title: Acute neurology during the COVID-19 pandemic: Supporting the front line.

text: Neurologists are affected by the COVID-19 pandemic in several key ways, including: a reduced ability to admit and accept in transfer critically ill neurologic patients due to census overflow; personal risk of exposure to COVID-19; and potentially redeployment of the acute neurologist workforce towards general medicine to assist our colleagues managing the surge of medical patients. As providers of inpatient and emergency-based acute neurologic care, we have been attempting to locally prepare for and manage the COVID-19 pandemic by focusing on 3 key areas: creating an integrated preparation plan that supports hospital measures; building an optimized, flexible, and redundant workforce; and maintaining a high level of neurologic care in our hospital and across our region despite limited transfer capabilities during the pandemic. This final concern is of key relevance in our region where our tertiary hospital supports numerous smaller community hospitals, typically by providing an open door to patient transfers. These hospitals are often in rural or frontier regions and are also affected by COVID-19, so not only are beginning to experience their own bed and clinician shortages,1 but are understandably nervous about what the pandemic means for the availability of traditional support systems for other non-COVID-related diseases.


title: Systematic review of cyanoacrylate embolization for refractory gastrointestinal fistulae: a promising therapy.

text: BACKGROUND Surgical management of gastrointestinal fistulae has been reported to carry a 30-day morbidity rate up to 82% and a mortality rate ranging from 2% to 4.8%; thus nonoperative alternatives are required. The aim of the present study was to assess the current experience on the use of cyanoacrylates in the management of these fistulae. METHODS A systematic review was carried out on Medline, Embase, The Cochrane database, Academic Search Complete, MedicLatina, and SciELO for English, Spanish, and Portuguese articles dealing with refractory fistulae by means of cyanoacrylate embolization therapy. Publication dates were restricted from 1969 to present. Outcome parameters were study design, number of participants, etiology of the fistula, approach, material used, success rate, complications, and mortality. RESULTS Electronic search yielded a total of 377 articles. After a meticulous screening, only 14 studies dealing with foregut/midgut fistulae and 6 addressing hindgut fistulae were included. All the included articles were prospective and retrospective case series. Cumulative success rate was 81% (range 0% to 100%) and 3 out of 203 patients (1%) developed minor complications. CONCLUSION Cyanoacrylate embolization of nearly all types of refractory gastrointestinal fistulae is a feasible and harmless technique. Prospective controlled studies are required to support the available evidence.


title: Patency of anterior circulation branch vessels after Pipeline embolization: longer-term results from 82 aneurysm cases.

text: OBJECTIVE The Pipeline Embolization Device (PED) has become increasingly used for the treatment of intracranial aneurysms. Given its high metal surface area coverage, there is concern for the patency of branch vessels that become covered by the device. Limited data exist regarding the patency of branch vessels adjacent to aneurysms that are covered by PEDs. The authors assessed the rate of intracranial internal carotid artery, anterior circulation branch vessel patency following PED placement at their institution. METHODS The authors retrospectively reviewed the records of 82 patients who underwent PED treatment between 2009 and 2014 and in whom the PED was identified to cover branch vessels. Patency of the anterior cerebral, posterior communicating, anterior choroidal, and ophthalmic arteries was evaluated using digital subtraction angiography preoperatively and postoperatively after PED deployment and at longer-term follow-up. RESULTS Of the 127 arterial branches covered by PEDs, there were no immediate postoperative occlusions. At angiographic follow-up (mean 10 months, range 3-34.7 months), arterial side branches were occluded in 13 (15.8%) of 82 aneurysm cases and included 2 anterior cerebral arteries, 8 ophthalmic arteries, and 3 posterior communicating arteries. No cases of anterior choroidal artery occlusion were observed. Patients with branch occlusion did not experience any neurological symptoms. CONCLUSIONS In this large series, the longer-term rate of radiographic side branch arterial occlusion after coverage by a flow diverter was 15.8%. Terminal branch vessels, such as the anterior choroidal artery, remained patent in this series. The authors' series suggests that branch vessel occlusions are clinically silent and should not deter aneurysm treatment with flow diversion.


title: Large inflammatory fibroid polyp of cardia managed laparoscopically - a case report and review of the literature.

text: Inflammatory fibroid polyp or Vanek's tumor of the gastrointestinal tract is a rare, benign neoplasm. The lesion may occur at any age but is commonest in the sixth and seventh decades and is more often found in women. It is mostly situated in the stomach, especially in the antrum. Symptoms depend on the location and the size of the lesion. We present a case of a 67-year-old woman with a large inflammatory polyp of the cardia with a diameter of 10 cm × 5.5 cm × 7.5 cm imitating gastrointestinal stromal tumor (GIST). The patient complained of abdominal pain, nausea and mild anemia. We performed laparoscopic topical excision of the tumor. The postoperative course was uneventful. The 6-month follow-up did not reveal recurrence. The clinical image of a large Vanek's tumor can imitate symptoms of gastric cancer or GIST. Topical laparoscopic excision with a 1-2 cm healthy wall margin is a sufficient and adequate way of treatment.


title: Low-Dose Volume-of-Interest C-Arm CT Imaging of Intracranial Stents and Flow Diverters.

text: BACKGROUND AND PURPOSE Volume-of-interest C-arm CT is a novel technique for imaging of intracranial high-contrast objects. We performed this study to evaluate the potential diagnostic value and radiation dose reduction of this technique for imaging of intracranial stents and flow diverters. MATERIALS AND METHODS Twenty-seven patients were imaged with a VOI C-arm CT scan following treatment with a flow diverter or stent-assisted coiling. The radiation dose-area product was recorded for VOI scans. For comparison, the dose-area product from 30 previously acquired consecutive full-view DynaCTs was used. Thermoluminescence dosimetry by using 35 evenly distributed thermoluminescence dosimeters in an anthropomorphic head phantom was also performed by using both conventional full field and VOI acquisitions. Three observers were presented with VOI images for assessment of the potential diagnostic value. RESULTS The dose-area product measurements showed an exposure reduction of 85% compared with the full field acquisitions used for comparison. The thermoluminescence dosimetry evaluations also showed a considerable dose reduction of 79.8% throughout the volume. For most of the evaluated cases, the observers thought that diagnostically useful information was provided by the VOI images (α = .810). Visualization of device details, such as the extent of opening, positioning, wall apposition, and aneurysm coverage, was judged of good diagnostic quality for most cases (88.9%-92.6%). CONCLUSIONS In this study, VOI C-arm CT provided high-quality diagnostic images of intracranial stents and flow diverters at a dramatic reduction of radiation exposure. Image content was thought to add useful information. It is a promising method to assess device status during procedures and at follow-up.


title: A review of the current management and treatment options for superficial venous insufficiency.

text: The recognition of lower extremity venous disease as a significant cause of morbidity and lower quality of life, afflicting up to 25 % of Western populations, has led to rapid and drastic improvements in treatment options as well as an increasing awareness of the disease. Superficial venous disease, a frequent medical problem encountered in clinical practices, is now a common reason for referral to providers offering a spectrum of interventions. Venous guidelines have been set forth by the American Venous Forum and Society for Vascular Surgery covering simple spider veins to chronic venous ulcerations. (Gloviczki et al. J Vas Surg 53:2S-48S, 2011) This review provides an overview of the modern management of varicose veins and venous insufficiency.


title: Highly sensitive and quantitative detection of the H274Y oseltamivir resistance mutation in seasonal A/H1N1 influenza virus.

text: A C-to-T transition mutation in the neuraminidase gene from seasonal A/H1N1 causes a His-to-Tyr mutation at amino acid position 275 (H274Y, universal N2 numbering), conferring resistance against oseltamivir (Tamiflu). This mutation was first detected in clinical samples in Europe during the 2007-2008 influenza season. Viruses with this mutation reached a prevalence of ∼11% by the end of the season in North American isolates tested by the CDC. We developed a highly sensitive and specific quantitative real-time reverse transcriptase PCR assay to detect the H274Y mutation. This assay utilizes a 5'-methyl-isocytosine (isoC) residue and fluorescent reporters on genotype-specific primers. During PCR, a quencher coupled to isoguanine (isoG) is site-specifically incorporated complementary to the isoC/dye, resulting in loss of fluorescence. Optimization of primers and assay conditions produced a limit of detection of 100 gene copies per reaction for both wild-type and H274Y genotypes. In samples with mixed populations, it can reliably detect as little as a 1% wild-type or 0.1% H274Y component. This high sensitivity makes the assay usable on samples with viral loads too low for dideoxy or pyrosequencing analysis. Additionally, the assay distinguishes seasonal A/H1N1 from A/H3N2, influenza B, or 2009 pandemic A/H1N1, making it useful for influenza virus subtyping as well as for drug resistance detection. We probed seasonal A/H1N1 samples from the 2005-2006, 2006-2007, and 2007-2008 influenza seasons. Data from the new assay closely matched available drug resistance genotype data previously determined by dideoxy sequencing. The H274Y mutation was only found in samples from the 2007-2008 season.


COVID-19 Q&A: Collaborating and coordinating keeps a zebrafish facility going.


title: Superficial venous insufficiency from the infernal to the endothermal.

text: This review presents the common diseases associated with superficial venous insufficiency of the leg. These include varicose veins, swelling, skin damage and ulceration. The benefits and rationale behind treatment are discussed, followed by the historical advances from ancient mortality and prayer to the modern endovenous revolution. Finally, an overview of modern treatment options will discuss the evidence supporting the gold standard of endothermal ablation and the cost effectiveness of treatment at this time of challenging resource limitation.


Sex and Gender Disparities in the COVID-19 Pandemic.


title: Outcomes of simultaneous large complex abdominal wall reconstruction and enterocutaneous fistula takedown.

text: BACKGROUND The surgical management of enterocutaneous fistulas (ECFs) in the setting of large abdominal wall defects can be challenging. We aimed to review our experience with simultaneous single-stage ECF takedown and complex abdominal wall reconstruction (AWR). METHODS Using a prospectively collected database, patients requiring surgical management of an ECF and AWR over a 5-year period were reviewed. RESULTS Thirty-seven patients (mean age = 58.6 years) underwent ECF repair/AWR. The mean hernia defect size was 426 ± 192 cm(2). Thirty-five (95%) patients required fascial releases to achieve abdominal wall closure. Thirty-six (97%) patients had sublay biologic mesh placed to reinforce the repair. Twenty-four (65%) patients developed a surgical site infection (8 superficial, 8 deep, and 8 organ space). Four patients developed an early anastomotic leak/refistulization. With a mean follow-up of 20 months, the hernia recurrence rate was 32% (n = 12). CONCLUSIONS The simultaneous reconstruction of ECF and complex abdominal wall defects resulted in successful single-stage management of these challenging cases in nearly 70% of patients in this series.


title: Retrospective Analysis of 61 Cases of Children Died of Viral Pneumonia.

text: Abstract Objective To retrospectively analyze the forensic pathological postmortem examination and clinical data of children who died of viral pneumonia in identification of cause of death cases and to discuss the clinical characteristics and pathological features of viral pneumonia in children, in order to provide reference to pathological diagnosis of viral pneumonia in children caused by 2019 novel coronavirus （2019-nCoV） infection. Methods Postmortem examination data from 61 cases of children whose causes of death were identified as viral pneumonia in recent years were collected from the Center of Forensic Identification, Southern Medical University. The gender, age, clinical symptoms and pathological features were comparatively analyzed. Results Among the 61 cases of children who died of viral pneumonia, most were within 2 years old （83.61%）, and a large proportion died within 2 weeks after the onset of the disease （91.80%）. Gross changes in postmortem examination included respiratory mucosal hyperemia, pleural effusion, pulmonary swelling, variegated pulmonary pleura and serosa, as well as focal pulmonary hemorrhage and pulmonary edema. A large proportion of sick children had enlarged mesenteric lymph nodes （83.61%） and thymic dysplasia （21.31%）. Histopathological changes included edema of alveoli and interstitial substance, pneumorrhagia，shedding of alveolar epithelial cells, serous and （or） fibrous exudation in the alveoli, formation of viral inclusions, formation of transparent membranes, infiltration of inflammatory cells that mainly consisted of macrophages and lymphocytes in interstitial substance and alveoli. Viral infections often affected the heart and gastrointestinal tract. Conclusion The clinical symptoms of children with viral pneumonia are difficult to notice, and because the immune systems of children are not fully developed and they have poor immunity, they can easily become severely ill and even die. Analyzing the forensic autopsies and the histopathological characteristics could provide reference for pathological diagnosis of viral pneumonia.


title: Business as usual? Psychological support at a distance.

text: The impact of COVID-19 has challenged the long accepted 'norm' in delivery of psychological therapy. Public policies designed to reduce transmission have made it extremely difficult to meet with service-users safely in the traditional face-to-face context. E-therapies have existed in theory and practice since technological progress has made them possible. They can offer a host of advantages over face-to-face equivalents, including improved access, greater flexibility for service-users and professionals, and cost savings. However, despite the emerging evidence and anticipated positive value, implementation has been slower than anticipated. Concerns have been raised by service-users, clinicians, and public health organisations, identifying significant barriers to the wide spread use of e-therapies. In the current climate, many clinicians are offering e-therapies for the first time, without prior arrangement or training, as the only viable option to continue to support their clients. This paper offers a clinically relevant review of the e-therapies literature, including effectiveness and acceptability dilemmas and challenges that need to be addressed to support the safe use and growth of e-therapies in psychology services. Further research is needed to better understand what might be lost and what gained in comparison to face-to-face therapy, and for which client groups and settings it might be most effective.


title: The 2019 novel coronavirus disease (COVID-19) pandemic: A review of the current evidence

text: A novel coronavirus (nCoV) spillover event, with its epicenter in Wuhan, People's Republic of China, has emerged as a public health emergency of international concern. This began as an outbreak in December 2019, and till February 28, 2020, there have been 83,704 confirmed cases of novel coronavirus disease 2019 (COVID-19) globally, with 2,859 deaths, resulting in an overall case fatality rate of 3.41 per cent (95% confidence interval 3.29-3.54%). By this time (February 28, 2020) 58 countries or territories and one international conveyance (Diamond Princess Cruise Ship) were affected. As a part of the global response to manage and contain the pandemic, major emphasis was placed on generating research intelligence to guide evidence-based responses to contain the virus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), owing to its genetic similarities with the SARS virus. This review summarizes the emerging evidence which can help guide the public health response, particularly in India. Key areas have been identified in which research needs to be conducted to generate critical intelligence for advising prevention and control efforts. The emergence of SARS-CoV-2 has once again exposed the weaknesses of global health systems preparedness, ability to respond to an infectious threat, the rapidity of transmission of infections across international borders and the ineffectiveness of knee-jerk policy responses to emerging/re-emerging infectious disease threats. The review concludes with the key learning points from the ongoing efforts to prevent and contain COVID-19 and identifies the need to invest in health systems, community-led response mechanisms and the need for preparedness and global health security.


title: Single port access transumbilical laparoscopic Roux-en-Y gastric bypass using the SILS Port: first reported case.

text: The emergence of natural orifice translumenal endoscopic surgery (NOTES) has brought significantly more attention to the single-incision transumbilical laparoscopic approach (SILS) for minimally invasive surgery. SILS combines the cosmetic advantage of NOTES with the technical familiarity of the conventional multiport laparoscopic approach. Additionally, SILS does not involve penetration of an organ, nor does it involve the steep learning curve and costly instruments associated with NOTES. Given these advantages, the authors believe that the single-incision transumbilical approach highlights the future direction of minimally invasive surgery. However, because of the associated technical challenges, the single-incision approach has not quite yet achieved the crossover to advanced surgical procedures that conventional multiport laparoscopy achieved in its early years. In this report, the authors present what is, to the best of their knowledge, the first reported case of a single-port access laparoscopic Roux-en-Y gastric bypass using the SILS Port placed through a single intraumbilical skin incision.


title: Mining the physical infrastructure: Opportunities, barriers and interventions in promoting structural components reuse.

text: Construction is the most resource intensive sector in the world. It consumes more than half of the total global resources; it is responsible for more than a third of the total global energy use and associated emissions; and generates the greatest and most voluminous waste stream globally. Reuse is considered to be a material and carbon saving practice highly recommended in the construction sector as it can address both waste and carbon emission regulatory targets. This practice offers the possibility to conserve resources through the reclamation of structural components and the carbon embedded in them, as well as opportunities for the development of new business models and the creation of environmental, economic, technical and social value. This paper focuses on the identification and analysis of existing interventions that can promote the reuse of construction components, and outlines the barriers and opportunities arising from this practice as depicted from the global literature. The main conclusions that derive from this study are that the combination of incentives that promote reuse of construction components and recycling of the rest of the construction materials with the provision of specialised education, skills and training would transform the way construction sector currently operates and create opportunities for new business development. Moreover, a typology system developed based on the properties and lifetime of construction components is required in order to provide transparency and guidance in the way construction components are used and reused, in order to make them readily available to designers and contractors. Smart technologies carry the potential to aid the development and uptake of this system by enabling efficient tracking, storage and archiving, while providing information relevant to the environmental and economic savings that can be regained, enabling also better decision-making during construction and deconstruction works. However, further research is required in order to investigate the opportunities and constraints of the use of these technologies.


title: Epidemiological and Clinical Characteristics of Patients with Middle East Respiratory Syndrome Coronavirus in Iran in 2014.

text: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was a great global concern in 2014. It has a wide range of manifestations that may differ in each area as well as high mortality. In this study, we report the epidemiological characteristics, history, clinical, and paraclinical information of all 5 patients from Iran with laboratory-confirmed MERS-CoV. All patients were from Kerman province. None of them had a history of travel, contact with animals, or consumption of camel milk products, however, all of the patients had contact with a person who had been in Saudi-Arabia and experienced respiratory infection. One of the 5 patients was a man and 2 passed away from the disease. Fever and respiratory symptoms were the most common symptoms, and 2 patients had watery diarrhea. Alveolar patterns were observed in all available chest radiograms, and 3 patients had elevated liver aminotransferase levels. Two of these patients had leukopenia, and none had renal failure. In conclusion, the results of this study underscore the need for all patients with acute respiratory symptoms with contact with a person who has recently traveled to Saudi-Arabia and experienced respiratory infection to be investigated for MERS-CoV.


title: Long-term effect on donor sites after components separation: a radiographic analysis.

text: BACKGROUND The long-term implications of components separation for the lateral oblique and rectus muscles remain unknown. The authors hypothesized that recreation of the tendinous insertion of the linea alba through components separation results in expansion of the rectus muscle with potential atrophy of the external obliques. METHODS The authors conducted a retrospective study analyzing preoperative and long-term postoperative computed tomographic scans for consecutive patients undergoing bilateral components separation at a single institution over a 5-year period. Standardized measurements (area, width, and thickness) were recorded for the rectus abdominis, external oblique, internal oblique, and transversus abdominis at the L3-L4 level on axial imaging. RESULTS Twenty-eight patients with a mean time to follow-up computed tomographic scan of 17.4±1.6 months were reviewed. After reconstruction of the linea alba, the right and left rectus muscles significantly increased in area (right, 38.8±6.3 percent; left, 35.7±6.6 percent; p<0.0001) and width (right, 51.8±9.9 percent; left, 39.9±7.4 percent; p<0.0001) while decreasing in thickness (right, -17.8±7.8 percent; left, -12.8±5.0 percent; p≤0.02). The right and left external oblique muscles significantly decreased in area (right, -10.7±4.7 percent; left, -8.92±4.01 percent; p≤0.03). In contrast, the internal oblique (right, 21.6±4.9 percent; left, 16.4±4.5 percent; p≤0.001) and transversus abdominis (right, 23.0±4.7 percent; left, 24.2±6.2 percent; p<0.0001) muscles increased significantly in area following surgery. CONCLUSIONS Reestablishing the midline with components separation results in expansion of the rectus muscle, atrophy of the external oblique muscle, and presumed compensatory hypertrophy of the internal oblique and transversus abdominis muscles. Future studies are needed to determine the functional implications of these changes. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.


title: Robotic assisted laparoscopic radical cystectomy with stentless intracorporeal modified Ves.Pa neobladder: early experience.

text: This study aimed at demonstrating the feasibility of robotic assisted laparoscopic radical cystectomy with pure intracorporeal modified Ves.Pa neobladder with stentless ureteroileal anastomosis. Pure intracorporeal robotic assisted laparoscopic technique has been recently developed with a select number of high-volume centers utilizing various operative and neobladder techniques. We reviewed the patient characteristics, operative details and perioperative courses in the two patients who have undergone robotic assisted laparoscopic radical cystectomy with pure intracorporeal modified Ves.Pa neobladder and one who has undergone the Hautmann W neobladder. These results were compared to other contemporary robotic neobladder series. We demonstrate technical success with similar operative and perioperative results with the modified Ves.Pa neobladder. The robotic pure intracorporeal modified Ves.Pa neobladder is a technically feasible operation and may be easier to perform compared to other neobladders. Initial experience suggests operative time and perioperative outcomes are similar to other robotic techniques.


title: Prevalence and clinical outcome of respiratory viral infections among children with cancer and febrile neutropenia.

text: Background: The role of respiratory viruses (RV) in children with cancer having febrile neutropenic episodes has not been well studied. The objectives of our study were to investigate the prevalence and clinical outcomes of Respiratory viral infection (RVI). Methods: Children with cancer and febrile neutropenia (FN) having acute respiratory infections (ARI) were considered as cases and febrile neutropenic cancer patients without ARI were considered as controls. A throat swab sample was obtained for the detection of 21-respiratory pathogens. Results: A total of 81 episodes of FN in cases and 37 episodes of FN in controls were included. Prevalence of RVI (at least 1 RV) was seen in 76.5% of cases and 48.6% of controls (p = 0.005). The mixed-respiratory viruses (co-infections of ≥2 viruses) were seen only in cases (26%) (p = 0.00). Rhinovirus (36.8%) and respiratory syncytial virus (13.6%) were the most frequently detected viruses. Median duration of fever before presentation was more in cases with RVI compared to without RVI [2 (1-5) days vs 1 (1-5) day (p = 0.012)]. The median total duration of febrile period was 4 (IQR, 3-6) days in cases with RVI and 3 (IQR, 1-4) days in cases without RVI (p = 0.005). The median duration of antibiotic days were longer in cases with RVI as compared to patients without RVI [9 (IQR, 7-17) days vs 7 (IQR, 6-10) days (p = 0.046)] respectively. Conclusion: There was high prevalence of RVI in children with cancer and FN; more in association with ARI. The RVI were associated with prolonged febrile period and days of antibiotics therapy.


title: Virus-mimetic polymer nanoparticles displaying hemagglutinin as an adjuvant-free influenza vaccine.

text: The generation of virus-mimetic nanoparticles has received much attention in developing a new vaccine for overcoming the limitations of current vaccines. Thus, a method, encompassing most viral features for their size, hydrophobic domain and antigen display, would represent a meaningful direction for the vaccine development. In the present study, a polymer-templated protein nanoball with direction oriented hemagglutinin1 on its surface (H1-NB) was prepared as a new influenza vaccine, exhibiting most of the viral features. Moreover, the concentrations of antigen on the particle surface were controlled, and its effect on immunogenicity was estimated by in vivo studies. Finally, H1-NB efficiently promoted H1-specific immune activation and cross-protective activities, which consequently prevented H1N1 infections in mice.


title: Percutaneous microwave ablation of renal angiomyolipomas in tuberous sclerosis complex to improve the quality of life: preliminary experience in an Italian center.

text: AIM To evaluate efficacy, safety and quality of life of the patients with renal angiomyolipomas (AMLs) associated with tuberous sclerosis complex (TSC) treated with percutaneous microwave ablation (MWA). MATERIALS AND METHODS Nine patients (7 females and 2 males; mean age 27.6 years, range 23-34), with 10 renal AMLs with a mean size of 6.3 cm (range 4.5-8.5) were treated with image-guided percutaneous MWA. Indications for treatment were the risk of rupture/hemorrhage due to size greater than 4 cm and symptomatology; in one case, a previous hemorrhage was the indication for treatment. During follow-up, the volume of the ablated AMLs and its relationship with the relief of symptoms were registered. Technical and clinical success, safety, and quality of life (QOL) were evaluated in a mean follow-up of 9 months (range 3-12). RESULTS Technical success was obtained in all cases. Clinical success was obtained in all cases; the volume of the ablated AMLs was not related with symptoms relief; all patients referred a significant improvement in their QOL, with a regularization of daily activities. There were no major procedural complications or delayed adverse events. A small self-limited post-procedural subcapsular hematoma was registered. Post-ablation syndrome was registered in 5 cases and was self-limited in all cases. CONCLUSIONS Symptoms relief, lower risk of hemorrhage and a normalized QOL were obtained in all patients with a safe and mini-invasive procedure.


title: Salvage surgery for a super-responder by gefitinib therapy for advanced lung cancer.

text: Salvage surgery after gefitinib therapy in a 66-year-old female with cT4N1M1a lung adenocarcinoma in the right middle lobe, which had gene mutation of epidermal growth factor receptor, is presented. The patient had bulky hilar lymph nodes, pleural dissemination, and pulmonary metastases in the ipsilateral lobes. After 3 courses of chemotherapy, the patient was treated with gefitinib, resulting in partial response, i.e. only the primary tumor and the middle lobe atelectasis remained. We performed the middle lobe lobectomy aimed at local control and pathological confirmation of the remaining tumor. Because the hilum of the middle lobe was occupied with scar tissue, its pulmonary vein had to be cut within the pericardium and its pulmonary artery and bronchus had to be transected simultaneously with a stapler. Pathological stage was yp-T2aN0N0 with Ef 2. For salvage surgery after good response to gefitinib therapy, it should be taken care to expose pulmonary vessels.


Endoscopic sleeve gastroplasty of the remnant stomach in Roux-en-Y gastric bypass: a novel approach to a gastrogastric fistula with weight regain.


title: Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods.

text: Alphaviral enzymes are synthesized in a single polypeptide. The nonstructural polyprotein (nsP) is processed by its nsP2 cysteine protease to produce active enzymes essential for viral replication. Viral proteases are highly specific and recognize conserved cleavage site motif sequences (~6-8 amino acids). In several Group IV viruses, the nsP protease(s) cleavage site motif sequences can be found in specific host proteins involved in generating the innate immune responses and, in some cases, the targeted proteins appear to be linked to the virus-induced phenotype. These viruses utilize short stretches of homologous host-pathogen protein sequences (SSHHPS) for targeted destruction of host proteins. To identify SSHHPS the viral protease cleavage site motif sequences can be inputted into BLAST and the host genome(s) can be searched. Cleavage initially can be tested using the purified nsP viral protease and fluorescence resonance energy transfer (FRET) substrates made in E. coli. The FRET substrates contain cyan and yellow fluorescent protein and the cleavage site sequence (CFP-sequence-YFP). This protease assay can be used continuously in a plate reader or discontinuously in SDS-PAGE gels. Models of the bound peptide substrates can be generated in silico to guide substrate selection and mutagenesis studies. CFP/YFP substrates have also been utilized to identify protease inhibitors. These in vitro and in silico methods can be used in combination with cell-based assays to determine if the targeted host protein affects viral replication.


title: Transumbilical single-incision laparoscopic resection of focal hepatic lesions.

text: BACKGROUND AND OBJECTIVES Transumbilical single-incision laparoscopic surgery (SILS) is gaining in popularity as a minimally invasive technique. The reduced pain and superior cosmetic appearance it affords make it attractive to many patients. For this study, we focused on SILS, analyzing the outcomes of transumbilical single-incision laparoscopic liver resection (SILLR) achieved at our institution between January 2010 and February 2013. PATIENTS AND METHODS Pre- and postoperative data from 17 patients subjected to transumbilical SILLR for various hepatic lesions (8 hemangiomas, 2 hepatocellular carcinomas, 2 metastases, 2 calculi of left intrahepatic duct, and 3 adenomas) were assessed. Altogether, eight wedge resections, seven left lateral lobectomies, a combination wedge resection/left lateral lobectomy, and a proximal left hemihepatectomy segmentectomy were performed, as well as four simultaneous laparoscopic cholecystectomies. In each instance, three ports were installed through an umbilical incision. Once vessels and bleeding were controlled, the lesion(s) were resected with 5-mm margins of normal liver. Resected tissues were then bagged and withdrawn through the umbilical incision. The follow-up period lasted for a minimum of 6 months. RESULTS All 17 patients were successfully treated through a single umbilical incision. The procedures required 55 to 185 minutes to complete, with blood loss of 30 to 830 mL. Subjects regained bowel activity 0.8 to 2.3 days postoperatively and were discharged after 3 to 10 days. There were few complications (23.5%), limited to pleural effusion, wound infection, and incisional hernia. CONCLUSIONS Transumbilical SILLR is challenging to perform through conventional laparoscopic instrumentation. The risk of bleeding and technical difficulties is high for lesions of the posterosuperior hepatic segment. Surgical candidates should be carefully selected to optimize the benefits of this technique.


title: Biopsychopharmacosocial approach to assess impact of social distancing and isolation on mental health in older adults.

text: It is impossible to predict or comprehend the impact of the ongoing COVID-19 pandemic. The UK Government's advice for vulnerable people, including older adults, to move towards self-isolation and social distancing is likely to reduce rates of transmission, the risk of severe illness and the impact on the acute health services. Although justified and necessary, this process of isolation is likely to have a negative impact on the mental health of these vulnerable groups, especially older people. It will become increasingly important for community health professionals to assess subtle changes in older persons' mental health, as the duration of this period of isolation remains unclear. The biopsychopharmacosocial model provides one method of assessing mental health and planning health and social care needs. This article hopes to guide community health professionals through the specifics of this assessment model in relation to the growing COVID-19 pandemic.


Management strategy of novel coronavirus (COVID-19) pneumonia in the radiology department: a Chinese experience.


title: Cardiovascular Risk Factors in Severely Obese Adolescents: The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Study.

text: IMPORTANCE Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group. OBJECTIVE To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children's Hospital in Columbus, Ohio; Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio; Texas Children's Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children's Hospital of Alabama in Birmingham. Consecutive patients aged 19 years or younger were offered enrollment in a long-term outcome study; the final analysis cohort consisted of 242 participants. MAIN OUTCOMES AND MEASURES This report examined the preoperative prevalence of CVD risk factors (ie, fasting hyperinsulinemia, elevated high-sensitivity C-reactive protein levels, impaired fasting glucose levels, dyslipidemia, elevated blood pressure, and diabetes mellitus) and associations between risk factors and body mass index (calculated as weight in kilograms divided by height in meters squared), age, sex, and race/ethnicity. Preoperative data were collected within 30 days preceding bariatric surgery. RESULTS The mean (SD) age was 17 (1.6) years and median body mass index was 50.5. Cardiovascular disease risk factor prevalence was fasting hyperinsulinemia (74%), elevated high-sensitivity C-reactive protein levels (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%). The risk of impaired fasting glucose levels, elevated blood pressure, and elevated high-sensitivity C-reactive protein levels increased by 15%, 10%, and 6%, respectively, per 5-unit increase in body mass index (P < .01). Dyslipidemia (adjusted relative risk = 1.60 [95% CI, 1.26-2.03]; P < .01) and elevated blood pressure (adjusted relative risk = 1.48 [95% CI, 1.16-1.89]; P < .01) were more likely in adolescent boys compared with adolescent girls. White individuals were at greater risk of having elevated triglyceride levels (adjusted relative risk = 1.76 [95% CI, 1.14-2.72]; P = .01) but were less likely to have impaired fasting glucose levels (adjusted relative risk = 0.58 [95% CI, 0.38-0.89]; P = .01). CONCLUSIONS AND RELEVANCE Numerous CVD risk factors are apparent in adolescents undergoing weight-loss surgery. Increasing body mass index and male sex increase the relative risk of specific CVD risk factors. These data suggest that even among severely obese adolescents, recognition and treatment of CVD risk factors is important to help limit further progression of disease.


title: Assessment of extended-release opioid analgesics for the treatment of chronic pain.

text: Approximately 3.8 million patients annually receive extended-release (ER) or long-acting opioid prescriptions in the outpatient setting, around half of which are written by primary care physicians. Compared with short-acting, immediate-release (IR) formulations, ER and oral long-acting opioid analgesics are associated with clinical advantages, such as extended periods of time during which drug plasma levels are within the therapeutic range, decreased peak-to-trough fluctuations, and prolonged analgesia over the dosing period. Additionally, ER opioids offer a more convenient, less frequent dosing regimen to chronic pain patients who are often taking several concomitant medications. The increased utilization of ER opioids has been accompanied by a rise in the misuse and abuse of these formulations. Certain pharmacokinetic parameters (e.g., longer time to maximum drug plasma concentration, lower maximum drug plasma concentration) may decrease the abuse potential of intact ER opioids by limiting the positive subjective and reinforcing effects relative to IR formulations. Putative abuse-deterrent formulations have also recently been introduced to impede physical manipulation of these formulations, or reduce the harm resulting from such behavior. Such formulations may represent an incremental advance to reduce non-oral forms of abuse. This article reviews the pharmacokinetic profiles and abuse-deterrent features of newer ER opioid analgesics for the treatment of moderate to severe chronic pain.


title: SARS-CoV-2 RNA in wastewater anticipated COVID-19 occurrence in a low prevalence area

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 200,000 reported COVID-19 cases in Spain resulting in more than 20,800 deaths as of April 21, 2020. Faecal shedding of SARS-CoV-2 RNA from COVID-19 patients has extensively been reported. Therefore, we investigated the occurrence of SARS-CoV-2 RNA in six wastewater treatments plants (WWTPs) serving the major municipalities within the Region of Murcia (Spain), the area with the lowest COVID-19 prevalence within Iberian Peninsula. Firstly, an aluminum hydroxide adsorption-precipitation concentration method was validated using a porcine coronavirus (Porcine Epidemic Diarrhea Virus, PEDV) and mengovirus (MgV). The procedure resulted in average recoveries of 10 ± 3.5% and 10 ± 2.1% in influent water (n = 2) and 3.3 ± 1.6% and 6.2 ± 1.0% in effluent water (n = 2) samples for PEDV and MgV, respectively. Then, the method was used to monitor the occurrence of SARS-CoV-2 from March 12 to April 14, 2020 in influent, secondary and tertiary effluent water samples. By using the real-time RT-PCR (RT-qPCR) Diagnostic Panel validated by US CDC that targets three regions of the virus nucleocapsid (N) gene, we estimated quantification of SARS-CoV-2 RNA titers in untreated wastewater waters of 5.4 ± 0.2 log(10) genomic copies/L on average. Two secondary water samples resulted positive (2 out of 18) and all tertiary water samples tested as negative (0 out 12). This environmental surveillance data were compared to declared COVID-19 cases at municipality level, revealing that members of the community were shedding SARS-CoV-2 RNA in their stool even before the first cases were reported by local or national authorities in many of the cities where wastewaters have been sampled. The detection of SARS-CoV-2 in wastewater in early stages of the spread of COVID-19 highlights the relevance of this strategy as an early indicator of the infection within a specific population. At this point, this environmental surveillance could be implemented by municipalities right away as a tool, designed to help authorities to coordinate the exit strategy to gradually lift its coronavirus lockdown.


title: Preoperative predictors of lymph node metastasis in clinical T1 adenocarcinoma.

text: Background The subcategory "solid component of tumor" is a new criterion of tumor categories in the updated eighth edition of the TNM classification. Nevertheless, the predictors of lymph node metastasis among patients with clinical T1 adenocarcinoma, based on the TNM classification 8th edition, remain unclear. This study aimed to identify the preoperative predictors of lymph node metastasis in clinical T1 adenocarcinoma by comparing clinicopathological characteristics between the groups with and without lymph node metastasis. Methods We performed a retrospective observational single-center study at the Sendai Kousei Hospital. From January 2012 to September 2019, we included 515 patients who underwent curative lobectomy or segmentectomy and mediastinal lymph node dissection among those with clinical T1 adenocarcinoma according to the UICC-TNM staging 8th edition. They were divided into two groups: those with lymph node metastasis (positive group) and those without (negative group). The clinicopathological factors were retrospectively analyzed and compared between the groups. Results In univariate analysis, carcinoembryonic antigen (>5.0 ng/mL) (P=0.0007), maximum standardized uptake (>3.5) (P<0.0001), clinical T factor (T1c) (P<0.0001), and consolidation tumor ratio (>0.85) (P<0.0001) were significant predictors of lymph node metastasis. Multivariate analysis revealed that maximum standardized uptake SUVmax (>3.5) (odds ratio =10.4, P<0.0001) was independently associated with lymph node metastasis. In univariate analysis, carcinoembryonic antigen (>5.0) (P=0.048) was the only predictor of lymph node metastasis among patients of cT1b, while no parameters were identified as significant predictors among patients of cT1c. Conclusions SUVmax and CEA are useful preoperative predictors of lymph node metastases in patients with clinical T1 adenocarcinoma, stratified to T1b and T1c, based on the 8th TNM classification.


title: Successes, revisions, and postoperative complications in 446 Mohs defect repairs.

text: OBJECTIVE To determine factors predictive of complications and the need for adjunctive treatments repair of facial Mohs defects. METHODS Charts of patients undergoing repair of facial defects from 2000 to 2010 in an academic facial plastic surgery practice were reviewed for patient medical history, tumor type, defect site and size, method of repair, postoperative sequelae, and adjunctive treatments. RESULTS A total of 446 Mohs defect repairs were analyzed. Average patient age was 61.54 ± 14.81 years. The average defect size was 17.55 ± 10.48 mm. Overall complications were fairly uncommon and required intervention in only 18.74%; other than postoperative corticosteroid injections, additional procedures were necessary in only 6.95% of patients. Female sex; Fitzpatrick skin type 3; upper lip and nasal defects; glabellar, superiorly based nasolabial, bilobed, and rhombic flaps; and dermal suture extrusion were associated with increased complications. The most common complications seen were scar erythema and flap pincushioning. The most common revision techniques performed/recommended were selective laser photothermolysis (3.59%) and scar excision (3.59%). CONCLUSION Repair of Mohs defects uncommonly requires adjunctive/revision techniques to reach satisfactory appearance. By understanding certain factors related to the patient, the defect, and the method of repair, surgeons can better choose reparative techniques and anticipate patient postoperative needs.


Severe necrotizing pneumonia in children, Houston, Texas, USA.


title: Evidence of Respiratory Syncytial Virus Spread by Aerosol. Time to Revisit Infection Control Strategies?

text: RATIONALE Respiratory syncytial virus (RSV) is a highly contagious pathogen with a huge global health impact. It is a major cause of hospital-acquired infection; a large number of those exposed develop infection. Those infected in hospital are at increased risk of a severe clinical course. Prevention of nosocomial spread currently focuses on spread by hand and large droplets. There is little research evidence to determine if aerosol spread of infectious RSV is possible. OBJECTIVES To determine if the air surrounding infants with RSV-positive bronchiolitis contains RSV in aerosolized particles that remain capable of causing infection. METHODS The amount of RSV contained in aerosolized particles produced by infants with bronchiolitis due to RSV was measured using viable impactor sampling. The ability of RSV contained in these particles to infect healthy and chronic obstructive pulmonary disease (COPD) human ciliated respiratory epithelium was determined. RESULTS We showed for the first time that infants with RSV-positive bronchiolitis nursed in a ward setting or ventilated in intensive care produced large numbers of aerosol particles containing RSV that remained infectious and were capable of infecting healthy and COPD human ciliated epithelium. A significant amount of RSV was found in particles with aerodynamic diameters less than 5 μm. CONCLUSIONS Many of the aerosolized particles that contained RSV in the air surrounding infants with bronchiolitis were sufficiently small to remain airborne for a significant length of time and small enough to be inhaled and deposited throughout the respiratory tract. It is likely that this leads to spread of infection to others, with dissemination of infection throughout the respiratory tract.


title: Federalism Complicates the Response to the COVID-19 Health and Economic Crisis: What Can Be Done?

text: Federalism has complicated the U.S. response to the novel coronavirus. States' actions to address the pandemic have varied widely, and federal and state officials have provided conflicting messages. This fragmented approach surely cost time and lives. Federalism will shape the long-term health and economic impacts of COVID-19, including plans for the future, for at least two reasons: First, federalism exacerbates inequities, as some states have a history of under-investing in social programs, especially in certain communities. Second, many of the states with the deepest needs are poorly equipped to respond to emergencies due to low taxes and distrust of government, leading to inadequate infrastructure. These dynamics are not new, but they have been laid bare by this crisis. What can policymakers do to address the inequities in health and economic outcomes that federalism intensifies? The first section of this paper offers a case study, using the Mississippi Delta to illustrate the role of federalism in perpetuating the connection between place, health, and economics. The second section examines challenges that safety net programs will face moving beyond the acute phase of COVID-19. Our final section explores near-, middle-, and long-term policy options to mitigate federalism's harmful side effects.


title: Long-term outcomes of percutaneous coronary interventions or coronary artery bypass grafting for left main coronary artery disease in octogenarians (from a Drug-Eluting stent for LefT main Artery registry substudy).

text: Percutaneous coronary intervention (PCI) with drug-eluting stents is an accepted alternative to surgery for the treatment of unprotected left main coronary artery (ULMCA) disease, but the long-term outcome in elderly patients is unclear. Aim of our study was to compare the clinical outcomes of octogenarians with ULMCA disease treated either with PCI with drug-eluting stents or coronary artery bypass grafting (CABG). The primary study end point was the composite of death, cerebrovascular accident, and myocardial infarction at follow-up. A total of 304 consecutive patients with ULMCA stenosis treated with PCI or CABG and aged ≥80 years were selected and analyzed in a large multinational registry. Two hundred eighteen were treated with PCI and 86 with CABG. During the hospitalization, a trend toward a higher mortality rate was reported in PCI-treated patients (3.5% vs 7.3%, p = 0.32). At a median follow-up of 1,088 days, the incidence of the primary end point was similar in the 2 groups (32.6% vs 30.2%, p = 0.69). Incidence of target vessel revascularization at follow-up was higher in PCI-treated patients (10% vs 4.2%, p = 0.05). At multivariate analysis, left ventricular ejection fraction was the only independent predictor of the primary end point (hazard ratio 0.95, 95% confidence interval 0.91 to 0.98, p = 0.001). After adjustment with propensity score, the revascularization strategy was not significantly correlated to the incidence of the primary end point (hazard ratio 0.98, 95% confidence interval 0.57 to 1.71, p = 0.95). In octogenarians, no difference was observed in the occurrence of the primary end point after PCI or CABG for the treatment of ULMCA disease. However, the rate of target vessel revascularization was higher in the PCI group.


title: Critical role of histone H3 lysine 27 demethylase Kdm6b in the homeostasis and function of medullary thymic epithelial cells.

text: Medullary thymic epithelial cells (mTECs) play a central role in the establishment of T cell central immunological tolerance by promiscuously expressing tissue-restricted antigens (TRAs) and presenting them to developing T cells, leading to deletion of T cells responding to self-antigens. However, molecular mechanisms especially epigenetic regulation of mTEC homeostasis and TRA expression remain elusive. Here we show that the H3K27 demethylase Kdm6b is essential to maintain the postnatal thymic medulla by promoting mTEC survival and regulating the expression of TRA genes. Moreover, mice lacking Kdm6b developed pathological autoimmune disorders. Mechanically, Kdm6b exerted its function by reducing repressive H3K27 trimethylation (H3K27me3) at the promoters of anti-apoptotic gene Bcl2 and a set of Aire-dependent TRA genes. Thus, our findings reveal a dual role of Kdm6b in the regulation of mTEC-mediated T cell central tolerance.


title: Partial auricular reconstruction with porous polyethylene frameworks and superficial temporoparietal fascia flap.

text: Untreated acquired auricular damage can be a psychological burden, especially for younger patients. The significance of auricular reconstruction in patients with microtia in terms of quality of life has already been demonstrated. In these patients the use of porous polyethylene combined with a temporoparietal fascia flap has proven to be a suitable method for achieving good cosmetic results. Here, we describe how to use porous polyethylene combined with an endoscopically harvested temporoparietal fascia flap and autologous skin grafts for the reconstruction of acquired partial auricle defects and present outcomes and patient benefit. Ten consecutive patients were asked to answer validated questionnaires [modified Glasgow Benefit Inventory (GBI)] determining the effects of partial ear reconstruction on their health-related quality of life. These patients were seen regularly in our outpatient clinic for documentation and postoperative counseling. All patients returned a valid questionnaire; 80% were satisfied with the esthetic result. In retrospect, all patients would again decide to undergo surgery. The mean total GBI score was 27.8 (median 29.2, p < 0.05) reflecting an improvement of the health-related quality of life due to the operation. Odd feeling, numbness and the formation of scar tissue were the main complaints. Partial auricular reconstruction using porous polyethylene combined with an endoscopically harvested temporoparietal fascia flap and autologous skin grafts yields good esthetic results and can significantly increase patient's health-related quality of life.


Covid-19: "Staggering number" of extra deaths in community is not explained by covid-19.


title: Crimean-Congo hemorrhagic fever virus entry and replication is clathrin-, pH- and cholesterol-dependent.

text: To date, the entry pathway and replication mechanisms for members of the family Bunyaviridae, and especially for Crimean-Congo hemorrhagic fever virus (CCHFV), are poorly understood. Considering the severity of disease and the widespread geographical occurrence of CCHFV, investigating viral entry is of great value for development of antivirals. In this study, we have shown that knockdown of clathrin by small interfering RNA significantly reduced CCHFV nucleocapsid protein and viral RNA levels, suggesting that CCHFV utilizes clathrin-dependent endocytosis. In contrast, caveolin-1, an important constituent of caveolae endocytosis, is not important in CCHFV infection. Moreover, treatment with drugs that are known to interfere with the formation of clathrin-coated pits (sucrose and chlorpromazine) or endosome acidification (bafilomycin A1 and NH(4)Cl) also supported a clathrin-dependent pathway in the entry process of CCHFV. Finally, we demonstrated that cholesterol depletion in the cell plasma membrane significantly inhibited CCHFV infection. In the presence of exogenous cholesterol, this process was reversed, suggesting that cholesterol is important in the life cycle of CCHFV.


title: Pipeline Embolization Device for Large/Giant or Fusiform Aneurysms: An Initial Multi-Center Experience in Korea.

text: PURPOSE The purpose of this study was to assess the safety and early outcomes of the Pipeline device for large/giant or fusiform aneurysms. MATERIALS AND METHODS The Pipeline was implanted in a total of 45 patients (mean age, 58 years; M:F=10:35) with 47 large/giant or fusiform aneurysms. We retrospectively evaluated the characteristics of the treated aneurysms, the periprocedural events, morbidity and mortality, and the early outcomes after Pipeline implantation. RESULTS The aneurysms were located in the internal carotid artery (ICA) cavernous segment (n=25), ICA intradural segment (n=11), vertebrobasilar trunk (n=8), and middle cerebral artery (n=3). Procedure-related events occurred in 18 cases, consisting of incomplete expansion (n=8), shortening-migration (n=5), transient occlusion of a jailed branch (n=3), and in-stent thrombosis (n=2). Treatment-related morbidity occurred in two patients, but without mortality. Both patients had modified Rankin scale (mRS) scores of 2, but had an improved mRS score of 0 at 1-month follow-up. Of the 19 patients presenting with mass effect, 16 improved but three showed no changes in their presenting symptoms. All patients had excellent outcomes (mRS, 0 or 1) during the follow-up period (median, 6 months; range, 2-30 months). Vascular imaging follow-up (n=31, 65.9%; median, 3 months, range, 1-25 months) showed complete or near occlusion of the aneurysm in 24 patients (77.4%) and decreased sac size in seven patients (22.6%). CONCLUSION In this initial multicenter study in Korea, the Pipeline seemed to be safe and effective for large/giant or fusiform aneurysms. However, a learning period may be required to alleviate device-related events.


title: Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial.

text: PURPOSE We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury. METHODS Using a 23 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO2 and to normoxia (arterial oxygen tension [PaO2] 10-15 kPa) or moderate hyperoxia (PaO2 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months. RESULTS In total 120 patients were included in the analyses. There was a clear separation in PaCO2 (p < 0.001) and PaO2 (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9-28.3 µg/l) in the low-normal PaCO2 group and 22.5 µg/l (14.2-34.9 µg/l) in the high-normal PaCO2 group, p = 0.400; and 22.3 µg/l (14.8-27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2-34.9 µg/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO2 and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes. CONCLUSIONS Both high-normal PaCO2 and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected. REGISTRATION ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.


title: In vivo SPECT and real-time gamma camera imaging of biodistribution and pharmacokinetics of siRNA delivery using an optimized radiolabeling and purification procedure.

text: Single photon emission computed tomography (SPECT) imaging provides a three-dimensional method for exactly locating gamma emitters in a noninvasive procedure under in vivo conditions. For characterization of siRNA delivery systems, molecular imaging techniques are extremely helpful to follow biodistribution under in experimental animal studies. Quantification of biodistribution of siRNA and nonviral delivery systems using this technique requires efficient methods to stably label siRNA with a gamma emitter (e.g., 111In or 99mTc) and to purify labeled material from excesses of radiolabel or linkers. In the following study, we have optimized labeling and purification of siRNA, which was then applied as free siRNA or after complexation with polyethylenimine (PEI) 25 kDa for in vivo real-time gamma camera and SPECT imaging. Quantification of scintillation counts in regions of interest(ROIs) was compared to conventional scintillation counting of dissected organs, and the data acquired by imaging was shown to corroborate that of scintillation counting. This optimization and proof of principle study demonstrates that biodistribution and pharmacokinetics of siRNA and the corresponding polyplexes can be determined using SPECT, leading to comparable results as conventional methodology.


title: Cost-Effectiveness of Treatment Options for Neuropathic Pain: a Systematic Review.

text: BACKGROUND Neuropathic pain significantly reduces an individual's quality of life and places a significant economic burden on society. As such, many cost-effectiveness analyses (CEAs) have been published for treatments available for neuropathic pain. OBJECTIVES The primary objective of this systematic review was to provide a detailed summary of the estimates of cost-effectiveness from published CEAs comparing available treatments for neuropathic pain. The secondary objectives were to identify the key drivers of cost-effectiveness and to assess the quality of published CEAs in neuropathic pain. METHODS We searched Embase, MEDLINE, Cochrane CENTRAL and seven other databases to identify CEAs reporting the costs, health benefits (e.g., quality-adjusted life-years or disability-adjusted life-years) and summary statistics, such as incremental cost-effectiveness ratios, of treatments for neuropathic pain. We excluded studies reporting diseases other than neuropathic pain, those for which the full text was not available (e.g., conference abstracts), studies not written in English or not published in peer-reviewed journals, and narrative reviews, editorials and opinion papers. Titles and abstract reviews, full-text reviews, and data extraction were all performed by two independent reviewers, with disagreement resolved by a third reviewer. Mean costs, health benefits, and summary statistics were reported and qualitatively compared across studies, stratified by time horizon. Drivers of cost-effectiveness were assessed using reported one-way sensitivity analyses. The quality of all included studies was evaluated using the Tufts CEA Registry Quality Score and study reporting using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist. RESULTS A total of 22 studies were identified and included in this systematic review. Included studies were heterogeneous in the treatments compared, methodology and design, perspectives, and time horizons considered, making cross-study comparisons difficult. No single treatment was consistently the most cost-effective across all studies, but tricyclic antidepressants were the preferred treatment at a willingness-to-pay threshold of $US50,000 per quality-adjusted life-year in several studies with a short time horizon and a US payer perspective. Among the 14 studies reporting one-way sensitivity analyses, drivers of cost-effectiveness included utility values for health states and the likelihood of pain relief with treatment. The quality of the identified CEAs was moderate to high, and overall reporting largely met CHEERS recommendations. LIMITATIONS To assess drivers of cost-effectiveness and quality, we only included studies with the full text available and thus excluded some CEAs that reported cost-effectiveness results. The heterogeneity of the included studies meant that the study results could not be synthesized and comparison across studies was limited. CONCLUSIONS Though many pulished studies have evaluated the cost-effectiveness of treatments for neuropathic pain, significant heterogeneity between CEAs prevented synthesis of the results. Standardized methodology and improved reporting would allow for more reliable comparisons across studies.


title: Short-term surgical outcomes of laparoscopy-assisted versus totally laparoscopic Billroth-II gastrectomy for gastric cancer: a matched-cohort study.

text: BACKGROUND To evaluate feasibility and benefits of intracorporeal anastomosis, we compared short-term surgical outcomes between laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) with Billroth-II (B-II) anastomosis for gastric cancer. METHODS Sixty patients underwent attempted B-II TLDG from 2011 through 2013. Patients who underwent B-II LADG prior to 2011 were matched to TLDG cases for demographics, comorbidities, tumor characteristics, and TNM stage. Perioperative and short-term surgical outcomes were compared between the two groups. RESULTS Clinicopathological characteristics of both groups were comparable. The B-II TLDG group had a shorter hospital stay (9.4 vs. 12.0 days, P = 0.038) and average incision size was smaller (3.5 vs. 5.4 cm, P = 0.030) than in the B-II LADG group. Anastomotic leakage was not recorded in either group, and there were no differences in the rates of perioperative complications and in inflammatory parameters between the two groups. CONCLUSIONS This study suggests that B-II TLDG is feasible, compared to B-II LADG, and that it has several advantages over LADG, including a smaller incision, a shorter hospital stay, and more convenience during surgery. However, prospective randomized controlled studies are still needed to confirm that B-II TLDG can be used as a standard procedure for LDG.


title: Model-based PEEP optimisation in mechanical ventilation.

text: BACKGROUND Acute Respiratory Distress Syndrome (ARDS) patients require mechanical ventilation (MV) for breathing support. Patient-specific PEEP is encouraged for treating different patients but there is no well established method in optimal PEEP selection. METHODS A study of 10 patients diagnosed with ALI/ARDS whom underwent recruitment manoeuvre is carried out. Airway pressure and flow data are used to identify patient-specific constant lung elastance (E lung) and time-variant dynamic lung elastance (E drs) at each PEEP level (increments of 5 cm H2O), for a single compartment linear lung model using integral-based methods. Optimal PEEP is estimated using E lung versus PEEP, Edrs-Pressure curve and E drs Area at minimum elastance (maximum compliance) and the inflection of the curves (diminishing return). Results are compared to clinically selected PEEP values. The trials and use of the data were approved by the New Zealand South Island Regional Ethics Committee. RESULTS Median absolute percentage fitting error to the data when estimating time-variant E drs is 0.9% (IQR = 0.5-2.4) and 5.6% [IQR: 1.8-11.3] when estimating constant E lung. Both E lung and E drs decrease with PEEP to a minimum, before rising, and indicating potential over-inflation. Median E drs over all patients across all PEEP values was 32.2 cmH2O/l [IQR: 26.1-46.6], reflecting the heterogeneity of ALI/ARDS patients, and their response to PEEP, that complicates standard approaches to PEEP selection. All E drs-Pressure curves have a clear inflection point before minimum E drs, making PEEP selection straightforward. Model-based selected PEEP using the proposed metrics were higher than clinically selected values in 7/10 cases. CONCLUSION Continuous monitoring of the patient-specific E lung and E drs and minimally invasive PEEP titration provide a unique, patient-specific and physiologically relevant metric to optimize PEEP selection with minimal disruption of MV therapy.


title: MA-NOS radical sigmoidectomy: report of a transvaginal resection in the human.

text: BACKGROUND With available laparoscopic and endoscopic instruments/technology a standard radical sigmoid resection is feasible and safe using transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS). METHODS The intervention was a transvaginal MA-NOS sigmoidectomy in a 78-year-old woman with a sigmoid adenocarcinoma. Maintaining triangulation the surgeon positioned himself at the right side of the patient and used the transvaginal trocar for dissection and stapling of both the inferior mesenteric vessels and the upper rectum. The colonic resection was performed extracorporeally in the conventional fashion and was followed by an intra-abdominal endoscopically assisted stapled anastomosis. RESULTS Advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All oncological principles governing resection and management were accomplished and the pathology examination confirmed a T3N1 lesion. The patient was discharged on the fourth postoperative day. CONCLUSION Transvaginal MA-NOS radical sigmoidectomy is a feasible and oncologically safe procedure. MA-NOS is a realistic option for avoiding the need of assisting incisions and related morbidity in the laparoscopic resection of large intra-abdominal lesions. Combined hybrid laparoscopic NOS in humans (MA-NOS) currently provides a safe and reliable way of defining future clinical applications and advantages of NOS and NOTES. Additionally, it stimulates the active development and evaluation of the underpinning technologies and instrumentation.


title: Association between Fellowship Training, Surgical Volume, and Laparoscopic Suturing Techniques among Members of the American Association of Gynecologic Laparoscopists.

text: Study Objective. To compare surgical volume and techniques including laparoscopic suturing among members of the American Association of Gynecologic Laparoscopists (AAGL) according to fellowship training status. Design. A web-based survey was designed using Qualtrics and sent to AAGL members. Results. Minimally invasive gynecologic surgery (FMIGS) trained surgeons were more likely to perform more than 8 major conventional laparoscopic cases per month (63% versus 38%, P < 0.001, OR [95% CI] = 2.78 [1.54-5.06]) and were more likely to perform laparoscopic suturing during these cases (32% versus 16%, P < 0.004, OR [95% CI] = 2.44 [1.25-4.71]). The non-fellowship trained (NFT) surgeons in private practice were less likely to perform over 8 conventional laparoscopic cases (34% versus 51%, P = 0.03, OR [95% CI] = 0.50 [0.25-0.99]) and laparoscopic suturing during these cases (13% versus 27%, P = 0.01, OR [95% CI] = 0.39 [0.17-0.92]) compared to NFT surgeons in academic practice. Conclusion. The surgical volume and utilization of laparoscopic suturing of FMIGS trained surgeons are significantly increased compared to NFT surgeons. Academic practice setting had a positive impact on surgical volume of NFT surgeons but not on FMIGS trained surgeons.


title: Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.

text: Hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery (CRS) holds promise as an adjunctive treatment strategy in malignancies affecting the peritoneal surface, effectively targeting remaining microscopic residual tumor. HIPEC increases concentrations of chemotherapy directly within the peritoneal cavity compared with the intravenous route and reduces the systemic side effects associated with prolonged adjuvant intraperitoneal exposure. Furthermore, hyperthermia increases tissue penetration and is synergistic with the therapeutic chemotherapy agents used. In ovarian cancer, evidence is building for its use in both primary and recurrent scenarios. In this review, we examine the history of HIPEC, the techniques used, and the available data guiding its use in primary and recurrent ovarian cancer.


title: Swine flu. Mexico's handling of A/H1N1 in comparative perspective.

text: Emerging infectious diseases (EIDs) pose international security threats because of their potential to inflict harm upon humans, crops, livestock, health infrastructure, and economies. Despite the scale of this threat, there are inherent limitations in preventing and controlling EIDs, including the scope of current disease surveillance efforts. All of this leads to the following questions in the context of Mexico's recent swine flu experience: What were the cultural, political, and economic challenges to Influenza A/H1N1 virus response in Mexico? By way of comparison, what can we learn from the U.S. experience in 1976 with A/New Jersey/76 (Hsw1N1), later referred to as H1N1? This article explores the comparative political economy of Mexico's handling of influenza virus A/H1N1 outbreak in 2009. Research provides notable observations-based on the strengths and weaknesses of each country's response--that can be used as a starting point of discussion for the design of effective EIDs surveillance programs in developing and middle-income countries. In the U.S., the speed and efficiency of the 1976 U.S. mobilization against H1N1 was laudable. Although the U.S. response to the outbreak is seldom praised, the unity of the scientific and political communities demonstrated the national ability to respond to the situation. Mexico's strongest characteristics were its transparency, as well as the cooperation the country exhibited with other nations, particularly the U.S. and Canada. While Mexico showed savvy in its effective management of public and media relations, as the article details, political, economic, and cultural problems persisted.


title: Transvaginal laparoscopically assisted endoscopic cholecystectomy: preliminary clinical results for a series of 43 cases in China.

text: BACKGROUND Transvaginal cholecystectomy has been performed successfully at several research institutions worldwide using natural orifice transluminal endoscopic surgery (NOTES) techniques. However, it is a growing new surgical concept in China. Several technical challenges hinder the safe clinical application of NOTES. This study investigated transvaginal endoscopic cholecystectomy performed with the assistance of a single umbilical trocar and achieved helpful initial clinical experience. METHODS From May 2009 to April 2010, a total of 43 transvaginal human cholecystectomies were performed. A single umbilical trocar was used for safe access and laparoscopic assistance during the operation. After the gallbladder had been removed through the vagina, the colpotomy was closed with absorbable stitches under direct vision. In addition, Student's t-test was performed for two samples to estimate the superiority of NOTES over a conventional laparoscopic cholecystectomy (LC) operation. RESULTS The procedure was successfully completed for all the patients. No intra- or post-operative complications occurred. The patients recovered promptly after surgery, and all were satisfied with ideal cosmetic outcomes. The postoperative pain, hospital stay, and cost of hospitalization with NOTES were much less than with conventional LC operations. CONCLUSIONS Although endoscopic instruments specifically designed for NOTES are not available, the addition of an umbilical trocar is an optimal way to allow safe performance of NOTES procedures in an easily reproducible manner. The authors' initial experience demonstrates that this hybrid technique is potentially feasible and effective for reducing postoperative pain and recovery times while improving the cosmetic results of transvaginal cholecystectomy.


title: Recurrent demyelination and remyelination in 37 young Bengal cats with polyneuropathy.

text: BACKGROUND With the exception of diabetic neuropathy, polyneuropathy associated with hyperchylomicronemia, and a few inherited polyneuropathies, peripheral neuropathies are poorly characterized in cats. A chronic polyneuropathy is described in a cohort of young Bengal cats. OBJECTIVE To characterize the clinical and histopathological features of a chronic-relapsing peripheral neuropathy in young Bengal cats. ANIMALS Thirty-seven young Bengal cats with clinical weakness consistent with peripheral neuropathy. METHODS Bengal cats were included in this study after a diagnosis of polyneuropathy was confirmed by muscle and peripheral nerve biopsy specimens. Pathological changes were characterized at the light and electron microscopic level and by morphometry. Clinical information and long-term outcome from case records of Bengal cats with histologically confirmed peripheral neuropathy were then assessed. RESULTS Nerve fiber loss within distal intramuscular nerve branches was a consistent finding in young Bengal cats with polyneuropathy. The most common abnormalities in peripheral nerve biopsies included inappropriately thin myelin sheaths and thinly myelinated fibers surrounded by supernumerary Schwann cell processes, indicative of repeated cycles of demyelination and remyelination. Recovery was common. Response to treatment could not be determined. CONCLUSIONS AND CLINICAL IMPORTANCE A chronic-relapsing form of polyneuropathy associated primarily with episodes of demyelination and remyelination was identified in young Bengal cats. The prognosis for recovery is good, although relapses are possible and there can be residual motor deficits.


title: Negative pressure therapy stimulates healing of critical-size calvarial defects in rabbits.

text: Negative pressure therapy (NPT) is the controlled application of subatmospheric pressure to wounds. It has been shown to stimulate healing across a broad spectrum of soft-tissue wounds, at least in part from the application of mechanical stress on cells and tissues in the wound environment. This study tests the hypothesis that application of NPT to cranial critical-size defects (CSD) in skeletally mature rabbits leads to osseous healing. NPT was delivered 1, 4, 6 or 10 days over CSD-containing calcium phosphate scaffolds placed in contact with intact dura. At 12 weeks after defect creation, NPT groups exhibited significantly greater defect bridging and bone within the scaffolds (P<0.01). Increasing duration of NPT did not result in a greater amount of bone within the scaffolds, but did increase the amount of bone distributed in the upper half of the scaffolds. Appearance of tissue within defects immediately following the removal of NPT at day 6 suggests alternating regions of dural compression and distention indicative of cell stretching. Dura and adjacent tissue were composed of multiple cell layers that extended up into the scaffolds, lining struts and populating pore spaces. An extracellular matrix densely populated with cells and capillaries, as well as larger vessels, infiltrated pores of NPT-treated scaffolds, while scattered spindle-shaped cells and sparse stroma are present within pores of control scaffolds. This rabbit model data suggest that NPT activates within mature dura a natural healing cascade that results in osseous tissue formation without the addition of exogenous factors or progenitor cells.


title: Cerebral near-infrared spectroscopy monitoring and neurologic outcomes in adult cardiac surgery patients: a systematic review.

text: BACKGROUND Near-infrared spectroscopy is used during cardiac surgery to monitor the adequacy of cerebral perfusion. In this systematic review, we evaluated available data for adult patients to determine (1) whether decrements in cerebral oximetry during cardiac surgery are associated with stroke, postoperative cognitive dysfunction (POCD), or delirium; and (2) whether interventions aimed at correcting cerebral oximetry decrements improve neurologic outcomes. METHODS We searched PubMed, Cochrane, and Embase databases from inception until January 31, 2012, without restriction on languages. Each article was examined for additional references. A publication was excluded if it did not include original data (e.g., review, commentary) or if it was not published as a full-length article in a peer-reviewed journal (e.g., abstract only). The identified abstracts were screened first, and full texts of eligible articles were reviewed independently by 2 investigators. For eligible publications, we recorded the number of subjects, type of surgery, and criteria for diagnosis of neurologic end points. RESULTS We identified 13 case reports, 27 observational studies, and 2 prospectively randomized intervention trials that met our inclusion criteria. Case reports and 2 observational studies contained anecdotal evidence suggesting that regional cerebral O(2) saturation (rSco(2)) monitoring could be used to identify cardiopulmonary bypass cannula malposition. Six of 9 observational studies reported an association between acute rSco(2) desaturation and POCD based on the Mini-Mental State Examination (n = 3 studies) or more detailed cognitive testing (n = 6 studies). Two retrospective studies reported a relationship between rSco(2) desaturation and stroke or type I and II neurologic injury after surgery. The observational studies had many limitations, including small sample size, assessments only during the immediate postoperative period, and failure to perform risk adjustments. Two randomized studies evaluated the efficacy of interventions for treating rSco(2) desaturation during surgery, but adherence to the protocol was poor in one. In the other study, interventions for rSco(2) desaturation were associated with less major organ injury and shorter intensive care unit hospitalization compared with nonintervention. CONCLUSIONS Reductions in rSco(2) during cardiac surgery may identify cardiopulmonary bypass cannula malposition, particularly during aortic surgery. Only low-level evidence links low rSco(2) during cardiac surgery to postoperative neurologic complications, and data are insufficient to conclude that interventions to improve rSco(2) desaturation prevent stroke or POCD.


title: Redefining undergraduate nurse teaching during the coronavirus pandemic: use of digital technologies.

text: During the current coronavirus pandemic, undergraduate nurse teaching is facing many challenges. Universities have had to close their campuses, which means that academics are working from home and may be coping with unfamiliar technology to deliver the theoretical part of the undergraduate nursing curriculum. Emergency standards from the Nursing and Midwifery Council have allowed theoretical instruction to be replaced with distance learning, requiring nursing academics to adapt to providing a completely virtual approach to their teaching. This article provides examples of tools that can be used to deliver the theoretical component of the undergraduate nursing curriculum and ways of supporting students and colleagues in these unprecedented times.


title: Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

text: The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.


Biomedical research: lessons from the last decade's crisis and austerity-stricken small countries for the current COVID-19-related crisis.


title: Acute traumatic patellar tendon rupture: Early and late results of surgical treatment of 38 cases.

text: INTRODUCTION Acute patellar tendon rupture is easy to diagnose but is still often overlooked. The aim of this study was to assess early and late results of surgical treatment of acute patellar tendon rupture. Our hypothesis was that functional outcome is satisfactory. METHODS A retrospective study included 38 knees in 37 patients (4 female, 33 male). Mean age was 42.6 ± 9.9 years (range, 23-81 years). Lesions comprised 15 tendon body ruptures, 20 avulsions from the tip of the patella and 3 avulsions from the anterior tibial tuberosity. Tendon repair was protected in more than 95% of cases by a reinforcement frame: hamstring (21 cases), synthetic ligament (12 cases) or metallic wire (3 cases). Results were evaluated in 2 steps: on patient files at a mean follow-up of 7.1 months (range, 3-24 months) to assess complications and early functional and radiological results; and by phone at a mean follow-up of 9.3 years (range, 19-229 months) in order to assess long-term functional outcome on Lysholm score and patient satisfaction. RESULTS Thirty-one knees were assessed at a mean 7.1 months. Mean knee flexion was 128.5° ± 7.5° (range, 85°-150°), extension -1° (range, -15° to 0°) and Caton-Deschamps index 0.96 (range, 0.57-1.29). Twenty-three knees were further assessed at a mean 9.3 years. Mean Lysholm score was 93.7 points (range, 61-100). Ninety-six percent of patients were satisfied or very satisfied with the result. All had returned to their previous job, and 20 had returned to sports activities, including 8 at pretrauma level. CONCLUSION Patellar tendon rupture has good prognosis if diagnosis and surgical treatment is early.


title: Effects of Varied Surgical Simulation Training Schedules on Motor-Skill Acquisition.

text: There have been many studies to evaluate the effect of training schedules on retention; however, these usually compare only 2 drastically different schedules, massed and distributed, and they have tended to look at declarative knowledge tasks. This study examined learning on a laparoscopic surgery simulator using a set of procedural or perceptual-motor tasks with some declarative elements. The study used distributed, massed, and 2 hybrid-training schedules that are neither distributed nor massed. To evaluate the training schedules, 23 participants with no previous laparoscopic experience were recruited and randomly assigned to 1 of the 4 training schedules. They performed 3 laparoscopic training tasks in eight 30-minute learning sessions. We compared how task time decreased with each schedule in a between-participants design. We found participants in all groups demonstrated a decrease in task completion time as the number of training sessions increased; however, there were no statistically significant differences in participants' improvement on task completion time between the 4 different training schedule groups, which suggested that time on task is more important for learning these tasks than the training schedule.


title: Discovering new medicines targeting helicases: challenges and recent progress.

text: Helicases are ubiquitous motor proteins that separate and/or rearrange nucleic acid duplexes in reactions fueled by adenosine triphosphate (ATP) hydrolysis. Helicases encoded by bacteria, viruses, and human cells are widely studied targets for new antiviral, antibiotic, and anticancer drugs. This review summarizes the biochemistry of frequently targeted helicases. These proteins include viral enzymes from herpes simplex virus, papillomaviruses, polyomaviruses, coronaviruses, the hepatitis C virus, and various flaviviruses. Bacterial targets examined include DnaB-like and RecBCD-like helicases. The human DEAD-box protein DDX3 is the cellular antiviral target discussed, and cellular anticancer drug targets discussed are the human RecQ-like helicases and eIF4A. We also review assays used for helicase inhibitor discovery and the most promising and common helicase inhibitor chemotypes, such as nucleotide analogues, polyphenyls, metal ion chelators, flavones, polycyclic aromatic polymers, coumarins, and various DNA binding pharmacophores. Also discussed are common complications encountered while searching for potent helicase inhibitors and possible solutions for these problems.


title: Arena Roof Technique for Complex Reconstruction After Extensive Chest Wall Resection.

text: Extensive primary resections or redos may produce significant chest wall defects requiring creative reconstructions in order to avoid reduction of the intrathoracic volume. We describe the successful use of an innovative technique for chest wall reconstruction based on the concept of roof coverage of sport arenas. In fact, titanium plates are anchored to the residual rib stumps along the parasternal and paravertebral lines. The acellular collagen matrix prosthesis was sutured to the free edges of the same titanium plates to create a roof, reproducing the chest wall dome geometric configuration. A 36-year-old female patient was diagnosed with an extensive desmoid tumor involving the lateral segments of second to fifth ribs on the right side. The arena roof technique allowed for adequate expansion of the uninvolved lung and optimal chest wall functional recovery.


title: Tracking the green invaders: advances in imaging virus infection in plants.

text: Bioimaging contributes significantly to our understanding of plant virus infections. In the present review, we describe technical advances that enable imaging of the infection process at previously unobtainable levels. We highlight how such new advances in subcellular imaging are contributing to a detailed dissection of all stages of the viral infection process. Specifically, we focus on: (i) the increasingly detailed localizations of viral proteins enabled by a diversifying palette of cellular markers; (ii) approaches using fluorescence microscopy for the functional analysis of proteins in vivo; (iii) the imaging of viral RNAs; (iv) methods that bridge the gap between optical and electron microscopy; and (v) methods that are blurring the distinction between imaging and structural biology. We describe the advantages and disadvantages of such techniques and place them in the broader perspective of their utility in analysing plant virus infection.


title: Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection.

text: A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced "cytokine storm" at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.


title: Long-term outcomes of gastric electrical stimulation in children with gastroparesis.

text: BACKGROUND Gastric electrical stimulation (GES) has been used in adults with gastroparesis. However its use has been limited in children. We describe the largest experience with GES in children with long-term outcomes. METHODS Data were collected on children who underwent GES over a 10-year period. Data regarding demographics, medical history, hospital course, and outcomes were collected and analyzed. Symptom scores (validated Likert scores) were compared using a paired Student's t test. RESULTS Overall, 97 patients underwent GES, and a majority were teenage Caucasian girls. Ninety-six had temporary GES (tGES), and 66 had improvement in their symptoms. A total of 67 underwent permanent implantation (pGES), and there was significant reduction in all individual symptoms (p<0.001) as well as the total symptom score (TSS) (p<0.0001) at 1, 6, 12, and >12 months. Recurrence of symptoms leading to device removal occurred in 7 cases. Forty-one patients had continued improvement in symptoms for over 12 months, with a mean follow-up of 3.5 years (range 1-9 years). CONCLUSIONS This study represents the largest experience of systematic application of GES in children. GES is a safe and effective therapy for selected children with intractable GP with continued symptomatic improvement at 1 year and beyond.


title: Analysis of Morbidity Data of 308 Cases of Laparoscopic Sleeve Gastrectomy--the Soroka Experience.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) became a prevalent bariatric procedure in Israel, while laparoscopic adjustable gastric banding (LAGB) was losing ground, due to high failure rates (40 % at 10 years). Many patients after LAGB failure choose LSG as a further bariatric surgery (secondary LSG). However, LAGB often impairs upper stomach anatomy and physiology, which may contribute to complications increased risk after secondary LSG, in comparison to surgery-naive obese patients choosing LSG (primary LSG). METHODS A retrospective cohort study was conducted on a prospective database, looking at morbidly obese patients for LSG surgery. All procedures were done by a single surgeon at the Soroka Medical Center between January 2008 and March 2013. Data were collected from hospitalization charts on demographics, biometric and bariatric status, medical and bariatric surgical history, post-LSG morbidity, and mortality. RESULTS Three hundred eight patients underwent LSG during the study period, 181 (58.8 %) had a primary LSG while 127 (41.2 %) had a secondary LSG. No mortality occurred in both groups. Odds ratio for major complication (leak, stenosis) was 3.12 [CI 0.90-10.75] among the secondary LSG group, compared to the primary LSG (p = 0.071). The risk for major complication was doubled (OR = 2, 95 % CI [1.36-3.06]) for each one of previous bariatric procedure underwent (p = 0.001). Significant differences were found between the two groups regarding number and length of readmissions and number of imaging tests (p value = 0.027, 0.022, and 0.049, respectively). CONCLUSIONS Primary LSG is a safe and efficient bariatric procedure. After failed LAGB, secondary LSG should be carefully considered, because of a potentially higher risk of complications.


title: Cosmetic outcomes and patient satisfaction compared between staples and subcuticular suture technique for wound closure after primary total knee arthroplasty: a randomized controlled trial.

text: INTRODUCTION Staples and subcuticular suture are commonly used wound closure techniques after total knee arthroplasty (TKA). To date, only a few studies have investigated the differences between these two wound closure methods in TKA. Accordingly, this study aimed to compare cosmetic outcome and patient satisfaction between staples and subcuticular suture for post-TKA wound closure. MATERIALS AND METHODS This prospective randomized controlled trial included patients scheduled to undergo TKA at the Department of Orthopaedic Surgery of Siriraj Hospital (Bangkok, Thailand) during June 2018-March 2019. Patients were randomized into the staples or subcuticular suture groups. Hollander Wound Evaluation Scale (HWES), cosmetic-visual analogue scale (VAS), and patient satisfaction-VAS were evaluated at the 6-week and 3-month follow-ups. Functional outcome by the modified Knee Society Knee Scoring System and wound complications were also assessed. RESULTS Sixty-two patients (31 per group) were included. There were no significant differences in the HWES, cosmetic-VAS, patient satisfaction-VAS, or wound complication rate between groups at the 6-week or 3-month follow-ups. Wound closure time was significantly shorter in the staples group (p < 0.001), but the total operative time was not significantly different between groups. Modified knee score was significantly better in the suture group at 6 weeks (p = 0.024), but there was no significant difference between groups at 3 months. Significant association was observed between patient satisfaction-VAS and cosmetic-VAS at the 6-week (p = 0.03) and 3-month (p = 0.021) follow-ups. CONCLUSION Subcuticular suture and staples were found to be comparable wound-closure options after TKA relative to cosmetic outcome, patient satisfaction, functional outcome, and wound complication rate at 3-months post-operation.