title: Exercise-Induced Brain Excitability Changes in Progressive Multiple Sclerosis: A Pilot Study.

text: BACKGROUND AND PURPOSE Even a single bout of aerobic exercise (AE) enhances corticospinal excitability (CSE), a biomarker of neuroplasticity. Because neurodegeneration limits capacity for neuroplasticity, it is not clear whether AE would induce CSE changes in people with progressive multiple sclerosis (MS). METHODS People with progressive MS (n = 10) requiring ambulatory assistive devices completed a graded maximal exercise test. Dual-energy x-ray absorptiometry was used to quantify body fat and lean mass. Before and following one 40-minute AE session using body weight-supported (<10% support) treadmill at moderate intensity, CSE was measured using transcranial magnetic stimulation. Variables included resting and active motor thresholds, motor evoked potential (MEP) amplitudes, recruitment curves, and length of the cortical silent period (CSP). RESULTS Aerobic exercise reduced inhibition (shorter CSP) and increased excitation (increased MEP amplitude) only in the hemisphere corresponding to the stronger hand. Controlling for age, higher fitness and lower body fat significantly predicted exercise-induced reduction in resting motor threshold (ΔR = +0.458, P = 0.046) and CSP (ΔR = +0.568, P = 0.030), respectively. DISCUSSION AND CONCLUSIONS Despite high levels of disability, capacity for exercise-induced neuroplasticity was retained among people with progressive MS. The hemisphere contralateral to the weaker hand was resistant to exercise-induced CSE changes, suggesting less neuroplastic potential. Lower fitness and higher body fat were associated with diminished exercise-induced CSE benefits, suggesting that therapists should consider interventions aimed at improving fitness and combating sedentarism to ultimately enhance the benefits of exercise on the brain.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A302).


title: S3 guidelines for intensive care in cardiac surgery patients: hemodynamic monitoring and cardiocirculary system.

text: Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie, DGTHG) and the German Society for Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin, DGAI) made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess the available monitoring methods with regard to indication, procedures, predication, limits, contraindications and risks for use. The differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilatators, inodilatators and calcium sensitizers and the use of intra-aortic balloon pumps will also be addressed. The guideline has been developed following the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).


title: D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial.

text: BACKGROUND D-dimer concentrations have not been evaluated extensively as a predictor of increased venous thromboembolism (VTE) risk in acutely ill, hospitalized medical patients. OBJECTIVES To analyze the relationships between D-dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649). PATIENTS/METHODS This was a multicenter, randomized, controlled trial. Patients aged ≥ 40 years, hospitalized for acute medical illnesses with risk factors for VTE received subcutaneous enoxaparin 40 mg once daily for 10 ± 4 days then placebo up to day 35, or oral rivaroxaban 10 mg once daily for 35 ± 4 days. Patients (n = 7581) were grouped by baseline D-dimer ≤ 2 × or > 2 × the upper limit of normal. VTE and major plus non-major clinically relevant bleeding were recorded at day 10, day 35, and between days 11 and 35. RESULTS The frequency of VTE was 3.5-fold greater in patients with high D-dimer concentrations. Multivariate analysis showed that D-dimer was an independent predictor of the risk of VTE (odds ratio 2.29 [95% confidence interval 1.75-2.98]), and had a similar association to established risk factors for VTE, for example cancer and advanced age. In the high D-dimer group, rivaroxaban was non-inferior to enoxaparin at day 10 and, unlike the low D-dimer group, superior to placebo at day 35 (P < 0.001) and days 11-35 (P < 0.001). In both groups, bleeding outcomes favored enoxaparin/placebo. CONCLUSIONS Elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high risk of VTE for whom extended anticoagulant prophylaxis may provide greater benefit than for those with low D-dimer concentrations.


To something, Covid is good: SFV 2.0.


title: Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies.

text: Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [(11)C]GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided >99% receptor occupancy for ≥24 h. Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D)≥22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1:1:1). Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study 733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31) p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD.


Survey of mechanical ventilators in US acute care hospitals: a baseline for critical care surge capacity planning.


title: Heat stress effects on bovine sperm cells: a chronological approach to early findings.

text: Testicular heat stress affects sperm quality and fertility. However, the chronology of these effects is not yet fully understood. This study aimed to establish the early sequential effects of heat stress in bull sperm quality. Semen and blood samples of Nellore breed bulls were collected and distributed into control and testicular heat stress (scrotal bags/96 h) groups. Semen samples were evaluated for sperm motility, abnormalities, plasma membrane integrity, acrosomal membrane integrity, mitochondrial membrane potential, sperm lipid peroxidation, seminal plasma lipid peroxidation, and DNA fragmentation. Blood plasma was also evaluated for lipid peroxidation. An increase in sperm abnormalities was observed 7 days following heat stress. After 14 days, sperm lipid peroxidation increased and mitochondrial membrane function, sperm motility, and plasma membrane integrity decreased. Heat stress effects were still observed after 21 days following heat stress. An increase in sperm DNA fragmentation was observed as a late effect after 28 days. Thus, the initial effects of heat stress (i.e., increasing sperm abnormalities and lipid peroxidation) suggest the presence of oxidative stress in the semen that alters mitochondrial function, sperm motility, plasma membrane integrity, and belatedly, DNA fragmentation. Although sperm abnormalities persisted and increased over time, sperm lipid peroxidation, in turn, increased only until 21 days after heat stress. In this regard, these findings provide a greater understanding of the chronological effects of experimentally induced heat stress on bovine sperm, providing valuable insights about spermatogenesis during the first 28 days following heat stress.


title: Effect of palm-based tocotrienols and tocopherol mixture supplementation on platelet aggregation in subjects with metabolic syndrome: a randomised controlled trial.

text: Tocotrienols, the unsaturated form of vitamin E, were reported to modulate platelet aggregation and thrombotic mechanisms in pre-clinical studies. Using a Food and Drug Administration (FDA)-approved cartridge-based measurement system, a randomised, double-blind, crossover and placebo-controlled trial involving 32 metabolic syndrome adults was conducted to investigate the effect of palm-based tocotrienols and tocopherol (PTT) mixture supplementation on platelet aggregation reactivity. The participants were supplemented with 200 mg (69% tocotrienols and 31% α-tocopherol) twice daily of PTT mixture or placebo capsules for 14 days in a random order. After 14 days, each intervention was accompanied by a postprandial study, in which participants consumed 200 mg PTT mixture or placebo capsule after a meal. Blood samples were collected on day 0, day 14 and during postprandial for the measurement of platelet aggregation reactivity. Subjects went through a 15-day washout period before commencement of subsequent intervention. Fasting platelet aggregation reactivity stimulated with adenosine diphosphate (ADP) did not show substantial changes after supplementation with PTT mixture compared to placebo (p = 0.393). Concomitantly, changes in postprandial platelet aggregation reactivity remained similar between PTT mixture and placebo interventions (p = 0.408). The results of this study highlight the lack of inhibitory effect on platelet aggregation after short-term supplementation of PTT mixture in participants with metabolic syndrome.


title: Planning for Reactivation of Ambulatory Care Settings Post-COVID-19 Pandemic Restrictions.

text: In response to COVID-19 pandemic social distancing restrictions, ambulatory care settings have largely transitioned to virtual health care delivery. As local, state, and federal officials discuss timelines for these restrictions to be lifted, ambulatory leadership is tasked with the responsibility of developing reactivation plans for its clinics to resume in-person care. This article discusses a method in which ambulatory leadership can determine the clinic's deficit in patient encounters, set a time period to return to normal operations, planning for space and scheduling changes, balancing in-person virtual visits, and thoughtfully communicating these plans to clinic staff and providers.


title: Laparoscopic versus single-incision cholecystectomy.

text: BACKGROUND Although recent reports demonstrate large series of single-incision cholecystectomies, few articles compare single-incision data with traditional laparoscopic cholecystectomy (LC) data. This article compares a large series of single-incision cholecystectomies to a series of traditional LCs performed at an urban tertiary-care center. METHODS A consecutive series of single-incision cholecystectomies was performed from August 2008 to March 2010. All cholecystectomies were attempted through a single incision on an intent-to-treat basis. Patient demographics, including height, weight, body mass index (BMI), pathologic diagnosis, ASA classification, operative time, complications, narcotic use, and length of stay (LOS), were recorded. Data for a matched cohort of patients undergoing a traditional four-port LC were gathered over a similar time period. Data were compared using a t test with a P<0.05 for significance. RESULTS Single-incision cholecystectomy was successful in 81 (76%) of 107 patients. The 26 (24%) converted cases showed a higher BMI (33.0±8.7 vs. 28.4±6.4 kg/m2, P<0.05) and longer operative times (98.3±33 vs. 76.1±23 min, P<0.003). Postoperatively, the converted patients had a longer LOS compared to that of the single-incision group (1.6±1.0 vs. 1.1±0.4 days, P=0.02). Overall, the single-incision group had longer operative times compared to the four-port LC group (81.5±28 vs. 69.1±21 min, P<0.004). However, after the tenth single-incision case, there was no difference in operative times. From a narcotic standpoint, the successful single-incision patients used significantly less narcotic versus the traditional LC group (20±22.7 vs. 32.3±31.2 mg, P=0.02). CONCLUSIONS The data suggests that individuals with a BMI over 33 may not be candidates for single-incision cholecystectomy. Those patients that undergo a successful single-incision laparoscopic cholecystectomy require fewer narcotics postoperatively and have a shorter LOS. Although this data is intriguing, the overall utility of single-incision procedures requires more analysis and potentially randomized trials.


title: A Comparison of Hemostatic Properties between Monopolar and Bipolar Hysteroscopic Surgery using Rotational Thromboelastometry: A Randomized Trial.

text: OBJECTIVE Systemic absorption of irrigation fluid can lead to a disturbed coagulation cascade. We compared the changes in hemostatic properties on using nonelectrolyte solution in monopolar hysteroscopic surgery (HS) with that on using isotonic saline in bipolar HS via rotational thromboelastometry (ROTEM) analysis. METHODS A total of 54 patients were randomized into 2 groups: 1 group underwent monopolar HS using a mixture of 2.7% sorbitol and 0.54% mannitol (the HSMP group), whereas the other group underwent bipolar HS using 0.9% isotonic saline (the HSBP group). The effects of these 2 methods on coagulation were assessed via pre and postoperative laboratory tests, including estimation of the international normalized ratio of prothrombin time and activated partial thromboplastin time and ROTEM analysis. In addition, the hemoglobin, hematocrit, and electrolyte levels and the platelet count were analyzed. RESULTS Patient characteristics, volume of irrigation fluid absorbed, and type of procedure were comparable between the 2 groups. There were no significant differences in the pre and postoperative values of ROTEM parameters between the 2 groups. Most postoperative ROTEM parameters, as compared with preoperative values, changed in both groups; clot formation time was prolonged, and the α-angle and maximum clot firmness were decreased. All ROTEM parameters were maintained within the normal range. Hematological parameters, including hemoglobin and hematocrit levels and platelet count, were significantly decreased postoperatively in both groups compared to the preoperative values. No pre and postoperative hematological and hemostatic parameters were significantly different between the 2 groups. CONCLUSION Irrigation fluid absorbed in healthy women during HS caused hypocoagulable changes in the blood, irrespective of the irrigant type, and no significant differences between HS using monopolar and bipolar electrodes were demonstrated.


Perioperative treatment with aspirin or clonidine and risk of acute kidney injury.


docid: iobkftnk

title: Swapping drills for dressings: redeployment of dentists to community nursing.

text: The COVID-19 pandemic has placed increased strain on many aspects of the NHS. Dentists have been identified as having skills transferable to support community nursing teams as part of the redeployment response. This article aims to explore the roles dentists have undertaken within the community setting and reflect on dentists' transferable skills, training and personal experiences during redeployment. Despite differences in healthcare delivery, both professions share skills surrounding professionalism, communication, raising concerns and consent. Community nurses have supported dentists through specific training and competencies so that the latter are equipped with skills to support roles including wound care, catheter care and medication administration. Dentists have been well-received by community nursing colleagues and patients during redeployment. This experience has enabled redeployed dentists to establish new skillsets while improving their appreciation for the fundamental role that community nurses play within society.


title: Use of a vessel sealing system versus conventional electrocautery for lung parenchymal resection: a comparison of the clinicopathological outcomes in porcine lungs.

text: PURPOSE LigaSure, a vessel sealing system, has been shown to have excellent hemostatic properties; however, its use for lung parenchymal resection has been limited. We herein examined the hemostatic properties and potential for inducing histological lung injury of the LigaSure system in non-anatomic pulmonary resection to estimate the feasibility of its clinical application. METHODS Non-anatomic pulmonary wedge resections of the right cranial, middle, and caudal lobes were performed in four pigs using the LigaSure system (Group A) or electrocautery (Group B). In each resection, the resection time, blood loss, and weight of the resected lung were measured. The thermal effect on the lung tissue was examined by means of intraoperative thermography and histology. RESULTS A total of 12 lung wedge resections were performed in each group. For an equivalent length of operation and weight of the resected lung parenchyma, Group A showed significantly lower blood loss and lower maximum and minimum temperatures of the lung tissue, as assessed by thermography, than Group B. The degree of thermal injury as estimated by a histological examination was lower in Group A than in Group B. CONCLUSION Our study suggests that the LigaSure system may be superior to conventional electrocautery, indicating its clinical usefulness for non-anatomic pulmonary resection.


title: Pulse oximeter plethysmograph variation and its relationship to the arterial waveform in mechanically ventilated children.

text: The variations induced by mechanical ventilation in the arterial pulse pressure and pulse oximeter plethysmograph waveforms have been shown to correlate closely and be effective in adults as markers of volume responsiveness. The aims of our study were to investigate: (1) the feasibility of recording plethysmograph indices; and (2) the relationship between pulse pressure variation (ΔPP), plethysmograph variation (ΔPOP) and plethysmograph variability index (PVI) in a diverse group of mechanically ventilated children. A prospective, observational study was performed. Mechanically ventilated children less than 11 years of age, with arterial catheters, were enrolled during the course of their clinical care in the operating room or in the pediatric intensive care unit. Real time monitor waveforms and trend data were recorded. ΔPP and ΔPOP were manually calculated and the relationships between ΔPP, ΔPOP and PVI were compared using Bland-Altman analysis and Pearson correlations. Forty-nine children were recruited; four (8%) subjects were excluded due to poor quality of the plethysmograph waveforms. ΔPP and ΔPOP demonstrated a strong correlation (r = 0.8439, P < 0.0001) and close agreement (Bias = 1.44 ± 6.4%). PVI was found to correlate strongly with ΔPP (r = 0.7049, P < 0.0001) and ΔPOP (r = 0.715, P < 0.0001). This study demonstrates the feasibility of obtaining plethysmographic variability indices in children under various physiological stresses. These data show a similarly strong correlation to that described in adults, between the variations induced by mechanical ventilation in arterial pulse pressure and the pulse oximeter plethysmograph.


title: [Risk assessment and early warning of imported COVID-19 in 21 cities, Guangdong province].

text: Objective: To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods: Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results: A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions: Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.


title: Improved outcome with combined US/CT guidance as compared to US guidance in percutaneous radiofrequency ablation of small renal masses.

text: BACKGROUND When performing percutaneous radiofrequency ablation (RFA) of small renal masses (SRM), use of optimized periprocedural image guidance is essential to secure curative outcome of the treatment. PURPOSE To retrospectively compare the short-term radiological and clinical outcomes of RFA under combined ultrasound (US) and computed tomography (CT) guidance with that of a previously performed US-guided series at the same institution. MATERIAL AND METHODS From November 2009 to November 2013, 60 patients (mean age, 70.1 years; range, 34-86 years) with renal masses measuring in the range of 13-50 mm in maximal diameter (mean diameter, 25.4 ± 6.8 mm) underwent percutaneous RFA with combined US/CT guidance. The technical success rate, recurrence-free survival, rate of complications, and the percentage change in the estimated glomerular filtration rate (eGFR) were compared with that of a previously published series of 41 patients with SRM treated with US-guided RFA between November 2002 and December 2008. RESULTS The tumor and patient characteristics were similar between the two treatment groups. The primary and secondary technical success rate was significantly higher in the group treated with combined US/CT guidance compared with the group treated with US guidance alone (100% and 100% vs. 82% and 91%, respectively). The local recurrence-free survival was significantly better in the combined US/CT-guided group than in the US-guided group (P = 0.016). There was no significant difference in the rate of overall complications (13% vs. 17%) or the mean percentage decrease in the eGFR after the respective treatment (1.1 ± 18.3% vs. 5.0 ± 11.7%). CONCLUSION The use of combined US/CT guidance when performing renal RFA resulted in superior primary and short-term outcome compared to the use of US guidance alone in patients treated at the same institution.


Timing of surgery after recovery from COVID-19 infection.


Avian Influenza Virus H5 Strain with North American and Eurasian Lineage Genes in an Antarctic Penguin.


title: Safety and feasibility of sleeve gastrectomy in morbidly obese patients following liver transplantation.

text: BACKGROUND Obesity, steroid-induced diabetes, hypercholesterolemia, and steatohepatitis can occur after liver transplantation and may respond to bariatric surgery. The safety and feasibility of bariatric surgery after liver transplantation is unknown. METHODS Nine morbidly obese patients with prior liver transplants underwent sleeve gastrectomy in a pilot program. Sleeve gastrectomy was chosen over gastric banding to avoid foreign body implantation, and over gastric bypass to maintain endoscopic access to the biliary system and reduce surgical complexity. We reviewed patient demographics, operative details, 30-day complications, weight loss, postoperative hepatic and renal functions, and resolution of comorbidities. RESULTS Sleeve gastrectomy was performed laparoscopically in eight patients and as an open procedure in one patient. The mean operative time was 165 min and mean postoperative length of stay was 5 days. Follow-up ranged from 3 to 36 months. In the first 30 days, there were three complications in three patients: mesh dehiscence after a synchronous incisional hernia repair, bile leak from the liver surface requiring laparoscopic drainage, and postoperative dysphagia that required reoperation. Calcineurin inhibitor levels and hepatic and renal functions remained stable. There were no episodes of graft rejection. At 3 months liver function tests remained stable. Excess weight loss averaged 55.5% at 6 months. CONCLUSION Sleeve gastrectomy is technically feasible after liver transplantation and resulted in weight loss without adversely affecting graft function and immunosuppression. Early complications may be more frequent as a result of adhesions of the left upper quadrant. Late complications were rare.


title: Laparoscopic Distal Pancreatectomy in Benign or Premalignant Pancreatic Lesions: Is It Really More Cost-Effective than Open Approach?

text: BACKGROUND Data regarding the quality of life in patients undergoing laparoscopic distal pancreatectomy are lacking and no studies have reported a real cost-effectiveness analysis of this surgical procedure. The aim of this study was to evaluate and compare the quality of life and the cost-effectiveness of a laparoscopic distal pancreatectomy with respect to an open distal pancreatectomy. METHODS Forty-one patients who underwent a laparoscopic distal pancreatectomy and 40 patients who underwent an open distal pancreatectomy were retrospectively studied as regards postoperative results, quality of life and cost-effectiveness analysis. The Italian neutral version of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30, version 3.0, was used to rate the quality of life. RESULTS Postoperative results were similar in the two groups; the only difference was that the first oral intake took place significantly earlier in the laparoscopic group than in the open group (P < 0.001). Regarding quality of life, the laparoscopic approach was able to ameliorate physical functioning (P = 0.049), role functioning (P = 0.044) and cognitive functioning (P = 0.030) and reduce the sleep disturbance scale (P = 0.050). The cost-effectiveness analysis showed that the acceptability curve for a laparoscopic distal pancreatectomy had a higher probability of being more cost-effective than an open distal pancreatectomy when a willingness to pay above 5400 Euros/quality-adjusted life years (QALY) was accepted. CONCLUSION Despite the limitations of the study, laparoscopic distal pancreatectomy can be considered not only safe and feasible but also permits a better quality of life and is acceptable in terms of cost-effectiveness to Italian and European health care services.


title: Right diaphragm injury: an unusual complication in single-port laparoscopic cholecystectomy.

text: Laparoscopic cholecystectomy (LC) is nowadays the standard method for cholecystectomy. Recently, surgeons attempt to introduce even less-invasive surgical procedures, such as single-port LC or LC through natural orifice transluminal endoscopic surgery (NOTES). The number of studies showing the feasibility of these techniques increased during the last years, but specific complications that correlated with these new techniques are still not apparent. Here, we report on a case with an unusual complication, iatrogenic right diaphragm injury in single-port LC. A 72-year-old man underwent single-port LC because of symptomatic cholecystolithiasis. During the operation, the long rigid straight forceps holding the fundus of the gallbladder slipped off toward the right diaphragm and caused a 1-cm full-thickness diaphragmatic tear. Laparoscopic suture repair was performed, and the patient recovered uneventfully. In using long forceps in single-port LC or transvaginal NOTES-LC, reticulating and bent instruments may avoid this unusual but possible complication in these operations.


title: Depressive Symptoms and Vegetarian Diets: Results from the Constances Cohort.

text: The association between depressive symptoms and vegetarian diets is controversial. This study examines the cross-sectional association between depressive symptoms and vegetarian diets while controlling for potential confounders. Among 90,380 subjects from the population-based Constances cohort, depressive symptoms were defined by a score ≥19 on the Centre of Epidemiologic Studies-Depression (CES-D) scale and diet types (omnivorous, pesco-vegetarian, lacto-ovo-vegetarian and vegan) were determined with a food frequency questionnaire. Associations between depressive symptoms and diet were estimated through logistic regressions adjusting for socio-demographics, other foods, alcohol and tobacco consumption, physical activity and health-related concerns; specificity analyses considered the exclusion of any other food group. Depressive symptoms were associated with pesco-vegetarian and lacto-ovo-vegetarian diets in multivariable analyses (Odds-Ratio [95% confidence interval]: 1.43 [1.19⁻1.72] and 1.36 [1.09⁻1.70], respectively), especially in case of low legumes intake (p for interaction < 0.0001), as well as with the exclusion of any food group (e.g., 1.37 [1.24⁻1.52], 1.40 [1.31⁻1.50], 1.71 [1.49⁻1.97] for meat, fish and vegetables exclusion, respectively). Regardless of food type, the Odds-Ratio of depressive symptoms gradually increased with the number of excluded food groups (p for trend < 0.0001). Depressive symptoms are associated with the exclusion of any food group from the diet, including but not restricted to animal products.


title: A histidine-rich linker region in peptidylglycine α-amidating monooxygenase has the properties of a pH sensor.

text: Decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. The two catalytic domains of peptidylglycine α-amidating monooxygenase (PAM), a type I integral membrane protein, catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. We explored the hypothesis that a conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and affects PAM trafficking by mutating these His residues to Ala (Ala-Gly-Ala-Ala; H3A). Purified recombinant wild-type and H3A linker peptides were examined using circular dichroism and tryptophan fluorescence; mutation of the His cluster largely eliminated its pH sensitivity. An enzymatically active PAM protein with the same mutations (PAM-1/H3A) was expressed in HEK293 cells and AtT-20 corticotrope tumor cells. Metabolic labeling followed by immunoprecipitation revealed more rapid loss of newly synthesized PAM-1/H3A than PAM-1; although release of newly synthesized monofunctional PHM/H3A was increased, release of soluble bifunctional PAM/H3A, a product of the endocytic pathway, was decreased. Surface biotinylation revealed rapid loss of PAM-1/H3A, with no detectable return of the mutant protein to secretory granules. Consistent with its altered endocytic trafficking, little PAM-1/H3A was subjected to regulated intramembrane proteolysis followed by release of a small nuclear-targeted cytosolic fragment. AtT-20 cells expressing PAM-1/H3A adopted the morphology of wild-type AtT-20 cells; secretory products no longer accumulated in the trans-Golgi network and secretory granule exocytosis was more responsive to secretagogue.


title: COVID-19 Recommendations From Ophthalmic and Plastic Reconstructive Surgery Societies Worldwide.

text: PURPOSE The COVID-19 pandemic has brought unprecedented challenges for oculoplastic surgeons worldwide, in terms of care delivery, medical equipment and at-risk patient management. To date, there are no centralized or compiled international COVID-19 guidelines for oculoplastic surgeons. METHODS We examined COVID-19 guidelines published by oculoplastic societies worldwide. All countries around the world were initially considered in this study, but only 9 oculoplastic societies met the inclusion criteria: (1) publicly available guidelines displayed on the oculoplastic society's website, or (2) guidelines received from the oculoplastic society after contacting them twice using the contact information on their website. RESULTS The 9 oculoplastic societies examined include: the American Society of Ophthalmic Plastic and Reconstructive Surgery, the British Oculoplastic Surgery Society, the Canadian Society of Oculoplastic Surgery, the European Society of Ophthalmic Plastic and Reconstructive Surgery, la Sociedad Española de Cirugía Plástica Ocular y Orbitaria, la Asociación Colombiana de Cirugía Plastica Ocular, the Asia Pacific Society of Ophthalmic Plastic & Reconstructive Surgery, the Oculoplastics Association of India, and the Philippine Society of Ophthalmic Plastic and Reconstructive Surgery. They all agree that urgent procedures should not be delayed, while non-necessary procedures (including all elective clinic services) should be postponed. When adequate protective equipment is available, oculoplastic surgeons must treat urgent cases. Eight out of 9 societies have provided recommendations on personal protective equipment use in order to prevent the spread of COVID-19 and to adequately protect mucous membranes. Other recommendations provided by certain societies are related to shelter in place measures, hand hygiene and surface disinfection protocols, patient triage, and thyroid eye disease management. CONCLUSIONS All 9 societies with published recommendations have provided valuable recommendations to their members, regarding urgency of care and infection control solutions (personal protective equipment, hand hygiene, telemedicine, and social isolation).


title: Dendritic cell-based vaccine research against cancer.

text: Therapeutic vaccines that treat cancers with the help of the patient's own immune system signify a feasible option for active immunotherapy against the disease. Dendritic cells (DCs) play a central role in modulating the immune response and thus can be wisely utilized as an immunotherapeutic strategy for cancer regimens. Advances in the knowledge of DC biology and function have led to the development of DC-based vaccines for cancer therapy. In the present review, we discuss the biology and function of DCs, their subsets and receptors, antigen loading and route of administration of DC vaccines, as well as active and passive targeting strategies for treating the cancer. We also discuss the preclinical and clinical status of these newly developed vaccines. Special attention should be given by the scientific community to the challenges that need to be solved for the successful implication of these vaccines in cancer therapy.


docid: btlitzih

title: Amino acid losses are lower during pre-dilution on-line HDF than HD of the same Kt/V for urea.

text: In this study, we investigated differences in amino acid losses between HD and pre-dilution on-line HDF with equal Kt/V for urea to determine which modality removes less amino acids from extravascular pools and ensures better nutrition. The subjects were patients receiving pre-dilution on-line HDF (n = 10) or HD (n = 10) at this hospital. Dialysis time was 4 h for all patients. In patients on HD, the blood flow rate was 200 mL/min and the dialysate flow rate was 463 ± 29.3 mL/min. In patients on pre-dilution on-line HDF, the blood flow rate was 240 ± 20 mL/min, the dialysate flow rate was 565.0 ± 42.5 mL/min, and the substitution flow rate (substitution volume) was 252.8 ± 26.4 mL/min (57.0 ± 6.0 L). Kt/V for urea was comparable between patients on HD and patients on pre-dilution on-line HDF (1.46 ± 0.25 vs. 1.46 ± 0.31). Amino acid loss and clear space were evaluated. Patients on pre-dilution on-line HDF lost significantly less glutamine and arginine (p < 0.01 and p = 0.032) and significantly less nonessential amino acids (NEAAs) than patients on HD (p = 0.013). They also had significantly lower clear space of total amino acids (TAAs), NEAAs, essential amino acids (EAAs), and branched-chain amino acids (BCAAs) than patients on HD (Total AA p = 0.019, NEAA p = 0.018, EAA p = 0.024, BCAA p = 0.042). When Kt/V for urea is equal, pre-dilution on-line HDF ensures better nutrition than does HD.


title: Efficacy and safety of tanezumab in the treatment of pain from bone metastases.

text: Patients with metastatic bone cancer report life-altering pain. Nerve growth factor is involved in pain signaling. Tanezumab, a nerve growth factor monoclonal antibody, has demonstrated efficacy in chronic pain. Placebo-controlled parent (NCT00545129; study 1003) and noncontrolled open-label extension (NCT00830180; study 1029) studies evaluated efficacy and safety of tanezumab in patients with painful bone metastases taking daily opioids. Patients in study 1003 received a single intravenous injection of 10 mg tanezumab or placebo and were followed up to 16 weeks. Efficacy analyses included change from baseline in daily average and worst pain at week 6 on an 11-point numeric rating scale. At week 8, patients could enroll in study 1029 and receive 4 infusions of 10 mg tanezumab at 8-week intervals with follow-up to 40 weeks. Safety assessments included adverse events and physical and neurologic examinations. Overall, 59 patients were randomized and treated (placebo, n = 30; tanezumab, n = 29). At the primary endpoint of study 1003, least squares mean (SE) difference in change from baseline in daily average pain vs placebo was -0.26 (0.45; P = 0.569). Post hoc analyses suggested that tanezumab had greater efficacy in patients with lower baseline opioid use and/or higher baseline pain. Mean (SE) pain scores in study 1029 were reduced through week 40 compared with study 1029 or 1003 baselines (-0.21 [0.76] and -1.27 [0.68], respectively). Adverse event incidence of study 1003 was similar between groups. Although the primary endpoint was not achieved, tanezumab may provide additional sustained analgesia in patients with metastatic bone pain taking daily opioids. Additional larger studies are warranted.


title: The treatment of chronic pleural empyema with laparoscopic omentoplasty. Initial report.

text: INTRODUCTION Pleural empyema is the most serious, life-threatening postoperative complication of pneumonectomy, observed after 1-12% of all pneumonectomies, with bronchopleural fistula being its main cause. AIM The aim of this publication is to present early outcomes of minimally invasive surgical management of pleural empyema. Patients were subjected to a single, complex procedure, consisting of the laparoscopic mobilization of the greater omentum and its transposition via the diaphragm into the pleural cavity to fill in the empyema cavity with the consecutive pleuro-cutaneous fistuloplasty (thoracoplasty). MATERIAL AND METHODS Between May 2011 and April 2013, 8 patients were qualified to undergo the procedure. The mean age was 61 years (range: 46-77 years). Presence of bronchopleural fistula was confirmed in 3 cases. The median time of treatment with thoracostomy was 14.5 months. RESULTS The mean operative time was 125 min. The mean duration of post-operative hospital stay was 13.5 days (range: 7-31 days). In 6 patients (75%) the objective of permanent resolution of pleural empyema was achieved. In total, 4 patients had complications: pleural empyema recurrence (2 patients), splenic injury, hiatal hernia, gastrointestinal bleed. Two patients with empyema recurrence had Staphylococcus aureus infections prior to surgery. They were successfully managed both with prolonged thoracic drainage and antibiotics. CONCLUSIONS Use of the greater omentum that was laparoscopically mobilized and transpositioned into the pleural cavity allows simultaneous management of the pleural empyema cavity and thoracostomy. The procedure is safe, with few direct complications. It is well tolerated and has at least a satisfactory cosmetic effect. The minimally invasive approach allows faster recovery and return to daily activities in comparison to the fully open technique.


title: Transmission and prevention of acute viral respiratory tract infections in hospitals.

text: PURPOSE OF REVIEW Transmission of acute respiratory tract viral infections in healthcare environments is a major problem worldwide. We review recent literature of viruses imported to hospitals from the local community and from abroad, their modes of transmission and measures required to reduce and contain them. RECENT FINDINGS Common causes of outbreaks include influenza viruses, respiratory syncytial virus, adenovirus, and coronaviruses. Major lethal outbreaks of viral respiratory infections in hospitals have been caused by coronaviruses imported from abroad by travelers. SUMMARY Although viruses circulating in the local community are common causes of hospital outbreaks, major outbreaks have been caused by the coronaviruses imported from abroad by travelers. A high degree of clinical awareness and rapid enforcement of infection control measures are required to prevent transmission and spread.


Saudi Arabia reveals 113 previously undisclosed cases of Middle Eastern respiratory syndrome.


title: REVASCAT: a randomized trial of revascularization with SOLITAIRE FR device vs. best medical therapy in the treatment of acute stroke due to anterior circulation large vessel occlusion presenting within eight-hours of symptom onset.

text: REVASCAT is a prospective, multicenter, randomized trial seeking to establish whether subjects meeting following main inclusion criteria: age 18-80, baseline National Institutes of Health Stroke Scale ≥6, evidence of intracranial internal carotid artery or proximal (M1 segment) middle cerebral artery occlusion, Alberta Stroke Program Early Computed Tomography score of >7 on non-contrast CT or >6 on diffusion-weighted magnetic resonance imaging , ineligible for or with persistent occlusion after intravenous alteplase and procedure start within 8 hours from symptom onset, have higher rates of favorable outcome when treated with the Solitaire FR embolectomy device compared to standard medical therapy alone The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days. Projected sample size is 690 patients. Estimated common odds ratio is 1●615. Randomization is performed under a minimization process using age, baseline NIHSS, therapeutic window, occlusion location and investigational center. The study follows a sequential analysis (triangular model) with the first approach to test efficacy at 174 patients and subsequent analyses (if necessary) at 346, 518, and 690 subjects. Secondary end-points are infarct volume evaluated on CT at 24 h, dramatic early favorable response, defined as NIHSS of 0-2 or NIHSS improvement ≥8 points at 24 h and successful recanalization in the Solitaire arm according to the thrombolysis in cerebral infarction (TICI) classification defined as TICI 2b or 3. Safety variables are mortality at 90 days, symptomatic intracranial haemorrhage rates at 24 hours and procedure related complications.


title: Eye care in the intensive care unit during the COVID-19 pandemic.

text: Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.


title: Identifying Prostate Surface Antigen Patterns of Change in Patients with Metastatic Hormone Sensitive Prostate Cancer Treated with Abiraterone and Prednisone.

text: BACKGROUND Despite treatment with abiraterone acetate and prednisone (AA/P), most patients with metastatic hormone sensitive prostate cancer (mHSPC) will develop castration-resistant disease (metastatic castration-resistant prostate cancer [mCRPC]). The early identification of who will progress on AA/P is limited. OBJECTIVE This study investigates the role of prostate surface antigen (PSA) kinetics as a predictor of progression in mHSPC patients treated with AA/P. PATIENTS AND METHODS All patients with mHSPC who initiated androgen deprivation therapy (ADT) and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. PSA-mCRPC was defined as a PSA rise at two consecutive time points. Patients were followed until first mCRPC or last contact after AA/P. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. The association between PSA profile at 3 months and PSA-mCRPC was examined using survival analysis. Radiographic progression (Rad-mCRPC) was also analyzed. RESULTS A total of 130 men with follow-up were included. The median (interquartile range [IQR]) follow-up time was 15.3 (10.5, 22.5) months. Eighty-two percent were Caucasian (median age 68.5 years); participants had a median (IQR) PSA of 16.8 (5.3, 48.0) ng/mL. Half of the patients had de novo disease, and 46.2% had high-risk disease (61% had a Gleason score ≥ 8, 16% had visceral disease, and 54% had three or more bony lesions). The greatest PSA percentage reduction from baseline after AA/P initiation occurred at the first 3 months (median 98.3%). The reduction at 6-12 months from baseline was small (99.7-100%). Patients without PSA-mCRPC had a significantly greater 3-month reduction of PSA values compared to patients who developed PSA-mCRPC (p interaction = 0.0002). 50.8% of patients were able to achieve a non-detectable PSA (median 13.1 months). PSA-mCRPC (n = 20) was observed from 4 to 24 months after AA/P, with the majority of events occurring within the first 12 months. Patients with PSA < 0.3 ng/mL (12-month PSA-mCRPC-free 94.5% vs. 69.4%, p = 0.0004) or a ≥ 98% reduction (94.9% vs. 68.0%, p = 0.0002) at 3 months had better PSA-mCRPC-free survival compared to their counterparts. Absolute reduction at 3 months was not associated with PSA-mCRPC. Similar PSA patterns were seen in those who had Rad-mCRPC compared to no Rad-mCRPC (p interaction < 0.05). CONCLUSION The degree of PSA decline at 3 months predicted serologic progression to mCRPC. Those who developed castration-resistant disease had higher PSA and a lower percentage reduction by 3 months. Tracking early PSA pattern changes may alert clinicians to poor treatment effect and potential progression; they should consider frequent PSA measurement and imaging, as well as the initiation of sequential therapy.


title: [Prevention of the complications related to the use of prosthetic meshes in prolapse surgery: guidelines for clinical practice - literature review].

text: OBJECTIVE To provide guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF), based on the best evidence available, concerning the adverse events related to surgical procedures involving the use of prosthetic meshes. MATERIALS AND METHODS French and English-language articles from Medline, PubMed, and the Cochrane Database were searched, using key words (mesh ; pelvic organ prolapse ; cystocele ; rectocele ; uterine prolapse ; complications ; adverse event ; sacral colpopexy ; extrusion ; infection...). RESULTS As with any surgery, it is recommended to provide a perioperative smoking cessation (expert opinion) and comply with the prevention of nosocomial infections (regulatory requirement). There is no evidence to recommend routine local or systemic estrogen therapy before or after prolapse surgery using mesh, regardless of the surgical approach (grade C). Antibiotic prophylaxis is recommended, regardless of the approach (expert opinion). It is recommended to seek a pre-operative urinary tract infection and treat it (expert opinion). The first cases should be made under the guidance of an experienced surgeon in the relevant technique (grade C). It is recommended not to place a non-absorbable synthetic mesh into the rectovaginal septum when a rectal injury occurs (expert opinion). The placement of a non-absorbable synthetic mesh into the vesicovaginal septum may be considered after the suture of a bladder injury if the suture is considered to be satisfactory (expert opinion). If a synthetic mesh is placed by vaginal route, it is recommended to use a macroporous polypropylene monofilament mesh (grade B). It is recommended not to use polyester mesh for vaginal surgery (grade B). It is allowed to perform a hysterectomy associated with the placement of a non-absorbable synthetic mesh placed by vaginal route but this is not routinely recommended (expert opinion). It is recommended to minimize the extent of the colpectomy (expert opinion). Laparoscopic approach is recommended for sacral colpopexy (grade C). It is recommended not to place and suture meshes by vaginal route when a sacral colpopexy is performed (grade B). It is recommended not to use silicone-coated polyester, porcine dermis, fascia lata, and polytétrafluoroéthylène meshes (grade B). It is recommended to use polyester (without silicone coating) or polypropylene meshes (grade C). Suture of the meshes to the promontory can be performed using thread/needle or tacker (grade C). A peritonization is recommended to cover the meshes (grade C). If hysterectomy is required, it is recommended to perform a subtotal hysterectomy (grade C). CONCLUSION Implementation of this guideline should decrease the prevalence of complications related to surgical procedures involving the use of prosthetic meshes.


title: Early report of a randomized comparative clinical trial of Strattice™ reconstructive tissue matrix to lightweight synthetic mesh in the repair of inguinal hernias.

text: PURPOSE Biologic grafts are rarely used for inguinal herniorrhaphy. The aim of this study was to compare the clinical outcomes between patients undergoing a Lichtenstein's hernioplasty with a porcine mesh versus a standard synthetic. METHODS A prospective, randomized, double-blinded multicenter, evaluation of inguinal hernia repair was conducted between 2008 and 2010. Lichtenstein hernioplasty was performed using Strattice™ or lightweight polypropylene (Ultrapro) mesh. Quality of life, pain, overall complication rate, and recurrence were measured. RESULTS One hundred and seventy-two patients were randomized to Strattice™ (n = 84) or Ultrapro (n = 88). At 3 months postoperatively, there were no differences on the occurrence or type of wound events [RR: 0.98 (95% CI 0.52-1.86, p = 0.69), Strattice™ (15 events) vs. Ultrapro (16 events)]. The mean level of impairment caused by the hernia, assessed by Activities Assessment Scale (AAS), significantly decreased postoperatively in both groups at 3 months (31% Strattice™ and 37% Ultrapro). Patients in the Strattice group reported significantly less postoperative pain during postoperative days 1 through 3 compared to Ultrapro patients. However, the amount of postoperative pain at 3 months, as assessed by the mean worst pain score on a visual analog scale and the Brief Pain Index, was similar between groups (95% CI 1.0-29.3). No hernia recurrences were observed in either group. CONCLUSIONS Strattice™ is safe and effective in repairing inguinal hernia, with comparable intra-operative and early postoperative morbidity to synthetic mesh. Long-term follow-up is necessary in order to know whether the clinical outcomes of Strattice are equivalent to standard synthetic mesh in patients undergoing Lichtenstein's hernioplasty.


Three Hypotheses About Children COVID19.


title: The impact of aptitude on the learning curve for laparoscopic suturing.

text: BACKGROUND Within surgery, several specialties demand advanced technical skills, specifically in the minimally invasive environment. METHODS Two groups of 10 medical students were recruited on the basis of their aptitude (visual-spatial ability, depth perception, and psychomotor ability). All subjects were tested consecutively using the ProMIS III simulator until they reached proficiency performing laparoscopic suturing. Simulator metrics, critical error scores, observed structured assessment of technical skills scores, and Fundamentals of Laparoscopic Surgery scores were recorded. RESULTS Group A (high aptitude) achieved proficiency after a mean of 7 attempts (range, 4-10). In group B (low aptitude), 30% achieved proficiency after a mean of 14 attempts (range, 10-16). In group B, 40% demonstrated improvement but did not attain proficiency, and 30% failed to progress. CONCLUSIONS Distinct learning curves for laparoscopic suturing can be mapped on the basis of fundamental ability. High aptitude is directly related to earlier completion of the learning curve. A proportion of subjects with low aptitude are unable to reach proficiency despite repeated attempts.


title: Global capacity for emerging infectious disease detection.

text: The increasing number of emerging infectious disease events that have spread internationally, such as severe acute respiratory syndrome (SARS) and the 2009 pandemic A/H1N1, highlight the need for improvements in global outbreak surveillance. It is expected that the proliferation of Internet-based reports has resulted in greater communication and improved surveillance and reporting frameworks, especially with the revision of the World Health Organization's (WHO) International Health Regulations (IHR 2005), which went into force in 2007. However, there has been no global quantitative assessment of whether and how outbreak detection and communication processes have actually changed over time. In this study, we analyzed the entire WHO public record of Disease Outbreak News reports from 1996 to 2009 to characterize spatial-temporal trends in the timeliness of outbreak discovery and public communication about the outbreak relative to the estimated outbreak start date. Cox proportional hazards regression analyses show that overall, the timeliness of outbreak discovery improved by 7.3% [hazard ratio (HR) = 1.073, 95% CI (1.038; 1.110)] per year, and public communication improved by 6.2% [HR = 1.062, 95% CI (1.028; 1.096)] per year. However, the degree of improvement varied by geographic region; the only WHO region with statistically significant (α = 0.05) improvement in outbreak discovery was the Western Pacific region [HR = 1.102 per year, 95% CI (1.008; 1.205)], whereas the Eastern Mediterranean [HR = 1.201 per year, 95% CI (1.066; 1.353)] and Western Pacific regions [HR = 1.119 per year, 95% CI (1.025; 1.221)] showed improvement in public communication. These findings provide quantitative historical assessment of timeliness in infectious disease detection and public reporting of outbreaks.


title: Unusual case of Lemierre's syndrome.

text: A young previously healthy patient presented with sepsis and cavitating pneumonia. Campylobacter rectus was isolated from blood cultures and subsequent CT neck showed an internal jugular vein thrombosis. Treatment was with antibiotics, anticoagulation and supportive management. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. Although a rare diagnosis since the use of penicillin for treatment of acute pharyngitis, it is being reported with increasing frequency. Usually associated with Fusobacterium spp, we believe that this is the first reported case of Lemierre's caused by C. rectus-an anaerobic member of the human oral cavity flora, usually associated with localised periodontal disease. The bacillus was isolated from blood during the acute presentation.


title: Colour of sputum is a marker for bacterial colonisation in chronic obstructive pulmonary disease.

text: BACKGROUND Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations. We assessed risk factors for bacterial colonisation in COPD. METHODS Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis. Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of > or =102 colony-forming units (CFU)/mL on quantitative bacterial culture. Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load. RESULTS A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated. Bacterial colonisation was demonstrated in 58 (48.7%) patients. Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour. Thirty-six patients (62% of those colonised) had a high bacterial load. More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture. In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001). Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum. CONCLUSIONS Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs. Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised.


title: Changes in cerebral oxygenation during early postnatal adaptation in newborns delivered by vacuum extraction measured by near-infrared spectroscopy.

text: BACKGROUND Newborns delivered by vacuum extraction quite often show clinical signs of a hemodynamic compromise, which is difficult to assess in terms of severity. The conventional means to measure the hemodynamic status are not sensitive enough to appreciate the severity of general, and more specifically of cerebral circulatory imbalance. The aim was to study cerebral tissue oxygenation during postnatal adaptation in these infants using near-infrared spectroscopy. METHODS The tissue hemoglobin index (THI), tissue oxygenation index (TOI), arterial oxygen saturation (pre-ductal SaO₂) and heart rate (HR) were recorded immediately after birth, and again after 12-24 hours of life in 15 newborns delivered by vacuum extraction due to fetal distress. A comparison with 19 healthy newborns delivered by elective cesarean section was performed. RESULTS Newborns delivered by vacuum extraction had significantly higher THI 10 to 15 minutes after birth. TOI and HR were significantly higher in the first 5 min and SaO₂ in the first 10 minutes but then did not differ from those after cesarean section. CONCLUSION Infants delivered by vacuum extraction following fetal distress show transient deviations in cerebral oxygenation and perfusion after birth which were not detectable after 24 hours.


title: Postoperative Epidural Hematomas in the Lumbar Spine.

text: Postoperative epidural hematomas are rare complications following lumbar spine surgery, but if they are not quickly identified and treated they can lead to permanent neurological deficits. Epidural hematomas occur in approximately 0.10%-0.24% of all spine surgeries, and despite the fact that multiple large studies have been performed attempting to identify risk factors for this complication, there is still significant debate about the effect of subfascial drains, postoperative anticoagulation, and antiplatelet medication on the incidence of postoperative hematoma. The purpose of this manuscript is to review the epidemiology, etiology, diagnosis, and treatment of patients who develop a postoperative lumbar epidural hematoma.


docid: zbzrnlji

title: Controlling COVID-19.


Covid-19's Impact on Podiatry in Chicago's Largest Public Hospital.


How to Discover Antiviral Drugs Quickly.


title: Long-chain rhenium and technetium glucosamine conjugates.

text: A series of five glucosamine-conjugated organometallic complexes of the tricarbonyl cores of technetium-99m and rhenium were made. Glucosamine was derivatized at the C-2 nitrogen with long chain alkyl spacers linked to either pyridyl-tert-nitrogen-phenol tridentate chelates or cyclopentadienyl ligating groups. The metal complexes of the tridentate ligands were formed by refluxing with [Re(CO)(3)(H(2)O)(3)]Br, or with a base and [(99m)Tc(CO)(3)(H(2)O)(3)](+). These ligands were found to be competent chelates in binding the [(99m)Tc(CO)(3)](+) core as radiolabeling yields ranged from 87 to 93% and the resulting complexes are stable to cysteine and histidine challenges for 24 h. The cyclopentadienyl analogues were formed using a double ligand transfer reaction for the rhenium complexes and a single ligand transfer for the technetium-99m complexes. All five rhenium complexes were tested as substrates of hexokinase; two of these complexes were tested as hexokinase inhibitors and they were found to be competent inhibitors, suggesting that they may be able to interact with hexokinase. MTT cytotoxicity studies were performed and the complexes tested were found to be non-toxic to the concentrations tested (100 microM or 1 mM). GLUT-1 mediated cell uptake studies were performed on all five technetium-99m complexes, and their cell entry was found to parallel their lipophilicities, suggesting that cellular uptake is by passive diffusion and is not mediated by GLUT-1.


title: Implementation Strategies to Enhance the Implementation of eHealth Programs for Patients With Chronic Illnesses: Realist Systematic Review.

text: BACKGROUND There is growing evidence of the positive effects of electronic health (eHealth) interventions for patients with chronic illness, but implementation of such interventions into practice is challenging. Implementation strategies that potentially impact implementation outcomes and implementation success have been identified. Which strategies are actually used in the implementation of eHealth interventions for patients with chronic illness and which ones are the most effective is unclear. OBJECTIVE This systematic realist review aimed to summarize evidence from empirical studies regarding (1) which implementation strategies are used when implementing eHealth interventions for patients with chronic illnesses living at home, (2) implementation outcomes, and (3) the relationship between implementation strategies, implementation outcomes, and degree of implementation success. METHODS A systematic literature search was performed in the electronic databases MEDLINE, Embase, PsycINFO, Scopus, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library. Studies were included if they described implementation strategies used to support the integration of eHealth interventions into practice. Implementation strategies were categorized according to 9 categories defined by the Expert Recommendations for Implementing Change project: (1) engage consumers, (2) use evaluative and iterative strategies, (3) change infrastructure, (4) adapt and tailor to the context, (5) develop stakeholder interrelationships, (6) use financial strategies, (7) support clinicians, (8) provide interactive assistance, and (9) train and educate stakeholders. Implementation outcomes were extracted according to the implementation outcome framework by Proctor and colleagues: (1) acceptability, (2) adoption, (3) appropriateness, (4) cost, (5) feasibility, (6) fidelity, (7) penetration, and (8) sustainability. Implementation success was extracted according to the study authors' own evaluation of implementation success in relation to the used implementation strategies. RESULTS The implementation strategies management support and engagement, internal and external facilitation, training, and audit and feedback were directly related to implementation success in several studies. No clear relationship was found between the number of implementation strategies used and implementation success. CONCLUSIONS This is the first review examining implementation strategies, implementation outcomes, and implementation success of studies reporting the implementation of eHealth programs for patients with chronic illnesses living at home. The review indicates that internal and external facilitation, audit and feedback, management support, and training of clinicians are of importance for eHealth implementation. The review also points to the lack of eHealth studies that report implementation strategies in a comprehensive way and highlights the need to design robust studies focusing on implementation strategies in the future. TRIAL REGISTRATION PROSPERO CRD42018085539; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85539.


title: Outcomes after Ross procedure in adult patients: A meta-analysis and microsimulation.

text: OBJECTIVE We conducted a meta-analysis to estimate the risk of adverse events, life expectancy, and event-free life expectancy after the Ross procedure in adults. METHODS We searched databases for reports evaluating the Ross procedure in patients aged more than or equal to 16 years of age. A microsimulation model was used to evaluate age- and gender-specific life expectancy for patients undergoing the Ross procedure. RESULTS Data were pooled from 63 articles totaling 19 155 patients from 20 countries. Perioperative mortality was 2.5% (95% confidence interval [CI]: 1.9-3.1; N = 9978). We found a mortality risk of 5.9% (95% CI: 4.8-7.2) at a mean follow-up of 7.2 years (N = 7573). The rate of perioperative clinically significant bleeding was 1.0% (95% CI: 0.1-3.0); re-exploration for bleeding 4.6% (95% CI: 3.1-6.3); postoperative clinically significant bleeding from 30 days until a mean of 7.1 years was 0.5% (95% CI: 0.2-1.0). At a mean of 6.9 years of follow-up, reintervention rate of any operated valve was 7.9% (95% CI: 5.7-10.3). The risk of valve thrombosis was 0.3% (95% CI: 0.2-0.5) at 7.6 years; peripheral embolism 0.3% (95% CI: 0.2-0.4) at 6.4 years; stroke 0.9% (95% CI: 0.7-1.2) at 6.5 years; and endocarditis 2.1% (95% CI: 1.6-2.6) at 8.0 years. Microsimulation reported a 40-year-old undergoing the Ross procedure to have a life expectancy of 35.4 years and event-free life expectancy of 26.6 years. CONCLUSIONS Ross procedure in nonelderly adults is associated with low mortality and low risk of adverse events both at short- and long-term follow-up. The surgical community must prioritize a large, expertize-based randomized controlled trial to definitively address the risks and benefits of the Ross procedure compared to conventional aortic valve replacement.


title: Chloroquine and COVID-19 - a potential game changer?

text: The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.


title: microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection.

text: Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. Our previous research showed that TGEV infection could induce mitochondrial dysfunction and upregulate miR-222 level. Therefore, we presumed that miR-222 might be implicated in regulating mitochondrial dysfunction induced by TGEV infection. To verify the hypothesis, the effect of miR-222 on mitochondrial dysfunction was tested and we showed that miR-222 attenuated TGEV-induced mitochondrial dysfunction. To investigate the underlying molecular mechanism of miR-222 in TGEV-induced mitochondrial dysfunction, a quantitative proteomic analysis of PK-15 cells that were transfected with miR-222 mimics and infected with TGEV was performed. In total, 4151 proteins were quantified and 100 differentially expressed proteins were obtained (57 upregulated, 43 downregulated), among which thrombospondin-1 (THBS1) and cluster of differentiation 47 (CD47) were downregulated. THBS1 was identified as the target of miR-222. Knockdown of THBS1 and CD47 decreased mitochondrial Ca2+ level and increased mitochondrial membrane potential (MMP) level. Reversely, overexpression of THBS1 and CD47 elevated mitochondrial Ca2+ level and reduced mitochondrial membrane potential (MMP) level. Together, our data establish a significant role of miR-222 in regulating mitochondrial dysfunction in response to TGEV infection.


title: Neurally adjusted ventilatory assist.

text: PURPOSE OF REVIEW Compared with the conventional forms of partial support, neurally adjusted ventilatory assist was repeatedly shown to improve patient-ventilator synchrony and reduce the risk of overassistance, while guaranteeing adequate inspiratory effort and gas exchange. A few animal studies also suggested the potential of neurally adjusted ventilatory assist in averting the risk of ventilator-induced lung injury. Recent work adds new information on the physiological effects of neurally adjusted ventilatory assist. RECENT FINDINGS Compared with pressure support, neurally adjusted ventilatory assist has been shown to improve patient-ventilator interaction and synchrony in patients with the most challenging respiratory system mechanics, such as very low compliance consequent to severe acute respiratory distress syndrome and high resistance and air trapping due to chronic airflow obstruction; enhance redistribution of the ventilation in the dependent lung regions; avert the risk of patient-ventilator asynchrony due to sedation; avoid central apneas; limit the risk of high (injurious) tidal volumes in patients with acute respiratory distress syndrome of varied severity; and improve patient-ventilator interaction and synchrony during noninvasive ventilation, irrespective of the interface utilized. SUMMARY Several studies nowadays prove the physiological benefits of neurally adjusted ventilatory assist, as opposed to the conventional modes of partial support. Whether these advantages translate into improvement of clinical outcomes remains to be determined.


title: Aspergillus PCR-based investigation of fresh tissue and effusion samples in patients with suspected invasive Aspergillosis enhances diagnostic capabilities.

text: Although it is a severe complication in immunocompromised patients, diagnosing invasive fungal disease (IFD), especially invasive aspergillosis (IA), remains difficult. In certain clinical scenarios, examining tissue samples for identification of the infectious organism becomes important. As culture-based methods rarely yield results, the performance of an Aspergillus-specific nested PCR in fresh tissue or pleural effusion samples was evaluated. Fresh tissue (n = 59) and effusion (n = 47) specimens from 79 immunocompromised patients were subjected to an Aspergillus-specific PCR assay. Twenty-six patients had proven (n = 20) or probable (n = 6) IFD, according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, while the remaining patients were classified as having either possible IFD (n = 30) or no IFD (n = 23). IA was identified as the underlying IFD in 21/26 proven/probable cases. PCR positivity was observed for 18/21 proven/probable and 6 possible IA cases; cases classified as no IA did not show positive signals. Patients with proven IFD (n = 5) with cultures positive for non-Aspergillus molds also had negative Aspergillus PCR results. Aspergillus PCR performance analysis yielded sensitivity and specificity values of 86% (95% confidence interval [CI], 65% to 95%) and 100% (95% CI, 86% to 100%), respectively, thus leading to a diagnostic odds ratio of >200. In this analysis, good diagnostic performance of the PCR assay for detection of IA was observed for tissue samples, while effusion samples showed lower sensitivity rates. PCR testing represents a complementary tool; a positive PCR result strengthens the likelihood of IA, whereas IA seems unlikely in cases with negative results but findings could indicate non-Aspergillus IFD. Thus, PCR testing of these specimens enhances the diagnostic capabilities.


title: Using wavelet coherence to characterize surface water infiltration into a low-lying karst aquifer.

text: Karstified carbonate aquifers may receive significant recharge contributions from losing streams, hence, the knowledge about surface water-groundwater (SW-GW) interactions is crucial with regard to water management (e.g. source protection zone delineation). The dynamics of SW-GW interactions may depend on factors such as the relative water levels between streams and aquifers, resulting in a temporal variation of exchange, which imposes complexity to the understanding of such dynamics. This study highlights the use of high-resolution time series and multi-resolution analysis to help to gain insights into such complex dynamics. Wavelet coherence (WTC) is applied on hourly time series of rainfall, stream and spring discharges of a low lying karstified spring catchment to yield a correlation in the time-frequency domain. This analysis provides comprehensive information on the overall impact of the river on the spring, which is supported by the cross-correlation function, as well as by more detailed information, including time-variant influences such as a threshold level of influence. Field observations of turbidity sampling at the spring appear to support this interpretation. This innovative approach relies on basic hydrological parameters, water level or discharge, and is therefore applicable to many other systems with such existing time series. This article is protected by copyright. All rights reserved.


title: Cardiac injury is associated with severe outcome and death in patients with Coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of observational studies.

text: Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide. Cardiac injury has been reported to occur in severe and death cases. This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection. Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study. Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection. Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection. Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.


docid: dztuluje

title: Methods of anorectal manometry vary widely in clinical practice: Results from an international survey.

text: BACKGROUND Ano-rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM between institutions to establish the status of current practice. METHODS A 50-item web-based questionnaire assessing analysis and interpretation of ARM was distributed by the International Anorectal Physiology Working Group via societies representing practitioners that perform ARM. Study methodology and performance characteristics between institutions were compared. KEY RESULTS One hundred and seven complete responses were included from 30 countries. Seventy-nine (74%) institutions performed at least two studies per week. Forty-nine centers (47%) applied conventional ARM (≤8 pressure sensors) and 57 (53%) high-resolution ARM (HR-ARM). Specialist centers were most likely to use HR-ARM compared to regional hospitals and office-based practice (63% vs 37%). Most conventional ARM systems used water-perfused technology (34/49); solid-state hardware was more frequently used in centers performing HR-ARM (44/57). All centers evaluated rest and squeeze. There was marked variation in the methods used to report results of maneuvers. No two centers had identical protocols for patient preparation, setup, study, and data interpretation, and no center fully complied with published guidelines. CONCLUSIONS & INFERENCES There is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co-operation to standardize ARM.


title: SARS-CoV-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma.

text: In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.


title: The Effect of Mobile App Interventions on Influencing Healthy Maternal Behavior and Improving Perinatal Health Outcomes: Systematic Review.

text: BACKGROUND Perinatal morbidity and mortality are significant public health issues with an enduring impact on the health and well-being of women and their families. Millions of pregnant women now download and use mobile applications to access, store, and share health information. However, little is known about the consequences. An investigation of their impact on perinatal health outcomes is particularly topical. OBJECTIVE To determine the effects of mobile app interventions during pregnancy on influencing healthy maternal behavior and improving perinatal health outcomes. METHODS Searches of PubMed, Embase, the Cochrane Library, CINAHL, WHO Global Health Library, POPLINE, and CABI Global Health were conducted with no date or language restrictions. Randomized and non-randomized studies were included if they reported perinatal health outcomes of interventions targeting pregnant women, using mobile apps compared with other communication modalities or with standard care. The primary outcome measure was the change in maternal behaviors (as defined by trial authors), by intervention goals. Two reviewers independently extracted data using standardized forms. RESULTS Four randomized controlled trials (RCTs) involving 456 participants were included. All studies targeted participants in early pregnancy; however, wide variation was evident in participant characteristics, intervention, and study outcomes measures. Three trials were based in hospital settings, comparing women using mobile apps with routine antenatal care. One community-based trial gave all participants a device to promote physical activity; the intervention arm was also given a mobile app. All studies reported data for the primary outcome measure, describing some benefit from the intervention compared with controls. However, few statistically significant primary or secondary outcomes were reported. Due to insufficient data, the planned meta-analysis and subgroup analyses were not performed. CONCLUSIONS Due to limited numbers, heterogeneity of interventions, comparators, and outcome measures, no firm conclusions can be drawn on the effects of mobile application interventions during pregnancy on maternal knowledge, behavior change, and perinatal health outcomes. As millions of women utilize mobile apps during pregnancy, rigorous studies are essential for health care and maternity care providers to optimally design, implement, and evaluate interventions.


title: Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia.

text: BACKGROUND Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. METHODS Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV. RESULTS There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08). CONCLUSIONS A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiological methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.


title: Radioimmunotherapy improves survival of rats with microscopic liver metastases of colorectal origin.

text: BACKGROUND Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors.


title: X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation.

text: Arenaviruses are important agents of zoonotic disease worldwide. The virions expose a tripartite envelope glycoprotein complex at their surface, formed by the glycoprotein subunits GP1, GP2 and the stable signal peptide. This complex is responsible for binding to target cells and for the subsequent fusion of viral and host-cell membranes for entry. During this process, the acidic environment of the endosome triggers a fusogenic conformational change in the transmembrane GP2 subunit of the complex. We report here the crystal structure of the recombinant GP2 ectodomain of the lymphocytic choriomeningitis virus, the arenavirus type species, at 1.8-Å resolution. The structure shows the characteristic trimeric coiled coil present in class I viral fusion proteins, with a central stutter that allows a close structural alignment with most of the available structures of class I and III viral fusion proteins. The structure further shows a number of intrachain salt bridges stabilizing the postfusion hairpin conformation, one of which involves an aspartic acid that appears released from a critical interaction with the stable signal peptide upon low pH activation.


title: Implications of ventricular arrhythmia "bursts" with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: a biosignature of direct myocellular injury "downstream of downstream".

text: AIMS Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia "bursts" (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR). METHODS AND RESULTS Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS (p=0.015). CONCLUSIONS Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive "biosignature" of optimal reperfusion than do single surrogate markers.


title: Cerebral oxygenation during different treatment strategies for a patent ductus arteriosus.

text: BACKGROUND Preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) are at risk for fluctuations in cerebral blood flow, but it is unclear how different hsPDA treatment strategies may affect cerebral oxygenation. OBJECTIVE To compare regional cerebral oxygen saturation (rSO(2)) as measured by near-infrared spectroscopy (NIRS) in very low birth weight (VLBW) infants with a hsPDA treated with conservative management, indomethacin, or surgical ligation. METHODS This prospective observational study enrolled 33 VLBW infants with a hsPDA diagnosed by echocardiogram and 12 control VLBW infants without a hsPDA. Infants had NIRS cerebral monitoring applied prior to conservative treatment, indomethacin, or surgical ligation. Cranial ultrasound and magnetic resonance imaging data were also collected. RESULTS Infants undergoing surgical ligation had a greater time period with >20% change in rSO(2) from baseline (30%) compared to those receiving indomethacin (7.4%, p = 0.001) or control infants without a hsPDA (2.6%, p = 0.0004). NIRS measures were not associated with abnormal neuroimaging in this small cohort. CONCLUSION These findings suggest that infants requiring surgical ligation for a hsPDA are at high risk for significant changes in cerebral oxygenation, whereas those receiving either indomethacin or conservative management maintain relatively stable cerebral oxygenation levels. Additional research is necessary to determine if NIRS monitoring identifies infants with a hsPDA at highest risk for brain injury.


title: Walking the dog: exploration of the contact networks between dogs in a community.

text: This study uses social network analysis to investigate potential contact among 214 dog-owning households in a UK community through their utilization of public space during walking. We identified a high level of potential contact between dog-owning households; most households walked their dogs in only a few areas but a small number visited many. Highly connected households were more likely to have multiple dogs, walk their dogs off lead, and own Working, Pastoral or some Terrier types. Similarly, most areas were only visited by a few households but a few were visited by many. Despite identification of subgroups of households and locations, we demonstrated high connectivity between dog-owning households, with minimum path lengths of two 'steps' (household-area-household, 74%) or four 'steps' (via two areas, 26%).


title: Virtual stenting of intracranial aneurysms: A pilot study for the prediction of treatment success based on hemodynamic simulations.

text: Endovascular treatment of intracranial aneurysms using flow-diverting devices has revolutionized the treatment of large and complex lesions due to its minimally invasive nature and potential clinical outcomes. However, incomplete or delayed occlusion and persistent intracranial aneurysm growth are still an issue for up to one-third of the patients. We evaluated two patients with intracranial aneurysm located at the internal carotid artery who were treated with flow-diverting devices and had opposite outcomes. Both patients presented with similar aneurysms and were treated with the same device, but after a 1-year follow-up, one case presented with complete occlusion (Case 1) and the other required further treatment (Case 2). To reproduce the interventions, virtual stents were deployed and blood flow simulations were carried out using the respective patient-specific geometries. Afterward, hemodynamic metrics such as aneurysmal inflow reduction, wall shear stresses, oscillatory shear, and inflow concentration indices were quantified. The hemodynamic simulations reveal that for both cases, the neck inflow was clearly reduced due to the therapy (Case 1: 19%, Case 2: 35%). In addition, relevant hemodynamic parameters such as time-averaged wall shear stress (Case 1: 35.6%, Case 2: 57%) and oscillatory shear (Case 1: 33.1%, Case 2: 26.7%) were decreased considerably. However, although stronger relative reductions occurred in the unsuccessful case, the absolute flow values in the successful case were approximately halved. The findings demonstrate that a high relative effect of endovascular devices is not necessarily associated with the desired treatment outcome. Instead, it appears that a successful intracranial aneurysm therapy requires a certain patient-specific inflow threshold.


title: Discovery of retroviral homologs in bats: implications for the origin of mammalian gammaretroviruses.

text: Gammaretroviruses infect a wide range of vertebrate species where they are associated with leukemias, neurological diseases and immunodeficiencies. However, the origin of these infectious agents is unknown. Through a phylogenetic analysis of viral gene sequences, we show that bats harbor an especially diverse set of gammaretroviruses. In particular, phylogenetic analysis places Rhinolophus ferrumequinum retrovirus (RfRV), a new gammaretrovirus identified by de novo analysis of the Rhinolophus ferrumequinum transcriptome, and six other gammaretroviruses from different bat species, as basal to other mammalian gammaretroviruses. An analysis of the similarity in the phylogenetic history between the gammaretroviruses and their bat hosts provided evidence for both host-virus codivergence and cross-species transmission. Taken together, these data provide new insights into the origin of the mammalian gammaretroviruses.


title: Application of a motion capture data glove for hand and wrist ergonomic analysis during laparoscopy.

text: OBJECTIVES This study aims to analyze the surgeons' hand spatial configuration during the use of two different instrument handles for laparoscopy, by obtaining information from the data glove CyberGlove®, and establishing existing risk levels for wrist disorders. MATERIAL AND METHODS Fifty surgeons participated in this study and were distributed into three groups (novices, intermediate and experts). Each subject carried out suturing and dissection tasks on a physical simulator, using axial-handled or ring-handled instruments, respectively. Hand and wrist positions were registered by the CyberGlove® and a modified RULA method was applied to establish appropriate risk levels for wrist disorders. RESULTS We found statistically significant differences in seven of the eleven glove sensors when comparing both tasks. RULA method showed that all subjects, with the exception of the experts using an axial-handled instrument, assume a prejudicial wrist posture during the practice of suturing and dissection tasks on the simulator. CONCLUSIONS Data glove CyberGlove® allows for the distinction between two laparoscopic exercises performed with different instruments. Also, laparoscopic intracorporeal suturing when performed with an axial-handled needle holder entails a more ergonomic posture for the wrist joint. Previous minimally invasive surgical experience is a positive influencing factor on the surgeons' wrist postures during laparoscopy.