) and FTA-ABS (Biocientifica SA, FTA-ABS, Argentina). Performances of both the assays were evaluated in statistical terms. Results: A total of 10,200 donor samples were evaluated. There were 10,124 confirmed concordant negatives. Thirty-eight samples were concordant positive. Thirty-eight samples (thirty samples were ICA positive and RPR negative and eight samples were RPR positive and ICA negative) were discordant. The sensitivity of ICA was higher (93%) as compared to that of RPR (66%), whereas the specificity of RPR was higher (83%) than that of ICA (66%). Positive predictive value (PPV) of both the tests was similar while negative predictive value (NPV) of ICA was higher (86%) than that of RPR (60%). Youden's index was 0.81 for ICA whereas it was 0.62 for RPR. Conclusion: ICA has a better sensitivity than the RPR and thus seems to be more appropriate test for screening in blood donors.

Purpose: To compare the visual performance of prototype contact lenses which extend depth-of-focus (EDOF) by deliberate manipulation of multiple higher-order spherical aberration terms and a commercially-available center-near lens (AIR OPTIX Aqua Multifocal, AOMF). Methods: This was a prospective, cross-over, randomized, single-masked (participant), short-term clinical trial where 52 participants (age 45–70 years) were stratified as low, medium or high presbyopes and wore EDOF and AOMF on different days. Objective measures comprised high and low contrast visual acuity (HCVA/LCVA, log MAR), and contrast sensitivity (log units) at 6 m; HCVA at 70 cm, 50 cm and 40 cm and stereopsis (seconds of arc) at 40 cm. HCVA at 70 cm, 50 cm and 40 cm were measured as “comfortable acuity” rather than conventional resolution acuity. Subjective measures comprised clarity-of-vision and ghosting at distance, intermediate and near, overall vision satisfaction and ocular comfort (1–10 numeric rating scale) and lens purchase (yes/no response). Statistical analysis included repeated measures ANOVA, paired t-tests and McNemar's test. Results: Significant differences between lens types were independent of strata (p ≥ 0.119). EDOF was significantly better than AOMF for HCVA at 40 cm (0.42 ± 0.18 vs. 0.48 ± 0.22, p = 0.024), stereopsis (98 ± 88 vs. 141 ± 114, p

The prognostic implications of preexisting atrial fibrillation (AF) and new-onset AF (NOAF) in transcatheter aortic valve implantation (TAVI) remain uncertain. This study assesses the epidemiology of AF in patients treated with TAVI and evaluates their outcomes according to the presence of preexisting AF or NOAF. A retrospective analysis of 708 patients undergoing TAVI from 2 heart hospitals was performed. Patients were divided into 3 study groups: sinus rhythm (n = 423), preexisting AF (n = 219), and NOAF (n = 66). Primary outcomes of interest were all-cause death and stroke both at 30-day and at 1-year follow-up. Preexisting AF was present in 30.9% of our study population, whereas NOAF was observed in 9.3% of patients after TAVI. AF and NOAF patients showed a higher rate of 1-year all-cause mortality compared with patients in sinus rhythm (14.6% vs 6.5% for preexisting AF and 16.3% vs 6.5% for NOAF, p = 0.007). No differences in 30-day mortality were observed between groups. In patients with AF (either preexisting and new-onset), those discharged with single antiplatelet therapy displayed higher mortality rates at 1 year (42.9% vs 11.7%, p = 0.006). Preexisting AF remained an independent predictor of mortality at 1-year follow-up (hazard ratio [HR] 2.34, 95% CI 1.22 to 4.48, p = 0.010). Independent predictors of NOAF were transapical and transaortic approach as well as balloon postdilatation (HR 3.48, 95% CI 1.66 to 7.29, p = 0.001; HR 5.08, 95% CI 2.08 to 12.39, p

Background Lamin A and C are nuclear filament proteins encoded by the LMNA gene. Mutations in the LMNA gene cause many congenital diseases known as laminopathies, including Emery–Dreifuss muscular dystrophy, Hutchinson–Gilford progeria syndrome, and familial dilated cardiomyopathy (DCM) with conduction disease. A missense mutation (N195K) in the A-type lamins results in familial DCM and sudden arrhythmic death. Objective The purpose of this study was to investigate the ion current mechanism of arrhythmia and DCM caused by the LaminA-N195K variant. Methods A homozygous mouse line expressing the Lmna-N195K mutation ( Lmna N195K/N195K ) that exhibited arrhythmia, DCM, and sudden death was used. Using whole cell patch-clamp technique, we measured action potential duration (APD), Na + currents (I Na ) in ventricular myocytes isolated from Lmna N195K/N195K , and wild-type mice. Results Both peak and late I Na were significantly ( P Lmna N195K/N195K ventricular myocytes. Similarly, Lmna N195K/N195K ventricular myocytes exhibited significant ( P 50 ] and 90% [APD 90 ] repolarization) and triggered activity. Acute application of ranolazine inhibited late I Na , shortened APD, and abolished triggered activity in Lmna N195K/N195K ventricular myocytes. Conclusion Inhibition of late I Na may be an effective therapy in preventing arrhythmia in patients with LmnaN195K mutation–related DCM.

Background: Hematopoietic progenitor stem cell transplantation (HPSCT) is used as a standard treatment option to improve outcome in hematological and nonhematological disorders. It is important for new HPSCT program to look at its patient outcome data and compare it with the published data to evaluate the efficacy of program. Aims: The aim was to compile and collate the patient outcome data of HPSCT and compare with published reports. Materials and Methods: Patient demographics, indications, stem cell harvest by apheresis, dose collected, infusion, engraftment, and follow-up data were collected from hospital information system from 2010 to 2013 in a tertiary care hospital. HPSCs were mobilized with granulocyte colony-stimulating factor, and harvests were done on the 5th day. Engraftment was decided for neutrophil when counts were 0.5 × 109/L and for platelets when counts were 20 × 109/L on two consecutive days without any transfusion support. Results: There were 133 harvests for 95 patients with various disorders; multiple myeloma was most common in autologous and acute lymphoblastic leukemia in allogeneic group. One hundred harvests were done for autologous and 33 for allogeneic HPSCT. In autologous group, of 66 patients, 60 (90.9%) received stem cell infusion at median dose of 4.63 × 106 CD34+ cells/kg. Similarly, in allogeneic group, of 29 patients, 27 (93.10%) received infusion at median dose of 5.8 × 106 CD34+ cells/kg. 58 (96.9%) patients and 25 (92.6%) engrafted in autologous and allogeneic group, respectively. The median time for neutrophils engraftment was 11 days in autologous group and 12 days in allogeneic group. The median time for platelet engraftment was 11.5 days in autologous group and 13 days in allogeneic group. The 100-day survival rate was 95% n = 57) in autologous group and 77.8% n = 21) in allogeneic group. Conclusion: This data analysis shows reasonably good results of HPSCTs with majority of patients surviving at 100-day follow-up.

e18529 Background: Head and Neck squamous cell carcinoma (HNSCC) represents approximately 5-10% of malignancies worldwide. Despite the advances in treatment modalities there lies a disparity in response, owing to the underlying molecular and genetic make up. In the era of precision medicine, it is important to profile each disease and customise treatment to improve the outcomes by identifying predictive or prognostic indicators at the molecular and genetic level. Methods: 100 patients with HNSCC, diagnosed at our centre from April 2015-17 were profiled by targeted deep sequencing for hotspot mutations in 48 cancer-related genes using Illumina’s TSCAP panel and MiSeq technology. The average coverage across 220 hot spots was greater than 1000X. Data was processed using Strand Avadis NGS. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis. The clinical data for these patients was collected retrospectively and analysed for treatment outcomes with standard therapy. The association of mutations with habits, stage at presentation, poor treatment outcomes and prognosis was also analysed. Results: Somatic variants were detected in 63.1% of cases. Genetic aberrations were identified in major RAS/RAF signalling pathway in 10 % of cases out of which HRAS activating mutations were the most common (n=4). HRAS was co-mutated with PI3KCA (n=3) and PTEN deletions (n=2). Based on the result, Cetuximab was discontinued in 2 patients with metastatic HNSCC. Other targetable mutations included ATM (n=1), STK11 (n=1), RB1 (n=1) and BRAF (n=1). Disruptive and non-disruptive mutations in TP53 alone were found in 43.8% of H&N cancers, varying widely among different histology with variable treatment outcome. Interestingly all metastatic/recurrent patients, with very short progression free survival of 9-12 months (PFS) post Cisplatinum based chemotherapy, were found to have mutated TP53. TP53 was also found to be co- mutated with ATM gene (n=1), an important prognostic marker, indicating poor response to chemotherapy and radiotherapy. The patients with recurrence and poorer prognosis (n =5) showed point mutations in codon regions 173 -273. Conclusions: Indian patients with HNSCC display a wide mutational landscape with specific actionable targets. Although traditional treatment modalities remain the standard of care, specific mutations may be utilised to customise treatment, prognosticate and predict outcomes.

Significance The present study highlights the differences between modern daily-disposable multifocal soft contact lenses to assist eye care practitioners in fitting presbyopic contact lens wearers. Purpose The purpose of this study was to compare visual performance of three daily-disposable multifocal contact lenses. Methods Presbyopes (n = 72) wore 1-Day Acuvue Moist Multifocal, BioTrue ONEday for Presbyopia, and Dailies AquaComfort Plus Multifocal for 1 week in a prospective, randomized, double-blind, crossover clinical trial. After 1 week, high- and low-contrast visual acuities (HCVA, LCVA) were measured between 6 m and 40 cm and stereopsis at 40 cm. Subjective performance was assessed with 1- to 10-point rating scales for clarity, ghosting, driving vision, vision stability, ease of focusing, overall vision satisfaction, and ocular comfort. Willingness to purchase was reported with categorical responses. Linear mixed models and χ tests were used for analysis, and level of significance was set at 5%. Results BioTrue provided better HCVA and LCVA at distance than did Acuvue Moist (P ≤ .03). Subjectively, Acuvue Moist was rated lowest for distance clarity, distance ghosting, and driving vision (P ≤ .05). Acuvue Moist provided better HCVA at 70 to 40 cm and LCVA at 1 m to 40 cm than did BioTrue (P ≤ .01) and better LCVA at 1 m to 50 cm than did AquaComfort Plus (P ≤ .02). AquaComfort Plus also provided better HCVA and LCVA at 50 and 40 cm than did BioTrue (P ≤ .03). Acuvue Moist provided better stereopsis than did BioTrue (P = .02). Subjectively, BioTrue was rated lowest for near clarity (P ≤ .007) and lower than Acuvue Moist for intermediate clarity and near ghosting (P ≤ .04). No other differences were found between lenses (P > .05). Conclusions BioTrue had better distance performance compared with near, whereas Acuvue Moist performed conversely. AquaComfort Plus performed reasonably overall.

BACKGROUND It is important to detect Latent Iron Deficiency (LID) to prevent development of an overt iron deficiency anemia. Early detection is difficult by using conventional hematological and biochemical parameters. Soluble transferrin receptor (sTfR) is presently the gold standard for diagnosing LID. We evaluated the utility of Reticulocyte Hemoglobin Equivalent (Ret-He), a newer hematological parameter, to predict LID in blood donors as compared to sTfR. METHODS This was a randomized prospective study performed on 501 donor samples over a period of three-months. All donors were included after administering medical history questionnaire and a brief physical examination in accordance with national guidelines (Hb ≥12.5). Additional samples were collected during donation according to the institutional standard operating procedure (SOP). All hemograms were performed on the Sysmex XE-2100 analyzer which included Ret-He. sTfR was measured in batch assays by ELISA (Biovendor, Czech Republic). Ret He

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null ( Lrrc10−/−) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10−/−mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10−/−mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10−/−cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His150of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis.

The presence of distant metastases is one of the most important predictive factors of poor outcomes in thyroid cancer patients. Apart from distant metastasis, sex, age, histopathological subtypes, and completeness of surgical resection are the other prognostic indicators of survival. Our attempt in this study is to analyze the presence of distant metastasis in operated patients of thyroid malignancy and evaluate these prognostic indicators in the metastatic subgroup. Objective: The objective of this study was to retrospectively analyze the presence and extent of distant metastasis among treated thyroid cancer patients. Materials and Methods: The postoperative radioiodine scan reports of the patients who presented to Health Care Global Enterprises Ltd., Bengaluru over a period of 8 years (January 2008 to December 2015) were analyzed. Results: Sixty-six patients out of the 499 patients evaluated (13.22%) had distant metastasis. Most of the patients with distant metastasis were females, aged 45 years and above and had papillary carcinoma of thyroid. Percentage of skeletal and pulmonary metastasis was almost equal in the study group. Conclusion: The patterns of distant metastasis were similar to the trends in literature, except for increased incidence of skeletal metastasis, more so in a follicular subtype of papillary carcinomas.

Background Genetic causes of dilated cardiomyopathy (DCM) are incompletely understood. LRRC10 (leucine‐rich repeat–containing 10) is a cardiac‐specific protein of unknown function. Heterozygous mutations in LRRC10 have been suggested to cause DCM, and deletion of Lrrc10 in mice results in DCM. Methods and Results Whole‐exome sequencing was carried out on a patient who presented at 6 weeks of age with DCM and her unaffected parents, filtering for rare, deleterious, recessive, and de novo variants. Whole‐exome sequencing followed by trio‐based filtering identified a homozygous recessive variant in LRRC10 , I195T. Coexpression of I195T LRRC10 with the L‐type Ca 2+ channel (Ca v 1.2, β 2CN2 , and α 2 δ subunits) in HEK293 cells resulted in a significant ≈0.5‐fold decrease in I Ca,L at 0 mV, in contrast to the ≈1.4‐fold increase in I Ca,L by coexpression of LRRC10 (n=9–12, P LRRC10 or I195T LRRC10 did not alter the surface membrane expression of Ca v 1.2. LRRC10 coexpression with Ca v 1.2 in the absence of auxiliary β 2CN2 and α 2 δ subunits revealed coassociation of Ca v 1.2 and LRRC10 and a hyperpolarizing shift in the voltage dependence of activation (n=6–9, P Lrrc10 −/− mice had significantly smaller I Ca,L , and coimmunoprecipitation experiments confirmed association between LRRC10 and the Ca v 1.2 subunit in mouse hearts. Conclusions Examination of a patient with DCM revealed homozygosity for a previously unreported LRRC10 variant: I195T. Wild‐type and I195T LRRC10 function as cardiac‐specific subunits of L‐type Ca 2+ channels and exert dramatically different effects on channel gating, providing a potential link to DCM.

Purpose The purpose of this study was to investigate the optical zone power profile of the most commonly prescribed soft contact lenses to assess their potential impact on peripheral refractive error and hence myopia progression. Methods The optical power profiles of six single vision and ten multifocal contact lenses of five manufacturers in the powers −1.00 D, −3.00 D, and −6.00 D were measured using the SHSOphthalmic (Optocraft GmbH, Erlangen, Germany). Instrument repeatability was also investigated. Results Instrument repeatability was dependent on the distance from the optical centre, manifesting unreliable data for the central 1 mm of the optic zone. Single vision contact lens measurements of −6.00 D lenses revealed omafilcon A having the most negative spherical aberration, lotrafilcon A having the least. Somofilcon A had the highest minus power and lotrafilcon A the biggest deviation in positive direction, relative to their respective labelled powers. Negative spherical aberration occurred for almost all of the multifocal contact lenses, including the centre-distance designs etafilcon A bifocal and omafilcon A multifocal. Lotrafilcon B and balafilcon A seem to rely predominantly on the spherical aberration component to provide multifocality. Conclusions Power profiles of single vision soft contact lenses varied greatly, many having a negative spherical aberration profile that would exacerbate myopia. Some lens types and powers are affected by large intra-batch variability or power offsets of more than 0.25 dioptres. Evaluation of power profiles of multifocal lenses was derived that provides helpful information for prescribing lenses for presbyopes and progressing myopes.

Context: Syphilis is a transfusion transmissible infections and it is mandatory to do serological test for syphilis (STS) on all donor blood samples. STS is usually based on detection of antibodies against the cardiolipin-lecithin antigen or against the Treponema-specific antigen. STS with good sensitivity and specificity helps enhance blood safety and consolidation of STS along with other transfusion transmittable infections such as human immunodeficiency virus, hepatitis-C virus, and hepatitis-B virus helps in reducing the errors and enhances efficiency. Aims: This study was designed to evaluate the performance of newly introduced VITROS ® syphilis Treponema pallidum agglutination (TPA) assay based on enhanced chemiluminescence principle for its analytical performance for use as a STS on donor blood samples at a tertiary care health center in National Capital Region, India. Materials and Methods: A total of 108 random blood units collected from the donors (both voluntary and replacement donors) and 28 known syphilis sero-reactive samples stored at −20°C, were used to evaluate the performance of VITROS ® syphilis TPA assay based on enhanced chemiluminescence assay on VITROS ® ECiQ immunodiagnostics system along with its analytical performance in terms of its sensitivity, precision, cross-reactivity and interference studies. Results: VITROS ® syphilis TPA showed 100% sensitivity and specificity with precision (20 days study) of

The incidence of small differentiated thyroid carcinomas is increasing worldwide in the recent years, especially tumours of size less than 2 cm in diameter. In this study, we have analysed the patterns of behaviour of small-sized thyroid carcinomas (

The discovery and exploitation of new drug targets is a key focus for both the pharmaceutical industry and aca- demic research. To provide an insight into trends in the exploitation of new drug targets, we have analysed different methods during the past six decades and advances made in drug target discovery. A special focus remains on different methods used for drug target discovery on infectious diseases such as Tuberculosis, Gastritis, Malaria, Trypanosomiasis and Leishmaniasis. We herewith provide a paradigm that is can be used for drug target discovery in the near future. Drug target discovery is a key step that drives drug dis- covery and development process. The cost to drug discovery and development is nearly $1.5 - 1.7 billion (1) and funding was one of the major problems to both academia and indus- try for the infectious diseases such as Tuberculosis, Gastritis, Malaria, Trypanosomiasis and Leishmaniasis. Tuberculosis (TB) is the greatest killer worldwide affect- ing 8.6 million and killing nearly 1.3 million people (2). Next to tuberculosis, malaria is recognized as the silent kil- ler. According to World Health Organization (WHO), 219 million cases of malaria were recorded, killing nearly 660,000 people (3). Leishmaniasis affects as many as 12 million people worldwide, with 1.5-2 million new cases each year and killing nearly 50,000 people. More than 90 percent of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil (4). Try- panosomiasis incidence affects nearly 1.5 million and 48000 death cases were reported all over the world (5). H. pylori infect more than 80 % of individuals in their upper gastroin- testinal tract playing an important role in natural stomach ecology (6). Acute infection of H. pylori leads to chronic gastritis and gastric ulcers. Once torrential bleeding occurs in acute stress gastritis, the death rate can be greater than 60%. High toll incidences of the infectious diseases suggest an immediate requirement for the discovery of novel drug tar- gets towards discovery and development of drugs for Tuber- culosis, Malaria, Trypanosomiasis, Leishmaniasis and Gas- tritis.

Objective of the study was to evaluate the reliability of Muller’s maneuver (MM) with the severity of obstructive sleep apnea (OSA) at the retropalatal level. Case series of 58 adult patients diagnosed to have OSA. Sleep apnoea clinic in a tertiary referral center in south India. Fifty-eight adult OSA patients underwent outpatient based MM under local anaesthesia. Collapse of hypopharynx and the retroglossal regions were assessed during a maximal inspiratory effort against the closed mouth and sealed nose (reverse valsalva). Correlation co efficient was used to compare MM grade with apnea–hypopnea index (AHI) scores. Severity of OSA based on AHI scores were compared with the results of Muller’s maneuver at the retropalatal level. The correlation coefficient was 0.213, hence no correlation was found, p value was 0.019, which was not statistically significant. MM is an useful tool for evaluation of upper airway collapse. The advantages include simplicity, cost-effectiveness, relatively easy to perform, thorough evaluation of upper airway. The pitfalls of the procedure includes the subjectiveness of the procedure and the fact that it is performed on awake patients and therefore remains an indirect estimation of obstruction that occurs during sleep. In our study, we did not find correlation between the severity of OSA based on the AHI scores and the collapse at the retropalate level assessed by the Muller’s maneuver.

BackgroundFibrinogen, the major clotting protein in blood plasma, plays key roles in blood coagulation and thrombosis. In this prospective cohort study, we measured patient's fibrinogen levels and common coagulation parameters before and after cardiopulmonary bypass (CPB) and examined their relationships with postoperative blood loss.

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P

IntroductionAmyloidosis is a disease entity characterized by the presence of proteinaceous material deposited extracellularly at various locations in the body and in the head and neck region.Materials and methodsWe present a case of macroglossia secondary to amyloidosis of the tongue in a 65-year-old male. He presented with gradually progressive diffuse enlargement of the tongue, difficulty in speech and progressive difficulty in breathing while sleeping. Patient was managed conservatively with steroids and alkylating agents.DiscussionThe most common sites of involvement in systemic amyloidosis are the tongue (63%) and the larynx (19%). Although lingual involvement is common, macroglossia as a presenting symptom, though pathognomonic is rare (5%). Amyloidosis of the tongue typically results in macroglossia, manifested by increased tongue volume, tongue protrusion beyond the alveolar ridge, speech impairment, drooling and dysphagia.ConclusionAmyloidosis of the tongue is almost always secondary to systemic disease. An extensive workup is required to differentiate between systemic and localized amyloidosis. The effect of treatment is difficult to estimate, and further research needs to be focused on this aspect. These obstacles can make the diagnosis and management of these lesions particularly challenging.How to cite this articleVamanshankar H, Nair AB, Correa M, Nayar RC. Macroglossia Secondary to Primary Amyloidosis of the Tongue. Int J Otorhinolaryngol Clin 2013;5(2):94-97.

Carotid body tumours are rare and mostly benign neoplasm. They are slow growing but can evade or exert pressure on neighbouring important neurovascular structures. Hence, surgical resection remains the treatment modality of choice for large tumours partially or completely encasing the carotid arteries. But the surgical resection of these tumours with minimum morbidity is challenging because of their highly vascular nature. Earlier literature has dealt with various aspects of management of carotid body tumours including classification, morbidity, work-up, embolisation and extent of resection. However, the options in techniques of dissection for carotid body tumours have not been elaborated much. Here, we describe a stepwise dissection technique of carotid body tumours from the internal carotid towards the external carotid artery. This surgical technique, named as "the internal to external (INT-EX) technique", provides better control of bleeding during the surgery, ease of dissection and lesser post-operative morbidity.

Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the "bestrophinopathies". These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca2+ signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca2+ regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, "disease in a dish" models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.

Purpose: To compare the visual performance of prototype contact lenses designed via deliberate manipulation of higher-order spherical aberrations to extend-depth-of-focus with two commercial multifocals, after 1 week of lens wear. Methods: In a prospective, participant-masked, cross-over, randomized, 1-week dispensing clinical-trial, 43 presbyopes [age: 42–63 years] each wore AIROPTIX Aqua multifocal (AOMF), ACUVUE OASYS for presbyopia (AOP) and extended-depth-of-focus prototypes (EDOF) appropriate to their add requirements. Measurements comprised high-contrast-visual-acuity (HCVA) at 6 m, 70 cm, 50 cm and 40 cm; low-contrast-visual-acuity (LCVA) and contrast-sensitivity (CS) at 6 m and stereopsis at 40 cm. A self-administered questionnaire on a numeric-rating-scale (1–10) assessed subjective visual performance comprising clarity-of-vision and lack-of-ghosting at various distances during day/night-viewing conditions and overall-vision-satisfaction. Results: EDOF was significantly better than AOMF and AOP for HCVA averaged across distances (p ≤ 0.038); significantly worse than AOMF for LCVA (p = 0.021) and significantly worse than AOMF for CS in medium and high add-groups (p = 0.006). None of these differences were clinically significant (≤2 letters). EDOF was significantly better than AOMF and AOP for mean stereoacuity (36 and 13 seconds-of-arc, respectively: p ≤ 0.05). For clarity-of-vision, EDOF was significantly better than AOP at all distances and AOMF at intermediate and near (p ≤ 0.028). For lack-of-ghosting averaged across distances, EDOF was significantly better than AOP (p

Background There are several studies on prevalence of individual infectious disease markers (mono-infection) in donors but none on prevalence of coinfection. Co-infection is significant as it leads to accelerated disease progression. We, therefore, evaluated the prevalence of co-infection among blood donors. Materials and methods The cross-sectional analysis was conducted in blood donors. All donors were tested for anti-HIV I and II, HBsAg, anti-HBC IgM, anti-HCV, Malaria and syphilis by chemiluminescence and ID-NAT assay. All reactive donor samples were confirmed by using confirmatory assays. Donors were grouped as mono-infected and co-infected. The student t -test was used for comparison. Results During the study period, a total of 106,238 blood donors were tested. Mean age of donors was 34.2 years and 94.2% of blood donors were males. 1776 (1.67%) donor samples were confirmed serologically reactive. 1714 (1.61%) samples were reactive for single marker (mono-infected) while 62 (0.05%) donors' samples exhibited co-infection. 18 donors were positive for HBV+HCV followed by HIV +syphilis (14). Conclusion We report for the first time the prevalence of different co-infection patterns in blood donors. Co-infection influence the disease progression; it would be important to investigate the co-infection prevalence in larger sample size.

Heart failure (HF) is a complex syndrome with inherent diagnostic challenges. We studied the scope of possibly inaccurately documented HF in a large health care system among patients assigned a primary diagnosis of HF at discharge. Through a retrospective record review and a classification schema developed from published guidelines, we assessed the probability of the documented HF diagnosis being accurate and determined factors associated with HF-related and non–HF-related hospital readmissions. An arbitration committee of 3 experts reviewed a subset of records to corroborate the results. We assigned a low probability of accurate diagnosis to 133 (19%) of the 712 patients. A subset of patients were also reviewed by an expert panel, which concluded that 13% to 35% of patients probably did not have HF (inter-rater agreement, kappa = 0.35). Low-probability HF was predictive of being readmitted more frequently for non-HF causes (p = 0.018), as well as documented arrhythmias (p = 0.023), and age >60 years (p = 0.006). Documented sleep apnea (p = 0.035), percutaneous coronary intervention (p = 0.006), non-white race (p = 0.047), and B-type natriuretic peptide >400 pg/ml (p = 0.007) were determined to be predictive of HF readmissions in this cohort. In conclusion, approximately 1 in 5 patients documented to have HF were found to have a low probability of actually having it. Moreover, the determination of low-probability HF was twice as likely to result in readmission for non-HF causes and, thus, should be considered a determinant for all-cause readmissions in this population.

To investigate if initial multifocal contact lens (MFCL) performance predicts short-term dispensing performance. A retrospective analysis of 55 participants (Px) in a masked, crossover, clinical trial, using ACUVUE OASYS for Presbyopia and AIR OPTIX AQUA Multifocal. Subjective questionnaires were administered at the following instances: initial fitting, two take home questionnaires (THQ) completed between days 2 and 4 and at assessment, ≥5 days after fitting. Questionnaires included vision clarity and lack of ghosting at distance, intermediate and near at day/night time points rated on a 1 to 10 (1-step, 10 most favorable) rating scale. Vision stability, vision while driving, overall vision satisfaction, willingness to purchase and comfort, as well as acuity-based measures were also collected. There were no statistical differences in comfort and vision at all distances, in vision stability or driving at either time points between THQ and assessment (P>0.05). However, there was a statistical decline in subjective overall vision satisfaction and comfort between fitting and assessment visits (P

A 53-year-old patient of schizoaffective disorder developed neuroleptic malignant syndrome (NMS) following treatment with haloperidol, clozapine and parenteral fluphenazine. He showed full recovery with immediate discontinuation of potential offenders and prompt treatment with a higher dose of bromocriptine and lorazepam along with management of aspiration pneumonia. Need for early recognition of NMS and treatment by a multidisciplinary team is discussed. How to cite this article Sharma R, Kashyap R. Successful Treatment of a Complicated Case of Neuroleptic Malignant Syndrome with a Higher Dose of Bromocriptine and Lorazepam. J Postgrad Med Edu Res 2015;49(2):88-90.

Background and objectives:The incidence of acquired laryngeal stenosis is increasing. This retrospective study aimed to assess the long term results of circumferential resection with end-to-end tracheal anastomosis for isolated post-intubation stenosis of the cervical trachea, and to review the relevant literature.Methods:Twelve male and two female patients (aged 16–30 years, mean age 24 years) treated between February 2003 and December 2008 were included. Hospital and office records were reviewed and relevant surgical details recorded.Results:Indications for tracheal resection anastomosis were post-intubation stenosis (78.57 per cent) and trauma (21.42 per cent). One to five tracheal rings were resected (i.e. 1–2.5 cm of cervical trachea). Tracheal anastomosis was considered successful if the patient remained asymptomatic for 24 months of close follow up (involving regular flexible bronchoscopy and neck X-ray). The anastomotic success rate was 92.85 per cent.Conclusion:Tracheal resection and end-to-end anastomosis is relatively safe and reliable for definitive treatment of benign tracheal stenosis in appropriate patients. Local application of mitomycin C prevents granulation and aids long term airway patency.

Plexus-chorioideuscarcinomataor malignant plexus papillomas are very rare malignancy; only few cases have been described in the literature. A 2.5-year-old girl, known case of choroid plexus carcinoma, presented with complaints of weakness of right upper limb and lower limb, decreased activity, altered sensorium and vomiting. After re-evaluation, she underwent re-excision of tumor and chemotherapy started.

Mutations in human ether-a-go-go-related gene 1 ( hERG) are linked to long QT syndrome type 2 (LQT2). hERG encodes the pore-forming α-subunits that coassemble to form rapidly activating delayed rectifier K+ current in the heart. LQT2-linked missense mutations have been extensively studied in noncardiac heterologous expression systems, where biogenic (protein trafficking) and biophysical (gating and permeation) abnormalities have been postulated to underlie the loss-of-function phenotype associated with LQT2 channels. Little is known about the properties of LQT2-linked hERG channel proteins in native cardiomyocyte systems. In this study, we expressed wild-type (WT) hERG and three LQT2-linked mutations in neonatal mouse cardiomyocytes and studied their electrophysiological and biochemical properties. Compared with WT hERG channels, the LQT2 missense mutations G601S and N470D hERG exhibited altered protein trafficking and underwent pharmacological correction, and N470D hERG channels gated at more negative voltages. The ΔY475 hERG deletion mutation trafficked similar to WT hERG channels, gated at more negative voltages, and had rapid deactivation kinetics, and these properties were confirmed in both neonatal mouse cardiomyocyte and human embryonic kidney (HEK)-293 cell expression systems. Differences between the cardiomyocytes and HEK-293 cell expression systems were that hERG current densities were reduced 10-fold and deactivation kinetics were accelerated 1.5- to 2-fold in neonatal mouse cardiomyocytes. An important finding of this work is that pharmacological correction of trafficking-deficient LQT2 mutations, as a potential innovative approach to therapy, is possible in native cardiac tissue.