Artificial Blood Development Implications for Military Medicine.

Massive hemorrhaging remains the most common cause of preventable battlefield deaths. Blood used for trauma care requires a robust donation network, capacity for long-term storage, and extensive and accurate testing. Bioengineering technologies could offer a remedy to these constraints in the form of blood substitutes-fluids that could be transfused into patients to provide oxygen, carry away waste, and aid in coagulation-that would be used in prolonged casualty care and in far-forward settings, overcoming the obstacles of distance and time. The different molecular properties of red blood cells (RBCs), blood substitutes, and platelet replacements contribute to their respective utilities, and each type is currently represented in ongoing clinical trials. Hemoglobin oxygen carriers (HBOCs) are the most advanced RBC replacements, many of which are currently being evaluated in clinical trials in the United States and other countries. Despite recent advancements, challenges remaining in the development of blood alternatives include stability, oxygen capacity, and compatibility. The continued research and investment in new technologies has the potential to significantly benefit the treatment of life-threatening emergency injuries, both on the battlefield and in the civilian sector. In this review, we discuss military blood-management practices and military-specific uses of individual blood components, as well as describe and analyze several artificial blood products that could be options for future battlefield use.

Factors Associated With Open Access Publishing Costs in Oncology Journals: Cross-sectional Observational Study.

BACKGROUND: Open access (OA) publishing represents an exciting opportunity to facilitate the dissemination of scientific information to global audiences. However, OA publishing is often associated with significant article processing charges (APCs) for authors, which may thus serve as a barrier to publication. OBJECTIVE: In this observational cohort study, we aimed to characterize the landscape of OA publishing in oncology and, further, identify characteristics of oncology journals that are predictive of APCs. METHODS: We identified oncology journals using the SCImago Journal & Country Rank database. All journals with an OA publication option and APC data openly available were included. We searched journal websites and tabulated journal characteristics, including APC amount (in US dollars), OA model (hybrid vs full), 2-year impact factor (IF), H-index, number of citable documents, modality/treatment specific (if applicable), and continent of origin. All APCs were converted to US-dollar equivalents for final analyses. Selecting variables with significant associations in the univariable analysis, we generated a multiple regression model to identify journal characteristics independently associated with OA APC amount. An audit of a random 10% sample of the data was independently performed by 2 authors to ensure data accuracy, precision, and reproducibility. RESULTS: Of 367 oncology journals screened, 251 met the final inclusion criteria. The median APC was US $2957 (IQR 1958-3450). The majority of journals (n=156, 62%) adopted the hybrid OA publication model and were based in Europe (n=119, 47%) or North America (n=87, 35%). The median (IQR) APC for all journals was US $2957 (1958-3540). Twenty-five (10%) journals had APCs greater than US $4000. There were 10 (4%) journals that offered OA publication with no publication charge. Univariable testing showed that journals with a greater number of citable documents (P<.001), higher 2-year IF (P<.001), higher H-index (P<.001), and those using the hybrid OA model (P<.001), or originating in Europe or North America (P<.001) tended to have higher APCs. In our multivariable model, the number of citable documents (ß=US $367, SD US $133; P=.006), 2-year IF (US $1144, SD US $177; P<.001), hybrid OA publishing model (US $991, SD US $189; P<.001), and North American origin (US $838, SD US $186; P<.001) persisted as significant predictors of processing charges. CONCLUSIONS: OA publication costs are greater in oncology journals that publish more citable articles, use the hybrid OA model, have a higher IF, and are based in North America or Europe. These findings may inform targeted action to help the oncology community fully appreciate the benefits of open science.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Factors Associated With Endowed Chair Allocation in Medical Oncology in the United States.

To explore persisting gender disparities across leadership roles in medicine, we examined factors associated with holding endowed chairs in US oncology divisions. In 2019, we identified 95 academic oncology divisions, using the Oncology Division Chiefs and Department Chairs listing in the American Society of Clinical Oncology myConnection forum. We collected public information on gender, degree, total National Institutes of Health funding as principal investigator, H-indices, publication and citation numbers, and graduation year and constructed a multivariable logistic regression model. All statistical tests were 2-sided. We identified 1087 oncology full professors. Of these, 287 (26.4%) held endowed chairs: 60 of 269 women (22.3%) vs 227 of 818 men (27.8%) (P = .08). On multivariable analysis, greater research productivity and National Institutes of Health funding were associated with having an endowed chair (P < .001), whereas gender was not (P = .45). Though sample size was limited, if gender differences are in fact smaller in certain subspecialties than other fields of internal medicine, insights might emerge to guide efforts to promote equity.

Postgraduate training in Cancer Genetics-a cross-specialty survey exploring experience of clinicians in Ireland.

BACKGROUND: As genomic profiling of constitutional and tumour-derived DNA becomes increasingly critical in cancer risk estimation, prognostication and treatment, there is a growing need for clinicians involved in cancer care to up-skill in Cancer Genetics. In the Republic of Ireland (ROI), this is particularly crucial, given a paucity of vocationally trained Clinical Geneticists per capita compared to other European countries. AIMS: We aimed to assess the self-reported confidence of postgraduate medical/surgical trainees in ROI in requesting, interpreting, and managing genomic data in patients with cancer, and to assess their selfreported experience, and demand for future training in this area. METHODS: A cross-sectional survey of postgraduate trainees in four specialties (Medical and Radiation Oncology, Surgery, and Obstetrics and Gynaecology (O&G)), training in ROI, was undertaken. A bespoke electronic questionnaire was designed to capture data regarding preceding experience, and confidence across several hypothetical clinical scenarios involving genomic testing. The survey was circulated to eligible participants by training programme administrators, after relevant institutional ethical approval. Data was collected anonymously. RESULTS: The study cohort included 62 respondents. A paucity of cancer genetics training at every level was demonstrated, with "hardly any" or "none at all" reported by 47(76%), 62(100%), and 50(81%) during undergraduate, core specialty, and higher specialist training, respectively. A relative lack of confidence in all clinical scenarios was apparent, particularly among Surgery/O&G trainees. Most respondents would value more training in Cancer Genetics. CONCLUSIONS: This study demonstrates an unmet need in dedicated Cancer Genetics training for postgraduate specialty trainees in ROI.

N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in more than 4 million deaths in the 20 months since the virus was discovered. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout and vaccine hesitancy. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of {beta}-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans. We tested GC as a potential countermeasure for COVID-19. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway and lungs. Our findings demonstrate a new application for soluble immunoadjuvants like GC for preventing severe disease associated with SARS-CoV-2. Single Sentence SummaryThe immunoadjuvant N-dihydrogalactochitosan diminishes SARS-CoV-2 disease in humanized ACE2 mice representing a new countermeasure against COVID-19.

Professor Hugh MacLean: one of the first British military research nephrologists and the pioneer of the first United Kingdom veterans' renal clinic.

Few people have been as successful in bringing together basic research, clinical science, and a contribution to military medicine as Professor Hugh MacLean. However, today he is almost forgotten. During World War 1, practicing within the realms of the new field of renal medicine, with minimal resources and in a military hospital, he conducted one of the first large-scale Medical Research Committee investigations into war nephritis involving 60,000 subjects. After the war he set up and practiced, amongst other specialties, in the field of veteran medicine and established the concept of the one-stop renal clinic. After achieving significant academic recognition, he was unfortunately affected by mental health problems, possibly related to his wartime experiences, which brought an illustrious career to an untimely end.

Trade-offs in moving citizen-based anuran call surveys online during the SARS-CoV-2 pandemic: Lessons from rural Appalachia, USA.

Citizen science approaches provide adaptable methodologies for enhancing the natural history knowledge of understudied taxa and engaging underserved populations with biodiversity. However, transitions to remote, virtual training, and participant recruitment in response to public health crises like the SARS-CoV-2 pandemic have the potential to disrupt citizen science projects. We present a comparison of outputs from a citizen science initiative built around call surveys for the Mountain Chorus Frog (Pseudacris brachyphona), an understudied anuran, in Appalachian Virginia, USA, prior to and during the SARS-CoV-2 pandemic. A transition to virtual training in this initiative did not lead to a decrease in scientific output and led to unexpected natural history insight about our focal taxon; however, a reliance on virtual instruction did decrease overall participation by local residents, particularly for rural K-12 students. We discuss the trade-offs exhibited by the adaptation of our initiative to a virtual format and provide recommendations for other citizen science initiatives facing similar restrictions in the face of current and future public health crises.

CRISPR-Mediated Single Nucleotide Polymorphism Modeling in Rats Reveals Insight Into Reduced Cardiovascular Risk Associated With Mediterranean G6PD Variant.

Epidemiological studies suggest that individuals in the Mediterranean region with a loss-of-function, nonsynonymous single nucleotide polymorphism (S188F), in glucose-6-phosphate dehydrogenase (G6pd) are less susceptible to vascular diseases. However, this association has not yet been experimentally proven. Here, we set out to determine whether the Mediterranean mutation confers protection from vascular diseases and to discover the underlying protective mechanism. We generated a rat model with the Mediterranean single nucleotide polymorphism (G6PDS188F) using CRISPR-Cas9 genome editing. In rats carrying the mutation, G6PD activity, but not expression, was reduced to 20% of wild-type (WT) littermates. Additionally, unbiased metabolomics analysis revealed that the pentose phosphate pathway and other ancillary metabolic pathways connected to the pentose phosphate pathway were reduced (P<0.05) in the arteries of G6PDS188F versus WT rats. Intriguingly, G6PDS188F mutants, as compared with WT rats, developed less large arterial stiffness and hypertension evoked by high-fat diet and nitric oxide synthase inhibition with L-NG-nitroarginine methyl ester. Intravenous injection of a voltage-gated L-type Ca2+ channel agonist (methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate; Bay K8644) acutely increased blood pressure in WT but not in G6PDS188F rats. Finally, our results suggested that (1) lower resting membrane potential of smooth muscle caused by increased expression of K+ channel proteins and (2) decreased voltage-gated Ca2+ channel activity in smooth muscle contributed to reduced hypertension and arterial stiffness evoked by L-NG-nitroarginine methyl ester and high-fat diet to G6PDS188F mutants as compared with WT rats. In summary, a mutation resulting in the replacement of a single amino acid (S188F) in G6PD, the rate-limiting enzyme in the pentose phosphate pathway, ascribed properties to the vascular smooth muscle that shields the organism from risk factors associated with vascular diseases.

Closed incision negative pressure therapy: Results of recent trials and recommendations for clinical practice.

BACKGROUND: Open abdominal surgery is associated with high rates of wound complications . Surgical site infection (SSI) is associated with prolonged length of stay, delayed treatment and high rates of readmission (1, 3, 4). Negative pressure wound therapy over closed incisions (ciNPWT) is a novel approach to prevention of SSI. We reviewed the outcomes of studies comparing ciNPWT and standard therapy in open abdominal wounds to assess the efficacy of the current evidence base. AIM: To assess the effect of negative pressure wound therapy used over closed incisions in open abdominal surgery. METHODS: Search of relevant terms was conducted on PubMed, Scopus and Cochrane to identify studies published between Jan 2006-Feb 2019. Studies were chosen based on specific inclusion criteria. Articles were screened to assess demographics, study design and outcomes. RESULTS: Seven retrospective and six prospective randomised controlled trials were identified for inclusion, totalling 3048 participants. 967 received ciNPWT and 2081 received standard treatment. Studies assessed a mix of surgeries (colorectal n = 6, pancreaticoduodenectomy n = 1, gynaecologic n = 1, acute care surgery n = 1, mixed open n = 2). ciNPWT was statistically significant in reducing SSI in 9 of 13 studies. CONCLUSION: ciNPWT in open abdominal surgery has demonstrated promising results for reducing SSI rate in some trials however, patient selection remains unclear. Recent randomized controlled trials have failed to demonstrate benefit overall with use of ciNPWT in open abdominal surgery. Further multicentre prospective trials are needed for cost-benefit analysis and appropriate patient-selection.

Ventricular substrate identification using close-coupled paced electrogram feature analysis.

AIMS: Substrate based catheter ablation strategies are widely employed for treatment of scar-related ventricular tachycardia (VT). We analysed intracardiac electrograms (EGMs) from close-coupled paced extrastimuli extracted from the EnSite Precision mapping system. We sought to characterize EGM responses of ventricular myocardium to varying coupling intervals from the right ventricular apex (RVA) in both healthy individuals and patients presenting with VT for catheter ablation. METHODS AND RESULTS: Extrastimuli were delivered from the RVA after estimation of the ventricular effective refractory period. Electrograms were recorded from high-density mapping catheters in the left ventricle and exported for analysis to MATLAB. Observational data were collected from 14 patients with ischaemic VT (mean age 72.4 ± 6.3 years, one female) and five controls (mean age 59.4 ± 7.4 years, one female). These derived data were used to inform an interventional strategy on a further 10 patients (mean age 64.7 ± 10.0 years; two female). Significant differences were observed in EGM duration (ED) and latency (LT) at all coupling intervals between VT patients and controls. Significant increases in ED and LT with decreased RVA coupling interval were observed at VT isthmuses. Abnormal responses derived from control subject data were used to classify four types of ventricular EGM response. Targeting sites with abnormal LT and ED significantly reduced VT inducibility (5/14 derivation patients to 0/10 intervention patients; P = 0.03). CONCLUSION: Paced electrogram feature analysis is a novel tool to characterize the ischaemic substrate. Association with VT isthmuses and early ablation results suggest a possible role in substrate ablation for ischaemic VT.

Contact-Force Guided Pulmonary Vein Isolation does not Improve Success Rate in Persistent Atrial Fibrillation Patients and Severe Left Atrial Enlargement: A 12-month Follow-Up Study.

BACKGROUND: Catheter ablation is a cornerstone treatment strategy in atrial fibrillation (AF). Left atrial (LA) size is one of the contributors in development of AF recurrences. The impact of contact-forced (CF) guided catheter ablation on the success rate of persistent AF patients with severe enlarged LA has not been investigated yet. METHODS: Sixty-six patients with diagnosis of longstanding persistent AF undergoing catheter ablation were enrolled. All patients underwent a standard transthoracic echocardiography according to the guidelines. LA size was considered severely enlarged when LA diameter was ≥ 50 mm. CF catheter ablation with a Tacticath Quartz catheter (St Jude Medical, St. Paul, MN, USA) was used in all patients. RESULTS: The mean age was 61.9 ± 9.9 years, and LAD 47.8 ± 11.6 mm. Among 66 patients with persistent AF, 32 (48%) patients were diagnosed with AF recurrences. Twenty-eight (42%) patients had severely enlarged LA. The recurrence of AF was comparable in patients with and without severe enlarged LA (47% vs. 42%, p=0.79). The recurrence of AF was lower in patients who underwent CF-guided ablation with a normal LA dimension (36 %, p=0.54). Procedure duration was longer in patients with severely enlarged LA. LA dimension was not significantly different between patients with and without AF recurrence (49.8 ± 7.9 mm vs. 45.9 ± 7.5 mm, p=0.15). LAD and was significantly correlated with the time to recurrence of AF (r:-0.60, p=0.02). CONCLUSION: Our preliminary findings have demonstrated that CF guided ablation does not improve the success rate in longstanding persistent AF patients with severe LA enlargement.

Coronary Sinus Electrograms May Predict New-onset Atrial Fibrillation After Typical Atrial Flutter Radiofrequency Ablation (CSE-AF).

BACKGROUND: Complex fractionated electrograms (EGMs) of the coronary sinus electrograms (CSEs) are employed as a target during radiofrequency ablations (RFA) of atrial fibrillation (AF). Anatomically, CSEs includes both of left atrium (LA), coronary sinus musculature and right atrium (RA) electrograms. AIM: To determine the significance of fractionated CSE and delayed potentials as a predictor of new-onset AF after radiofrequency ablation (RFA) of isolated atrial flutter (AFL). METHODS: Consecutive patients underwent AFL ablation. Fractionated and/or continuous discrete activities were recorded from coronary sinus electrograms during sinus rhythm and during pacing. Earliest CSE to the S nadir or peak R in milliseconds was recorded and considered as propagation delay for EGMs. RESULTS: Forty patients were included during a mean follow-up period of 55.1± 15.8 months. Twenty patients (50 %) developed AF while the remaining 20 patients maintained sinus rhythm(SR) during the follow-up period. Proximal and mid CSEs were significantly fractionated in AF group compared to group with no AF development (65 % and 60% Vs. 35 % and 30 %, p = 0.03, respectively). However, during pacing from distal duo-decapolar catheter (pole 1-2), distal CSEs alone were significantly fractionated (p < 0.05) compared to SR group. Significant delayed propagation of proximal CSE during pacing and in sinus rhythm were observed in AF group (12.3 ± 9.2 ms vs 7.1 ± 3.6 ms, p = 0.03) and (7.2 ± 2.9 ms Vs 8.1 ± 4.6 ms, p= 0.02) in the same order. CONCLUSION: Incidence of AF is associated with fractionated proximal and mid CSE in sinus rhythm and distal CSE during paced rhythm after isolated AFL ablation. Delayed proximal CSE propagation is correlated with AF incidence.

Gold-tip versus contact-sensing catheter for cavotricuspid isthmus ablation: A comparative study.

OBJECTIVE: Radiofrequency (RF) ablation is a highly successful procedure for the management of typical atrial flutter (AFL), an abnormal heart rhythm originating within the atria. There is no strong evidence that the use of contact force (CF) has any impact on procedural duration or acute success in the management of cavotricuspid isthmus (CTI)-dependent AFL. The aim of this study was to compare acute procedural parameters using a non-CF, 4-mm, gold-tip, irrigated catheter and a CF-sensing catheter in patients with AFL. METHODS: This was a retrospective cohort study. Consecutive patients who underwent typical AFL catheter ablation with either a gold-tip or CF-sensing catheter were enrolled. The procedural parameters obtained were: time to achieve bidirectional block, time to terminate AFL, total duration of RF application, procedure duration, fluoroscopy time, acute reconnection within 20 minutes following the last RF application, and procedural complications. RESULTS: Of the 40 patients screened, 37 were included in the study. The procedural endpoint of bidirectional isthmus block was achieved in all patients. The use of gold-tip catheters was associated with a shorter length of time to achieve bidirectional block (median time: 20.0 minutes [interquartile range {IQR}: 12.0-28.0 minutes]) compared with a median time of 36.0 minutes (IQR: 12.0-53.0 minutes; p=0.048) in the CF group. Furthermore, there was a trend toward reduced procedural duration in favor of the gold-tip catheter (median goldtip: 74.0 minutes [IQR: 57.0-84.0 minutes]; median CF: 85.0 minutes [IQR: 57.0-107.0 minutes]; p=0.171). A greater requirement for the use of long sheaths was observed in cases where the CF catheter was employed for the procedure (CF: 11, 57.9 %; non-CF: 1, 5.6%; p=0.005). CONCLUSION: The time required to achieve bidirectional block, which is also reflected in the procedural time, was less when using a gold-tip catheter, and there was less need for the use of a long sheath. Further studies may be useful to evaluate this finding.

Use of Intraprocedural Ibutilide During Stepwise Ablation of Long-Standing Persistent Atrial Fibrillation.

PURPOSE: Catheter ablation is an effective therapy for symptomatic atrial fibrillation (AF). The aim of this study was to assess the effect of ibutilide administration in patients with long standing persistent AF undergoing catheter ablation. METHODS: We included 25 patients undergoing stepwise catheter ablation with ibutilide 1.0 mg infused prior to mapping and ablation as first step. Procedural and long-term outcomes were compared to a matched cohort of 25 patients in which ibutilide was not used but all other steps remained the same. RESULTS: Mean age of the cohort was 65.6±8.2 years, and duration of persistent AF 71.7±96.8 months. Termination to sinus rhythm (SR) directly or through an atrial tachycardia (AT) was achieved in 88% of patients administered ibutilide (32% SR/68% AT) vs. 64% in the control group. Ibutilide was associated with increased AF mean cycle-length (mCL) (208.3±31.6 vs. 156.0±23.7 ms; p<0.001) and decreased CFE mean surface area (29.2±20.2% vs. 47.3±13.7%; p=0.002). Procedure and radiofrequency (RF) times were less in the ibutilide group (288.8±49.6 vs. 335.3±47.4 min and 66.0±16.0 vs. 78.0±18.2 min; p=0.002 and 0.029 respectively). The 1-year recurrence was 44% in the ibutilide group and 60% in the control groups (p=0.29). Ibutilide patients had significantly reduced ShEn (6.1±0.14 vs. 7.09±0.14; p<0.001) and ShEn was higher in patients that recurred (6.47±0.24 vs. 5.73±0.15; p<0.001). CONCLUSION: In long-standing persistent AF the use of ibutilide in the context of a stepwise ablation results in increased AF mCL, reduction of fractionation and ShEn and higher rates of AF termination, more often through an intermediate AT. Procedure and RF times are also decreased, without compromising long-term outcomes.

Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial.

Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.

Coring Recanalization of a Chronically Occluded Left Subclavian Vein.

A coring technique is an effective strategy to overcome short linear segmental chronic occlusions in subclavian veins caused by previously implanted leads. We present the case of an 82-year-old male who was transferred from a primary care center for consideration for implantable cardioverter-defibrillator placement following an episode of sustained monomorphic ventricular tachycardia and hemodynamic compromise that required direct-current cardioversion. A coring technique was successfully used in this patient.

Relative timing of near-field and far-field electrograms can determine the tachyarrhythmia site of origin.

BACKGROUND: Despite improving algorithms, inappropriate shocks for supraventricular tachycardia (SVT) still occur in a significant number of patients with implantable cardioverter-defibrillators (ICDs). This makes the discovery of novel discriminators that use existing ICD hardware an attractive proposition. OBJECTIVE: We hypothesized that the delay of activation onset from the device-detected, far-field electrogram (EGM) to the near-field, bipole EGM would allow the differentiation of ventricular tachycardias (VTs) from SVTs. METHODS: Proof of principle was demonstrated by rapid pacing in the right atrium, right ventricle, and left ventricle in healthy patients undergoing atrial fibrillation ablation procedures (n = 17). Using real-life ICD recordings, the equivalent measurements were made in a derivation cohort (n = 26) and cutoff predictive values obtained. Finally, the selected values were validated in a separate group of recordings (n = 82). RESULTS: In healthy patients, significant differences in the far-field to near-field EGM activation onsets were observed between right atrial (14.7 ± 2.7 ms), right ventricular (36.3 ± 8 ms), and left ventricular (57.8 ± 10.3 ms; P < .001) pacing. In the derivation ICD cohort, the median far-field to near-field onset delay was significantly shorter in SVT (24.5 ms; interquartile range, 15.3-47.5 ms) than in VT (118.5 ms; interquartile range, 102.5-131.5 ms) (P < .001). Using a cutoff of 100 ms in the validation cohort, SVT was successfully discriminated from VT with a sensitivity and specificity of 88% and a negative predictive value of 94.2%. CONCLUSION: The delay between far-field and near-field EGMs offers a potential new discrimination tool to reduce inappropriate ICD therapies and aid interpretation of single-lead device tracings.

Effectiveness of immature Mangifera indica Linn (mango) fruit in reducing the Ascaris lumbricoides infection among children: a non-inferiority randomized controlled trial / The Health Sciences Journal

INTRODUCTION@#This study aimed to compare the effectiveness of immature Magnifera indica L. (mango) fruit with albendazole in reducing Ascaris lumbricoides infection among children.@*METHODS@#Children aged 2 to 14 years were enrolled in a randomized, controlled, non-inferiority trial. Participants were randomly allocated to receive 250 mL immature mango fruit puree daily for 3 days or one dose of albendazole 400 mg tablet. Egg reduction rates and cure rates were computed and compared. Adverse effects were monitored during and after administration of treatment.@*RESULTS@#There was a statistically significant decrease between the pre- and post-treatment EPG of those who took immature mango fruit (p < 0.001) and those who took albendazole (p < 0.001). There was a higher ERR and CR for the albendazole group, but the difference was not significant (p = 0.472, p = 785, respectively). Risk analysis of reduction in intensity showed mango is non-inferior to albendazole (RR = 0.80, 95% CI 0.67, 0.97; p = 0.026). Risk analysis of cure showed mango is noninferior to albendazole in both PP (RR = 0.92, 95% CI 0.68, 1.25; p = 0.607) and ITT (RR=0.79, 95% CI 0.58, 1.08; p = 0.139).@*CONCLUSION@#Immature Mangifera indica Linn is non-inferior to albendazole in terms of effectiveness in the reduction of ascariasis infection.