A multicenter prospective observational study on the use of type and screen method versus conventional type and crossmatch policy for pre-transfusion testing in the Indian population.

Despite knowing the benefits of the type and screen (TS) method in pre-transfusion testing (PTT), most transfusion centers in developing countries continue to be reluctant to adopt a TS strategy over the conventional type and antihuman globulin (AHG) crossmatch (TX) policy in their routine laboratory practice because of the cost of obtaining antibody screening reagents. To generate strong evidence, this multicenter, observational study was conducted in which we collected data prospectively over a 1-year period from six major blood centers in India. The primary objective of this study was to identify the discordance between TS and TX results. A secondary objective was to identify the allo-antibody specificity in patients with positive antibody detection tests. All patients with orders for red blood cell transfusion who met patient selection criteria were subjected to parallel testing by column agglutination technology (CAT) for both the antibody detection test (screen) using a commercial three-cell panel and for the AHG crossmatch. A total of 21,842 patients were tested. In 148 patients with incompatible crossmatches, samples from six patients gave negative results with the antibody detection test, whereas the antibody detection test was positive in samples from 118 patients among the 21,694 crossmatch-compatible cases. The TS approach achieved a positive percent agreement of 95.95 and was found to be significantly effective in preventing the transfusion of serologically incompatible blood. The risk associated with abbreviating the AHG crossmatch was found to be 0.009 percent. Most of the identified clinically significant alloantibodies were directed to Rh antigens (D>E>c>C>e), followed by anti-K and anti-M. This study has generated sufficient robust data for the Indian population by including patients from all major geographical areas of the country and concluded a satisfactory agreement level as well as non-inferiority to the current PTT policy. Therefore, TS policy can be implemented in developing countries with no compromise on blood safety, provided sufficient technical and infrastructural support are available.

An unusual presentation of synchronous bladder metastases from an oesophageal adenocarcinoma.

Adenocarcinoma of the bladder is a rare form of malignancy accounting for fewer than 2% of bladder tumours. It is most commonly a result of direct invasion from prostatic, rectal or gynaecological primaries and less commonly presents from distant haematological or lymphatic metastasis. We report a rare case of oesophageal carcinoma metastasising to the bladder. It involves a 71-year-old man with progressive dysphagia and diagnostic computerised tomography findings of thickening in the oesophagus, bladder and common bile duct. Subsequent endoscopic biopsies of the oesophageal and bladder abnormalities showed immunohistochemical features consistent with upper gastrointestinal malignancy. This report aims to add to current clinical evidence of this route of metastasis and also highlight some of the key markers used by pathologists in interpretation of specimens. It also emphasises the essential role of a multidisciplinary approach for the diagnosis of such rare conditions.

Clinicopathological features of Differentiated Thyroid Cancer presenting in the UK versus internationally: An observational cohort study.

INTRODUCTION: Very little data are available regarding differentiated thyroid cancer (DTC) managed in the UK, and no UK patients are included in the evidence base upon which international guidelines are based. Therefore, the aim of this study was to compare the clinicopathological features of patients with DTC presenting in a UK population with international patient cohorts. PATIENTS AND METHODS: Data were collected from a prospectively held multi-disciplinary team records from January 2009 to December 2016. The local cohort was compared with cohorts from across the world based on clinicopathological features. Ethical approval was obtained by Lothian Caldicott Guardian (Ref 16 133). RESULTS: 444 cases were diagnosed locally with a median age of 48 years (range 16-86 years). 78% of patients were female. 25% of our patients had follicular carcinoma with an overall N1 rate of 20%. Distant disease was recorded in 5% cases. In comparison with international data, our local cohort had a higher rate of follicular thyroid carcinoma. Variation was seen in terms of age, gender distribution, primary tumour size, nodal and distant disease. In Korea, where thyroid cancer screening has been undertaken, smaller tumours, higher rates of nodal disease and lower rates of distant disease are described. CONCLUSION: In our centre, a higher rate of males is treated with larger primary disease and a higher percentage of follicular carcinoma. The reasons for this geographic variation in clinicopathological features in the UK are unclear. As a result, caution should be applied in translating the international move towards a more conservative approach to DTC in the UK in comparison with other areas of the world.

Oncological outcomes in differentiated thyroid cancer in South East Scotland.

BACKGROUND: Differentiated thyroid cancer (DTC) is increasing in incidence but little is known about oncological outcomes for patients treated in the UK. Internationally there is a move toward conservative treatment of DTC. However, this is based on evidence from outside the UK. The aim of this study was to analyse oncological outcomes for a contemporary cohort of patients treated in a UK centre. METHODS: Review of 470 consecutive prospectively recorded cases of DTC from the South East of Scotland endocrine MDT 2009-2018. Data on patient, tumour and treatment details as well as recurrence and survival details were extracted from the electronic patient record. RESULTS: Of 470 patients female:male ratio was 3.4:1, median age at presentation was 48 years (range 16-86 years). Overall 193 (41%), 134 (29%), 119 (25%) and 22 (5%) patients were p T1, T2, T3, and p T4 respectively. 385 patients (82%) were pN0, 31 patients (7%) were pN1a and 53 patients (11%) were pN1b. 19 patients (4%) were M1. Of 470 patients 350 (74%) had papillary thyroid carcinoma, 120 patients (26%) had follicular carcinoma. Surgical management was lobectomy, isthumusectomy, total thyroidectomy and lobectomy then completion thyroidectomy in 14%,1%, 41% and 43% cases respectively. 64% patients received radioactive Iodine (RAI) therapy. With a median follow-up of 70 months (range 4-124 months), 5 years overall survival and disease specific survival were 96.7% and 98.5% respectively. The 5 year local recurrence free survival (LRFS), regional recurrence free survival (RRFS), locoregional recurrence free survival (LRRFS), distant recurrence free survival (DRFS) and any recurrence free survivals were 100%, 95.8%, 95.8%, 98.3% and 95% respectively. CONCLUSION: Oncological outcomes for patients treated with DTC were excellent, in keeping with experience from international groups, suggesting that a move towards conservative treatment in the UK seems reasonable.

The impact of completion thyroidectomy.

INTRODUCTION: The oncological benefit of completion thyroidectomy (CT) following thyroid lobectomy (TL) is presumed to be similar to that of upfront total thyroidectomy(TT), from a patient's perspective the risk and inconvenience of further surgery adds significantly to the impact of the overall treatment. The aim of this study is to assess the impact of CT in terms of the duration of admission and associated complications. METHODS: A study of consecutive patients with DTC identified from prospective MDT records of South-East Scotland from 2009 to 2015. Surgical data was extracted from electronic medical record. RESULTS: Of 361 patients diagnosed with DTC, 161 (45%) had CT. The median postoperative stay was 1 day (range 1-5days). In total 22 patients (14%)suffered complications. Four patients (3%) developed postoperative haematoma. Two (1%) had an identified permanent nerve palsy on the completion side. 13 patients (8%) remained on calcium supplementation for more than 6 months postoperatively and three patients (2%) developed wound complications. CONCLUSIONS: Our study confirms that CT is regularly performed (45%). Recent changes in international guidelines recognize increasing number of patients as eligible for a conservative approach but recommend CT based on whether upfront TT would have been recommended if the TL pathology were known from the outset. Such an approach fails to consider the additional risk and inconvenience of CT on the overall patient experience. Due to a relatively high rate of complications, only those patients who are most likely to benefit from further surgery to facilitate adjuvant radioactive iodine should be offered additional surgery.

Factors associated with intention to engage in self-protective behavior: The case of over-the-counter acetaminophen products.

BACKGROUND: Inappropriate use of acetaminophen products is a concern due to the severe liver damage associated with intentional or accidental overdose of these products. In 2009, the U.S. Food and Drug Administration (FDA) issued more severe organ-specific warnings for the acetaminophen Drug Facts label to improve protective behavior among patients. However, it is not clear how patients react to such interventions by the FDA. OBJECTIVE: The objective of this study was to evaluate the factors influencing patients' intention to engage in protective behavior while using acetaminophen products after reading the Drug Facts label. The study specifically looked at the relationship between four Protection Motivation Theory-based risk cognition factors and the intention to engage in protective behavior. METHODS: An experimental, cross-sectional, field study was conducted using self-administered questionnaires at four community pharmacies in Houston, TX. Two hundred surveys were collected from adults visiting the selected pharmacy stores. Participants were exposed to a simulated label (i.e. Drug Facts label) containing organ-specific warnings for over-the-counter (OTC) acetaminophen products. Risk cognition measures (i.e. measures of perceived severity, perceived vulnerability, response efficacy, and self-efficacy) and measures of intention to engage in protective behavior (always reading warnings, using products with more caution, and consulting a pharmacist/physician) were recorded. Pearson correlation and multiple linear regression analyses, controlling for demographic and behavioral characteristics of the participants, were performed. RESULTS: Bivariate analyses indicated that an increase in perceived severity, perceived vulnerability and response efficacy were associated with a higher intention to engage in protective behavior. Findings from the multiple regression indicated that increase in perceived severity of liver damage, belonging to a non-healthcare occupation, no history of acetaminophen use and no history of alcohol consumption were associated with a higher intention to engage in protective behavior. CONCLUSION: Higher risk cognition of liver damage associated with inappropriate use of OTC acetaminophen products leads to greater intention to engage in protective behavior while using such products. Developing interventions targeted towards improving reading and adhering to the Drug Facts label could improve risk cognition, and thus improve patients' intention to engage in protective behavior. Regular acetaminophen users, heavy alcohol consumers and healthcare professionals might need other interventions apart from the Drug Facts label to improve their likelihood to engage in protective behavior.

Pooled platelet product using the Acrodose plus system: evaluation of feasibility, safety and efficacy.

BACKGROUND: Pooling of whole blood-derived platelets is not practiced in India. Currently available data shows that pooled platelets are equivalent in quality and less costly when compared with apheresis platelets. AIM: To evaluate feasibility, safety and efficacy of pooled platelets using the Acrodose Plus system. MATERIAL AND METHODS: Standardization of platelet pooling procedure was done. Sterile docking device was used to maintain closed system. Pools of ABO compatible platelets (N=40) as well as ABO incompatible (N=10) pooled platelets were studied. ABO antibody titers were studied before and after pooling in case of ABO incompatible platelet pools. Corrected count increments (CCIs) (at 1h and 24h) were noted after transfusion of pooled platelets and Apheresis platelets in matched patient groups. RESULTS: Loss of platelet product due to pooling and leucodepletion was not statistically significant (p=0.23). Leucodepletion >3 log was achieved in all pooled platelets. The total platelet content, time taken for procedure and pH were within acceptable limits. There were no issues related to platelet availability and turn around time during the study period. There was a reduction in the ABO antibody titers after pooling in case of the ABO incompatible pools. None of the pooled platelets showed evidence of bacterial contamination on testing with eBDS system at 18 h and 24h intervals after pooling. CCI with pooled platelets was equivalent to that with apheresis platelets at 1h (p=0.36) and 24h (p=0.15). CONCLUSION: Whole blood derived platelets can be pooled safely using closed system without altering the platelet quality in vitro as well as in vivo survival post transfusion. Pooled platelets can be a cost effective and safe alternative to thrombocytopenic patients whose transfusion requirements cannot be fulfilled with apheresis platelets alone.

Raman microscopy for noninvasive imaging of pharmaceutical nanocarriers: intracellular distribution of cationic liposomes of different composition.

Nanotechnology is playing an increasing role in targeted drug delivery into pathological tissues. Drug-loaded pharmaceutical nanocarriers can be delivered into diseased sites by passive targeting (spontaneous accumulation of nanocarriers in the areas with affected vasculature) or by active targeting (via site-specific ligands attached to the surface of drug-loaded nanocarriers). Subsequent level of targeting requires cellular internalization of nanocarriers and their specific association with certain individual cell organelles. The control over intracellular distribution of pharmaceutical nanocarriers requires effective and noninvasive methods of their visualization inside cells. In an attempt to enhance cellular internalization of pharmaceutical nanocarriers and their association with mitochondria specifically, we have prepared three types of cationic liposomes and investigated their intracellular distribution. The analysis was performed using Raman microspectroscopy in order to provide morphological information as well as biochemical signatures of the sample. It was demonstrated that Raman microscopy allows evaluation of the extent of mitochondrial association depending on the liposome composition.

Inventory management.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.

Laparoscopic correction of chronic uterine inversion.

A 24-year-old woman had chronic uterine inversion after failed manual reversion of acute uterine inversion following a full-term vaginal delivery. After 2 failed attempts at manual reversion under general anesthesia, operative laparoscopy was performed. After infiltration of the pubovesicocervical fascia with dilute adrenaline in saline solution and division of the uterovesical fold, the anterior cervix and uterus were incised vertically, the inversion corrected, and the incision closed in 2 layers with 1-0 polyglactin 910 interrupted sutures. Postoperatively, estradiol valerate was administered for 30 days. Repeat endoscopy 4 months later revealed a normal uterine cavity. Adhesions between the anterior uterine wall and the anterior abdominal wall were divided, and chromopertubation revealed bilaterally patent fallopian tubes bilaterally.

Rhabdomyolysis due to an uncommon interaction of ciprofloxacin with simvastatin.

A case report of a ciprofloxacin and simvastatin interaction is presented. The addition of ciprofloxacin to chronic simvastatin therapy led to the development of rhabdomyolysis. As ciprofloxacin is a weak inhibitor of CYP3A4, it is very likely that other mechanisms involving the ATP-binding cassette drug efflux transporter family played a role in this drug interaction.

Application quantum and physico chemical molecular descriptors utilizing principal components to study mode of anticoagulant activity of pyridyl chromen-2-one derivatives.

Factors II, V, VII and Xa have materialized as a key enzymes for the intervention of blood coagulation cascade and for the development of new anti thrombotic agents. The combined density functional quantum mechanical/molecular mechanical (QM/MM) approach has been used to access inhibition of prothrombin and thrombin production. The biological activities of coumarin derivatives as clotting factor inhibitors was quantitatively analyzed in terms of physicochemical parameters utilizing the principal component analysis. Structural requirements for maximal potency were derived from the results of a quantitative structure activity relationship analysis.

Antihyperglycemic Activity of Various Fractions of Cassia auriculata Linn. in Alloxan Diabetic Rats.

Present work describes the potent antidiabetic fraction from flowers of Cassia auriculata Linn. Hydromethanolic extract along with its ethyl acetate and n-butanol fractions were evaluated for antidiabetic activity in alloxan-induced diabetes in rats. The n-butanol fraction exhibited significant reduction (p<0.001) in blood glucose levels and was also found effective in restoring the blood lipids and proteins to normal level. The activity was found comparable with standard drug phenformin. The hydromethanolic extract and its fractions were subjected to preliminary qualitative chemical investigations which indicated the presence of phenolic compounds, carbohydrates, tannins, steroids and amino acids.

Evaluation of hemoglobin of blood donors deferred by the copper sulphate method for hemoglobin estimation.

INTRODUCTION: The copper sulphate (CuSO4) specific gravity test for Hb screening tends to give inappropriate failures. This prompted us to compare it with alternate screening methods. AIM: To study the impact of inaccuracy of CuSO4 method on donor deferral. METHODS: Capillary and venous blood samples of 400 potential blood donors failing the primary Hb screening using appropriately standardized CuSO4 test (specific gravity 1.053) were tested by Hemocue photometer, the Hb colour scale, Cyanmethemoglobin method as well as the automated hematology analyser, which was considered as the standard reference method. RESULTS: One hundred and sixteen donors (29%) who failed the CuSO4 test had true Hb levels >12.5 g/dl. The Hb levels of 131 (32.8%) deferred donors were between 12 and 12.5 g/dl. The sensitivity of Hemocue, Hb colour scale and Cyanmethemoglobin was 99%, 97% and 96% and their specificity was 45%, 93% and 46%, respectively. The positive predictive values (PPV) of Hemocue and Cyanmethemoglobin methods were low (43% and 44%, respectively) but their negative predictive values (NPV) were high (99%, and 97%, respectively). The Hb colour scale had an overall best performance with a PPV of 96% and NPV of 95%. CONCLUSION: The Hemoglobin colour scale which is inexpensive, convenient for field testing and has the overall best performance, is the most suitable for donor Hb screening. Since its readability is 12 g/dl, lowering the donor Hb threshold to 12 g/dl should be actively considered.

Red cell hemolysis during processing and storage.

INTRODUCTION: Apart from the visual assessment, measurement of plasma hemoglobin in the supernatant from red cell units provides an objective measure of the extent of hemolysis during storage. STUDY DESIGN AND METHODS: Packed red cells (N=50), 25 units each in triple (CPD-A1 and SAGM) and quadruple (CPD-A1 and ADSOL) blood bags were evaluated for plasma hemoglobin by the tetramethylbenzidiene (TMB) method on day 1, 7, 14, 21 and 28 of collection. The hemoglobin, hematocrit, MCV, LDH and potassium levels were also noted. Whole blood units (N=25) were used as controls. RESULTS: Hemolysis increased in all the stored red cell units. Plasma hemoglobin increased significantly in the first week of storage. The hemolysis, LDH and potassium levels were found to be significantly higher in the red cell units harvested from the triple blood bags. However, on day 28 of storage, free hemoglobin in all the red cell units was much below the 0.8% hemolysis. CONCLUSION: Hemolysis of the red cells increases due to processing and during storage and is maximum during the first week. Adequate process control and proper storage facilities should be ensured to minimize the hemolysis of red cells during processing and storage.

"SMART" drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers.

To develop targeted pharmaceutical carriers additionally capable of responding to certain local stimuli, such as decreased pH values in tumors or infarcts, targeted long-circulating PEGylated liposomes and PEG-phosphatidylethanolamine (PEG-PE)-based micelles have been prepared with several functions. First, they are capable of targeting a specific cell or organ by attaching the monoclonal antimyosin antibody 2G4 to their surface via pNP-PEG-PE moieties. Second, these liposomes and micelles were additionally modified with biotin or TAT peptide (TATp) moieties attached to the surface of the nanocarrier by using biotin-PE or TATp-PE or TATp-short PEG-PE derivatives. PEG-PE used for liposome surface modification or for micelle preparation was made degradable by inserting the pH-sensitive hydrazone bond between PEG and PE (PEG-Hz-PE). Under normal pH values, biotin and TATp functions on the surface of nanocarriers were "shielded" by long protecting PEG chains (pH-degradable PEG(2000)-PE or PEG(5000)-PE) or by even longer pNP-PEG-PE moieties used to attach antibodies to the nanocarrier (non-pH-degradable PEG(3400)-PE or PEG(5000)-PE). At pH 7.4-8.0, both liposomes and micelles demonstrated high specific binding with 2G4 antibody substrate, myosin, but very limited binding on an avidin column (biotin-containing nanocarriers) or internalization by NIH/3T3 or U-87 cells (TATp-containing nanocarriers). However, upon brief incubation (15-30 min) at lower pH values (pH 5.0-6.0), nanocarriers lost their protective PEG shell because of acidic hydrolysis of PEG-Hz-PE and acquired the ability to become strongly retained on an avidin column (biotin-containing nanocarriers) or effectively internalized by cells via TATp moieties (TATp-containing nanocarriers). We consider this result as the first step in the development of multifunctional stimuli-sensitive pharmaceutical nanocarriers.

Ecotoxicological effect of grounded MV River Princess on the intertidal benthic organisms off Goa.

The ecotoxicological effects of oil spill from the grounded vessel MV River Princess on the intertidal benthic organisms of Sinquerim-Candolim beach at Goa were investigated. An intertidal expanse of 1 km on either side of the grounded vessel was selected to evaluate the concentration of total petroleum hydrocarbon (TPH) in the sediment and its effects on the composition, abundance and diversity of micro-, meio- and macrobenthos. TPH in the intertidal sediment ranged from 7.8 to 89 microg g(-1) (mean 35.44+/-26.35 SD). Microbenthos comprised of microalgae, protozoans and juvenile forms of meiobenthos. Apart from juvenile nematodes, which were abundant, Coscinodiscus spp., Navicula spp., and Nitzschia spp. representing microalgae were also observed in microbenthic samples. Meiobenthos was represented by 13 taxa and their total density ranged between 92 and 1057 nos. 10 cm(-2). Maximum meiobenthic abundance of 1057 nos. 10 cm(-2) was observed at Sinquerim. Nematodes were the dominant meiobenthic taxa followed by turbellarians and harpacticoid copepods. The macrobenthos was numerically dominated by polychaetes, followed by crustaceans whereas bivalve molluscs were less represented. There was substantial increase in the petroleum concentration in the beach sediment compared to the previously reported values and highest TPH (89 microg g(-1) sediment) values were in the vicinity of the grounded vessel. The polychaete/amphipod ratio and cumulative and partial dominance abundance-biomass curves showed significant negative impact of TPH on macrofauna. The benthic community structure also showed measurable changes, as there was significant decrease (60%) in the number of species. Given that the microalgal counts were low in sediment, it is assumed that the intertidal meiofauna was possibly using oil-degrading bacteria as alternate food source. In conclusion, the results reported here suggest that the grounded ore carrier is not only detrimental to the beach community, that may take longer time for recovery, but also affects the beach morphology which may have long-term impact on local fishery.

Correlation of CD34+ cell yield in peripheral blood progenitor cell product with the pre-leukapheresis cell counts in peripheral blood.

INTRODUCTION: Accurate timing of the leukapheresis procedures is of paramount importance to get the best possible CD34+ cell yield in the minimum number of leukapheresis procedures. AIM: To find if pre-harvest CD34+ cell concentration in peripheral blood correlates with CD34+ cells in the product. MATERIAL AND METHODS: Sixty Leukapheresis procedures were performed for 25 patients (8 autologous and 17 allogeneic transplants) with hematological malignancies. Statistical analysis was performed to correlate the pre-harvest CD34+ cell count and the CD34+ cell yield. Volume processed during PBPC harvests was three times the blood volume. RESULTS: The best correlation was found between the leukapheresis product CD34+ cell count and the pre-harvest PB-CD34+ cell count (PCC=0.674) when compared with the other pre-harvest PB cell counts viz., WBC (PCC=0.229) and MNC (PCC=0.324). This correlation was better in the allogeneic harvest (PCC = 0.645) than the autologous harvest procedures (PCC = 0.348). Correlation analysis based on paired samples from the 60 leukapheresis procedures showed that when the pre-leukapheresis PB-CD34+ cell count was >20x10(3)/ul a yield of >1x10(6) CD34+ cells/Kg could be obtained in 95% of the cases and >2x10(6) CD34+ cells /Kg could be harvested in 68% of cases whereas when the pre-leukapheresis PB-CD34+ cell count was <5x10(3)/microl the yield was <1x10(6) CD34+ cells/Kg in 81% of the procedures. CONCLUSION: The yield of CD34+ cells in PBPC harvests depends on the pre-harvest CD34+ cell concentration and therefore it is more useful than the pre-harvest WBC or MNC counts for predicting the appropriate timing of the harvests and also to achieve the best possible yield of CD34+ cells.