Effectiveness of Preparedness Training Delivered to Pre-final and Final Year Nursing Undergraduates to Combat COVID-19: A Need-based Initiative.

A major concern during the COVID-19 pandemic has been the shortage of manpower for patient care. The recommendation of various authorised bodies encouraged the training of students from medical, nursing, and allied fields to manage COVID-19 cases by tele-consultation and monitoring of mild cases under the supervision of faculty. Anticipating a further shortage of human resources, leading to dire consequences, preparedness training for the final year and pre-final nursing undergraduates was initiated. The current study was conducted to evaluate the effectiveness of and feedback on COVID-19 preparedness training delivered to final-and pre-final-year undergraduate nursing students. A 3-day training was given to pre-final and final year nursing undergraduates on ECG, COVID-19 management protocols, personal protective equipment "donning and doffing", "hand hygiene", "biomedical waste management", "contact tracing" and cleaning and disinfection and simulation-based skills. Scores before and after training were conducted and mean scores were compared using a paired t-test. In total, 154 nursing students participated in the training program. Mean pre-test and post-test scores included: general instructions (21.69±2.5 and 25.09±3.29); skill procedures (5.4±1.21 and 6.3±1.2) and COVID management (22.84±3.26 and 26.48±2.06). There was a statistically significant improvement in knowledge and skills in all training sessions (p=0.0001). The mean post-test scores obtained at the OSCE stations for cardiac monitoring, prone positioning, compression-only CPR, airway, ECG and ABG ranged from 97.0% to 100.0% and all participants scored >70.0%. About 92.8% of the students felt that hands-on training enhanced their learning experiences. A need-based initiative of training final-and pre-final-year nursing students in COVID-19 support care effectively and efficiently created a skilled workforce.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Photoemission Spectroscopy Using Virtual Photons Emitted by Positron Sticking: A Complementary Probe for Top-Layer Surface Electronic Structures.

We present a spectroscopic method which utilizes virtual photons to selectively measure the electronic structure of the topmost atomic layer. These virtual photons are created when incident positrons transition from vacuum states to bound surface states on the sample surface and can transfer sufficient energy to excite electrons into the vacuum. The short interaction range of the virtual photons restricts the penetration depth to approximately the Thomas-Fermi screening length. Measurements and analysis of the kinetic energies of the emitted electrons made on a single layer of graphene deposited on Cu and on the clean Cu substrate show that the ejected electrons originate exclusively from the topmost atomic layer. Moreover, we find that the kinetic energies of the emitted electrons reflect the density of states at the surface. These results demonstrate that this technique will be a complementary tool to existing spectroscopic techniques in determining the electronic structure of 2D materials and fragile systems due to the absence of subsurface contributions and probe-induced surface damage.

Revised workflow practices in the management of acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic.

OBJECTIVE: To document changes in evaluation protocols for acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic, and to analyse concordance between clinical and histopathological diagnoses based on new practice guidelines. METHODS: Protocols for the evaluation of patients with suspected acute invasive fungal sinusitis both prior and during the coronavirus disease 2019 period are described. A retrospective analysis of patients presenting with suspected acute invasive fungal sinusitis from 1 May to 30 June 2021 was conducted, with assessment of the concordance between clinical and final diagnoses. RESULTS: Among 171 patients with high clinical suspicion, 160 (93.6 per cent) had a final histopathological diagnosis of invasive fungal sinusitis, concordant with the clinical diagnosis, with sensitivity of 100 per cent, positive predictive value of 93.6 per cent and negative predictive value of 100 per cent. CONCLUSION: The study highlights a valuable screening tool with good accuracy, involving emphasis on 'red flag' signs in high-risk populations. This could be valuable in situations demanding the avoidance of aerosol-generating procedures and in resource-limited settings facilitating early referral to higher level care centres.

Constellation-based identification of linear and nonlinear OSNR using machine learning: a study of link-agnostic performance.

We demonstrate accurate estimation of generalized optical signal to noise ratio (GOSNR) for wavelength division multiplexed fiber communication systems using an experimentally trained multi-tasking convolutional neural network while simultaneously estimating linear and nonlinear noise contributions. Using dual-polarized 32-GBaud 16QAM DWDM links we extract learnable features from constellation density matrices and accurately estimate GOSNR while simultaneously estimating linear and nonlinear contributions. Estimation of the OSNRASE, OSNRNL and GOSNR are demonstrated with < 0.5 dB mean absolute error. We also assess the universality of our model within the regime of metro networks by cross-training with data from such links comprised of different fiber types. We demonstrate a path to a practical universal training method that includes additional link parameters. The methods do not require contiguous high-speed sampling, additional hardware nor transmission of special symbols or patterns and are readily implemented in deployed systems.

Nasopharyngeal colonization of otopathogens in South Indian children with acute otitis media - A case control pilot study.

BACKGROUND: Acute otitis media (AOM) is an inflammatory disease of the middle ear causing significant morbidity in early childhood. A pilot study was undertaken to identify the role of various risk factors South Indian children with AOM, especially the role of nasopharyngeal otopathogens. METHODOLOGY: A prospective case control pilot study was conducted in children aged below six years, presenting to a single tertiary care from 2018 to 2019. Fifty cases with AOM and 45 age and gender matched controls were recruited. Two nasopharyngeal swabs were collected, one was processed for bacterial culture. The other swab was processed according to the CDC recommended broth enrichment method to identify carriage of S. pneumoniae. Subsequent serotyping was done by Quellung method and conventional sequential multiplex PCR. RESULT: Otalgia was the major presentation seen in 92% of the children with AOM. None of the clinical and demographic characteristics were found to be statistically significant between the cases and controls. The most common otopathogen was S. pneumoniae (55%) followed by H. influenza (29%). The common S. pneumoniae serotypes encountered were 11A and 19F.Nasopharyngeal colonization with S. pneumoniae [OR 6.57, p < 0.003] and H. influenzae [OR14.18, p < 0.003] were significant risk factors for AOM in children. The risk increased with co-colonization (OR 13.89,p < 0.003). CONCLUSION: This study strengthens the significant association between nasopharyngeal colonization of otopathogens and AOM as a risk factor that is enhanced by co-colonization.S. pneumoniae was the main otopathogen in this population, serotypes 11A and 19F being the most common.

Effect of preoperative oral administration of steroids in comparison to an anti-inflammatory drug on postoperative pain following single-visit root canal treatment - a double-blind, randomized clinical trial.

AIM: This randomized, double-blinded, clinical trial evaluated the effect of oral premedication of piroxicam, prednisolone, dexamethasone or placebo on postoperative pain after single-visit root canal treatment in teeth with symptomatic irreversible pulpitis and symptomatic apical periodontitis. METHODOLOGY: The trial is reported according to the Preferred Reporting Items for RAndomized Trials in Endodontics (PRIRATE) 2020 guidelines. The protocol was registered at the clinical trial registry (India) (CTRI/2019/06/019818). In total, 160 patients, assigned to four groups, received orally either 20 mg piroxicam, 20 mg prednisolone, 4 mg dexamethasone or a placebo 60 min before root canal treatment. Patients recorded their postoperative pain intensity at 6, 12, 24, 48 and 72 h using a 10-cm visual analogue scale. Intergroup comparison was performed using Kruskal-Wallis tests with post hoc analysis using Dunns test. Incidence of pain was analysed using chi-square tests. A P value < 0.05 was considered to be statistically significant. Binary logistic regression was used to determine the odds of postoperative pain, with incidence of pain as the dependent variable and intervention groups, gender, age and type of tooth as independent variables. RESULTS: In total, 156 patients were analysed in the trial, since four patients dropped out during follow-up. All drugs were associated with a significantly lower incidence of postoperative pain compared to the placebo at 6 h (P = 0.009), 12 h (P = 0.003) and 24 h (P = 0.008). Mean intensity of pain was significantly more intense at 6, 12 and 24 h with the use of placebo in comparison to the other three intervention groups (P < 0.05). Intensity of pain was not significantly different between the premedications used (P > 0.05). One patient in the piroxicam group reported gastritis, whereas no adverse effects were recorded in other groups. CONCLUSION: Preoperative oral administration of a single dose of 4 mg dexamethasone, 20 mg piroxicam or 20 mg prednisolone reduced the incidence and severity of postoperative pain following single-visit root canal treatment compared to a placebo in patients with symptomatic irreversible pulpitis and symptomatic apical periodontitis up to 24 h. The odds of postoperative pain at 24 h for patients premedicated with 4 mg dexamethasone or 20 mg piroxicam or 20 mg prednisolone were 5.3 times, 3.4 times and 2.5 times less compared to the placebo, respectively.

Ultrasound imaging for the differential diagnosis of periapical lesions of endodontic origin in comparison with histopathology - a systematic review and meta-analysis.

BACKGROUND: Differentiating periapical lesions is important for treatment planning and subsequent treatment outcome. OBJECTIVE: To assess the diagnostic accuracy of ultrasound imaging for the differentiation of periapical lesions in comparison with histopathology. METHODS: PubMed, Scopus, Embase, Web of Science and ProQuest databases were searched for clinical studies published until June 2020 that evaluated the use of ultrasound (US) imaging for differential diagnosis of periapical lesions and used histopathology as the reference standard. Animal studies, laboratory-based studies, reviews and clinical studies not using a reference standard were excluded. Risk of bias (RoB) assessment was performed using a modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The random effects model was used for quantitative analysis of the data, and the Deeks test was used for calculating publication bias. Quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twelve articles were included in the systematic review, out of which ten articles were quantitatively assessed. All the articles had a high RoB and concerns regarding applicability in the patient selection domain. For the index test domain, seven articles had low and the remaining five had unclear RoB and concerns regarding applicability. In the reference standard domain, low RoB and concerns regarding applicability were observed for all the articles. The RoB was low in flow and timing domains in all the articles except for one, where it was high. Summary estimates of sensitivity and specificity of US to diagnose periapical granulomas were 0.94 and 0.98, whereas for periapical cysts it was 0.98 and 0.99, respectively. Area under the curve for diagnosis of both periapical granulomas and periapical cysts was 0.99. All the included articles had inherent publication bias. Quality of evidence using GRADE, for sensitivity, was moderate for periapical granulomas and high for periapical cysts, whereas for specificity, it was high for periapical granulomas and low for periapical cysts. DISCUSSION: The available evidence is considered to be of low quality due to the observational nature of the studies and inherent publication bias. CONCLUSION: Although the sensitivity and specificity for differentiating periapical cysts and periapical granulomas using US were high, taking the quality of evidence into consideration, it can serve as an additional tool in differential diagnosis of periapical lesions.

Direct evidence for low-energy electron emission following O LVV Auger transitions at oxide surfaces.

Oxygen, the third most abundant element in the universe, plays a key role in the chemistry of condensed matter and biological systems. Here, we report evidence for a hitherto unexplored Auger transition in oxides, where a valence band electron fills a vacancy in the 2s state of oxygen, transferring sufficient energy to allow electron emission. We used a beam of positrons with kinetic energies of [Formula: see text] eV to create O 2s holes via matter-antimatter annihilation. This made possible the elimination of the large secondary electron background that has precluded definitive measurements of the low-energy electrons emitted through this process. Our experiments indicate that low-energy electron emission following the Auger decay of O 2s holes from adsorbed oxygen and oxide surfaces are very efficient. Specifically, our results indicate that the low energy electron emission following the Auger decay of O 2s hole is nearly as efficient as electron emission following the relaxation of O 1s holes in [Formula: see text]. This has important implications for the understanding of Auger-stimulated ion desorption, Coulombic decay, photodynamic cancer therapies, and may yield important insights into the radiation-induced reactive sites for corrosion and catalysis.

Pediatric nasal dermoid- a decade's experience from a South Indian tertiary care centre.

INTRODUCTION: Nasal dermoid sinus cyst (NDSC) are uncommon congenital lesions in children. OBJECTIVE: To review the clinical and radiological presentation and study the surgical outcomes of this uncommon lesion. METHOD: Retrospective chart review of all children diagnosed with nasal dermoid from 2010 to 2020 at a tertiary referral hospital in South India was executed. The medical records were reviewed for demographics, lesion characteristics, imaging, operative details, and outcomes and literature review was performed. RESULT: A total of 25 children [Mean age 3.7 yrs (Range 2-9 yrs)] with nasal dermoid sinus cysts were treated in the last decade. While 13 presented with a sinus, 11 presented with cyst and 1 had both. The lesions mainly involved the upper third of the nose in 10 children, middle one third in 6 and upper one third in 9 children. All underwent Magnetic Resonance Imaging, in 11 Computed Tomography also was done. A flow chart of the lesion characteristics and its management has been presented. Intraoperatively intracranial extension was present in four children. The approach to intracranial extension and corresponding literature review has been presented. Follow up ranged from one to six years. (Median 3.5 yrs) and no recurrence or complication was noted. CONCLUSION: Nasal dermoid is an uncommon congenital anomaly. Preoperative evaluation must include imaging to assess extent and rule out intracranial extension. Surgical strategy depends on whether presentation is as sinus or cyst and location and extent of lesion. All surgical approaches have a good surgical and cosmetic outcome.

Development of a surgical assessment tool for national policy monitoring & evaluation in Ethiopia: A quality improvement study.

BACKGROUND: A baseline assessment of surgical capacity is recommended as a first-step to surgical system strengthening in order to inform national policy. In Ethiopia, the World Health Organization's Tool for Situational Analysis (WHO SAT) was adapted to assess surgical, obstetric, and anesthesia capacity as part of a national initiative: Saving Lives Through Safe Surgery (SaLTS). This study describes the process of adapting this tool and initial results. MATERIALS AND METHODS: The new tool was used to evaluate fourteen hospitals in the Southern Nations, Nationalities, and People's Region of Ethiopia between February and March 2017. Two analytic methods were employed. To compare this data to international metrics, the WHO Service Availability and Readiness Assessment (SARA) framework was used. To assess congruence with national policy, data was evaluated against Ethiopian SaLTS targets. RESULTS: Facilities had on average 62% of SARA items necessary for both basic surgery and comprehensive surgery. Primary, general, and specialized facilities offered on average 84%, 100%, and 100% of SARA basic surgeries, and 58%, 73% and 90% of SARA comprehensive surgeries, respectively. An average of 68% of SaLTS primary surgeries were available at primary facilities, 83% at general facilities, and 100% at specialized facilities. General and specialized hospitals offered an average of 80% of SaLTS general surgeries, while one specialized hospital offered 38% of SaLTS specialized surgeries. CONCLUSION: While the modified SaLTS Tool provided evaluation against Ethiopian national benchmarks, the resultant assessment was much lengthier than standard international tools. Analysis of results using the SARA framework allowed for comparison to global standards and provided insight into essential parts of the tool. An assessment tool for national surgical policy should maintain internationally comparable metrics and incorporation into existing surveys when possible, while including country-specific targets.

Eugenia jambolana extract reduces the systemic exposure of Sitagliptin and improves conditions associated with diabetes: A pharmacokinetic and a pharmacodynamic herb-drug interaction study.

Eugenia jambolana (EJ) is an Indian traditional herb widely used for the treatment of diabetes mellitus. This herb is globally marketed as single or multi herb formulations. Many diabetes patients consume EJ extract oral hypoglycemic drugs together. This calls for a need to assess risks versus benefit of this co-administration. In present investigation, pharmacodynamic and pharmacokinetic interactions of aqueous extract of EJ seeds at the dose of 400 mg/kg are studied with 10 mg/kg of oral hypoglycaemic drug sitagliptin (SITA) by co-administrating them for 28 days in streptozotocin (STZ) induced diabetic rats. The pharmacokinetic parameters of SITA were determined using HPLC-ESI-MS/MS and it was found that the combination treatment reduces the systemic exposure of SITA by showing 38.70% reduction in concentration maximum (Cmax) and 22.40% reduction in area under curve (AUC). Despite low levels of SITA, the combination demonstrated a significant reduction in blood glucose level when compared with individual drug and individual extract administered groups during pharmacodynamic study. In addition, the liver function, the kidney function and the lipid parameters were found to be significantly improved and beneficial effects were found with respect to food intake and water intake and urine output in case of combination treatment groups when compared with individual treatment groups. Histopathological examination of pancreatic tissue suggests its significant recovery of having normal acinus with better cell protection in combination treatment. In conclusion, the combination treatment demonstrated reduced systemic exposure of SITA without compromising on its antihyperglycemic activity and improvement in conditions associated with diabetes.

Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes.

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

Coenzyme Q10 ameliorates cadmium induced reproductive toxicity in male rats.

This study aimed at investigating the protective role of CoQ10 against cadmium (Cd)-induced reproductive toxicity in male rats. Adult male Wistar rats were exposed to an acute dose of Cd (25 mg/kg bwt; Cd group), Cd+CoQ10 (25 mg/kg bwt Cd+10 mg CoQ10; Cd-Q10 group) and distilled water (control) in vivo for 15 consecutive days and semen quality was assessed. A significant reduction was noted in sperm concentration, progressive motility, morphology and DNA integrity in both Cd- and Cd-Q10 groups in comparison to control indicating Cd-induced testicular lipid per oxidation (LPO) and decline in indigenous antioxidant defense system as measured by total antioxidant capacity (TAC) (p<0.05). However, simultaneous co-administration of CoQ10 along with Cd (Cd-Q10 group) was able to improve sperm concentration, motility, progressive motility, morphology, DNA integrity, and testicular TAC as well as lower LPO compared to Cd group (p<0.05). Results indicate that used dose of CoQ10 is capable of moderately ameliorating reproductive toxicity of Cd by improving semen quality and reducing testicular oxidative stress.

Modified staged repair of bladder exstrophy: a strategy to prevent penile ischemia while maintaining advantage of the complete primary repair of bladder exstrophy.

INTRODUCTION: Penile ischemic injury is a reported catastrophic complication after complete primary repair of exstrophy (CPRE). Aiming to improve the bladder exstrophy-epispadias repair outcomes, the study institution adopted a modified staged exstrophy repair to incorporate the advantages of CPRE by avoiding concurrent epispadias repair and adding bilateral ureteral re-implantation and bladder neck tailoring (staged repair of bladder exstrophy with bilateral ureteral re-implantation [SRBE-BUR]) at the initial repair. It was hypothesized that such modifications minimize penile complications and prevent upper tract deterioration while enhancing bladder resistance and consequent capacity. Here, a comparative series of outcomes between CPRE and SRBE-BUR is reported. METHODS: A retrospective cohort study including all exstrophy-epispadias male neonates managed in the study institution from January 2000 to December 2014 was performed. Patients were divided into those who underwent CPRE-BUR (group 1) and SRBE-BUR (group 2) (Figure). Baseline characteristics, peri-operative data, and long-term surgical outcomes were collected and analyzed for between-group comparison. Fisher exact and Mann-Whitney U tests were performed for statistical analysis. RESULTS: A total of 21 eligible patients were included: 10 in group 1 and 11 in group 2. Baseline characteristics were comparable. Two patients in group 1 had intra-operative penile ischemic injury (one with subsequent penile tissue loss), whereas none of the group 2 patients had intra-operative complications. No significant difference between the groups was noted for operative time; however, significantly lesser blood loss was noted in group 2. Comparable long-term surgical outcomes such as additional surgical intervention, urinary continence, bladder capacity, vesicoureteral reflux, hydronephrosis and recurrent urinary tract infections (UTIs) were noted. In addition, although subjective, better penile length and cosmesis were achieved by staging the repair (Figure). CONCLUSION: The SRBE with bilateral ureteral re-implantation is a safe alternative for the repair of the exstrophy-epispadias repair as it prevents the catastrophic complication of penile tissue loss, while having comparable long-term outcomes with the CPRE. Delaying epispadias repair avoids penile injury besides possible improvement of its overall cosmesis.

Effect of Lactobacillus rhamnosus and Bifidobacterium lactis on gingival health, dental plaque, and periodontopathogens in adolescents: a randomised placebo-controlled clinical trial.

To determine the effect of a probiotic combination of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis BB-12 on the gingival health, dental plaque accumulation, and the oral carriage of four putative periodontal pathogens in healthy adolescents. 108 schoolboys, aged 13-15 years, participated in this study. They were divided into two groups: probiotics (n=54) and placebo (n=54). Both groups received two probiotic-laced or placebo lozenges twice a day during a four-week period. Plaque Index (PI) and Gingival Index (GI) were recorded at baseline and after four weeks. Salivary and plaque carriage of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum were also monitored likewise. 101 subjects completed the study. A statistically significant reduction in GI was seen in the probiotic group as compared to the placebo group (P=0.012). A reduction in PI was found for both groups, with no difference observed between the groups after intervention (P=0.819). Probiotic lozenges significantly reduced levels of A. actinomycetemcomitans and F. nucleatum in saliva and plaque (P<0.05) and levels of P. gingivalis in plaque (P<0.05), while no significant changes were found in the control group. A significant reduction (P<0.001) was also noted in the total salivary bacterial counts of the test group. The short-term daily consumption of LGG and BB-12 probiotic lozenges improved the gingival health in adolescents and decreased the microbial counts of A. actinomycetemcomitans, and P. gingivalis. Hence probiotic supplements may serve as a simple adjunct to standard oral care for promoting the oral health in adolescents.

Evaluation of Echinococcus granulosus recombinant EgAgB8/1, EgAgB8/2 and EPC1 antigens in the diagnosis of cystic echinococcosis in buffaloes.

Three recombinant proteins of Echinococcus granulosus including two antigen B sub-units EgAgB8/1 and EgAgB8/2 and Echinococcus protoscolex calcium binding protein 1 (EPC1) were expressed in prokaryotic expression vectors. The diagnostic potential of these three recombinant proteins was evaluated in the detection of cystic echinococcosis in buffaloes in IgG-ELISA. The EgAgB8/1 and EgAgB8/2 recombinant proteins reacted fairly with the hydatid infected buffaloes with sensitivity of 75.0% and 78.6%, respectively and specificity of 75.8% while EPC1 recombinant protein showed higher sensitivity (89.3%) but lower specificity (51.5%). Cross-reactivity of these three antigens was assayed with buffalo sera naturally infected with Explanatum explanatum, Paramphistomum epiclitum, Gastrothylax spp., Fasciola gigantica and Sarcocystis spp. EgAgB8/1 and EPC1 antigens cross-reacted with all these sera while EgAgB8/2 showed no cross-reaction with Sarcocystis spp. and reacted with some of the E. explanatum infected buffalo sera. This study explores the potential of three hydatid antigens viz. EgAgB8/1, EgAgB8/2 and EPC1 for their diagnostic potential in buffaloes positive for cystic echinococcosis.

Clinical and molecular characterization of patients with cancer of unknown primary in the modern era.

BACKGROUND: On the basis of historical data, patients with cancer of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than 1 year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next-generation sequencing in the evaluation and treatment of patients with CUP. PATIENTS AND METHODS: Under Institutional Review Board approval, we identified all CUP patients evaluated at our institution over a recent 2-year period. We documented demographic information, clinical outcomes, pathologic evaluations, next-generation sequencing of available tumor tissue, use of targeted therapies, and clinical trial enrollment. RESULTS: We identified 333 patients with a diagnosis of CUP evaluated at our institution from 1 January 2014 through 30 June 2016. Of these patients, 150 had targeted next-generation sequencing carried out on available tissue. Median overall survival in this cohort was 13 months. Forty-five of 150 (30%) patients had potentially targetable genomic alterations identified by tumor molecular profiling, and 15 of 150 (10%) received targeted therapies. Dominant mutation signatures were identified in 21 of 150 (14%), largely implicating exogenous mutagen exposures such as ultraviolet radiation and tobacco. CONCLUSIONS: Patients with CUP represent a heterogeneous population, harboring a variety of potentially targetable alterations. Next-generation sequencing may provide an opportunity for CUP patients to benefit from novel personalized therapies.

Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL.

ARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. A total of 200 patients were recruited to assess the primary end point of complete remission (CR) rates according to IWCLL criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following a pre-planned interim analysis. At final analysis, CR rates were 76 FCR vs 55% FCM-miniR (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.73). MRD-negativity rates were 54 FCR vs 44% FCM-miniR. More participants experienced serious adverse reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy.

Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL.

ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. Two hundred and fifteen patients were recruited to assess the primary end point of complete remission (CR) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8 FCR vs 69.3% FCM-R (adjusted odds ratio (OR): 0.97; 95% confidence interval (CI): (0.53-1.79), P=0.932). MRD-negativity rates were 59.3 FCR vs 50.5% FCM-R (adjusted OR: 0.70; 95% CI: (0.39-1.26), P=0.231). During treatment, 60.0% (n=129) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy.