title: Management of Large Cecal Polyps: When Can the Ileocecal Valve Be Spared?

text: BACKGROUND Endoscopic mucosal resection comprises the first-line treatment for large cecal polyps. With up to 14% of unresectable colonic polyps harboring malignancy, the management of endoscopically unresectable cecal polyps remains an oncologic right hemicolectomy, which can be associated with substantial postoperative morbidity. OBJECTIVE This study compares the outcomes of patients with cecal polyps who underwent either endoscopic mucosal resection, a cecectomy, or a right hemicolectomy. DATA SOURCES Patients undergoing either endoscopic mucosal resection, partial cecectomy, or right hemicolectomy from 2008 to 2017 at a single tertiary care institution were selected. STUDY SELECTION This was a retrospective cohort study. MAIN OUTCOME MEASURES The primary outcomes measured were the rate of malignancy, complication rate, estimated blood loss, and hospital length of stay between surgical cohorts. RESULTS One hundred twenty-nine patients with cecal polyps were identified, of which 52 were referred for surgery. Nineteen underwent partial cecectomy and 33 (27.3%) underwent right hemicolectomy. Two patients undergoing cecectomy required conversion to hemicolectomy because the resected specimen did not contain the polyp. The 2 surgical cohorts did not differ significantly regarding age, sex, or ASA classification. Procedural complication rates were higher among those undergoing hemicolectomy compared with those undergoing cecectomy (37.1% versus 5.9%, p = 0.02). Estimated blood loss (50 vs 10 mL, p = 0.02), operative duration (98 vs 76 minutes, p = 0.009), and length of stay (4 vs 2 days, p < 0.001) were higher in patients undergoing hemicolectomy than in those undergoing cecectomy. No invasive malignancies were identified on final pathology within the cecectomy cohort. LIMITATIONS Single-institution data and retrospective design were limitations of this study. CONCLUSIONS In tertiary centers, the majority of large cecal polyps are benign and can be addressed by using endoscopic mucosal resection. When involvement of the appendiceal orifice or ileocecal valve precludes endoscopic treatment, surgical resection is the standard of care. In the subset of cases not involving the ileocecal valve and without preoperative evidence of malignancy, partial cecectomy spares the ileocecal valve and can offer reduced postoperative morbidity compared with a formal right hemicolectomy. See Video Abstract at http://links.lww.com/DCR/A674.


title: Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans.

text: PURPOSE Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. The purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans. METHODS Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application. RESULTS Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 h in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores). CONCLUSION This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases.


title: Early diffuse recurrence of hepatocellular carcinoma after percutaneous radiofrequency ablation: analysis of risk factors.

text: OBJECTIVE To evaluate the risk factors affecting early diffuse recurrence within 1 year of percutaneous ultrasound-guided radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS Out of 146 patients who received transcatheter arterial chemoembolisation (TACE) for treatment of recurrent HCC after percutaneous ultrasound-guided RFA, we selected 23 patients with early diffuse recurrence. Early diffuse recurrence was defined as three or more new recurrent HCCs within 1 year of initial RFA. As a control group, we selected 23 patients, matched exactly for age and sex, in which there was no local tumour progression or new recurrence after RFA. To analyse the risk factors, we examined patient factors and tumour factors. RESULTS Recurrent tumours occurred from 30 to 365 days after RFA (median time, 203 days). Univariate analysis indicated that larger tumour size and poorly defined margin were significant risk factors (P < 0.05). Multivariate analysis indicated that poorly defined margin was a significant risk factor (P < 0.05). CONCLUSION Larger tumour size and poorly defined margin may be risk factors for early diffuse recurrence of HCC within 1 year of RFA. Tumours with such risk factors should be treated with a combination of TACE to minimise the potential for therapeutic failure.


title: Muscarinic receptors modulate Nerve Growth Factor production in rat Schwann-like adipose-derived stem cells and in Schwann cells.

text: Regenerative capability of the peripheral nervous system after injury is enhanced by Schwann cells (SCs) producing several growth factors. The clinical use of SCs in nerve regeneration strategies is hindered by the necessity of removing a healthy nerve to obtain the therapeutic cells. Adipose-derived stem cells (ASCs) can be chemically differentiated towards a SC-like phenotype (dASCs), and represent a promising alternative to SCs. Their physiology can be further modulated pharmacologically by targeting receptors for neurotransmitters such as acetylcholine (ACh). In this study, we compare the ability of rat dASCs and native SCs to produce NGF in vitro. We also evaluate the ability of muscarinic receptors, in particular the M2 subtype, to modulate NGF production and maturation from the precursor (proNGF) to the mature (mNGF) form. For the first time, we demonstrate that dASCs produce higher basal levels of proNGF and mature NGF compared to SCs. Moreover, muscarinic receptor activation, and in particular M2 subtype stimulation, modulates NGF production and maturation in both SCs and dASCs. Indeed, both cell types express both proNGF A and B isoforms, as well as mNGF. After M2 receptor stimulation, proNGF-B (25 kDa), which is involved in apoptotic processes, is strongly reduced at transcript and protein level. Thus, we demonstrate that dASCs possess a stronger neurotrophic potential compared to SCs. ACh, via M2 muscarinic receptors, contributes to the modulation and maturation of NGF, improving the regenerative properties of dASCs.


title: N-butyl cyanoacrylate embolization using a detachable tip microcatheter: initial experience.

text: INTRODUCTION Endovascular embolization of intracranial vascular malformations with N-butyl cyanoacrylate (nBCA) using a detachable tip microcatheter allows prolonged injection and decreases the risk of catheter retention. METHODS Between March and December 2013, the Apollo 1.5 cm detachable tip microcatheter was used in five patients after being approved by both the Food and Drug Administration and the institutional review board as a compassionate use device. Nine pedicles were embolized and the follow-up ranged from 1 to 3 months. RESULTS Five of the nine catheter tips detached. The length of reflux was not directly associated with the detachment of the distal tip. There were no cases of premature microcatheter detachment during navigation, manipulation with multiple microguidewire reintroduction and guidance. There was no leak of embolic agent at the detachment zone. Follow-up showed the detached tip to be stable without migration. CONCLUSIONS A detachable tip microcatheter offers an advance in the safety and effectiveness of nBCA embolization. Catheter retrieval becomes more controlled and less traumatic. Our initial experience is encouraging, and more experience is needed to categorically ascertain its safety and efficacy.


title: Angiotensin converting enzyme 2 and the kidney.

text: PURPOSE OF REVIEW Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes angiotensin II (AngII). AngII levels can be modulated by ACE2 in tissues where the enzyme is highly expressed, such as the kidney. In the kidney, ACE2 has the potential to regulate the intrarenal renin-angiotensin system (RAS), which can impact blood pressure and renal injury. Thus, in disease states where the RAS is often upregulated, the function of ACE2 plays a particularly important role. This review highlights the results of recent studies that demonstrate the interplay between ACE2 and the kidney under normal and pathological conditions. RECENT FINDINGS ACE2 has been reported to play a key role in renal and cardiovascular function. Recent studies have implicated shedding of the membrane-bound ectodomain of ACE2 as one way in which the enzyme can be regulated and enzymatic activity altered. This posttranslational modification releases a fragment which retains enzymatic activity, and thus provides a novel mechanism by which the RAS can be altered in response to physiological stimuli. Decreased ACE2 activity is associated with increased blood pressure, diabetes, and oxidative stress, whereas, increased levels of ACE2 appear to be renoprotective. SUMMARY A growing body of evidence, involving both experimental and human studies, points out the crucial role that ACE2 plays on the modulation of renal injury. Thus, therapeutic targets aiming to increase ACE2 activity and the ACE2-Ang(1-7)-MasR axis could potentially become clinically relevant, especially in disease states where the renal RAS is upregulated.


title: Application of Enhanced Recovery After Surgery in Single-incision Laparoscopic Distal Gastrectomy.

text: BACKGROUND Recently, enhanced recovery after surgery (ERAS) was widely used in the perioperative management of gastric cancer. The study aimed to evaluate the safety and effectiveness of ERAS in single-incision laparoscopic distal gastrectomy (SIDG). MATERIALS AND METHODS A total of 90 patients who received laparoscopic gastric cancer resection were divided into 3 groups: group A (n=30), underwent traditional multiport laparoscopic distal gastrectomy with conventional perioperative management; group B (n=30) underwent traditional multiport laparoscopic distal gastrectomy with ERAS concept; and group C (n=30), underwent SIDG with ERAS concept. Clinical data and gut function were assessed in 3 groups. RESULTS There were no significant differences in terms of postoperative complication, number of resected lymph nodes and blood loss among 3 groups. However, operation time was longer (P=0.003) and treatment cost was higher (P<0.001) in group C than that in group A and B. Group C had faster recovery of bowel function (P<0.001), shorter postoperative hospital stay (P=0.002), and less postoperative complication (P=0.044) than those in group A. There were no significant differences in terms of recovery of bowel function and postoperative hospital stay between group C and B (all P>0.05). The white blood cell counts were lower than group A and B (all P<0.05) and C-reactive protein in group C were lower than group A (P<0.05) and B (P>0.05). CONCLUSIONS The findings suggest that SIDG with ERAS may be a feasible and safe procedure for early gastric cancer because it provides a favorable cosmetic result while not compromising postoperative complications, number of resected lymph nodes, and blood loss.


title: Fighting pandemics: Inspiration from Islam.

text: Infectious disease has killed more people than any other cause throughout history. The current pandemic of coronavirus disease (COVID-19) has again revealed how vulnerable we remain. Muslims constitute the world's second-largest religious group, making up about a quarter of the world population. They have distinctive faith and culture, pertaining to their religious beliefs and practices that need special attention, in situations such as current COVID-19 pandemic. Congregational prayers are an indispensable part of Islamic culture. Performance of obligatory prayers in congregation is compulsory and mandatory for every Muslim adult male who has no excuse for not doing so. But, doing so during a pandemic can help in the spread of the COVID-19. Muslims look up to the Holy Qur'an and teachings of Prophet (PBUH) (Hadiths) for guidance under all the circumstances. In this review we will cover how Islamic teaching can guide us to manage pandemics like COVID-19.


What I learnt from studying doctors' mental health over 20 years-an essay by Jenny Firth-Cozens.


title: Effect of diclofenac on cyclooxygenase-2 levels and early breaking strength of experimental colonic anastomoses and skin incisions.

text: BACKGROUND Recently, there has been a focus on the effect of the nonsteroidal anti-inflammatory drugs on the anastomotic leakage rate after colorectal surgery. METHODS An experimental, randomized, placebo-controlled prospective study on 32 male Wistar rats was carried out. We examined the effect of diclofenac 4 mg/kg/day on the cyclooxygenase-2 (COX-2) enzyme in the anastomotic tissue and on the breaking strength of anastomotic and incisional wounds. The operation was performed with colonic resection and hand-sewn anastomosis. After 3 days, the rats were sacrificed and the breaking strength and the COX-2 content of the anastomosis were measured. RESULTS There was a significantly reduced level of COX-2 in the rats treated with diclofenac (p = 0.001); no significant differences in any of the breaking strength measurements and no significant correlation between COX-2 levels and breaking strength of the anastomotic or incisional wounds could be found (p = 0.073 and p = 0.727). CONCLUSION This study for the first time showed that a diclofenac dose of 4 mg/kg/24 h was sufficient to reduce the level of COX-2 enzymes in the anastomotic tissue in rats. This inhibition of the inflammatory response did not lead to reduced breaking strength of either anastomotic or incisional wounds. Whether there is a detrimental effect of COX inhibition on colorectal anastomoses in the clinical setting remains controversial.


title: Single-incision totally extraperitoneal inguinal hernia repair: our initial 100 cases and comparison with conventional three-port laparoscopic totally extraperitoneal inguinal hernia repair.

text: PURPOSE To compare the outcomes of single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS-TEP) and conventional three-port totally extraperitoneal (TEP) repair. METHODS We performed a retrospective analysis of 137 patients (SILS-TEP, 100; conventional TEP, 37) scheduled to undergo elective inguinal hernia from January 2011 to July 2013 at Osaka Police Hospital. RESULTS There were no significant differences in the patient demographics. There were no significant differences in the length of the operation between the two groups (SILS-TEP group, 93 min vs. conventional TEP group, 92 min for unilateral hernias, p = 0.8; SILS-TEP group, 142 min vs. conventional TEP, 128 min for bilateral hernias, p = 0.4). The postoperative hospital stay, total medical charge for the hospital stay and the numerical rating scale before and 3 months after surgery were comparable in both groups. Two cases treated by SILS-TEP repair were converted to conventional three-port TEP repair (one case) and mesh-plug method (one case). The postoperative complications were comparable in both groups, and these were managed conservatively. One recurrence (2 %, 1/37) developed in the conventional TEP group, compared with 0 recurrences (0/100) in the SILS-TEP group. CONCLUSIONS SILS-TEP repair seems to be safe and feasible, with no significant differences in the total medical charges for the hospital stay or the postoperative pain score 3 months after surgery compared with conventional three-port TEP repair.


title: White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies.

text: Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural underpinnings of alcohol teratogenesis. This technique can detect alterations in white matter in neurodevelopmental disorders, such as fetal alcohol spectrum disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted on individuals with prenatal alcohol exposure (PAE). These studies confirm the widespread nature of brain damage in PAE by reporting diffusivity alterations in commissural, association, and projection fibers; and in relation to increasing cognitive impairment. Reduced integrity in terms of lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported more consistently in the corpus callosum, cerebellar peduncles, cingulum, and longitudinal fasciculi connecting frontal and temporoparietal regions. Although these interesting results provide insight into FASD neuropathology, it is important to investigate the clinical diversity of this disorder for better treatment options and prediction of progression. The aim of this review is to provide a summary of different patterns of neural structure between PAE and typically developed individuals. We further discuss the association of alterations in diffusivity with demographic features and symptomatology of PAE. With the accumulated knowledge of the neural correlates of FASD presenting symptoms, a comprehensive understanding of the heterogeneity in FASD will potentially improve the disease management and will highlight the diagnostic challenges and potential areas of future research avenues, where neural markers may be beneficial.


title: Keeping the Family in Family Medicine.

text: In this personal reflection, as a Family Medicine resident at an Academic Center in Northeast Florida, as well as being a chronic illness patient myself, I explore the notion of dying alone and away from family. Although COVID-19 has changed the practice of medicine in many ways, prior to that, and before the instillation of hospital no-visitor policies and stay at home orders, I experienced a case of a patient dying alone in the hospital. These chronicles that case and the impact it had on me afterward in regard to my own family and how I hope the future of medicine can address this.


title: From SARS coronavirus to novel animal and human coronaviruses.

text: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic.


title: Assessing sinus aerosol deposition: benefits of SPECT-CT imaging.

text: PURPOSE Aerosol inhalation therapy is one of the methods to treat rhinosinusitis. However the topical drug delivery to the posterior nose and paranasal sinuses shows only limited efficiency. A precise sinusal targeting remains a main challenge for aerosol treatment of sinus disorders. This paper proposes a comparative study of the nasal deposition patterns of micron and submicron particles using planar gamma-scintigraphy imaging vs. a new 3-dimensional (3D) imaging approach based on SPECT-CT measurements. METHODS Radiolabelled nebulizations have been performed on a plastinated model of human nasal cast coupled with a respiratory pump. First, the benefits provided by SPECT-CT imaging were compared with 2D gamma-scintigraphy and radioactive quantification of maxillary sinus lavage as reference for the sonic 2.8 μm aerosol sinusal deposition. Then, the impact on nasal deposition of various airborne particle sizes was assessed. RESULTS The 2D methodology overestimates aerosol deposition in the maxillary sinuses by a factor 9 whereas the 3D methodology is in agreement with the maxillary sinus lavage reference methodology. Then with the SPECT-CT approach we highlighted that the higher particle size was mainly deposited in the central nasal cavity contrary to the submicron aerosol particles (33.8 ± 0.6% of total deposition for the 2.8 μm particles vs. 1 ± 0.3% for the 230 nm particles). CONCLUSION Benefits of SPECT/CT for the assessment of radiolabelled aerosol deposition in rhinology are clearly demonstrated. This 3D methodology should be preferentially used for scintigraphic imaging of sinusal deposition in Human.


title: Comparative clinical study of Bactigras and Telfa AMD for skin graft donor-site dressing.

text: The Bactigras(®) paraffin tulle coated with chlorhexidine is normally used for the treatment of donor-site wounds in burn patients who received split-thickness skin grafts in several centers. It has some disadvantages, such as adhesion to wound surfaces and pain from the irritation caused by this dressing. The Telfa AMD(®), a non-adherent wound dressing which consists of absorbent cotton fibers impregnated with polyhexamethylene biguanide enclosed in a sleeve of thermoplastic polymers, is a new option for donor-site wound care which causes less adherence to the wound. The purpose of this study was to compare clinical efficacy of these two dressings for the management of donor-site wounds. Thirty-two patients who received split-thickness skin grafts by donor site harvesting from the thigh were enrolled in this study and randomized into two groups receiving either the Bactigras(®) or the Telfa AMD(®) wound treatment. Re-epithelialization, pain, infection and cost-effectiveness analyses were compared between both groups. The results showed that there was no significant difference in age, area of donor sites or length of hospital stays between the groups (p > 0.05). However, the day of re-epithelialization (≥90%) was significantly shorter in patients treated with the Telfa AMD(®) compared to the Bactigras(®) group (14.00 ± 3.05 vs. 9.25 ± 1.88 days for Bactigras(®) and Telfa AMD(®) groups, respectively, p < 0.001). The average pain score was also significantly lower in the Telfa AMD(®) group (1.57 ± 0.55 vs. 4.70 ± 1.16, p < 0.001). There was no difference in the cost of treatment between the groups (4.64 ± 1.97 vs. 5.72 ± 2.54 USD, p = 0.19). This study indicated that the Telfa AMD(®) was an effective dressing for the treatment of donor-site wounds.


title: Late-onset bronchopleural fistula after lobectomy and adjuvant chemotherapy for lung cancer: A case report and review of the literature.

text: RATIONALE Late-onset bronchopleural fistula (BPF) induced by chemotherapy after lobectomy for lung cancer is rarely reported, lacking reliable preventive approaches. A timely identification and individualized treatment is essential for prognosis. PATIENT CONCERNS A 52-year-old female patient complained of fever, productive cough, and fatigue 1 week after adjuvant chemotherapy following right lower lobectomy and systemic mediastinal lymph node dissection. Chest computed tomography (CT) indicated pneumothorax and thick-walled empyema cavity within her right-sided thorax. DIAGNOSES The patient was diagnosed as late-onset BPF based on clinical manifestation and chest radiography. INTERVENTIONS In addition to antibiotics, a chest tube was reinserted under CT guidance, and vacuum suction was utilized for continuous drainage. Next cycle of adjuvant chemotherapy was terminated. OUTCOMES The empyema cavity was gradually closed in 1 month after conservative treatment, and the patient survived with good condition up to now. LESSONS Late-onset BPF should be kept in mind when the patient suffered from productive cough and chills during postoperative chemotherapy. And a prompt conservative management might be effective.


title: Effects of anti-VEGF on predicted antibody biodistribution: roles of vascular volume, interstitial volume, and blood flow.

text: BACKGROUND The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. METHODOLOGY/PRINCIPAL FINDINGS Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. CONCLUSIONS/SIGNIFICANCE These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF.


Immune biomarker-based enrichment in sepsis trials.


title: Programmed -1 frameshifting efficiency correlates with RNA pseudoknot conformational plasticity, not resistance to mechanical unfolding.

text: Programmed -1 frameshifting, whereby the reading frame of a ribosome on messenger RNA is shifted in order to generate an alternate gene product, is often triggered by a pseudoknot structure in the mRNA in combination with an upstream slippery sequence. The efficiency of frameshifting varies widely for different sites, but the factors that determine frameshifting efficiency are not yet fully understood. Previous work has suggested that frameshifting efficiency is related to the resistance of the pseudoknot against mechanical unfolding. We tested this hypothesis by studying the mechanical properties of a panel of pseudoknots with frameshifting efficiencies ranging from 2% to 30%: four pseudoknots from retroviruses, two from luteoviruses, one from a coronavirus, and a nonframeshifting bacteriophage pseudoknot. Using optical tweezers to apply tension across the RNA, we measured the distribution of forces required to unfold each pseudoknot. We found that neither the average unfolding force, nor the unfolding kinetics, nor the parameters describing the energy landscape for mechanical unfolding of the pseudoknot (energy barrier height and distance to the transition state) could be correlated to frameshifting efficiency. These results indicate that the resistance of pseudoknots to mechanical unfolding is not a primary determinant of frameshifting efficiency. However, increased frameshifting efficiency was correlated with an increased tendency to form alternate, incompletely folded structures, suggesting a more complex picture of the role of the pseudoknot involving the conformational dynamics.


title: Anti-IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL). A Placebo-controlled, Double-Blind Study.

text: RATIONALE Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. OBJECTIVES To study the effect of mepolizumab on virus-induced immune responses in mild asthma. METHODS Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV1, FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. MEASUREMENTS AND MAIN RESULTS Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV1, FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. CONCLUSIONS Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils. Clinical trial registered with www.clinicaltrials.gov (NCT 01520051).


title: Are you suffering from a large arterial occlusion? Please raise your arm!

text: Background and purpose Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke. Methods Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined. Results The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively. Conclusions Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions.


title: Difficult tracheal tube passage and subglottic airway injury during intubation with the GlideScope® videolaryngoscope: a randomised, controlled comparison of three tracheal tubes.

text: Difficulty during placement of the tracheal tube is a known problem when intubating with the GlideScope® , which may lead to subglottic airway injury. This randomised, controlled clinical trial was designed to compare the resistance to passage of PVC (polyvinyl chloride), reinforced or BlockBuster tracheal tubes during intubation with the GlideScope. Secondary outcomes included the time taken to intubate and assessment of subglottic airway injury. One-hundred and seventy-seven patients were included in the data analysis. There was difficult tracheal tube passage (moderate or severe resistance) in 15 (21.4%) patients using the PVC tube compared with 4 (7.4%) and 1 (1.9%) using the reinforced and BlockBuster tubes, respectively (p = 0.003 for PVC vs. BlockBuster). The median (IQR [range]) time taken to intubate was 35 (27-45 [15-115]) s, 25 (20-27 [15-110]) s and 25 (22-30 [16-90]) s, respectively, (p < 0.001 for PVC vs. reinforced as well as PVC vs. BlockBuster). Subglottic airway injury, assessed using a fibreoptic bronchoscope after extubation, was higher with the PVC tube (p < 0.001) and the reinforced tube (p = 0.012) compared with the BlockBuster tube. We conclude that the BlockBuster tracheal tube is a better choice for orotracheal intubation with the GlideScope than PVC or reinforced tubes.


title: Single-portal access laparoscopic radical nephrectomy for renal cell carcinoma in transplant patients: the first experience.

text: We present the details of the first three single-portal access laparoscopic radical nephrectomies (S-Portal-RN) performed in patients with a malignant renal tumour that developed after a renal transplant. The mean operative time was 171.6 ± 37.5 min, with a mean blood loss of 126.6 ± 25.1 ml. A single small skin incision (5 cm) was performed to remove the kidney. No significant difference in glomerular filtration rate was observed postoperatively. The postoperative recovery was uneventful with favourable short-term outcomes and high patient satisfaction at the 2-mo follow-up. We believe that S-Portal-RN for renal cancer after a renal transplant can be performed without increased risks for the patients or for the transplanted kidney.


title: The link between anemia and adverse outcomes in patients with acute coronary syndrome.

text: INTRODUCTION Anemia is one of the most frequent comorbidities in acute coronary syndrome (ACS) patients and is associated with a significant impact on clinical outcomes. This review summarizes the knowledge and updated management of anemia in the setting of ACS. Areas covered: We provide a review on the prevalence, pathophysiology, prognosis, impact, and updated management of anemia. Expert opinion: Patients with anemia represent a therapeutic challenge in the setting of acute coronary syndrome and require specific acute and chronic management. Despite the high prevalence of anemia and the large amount of data confirming its strong impact on short- and long-term outcomes, a commonly used and accurate definition in the context of patients undergoing percutaneous coronary intervention and stent implantation for ACS is still lacking. Furthermore, therapeutic options to address anemia remain limited. The combined use of risk scores to identify high-risk characteristics for adverse bleeding or thrombotic events may guide individualized treatment of anemic patients, for example, by selecting an antiplatelet regimen aimed at minimizing bleeding or thrombotic risk. The optimal strategy for blood transfusion is currently being evaluated by an ongoing randomized trial.


title: Laparoscopic colpotomy using monopolar electrocautery: does power really matter?

text: OBJECTIVE The purpose of this study was to assess the extent and rate of vaginal tissue injury associated with the utilization of various monopolar electrosurgical power settings when laparoscopically transecting vaginal tissue. METHODS This is an Institutional Animal Care and Use Committee-approved prospective, paired, single-blinded study. Externalized porcine vagina was transected using monopolar energy at 30, 50, and 80 W in the cut mode with laparoscopic Endo Shears. The slides were prepared and stained with both hematoxylin-eosin and Masson trichrome and were examined by board-certified veterinary pathologists blinded to the study. RESULTS There were 18 swine; each animal was tested on all 3 power settings (n = 54). Tissue injury was measured to a mean (SD) of 767 (519) μm at 30 W, 690 (600) μm at 50 W, and 556 (470) μm at 80 W. When comparing the monopolar settings, the results were as follows: 30 versus 50 W (P = 0.33), 30 versus 80 W (P = 0.067), and 50 versus 80 W (P = 0.17). The mean (SD) time for complete transection was measured at each power setting (n = 18), with 35.8 (5.4) seconds for 30 W, 13.5 (5.5) seconds for 50 W, and 8.4 (5.1) seconds for 80 W (P < 0.001). There was a statistically significant difference in the mean (SD) rates of injury, with 20.8 (8.8) μm/s at 30 W, 39.8 (11.8) μm/s at 50 W, and 50.1 (19.2) μm/s at 80 W (P = 0.01). CONCLUSIONS Using various power settings of monopolar energy may not make a significant difference in swine vaginal tissue damage at the time of colpotomy. However, there was a significant difference in the times and rates at which tissue was transected when using higher powers. We recommend using the 50- or 80-W setting, as this will likely decrease surgical times without altering vaginal tissue damage.


Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems.


title: Vortioxetine for attention deficit hyperactivity disorder in adults: A randomized, double-blind, placebo-controlled, proof-of-concept study.

text: BACKGROUND: Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances. AIMS: This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design. METHODS: Patients aged 18-55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227). In study stage II, placebo non-responders (AISRS total score reduction <30% from stage I baseline) were re-randomized with a 1:1:1 ratio to six weeks of vortioxetine 10 or 20 mg/day, or placebo ( n = 59). RESULTS: Across the two study stages combined, ADHD symptoms improved by approximately eight AISRS points in all treatment groups, showing no difference from placebo for either dose of vortioxetine, the study thus failing to meet its primary endpoint. However, both doses of vortioxetine separated from placebo in improving overall patient functioning, as measured by the Sheehan Disability Scale. CONCLUSION: Studies are warranted to further investigate this suggested benefit of a multimodal antidepressant for patient functioning in ADHD while addressing issues of non-adherence and placebo response. The study confirmed vortioxetine 10 mg and 20 mg as generally well-tolerated.


title: Barriers and enablers to patient recruitment for randomised controlled trials on treatment of chronic wounds: A systematic review.

text: Randomised controlled trials represent the gold standard in intervention efficacy evaluation. However, suboptimal recruitment affects completion and the power of a therapeutic trial in detecting treatment differences. We conducted a systematic review to examine the barriers and enablers to patient recruitment for randomised controlled trials on chronic wound treatment. Review registration was under PROSPERO 2017:CRD42017062438. We conducted a systematic search of Ovid MEDLINE, EBSCOhost CINAHL, Ovid Cochrane Library, Ovid EMBASE, and Ovid PsycINFO databases in June 2017 for chronic wound treatment randomised controlled trials. Twenty-seven randomised controlled trials or qualitative studies met the inclusion criteria. Among the 24 randomised controlled trials, 21 were assessed as low quality in relation to recruitment, and 3 were assessed as high quality. All 27 studies reported barriers to recruitment in chronic wound randomised controlled trials. The reported barriers to recruitment were: study-related, patient-related, clinician-related, health system-related, and/or operational-related. No study reported recruitment enablers. To enhance randomised controlled trial recruitment, we propose the need for improved integration of research and clinical practice. To alleviate the problems arising from inadequate reporting of randomised controlled trials, the Consolidated Standards of Reporting Trials Statement could include an additional item on recruitment barriers. This approach will allow for increased awareness of the potential barriers to recruitment for Randomised controlled trials (RCTs) in both wound management and other health care research.


title: Development of bilateral tension pneumothorax under anesthesia in a Boerhaave's syndrome patient: a case report.

text: A 33-year-old male visited the emergency room with abdominal pain which developed after a vomiting episode. Based on the pneumomediastinum findings from a chest radiograph and a contrast-enhanced chest and abdominal computed tomography scan, the patient was diagnosed with Boerhaave's syndrome. Preoperative radiologic findings showed no pneumothorax or pleural effusion. Once anesthesia was administered, the patient developed near complete cardiopulmonary collapse due to a bilateral tension pneumothorax, which was treated by bilateral thoracentesis, followed by chest tube insertion. Despite a left side rupture, the damaged right lung was unable to overcome single right ventilation, so the surgery was completed via right thoracotomy. The ruptured site was treated, and the patient was transferred to the intensive care unit. We discuss the anesthetic implications of this disease and how to prevent fatal complications.


title: How Flow Reduction Influences the Intracranial Aneurysm Occlusion: A Prospective 4D Phase-Contrast MRI Study.

text: BACKGROUND AND PURPOSE Flow-diverter stents are widely used for the treatment of wide-neck intracranial aneurysms. Various parameters may influence intracranial aneurysm thrombosis, including the flow reduction induced by flow-diverter stent implantation, which is assumed to play a leading role. However, its actual impact remains unclear due to the lack of detailed intra-aneurysmal flow measurements. This study aimed to clarify this relationship by quantitatively measuring the intra-aneurysmal flow using 4D phase-contrast MR imaging. MATERIALS AND METHODS We acquired prospective pre- and post-stent implantation 4D phase-contrast MR imaging data of a consecutive series of 23 patients treated with flow-diverter stents. Velocity field data were combined with the intraprocedural 3D angiogram vessel geometries for precise intracranial aneurysm extraction and partial volume correction. Intra-aneurysmal hemodynamic modifications were compared with occlusion outcomes at 6 and 12 months. RESULTS The averaged velocities at systole were lower after flow-diverter stent implantation for all patients and ranged from 21.7 ± 7.1 cm/s before to 7.2 ± 2.9 cm/s after stent placement. The velocity reduction was more important for the group of patients with aneurysm thrombosis at 6 months (68.8%) and decreased gradually from 66.2% to 55% for 12-month thrombosis and no thrombosis, respectively (P = .08). CONCLUSIONS We propose an innovative approach to measure intracranial flow changes after flow-diverter stent implantation. We identified a trend between flow reduction and thrombosis outcome that brings a new insight into current understanding of the flow-diversion treatment response.


title: Hunting with lead: association between blood lead levels and wild game consumption.

text: BACKGROUND Wild game hunting is a popular activity in many regions of the United States. Recently, the presence of lead fragments in wild game meat, presumably from the bullets or shot used for hunting, has raised concerns about health risks from meat consumption. OBJECTIVE This study examined the association between blood lead levels (PbB) and wild game consumption. METHODS We recruited 742 participants, aged 2-92 years, from six North Dakota cities. Blood lead samples were collected from 736 persons. Information on socio-demographic background, housing, lead exposure source, and types of wild game consumption (i.e., venison, other game such as moose, birds) was also collected. Generalized estimating equations (GEE) were used to determine the association between PbB and wild game consumption. RESULTS Most participants reported consuming wild game (80.8%) obtained from hunting (98.8%). The geometric mean PbB were 1.27 and 0.84 microg/dl among persons who did and did not consume wild game, respectively. After adjusting for potential confounders, persons who consumed wild game had 0.30 microg/dl (95% confidence interval: 0.16-0.44 microg/dl) higher PbB than persons who did not. For all game types, recent (<1 month) wild game consumption was associated with higher PbB. PbB was also higher among those who consumed a larger serving size (> or = 2 oz vs. <2 oz); however, this association was significant for 'other game' consumption only. CONCLUSIONS Participants who consumed wild game had higher PbB than those who did not consume wild game. Careful review of butchering practices and monitoring of meat-packing processes may decrease lead exposure from wild game consumption.


title: The roles of chemokines in rabies virus infection: overexpression may not always be beneficial.

text: It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1alpha further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.


title: Increases in electroencephalogram and electromyogram variability are associated with an increased incidence of intraoperative somatic response.

text: BACKGROUND sBIS, the variability of the Bispectral Index (BIS), sEMG, the variability of facial electromyogram power (EMG), and the Composite Variability Index (CVI) are 3 new measures of electroencephalogram and EMG variability. CVI is a single measure of the combined variability in BIS and EMG. We investigated whether increases in these variables are associated with intraoperative somatic responses. METHODS This multicenter study included 120 patients undergoing elective, noncardiac surgery from 4 different sites. General anesthesia was maintained using propofol and remifentanil at 2 of the sites and sevoflurane and remifentanil at the 2 other sites. Propofol or sevoflurane was adjusted to maintain BIS between 45 and 60. Clinicians were blinded to CVI (v2.0) at all times, and remifentanil infusions were adjusted at the discretion of the clinician. The times of all intraoperative somatic events, defined as movement, grimacing, or eye opening, were recorded. Offline, the maintenance phase of each case was divided into consecutive, nonoverlapping, 10-minute segments. Segments were identified as containing a somatic event or containing no events. For each segment, mean sBIS, sEMG, and CVI and the heart rate (HR) range and mean arterial blood pressure range were calculated. To quantify how effectively each variable discriminated between somatic event segments and nonevent segments, we computed the area under the receiver operating characteristic (ROC) curve for each variable. Finally, we observed the time course of sBIS, sEMG, CVI, and the HR range before each somatic event and characterized the earliest time before the somatic event at which each variable was able to discriminate between the somatic events and a specified set of nonevents. RESULTS The analysis included 33 somatic event segments and 829 nonevent segments from 105 surgical cases. The areas under the ROC curve (±SE) for sBIS, sEMG, and CVI were 0.83 ± 0.04, 0.92 ± 0.02, and 0.89 ± 0.03, respectively. The areas under the ROC curve for HR range and mean arterial blood pressure range were 0.77 ± 0.03 and 0.68 ± 0.05, respectively. CVI, sBIS, and sEMG all demonstrated higher average values before upcoming somatic events when compared with nonevents. HR range only showed a difference within a few seconds before the somatic event. CONCLUSION sBIS, sEMG, and CVI, measures of electroencephalogram and EMG variability, increased when intraoperative somatic events occurred. sBIS, sEMG, and CVI discriminated between 10-minute segments that contained a somatic event and those segments that did not contain an event better than changes in HR and mean arterial blood pressure. Furthermore, CVI increases before somatic events began earlier than HR changes and may provide caregivers with an early warning of potentially inadequate antinociception.


title: Visual Aids for Patient, Family, and Physician Decision Making About Endovascular Thrombectomy for Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Rapid decision making optimizes outcomes from endovascular thrombectomy for acute cerebral ischemia. Visual displays facilitate swift review of potential outcomes and can accelerate decision processes. METHODS From patient-level, pooled randomized trial data, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of endovascular thrombectomy for patients with acute cerebral ischemia and large vessel occlusion using (1) automated (algorithmic) and (2) expert-guided joint outcome table specification. RESULTS For the full 7-category modified Rankin Scale, thrombectomy added to IV tPA (intravenous tissue-type plasminogen activator) alone had number needed to treat to benefit 2.9 (95% confidence interval, 2.6-3.3) and number needed to harm 68.9 (95% confidence interval, 40-250); thrombectomy for patients ineligible for IV tPA had number needed to treat to benefit 2.3 (95% confidence interval, 2.1-2.5) and number needed to harm 100 (95% confidence interval, 62.5-250). Visual displays of treatment effects on 100 patients showed: with thrombectomy added to IV tPA alone, 34 patients have better disability outcome, including 14 more normal or near normal (modified Rankin Scale, 0-1); with thrombectomy for patients ineligible for IV tPA, 44 patients have a better disability outcome, including 16 more normal or nearly normal. Displays also showed that harm (increased modified Rankin Scale final disability) occurred in 1 of 100 patients in both populations, mediated by increased new territory infarcts. The person-icon figures integrated these outcomes, and early side-effects, in a single display. CONCLUSIONS Visual decision aids are now available to rapidly educate healthcare providers, patients, and families about benefits and risks of endovascular thrombectomy, both when added to IV tPA in tPA-eligible patients and as the sole reperfusion treatment in tPA-ineligible patients.


title: Bovine herpesvirus-1: Genetic diversity of field strains from cattle with respiratory disease, genital, fetal disease and systemic neonatal disease and their relationship to vaccine strains.

text: Bovine herpesvirus-1 (BoHV-1) causes disease in cattle with varied clinical forms. In the U.S. there are two BoHV1 subtypes, BoHV-1.1 and BoHV-1.2b. Control programs in North America incorporate modified live (MLV) or killed (KV) viral vaccines. However, BoHV-1 strains continue to be isolated from diseased animals or fetuses after vaccination. It is possible to differentiate BoHV-1 wild-type from MLV vaccine strains by determining their single nucleotide polymorphism (SNP) patterns through either whole-genome sequencing or PCR sequencing of genomic regions containing vaccine-defining SNPs. To determine the BoHV-1 subtype in clinical isolates and their relationship to MLV strains, 8 isolates from varied clinical disease at three different laboratories in the U.S. were sequenced and phylogenetically analyzed. Five samples were isolated within the past 5 years from New York and 3 were archived samples recovered 35 years prior from Oklahoma and Louisiana. Based on phylogenetic analysis, four of the cases appeared to be due to an MLV vaccine: 3 cases of aborted fetuses and one neonate with systemic BoHV-1 disease. One aborted fetus was from a herd with no reported history of MLV vaccination in two years. The remaining four isolates did not group with any MLV vaccines: two were associated with bovine respiratory disease, one with vulvovaginitis, and a fourth was determined to be a BoHV-1.2b respiratory isolate. Recovery of BoHV-1.1 that is very closely related to an MLV vaccine virus from a herd not receiving vaccines in an extended period prior to its isolation suggests that MLV viruses may remain latent or circulate within herds for long periods.


title: Laparoscopic management for non-traumatic colon perforation in children.

text: PURPOSE Although recent reports have seen an increase in acceptance of laparoscopic surgery as treatment for traumatic colon injury, its role in the management of non-traumatic colon perforation in children has not been reported. In this study, we review our experience in laparoscopic non-resectional management for children who presented with non-traumatic colonic perforation. METHODS Between October 2003 and May 2011, 15 children who had been diagnosed with colonic perforation and underwent laparoscopic surgery were included in the study. Their medical records were reviewed for analysis. RESULTS The clinical manifestation of non-traumatic colon perforation in children was non-specific. The most likely aetiology was infective colitis. Solitary perforation at the caecum was the most common finding. The exact perforation site could not be identified in 3 patients. Nine patients had primary closure while 3 patients underwent wedge resection. The single trocar laparoscopic surgery was successful in 12 patients. The mean postoperative hospital stay was 7.3 days. CONCLUSION For children presenting with suspected non-traumatic colon perforation, laparoscopic management is the desirable approach. The peritoneal lavage, wedge excision and primary repair can be performed with single trocar techniques and is associated with minimal morbidity. Future prospective studies are needed to compare this minimally invasive approach with conventional open surgery.


title: Deep sequencing identifies viral and wasp genes with potential roles in replication of Microplitis demolitor Bracovirus.

text: Viruses in the genus Bracovirus (BV) (Polydnaviridae) are symbionts of parasitoid wasps that specifically replicate in the ovaries of females. Recent analysis of expressed sequence tags from two wasp species, Cotesia congregata and Chelonus inanitus, identified transcripts related to 24 different nudivirus genes. These results together with other data strongly indicate that BVs evolved from a nudivirus ancestor. However, it remains unclear whether BV-carrying wasps contain other nudivirus-like genes and what types of wasp genes may also be required for BV replication. Microplitis demolitor carries Microplitis demolitor bracovirus (MdBV). Here we characterized MdBV replication and performed massively parallel sequencing of M. demolitor ovary transcripts. Our results indicated that MdBV replication begins in stage 2 pupae and continues in adults. Analysis of prereplication- and active-replication-stage ovary RNAs yielded 22 Gb of sequence that assembled into 66,425 transcripts. This breadth of sampling indicated that a large percentage of genes in the M. demolitor genome were sequenced. A total of 41 nudivirus-like transcripts were identified, of which a majority were highly expressed during MdBV replication. Our results also identified a suite of wasp genes that were highly expressed during MdBV replication. Among these products were several transcripts with conserved roles in regulating locus-specific DNA amplification by eukaryotes. Overall, our data set together with prior results likely identify the majority of nudivirus-related genes that are transcriptionally functional during BV replication. Our results also suggest that amplification of proviral DNAs for packaging into BV virions may depend upon the replication machinery of wasps.


Can existing live vaccines prevent COVID-19?


Reply to the Letter to the Editor, "Tracheostomy in the COVID-19 Era: The Apneic Approach".


China's 50% caesarean delivery rate: is it too high?


Cancer and Coronavirus Disease 2019 (COVID-19)-Facing the "C Words".


title: Transumbilical single port laparoscopic surgery for the treatment of concomitant disease.

text: BACKGROUND We report our experience of transumbilical single port laparoscopic surgery (TUSPLS) for multiple concomitant intraabdominal pathologies, and assess the feasibility of this technique with several technical tips. METHODS Various combined procedures using TUSPLS were performed since April, 2008. All records of concomitant laparoscopic procedures using TUSPLS were searched at three hospitals. RESULTS Forty-one patients underwent 82 combined procedures using TUSPLS in a single session. The perioperative outcomes of simultaneously performed cholecystectomy and ovarian cystectomy using TUSPLS (n = 14) are compared with those of using CLS (n = 11). The operating time was significantly longer with the TUSPLS method than with the CLS method. However, postoperative convalescent outcomes such as postoperative hospital stay, VAS pain score, and required analgesics showed no differences between the two methods. Also, there were no significant operative complications associated with the two methods. Fewer trocars were used with the TUSPLS method. CONCLUSIONS Combined laparoscopic procedures for various concomitant pathologies in the abdomen can be performed using transumbilical single port laparoscopic surgery without increasing morbidity or hospital stay in patients with acceptable risk.


title: Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral Metastases.

text: BACKGROUND AND PURPOSE Percutaneous cryoablation has emerged as a minimally invasive technique for the management of osseous metastases. The purpose of this study was to assess the safety and effectiveness of percutaneous imaging-guided spine cryoablation for pain palliation and local tumor control for vertebral metastases. MATERIALS AND METHODS Imaging-guided spine cryoablation was performed in 14 patients (31 tumors) with vertebral metastases refractory to conventional chemoradiation therapy or analgesics, to achieve pain palliation and local tumor control in this retrospective study. Spinal nerve and soft-tissue thermal protection techniques were implemented in all ablations. Patient response was evaluated by a pain numeric rating scale administered before the procedure and 1 week, 1 month, and 3 months after the procedure. Pre- and postprocedural analgesic requirements (expressed as morphine-equivalent dosages) were also analyzed at the same time points. Pre- and postprocedural cross-sectional imaging was evaluated in all patients to assess local control (no radiographic evidence of disease at the treated sites). Complications were monitored. Analysis of the primary end points was undertaken via paired-comparison procedures by using the Wilcoxon signed rank test. RESULTS Thirty-one tumors were ablated in 14 patients (9 women and 5 men; 20-73 years of age; mean age, 53 years). The most common tumor location was in the lumbar spine (n = 14, 45%), followed by the thoracic spine (n = 8, 26%), sacrum (n = 6, 19%), coccyx (n = 2, 6%), and cervical spine (n = 1, 3%). There were statistically significant decreases in the median numeric rating scale score and analgesic usage at 1-week, 1-month, and 3-month time points (P < .001 for all). Local tumor control was achieved in 96.7% (30/31) of tumors (median follow-up, 10 months). Two patients had transient postprocedural unilateral lower extremity radiculopathy and weakness. CONCLUSIONS Percutaneous imaging-guided spine cryoablation is a safe and effective treatment for pain palliation and local tumor control for vertebral metastases.


title: Diagnosis and management of rare inferior vena cava leiomyosarcoma guided by a novel minimally invasive vascular biopsy technique.

text: Primary vascular tumors such as vascular leiomyosarcomas are rare, but exhibit markedly different characteristics than tumors that invade the vasculature from a secondary source. Establishing a diagnosis is essential in determining the appropriate treatment plan, but obtaining a histologic specimen may prove challenging and carry significant risks. Minimally invasive endovascular biopsy techniques can be pivotal in the diagnosis-and thus in the management-of vascular tumors. We present a case of a primary inferior vena cava leiomyosarcoma, not able to be adequately assessed by noninvasive imaging and deemed too risky to be approached with traditional percutaneous biopsy techniques. Accurate diagnosis of such tumors is critical, as the success of surgical resection, although high risk, depends greatly upon the type, location, and extent of malignancy.


title: Steroids in cardiac surgery: a systematic review and meta-analysis.

text: BACKGROUND Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery. METHODS We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I2 = 0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989 patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04-1.31; P=0.008; I2=0%]. New onset atrial fibrillation was lower in the steroid group [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91, 95% CI, 0.86-0.96, P=0.0005, I2=43%]; this beneficial effect was limited to small trials (P for interaction <0.00001). CONCLUSIONS After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect.


title: The Muffling of Healthcare: Assessing the Impact of Personal Protective Equipment on Speaking Volume in an Endoscopy Centre.

text: Personal protective equipment (PPE) is crucial in the COVID-19 epidemic[1] but muffle speech, with potential for medical error. While wearing Powered Air-Purifying Respirator (PAPR) adds 76 Db of background noise to the user[2], objectively quantifying this effect remains a knowledge gap with implications on human factors[3] and safety.


title: Shortening of the twitch stabilization period by tetanic stimulation in acceleromyography in infants, children and young adults (STSTS-Study): a prospective randomised, controlled trial.

text: Acceleromyography is characterised by an increase of the twitch response T1 (first twitch of the train-of-four [TOF]) during first 30 min of monitoring known as the staircase phenomenon. In adults the staircase phenomenon can be avoided by tetanic prestimulation. This study examined, if tetanic prestimulation eliminates the staircase phenomenon in children. After written informed consent, the neuromuscular function of 80 children, 10 in each age group (< 6 months, 6-12 months, 12-24 months, 2-3 years, 3-6 years, 6-12 years, 12-18 years, and ≥ 18 years) was measured on both arms simultaneously over 30 min under general anaesthesia. The ulnaris nerve was stimulated using the TOF technique every 15 s. The twitch response (T1, TOF ratio [TOFR]) was measured by acceleromyography. Before calibration, tetanic prestimmulation (50 Hz for 5 s) was administered to one randomly selected arm. The effect of tetanic prestimulation and age was analysed using general linear models based on the normalized T1 and TOFRs of both arms. Tetanic prestimulation significantly affected T1 values avoiding the staircase phenomenon (p < 0.0001). After 5.8 min [1.0-17.2 min] the normalized T1 values increased to 117% [102-147%] without prestimulation (p < 0.0001) independent of the age group (p = 0.539). The normalized TOFR was stable throughout the observation period of 30 min 100% [95-107%]. Infants (> 12 weeks), children, and young adults (< 18 years) develop similar characteristics of the staircase phenomenon than adults. Tetanic prestimulation prevents the staircase phenomenon in these age groups. The stability of the TOFR reading confirms its value to monitor neuromuscular function over time.Registration: The study was registered as NCT02552875 on Clinical Trials.gov on July 29, 2014.


title: Physicomechanical evaluation of polypropylene, polyester, and polytetrafluoroethylene meshes for inguinal hernia repair.

text: BACKGROUND For meshes to be used effectively for hernia repair, it is imperative that engineers and surgeons standardize the terminology and techniques related to physicomechanical evaluation of these materials. The objectives of this study were to propose standard techniques, perform physicomechanical testing, and classify materials commonly used for inguinal hernia repair. STUDY DESIGN Nine meshes were evaluated: 4 polypropylene, 1 polyester, 1 polytetrafluoroethylene, and 3 partially absorbable. Physical properties were determined through image analysis, laser micrometry, and density measurements. Biomechanical properties were determined through suture retention, tear resistance, uniaxial, and ball burst testing with specimens tested in 2 different orientations. A 1-way ANOVA with Tukey's post-test or a t-test were performed, with p < 0.05. RESULTS Significant differences were observed due to both mesh type and orientation. Areas of interstices ranged from 0.33 ± 0.01 mm² for ProLite (Atrium Medical Corp) and C-QUR Lite (Atrium Medical Corp) Large to 4.10 ± 0.06 mm² for ULTRAPRO (Ethicon), and filament diameters ranged from 99.00 ±8.1 μm for ProLite Ultra (Atrium Medical Corp) and C-QUR Lite Small to 338.8 ± 3.7 μm for Parietex Flat Sheet TEC (Covidien). These structural characteristics influenced biomechanical properties such as tear resistance and tensile strength. ProLite Ultra, C-QUR Lite Small, ULTRAPRO and INFINIT (WL Gore & Associates) did not resist tearing as effectively as the others. All meshes exhibited supraphysiologic burst strengths except INFINIT and ULTRAPRO. CONCLUSIONS Significant differences exist between the physicomechanical properties of polypropylene, polyester, polytetrafluoroethylene, and partially absorbable mesh prostheses commonly used for inguinal hernia repair. Orientation of the mesh was also shown to be critical for the success of meshes, particularly those demonstrating anisotropy.


title: Laparoscopic surgical box model training for surgical trainees with limited prior laparoscopic experience.

text: BACKGROUND Surgical training has traditionally been one of apprenticeship, where the surgical trainee learns to perform surgery under the supervision of a trained surgeon. This is time consuming, costly, and of variable effectiveness. Training using a box model physical simulator is an option to supplement standard training. However, the value of this modality on trainees with limited prior laparoscopic experience is unknown. OBJECTIVES To compare the benefits and harms of box model training for surgical trainees with limited prior laparoscopic experience versus standard surgical training or supplementary animal model training. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to May 2013. SELECTION CRITERIA We planned to include all randomised clinical trials comparing box model trainers versus other forms of training including standard laparoscopic training and supplementary animal model training in surgical trainees with limited prior laparoscopic experience. We also planned to include trials comparing different methods of box model training. DATA COLLECTION AND ANALYSIS Two authors independently identified trials and collected data. We analysed the data with both the fixed-effect and the random-effects models using Review Manager 5. For each outcome, we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat analysis whenever possible. MAIN RESULTS We identified eight trials that met the inclusion criteria. One trial including 17 surgical trainees did not contribute to the meta-analysis. We included seven trials (249 surgical trainees belonging to various postgraduate years ranging from year one to four) in which the participants were randomised to supplementary box model training (122 trainees) versus standard training (127 trainees). Only one trial (50 trainees) was at low risk of bias. The box trainers used in all the seven trials were video trainers. Six trials were conducted in USA and one trial in Canada. The surgeries in which the final assessments were made included laparoscopic total extraperitoneal hernia repairs, laparoscopic cholecystectomy, laparoscopic tubal ligation, laparoscopic partial salpingectomy, and laparoscopic bilateral mid-segment salpingectomy. The final assessments were made on a single operative procedure.There were no deaths in three trials (0/82 (0%) supplementary box model training versus 0/86 (0%) standard training; RR not estimable; very low quality evidence). The other trials did not report mortality. The estimated effect on serious adverse events was compatible with benefit and harm (three trials; 168 patients; 0/82 (0%) supplementary box model training versus 1/86 (1.1%) standard training; RR 0.36; 95% CI 0.02 to 8.43; very low quality evidence). None of the trials reported patient quality of life. The operating time was significantly shorter in the supplementary box model training group versus the standard training group (1 trial; 50 patients; MD -6.50 minutes; 95% CI -10.85 to -2.15). The proportion of patients who were discharged as day-surgery was significantly higher in the supplementary box model training group versus the standard training group (1 trial; 50 patients; 24/24 (100%) supplementary box model training versus 15/26 (57.7%) standard training; RR 1.71; 95% CI 1.23 to 2.37). None of the trials reported trainee satisfaction. The operating performance was significantly better in the supplementary box model training group versus the standard training group (seven trials; 249 trainees; SMD 0.84; 95% CI 0.57 to 1.10).None of the trials compared box model training versus animal model training or versus different methods of box model training. AUTHORS' CONCLUSIONS There is insufficient evidence to determine whether laparoscopic box model training reduces mortality or morbidity. There is very low quality evidence that it improves technical skills compared with standard surgical training in trainees with limited previous laparoscopic experience. It may also decrease operating time and increase the proportion of patients who were discharged as day-surgery in the first total extraperitoneal hernia repair after box model training. However, the duration of the benefit of box model training is unknown. Further well-designed trials of low risk of bias and random errors are necessary. Such trials should assess the long-term impact of box model training on clinical outcomes and compare box training with other forms of training.


title: Functional connectivity patterns of medial and lateral macaque frontal eye fields reveal distinct visuomotor networks.

text: It has been previously shown that small- and large-amplitude saccades have different functions during vision in natural environments. Large saccades are associated with reaching movements toward objects, whereas small saccades facilitate the identification of more detailed object features necessary for successful grasping and manual manipulation. To determine whether these represent dichotomous processing streams, we used resting-state functional MRI to examine the functional connectivity patterns of the medial and lateral frontal eye field (FEF) regions that encode large- and small-amplitude saccades, respectively. We found that the spontaneous blood oxygen level-dependent signals of the medial FEF were functionally correlated with areas known to be involved in reaching movements and executive control processes, whereas lateral FEF was functionally correlated with cortical areas involved in object processing and in grasping, fixation, and manipulation of objects. The results provide strong evidence for two distinct visuomotor network systems in the primate brain that likely reflect the alternating phases of vision for action in natural environments.


title: Genioglossus activity available via non-arousal mechanisms vs. that required for opening the airway in obstructive apnea patients.

text: It is generally believed that reflex recruitment of pharyngeal dilator muscles is insufficient to open the airway of obstructive apnea (OSA) patients once it is closed and, therefore, that arousal is required. Yet arousal promotes recurrence of obstruction. There is no information about how much dilator [genioglossus (GG)] activation is required to open the airway (GG Opening Threshold) or about the capacity of reflex mechanisms to increase dilator activity before/without arousal (Non-Arousal Activation). The relationship between these two variables is important for ventilatory stability. We measured both variables in 32 OSA patients (apnea-hypopnea index 74 ± 42 events/h). GG activity was monitored while patients were on optimal continuous positive airway pressure (CPAP). Zopiclone was administered to delay arousal. Maximum GG activity (GG(MAX)) and airway closing pressure (P(CRIT)) were measured. During stable sleep CPAP was decreased to 1 cmH(2)O to induce obstructive events and the dial-downs were maintained until the airway opened with or without arousal. GG activity at the instant of opening (GG Opening Threshold) was measured. GG Opening Threshold averaged only 10.4 ± 9.5% GG(Max) and did not correlate with P(CRIT) (r = 0.04). Twenty-six patients had >3 openings without arousal, indicating that Non-Arousal Activation can exceed GG Opening Threshold in the majority of patients. GG activity reached before arousal in Arousal-Associated Openings was only 5.4 ± 4.6% GG(MAX) below GG Opening Threshold. We conclude that in most patients GG activity required to open the airway is modest and can be reached by non-arousal mechanisms. Arousals occur in most cases just before non-arousal mechanisms manage to increase activity above GG Opening Threshold. Measures to reduce GG Opening Threshold even slightly may help stabilize breathing in many patients.


Vulnerability of people with schizophrenia to COVID-19.


title: Usefulness of Hydrogel-Coated Coils in Embolization of Pulmonary Arteriovenous Malformations.

text: PURPOSE To evaluate the usefulness of hydrogel-coated coils for preventing recanalization after coil embolization of pulmonary arteriovenous malformations (PAVMs). MATERIALS AND METHODS Thirty-seven consecutive patients with 57 untreated PAVMs underwent coil embolization with hydrogel-coated coils between January 2013 and Jun 2017. The mean age was 49 years (range 9-83 years), and there were seven male patients and 30 female patients. The median size of the feeding artery was 3.7 mm (range 1.5-6.1 mm), and the median size of the venous sac was 9.3 mm (range 2.6-36.6 mm). For all PAVM, embolization was attempted using 0.018-in. hydrogel-coated coils with or without other coils (0.0135-0.018-in. bare platinum coils and fibered platinum coils). Technical success rate, recanalization rate, and complications were evaluated. Technical success was defined as completion of embolization using hydrogel-coated coils. Recanalization was evaluated with time-resolved magnetic resonance angiography and/or pulmonary angiography. RESULTS In 56 of 57 PAVMs, embolization was successfully performed with hydrogel-coated coils. Therefore, the technical success rate was 98% (56/57). The number of PAVMs at risk was 56, 42, 18, and 12 at 0, 12, 24, and 36 months, respectively. There was no recanalization with a mean follow-up period of 19 months (range 2-47 months) in 56 PAVMs embolized with hydrogel-coated coils. There were no major complications. As a minor complication, local pain was observed in 8 of 43 sessions (19%) after embolization. CONCLUSIONS Hydrogel-coated coils may be useful for preventing recanalization after the embolization of PAVMs.


title: Clinical Outcomes of Esophagojejunostomy in Totally Laparoscopic Total Gastrectomy: A Multicenter Study.

text: PURPOSE To examine the short-term outcomes of intracorporeal anastomosis during totally laparoscopic total gastrectomy retrospectively at multiple institutions. PATIENTS AND METHODS We collected data of the patients who had undergone totally laparoscopic total gastrectomy at 4 institutions. All patients received an intracorporeal esophagojejunostomy. RESULTS Of the 215 patients evaluated, 147 underwent functional end-to-end anastomosis (FEEA) as the intracorporeal esophagojejunostomy (FEEA group), and 68 patients received a circular stapler anastomosis (Circular group). The rate of tumor invasion to the esophagus was significantly higher in the Circular group than in the FEEA group (33% vs. 6%, respectively; P<0.0001). Univariate and multivariate analyses revealed that the circular stapler anastomosis and high preoperative BMI were statistically significant risk factors for postoperative leakage. However, the rates of complications and mortality were not significantly different between groups. CONSIDERATION Our results showed that each type of esophagojejunostomy is safe and feasible for patients with gastric cancer with acceptable morbidity and mortality.


title: Computed Tomography Angiography in the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Study.

text: BACKGROUND The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) study validated noninvasive imaging tests of intracranial atherosclerosis against catheter angiography in a prospective, blinded, multicenter setting. Critical evaluation of transcranial Doppler (TCD) and magnetic resonance angiography in the SONIA study standardized their performance and interpretation. We performed a similar analysis of computed tomography angiography (CTA) for the detection of intracranial stenosis. METHODS Multicenter standardization of image acquisition and blinded, central interpretation of CTA performance were conducted in concert with the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. Measurements of the intracranial arterial diameter were obtained to derive stenosis values. Correlation with catheter angiography was used to assess CTA performance characteristics. RESULTS CTA measurements of intracranial stenosis were obtained in 120 vessel segments, with angiographic correlation in 52. CTA was performed as a noninvasive study prior to conventional angiography. CTA stenoses of 50-99% or a flow gap were identified in 15 of 52 vessel segments, stenoses of <50% in 5 of 52, and normal arterial diameters in 32 of 52 vessel segments. Based on the digital subtraction angiography (DSA) stenosis defined as 50-99%, the positive predictive value (PPV) of CTA was only 46.7% (95% CI 21.3-73.4) and the negative predictive value (NPV) was 73.0% (95% CI 55.9-86.2). For DSA stenosis defined as 70-99%, the PPV of CTA was 13.3% (95% CI 1.7-40.5) and the NPV was 83.8% (95% CI 68.0-93.8). CONCLUSIONS CTA can accurately rule out the presence of severe stenosis due to intracranial atherosclerosis and may eliminate the need for angiography in many cases. Further prospective, blinded evaluation of CTA and optimization of cutpoints to predict angiographic disease will facilitate future trials of intracranial atherosclerosis.


title: Should Intermittent Mandatory Ventilation Be Abolished?

text: Intermittent mandatory ventilation (IMV) was introduced nearly 50 years ago. Despite the initial fanfare and early adoption by many, the role of IMV continues to be questioned. The use of small tidal volumes complicates the application of IMV, and issues with work of breathing, weaning and lack of clear advantages have many calling for a moratorium on its use. Spontaneous breathing, however, has a number of salutatory effects on gas exchange, the distribution of ventilation, and hemodynamics. These issues will be explored in light of a growing body of evidence.


title: The partial myocutaneous gluteal flap reconstruction of extralevator abdominoperineal defects in irradiated patients.

text: Reconstruction of the irradiated perineum has posed a consistent reconstructive challenge historically. The evolution of reconstructive techniques must mirror advances in neoadjuvant treatment and surgery for low rectal cancer. The purpose of this study was to evaluate the perineal healing in a cohort of patients, of whom a majority had laparoscopic tumor excision and partial myocutaneous gluteal flap reconstruction. There were 11 patients in this cohort; 8 primary reconstructions and 3 salvage cases. Complete healing was measured as the cessation of all dressings. There were no returns to theater for flap-related surgery. Mean postreconstruction inpatient stay was 16.5 days. All patients healed completely. Mean time to healing was 42 days. This method has been successful for primary and salvage reconstruction in patients having laparoscopic or open surgery; thus, averting the major morbidity associated with failed reconstruction as reported for most of other reconstructive modalities in these patients.


title: Thrombus formation in the pulmonary vein stump after left upper lobectomy: a report of four cases.

text: Left upper lobectomy may be followed by complications such as thrombus formation in a stump of the left superior pulmonary vein (LSPV), which may cause systemic embolization. We have encountered four such cases, which account for 3.4% of all left upper lobectomies performed at our institution. Right renal infarction was observed in one of these four cases; the remaining cases were asymptomatic, with the thrombus incidentally detected by enhanced computed tomography (CT). The postoperative duration for the detection of the thrombus varied from 4 days to 24 months. Even in a case in which the superior pulmonary vein (PV) was divided by posterolateral thoracotomy, CT showed that the stump was long enough intrapericardially for thrombus formation. Anticoagulant therapy was administered in all the cases, resulting in dissipation of the thrombus. Therefore, when a thrombus is detected in a pulmonary stump, an anticoagulant should be administered.


title: Photodynamic therapeutic ablation for peripheral pulmonary malignancy via electromagnetic navigation bronchoscopy localization in a hybrid operating room (OR): a pioneering study.

text: Background With the aid of electromagnetic navigation bronchoscopy (ENB), it has become possible to approach peripheral lung tumors from the airway. Meanwhile, local ablation using photodynamic therapy (PDT) has shown increasing promise in the realm of lung cancer treatment. The purpose of this study was to explore an alternative ablation method using PDT with SuperDimension ENB localization in a hybrid operating theater. Methods Our study includes patients with primary or metastatic lung cancer who underwent PDT via ENB in the hybrid operating room (OR) of National Taiwan University Hospital between January 2016 and January 2017. ENB with the SuperDimension Navigation System (7th edition) was performed before PDT ablation to localize the target lesions. PDT ablation was performed with the assistance of intraoperative Dyna-computed tomography (Dyna-CT). Tumor response was evaluated by CT 3 months after the procedure. Results Three patients underwent lung interstitial PDT via the aid of ENB during the study period. The mean size of the nodules was 21.3 mm. The mean navigation time was 14.3 minutes. In all cases, the target pulmonary nodule was ablated by PDT successfully. No major procedure-related complications occurred. One patient suffered from skin hypersensitivity one month after the procedure. The follow-up CT showed significant tumor shrinkage for all the patients. They were all discharged without incident a few days after the procedure as scheduled. Conclusions PDT with SuperDimension ENB guidance in the hybrid OR is a novel and feasible approach to control peripheral lung malignancy.


title: Real-world management of hyperkalemia with patiromer among United States Veterans.

text: Objective: Patiromer is a sodium-free, non-absorbed, potassium (K+) binder approved for the treatment of hyperkalemia (HK). Among US Veterans with HK, this retrospective, observational cohort study evaluated patiromer utilization, RAASi continuation, and K+ concentration change following patiromer initiation.Methods: Using data from the Veterans Affairs Corporate Data Warehouse, Veterans with HK (K+ ≥5.1 mmol/L) were included upon patiromer initiation (index date) during the study period (1/2016-8/2018). All patients had heart failure (HF), diabetes, or chronic kidney disease (CKD). Patients with end-stage renal disease were excluded. The following outcomes were assessed within 6-months post-patiromer initiation: patiromer utilization (using proportion of days covered); K+ concentration change (pre- vs post-initiation); and RAASi continuation.Results: 288 Veterans with HK were included. Baseline characteristics were: median age 70 years, African-American race 24%, diabetes 83%, HF 32%, CKD 95%, and median K+ concentration 5.7 mmol/L. At 1, 3, and 6 months post-index, the median patiromer PDC was 100%, 66%, and 44%, respectively. K+ concentration reductions post-patiromer initiation were, on average, - 1.0 mmol/L (P < 0.001). At 3-6 months, 71% of patiromer initiators had K+ <5.1 mmol/L and 95% had K+ <5.5 mmol/L. RAASi therapy was continued in >80%-90% of patiromer-treated patients.Conclusions: The real-world utilization results suggest patiromer is used for the chronic management of HK. Clinically relevant K+ concentration reductions were observed at all study time points. The successful management of HK may have contributed to the observed high rate of RAASi therapy continuation. Further research is warranted to corroborate and extend these findings.


title: CD59 association with infectious bronchitis virus particles protects against antibody-dependent complement-mediated lysis.

text: CD59 protein functions as a negative regulator of the terminal pathway of the complement system by binding to the C8/C9 factors. To date, little is known about the role of CD59 in coronavirus infectious bronchitis virus (IBV) infection. In this study, we discovered that CD59 was downregulated in IBV-infected cells and was associated with IBV virions. This association protected IBV particles from antibody-dependent complement-mediated lysis. IBV titres in the supernatant were significantly increased when CD59 proteins were overexpressed in cells followed by IBV infection, and this observation was further supported by knockdown or cleavage of CD59. Because no considerable change in IBV N protein and viral RNA levels was detected in total cell lysates prepared from the overexpression, knockdown or cleavage of CD59 groups, our data indicated that CD59 was involved in IBV particle release and that IBV had evolved a mechanism to utilize CD59 to evade complement-mediated destruction.


title: Relationship of A1 segment hypoplasia to anterior communicating artery aneurysm morphology and risk factors for aneurysm formation.

text: OBJECTIVE Hypoplasia of the A1 segment of the anterior cerebral artery is frequently observed in patients with anterior communicating artery (ACoA) aneurysms. The effect of this anatomical variant on ACoA aneurysm morphology is not well understood. METHODS Digital subtraction angiography images were reviewed for 204 patients presenting to the authors' institution with either a ruptured or an unruptured ACoA aneurysm. The ratio of the width of the larger A1 segment to the smaller A1 segment was calculated. Patients with an A1 ratio greater than 2 were categorized as having A1 segment hypoplasia. The relationship of A1 segment hypoplasia to both patient and aneurysm characteristics was then assessed. RESULTS Of 204 patients that presented with an ACoA aneurysm, 34 (16.7%) were found to have a hypoplastic A1. Patients with A1 segment hypoplasia were less likely to have a history of smoking (44.1% vs 62.9%, p = 0.0410). ACoA aneurysms occurring in the setting of a hypoplastic A1 were also found to have a larger maximum diameter (mean 7.7 vs 6.0 mm, p = 0.0084). When considered as a continuous variable, increasing A1 ratio was associated with decreasing aneurysm dome-to-neck ratio (p = 0.0289). There was no significant difference in the prevalence of A1 segment hypoplasia between ruptured and unruptured aneurysms (18.9% vs 10.7%; p = 0.1605). CONCLUSIONS Our results suggest that a hypoplastic A1 may affect the morphology of ACoA aneurysms. In addition, the relative lack of traditional risk factors for aneurysm formation in patients with A1 segment hypoplasia argues for the importance of hemodynamic factors in the formation of ACoA aneurysms in this anatomical setting.


The Coronavirus Epidemic.


title: Health care access of informal waste recyclers in Johannesburg, South Africa.

text: INTRODUCTION Informal waste recyclers contribute significantly to waste removal in South Africa. Waste recyclers face health hazards which are associated with handling and disposal of waste, a lack of personal protective wear and inaccessibility to occupational health care services. Consequently, accessing health care within the public health care sector is important for health outcomes in this population. This study assesses health care access of informal waste recyclers in South Africa to establish baseline information for health planning for potential inclusion of informal waste recyclers into occupational health services. METHODS A cross-sectional study of informal waste recyclers in two landfill sites in Johannesburg was conducted from March 2018. A standardized structured questionnaire was used to collect information on sociodemographic details, health care utilization, barriers to access and acceptability and affordability of health care. Factors associated with health care utilization were assessed using logistic regression. RESULTS A total of 363 informal waste recyclers were included in the study. Less than half of informal waste recyclers (41.0%) used health care facilities in the last 12 months. Those who accessed services chose to use facilities close to where they live (87.0%). Barriers to accessing health care services included long waiting periods (36.6%), being unable to take time off work (26.3%) and transport problems (13%). In the univariate analysis, factors such as gender and being treated well at the clinic and location of the health care facility were associated with health care utilization (OR: 1.97, p = 0.05, OR: 1.94, p = 0.02, OR: 0.65, p = 0.04 respectively). CONCLUSION Informal waste recyclers face numerous challenges to accessing health care. Specific to their informal trade, barriers to health care utilization are related to financial repercussions due to the informal nature of their work.


title: Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic.

text: Importance During the coronavirus disease 2019 (COVID-19) pandemic, several cases of chilblains have been reported. Objective To determine if chilblains are associated with COVID-19. Design, Setting, and Participants This monocentric case series was conducted at the Department of Dermatology at Cliniques universitaires Saint-Luc, a tertiary care hospital in Brussels, Belgium, between April 10 and April 17, 2020. We evaluated a total of 31 referred patients who had recently developed chilblains. Main Outcomes and Measures Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on nasopharyngeal swabs for all patients and in skin biopsy specimens for 22 patients. Blood samples from all patients were tested for specific anti-SARS-CoV-2 immunoglobulin (Ig) M and IgG antibodies. All patients had extended blood analyses. Histologic (22 patients) and immunofluorescence examinations (15 patients) were performed on the skin biopsy specimens. Results The 31 patients were generally in good health; most were teenagers or young adults, and 19 were women. Histopathologic analysis of skin biopsy specimens (22 patients) confirmed the diagnosis of chilblains and showed occasional lymphocytic or microthrombotic phenomena. Immunofluorescence analyses showed vasculitis of small-diameter vessels in 7 patients. In all patients, SARS-CoV-2 RNA remained undetected by RT-PCR on nasopharyngeal swabs and in biopsy samples of the skin lesions. The IgM and IgG antibody titers were negative for SARS-CoV-2 in all patients (<1.0 arbitrary unit/mL). No significant abnormalities in blood test results were suggestive of systemic disease. Antinuclear antibody titers were low in 7 patients and higher in 1 patient. Conclusions and Relevance Chilblains appeared not to be directly associated with COVID-19 in this case series. Lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.


title: The COVID-19 pandemic in Australia: Lessons learnt.

text: This paper evaluated the unique challenges of Australians in relation to the global novel coronavirus (COVID-19) pandemic. The 2019-2020 bushfires and COVID-19 outbreak have increased rates of anxiety and distress in Australia. On the contrary, unprecedented spending by the Australian Government on health care, employment, and housing has potentially lowered anxiety and stress for some Australians. Research is required to monitor the potential long-term mental health consequences of COVID-19 in Australia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).