title: Comparative Retrospective Study of Tension-Free Vaginal Mesh Surgery, Native Tissue Repair, and Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse Repair.

text: Methods We identified that 308 women who had undergone surgical repair of POP were followed up for at least 6 months. Recurrence rates of POP after tension-free vaginal mesh (TVM) surgery (n = 243), native tissue repair (NTR) (vaginal hysterectomy with colpopexy, anterior and posterior colpoplasty, or circumferential suturing of the levator ani muscles and apical repair by transvaginal sacrospinous ligament fixation (SSLF)) (NTR; n = 31), and laparoscopic sacrocolpopexy after subtotal hysterectomy (LSC; n = 34) were compared. Presence of mesh erosion was also recorded. Results Patients who underwent LSC were significantly younger (65.32 ± 3.23 years) than those who underwent TVM surgery (69.61 ± 8.31 years). After TVM surgery, the rate of recurrence (over POP-Q stage II) was 6.17% (15/243) and was highest in patients with advanced POP. The recurrence rate in patients who underwent NTR procedure was 3.23% (1/34) and that in patients who underwent LSC was 11.76% (4/11). There was no statistically significant difference in the recurrence rate between the three types of surgery. There were 13 cases (5.35%) of mesh erosion after TVM surgery and none after LSC surgery. The risk of mesh erosion was correlated with having had total TVM surgery but not with patient age or POP stage. Repeat procedures were performed in 5 women (2.14%) who underwent TVM surgery and 1 (2.94%) who underwent LSC. No patient underwent repeat surgery after NTR. There was no statistically significant difference in the reoperation rate between the three types of surgery. Conclusion Our study suggested that TVM surgery, NTR, and LSC have comparable outcomes as for the postoperative recurrence rate and mesh erosion. However, the outcomes of each technique need to be carefully evaluated over a long period of time.


title: Avian bornavirus associated with fatal disease in psittacine birds.

text: Thanks to new technologies which enable rapid and unbiased screening for viral nucleic acids in clinical specimens, an impressive number of previously unknown viruses have recently been discovered. Two research groups independently identified a novel negative-strand RNA virus, now designated avian bornavirus (ABV), in parrots with proventricular dilatation disease (PDD), a severe lymphoplasmacytic ganglioneuritis of the gastrointestinal tract of psittacine birds that is frequently accompanied by encephalomyelitis. Since its discovery, ABV has been detected worldwide in many captive parrots and in one canary with PDD. ABV induced a PDD-like disease in experimentally infected cockatiels, strongly suggesting that ABV is highly pathogenic in psittacine birds. Until the discovery of ABV, the Bornaviridae family consisted of a single species, classical Borna disease virus (BDV), which is the causative agent of a progressive neurological disorder that affects primarily horses, sheep, and some other farm animals in central Europe. Although ABV and BDV share many biological features, there exist several interesting differences, which are discussed in this review.


title: In silico virtual screening approaches for anti-viral drug discovery

text: Despite the considerable advances in medical and pharmaceutical research during the past years, diseases caused by viruses have remained a major burden to public health. Virtual in silico screening has repeatedly proven to be useful to meet the special challenges of antiviral drug discovery. Large virtual compound libraries are filtered by different computational screening methods such as docking, ligand-based similarity searches or pharmacophore-based screening, reducing the number of candidate molecules to a smaller set of promising candidates that are then tested biologically. This rational approach makes the drug discovery process more goal-oriented and saves resources in terms of time and money. In this review we discuss how different virtual screening techniques can be applied to antiviral drug discovery, present recent success stories in this field and finally address the main differences between the methods.


title: Virus-infected alveolar epithelial cells direct neutrophil chemotaxis and inhibit their apoptosis.

text: The alveolar epithelium is a critical target for pulmonary viruses and can produce proinflammatory cytokines and chemokines upon viral infection. However, the molecular interactions between virus-infected alveolar epithelial cells and inflammatory cells, including polymorphonuclear leukocytes (PMNs), have not been thoroughly characterized. Rat coronavirus (RCoV) is used as a model to study the immune response to viral infection in the lung of the natural host. We have developed an in vitro model to characterize the response of PMNs to RCoV-infected type I-like alveolar epithelial (AT1) cells, the primary target for RCoV infection in the alveoli. Multiple CXC chemokines that signal through CXCR2 were required for PMN chemotaxis toward medium from RCoV-infected AT1-like cells (RCoV-AT1). Furthermore, RCoV-AT1 inhibited spontaneous PMN apoptosis, including activation of effector caspase 3 and initiator caspases 8 and 9. Use of a selective inhibitor of CXCR2, SB265610, demonstrated that CXCR2 signaling was required for RCoV-AT1-mediated inhibition of PMN apoptosis. These data suggest that CXC chemokines produced by RCoV-infected AT1-like cells inhibit PMN apoptosis during infection. These studies provide new insight into the molecular mechanisms whereby alveolar epithelial cells direct the functions of PMNs during viral infection of the lung.


title: Symptoms and responses to critical incidents in paramedics who have experienced childhood abuse and neglect.

text: BACKGROUND Mental and physical symptoms are common in paramedics, which may relate to high work stress, including critical incidents. As previous trauma is a risk factor for psychological symptoms after exposure to critical incidents, the prevalence of childhood experiences with abuse and neglect and paramedics' adaptation to critical incidents may be important. METHODS 635 paramedics were surveyed regarding childhood experiences of physical, sexual or emotional abuse as well an index critical incident from the past, acute stress responses to that event and current mental and physical symptoms. A comparison group of 159 female hospital-based healthcare workers completed the same survey of childhood abuse and neglect in a separate study. RESULTS 232 paramedics (36.5%) responded. Among these, physical, sexual or emotional childhood abuse was reported by 38.4%. Female paramedics reported significantly more emotional and physical abuse and neglect than female hospital workers. Paramedics who reported childhood abuse or neglect more frequently experienced signs of acute stress immediately following the index critical incident and for the following 2 weeks. Childhood abuse and neglect were associated with significantly higher scores for depressive symptoms, physical symptoms and burnout, and a higher prevalence of 'cases' scoring above thresholds of clinical significance. CONCLUSION Childhood abuse may be more common in paramedics than in other healthcare workers, at least in women. Childhood abuse and neglect is associated with acute stress responses to critical incidents and to current physical and mental symptoms. These results are based on a low response rate and may not be generalisable.


A novel running annuloplasty suture technique for robotically assisted mitral valve repair.


title: Cerebellar degeneration in adult spinal muscular atrophy patients.

text: BACKGROUND Spinal muscular atrophy (SMA) is a genetic motor neuron disease related to deletions in the SMN1 gene. There is mounting evidence that the disease is not restricted to motor neurons. In this neuroimaging study, we aimed to investigate the presence of in-vivo cerebellar damage in adult SMA patients not treated with disease-modifying treatment. METHODS Twenty-five molecularly confirmed patients with SMA type III or IV and 25 healthy controls underwent MRI with cerebellar focused structural analysis by the CERES automated pipeline. Volumetry (total and gray matter-GM) as well as cortical thickness of the cerebellar lobules were compared in both groups. Full clinical and demographic data were then assessed for correlations with cerebellar imaging findings. RESULTS Volumes of cerebellar lobules VIIIB (right), IX and X were significantly smaller in patients with SMA. Lobule IX also had GM atrophy in comparison to controls. We found no significant correlation between clinical findings and cerebellar damage. CONCLUSIONS Neuroimaging detects cerebellar structural changes in adult SMA patients, suggesting that neurodegeneration is not confined to the lower motor neurons in the disease.


title: Humoral and cellular immune responses induced by 3a DNA vaccines against severe acute respiratory syndrome (SARS) or SARS-like coronavirus in mice.

text: Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8(+) T cells and interleukin-2 (IL-2) mainly by CD4(+) T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.


title: Molecular epidemiology of rhinoviruses in Cyprus over three consecutive seasons.

text: Human rhinoviruses (HRVs) are widespread respiratory pathogens and a major cause of acute respiratory tract infections. The aim of this study was to investigate the molecular epidemiology of rhinovirus infections in children in Cyprus over three consecutive winter seasons. From a total of 116 rhinovirus-positive samples, 68 were sequenced in the 5'-UTR and VP4/VP2 regions. Thirty-six (52.9%) samples were identified as HRV-A and 27 (39.7%) as HRV-C, with only five (7.4%) samples belonging to the HRV-B species. Of these, a total of 46 different genotypes were identified. In the VP2/VP4 phylogenetic tree all strains clustered in three different well-defined clades, whereas the 5'-UTR tree exhibited clades with a mixed clustering of HRV-A and HRV-C strains reflecting the evolutionary history of recombination between HRV-A and HRV-C that has been observed previously. In summary, a high intra- and inter-season diversity of HRV types was observed. Despite its geographical isolation the frequency of HRV species in Cyprus is comparable to that reported in other regions of the world supporting the concept of an unrestricted global circulation. This study assesses, for the first time, the epidemiology of rhinovirus infections in Cypriot children and will be helpful to clinicians and researchers interested in the treatment and control of viral respiratory tract infections.


title: Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations.

text: OBJECTIVE Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue haemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHOD Systematic review of the literature from 1990 to 30 October 2007 including English publications comparing dengue and OFI. RESULTS Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children only, and four assessed adults only. Patients with dengue had significantly lower platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of petechiae than OFI patients. Higher frequencies of myalgia, rash, haemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher haematocrits were reported in adult patients with dengue but not in children. Most multivariable models included platelet count, WBC, rash, and signs of liver damage; however, none had high statistical validity and none considered changes in clinical features over the course of illness. CONCLUSIONS Several individual clinical and laboratory variables distinguish dengue from OFI; however, some variables may be dependent on age. No published multivariable model has been validated. Study design, populations, diagnostic criteria, and data collection methods differed widely across studies, and the majority of studies did not identify specific aetiologies of OFIs. More prospective studies are needed to construct a valid and generalizable algorithm to guide the differential diagnosis of dengue in endemic countries.


Regulatory obstacles affecting ecological studies in the ICU.


Clinical course, severity and mortality in a cohort of patients with COVID-19 with rheumatic diseases.


title: An update on our response to Covid-19.

text: BVA is working hard to keep the veterinary profession informed and supported during these challenging and unpredictable times.


title: Lung Entrapment between the Pectus Bar and Chest Wall after Pectus Surgery: An Incidental Finding during Video-Assisted Thoracoscopic Surgery.

text: We report a case of an entrapped lung after the pectus bar repair of a pectus deformity. The entrapped lung was found incidentally during video-assisted thoracoscopic surgery (VATS) for pneumothorax. Based on VATS exploration, multiple bullae seemed to be the cause of the pneumothorax, but the entrapped lung was suspected to have been a cause of the air leakage.


title: Cyanoacrylate glue for intra-abdominal mesh fixation of polypropylene-polyvinylidene fluoride meshes in a rabbit model.

text: BACKGROUND Cyanoacrylate glues are tissue adhesive with high adherent and hemostatic properties. The aim of this study was to evaluate the efficacy of cyanoacrylates glue for polypropylene-polyvinylidene fluoride (PP-PVDF) intraperitoneal onlay mesh (IPOM) fixation in a rabbit model. MATERIALS AND METHODS In 40 New Zealand white rabbits, three pieces (3×3cm) of a PP-PVDF mesh (n=120) were fixed in IPOM technique on both sides of a midline laparotomy. For mesh fixation we used spiral tacks, nonabsorbable sutures, or cyanoacrylate glue in a randomized manner. All animals were killed after 12 wk. The prosthetic materials were excised en bloc with the anterior abdominal wall for evaluation of the tensile strength and histologic analysis. Results are presented as mean and standard deviation. RESULTS Meshes fixed with glue showed a significantly higher tenacity of adhesions (2.75±0.97) compared with those with tacks (2.44±0.97 sutures versus 1.91±0.92 tacks). The percentage of adhesions in the glue group was comparable to the suture group (36.50% ± 27.60% glue, 37.62% ± 27.36% suture). The tensile strength of stapled and sutured meshes was significantly higher than the tensile strength glued mesh (14.15±0.97N suture versus 14.84±0.74 stapler versus 9.64±0.78N glue). Mesh shrinkage was irrespective of the fixation technique. The inflammation reaction was more pronounced in the glue group. CONCLUSIONS Although cyanoacrylate glue showed a considerable cellular ingrowth in this rabbit model, sutures and tacks proved to be superior for IPOM fixation of PP-PVDF meshes in terms of tensile strength.


Reply to: Cigarette Smoking and COVID-19: A Complex Interaction.


title: Robot-assisted single-site compared with laparoscopic single-incision cholecystectomy for benign gallbladder disease: protocol for a randomized controlled trial.

text: BACKGROUND Recent advances in robotic technology suggest that the utilization of the da Vinci Single-Site™ platform for cholecystectomy is safe, feasible and results in a shorter learning curve compared to conventional single-incision laparoscopic cholecystectomy. Moreover, the robot-assisted technology has been shown to reduce the surgeon's stress load compared to standard single-incision laparoscopy in an experimental setup, suggesting an important advantage of the da Vinci platform. However, the above-mentioned observations are based solely on case series, case reports and experimental data, as high-quality clinical trials to demonstrate the benefits of the da Vinci Single-Site™ cholecystectomy have not been performed to date. METHODS This study addresses the question whether robot-assisted Single-Site™ cholecystectomy provides significant benefits over single-incision laparoscopic cholecystectomy in terms of surgeon's stress load, while matching the standards of the conventional single-incision approach with regard to peri- and postoperative outcomes. It is designed as a single centre, single-blinded randomized controlled trial, which compares both surgical approaches with the primary endpoint surgeon's physical and mental stress load at the time of surgery. In addition, the study aims to assess secondary endpoints such as operating time, conversion rates, additional trocar placement, intra-operative blood loss, length of hospital stay, costs of procedure, health-related quality of life, cosmesis and complications. Patients as well as ward staff are blinded until the 1st postoperative year. Sample size calculation based on the results of a previously published experimental setup utilizing an estimated effect size of surgeon's comfort of 0.8 (power of 0.8, alpha-error level of 0.05, error margin of 10-15%) resulted in a number of 30 randomized patients per arm. DISCUSSION The study is the first randomized controlled trial that compares the da Vinci Single Site™ platform to conventional laparoscopic approaches in cholecystectomy, one of the most frequently performed operations in general surgery. TRIAL REGISTRATION This trial is registered at clinicaltrials.gov (trial number: NCT02485392 ). Registered February 19, 2015.


title: NewB for newbies: a randomized control trial training housestaff to perform neonatal intubation with direct and videolaryngoscopy.

text: BACKGROUND Competency rates in neonatal intubation among pediatric residents are low and currently not meeting ACGME/AAP standards. AIMS The aim of this study was to compare standard bedside teaching of neonatal endotracheal intubation to a computer module, as well as introduce residents to the emerging technology of videolaryngoscopy. METHODS The study population consisted of The University of Texas Health Science Center at San Antonio Pediatric interns/residents and PGY-1 Anesthesia interns rotating through the NICU. Prior to participating in the study, the residents completed a survey addressing past experiences with intubation, comfort level, and prior use of direct and videolaryngoscopy. Participants then performed timed trials of both direct and videolaryngoscopy on the SimNewB(®). They had up to three attempts to successfully intubate, with up to 30 s on each attempt. After randomization, participants received one of the following teaching interventions: standard, computer module, or both. This was followed by a second intubation trial and survey completion. RESULTS Thirty residents were enrolled in the study. There was significant improvement in time to successful intubation in both methods after any teaching intervention (direct 22.0 ± 13.4 s vs 14.7 ± 5.9 s, P = 0.002 and videolaryngoscopy 42.2 ± 29.3 s vs 26.8 ± 18.6 s, P = 0.003). No differences were found between the types of teaching. Residents were faster at intubating with direct laryngoscopy compared to videolaryngoscopy before and after teaching. By the end of the study, only 33% of residents preferred using videolaryngoscopy over direct laryngoscopy, but 76% felt videolaryngoscopy was better to teach intubation. CONCLUSIONS Both standard teaching and computer module teaching of neonatal intubation on a mannequin model results in improved time to successful intubation and overall improved resident confidence with intubation equipment and technique. Although intubation times were lower with direct laryngoscopy compared to videolaryngoscopy, the participating residents felt that videolaryngoscopy is an important educational tool.


title: A revisit on older adults suicides and Severe Acute Respiratory Syndrome (SARS) epidemic in Hong Kong.

text: BACKGROUND The Severe Acute Respiratory Syndrome (SARS) outbreak in 2003 had an enormous impact on Hong Kong society and the suicide rate was also at its historical high, 18.6 per 100,000. The most significant increase was found among the older adults aged 65 or above. METHODS Poisson Regression Models were used to examine impact of the SARS epidemic on older adults suicides in Hong Kong. A complete set of the suicide statistics for the period 1993-2004 from the Coroners' Court were made available for the analysis. Chi-square test was used to compare the profile of the older adult suicide cases in the pre-SARS, peri-SARS and post-SARS periods. RESULTS It showed an excess of older adults suicides in April 2003, when compared to the month of April of the other years. A trough, instead of the usual summer peak, was observed in June, suggesting some of the older adults suicides might have been brought forward. On a year basis, the annual older adult's suicide rates in 2003 and 2004 were significantly higher than that in 2002, suggesting the suicide rate did not return to the level before the SARS epidemic. Based on the Coroners' suicide death records, overall severity of illness, level of dependency and worrying of having sickness among the older adult suicides were found to be significantly different in the pre-SARS, peri-SARS and post-SARS periods. CONCLUSION The SARS epidemic was associated with an increase in older adults' suicide rate in April 2003 and some suicide deaths in June 2003 might have been brought forward. Moreover, an increase in the annual older adults' suicide rate in 2003 was observed and the rate in 2004 did not return to the level of 2002. Loneliness and disconnectedness among the older adults in the community were likely to be associated with the excess older adults' suicides in 2003. Maintaining and enhancing mental well being of the public over the period of epidemic is as important as curbing the spread of the epidemic. Attention and effort should also be made to enhance the community's ability to manage fear and anxiety, especially in vulnerable groups over the period of epidemic to prevent tragic and unnecessary suicide deaths.


title: The Question of Whether to Remain on Therapy for Chronic Rheumatic Diseases in the Setting of the Covid-19 Pandemic.

text: We appreciate our Italian colleagues' interest in our editorial denoting the rheumatologist's role in helping to diagnose and treat cytokine storm syndrome (CSS) in the setting of the Covid-19 panemic (1). It is encouraging that none of the 123 pediatric rheumatology patients (primarily juvenile idiopathic arthritis) on background biological disease modifying anti-rheumatic drug (bDMARD) therapies in Milan, Italy surveyed over a 7-week period from February 25 through April 14, 2020 (during which time Covid-19 was hyper-endemic there) had either confirmed or suspected Covid-19 (2).


title: The future of conferences, today: Are virtual conferences a viable supplement to "live" conferences?

text: During the COVID-19 pandemic, virtual conferences provide a much-needed alternative to cancelled meetings. Here are insights and lessons from organizing a virtual meeting.


title: Pulmonary artery stents in the recent era: Immediate and intermediate follow-up.

text: BACKGROUND Long-term follow-up after stent dilation of native and acquired pulmonary artery stenosis is scarce in the pediatric population. Most cohorts include a myriad of anatomies and associated conditions. METHOD In order to establish objective performance criteria, we performed a retrospective review of all patients who underwent unilateral pulmonary artery stenting in biventricular physiology at three centers from June 2006 to June 2011. RESULTS Fifty-eight patients received 60 stents with Palmaz Genesis stent used most commonly (78%). Average age at implantation was 10.4 ± 10.3 years and weight 31.6 ± 21.8 kg. The immediate success rate was 98%, with improvement in minimal diameter from 5.1 ± 2 cm to 10.6 ± 3 cm (P < 0.01). There were 10 complications (7 major and 3 minor) and no acute mortality. One-year follow-up studies were available in 48 patients (83%), including echocardiogram (60%), catheterization (28%), MRI (29%), and lung perfusion (31%). Follow-up echocardiogram showed mild increase in stent gradient, from 5.7 ± 6.7 mm Hg post-procedure to 17.1 ± 11.7 mm Hg. Follow-up catheterization showed no significant change in minimal stent diameter (8.8 ± 2.6 to 7.8 ± 2.3 mm), gradient (7.7 ± 8.4 to 12.6 ± 12.2 mm Hg), or right ventricular pressures (43.7 ± 9 to 47.7 ± 10.5 mm Hg). Nine patients (16%) underwent scheduled stent redilation over a period of 12 days to 25 months. CONCLUSION In conclusion, stent implantation shows excellent immediate and 1-year follow-up results with maintenance of improved caliber of the stented vessel and lowered right ventricular systolic pressures.


title: Health outcomes related to the provision of free, tangible goods: A systematic review.

text: BACKGROUND Free provision of tangible goods that may improve health is one approach to addressing discrepancies in health outcomes related to income, yet it is unclear whether providing goods for free improves health. We systematically reviewed the literature that reported the association between the free provision of tangible goods and health outcomes. METHODS A search was performed for relevant literature in all languages from 1995-May 2017. Eligible studies were observational and experimental which had at least one tangible item provided for free and had at least one quantitative measure of health. Studies were excluded if the intervention was primarily a service and the free good was relatively unimportant; if the good was a medication; or if the data in a study was duplicated in another study. Covidence screening software was used to manage articles for two levels of screening. Data was extracted using an adaption of the Cochrane data collection template. Health outcomes, those that affect the quality or duration of life, are the outcomes of interest. The study was registered with PROSPERO (CRD42017069463). FINDINGS The initial search identified 3370 articles and 59 were included in the final set with a range of 20 to 252 246 participants. The risk of bias assessment revealed that overall, the studies were of medium to high quality. Among the studies included in this review, 80 health outcomes were statistically significant favouring the intervention, 19 health outcomes were statistically significant favouring the control, 141 health outcomes were not significant and significance was unknown for 28 health outcomes. INTERPRETATION The results of this systematic review provide evidence that free goods can improve health outcomes in certain circumstances, although there were important gaps and limitations in the existing literature.


The Art of Health Promotion: linking research to practice.


title: Ultrasonography-guided surgical clip placement for tumor localization in patients undergoing neoadjuvant chemotherapy for breast cancer.

text: PURPOSE We investigated the feasibility of using surgical clips as markers for tumor localization and their effect on the imaging evaluation of treatment responses after neoadjuvant chemotherapy (NAC). METHODS A total of 16 breast cancers confirmed by needle biopsy in 15 patients were included in this study from October 2012 to June 2014. Under ultrasonography (US)-guidance, the surgical clips were placed prior to NAC. Additional mammography, breast US, and breast magnetic resonance examinations were performed within 10 days before surgery. The time period from marker insertion to operation date was documented. Images acquired via the three modalities were evalu-ated for the following parameters: location of clip, clip migration (>1 cm), the presence of complications from clip placement, and the effect of clips on the assessment of treatment. RESULTS The mean time period was 128.6±34.4 days (median, 132.0 days) from the date of clip insertion to the date of surgery. The mean number of inserted clips was 2.3±0.7 (median, 2.0). Clip migration was not visualized by imaging in any patient, and there were no complications reported. Surgical clips did not negatively affect the assessment of treatment responses to NAC. CONCLUSION Surgical clips may replace commercial tissue markers for tumor localization in breast cancer patients undergoing NAC without migration. Surgical clips are well tolerated and safe for the patient, easily visualized on imaging, do not interfere with treatment response, and are cost-effective.


title: Electrical stimulation of alpha oscillations stabilizes performance on visual attention tasks.

text: Neural oscillations in the alpha band (7-13 Hz) have long been associated with reductions in attention. However, recent studies have suggested a more nuanced perspective in which alpha oscillations also facilitate processes of cognitive control and perceptual stability. Transcranial alternating current stimulation (tACS) over occipitoparietal cortex at 10 Hz (alpha-tACS) can selectively enhance EEG alpha power. To assess the contribution of alpha oscillations to attention, we delivered alpha-tACS across 4 experiments while 178 participants performed sustained attention tasks. Poor performance on all visual tasks was previously associated with increased EEG alpha power. We therefore predicted initially that alpha-tACS would consistently impair visual task performance. However, alpha-tACS was instead found to prevent deteriorations in visual performance that otherwise occurred during sham- and 50 Hz-tACS. This finding was observed in 2 experiments, using different sustained attention tasks. In a separate experiment, we also found that alpha-tACS limited improvements on a visual task where learning was otherwise observed. Consequently, alpha-tACS appeared to exert a consistently stabilizing effect on visual attention. Such effects were not seen in an auditory control task, indicating specificity to the visual domain. We suggest that these results are most consistent with the view that alpha oscillations facilitate processes of top-down control and attentional stability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


title: Evaluation of the biodegradable peripheral Igaki-Tamai stent in the treatment of de novo lesions in the superficial femoral artery: the GAIA study.

text: OBJECTIVES This study sought to evaluate the safety and performance of the Igaki-Tamai (Igaki Medical Planning Company, Kyoto, Japan) biodegradable stent in patients with occlusive superficial femoral artery (SFA) disease. BACKGROUND Poly-L-lactic acid (PLLA) biodegradable stents have been shown to be effective in the coronaries, but no data are available regarding their efficacy in the femoral artery. METHODS A prospective, multicenter, nonrandomized study enrolled 30 patients with symptomatic de novo SFA disease undergoing implantation of Igaki-Tamai bioresorbable stents. Clinical examinations and duplex ultrasound were prospectively performed after 1, 6, 9, and 12 months. The main study endpoints were technical success, restenosis rate, rate of target lesion revascularization (TLR), changes in ankle-brachial index (ABI), and quality of life by evaluating the walking impairment questionnaire (WIQ). Safety was assessed by monitoring the occurrence of major adverse clinical events and serious adverse events. RESULTS The mean age of the patients was 67.7 years, and 77% were male. The mean lesion length was 5.9 cm. Mean diameter stenosis was reduced from 89.9% to 6.2%, after stent implantation. Technical success was 96.7%. Binary restenosis rate for the 6 and 12 months follow-up was 39.3% and 67.9%, respectively. The TLR rate was 25.0% after 6 months and 57.1% after 12 months. All TLR were successful; the secondary patency rate after 1 year was 89.3%. Between baseline and 12 months, ABI increased in 53.6% of patients. Functional endpoints (WIQ), even if affected by a relatively high reintervention rate, showed improvement in most of the patients. CONCLUSIONS The GAIA (Evaluation of the Biodegradable Peripheral Igaki-Tamai Stent in the Treatment of De Novo Lesions in the Superficial Femoral Artery) study shows that when using biodegradable PLLA stents (Igaki-Tamai), the immediate angiographic results are comparable to the results of metal stents, achieving a high secondary patency rate after 1 year. Modifications of stent characteristics and technical modifications are needed with the goal to reduce the restenosis rate during the reabsorption period.


title: [Materialism and dialectics of epidemic prevention and control: only by respecting science can we do more with less].

text: The epidemic caused by COVID-19 has been highly concerned by the international community including World Health Organization (WHO). This is an ongoing battle for human life and health. We should always remember and learn lessons from the past, which could be promoted to all over the country, even the world. Many phenomena and problems in the work of epidemic prevention, control and treatment are worthy of our deep reflection. We should use scientific approach and dialectical materialism to make a practical and realistic summary. The purpose is to win the battle as soon as possible, and more importantly, to avoid repeating the same mistakes and prevent pestilence before it happens.


Olfactory Dysfunction in COVID-19.


title: Emerging paramyxoviruses: molecular mechanisms and antiviral strategies.

text: In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this family) were first identified in the 1990s in Australia, Malaysia and Singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. Other paramyxoviruses, such as Menangle virus, Tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.


Mitigating the psychological effects of social isolation during the covid-19 pandemic.


Screams on a Zoom call: the theory of homeworking with kids meets reality.


title: An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds.

text: We developed a multi-functional construct capable of controlled delivery of bioactive substances that can improve wound repair by supporting the intrinsic ability of the skin to heal. We synthesized electrospun scaffolds-composed of a blend of the degradable polymers poly(l-lactide) (PLA) or polycaprolactone (PCL)-that produce highly efficient non-viral in vivo gene delivery to cells in the wound bed, provide a protective barrier during early wound healing, and support cell migration and growth. This multi-functional material was tested for its influence on wound healing: scaffolds were loaded with plasmids encoding keratinocyte growth factor (KGF) and applied to full-thickness wounds in mice. Compared to scaffolds with control plasmids, animals receiving the KGF plasmid-loaded scaffold produced significant enhancements in wound healing, which was quantified by improvements in the rate of wound re-epithelialization, keratinocyte proliferation, and granulation response. Further, we quantified the expression level of endogenous and plasmid-derived KGF in wound samples: qRT-PCR on wound sections revealed a correlation between the levels of plasmid-derived protein expression and histological analysis of wound healing, revealing an inverse relationship between the expression level of exogenous KGF and the size of the unhealed epithelial layer in wounds. Our findings suggest that engineered nanofiber PLA/PCL scaffolds are capable of highly efficient controlled DNA delivery and are promising materials for treatment of cutaneous wounds.


title: Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells.

text: The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.


Corticosteroids for Common Palliative Care Symptoms #395.


title: Angiotensin-converting enzymes and drug discovery in cardiovascular diseases.

text: Angiotensin-converting enzyme (ACE) is a major target in the treatment of cardiovascular diseases (CVDs). In addition to ACE, ACE2 - which is a homolog of ACE and promotes the degradation of angiotensin II (Ang II) to Ang (1-7) - has been recognized recently as a potential therapeutic target in the management of CVDs. This article reviews different metabolic pathways of ACE and ACE2 (Ang I-Ang II-AT1 receptors and Ang I-Ang (1-7)-Mas receptors) in the regulation of cardiovascular function and their potential in new drug development in the therapy of CVDs. In addition, recent progress in the study of angiotensin and ACE in fetal origins of CVD, which might present an interesting field in perinatal medicine and preventive medicine, is briefly summarized.


title: Liver Biochemistries in Hospitalized Patients With COVID-19.

text: Coronavirus disease 2019 (COVID-19) leads to elevated liver biochemistries in approximately half of patients on presentation. To date, data are limited regarding the trend of liver biochemistries over the course of illness. We aimed to evaluate the trend, etiology, and outcomes associated with liver biochemistries in COVID-19. A total of 60 patients with COVID-19 were admitted between March 21 and March 28, 2020. Mean age was 57 years, 65% were male and 28% were Hispanic. At study conclusion, 6 patients were deceased, 28 discharged, and 26 remained admitted. Patients who remained admitted were followed for median 12 days. Of 60 patients, 41 (69%) had at least one abnormal liver biochemistry on admission. Median aspartate aminotransferase (AST) was higher than alanine aminotransferase (ALT) at admission (46 vs. 30 U/L) and during the hospital course. Aminotransferases rose above normal in 54 (93%) patients, while alkaline phosphatase and total bilirubin elevations were rare. Ten (17%) patients developed aminotransferases more than 5 times the upper limit of normal. AST highly correlated with ALT throughout the illness course (r = 0.97; P < 0.0001), whereas correlations with markers of muscle injury and inflammation were weak. Statin use was common prior to (40%) and during admission (80%) at our center, with no difference in peak liver biochemistries between users and non-users. No demographic or comorbid illness was associated with liver injury. Admission AST (69 vs. 49; P < 0.05), peak AST (364 vs. 77; P = 0.003), and peak ALT (220 vs. 52; P = 0.002) were higher in intubated patients. Conclusion: AST-dominant aminotransferase elevation is common in COVID-19, mirrors disease severity, and appears to reflect true hepatic injury.


title: Developing your career in an age of team science.

text: Academic institutions and researchers are becoming increasingly involved in translational research to spur innovation in addressing many complex biomedical and societal problems and in response to the focus of the National Institutes of Health and other funders. One approach to translational research is to develop interdisciplinary research teams. By bringing together collaborators with diverse research backgrounds and perspectives, these teams seek to blend their science and the workings of the scientists to push beyond the limits of current research.While team science promises individual and team benefits in creating and implementing innovations, its increased complexity poses challenges. In particular, because academic career advancement commonly focuses on individual achievement, team science might differentially impact early stage researchers. The need to be recognized for individual accomplishments to move forward in an academic career may give rise to research team conflicts. Raising awareness to career-related aspects of team science will help individuals (particularly trainees and junior faculty) take steps to align their excitement and participation with the success of both the team and their personal career advancement.


title: Diagnostic Yield of Combined Pulmonary Cryobiopsies and Electromagnetic Navigation in Small Pulmonary Nodules.

text: Background An increasing number of pulmonary nodules of unknown nature are detected as a result of screening by CT in high lung cancer risk patients. Objectives The purposes of this study were to assess the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) combined with transbronchial lung cryobiopsy (TBLC) and to compare it with standard transbronchial biopsy (TBB) in pulmonary nodules of less than 2 cm in diameter. Methods We prospectively included 32 patients (18 men and 14 women, mean age 68 ± 9 years) with nodules of less than 2 cm in diameter and no metastasis at 18FDG PET-CT. The nodule position was determined by ENB, radial endobronchial ultrasonography miniprobe, and fluoroscopy. Eight samples were obtained, six by TBB and two by TBLC. Results Nodule diameter averaged 16 ± 3 mm. Twenty-five nodules were malignant and 18 were surgically resected. Surgery was avoided in four patients as the biopsies revealed a benign disease. The samples obtained by TBLC were five times larger than those by TBB. The diagnostic yields of TBLC and TBB were 69% and 38%, respectively (p=0.017). Adverse events consisted in 15 mild or moderate bleedings and one pneumothorax. Conclusions In the setting of peripheral pulmonary lesions of less than 20 mm in diameter, ENB-combined TBLC is feasible and safe, provides larger samples, and has higher diagnostic yield than TBB.


title: Primary adrenal leiomyosarcoma with lymph node metastasis: a case report.

text: BACKGROUND Leiomyosarcomas typically originate in smooth muscle cell. Leiomyosarcoma potentially arising from the adrenal gland is an extremely rare mesenchymal tumors associated with delayed diagnosis and poor prognosis. CASE PRESENTATION A 34-year-old man visited our department complaining of right hypochondriac pain. Computed tomography demonstrated a solid mass measuring 5.2 cm in diameter above the right kidney, corresponding to the right adrenal gland, and a lymph node mass, which appeared to have invaded the IVC wall. Right adrenalectomy and lymphadenectomy were performed. A microscopic examination revealed primary adrenal leiomyosarcoma with lymph node metastasis. No adjuvant therapy was performed, and the patient remains recurrence-free at 10 months postoperatively. CONCLUSIONS We experienced a very rare case of primary adrenal leiomyosarcoma. Aggressive surgical resection including vascular reconstruction may be associated with improved survival.


title: Red blood cell transfusion-related necrotizing enterocolitis in very-low-birthweight infants: a near-infrared spectroscopy investigation.

text: BACKGROUND Recent evidence suggests that antecedent red blood cell (RBC) transfusions increase the risk for necrotizing enterocolitis (NEC), the most common gastrointestinal emergency encountered by very-low-birthweight (VLBW) infants. The underlying mechanism for this association is unknown. Altered oxygenation of the mesenteric vasculature during RBC transfusion has been hypothesized to contribute to NEC development and was investigated in this study. STUDY DESIGN AND METHODS Oxygenation patterns among four VLBW infants who developed transfusion-related NEC (TR-NEC) were compared to four VLBW infants with similar gestational age who were transfused but did not develop NEC (non-NEC). Cerebral and mesenteric patterns were recorded before, during, and 48 hours after RBC transfusion using near-infrared spectroscopy (NIRS) technology. Percentage change from mean baseline regional oxygen saturation values and cerebrosplanchnic oxygenation ratios were analyzed. RESULTS All TR-NEC infants (24-29 weeks' gestation; 705-1080 g) demonstrated greater variation in mesenteric oxygenation patterns surrounding transfusions than non-NEC infants (27.6-30 weeks' gestation; 980-1210 g). TR-NEC infants received larger mean volumes of total blood (27.75 ± 8.77 mL/kg) than non-NEC infants (15.25 ± 0.5 mL/kg). CONCLUSION Wide fluctuation and decreases in mesenteric oxygenation patterns are more pronounced in TR-NEC infants, especially before TR-NEC onset, compared to non-NEC infants. Greater total volume of infused blood was associated with TR-NEC in preterm infants. Using NIRS, larger prospective studies are needed to further evaluate potential risk factors for NEC in this high-risk population.


title: The inverted-v chevron umbilicoplasty for breast reconstruction and abdominoplasty.

text: The umbilicoplasty is a key component of abdominoplasty and closure of autologous abdominal wall donor sites in breast reconstruction (TRAM/DIEP). The aesthetically-pleasing umbilicus tends to be small and vertically-oriented in nature, with superior hooding and shadow, inferior retraction and slope, and positioning at the topmost level of the iliac crest. In this Featured Operative Technique, the authors describe their technique for performing an inverted-V chevron umbilicoplasty, which is their method of choice for restoring the umbilicus to an aesthetic and youthful appearance with minimal scarring.


title: Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care.

text: The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes-contact, droplet, and inhalation-to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 µm) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m3 on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission.


title: Single centre experience of flow diverter treatment of complex intracranial aneurysms from South India: Intermediate and long-term outcomes.

text: Background and Purpose To report the intermediate and long-term clinical and angiographic outcomes of the treatment of complex intracranial aneurysms with flow diverter (FD) stents. Setting A tertiary care centre from south India. Materials and Methods Patients treated with FD stents were retrospectively analyzed. The clinical demographics, technical success, angiographic, and long-term outcomes were recorded. Results A total of 13 patients underwent FD treatment, in whom 11 procedures were successful. The cohort included large or giant intracranial aneurysms and recurrent aneurysms following conventional endovascular treatment. Major morbidity was observed in 1 patient, who developed basal ganglia bleed that needed evacuation. Minor complications were seen in 36% of patients without clinical sequelae. Significant obliteration of aneurysm was noted on 1 month computed tomography angiogram in >80% of the patients. Angiographic complete obliteration was noted in 89% of the patients at 6 months. Cranial nerve deficits were noted in 2 patients that improved on subsequent follow up. There was no mortality observed in this cohort. Conclusion FD treatment of complex cerebral aneurysms was associated with favorable clinical and angiographic outcomes in the intermediate and long-term follow up. Minor complications were common, which needed to be effectively managed to prevent major catastrophic events. The steep learning curve influenced the technical success of the procedure.


title: Investigation into the utility of an immunocytochemical assay in body cavity effusions for diagnosis of feline infectious peritonitis.

text: Objectives Feline coronaviruses (FCoVs) exist as two biotypes, feline enteric coronavirus and feline infectious peritonitis virus. Although feline infectious peritonitis (FIP) is a very common disease, the ante-mortem diagnosis of this disease still remains a challenge. Immunofluorescence staining of FCoV in macrophages in effusion has been considered as the reference standard for the diagnosis, but recently this method has been shown to have lower specificity than previously reported. In addition, this method is not widely available and requires the use of fluorescence microscopes. Therefore, it was the aim of this study to evaluate the diagnostic potential of an immunocytochemical (ICC) assay using body cavity effusion. Methods Effusion samples from 27 cats with immunohistochemically confirmed FIP and 29 cats with suspected FIP but a definitive diagnosis of another disease were examined. ICC specimens were evaluated with respect to positive immunostaining. In addition, effusion samples were stained with haematoxylin and eosin and evaluated cytologically. Results A diagnostic sensitivity of 85.2% was recorded for effusion specimens (95% confidence interval [CI] 66.3-95.8), while the diagnostic specificity was only 72.4% (95% CI 52.8-87.3). Conclusions and relevance Once the clinical disease of FIP develops in a cat, it always leads to death, and most of the cats are euthanased within a few days or weeks. As false-positive results might lead to euthanasia of cats suffering from potentially treatable diseases, the diagnostic specificity of a diagnostic tool is the most important factor in a fatal disease like FIP. Thus, the diagnostic utility of this test proved to be insufficient and positive ICC results should be interpreted with caution. Nevertheless, full-body necropsy could not be performed in 13/29 control cats. It is possible that these cats actually suffered from early-stage FIP and that this fact might have influenced the diagnostic specificity of the ICC. Based on the results of the present study, however, ICC of effusion samples currently cannot be recommended to confirm a suspicion of FIP.


title: Management of the Interventional Stroke Patient.

text: OPINION STATEMENT The acute treatment of major ischemic stroke has been revolutionized by strong and consistent evidence from multiple randomized trials. Endovascular treatment by mechanical thrombectomy will be increasingly chosen as an adjunctive or alternative to intravenous thrombolysis. To apply this form of stroke treatment is associated with the challenge of optimal periinterventional treatment. The patient has to be identified, counselled, prepared, monitored, cardiovascularly stabilized, possibly sedated and ventilated, and postprocedurally treated in the optimal way. However, most aspects of periinterventional treatment have as yet not been clarified and require prospective research. Among these, the question of general anesthesia vs conscious sedation has received most attention and may be the most crucial one. Based on a great amount of retrospective data, it appears reasonable to start the intervention under conscious sedation of the non-intubated patient with standby measures for emergent intubation, until prospective randomized trials have clarified that issue. Periinterventional management will significantly affect the success of recanalization.


title: Modeling the pharmacokinetics and pharmacodynamics of sevoflurane using compartment models in children and adults.

text: BACKGROUND Sevoflurane pharmacokinetics have been traditionally described using physiological models, while pharmacodynamics employed the use of minimal alveolar concentration. AIMS The integrated pharmacokinetic-pharmacodynamic relationship of sevoflurane in both adults and children was reviewed using compartment models. We wished to delineate age-related changes in both pharmacokinetics and pharmacodynamics. METHODS The bispectral index and sevoflurane endtidal concentration were continuously measured in 50 patients, aged 3-71 years, scheduled for minor surgery. During maintenance of anesthesia and after stable bispectral index values of 60-65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 minutes or until BIS 40 and then decreased. Data were analyzed using mammillary compartments with nonlinear mixed effects population modeling. The covariate effects of age and size were investigated. RESULTS A three-compartment PK model adequately described sevoflurane pharmacokinetics. Size standardization using allometry explained clearance and volume changes with age. The equilibration half-time (1.48 minutes) increased with age, but could be predicted using allometry in those under 40 years. The effect site concentration eliciting half the maximum response at age 40 years was 1.3% (95%CI 1.22, 1.42) decreased with age from 1.6% at 3 years to 1.1% at 70 years. CONCLUSION Pharmacokinetic compartment models offer an alternative method to describe inhalation anesthetic drug disposition and effects.


title: Pilot study of pulmonary arterial branch sealing using energy devices in an ex vivo model.

text: OBJECTIVE Vascular endostaplers are bulky and can be dangerous when dividing small pulmonary arterial (PA) branch vessels during video-assisted thoracoscopic lobectomy. We aimed to evaluate and compare the immediate efficacy of modern energy sealing devices in an ex vivo PA sealing model. METHODS Patients undergoing anatomical lung resection or lung transplantation were recruited for a prospective cohort pilot study. Four devices were evaluated: Harmonic Ace (Ethicon, Cincinnati, Ohio), Thunderbeat (Olympus, Tokyo, Japan), LigaSure (Covidien, Boulder, Colo), and Enseal (Ethicon; Cincinnati, Ohio). After anatomical lung resection, the PA branches were dissected in vitro. Sealing was then performed with 1 of the sealing devices, the vessel was slowly pressurized, and the bursting pressure was recorded. RESULTS Forty-nine PA branches were sealed in 14 patients. The mean PA branch diameter was 7.4 mm (1.8-14.5 mm). Ten patients had normal PA pressure and 3 had PA hypertension. The mean bursting pressure in each was as follows: Harmonic Ace group, 415.5 mm Hg (137.1-1388.4 mm Hg), Thunderbeat group, 875 mm Hg (237.1-2871.3 mm Hg); LigaSure group, 214.7 mm Hg (0-579.6 mm Hg); Enseal group, 133.7 mm Hg (0-315.38 mm Hg). There were 2 complete sealing failures: LigaSure (diameter 6.78 mm) and Enseal (diameter 8.3 mm). CONCLUSIONS In this pilot study to examine energy sealing of PA branches in a simulated ex vivo model, vascular sealing using energy was effective and was able to sustain high intraluminal bursting pressures. Further research is needed to determine the in vivo and long-term safety of PA branch energy sealing.


title: Comparison of 30-day mortality models for profiling hospital performance in acute ischemic stroke with vs without adjustment for stroke severity.

text: CONTEXT There is increasing interest in reporting risk-standardized outcomes for Medicare beneficiaries hospitalized with acute ischemic stroke, but whether it is necessary to include adjustment for initial stroke severity has not been well studied. OBJECTIVE To evaluate the degree to which hospital outcome ratings and potential eligibility for financial incentives are altered after including initial stroke severity in a claims-based risk model for hospital 30-day mortality for acute ischemic stroke. DESIGN, SETTING, AND PATIENTS Data were analyzed from 782 Get With The Guidelines-Stroke participating hospitals on 127,950 fee-for-service Medicare beneficiaries with ischemic stroke who had a score documented for the National Institutes of Health Stroke Scale (NIHSS, a 15-item neurological examination scale with scores from 0 to 42, with higher scores indicating more severe stroke) between April 2003 and December 2009. Performance of claims-based hospital mortality risk models with and without inclusion of NIHSS scores for 30-day mortality was evaluated and hospital rankings from both models were compared. MAIN OUTCOMES MEASURES Model discrimination, hospital 30-day mortality outcome rankings, and value-based purchasing financial incentive categories. RESULTS Across the study population, the mean (SD) NIHSS score was 8.23 (8.11) (median, 5; interquartile range, 2-12). There were 18,186 deaths (14.5%) within the first 30 days, including 7430 deaths (5.8%) during the index hospitalization. The hospital mortality model with NIHSS scores had significantly better discrimination than the model without (C statistic, 0.864; 95% CI, 0.861-0.867, vs 0.772; 95% CI, 0.769-0.776; P < .001). Among hospitals ranked in the top 20% or bottom 20% of performers by the claims model without NIHSS scores, 26.3% were ranked differently by the model with NIHSS scores. Of hospitals initially classified as having "worse than expected" mortality, 57.7% were reclassified to "as expected" by the model with NIHSS scores. The net reclassification improvement (93.1%; 95% CI, 91.6%-94.6%; P < .001) and integrated discrimination improvement (15.0%; 95% CI, 14.6%-15.3%; P < .001) indexes both demonstrated significant enhancement of model performance after the addition of NIHSS. Explained variance and model calibration was also improved with the addition of NIHSS scores. CONCLUSION Adding stroke severity as measured by the NIHSS to a hospital 30-day risk model based on claims data for Medicare beneficiaries with acute ischemic stroke was associated with considerably improved model discrimination and change in mortality performance rankings for a substantial portion of hospitals.


title: Detection of respiratory viruses with a multiplex polymerase chain reaction assay (MultiCode-PLx Respiratory Virus Panel) in patients with hematologic malignancies.

text: Respiratory viral pathogens are a common cause of morbidity in patients with hematologic malignancies. Sensitive molecular assays have increased the detection of common respiratory viruses and expanded the panel of detectable viruses. Both a rapid viral culture with direct fluorescence antibody (DFA) staining and a PCR-based assay (MultiCode-PLx Respiratory Virus Panel) were performed on patients with hematologic malignancies, who underwent collection of a nasopharyngeal swab or bronchoalveolar lavage from October 2006 to April 2007. Eighty-two samples from 70 patients were obtained; all patients had upper respiratory tract symptoms. Respiratory viruses were detected in 10 samples (12%) by conventional virological methods and in 31 samples (38%) by the MultiCode-PLx assay. This increased diagnostic yield resulted from better sensitivity for those viruses detectable by both methods and detection of viruses not covered by the antigen detection/rapid culture method (human metapneumovirus, coronaviruses and rhinoviruses). The MultiCode-PLx assay frequently identified respiratory viral infections which are not detected by rapid viral culture/DFA; 40% of these patients had pneumonia in addition to the upper respiratory tract symptoms. Improved diagnostics for respiratory viruses may lead to more effective management and better outcomes in this patient population.


title: The Effect of Phase Change Material on Recovery of Neuromuscular Function Following Competitive Soccer Match-Play.

text: Aim: Cryotherapy is commonly implemented following soccer match-play in an attempt to accelerate the natural time-course of recovery, but the effect of this intervention on neuromuscular function is unknown. The aim of the present study was to examine the effect of donning lower-body garments fitted with cooled phase change material (PCM) on recovery of neuromuscular function following competitive soccer match-play. Methods: Using a randomized, crossover design, 11 male semi-professional soccer players wore PCM cooled to 15°C (PCMcold) or left at ambient temperature (PCMamb; sham control) for 3 h following soccer match-play. Pre-, and 24, 48, and 72 h post-match, participants completed a battery of neuromuscular, physical, and perceptual tests. Maximal voluntary contraction force (MVC) and twitch responses to electrical (femoral nerve) and magnetic (motor cortex) stimulation (TMS) during isometric knee-extension and at rest were measured to assess central nervous system (CNS) (voluntary activation, VA) and muscle contractile (quadriceps potentiated twitch force, Qtw,pot) function. Fatigue and perceptions of muscle soreness were assessed via visual analog scales, and physical function was assessed through measures of jump [countermovement jump (CMJ) height and reactive strength index (RSI)] performance. A belief questionnaire was completed pre- and post-intervention to determine the perceived effectiveness of each garment. Results: Competitive soccer match-play elicited persistent decrements in MVC, VA measured with femoral nerve stimulation, Qtw,pot, as well as reactive strength, fatigue and muscle soreness (P < 0.05). Both MVC and VA were higher at 48 h post-match after wearing PCMcold compared with PCMamb (P < 0.05). However, there was no effect of PCM on the magnitude or time-course of recovery for any other neuromuscular, physical function, or perceptual indices studied (P > 0.05). The belief questionnaire revealed that players perceived that both PCMcold and PCMamb were moderately effective in improving recovery, with no difference between the two interventions (P = 0.56). Conclusion: Although wearing cooled PCM garments improved MVC and VA 48 h following match-play, the lack of effect on measures of physical function or perceptual responses to match-play suggest that PCM offers a limited benefit to the recovery process. The lack of effect could have been due to the relatively small magnitude of change in most of the outcome measures studied.


title: Endotrol-tracheal tube assisted endotracheal intubation during video laryngoscopy.

text: Video laryngoscopes allow indirect visualization of the glottis and provide superior views of the glottis compared to direct laryngoscopes in patients with both normal and difficult airways, but it may be difficult to advance the endotracheal tube (ETT) through the vocal cords into the trachea, unless a stylet is used. We propose that the Endotrol(®) ETT may be an effective tool to facilitate video laryngoscope-assisted orotracheal intubation without the use of a stylet. After obtaining written and oral informed consent, 60-adult patients scheduled for elective surgery requiring general anesthesia with orotracheal intubation were enrolled. Patients were randomized, respectively, to 1 of 4 groups: Group A(1), (15 patients): McGrath(®) with Endotrol(®) ETT; Group A(2), (15 patients): McGrath(®) with GlideRite(®)-styletted standard ETT; Group B(1), (15 patients): GlideScope(®) with Endotrol(®) ETT; Group B(2), (15 patients): GlideScope(®) with GlideRite(®)-styletted standard ETT. Statistical analysis was performed with Stata (Stata Corp v10, College Station). Mean time to intubation was longer in the Endotrol(®) groups compared to the GlideRite(®) groups: 60.1 (31.6) vs. 44.4 (27.6) s (p < 0.05). It was subjectively more difficult to intubate using the Endotrol(®) than with a GlideRite(®)-styletted ETT (difficulty score median [range] 2 [1-5] vs. 1 [1-3], respectively). Three intubations using the Endotrol(®) were characterized as difficult, whereas there were no difficult intubations with the GlideRite(®)stylet. The Endotrol(®) ETT, as compared to a standard ETT with a non-malleable stylet, is associated with longer intubation times and a subjective increase in difficulty of use. It may, however, still be a clinically viable alternative in video laryngoscope-assisted orotracheal intubation when use of a rigid stylet is undesirable.


Supraclavicular or interscalene brachial plexus block for rotator cuff repair?


title: Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery.

text: BACKGROUND Because etomidate impairs adrenal function and blunts the cortisol release associated with surgical stimulus, we hypothesized that patients induced with etomidate suffer greater mortality and morbidity than comparable patients induced with propofol. METHODS We evaluated the electronic records of 31,148 ASA physical status III and IV patients who had noncardiac surgery at the Cleveland Clinic. Among these, anesthesia was induced with etomidate and maintained with volatile anesthetics in 2616 patients whereas 28,532 were given propofol for induction and maintained with volatile anesthetics. Two thousand one hundred forty-four patients given etomidate were propensity matched with 5233 patients given propofol and the groups compared on 30-day postoperative mortality, length of hospital stay, cardiovascular and infectious morbidities, vasopressor requirement, and intraoperative hemodynamics. RESULTS Patients given etomidate had 2.5 (98% confidence interval [CI], 1.9-3.4) times the odds of dying than those given propofol. Etomidate patients also had significantly greater odds of having cardiovascular morbidity (odds ratio [OR] [98% CI]: 1.5 [1.2-2.0]), and significantly longer hospital stay (hazard ratio [95% CI]: 0.82 [0.78-0.87]). However, infectious morbidity (OR [98% CI]: 1.0 [0.8-1.2]) and intraoperative vasopressor use (OR [95% CI] 0.92: [0.82-1.0]) did not differ between the agents. CONCLUSION Etomidate was associated with a substantially increased risk for 30-day mortality, cardiovascular morbidity, and prolonged hospital stay. Our conclusions, especially on 30-day mortality, are robust to a strong unmeasured binary confounding variable. Although our study showed only an association between etomidate use and worse patients' outcomes but not causal relationship, clinicians should use etomidate judiciously, considering that improved hemodynamic stability at induction may be accompanied by substantially worse longer-term outcomes.


title: Interferon gamma modulation of disease manifestation and the local antibody response to alphavirus encephalomyelitis.

text: Infection of mice with Sindbis virus (SINV) produces encephalomyelitis and provides a model for examination of the central nervous system (CNS) immune response to alphavirus infection. Clearance of infectious virus is accomplished through a cooperative effort between SINV-specific antibody and IFN-γ, but the regulatory interactions are poorly understood. To determine the effects of IFN-γ on clinical disease and the antiviral immune response, C57BL/6 mice lacking IFN-γ (Ifng-/-) or IFN-γ receptor (Ifngr1-/-) were studied in comparison to WT mice. Maximum production of Ifng mRNA and IFN-γ protein in the CNS of WT and Ifngr1-/- mice occurred 5-7 days after infection, with higher levels of IFN-γ in Ifngr1-/- mice. Onset of clinical disease was earlier in mice with impaired IFN-γ signalling, although Ifngr1-/- mice recovered more rapidly. Ifng-/- and Ifngr1-/- mice maintained body weight better than WT mice, associated with better food intake and lower brain levels of inflammatory cytokines. Clearance of infectious virus from the spinal cords was slower, and CNS, but not serum, levels of SINV-specific IgM, IgG2a and IgG2b were lower in Ifngr1-/- and Ifng-/- mice compared to WT mice. Decreased CNS antiviral antibody was associated with lower expression of mRNAs for B-cell attracting chemokines CXCL9, CXCL10 and CXCL13 and fewer B cells in the CNS. Therefore, IFN-γ signalling increases levels of CNS pro-inflammatory cytokines, leading to clinical disease, but synergistically clears virus with SINV-specific antibody at least in part by increasing chemokine production important for infiltration of antibody-secreting B cells into the CNS.


Early Observation and Mitigation of Challenges in Diabetes Management of COVID-19 Patients in Critical Care Units.


title: Predictors of remission with placebo using an integrated study database from patients with major depressive disorder.

text: OBJECTIVE To identify predictors of remission with placebo treatment in double-blind randomized controlled trials (RCTs) in major depressive disorder (MDD). METHOD A total of 1017 placebo-treated patients with baseline Hamilton Depression rating scale (HAMD) total ≥15 from eight duloxetine RCTs were included. Remission was defined as endpoint (7-8 weeks) HAMD total ≤7. Data were randomly split into training data (N = 813, 80%) for model selection and test data (N = 204, 20%) for validation. Logistic regression and classification and regression tree (CART) methods were used to identify predictors of remission. Predictive accuracy of models was assessed by Receiver Operator Characteristic (ROC) curves. RESULTS Baseline predictors for remission with placebo consistently identified with the logistic regression and CART analysis were less severe depressive symptoms (based on HAMD core symptoms), younger age, less anxiety (based on HAMD anxiety/somatization), and shorter current MDD episode duration. Associated cut-off values from the CART method characterized patient groups according to their remission likelihood. However, the predictive accuracy was modest for both methods with areas under the ROC curve of 0.6-0.65 based on test data. CONCLUSION The derived models, although of limited value for predicting remission in individual patients, may be useful for adjusting for placebo effects in clinical trials.


title: The perils of practicum in the time of COVID-19: A graduate student's perspective.

text: The COVID-19 pandemic has placed competing demands on many graduate students working at practica. Though graduate programs seek to minimize potential sources of exposure to the virus, some practicum sites rely on students as essential staff. At the same time, although some students may wish to eliminate this source of potential exposure to the virus, other students may consider the opportunity to fulfill their practicum duties at a time of crisis an important part of their educational experience. Guidance published by the Association of Psychology Postdoctoral and Internship Centers regarding internship students provides at least a starting point for programs to develop policies that allow students to make informed decisions about their practicum training. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Nucleotide Sequence Analysis of S1 Gene among Iranian Avian Infectious Bronchitis Viruses Isolated during 2001-2002.

text: Infectious bronchitis (IB) virus genome codes for four structural proteins, among which the S1 subunit of spike glycoprotein comprises the major epitopes to induce neutralizing antibodies. This study involved the comparison of the full S1 sequences of five IB viruses, namely two Massachusetts and three 793/B serotypes, isolated from IB outbreaks during 2001-2002, with all other Iranian and foreign 793/B isolates and 10 known serotypes. Analysis of S1 subunit showed three unique amino acid changes at positions 349 (V to L), 392 (T to N), and 393 (Q or R to T or K or S) for the Iranian 793/B isolates, compared to those of the foreign 793/B isolates reported before 2006 (onset of vaccination with 793/B vaccine in Iran). They were used as amino acid markers for the differentiation of Iranian 793/B isolates for years. Sequence alignment of the Iranian isolates with those of the foreign ones reported after 2006 demonstrated that amino acids 392 and 393 were no longer considered as amino acid markers, and only the change in amino acid 349 still remained specific to the Iranian 793/B isolates. Phylogenetic tree sequence analysis revealed that the Iranian 793/B isolates were closely related indicating that they came from a single source, more probably from France. There was a very close correlation between the first detection of 793/B serotype and the time of French chicken meat importation. Moreover, it was shown that one of the Massachusetts isolates was completely identical with the H120 vaccine strain. Furthermore, the other Massachusetts isolate with two amino acid changes at positions 64 (G to E) and 95 (S to R) was very similar to this vaccine strain. It seems that the latter isolate is a passaged chicken H120 vaccine strain.


title: Mechanical properties and fibrin characteristics of endovascular coil-clot complexes: relevance to endovascular cerebral aneurysm repair paradigms.

text: BACKGROUND Although coil embolization is known to prevent rebleeding from acutely ruptured cerebral aneurysms, the underlying biological and mechanical mechanisms have not been characterized. We sought to determine if microcoil-dependent interactions with thrombus induce structural and mechanical changes in the adjacent fibrin network. Such changes could play an important role in the prevention of aneurysm rebleeding. METHODS The stiffness of in vitro human blood clots and coil-clot complexes implanted into aneurysm phantoms were measured immediately after formation and after retraction for 3 days using unconfined uniaxial compression assays. Scanning electron microscopy of the coil-clot complexes showed the effect of coiling on clot structure. RESULTS The coil packing densities achieved were in the range of clinical practice. Bare platinum coils increased clot stiffness relative to clot alone (Young's modulus 6.9 kPa and 0.83 kPa, respectively) but did not affect fibrin structure. Hydrogel-coated coils prevented formation of a clot and had no significant effect on clot stiffness (Young's modulus 2 kPa) relative to clot alone. Clot age decreased fiber density by 0.2 fibers/µm(2) but not the stiffness of the bare platinum coil-clot complex. CONCLUSIONS The stiffness of coil-clot complexes is related to the summative stiffness of the fibrin network and associated microcoils. Hydrogel-coated coils exhibit significantly less stiffness due to the mechanical properties of the hydrogel and the inhibition of fibrin network formation by the hydrogel. These findings have important implications for the design and engineering of aneurysm occlusion devices.


title: Laparoendoscopic single-site surgery in gynecology: review of literature and available technology.

text: The objective of this article was to review the published literature on laparoendoscopic single-site surgery (LESS) in gynecology and to present current advances in instruments used in LESS surgery. Inasmuch as LESS surgery is relatively new, the current literature on use of this technique in gynecology is somewhat limited. Sixteen articles were available for the literature review: 10 case series, 2 comparative studies, 3 case reports, and 1 surgical technique demonstration. In recent years, however, improvements in traditional laparoscopic techniques and availability of more advanced instruments has made single-incision laparoscopy more feasible and safer for the patient. There is increasing interest in LESS surgery both as an alternative to traditional laparoscopy and as an adjunct to robotic surgery when performing complicated procedures through a single incision. Although LESS surgery provides another option in the arena of minimally invasive gynecologic surgery, the ultimate role of this approach remains to be determined.


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Carbon dioxide embolism during transanal total mesorectal excision (taTME).


title: Transanal total mesorectal excision for locally advanced middle-low rectal cancers.

text: BACKGROUND This study investigated the results of transanal total mesorectal excision (TaTME) combined with laparoscopy for locally advanced mid-low rectal cancer. METHODS Patients with mid-low locally advanced rectal cancer (T3 category or above and/or N+) who underwent rectal resection with TaTME technique were enrolled prospectively. Patients who had distant metastasis, multiple malignancies, intestinal obstruction or perforation, or a clinical complete response to chemoradiotherapy were excluded. Postoperative results, including morbidity, circumferential resection margin (CRM) assessment, short-term survival and functional outcomes, were analysed. RESULTS Thirty-eight patients, with 25 mid and 13 low rectal tumours, who had elective resection by TaTME from March 2015 to September 2018 were included. There were 25 men and 13 women. Mean(s.d.) age was 58·2(16·4) years and mean(s.d.) BMI was 24·2(2·5) kg/m2 . Tumours were 3-9 cm from the anal verge. Mean(s.d.) duration of surgery was 210(42) min. All patients had hand-sewn anastomoses and protective ileostomies. There were no conversions, abdominal perineal resections or postoperative deaths. Four patients had a complication, including three presacral abscesses, all managed by transanastomotic drainage. At 3 months after ileostomy closure, all patients had perfect continence. Apart from a greater tumour diameter in patients with low rectal cancers (6·0 cm versus 4·6 cm in those with mid rectal tumours; P = 0·035), clinical features were similar in the two groups. CRM positivity was greater for low than for mid rectal tumours (3 of 13 versus 0 of 25 respectively; P = 0·034), and more patients with a low tumour had TME grade 2 (4 of 13 versus 1 of 25; P = 0·038). There was no difference in oncological outcomes at 17 months. CONCLUSION Although this study cohort was small, special attention should be paid to bulky low rectal tumours to reduce the rate of CRM positivity.


title: Intra-arterial versus intra venous contrast-enhanced computed tomography of the equine head.

text: BACKGROUND The anatomical complexity of the horse's head limits the abilities of radiography. Computed tomography (CT) in combination with contrast enhanced CT is used more often for diagnosing various head pathology in horses. The objective of this study was to compare intravenous and intra-arterial contrast-enhancement techniques and describe normal and abnormal contrast enhancement in the horse's head. RESULTS All 24 horses included in the study recovered without complication from the procedures. Compared to the pre-contrast studies, post-contrast studies showed significant contrast enhancement in the pituitary gland (IA: p < 0.0001; IV: p < 0.0001), IA nose septum (p = 0.002), nose mucosa (IA: p < 0.0001; IV: p = 0.02), parotid salivary gland (IA: p < 0.0001; IV p < 0.0001), cerebrum (IA: p < 0.0001; IV: p < 0.0001), rectus capitis muscle (IA: p < 0.0001; IV p = 0.001), IA temporal muscle (p < 0.0001), IA masseter muscle (p <0.0001) and IV brainstem (p = 0.01). No significant contrast enhancement was seen in the eye (IA: p = 0.23; IV p = 0.33), tongue (IA p = 0.2; IV p = 0.57), IA brainstem (p = 0.88), IV nose septum (p = 0.26), IV temporal muscle (p = 0.09) and IV masseter muscle (p = 0.46). Three different categories of abnormal enhancement were detected: a strong vascularised mass, an enhanced rim surrounding an unenhanced structure and an inflamed anatomical structure with abnormal contrast enhancement. CONCLUSION Using the intra-arterial technique, similar contrast enhancement is achieved using less contrast medium compared to the intravenous technique. And a potential major advantage of the IA technique is the ability to evaluate lesions that are characterized by increased blood flow. Using the intravenous technique, a symmetrical and homogenous enhancement is achieved, however timing is more crucial and the contrast dosage is more of influence in the IV protocol. And a potential major advantage of the IV technique is the ability to evaluate lesions that are characterized by increased vascular permeability. Knowing the different normal contrast enhancement patterns will facilitate the recognition of abnormal contrast enhancements.


title: Failure of respiratory defenses in the pathogenesis of bacterial pneumonia of cattle.

text: The respiratory system is well defended against inhaled bacteria by a dynamic system of interacting layers, including mucociliary clearance, host defense factors including antimicrobial peptides in the epithelial lining fluid, proinflammatory responses of the respiratory epithelium, resident alveolar macrophages, and recruited neutrophils and monocytes. Nevertheless, these manifold defenses are susceptible to failure as a result of stress, glucocorticoids, viral infections, abrupt exposure to cold air, and poor air quality. When some of these defenses fail, the lung can be colonized by bacterial pathogens that are equipped to evade the remaining defenses, resulting in the development of pneumonia. This review considers the mechanisms by which these predisposing factors compromise the defenses of the lung, with a focus on the development of bacterial pneumonia in cattle and supplemented with advances based on mouse models and the study of human disease. Deepening our understanding of how the respiratory defenses fail is expected to lead to interventions that restore these dynamic immune responses and prevent disease.


title: Reprocessing semicritical items: Current issues and new technologies.

text: Semicritical medical devices are defined as items that come into contact with mucous membranes or nonintact skin (eg, gastrointestinal endoscopes, endocavitary probes). Such medical devices minimally require high-level disinfection. Because many of these items are temperature sensitive, low-temperature chemical methods are usually used rather than steam sterilization. Strict adherence to current guidelines is required because more outbreaks have been linked to inadequately cleaned or disinfected endoscopes and other semicritical items undergoing high-level disinfection than any other reusable medical device.


title: An alternative technique of the superselective catheterization of the ophthalmic artery for intra-arterial chemotherapy of the retinoblastoma: retrograde approach through the posterior communicating artery to the ophthalmic artery.

text: INTRODUCTION Superselective intra-arterial chemotherapy (IAC) in retinoblastoma has recently become a popular treatment option. In this study, we purposed to investigate the effectiveness of the technique of "retrograde approach through the posterior communicating artery to the ophthalmic artery (OA)" for IAC. METHODS A total of 12 unilateral retinoblastomas were treated with IAC in 29 sessions from October 2011 to November 2013. Of the 12 patients, 6 were male and 6 were female, with ages ranging from 12 to 72 months with a median age of 27.6 months. Left-to-right ratio for affected eye was 6/6. In the first 4 patients, we used the ipsilateral internal carotid artery (ICA) to reach the OA of the affected globe (10 sessions). Then, we used the vertebral artery, basilary artery, ipsilateral/contralateral P1 segment of the posterior cerebral artery, and ipsilateral/contralateral posterior communicating artery, respectively, to reach inside the OA at next 15 sessions. RESULTS At ipsilateral approach, fluoroscopy total time ranged from 16 to 34 min (mean 21.5 min), and the angle between ophthalmic segment of the ICA and proximal segment of the OA was ranged between 34° and 77° with an average angle of 53.4°. At retrograde approach, fluoroscopy total time ranged from 3 to 12 min (mean 7.5 min), and the angle between ophthalmic segment of the ICA and proximal segment of the OA was ranged between 147° and 178° with an average angle of 148.3°. CONCLUSION Retrograde approach makes the IAC procedure easier in retinoblastoma patients and shortens the fluoroscopy time.


title: Heterologous boosting with recombinant VSV-846 in BCG-primed mice confers improved protection against Mycobacterium infection.

text: Tuberculosis (TB) remains a major health problem worldwide, and the development of effective vaccines is urgently needed. Vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as primer and modified vaccinia virus Ankara strain expressing the mycobacterial antigen Ag85A (MVA85A) as booster may increase the protective efficacy of BCG. In addition, vaccination with the recombinant viral vaccine vesicular stomatitis virus (VSV)-846 (Rv3615c, Mtb10.4, and Rv2660c) can elicit a remarkable T-cell-mediated immune response and provide an effective long-term protection after the BCG challenge. In this study, we used VSV-846 to boost BCG and evaluated its immunogenicity in BALB/c mice. In this prime-boost approach, boosting with VSV-846 significantly enhanced IFN-γ CD4 T cell responses, which are crucial for anti-TB immune responses. Moreover, VSV-846 boosting significantly reduced pathology compared with mock vaccination, and decreased the bacterial loads in lung tissues compared with BCG or VSV-846 vaccination alone. The analysis of vaccine-induced immunity identified that polyfunctional T cells might contribute to the enhanced protection by VSV-846 boosting. This study proved that viral booster VSV-846 in mice improved the protection against mycobacteria infection, which could be helpful in designing an efficient vaccination strategy against TB in humans.


title: Single-incision subxiphoid approach for bilateral metastasectomy.

text: We report a case of single-incision bilateral partial lung resection using the subxiphoid approach. This approach requires a 3-cm incision in the abdomen, making it aesthetically favorable. In addition, it does not cause postoperative intercostal neuropathy, and postoperative pain is minimal because the intercostal space is bypassed. Moreover, this technique enables exposure to both lungs through a single incision and has potential for widespread use if maneuverability can be increased by improving the instruments used.


title: Flow Diversion for Ophthalmic Artery Aneurysms.

text: Endovascular treatments of ophthalmic segment aneurysms are commonly used but visual outcomes remain a concern. We performed a retrospective review of patients with carotid-ophthalmic aneurysms treated with flow diversion from June 2009 to June 2015. The following outcomes were studied through chart review: visual outcomes, complications, postoperative stroke and intraparenchymal hemorrhage, and clinical outcomes. Angiographic outcomes were studied with angiography and MRA at 6 months, 1 year, and 3 years. We evaluated 50 carotid-ophthalmic aneurysms in 48 patients, among whom 44 patients with 46 aneurysms underwent treatment. The mean clinical follow-up was 29 ± 22 months (range, 0-65 months). There were no permanent adverse visual outcomes. There was 1 death because of late intraparenchymal hemorrhage (2.2%). Six-month angiography showed complete occlusion in 24 of 37 patients (64.9%), and 3-year angiography results showed occlusion in 24 of 25 patients (96%). In conclusion, flow diversion is a safe and effective treatment for carotid-ophthalmic aneurysms in carefully selected patients. The risk of adverse visual outcomes is low, and most aneurysms progress to complete occlusion.


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title: Capillary nano-immunoassays: advancing quantitative proteomics analysis, biomarker assessment, and molecular diagnostics.

text: There is an emerging demand for the use of molecular profiling to facilitate biomarker identification and development, and to stratify patients for more efficient treatment decisions with reduced adverse effects. In the past decade, great strides have been made to advance genomic, transcriptomic and proteomic approaches to address these demands. While there has been much progress with these large scale approaches, profiling at the protein level still faces challenges due to limitations in clinical sample size, poor reproducibility, unreliable quantitation, and lack of assay robustness. A novel automated capillary nano-immunoassay (CNIA) technology has been developed. This technology offers precise and accurate measurement of proteins and their post-translational modifications using either charge-based or size-based separation formats. The system not only uses ultralow nanogram levels of protein but also allows multi-analyte analysis using a parallel single-analyte format for increased sensitivity and specificity. The high sensitivity and excellent reproducibility of this technology make it particularly powerful for analysis of clinical samples. Furthermore, the system can distinguish and detect specific protein post-translational modifications that conventional Western blot and other immunoassays cannot easily capture. This review will summarize and evaluate the latest progress to optimize the CNIA system for comprehensive, quantitative protein and signaling event characterization. It will also discuss how the technology has been successfully applied in both discovery research and clinical studies, for signaling pathway dissection, proteomic biomarker assessment, targeted treatment evaluation and quantitative proteomic analysis. Lastly, a comparison of this novel system with other conventional immuno-assay platforms is performed.


title: Local Control by Radiofrequency Thermal Ablation Increased Overall Survival in Patients With Refractory Liver Metastases of Colorectal Cancer.

text: Radiofrequency thermal ablation (RFA) is widely used for local solitary liver tumor control. However, the benefit of RFA for colorectal cancer with liver metastases, which is refractory to chemotherapy, remains unknown.We retrospectively enrolled 70 consecutive colorectal adenocarcinoma patients, who had synchronous liver metastases, who were refractory to chemotherapy, and whose life expectancy was >6 months, into this study to investigate the outcomes of RFA and associated prognostic factors. RFA was introduced to all of these patients during the enrollment. The time interval from RFA to recurrence of liver metastases and overall survival was recorded. Age, sex, carcinoembryonic antigen level, primary tumor location, postoperative adjuvant chemotherapy regimens, and the size and number of metastatic liver lesions were recorded. Cox regression analysis was used to determine the prognostic significance.Thirty-nine patients accepted RFA during chemotherapy, whereas 31 chose to receive chemotherapy alone. Patients with ≤5 and >5 liver metastases had median survival durations of 28 and 17 months, respectively (P = 0.018). The dominant liver tumor size (<5 vs ≥5 cm) was significantly associated with median survival (30 vs 17 months, respectively; P = 0.038), as was the carcinoembryonic antigen level (35 vs 16 months for ≤200 vs >200 ng/mL respectively; P = 0.029). Besides, radiofrequency thermal ablation plus chemotherapy was associated with a better median overall survival than chemotherapy alone (29 vs 12 months, respectively; P = 0.002). In multivariate analysis, only radiofrequency thermal ablation treatment and number of liver tumors were significant prognostic factors for survival. Our result further revealed that patients treated with radiofrequency thermal ablation had longer progression-free intervals than those treated with chemotherapy alone (18 vs 9 months, respectively; P = 0.001). Hence, radiofrequency thermal ablation is a safe and effective adjunct treatment to chemotherapy.


title: Glycan regulation of ER-associated degradation through compartmentalization.

text: The internal environment of the eukaryotic cell is divided by membranes into various organelles, containing diverse functional subcompartments, which allow complex cellular life. The quality control of newly made secretory proteins relies on the ability of the endoplasmic reticulum (ER) to segregate and compartmentalize molecules at different folding states. These folding states are communicated by N-glycans present on most secretory proteins. In ER-associated degradation (ERAD), protein molecules that have been identified as terminally misfolded are sent for degradation at the cytosolic proteasomes after being dislocated from the ER to the cytosol. This review will focus on how misfolded glycoprotein molecules are segregated from their properly folded counterparts and targeted to ERAD. The pathway involves compartmentalization, which is intimately linked to differential N-glycan processing. Recent data suggests that these processes are very dynamic, and include transient assembly of ERAD machinery complexes.


title: Early results of robotically assisted mitral valve repair in a single institution: report of the first 100 cases.

text: OBJECTIVE Robotically assisted mitral valve repair was approved for use in Japan in April 2018. The study objective was to assess the safety and clinical outcomes of robotic mitral valve surgery in the first 100 cases performed in our center. METHODS We reviewed the first 100 patients who underwent robotic primary mitral valve repair, including concomitant procedures, from April 2018 to August 2019. The cause of mitral valve disease was degenerative (n = 94), endocarditis (n = 2), functional (n = 2), and other (n = 2). RESULTS There was no in-hospital or 30-day mortality. Mitral valve repair was completed in all patients. Only one patient required conversion to full sternotomy due to left ventricular apex bleeding. In echocardiography performed before hospital discharge, the mitral regurgitation was graded as none or trivial in 94 patients (94%) and mild in 4 (4%). Only two patients required surgical re-intervention due to postoperative hemolysis with moderate mitral regurgitation. For patients who underwent the mitral valve procedure alone, the median times of the total operation, cardiopulmonary bypass, aortic clamping, and console usage were 185, 112, 71, and 60 min, respectively. The learning curve showed that the operation time decreased slightly during the first ten cases and then plateaued at a mean of approximately 180 min. CONCLUSIONS Robotically assisted mitral valve repair was feasible, safe, and therapeutically effective in the first 100 cases, with a minimal learning curve. The robotically assisted approach provides a high-quality surgical view and tremorless suture/cut handling, which will contribute to further development of minimally invasive mitral valve surgery.