title: Temperature sensitive liposomes combined with thermal ablation: Effects of duration and timing of heating in mathematical models and in vivo.

text: BACKGROUND Temperature sensitive liposomes (TSL) are nanoparticles that rapidly release the contained drug at hyperthermic temperatures, typically above ~40°C. TSL have been combined with various heating modalities, but there is no consensus on required hyperthermia duration or ideal timing of heating relative to TSL administration. The goal of this study was to determine changes in drug uptake when heating duration and timing are varied when combining TSL with radiofrequency ablation (RF) heating. METHODS We used computer models to simulate both RF tissue heating and TSL drug delivery, to calculate spatial drug concentration maps. We simulated heating for 5, 12 and 30 min for a single RF electrode, as well as three sequential 12 min ablations for 3 electrodes placed in a triangular array. To support simulation results, we performed porcine in vivo studies in normal liver, where TSL filled with doxorubicin (TSL-Dox) at a dose of 30 mg was infused over 30 min. Following infusion, RF heating was performed in separate liver locations for either 5 min (n = 2) or 12 min (n = 2). After ablation, the animal was euthanized, and liver extracted and frozen. Liver samples were cut orthogonal to the electrode axis, and fluorescence imaging was used to visualize tissue doxorubicin distribution. RESULTS Both in vivo studies and computer models demonstrate a ring-shaped drug deposition within ~1 cm of the visibly coagulated tissue. Drug uptake directly correlated with heating duration. In computer simulations, drug concentration increased by a factor of 2.2x and 4.3x when heating duration was extended from 5 to either 12, or 30 minutes, respectively. In vivo, drug concentration was by a factor of 2.4x higher at 12 vs 5 min heating duration (7.1 μg/g to 3.0 μg/g). The computer models suggest that heating should be timed to maximize area under the curve of systemic plasma concentration of encapsulated drug. CONCLUSIONS Both computer models and in vivo study demonstrate that tissue drug uptake directly correlates with heating duration for TSL based delivery. Computational models were able to predict the spatial drug delivery profile, and may serve as a valuable tool in understanding and optimizing drug delivery systems.


title: Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.

text: Hypoxia and inflammation are closely intertwined phenomena. Critically ill patients often suffer from systemic inflammatory conditions and concurrently experience short-lived hypoxia. We evaluated the effects of short-term hypoxia on systemic inflammation, and show that it potently attenuates pro-inflammatory cytokine responses during murine endotoxemia. These effects are independent of hypoxia-inducible factors (HIFs), but involve augmented adenosine levels, in turn resulting in an adenosine 2B receptor-mediated post-transcriptional increase of interleukin (IL)-10 production. We translated our findings to humans using the experimental endotoxemia model, where short-term hypoxia resulted in enhanced plasma concentrations of adenosine, augmentation of endotoxin-induced circulating IL-10 levels, and concurrent attenuation of the pro-inflammatory cytokine response. Again, HIFs were shown not to be involved. Taken together, we demonstrate that short-term hypoxia dampens the systemic pro-inflammatory cytokine response through enhanced purinergic signaling in mice and men. These effects may contribute to outcome and provide leads for immunomodulatory treatment strategies for critically ill patients.


title: Single-port laparoscopic totally extraperitoneal inguinal hernia repair with the TriPort system: initial experience.

text: BACKGROUND Since the early 1990s, the laparoscopic approach to inguinal hernia repair using three ports has gained increased popularity worldwide. Recently, single-incision laparoscopic surgery to reduce the invasiveness of traditional laparoscopy further is under development. This study aimed to assess the safety and feasibility of the single-port approach for laparoscopic totally extraperitoneal (TEP) repair of inguinal hernia and to report the authors' initial experience using the TriPort system. METHODS Between 18 October 2008 and 1 April 2009, 19 single-incision laparoscopic TEP repairs of inguinal hernia were performed for 16 patients at the Royal Surrey County Hospital, Guildford, United Kingdom. Data regarding patient demographics, type of hernia, operating time, complications, postoperative hospital stay, and recurrence were prospectively collected. The length of the incision at the time of the operation and at a clinic follow-up visit also was measured. RESULTS All 16 patients were men, ranging in age from 21 to 87 years. Of the 16 men, 13 had a unilateral inguinal hernia. For 7 of the 13 men, the hernia was on the left side. The median operating time was 40 min for unilateral hernia and 70 min for bilateral hernia. There were no intraoperative complications and no deaths. Discharge was on the same day for 12 of the men, and within 24 h for the remaining 4 men. Minor wound complications developed for two men. One man reported transient pain in his testicle. There was no evidence of early recurrence during a median follow-up period of 72.5 days. The median incision length was 30 mm, and the median scar length at the clinic follow-up visit was 25 mm. CONCLUSION The authors' experience has shown that single-port laparoscopic TEP inguinal hernia repair with the TriPort system is safe and feasible. Prospective randomized studies comparing single-access and conventional multiport laparoscopic TEP repairs with long-term follow-up evaluation are needed to confirm the authors' initial experience.


title: Development and execution of a pandemic preparedness plan: Therapeutic medical physics and radiation dosimetry during the COVID-19 crisis.

text: The SARS-CoV-2 coronavirus pandemic has spread around the world including the United States. New York State has been hardest hit by the virus with over 380 000 citizens with confirmed COVID-19, the illness associated with the SARS-CoV-2 virus. At our institution, the medical physics and dosimetry group developed a pandemic preparedness plan to ensure continued operation of our service. Actions taken included launching remote access to clinical systems for all dosimetrists and physicists, establishing lines of communication among staff members, and altering coverage schedules to limit on-site presence and decrease risk of infection. The preparedness plan was activated March 23, 2020, and data were collected on treatment planning and chart checking efficiency for 6 weeks. External beam patient load decreased by 25% during the COVID-19 crisis, and special procedures were almost entirely eliminated excepting urgent stereotactic radiosurgery or brachytherapy. Efficiency of treatment planning and chart checking was slightly better than a comparable 6-week interval in 2019. This is most likely due to decreased patient load: Fewer plans to generate and more physicists available for checking without special procedure coverage. Physicists and dosimetrists completed a survey about their experience during the crisis and responded positively about the preparedness plan and their altered work arrangements, though technical problems and connectivity issues made the transition to remote work difficult. Overall, the medical physics and dosimetry group successfully maintained high-quality, efficient care while minimizing risk to the staff by minimizing on-site presence. Currently, the number of COVID-19 cases in our area is decreasing, but the preparedness plan has demonstrated efficacy, and we will be ready to activate the plan should COVID-19 return or an unknown virus manifest in the future.


title: Serologic Evaluation of MERS Screening Strategy for Healthcare Personnel During a Hospital-Associated Outbreak.

text: To evaluate the appropriateness of the screening strategy for healthcare personnel (HCP) during a hospital-associated Middle East Respiratory Syndrome (MERS) outbreak, we performed a serologic investigation in 189 rRT-PCR-negative HCP exposed and assigned to MERS patients. Although 20%-25% of HCP experienced MERS-like symptoms, none of them showed seroconversion by plaque reduction neutralization test (PRNT). Infect Control Hosp Epidemiol 2017;38:234-238.


title: Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2.

text: BACKGROUND AND PURPOSE Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes. METHODS A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively). CONCLUSIONS Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors. TRIAL REGISTRATION NUMBER URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.


title: Altered amygdalar volume and functional connectivity in primary dysmenorrhoea during the menstrual cycle.

text: BACKGROUND Primary dysmenorrhoea (PDM), characterized as menstrual pain without pelvic pathology, is associated with pain-related negative mood and hormone fluctuations. Previous studies strongly supported the link between pain and negative mood in affected individuals; however, it remains largely unknown in patients with PDM. METHODS We focused on the effects how spontaneous pain, negative mood and hormone levels played on the central nervous system in 34 PDM women and 33 matched healthy controls across their cycles (periovulatory phase and menstruation phase) by using T1-weighted and functional imaging. Voxel-based morphometry and functional connectivity (FC) analyses were performed to evaluate brain structural and functional changes. Hormone concentrations (oestradiol, progesterone and cortisol) were also obtained. RESULTS Abnormal state-related GM volume in the amygdala was found between periovulatory and menstruation phases in PDM. Furthermore, larger amygdalar volume was observed in patients' menstruation phase, which was significantly correlated with higher levels of cortisol. In addition, we found increased amygdala-seeded FC in vlPFC, which may be associated with pain intensity and negative mood in PDM women during the pain state. CONCLUSIONS Taken together, we found women with PDM had structural and functional abnormalities in the amygdala, which associated with stress hormone levels, pain intensity and negative mood, may reflect disturbed emotional and pain modulation in women with PDM. SIGNIFICANCE Our findings provide further evidence of amygdala-related abnormalities, which may be associated with pain-related affective distress and hormonal fluctuations in women with PDM, and complement the brain mechanism investigations for the pathophysiology of PDM.


title: Does endo-tracheal tube clamping prevent air leaks and maintain positive end-expiratory pressure during the switching of a ventilator in a patient in an intensive care unit? A bench study.

text: OBJECTIVES When patients with acute respiratory distress syndrome are moved out of an intensive care unit, the ventilator often requires changing. This procedure suppresses positive end expiratory pressure and promotes lung derecruitment. Clamping the endotracheal tube may prevent this from occurring. Whether or not such clamping maintains positive end-expiratory pressure has never been investigated. We designed a bench study to explore this further. HOW THE STUDY WAS DONE We used the Elysee 350 ventilator in 'volume controlled' mode with a positive end-expiratory pressure of 15 cmH2O, connected to an endotracheal tube with an 8 mm internal diameter inserted into a lung model with 40 ml/cmH2O compliance and 10 cmH2O/L/s resistance. We measured airway pressure and flow between the distal end of the endotracheal tube and the lung model. We tested a plastic, a metal, and an Extra Corporeal Membrane Oxygenation clamp, each with an oral/nasal, a nasal, and a reinforced endotracheal tube. We performed an end-expiratory hold then clamped the endotracheal tube and disconnected the ventilator. We measured the change in airway pressure and volume for 30 s following the disconnection of the ventilator. RESULTS Airway pressure decreased thirty seconds after disconnection with all combinations of clamp and endotracheal tube. The largest fall in airway pressure (-17.486 cmH2O/s at 5 s and -18.834 cmH2O/s at 30 s) was observed with the plastic clamp combined with the reinforced endotracheal tube. The smallest decrease in airway pressure (0 cmH2O/s at 5 s and -0.163 cmH2O/s at 30 s) was observed using the Extra Corporeal Membrane Oxygenation clamp with the nasal endotracheal tube. CONCLUSIONS Only the Extra Corporeal Membrane Oxygenation clamp was efficient. Even with an Extra Corporeal Membrane Oxygenation clamp, it is important to limit the duration the ventilator is disconnected to a few seconds (ideally 5 s).


title: Mechanical thrombectomy in tandem occlusion: procedural considerations and clinical results.

text: INTRODUCTION Acute tandem occlusions of the cervical and distal internal carotid artery (ICA) or middle cerebral artery (MCA) are associated with major stroke with intravenous (i.v.) thrombolysis alone in approximately 90 % of patients. The data on endovascular management of tandem occlusions is still limited. The purpose of this study was to review technical aspects and the current state of the literature on acute ICA stenting in combination with stent retriever-based intracranial thrombectomy. METHODS We retrospectively reviewed the data of 37 consecutive patients with tandem occlusions including clinical parameters, angiographic results, procedural aspects, complications, and hemorrhages. RESULTS Median National Institutes of Health Stroke Scale (NIHSS) on admission was 17 (3-30). Intracranial thrombectomy was performed prior to ICA stenting in 25/37 (67.6 %) and after stenting in 12/37 (32.4 %) patients. ICA stenting was successful in all cases, and a thrombolysis in cerebral infarction (TICI) scale 2b/3 result was achieved in 27/37 (73 %) cases. The mean angiography time was significantly shorter in the "thrombectomy first" group (43.1 ± 30.8 vs. 110.8 ± 43.0 min, p < 0.001), and more patients had favorable outcomes after 3 months (13/25 = 52.0 vs. 4/12 = 33.3 %, p = 0.319). In this group, intermediate catheters were used and successfully prevented embolism to unaffected territories in all cases. CONCLUSION Acute stenting of the cervical ICA in combination with intracranial thrombectomy was technically feasible and safe in our series. Thrombectomy prior to proximal stenting was associated with shorter reperfusion times and a tendency towards better clinical outcome leading to a good outcome in about 50 % of the patients. Therefore, we recommend this approach in tandem occlusion requiring stent angioplasty.


title: Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.

text: The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.


title: Perspectives on Open Science and scientific data sharing:an interdisciplinary workshop.

text: Looking at Open Science and Open Data from a broad perspective. This is the idea behind "Scientific data sharing: an interdisciplinary workshop", an initiative designed to foster dialogue between scholars from different scientific domains which was organized by the Istituto Italiano di Antropologia in Anagni, Italy, 2-4 September 2013.We here report summaries of the presentations and discussions at the meeting. They deal with four sets of issues: (i) setting a common framework, a general discussion of open data principles, values and opportunities; (ii) insights into scientific practices, a view of the way in which the open data movement is developing in a variety of scientific domains (biology, psychology, epidemiology and archaeology); (iii) a case study of human genomics, which was a trail-blazer in data sharing, and which encapsulates the tension that can occur between large-scale data sharing and one of the boundaries of openness, the protection of individual data; (iv) open science and the public, based on a round table discussion about the public communication of science and the societal implications of open science. There were three proposals for the planning of further interdisciplinary initiatives on open science. Firstly, there is a need to integrate top-down initiatives by governments, institutions and journals with bottom-up approaches from the scientific community. Secondly, more should be done to popularize the societal benefits of open science, not only in providing the evidence needed by citizens to draw their own conclusions on scientific issues that are of concern to them, but also explaining the direct benefits of data sharing in areas such as the control of infectious disease. Finally, introducing arguments from social sciences and humanities in the educational dissemination of open data may help students become more profoundly engaged with Open Science and look at science from a broader perspective.


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title: Diaphragmatic hernia following liver resection: case series and review of the literature.

text: BACKGROUNDS/AIMS Postoperative diaphragmatic hernia, following liver resection, is a rare complication. METHODS Data of patients who underwent major hepatectomy for liver tumors, between 2011 and 2015 were retrospectively reviewed. The literature was searched for studies reporting the occurrence of diaphragmatic hernia following liver resection. RESULTS Diaphragmatic hernia developed in 2.3% of patients (3/131) with a median delay of 14 months (4-31 months). One patient underwent emergency laparotomy for bowel obstruction and two patients underwent elective diaphragmatic hernia repair. At last follow-up, no recurrences were observed. Fourteen studies including 28 patients were identified in the literature search (donor hepatectomy, n=11: hepatectomy for liver tumors, n=17). Diaphragmatic hernia was repaired emergently in 42.9% of cases and digestive resection was necessary in 28.5% of the cases. One patient died 3 months after hepatectomy, secondary to sepsis, from a segment of small bowel that perforated into the diaphragmatic hernia. CONCLUSIONS Although rare, diaphragmatic hernia should be considered as an important complication, especially in living donor liver transplant patients. Diaphragmatic hernia should be repaired surgically, even for asymptomatic patients.


title: Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.

text: BACKGROUND AND OBJECTIVES Previous reports on the outbreak of coronavirus disease 2019 were on the basis of data from the general population. Our study aimed to investigate the clinical features of patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this retrospective, single-center study, we included 49 hospitalized patients on maintenance hemodialysis and 52 hospitalized patients without kidney failure (controls) with confirmed coronavirus disease 2019 at Tongren Hospital of Wuhan University from January 30, 2020 to March 10, 2020. Demographic, clinical, laboratory, and radiologic characteristics and treatment and outcomes data were analyzed. The final date of follow-up was March 19, 2020. RESULTS The median age of 101 patients was 62 years (interquartile range, 49-72). All patients were local residents of Wuhan. In terms of common symptoms, there were differences between patients on hemodialysis and controls (fatigue [59% versus 83%], dry cough [49% versus 71%], and fever [47% versus 90%]). Lymphocyte counts were decreased (0.8×109/L [patients on hemodialysis] versus 0.9×109/L [controls], P=0.02). Comparing patients on hemodialysis with controls, creatine kinase-muscle and brain type, myoglobin, hypersensitive troponin I, B-type natriuretic peptide, and procalcitonin were increased, and the percentage of abnormalities in bilateral lung was higher in computed tomographic scan (82% versus 69%, P=0.15) and unilateral lung was lower (10% versus 27%, P=0.03). Common complications including shock, acute respiratory distress syndrome, arrhythmia, and acute cardiac injury in patients on hemodialysis were significantly higher. Compared with controls, more patients on hemodialysis received noninvasive ventilation (25% versus 6%, P=0.008). As of March 19, 2020, three patients on hemodialysis (6%) were transferred to the intensive care unit and received invasive ventilation. Seven patients on hemodialysis (14%) had died. CONCLUSIONS The main symptoms of coronavirus disease 2019 pneumonia, including fever and cough, were less common in patients on hemodialysis. Patients on hemodialysis with coronavirus disease 2019 were at higher risk of death.


title: Plant as a plenteous reserve of lectin.

text: Lectins are clusters of glycoproteins of nonimmune foundation that combine specifically and reversibly to carbohydrates, mainly the sugar moiety of glycoconjugates, resulting in cell agglutination and precipitation of glycoconjugates. They are universally distributed in nature, being established in plants, fungi, viruses, bacteria, crustacea, insects, and animals, but leguminacae plants are rich source of lectins. The present review reveals the structure, biological properties, and application of plant lectins.


title: Implantation of prophylactic nonabsorbable intraperitoneal mesh in patients with peritonitis is safe and feasible.

text: BACKGROUND Patients with peritonitis undergoing emergency laparotomy are at increased risk for postoperative open abdomen and incisional hernia. This study aimed to evaluate the outcome of prophylactic intraperitoneal mesh implantation compared with conventional abdominal wall closure in patients with peritonitis undergoing emergency laparotomy. METHOD A matched case-control study was performed. To analyze a high-risk population for incisional hernia formation, only patients with at least two of the following risk factors were included: male sex, body mass index (BMI) >25 kg/m(2), malignant tumor, or previous abdominal incision. In 63 patients with peritonitis, a prophylactic nonabsorbable mesh was implanted intraperitoneally between 2005 and 2010. These patients were compared with 70 patients with the same risk factors and peritonitis undergoing emergency laparotomy over a 1-year period (2008) who underwent conventional abdominal closure without mesh implantation. RESULTS Demographic parameters, including sex, age, BMI, grade of intraabdominal infection, and operating time were comparable in the two groups. Incidence of surgical site infections (SSIs) was not different between groups (61.9 vs. 60.3 %; p = 0.603). Enterocutaneous fistula occurred in three patients in the mesh group (4.8 %) and in two patients in the control group (2.9 %; p = 0.667). The incidence of incisional hernia was significantly lower in the mesh group (2/63 patients) than in the control group (20/70 patients) (3.2 vs. 28.6 %; p < 0.001). CONCLUSIONS Prophylactic intraperitoneal mesh can be safely implanted in patients with peritonitis. It significantly reduces the incidence of incisional hernia. The incidences of SSI and enterocutaneous fistula formation were similar to those seen with conventional abdominal closure.


title: Single-incision laparoscopic cholecystectomy: will it succeed as the future leading technique for gallbladder removal?

text: BACKGROUND The quest for less traumatic abdominal approaches is changing paradigms in times of minimally invasive surgery. While natural orifice translumenal endoscopic surgery remains experimental, the single-incision approach could be the future of gallbladder surgery. METHODS Prospectively collected data from 875 patients subjected to conventional single-incision laparoscopic cholecystectomy (SILC) or 4-port [laparoscopic cholecystectomy (LC)] were retrospectively analyzed and discussed with the current literature. RESULTS Between 2008 and 2011, 201 (23%) SILCs and 674 (77%) LCs were performed. Mean age was 51.7±17.5 years (SILC: 45.1 vs. LC: 53.7 y). Patients were predominantly female (SILC: 75.1% vs. LC: 56.5%). Preoperative body mass index was 27.4±9.1 (SILC: 26.4 vs. LC: 27.8; P<0.05) and American Society of Anesthesiologists' score counted 1.67±0.57 in SILC and 1.86±0.7 in LC patients. Acute inflammation of the gallbladder (AIG) was not considered as a contraindication for SILC (AIG in SILC: 17.4% vs. LC: 35.5%). The mean operative time was significantly lower in the SILC group (SILC: 71±31 vs. LC: 79±27 min) and duration of postoperative hospital stay was shorter (SILC: 3.2±1.7 vs. LC: 4.5±2.6 d). No significant difference was observed between SILC and LC in any of the registered complications, including postoperative bleeding, trocar hernias, wound infection, abdominal abscess formation, bile duct injury, or cystic duct leakage. CONCLUSIONS In the near future SILC could overrule conventional LC as the leading technique for gallbladder surgery. Our data reconfirm an excellent risk profile for SILC that is equal to that of LC. Large multicenter randomized controlled trials will be required to finally legitimize SILC as the succeeding principal method.


title: Using non-invasive bi-level positive airway pressure ventilator via tracheostomy in children with congenital central hypoventilation syndrome: two case reports.

text: INTRODUCTION Due to the economic downturn in Thailand, two baby girls with congenital central hypoventilation syndrome had to wait for several months to obtain definite diagnosis and long-term mechanical ventilation. Genetic investigation later revealed 20/25 polyalanine expansion of PHOX2B gene in both girls. In this report we highlight the use of non-invasive bi-level positive airway pressure ventilators via tracheostomy, overnight end-tidal carbon dioxide trend graphs and outcomes of the patients whose diagnosis and treatment were delayed. CASE PRESENTATION Case 1: A Thai baby girl showed symptoms of apnea and cyanosis from birth and required invasive mechanical ventilation via tracheostomy during sleep. At 5 months, she unfortunately was discharged from the hospital without any ventilatory support due to financial problems. She subsequently developed cor pulmonale, respiratory failure and generalized edema and was referred to us when she was 9-months old. An overnight polysomnogram was consistent with a central hypoventilation disorder, in which the severity of oxygen desaturation and hypercapnia was worsening during non-rapid eye movement compared to rapid eye movement sleep. At 12 months she was allowed to go home with a conventional home ventilator. The ventilator was changed to bi-level positive airway pressure when she was 4-years old. After she received adequate home ventilation, she thrived with normal growth and development. Case 2: A Thai baby girl developed apnea and cyanosis from the age of 5 weeks, requiring ventilatory support (on and off) for 5 months. After being extubated, she had been put on supplemental oxygen via nasal cannula for 2 months. She was then referred to us when she was 7-months old. An overnight end-tidal carbon dioxide trend graph revealed marked hypercapnia without increase in respiratory rate. An overnight polysomnogram was consistent with a central hypoventilation disorder. Since 9 months of age she has been on home bi-level positive airway pressure via tracheostomy without any complications. Genetic testing confirmed 20/25 polyalanine expansions of PHOX2B gene in both girls. CONCLUSIONS Bi-level positive airway pressure, originally designed as a non-invasive ventilator, was found to work effectively and safely, and may be used as an invasive ventilator via tracheostomy in young children with congenital central hypoventilation syndrome.


title: Optimal use of advanced technology.

text: The Asian Pacific Society of Respirology held its 13th Congress in Bangkok, Thailand, between 19 and 22 November 2008. It was attended by over 1500 delegates from around the world, particularly well represented by delegates from the Asia Pacific Rim. The congress was highlighted by an excellent scientific program, preceded by an educational course on pulmonary laboratory practices and several postgraduate courses. Office bearers representing the American Thoracic Society, European Respiratory Society and American College of Chest Physicians, among others, made significant contributions, further enhancing the high-quality faculty.


title: CT in relation to RT-PCR in diagnosing COVID-19 in The Netherlands: A prospective study.

text: INTRODUCTION Early differentiation between emergency department (ED) patients with and without corona virus disease (COVID-19) is very important. Chest CT scan may be helpful in early diagnosing of COVID-19. We investigated the diagnostic accuracy of CT using RT-PCR for SARS-CoV-2 as reference standard and investigated reasons for discordant results between the two tests. METHODS In this prospective single centre study in the Netherlands, all adult symptomatic ED patients had both a CT scan and a RT-PCR upon arrival at the ED. CT results were compared with PCR test(s). Diagnostic accuracy was calculated. Discordant results were investigated using discharge diagnoses. RESULTS Between March 13th and March 24th 2020, 193 symptomatic ED patients were included. In total, 43.0% of patients had a positive PCR and 56.5% a positive CT, resulting in a sensitivity of 89.2%, specificity 68.2%, likelihood ratio (LR)+ 2.81 and LR- 0.16. Sensitivity was higher in patients with high risk pneumonia (CURB-65 score ≥3; n = 17, 100%) and with sepsis (SOFA score ≥2; n = 137, 95.5%). Of the 35 patients (31.8%) with a suspicious CT and a negative RT-PCR, 9 had another respiratory viral pathogen, and in 7 patients, COVID-19 was considered likely. One of nine patients with a non-suspicious CT and a positive PCR had developed symptoms within 48 hours before scanning. DISCUSSION The accuracy of chest CT in symptomatic ED patients is high, but used as a single diagnostic test, CT can not safely diagnose or exclude COVID-19. However, CT can be used as a quick tool to categorize patients into "probably positive" and "probably negative" cohorts.


title: The good, the bad & the hoax: when publication instantaneously impacts treatment strategies for COVID-19.

text: The COVID-19 pandemic is an unprecedented situation with physicians awaiting information on therapeutic advances to an extent hardly ever seen in medical history.….


title: Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis: preliminary studies in a porcine model.

text: PURPOSE Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. MATERIALS AND METHODS Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. RESULTS From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4-5.8×10(7) autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely degraded. CONCLUSION It is technically feasible and biologically sound to deliver autologous BM-MSCs to the distraction site immediately after osteotomy using a Gelfoam scaffold to enhance mandibular DO.


title: Neurocognitive and executive functioning in adult survivors of congenital heart disease.

text: OBJECTIVE Congenital heart disease (CHD) can affect the developing central nervous system, resulting in neurocognitive and behavioral deficits. Preoperative neurological abnormalities as well as sequelae of the open heart operations required to correct structural abnormalities of the heart contribute to these deficits. There are few studies examining the neurocognitive functioning of adults with CHD. This study sought to investigate multiple domains of neurocognitive functioning in adult survivors of CHD who had childhood cardiac surgery with either moderate or severe disease complexity. DESIGN A total of 48 adults (18-49 years of age) who had undergone cardiac surgery for CHD prior to five years of age participated in the study. CHD severity was classified as moderate or severe according to the 32nd Bethesda Guidelines. A computerized battery of standardized neurocognitive tests (CNS-Vital Signs), a validated rating scale of executive functioning, and demographic questionnaires were administered. RESULTS There were no significant differences between the moderate CHD group and normative data on any cognitive measure. In contrast, the severe CHD group differed from norms in multiple domains: psychomotor speed, processing speed, complex attention, reaction time, and on the overall neurocognitive index. Number of surgeries was strongly related to worse executive functioning. There was no association between age at first surgery or time since last surgery and neuropsychological functioning. Number of surgeries was also unrelated to neurocognitive test performance. CONCLUSIONS Patients with severe CHD performed significantly worse on measures of processing speed, attention, and executive functioning. These findings may be useful in the long-term care of adults with congenital heart disease.


title: Expression of cystic fibrosis transmembrane conductance regulator in paracervical ganglia.

text: The cystic fibrosis transmembrane conductance regulator (CFTR) is an important protein that acts as a chloride channel and regulates many physiological functions, including salt transport and fluid flow. Mutations in the gene encoding the CFTR protein cause cystic fibrosis. CFTR is expressed in the epithelial cells of the lungs, pancreas, intestines, and other organs. In the peripheral and central nervous system, CFTR expression has been detected in the neurons of rat brains, ganglion cells of rat hearts, human hypothalamus, human spinal cord, and human spinal and sympathetic ganglia. However, CFTR has not been identified in other parts of the nervous system. In this study, we used immunohistochemistry, in situ hybridization, and laser-assisted microdissection (LMD) followed by reverse transcriptase (RT) PCR to identify CFTR proteins and messenger RNA in human and rat paracervical ganglion cells. CFTR and its gene expression were both detected in paracervical ganglion cells, a finding that might link this important protein to the neuronal regulation of female urogenital function. These findings could provide new insights into the symptoms related to the reproductive system frequently observed in female cystic fibrosis patients.


title: Electrical stimulation of sacral dermatomes can suppress aberrant urethral reflexes in felines with chronic spinal cord injury.

text: AIMS Uncoordinated reflex contractions of the external urethral sphincter (EUS) are a major component of voiding dysfunction after neurologic injury. Patterned stimulation of sacral afferent pathways can reduce abnormal EUS reflexes after acute spinal cord injury (SCI); however, effectiveness following chronic SCI is unknown. METHODS Four adult male cats were implanted with bilateral extradural sacral root electrodes to allow bladder activation and underwent subsequent spinal transection (T10-12). Nine weeks after SCI urethral and bladder pressures were recorded with and without sacral afferent stimulation. Surface electrodes were applied to sacral and lumbar dermatomes and stimulus amplitude set below the muscle fasciculation threshold. The stimulation pattern was varied by on/off times of fixed frequency at each location. RESULTS Reflexive EUS contractions were observed in all animals after chronic SCI. Patterned sacral dermatome stimulation reduced EUS reflex rate and amplitude in two of four cats. Suppression was dependent on both the stimulus location and pattern. Sacral locations and a stimulation pattern of (0.75 sec on, 0.25 sec off, 20 Hz) were effective in both responder animals. CONCLUSIONS Patterned sacral dermatome stimulation can reduce abnormal urethral reflexes following chronic SCI. Reflex suppression is dependent on both the stimulation location and stimulus pattern. Reduction of reflexive EUS activity after chronic SCI with this non-destructive and non-invasive approach may provide an advance for the treatment of detrusor-sphincter-dyssynergia.


title: The vascular occlusion test using multispectral imaging: a validation study : The VASOIMAGE study.

text: Multispectral imaging (MSI) is a new, non-invasive method to continuously measure oxygenation and microcirculatory perfusion, but has limitedly been validated in healthy volunteers. The present study aimed to validate the potential of multispectral imaging in the detection of microcirculatory perfusion disturbances during a vascular occlusion test (VOT). Two consecutive VOT's were performed on healthy volunteers and tissue oxygenation was measured with MSI and near-infrared spectroscopy (NIRS). Correlations between the rate of desaturation, recovery and the hyperemic area under the curve (AUC) measured by MSI and NIRS were calculated. Fifty-eight volunteers were included. The MSI oxygenation curves showed identifiable components of the VOT, including a desaturation and recovery slope and hyperemic area under the curve, similar to those measured with NIRS. The correlation between the rate of desaturation measured by MSI and NIRS was moderate: r = 0.42 (p = 0.001) for the first and r = 0.41 (p = 0.002) for the second test. Our results suggest that non-contact multispectral imaging is able to measure changes in regional oxygenation and deoxygenation during a vascular occlusion test in healthy volunteers. When compared to measurements with NIRS, correlation of results was moderate to weak, most likely reflecting differences in physiology of the regions of interest and measurement technique.


title: Early angiographic occlusion of ruptured blister aneurysms of the internal carotid artery using the Pipeline Embolization Device as a primary treatment option.

text: BACKGROUND Data on the timing, durability and occlusion rate of treating ruptured blister cerebral aneurysms using the Pipeline Embolization Device (PED) are limited. CLINICAL PRESENTATION Three patients who presented with subarachnoid hemorrhages from ruptured blister aneurysms of the internal carotid arteries were treated with the PED. RESULTS Aneurysmal occlusion with reconstruction of the parent vessels occurred angiographically using the PED as a primary treatment modality. All three patients were treated successfully without immediate or delayed complications and remained neurologically intact during the 6-month follow-up period. CONCLUSIONS Complete occlusion of a ruptured blister aneurysm can occur immediately after PED placement. In ruptured blister aneurysms with contrast stagnation after PED treatment, early angiographic occlusion was confirmed as early as 6 weeks and continued with medium-term durability.


Influenza A(H1N1) and pandemic preparedness under the rule of international law.


title: CONTROLS TO MINIMIZE DISRUPTION OF THE PHARMACEUTICAL SUPPLY CHAIN DURING THE COVID-19 PANDEMIC.

text: This article reviews currently available scientific literature related to the epidemiology, infectivity, survival, and susceptibility to disinfectants of Coronaviruses, in the context of the controls established to meet Good Manufacturing Practice regulations and guidance, and the public health guidance issued specifically to combat the Covid-19 pandemic. The possible impact of the COVID-19 pandemic on the pharmaceutical supply chain is assessed and recommendations are listed for risk mitigation steps to minimize supply disruption to pharmaceutical drug products. Areas addressed include a brief history of the COVID-19 viral pandemic, a description of the virus, the regulatory response to the pandemic, the screening of employees, the persistence on inanimate surfaces, cleaning and disinfection of manufacturing facilities, use of GMP-mandated personal protective equipment to counter the spread of the disease, the role of air changes in viral clearance, approaches to risk assessment and mitigation. Biological medicinal products have a great record of safety, yet the cell cultures used for production can be susceptible to viruses, and contamination events have occurred. Studies on SARS-CoV-1 for its ability to replicate in various mammalian cell lines used for biopharmaceutical manufacturing suggest SARS-CoV-2 poses low risk and any contamination would be detected by currently used adventitious virus testing. The consequences of the potential virus exposure of manufacturing processes, as well as the effectiveness of mitigation efforts are discussed. The pharmaceutical supply chain is complex, traversing many geographies and companies that range from large multinationals to mid and small size operations. This paper recommends practices that can be adopted by all companies, irrespective of their size, geographic location, or position in the supply chain.


title: Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours.

text: PURPOSE Peptide receptor radionuclide therapy using β-emitting radiolabelled somatostatin analogues like DOTA,Tyr3-octreotate shows beneficial results in patients suffering from somatostatin receptor overexpressing tumours. However, after high-dose therapy partial renal reabsorption of radiopeptides may lead to nephrotoxicity. Co-infusion of lysine/arginine lowers renal retention of these radiopeptides without affecting tumour uptake. Recently co-administration of Gelofusine has been described to have a comparable kidney-protecting effect in rats. In the present study optimal dosing of Gelofusine co-administration was studied in tumour-bearing rats. METHODS Doses of 40, 80, 120 or 160 mg/kg Gelofusine were co-injected with 15 µg DOTA,Tyr3-octreotate, labelled with 3 MBq 111In for biodistribution (24 h post-injection, n = 4 per group) and with 60 MBq 111In for microSPECT imaging experiments at 3, 24 and 48 h post-injection. An additional group of rats received 80 mg/kg Gelofusine plus 400 mg/kg lysine co-injection. Biodistribution studies were performed both in older (475 g) and younger (300 g) rats, the latter bearing CA20948 tumours. RESULTS Co-injection of 40 mg/kg Gelofusine resulted in 40-50% reduction of renal uptake and retention of 111In-DOTA,Tyr3-octreotate, whereas higher doses further increased the reduction to 50-60% in both groups of rats. Combining Gelofusine and lysine caused 70% reduction of renal uptake. The uptake of radiolabelled octreotate both in somatostatin receptor-expressing normal tissues and tumours was not affected by Gelofusine co-injection. CONCLUSION In rats co-injection of 80 mg/kg Gelofusine resulted in maximum reduction of renal retention of 111In-DOTA,Tyr3-octreotate, which was further improved when combined with lysine. Tumour uptake of radiolabelled octreotate was not affected, resulting in an increased tumour to kidney ratio.


docid: wmvihsfi

title: Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans.

text: The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.


title: Prior treatment does not influence the performance or early outcome of per-oral endoscopic myotomy for achalasia.

text: INTRODUCTION Per-oral endoscopic myotomy (POEM) is an emerging treatment for achalasia. Pneumatic dilation, botulinum toxin injection, and previous myotomy increase the difficulty of subsequent Heller myotomy, but their impact on POEM remains unknown. The purpose of this study was to compare patients who had undergone prior treatment for their achalasia to those undergoing POEM as an initial therapy. METHODS AND PROCEDURES All patients undergoing POEM were entered into a prospective database from August 2012 to October 2014. Data collected included demographics, dysphagia and symptom survey scores, operative time, clips required for mucosotomy closure, perioperative complications and length of hospital stay. RESULTS Forty-five patients underwent POEM during the study period. Fifteen (30%) had undergone previous treatment (seven Botox injection, five pneumatic dilation and three Heller myotomy). Primary POEM patients were younger than those who had had prior treatment (mean age 46 ± 17 vs. 64 ± 12 years, p < 0.001), but gender, body mass index and ASA class were not significantly different. There were no conversions to Heller myotomy or perioperative complications in either group. Operative time for primary POEM was 103 ± 27 versus 102 ± 29 min following prior treatment (p = 0.84). Mucosotomy closure required a median 7 (4-16) and 8 (5-16) clips, respectively (p = 0.08). Length of stay was 1 day in each group. Median dysphagia scores decreased from 4 (0-5) to 1 (0-4) following primary POEM and 4 (0-5) to 0 (0-4) in the prior treatment group (p = 0.45) during a median follow-up of 10 months (5-17 months). All patients in each group expressed satisfaction with their procedure and would undergo the procedure again given the benefit of hindsight. CONCLUSION Per-oral endoscopic myotomy is a safe and effective treatment for achalasia which improves dysphagia and disease-specific quality of life. Previous endoscopic or laparoscopic treatment of achalasia does not affect the performance or early outcome of POEM.


Coronavirus lockdowns have changed the way Earth moves.


title: Tracheotomia az új típusú koronavírus okozta járvány idején(A COVID-19-pandémia orvosszakmai kérdései).

text: Recently, 6 percent of COVID-19 patients required prolonged mechanical ventilation due to severe respiratory failure. Early tracheostomy prevents the risk of postintubation upper airway stenosis. In the pandemic, all surgical interventions that generate aerosol increase the risk of contamination of the medical staff, for which reason the "traditional" indications of tracheostomy have to be revised. Authors present their recommendations based on international experiences. Orv Hetil. 2020; 161(19): 767-770.


title: Single-incision robotic colectomy (SIRC): Current status and future directions.

text: By combining laparo-endoscopic single-site surgery (LESS) techniques with the da Vinci robotic platform, single-incision robotic colectomy (SIRC) aims to further minimize incision-related complications and improve cosmetic outcomes from the current standard of care, laparoscopic colectomy. While there is limited literature on SIRC, all available reports suggest SIRC to be a safe and feasible procedure in terms of perioperative outcomes. Future research should focus on further clarification of proposed benefits of SIRC such as cosmetics, ergonomics, incidence of incision-related complications, and long-term oncologic outcomes.


title: Evaluation of THUNDERBEAT® in open liver resection- a single-center experience.

text: BACKGROUND THUNDERBEAT® (TB) (Olympus Medical Systems Corp., Tokyo, Japan) is a dynamic energy system device that simultaneously delivers ultrasonically generated frictional heat energy and electrically generated bipolar energy. TB is being routinely used in various operative procedures, however, less is known about its utility in liver resection. We, herein, report our early experience of using TB in open liver resection particularly in patients with normal or near-normal liver parenchyma. METHODS We retrospectively reviewed the clinical characteristics, and evaluated the perioperative outcome of twenty-eight patients who underwent liver resection with TB, and twenty-four patients who underwent liver resection with basic procedure in our institution. The resection type was stratified into: major hepatectomy; resection of 3 or more than 3 Couinauds segments, and minor hepatectomy; resection of less than 3 Couinauds segments. RESULTS Liver resection time (mean ± SD) in TB group with major hepatectomy was significantly shorter: 16.7 ± 8.8 compared to 62.8 ± 39.4 min in basic procedure group (P < 0.0001). Accordingly, the liver resection time (mean ± SD) in TB group with minor hepatectomy was also significantly shorter, 8.3 ± 2.9 min compared to 45.2 ± 23.9 min in liver resection with basic procedure (P < 0.001). No significant difference was observed between the groups in terms of intraoperative blood transfusion ratio, postoperative complication and postoperative liver dysfunction. CONCLUSION TB as a new energy device can offer a safe, reliable and substantially rapid liver resection particularly in patients with normal or near-normal liver parenchyma.


title: Get the message? A scoping review of physical activity messaging.

text: BACKGROUND Understanding how to create and deliver effective physical activity (PA) messages for and to various population subgroups may play a role in increasing population PA levels. This scoping review aimed to provide an overview of what is known about PA messaging and highlight key research gaps. METHODS We followed a 5-stage protocol proposed by Arksey & O'Malley and the Preferred Reporting Items For Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews checklist. Stage 1: research questions were identified. Stage 2: we identified relevant studies by searching electronic databases, contacting existing networks and hand searching reference lists. Stage 3: studies were screened in Covidence™ software. Stage 4: study data were extracted and charted. Stage 5: findings from included studies were collated, summarised and reported in two ways: (1) a descriptive numerical analysis providing insight into extent, nature and distribution of the included studies, and (2) a narrative summary summarizing the evidence reviewed organised by messaging concepts and by population subgroup. RESULTS A total of 9525 references were imported into Covidence™ for screening. Of these, 123 studies were included in final analysis. We found that PA messaging evidence is complex and multidimensional in nature, with numerous concepts to consider when creating or evaluating messages. The extent to which these different PA messaging concepts have been researched is variable. Where research has accumulated and evidence is consistent, it supports the following: (1) PA messages should be framed positively and highlight short-term outcomes specifically relating to social and mental health, (2) message content should be tailored or targeted to intended recipient(s), and (3) when developing messages, formative research, psychological theory and/or social marketing principles should be used. CONCLUSION While it is unlikely to address global inactivity on its own, PA messaging may play a valuable role improving population PA levels. However, it is a complex and multidimensional concept and greater understanding is still needed. We present a synthesis of the existing evidence, highlighting key areas where evidence has accumulated and where gaps lie, as well as recommendations for PA messaging to different population subgroups.


title: Evaluation of modified Estimation of Physiologic Ability and Surgical Stress in gastric carcinoma surgery.

text: BACKGROUND We recently modified our prediction scoring system "Estimation of Physiologic Ability and Surgical Stress" and have designated the current version mE-PASS. This scoring system has been designed to obtain predicted postoperative mortality rates before surgery and this study was performed to assess its usefulness in elective surgery for gastric carcinoma. METHODS We investigated seven variables for mE-PASS and evaluated the postoperative course in 3,449 patients who underwent elective surgery for gastric carcinoma in Japan between August 20, 1987 and April 9, 2007, in order to quantify the predicted in-hospital mortality rates (R). The calibration and discrimination power of R were assessed using the Hosmer-Lemeshow test and the area under the receiver operating characteristic curve (AUC), respectively. The ratios of observed-to-estimated mortality rates (OE ratios) were quantified as a measure of quality. RESULTS The overall postoperative morbidity and mortality rates were 19.0 and 2.0%, respectively. R demonstrated good power in calibration (χ(2) value, 12.5; df 8; P = 0.89) as well as discrimination (AUC, 95% confidence intervals: 0.80, 0.75-0.85). The OE ratios between hospitals ranged from 0.44 to 1.8. Overall, the OE ratios seemed to improve with time (OE ratio, 95% confidence intervals: 1.3, 0.73-2.4 for the early period between 1987 and 2000; 1.0, 0.59-1.7 for the middle period between 2001 and 2004; and 0.65, 0.36-1.2 for the late period between 2005 and 2007). CONCLUSION Based on these findings, mE-PASS might be useful for medical decision-making and for assessing the quality of care in elective surgery for gastric carcinoma.


title: Single-incision laparoscopic colorectal surgery: a report of 33 cases in Saudi Arabia.

text: BACKGROUND Single-incision laparoscopic surgery (SILS) has gained worldwide acceptance as a minimally invasive technique in colorectal procedures since its introduction in 2008. However, case series on its feasibility and safety in Saudi Arabia are lacking. OBJECTIVE Evaluate the operative results and clinical outcome of single-port laparoscopic procedures in colorectal surgeries. DESIGN Retrospective. SETTING This study was conducted at King Khalid university Hospital, Riyadh, Saudi Arabia. PATIENTS AND METHODS Demographic and clinical data, including pathology, and intraoperative and postoperative outcomes, were prospectively collected in patients undergoing SILS. This study was conducted during the period from January 2010 and October 2014. MAIN OUTCOME MEASURES Demographic and postoperative outcomes in patients undergoing SILS colectomies. RESULTS Thirty-three (33) patients underwent SILS. The mean (SD) age was 51 years (18.2 years), and the average body mass index was 26.6 (6.9) kg/m2. Patients were primarily diagnosed with cancer (n=20/33, 61%), inflammatory bowel disease (n=12/33, 36%) and diverticulitis (n=1/33, 3%). Procedures included anterior resection (n=9/33, 27%), ileocecal resection (n=8/33 24%), hemicolectomy (n=7/33, 21%), extended right hemicolectomy (n=5/33, 15%) and total colectomy (n=4/33, 12%). The mean SD operative time was 212 minutes (76.4 minutes). The mean SD size of the extraction incision was 4.2 (1.7) cm. Six percent of the cases were converted to open (n=2/33), and 9% required placement of an extra port (n=3/33). Four (12%) patients had intraoperative complications, and 30% experienced postoperative complications. The average length of hospital stay was 6.4 (4.3) days. COCNLUSIONS SILS is technically feasible and safe for patients undergoing colorectal surgery with no unusual complications. However, comparative studies are necessary to validate the potential benefits of SILS over conventional colorectal laparoscopic surgery. LIMITATIONS The study lacked a comparison to conventional open procedures. Additionally, some evaluation criteria were not considered, including cosmesis, pain control, patient satisfaction and cost effectiveness.


title: Live-cell imaging and ultrastructural analysis reveal remarkable features of cultured porcine gonocytes.

text: Gonocytes in the neonatal testis have male germline stem cell potential. The objective of the present study was to examine the behavior and ultrastructure of gonocytes in culture. Neonatal porcine testis cells were cultured for 4 weeks and underwent live-cell imaging to explore real-time interactions among cultured cells. This included imaging every 1 h from day 0 to day 3, every 2 h from day 4 to day 7, and every 1 h for 24 h at days 14, 21, and 28. Samples also underwent scanning electron microscopy, transmission electron microscopy, morphometric evaluations, immunofluorescence, and RT-PCR. Live-cell imaging revealed an active amoeboid-like movement of gonocytes, assisted by the formation of extensive cytoplasmic projections, which, using scanning electron microscopy, were categorized into spike-like filopodia, leaf-like lamellipodia, membrane ruffles, and cytoplasmic blebs. In the first week of culture, gonocytes formed loose attachments on top of a somatic cell monolayer and, in week 2, formed grape-like clusters, which, over time, grew in cell number. Starting at week 3 of culture, some of the gonocyte clusters transformed into large multinucleated embryoid body-like colonies (EBLCs) that expressed both gonocyte- and pluripotent-specific markers. The number and diameter of individual gonocytes, the number and density of organelles within gonocytes, as well as the number and diameter of the EBLCs increased over time (P < 0.05). In conclusion, cultured porcine gonocytes displayed extensive migratory behavior facilitated by their various cytoplasmic projections, propagated, and transformed into EBLCs that increased in size and complexity over time.


title: Single access retroperitoneoscopic adrenalectomy (SARA)--one step beyond in endocrine surgery.

text: INTRODUCTION Today, endoscopic adrenalectomy has become a gold standard in endocrine surgery. METHOD AND RESULTS To minimize the morbidity and improve cosmesis, a single access retroperitoneoscopic adrenalectomy (SARA) has been developed. Patients were placed in prone position. Through a single 1.5 cm skin incision at the tip of the 12th rib the creation of the retroperitoneal space and the dissection of the adrenal gland were performed. SARA was used in five patients with adrenal tumors (size: 1-4 cm; four right, one left). Operating time ranged from 35 to 70 min, mean blood loss was <10 ml. No perioperative or postoperative complications were noticed. Mean hospital stay was 2 days. CONCLUSIONS SARA is feasible and represents a new horizon in endocrine surgery.


title: Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

text: Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04323527.


docid: kpkrejvg

title: Picornaviral 3C protease inhibitors and the dual 3C protease/coronaviral 3C-like protease inhibitors.

text: IMPORTANCE OF THE FIELD Picornaviruses are small non-enveloped RNA viruses with genomic RNA of 7500 - 8000 nucleotides, whereas coronaviruses (CoV) are RNA viruses with larger genome of 27 - 32 kb. Both types of viruses translate their genetic information into polyprotein precursors that are processed by virally encoded 3C proteases (3C(pro)) and 3C-like proteases (3CL(pro)), respectively, to generate functional viral proteins. The most studied human rhinoviruses (HRV) belonging to picornaviridae family are the main etiologic agents of the common cold. Due to lack of effective drugs, 3C(pro) has served as an excellent target for anti-viral intervention and considerable efforts have been made in the development of inhibitors. Interestingly, the inhibitors of 3C(pro) cannot inhibit 3CL(pro) potently without modification due to subtle differences in their active-site structures, but a group of common inhibitors against 3C(pro) and 3CL(pro) were found recently. AREAS COVERED IN THIS REVIEW The inhibitors against 3C(pro) reported in the literatures and patents, with a focus on those inhibiting HRV and the dual picornaviral 3C(pro)/coronaviral 3CL(pro) inhibitors, are summarized in this review. WHAT THE READERS WILL GAIN Readers will rapidly gain an overview of the individual and dual 3C(pro) inhibitors and the structural basis for discriminating them. TAKE HOME MESSAGE In the future, more selective potent inhibitors against each protease and dual inhibitors against both proteases can be further developed to treat the diseases caused by picornaviruses and CoV.


docid: rzsxgbaa

title: Inferior approach instead of standard "pull-down" technique for transseptal puncture in difficult anatomy.


title: Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. METHODS We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. RESULTS Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant (P=0.67 and P=0.87, respectively). The same applied for occurrence of symptomatic hemorrhage (P=0.39 for hyperglycemia, P=0.39 for admission serum glucose). CONCLUSIONS We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. CLINICAL TRIAL REGISTRATION URL: www.isrctn.com. Unique identifier: ISRCTN10888758.


title: Patient-related medical risk factors for periprosthetic joint infection of the hip and knee.

text: Despite advancements and improvements in methods for preventing infection, periprosthetic joint infection (PJI) is a significant complication following total joint arthroplasty (TJA). Prevention is the most important strategy to deal with this disabling complication, and prevention should begin with identifying patient-related risk factors. Medical risk factors, such as morbid obesity, malnutrition, hyperglycemia, uncontrolled diabetes mellitus, rheumatoid arthritis (RA), preoperative anemia, cardiovascular disorders, chronic renal failure, smoking, alcohol abuse and depression, should be evaluated and optimized prior to surgery. Treating patients to get laboratory values under a specified threshold or cessation of certain modifiable risk factors can decrease the risk of PJI. Although significant advances have been made in past decades to identify these risk factors, there remains some uncertainty regarding the risk factors predisposing TJA patients to PJI. Through a review of the current literature, this paper aims to comprehensively evaluate and provide a better understanding of known medical risk factors for PJI after TJA.


title: Safe and simplified endoscopic technique in transvaginal NOTES.

text: Although main obstacles for entry routes (transgastric, transvesical, and transrectal) in natural orifices transluminal endoscopic surgery are closure of the incision and infection issues, the transvaginal route seems to be the most used. There is no doubt that classic colpotomy is a valid option. Nevertheless, this approach can be difficult and time consuming. From our experience with fertiloscopy via vaginal access and using an existing disposable trocar, we describe a new safe and simple technique for transvaginal natural orifices transluminal endoscopic surgery.


Computed tomography manifestations of COVID-19 pneumonia.


title: The compromise of virtual screening and its impact on drug discovery.

text: Introduction: Docking and structure-based virtual screening (VS) have been standard approaches in structure-based design for over two decades. However, our understanding of the limitations, potential, and strength of these techniques has enhanced, raising expectations. Areas covered: Based on a survey of reports in the past five years, we assess whether VS: (1) predicts binding poses in agreement with crystallographic data (when available); (2) is a superior screening tool, as often claimed; (3) is successful in identifying chemical scaffolds that can be starting points for subsequent lead optimization cycles. Data shows that knowledge of the target and its chemotypes in postprocessing lead to viable hits in early drug discovery endeavors. Expert opinion: VS is capable of accurate placements in the pocket for the most part, but does not consistently score screening collections accurately. What matters is capitalization on available resources to get closer to a viable lead or optimizable series. Integration of approaches, subjective hit selection guided by knowledge of the receptor or endogenous ligand, libraries driven by experimental guides, validation studies to identify the best docking/scoring that reproduces experimental findings, constraints regarding receptor-ligand interactions, thoroughly designed methodologies, and predefined cutoff scoring criteria strengthen VS's position in pharmaceutical research.


Can 3D printing of oral drugs help fight the current COVID-19 pandemic (and similar crisis in the future)?


title: The first North American use of the Pipeline Flex flow diverter.

text: Flow diversion for the management of intracranial aneurysms represents a paradigm shift in how aneurysms are managed. The Pipeline embolization device (PED) is, to date, the only flow diverter approved for use in the USA by the Food and Drug Administration. Limitations and complications with new treatment strategies are inevitable, and with the PED there have been reports of complications, most commonly with challenging deployments. Once deployment has been initiated, the device is 'one-way'; it can only be deployed further or removed. Yet, situations arise in which the ability to recapture or reposition the device would be advantageous. A second-generation Pipeline has been developed that addresses these concerns. We report the first use in North America of this second-generation Pipeline device: the Pipeline Flex. We discuss our rationale for using the device, our impressions of its operation, and the relevant literature concerning the current state of flow diversion.


COVID-19 Pandemic and JBJS.


Call for transparency of COVID-19 models.


docid: ubnzkfwz

title: VCAM-1/α4β1 integrin interaction is crucial for prompt recruitment of immune T cells into the brain during the early stage of reactivation of chronic infection with Toxoplasma gondii to prevent toxoplasmic encephalitis.

text: Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNAs for CD3δ, CD4, CD8β, gamma interferon (IFN-γ), and inducible nitric oxide synthase (NOS2) (an effector molecule to inhibit T. gondii growth) and the numbers of CD4(+) and CD8(+) T cells in the brain were significantly less in mice treated with anti-α4 integrin antibody than in those treated with control antibody at 3 days after sulfadiazine discontinuation. At 6 days after sulfadiazine discontinuation, cerebral tachyzoite-specific SAG1 mRNA levels and numbers of inflammatory foci associated with tachyzoites were markedly greater in anti-α4 integrin antibody-treated than in control antibody-treated animals, even though IFN-γ and NOS2 mRNA levels were higher in the former than in the latter. These results indicate that VCAM-1/α4β1 integrin interaction is crucial for prompt recruitment of immune T cells and induction of IFN-γ-mediated protective immune responses during the early stage of reactivation of chronic T. gondii infection to control tachyzoite growth.


docid: bedygxjs

title: Reply to Letter to the Editor: Surgery in the COVID-19 Phase 2 Italian scenario: lessons learned in Northern Italy spoke hospitals.


title: Clinical management of an ectopic egg in a Timneh African grey parrot (Psittacus erithacus timneh).

text: CASE DESCRIPTION A 13-year-old female Timneh African grey parrot (Psittacus erithacus timneh) was evaluated because of the presence of a bald patch of skin caudal to the sternum and increased territorial and nesting behavior of 2 weeks' duration. CLINICAL FINDINGS Whole-body radiography revealed a mineralized egg of normal size and shape. However, no oviposition occurred, and the bird had no signs consistent with dystocia. After 7 days, repeated radiography revealed that the egg had rotated by approximately 180° along its short axis, leading to a diagnosis of ectopic egg retention, which was supported by the results of ultrasonography. TREATMENT AND OUTCOME Surgical removal of the ectopic egg was performed by means of a ventral midline approach 14 days after administration of leuprolide acetate (800 μg/kg [364 μg/lb], IM). No intracoelomic abnormalities, such as coelomitis or oviductal disease, were diagnosed, and the bird recovered without complications. Physical examination and whole-body radiography at 8 months and a follow-up phone call with the owner at 16 months after surgical treatment revealed no evidence of ectopic egg recurrence or reproductive behavior. CLINICAL RELEVANCE Clinical management of ectopic egg retention differs considerably from treatment of intraoviductal egg binding. Therefore, careful evaluation of avian patients with radiographic evidence of egg binding should be performed to avoid possible iatrogenic deterioration of the patient's condition, secondary to inappropriate treatment attempts such as hormonal induction of oviposition or attempts to remove the retained egg via the cloaca. Repeated radiography and ultrasonography and close monitoring of the patient's general condition as well as the lack of clinical signs consistent with dystocia will facilitate the diagnosis of ectopic egg retention.


title: The role of viruses in the clinical presentation of chronic rhinosinusitis.

text: BACKGROUND The role of viruses in chronic rhinosinusitis (CRS) is poorly understood. In part, this is secondary to difficulty in isolating viruses. Although traditional detection methods for respiratory viruses have had little clinical utility, modern viral screening techniques that use molecular sequencing are now both rapid and feasible, which makes analysis of the paranasal sinus microbiome more accessible. OBJECTIVE To detect respiratory viruses in the paranasal sinuses of patients with CRS and of healthy controls as well as to correlate clinical and radiographic measures of CRS with viral presence. METHODS In this prospective study, 13 patients with CRS with nasal polyposis (CRSwNP) and 8 patients without nasal polyposis (CRSsNP) were enrolled and compared with 14 healthy controls. Samples were obtained from the paranasal sinuses and were screened for viral DNA with polymerase chain reaction--based sequencing techniques. Typical symptoms of CRS, the Sinonasal Questionnaire, and objective measures, including the modified Lund-Mackay and modified Lund-Kennedy scores were obtained. RESULTS Eighty percent of the positive screens (4/5) were found in patients with CRSsNP, whereas 20% of the positive tests (1/5) were in the CRSwNP group, and none of the controls tested positive (p = 0.0029). Coronavirus was the most common virus detected. Sinonasal Questionnaire scores of the patients with CRS who tested positive for viruses were higher but not statistically different than those without a positive screen (p = 0.31). Radiographic and endoscopic measures of disease were not significantly different in the setting of a positive viral screen (p = 0.12 and 0.11 respectively). CONCLUSION Although traditionally difficult, advances in molecular sequencing enhance detection of viruses in the sinonasal tract. In this study, respiratory viruses were more commonly isolated from patients with CRS compared with healthy controls. Moreover, viral infection may play a greater role in symptom exacerbation in CRSsNP than in CRSwNP. These findings warrant further investigation into the role of the viral microbiome in CRS.


title: Simple classification and clinical outcomes of angiographic dissection after balloon angioplasty for femoropopliteal disease.

text: OBJECTIVE Angiographic dissection is considered to be associated with restenosis. However, little is known about the impact of the severity of angiographic dissection on future restenosis. METHODS A total of 319 consecutive de novo femoropopliteal lesions were treated by balloon angioplasty alone. All of these lesions were divided into three groups: group A, no angiographic dissection; group B, mild dissection, the width of the dissection was less than one-third of the lumen; and group C, severe dissection, the width of the dissection was more than one-third of the lumen. Kaplan-Meier analysis estimated the primary patency rate at 3 years between the groups. RESULTS The primary patency rates at 3 years were 66.0% in group A, 63.8% in group B, and 32.5% in group C (log-rank, P < .001). Cox proportional hazards analysis revealed that a lesion length >100 mm (hazard ratio, 1.734; 95% confidence interval, 1.099-2.735; P = .018) and severe angiographic dissection (hazard ratio, 1.956; 95% confidence interval, 1.276-2.997; P = .002) were predictors of primary patency loss at 3 years. When the lesions were divided into two groups according to the lesion length >100 mm or not, angiographic dissection had a larger impact on restenosis in a long lesion >100 mm (≤100 mm: 65.5% in group A, 75.6% in group B, and 48.0% in group C [log-rank, P = .015]; >100 mm: 68.8% in group A, 42.5% in group B, and 24.2% in group C [log-rank, P = .017]). CONCLUSIONS Severe angiographic dissection was associated with future restenosis after balloon angioplasty for femoropopliteal lesions, but mild angiographic dissection was not. Angiographic dissection had more impact on future restenosis particularly in treated long lesions. Stents might not be necessary in short lesions with mild dissection.


title: COVID-19 Pandemic: Hopes from Proteomics and Multiomics Research.

text: The successful sequencing of the novel coronavirus SARS-CoV-2 nucleic acid paved the way for exploration of omics systems science and integrative biology research approaches for combating this unprecedented planetary health challenge. Omics-scale studies on this viral infection are emerging rapidly and offer a tremendous potential to unravel the puzzles of the SARS-CoV-2 pathobiology, and ways forward for diagnostic and therapeutic innovation.


title: Development of a loop-mediated isothermal amplification targeting a gene within the pyruvate dehydrogenase complex, the pdhA gene, for rapid detection of Mycoplasma gallisepticum.

text: Mycoplasma gallisepticum infections impose a significant economic burden on the poultry industry. In the current study, a loop-mediated isothermal amplification (LAMP) assay was developed and optimized to detect M. gallisepticum based on a gene within the pyruvate dehydrogenase complex, the pdhA gene, which codes for the major subunit (E1α) in the complex. The reaction conditions were optimized, and the specificity was confirmed by successful amplification of several M. gallisepticum strains, while no amplification was detected with 20 other major bacterial and viral pathogens of poultry. Additionally, the LAMP assay achieved 10-fold higher sensitivity than an existing polymerase chain reaction (PCR) method. The LAMP assay was applied to swab samples collected from poultry farms and compared with PCR. The positive detection rate was 20.2% (37/183) by LAMP and 13.1% (24/183) by PCR. The LAMP assay could provide a cost-effective, quick, and sensitive method for the detection of M. gallisepticum.


title: Novel Totally Laparoscopic Endolumenal Rectal Resection With Transanal Natural Orifice Specimen Extraction (NOSE) Without Rectal Stump Opening: A Modification of Our Recently Published Clean Surgical Technique in a Porcine Model.

text: Our group has recently described a novel technique for clean endolumenal bowel resection, in which abdominal and transanal approaches were used. In the current study, 2 modifications of this procedure were tested for feasibility in a porcine model. A laparoscopic approach to the peritoneal cavity was employed in rectal mobilization; this was followed by a transanal rectorectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. Once IPT was established, a second ligature was placed around the rectum approximating the proximal and distal resection margins. This was followed by a purse string suture through 2 bowel walls, encircling the shaft of the anvil just proximal to the ligatures. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls distal to the previously placed purse string suture and ligatures. The anastomosis was achieved by applying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. Although, this is a novel and evolving procedure, its minimally invasive nature, as well as aseptic bowel manipulation during endolumenal rectal resection, has the potential to limit the complications associated with abdominal wall incision and surgical site infection.


title: Disastrous events and political failures.

text: Response to the Ebola crisis (ongoing event) has been less than efficient. It has been monitored less than adequately by the international community and has been coordinated poorly in the USA. The event is used as a platform to examine deficiencies in public health infrastructure, the limits of its political and financial support, and how political outcomes can be affected. The need to tease out the political determinants implicit in policy failure and disaster management is argued in this Editorial. Failures mentioned include in the Balkans and in Greece with ongoing austerity. Comments on the real heroes of Ebola on the ground in Africa and the need for a charismatic role for political leaders in public health are also included.


title: Laparoscopic versus open parenchymal preserving liver resections in the posterosuperior segments: a case-matched study.

text: BACKGROUND Patients with lesions in the posterosuperior (PS) segments of the liver have been considered poor candidates for laparoscopic liver resection (LLR). This study aims to compare short-term outcomes of LLR and open liver resections (OLR) in the PS segments. METHODS This multicenter study consisted of all patients who underwent LLR in the PS segments and all patients who underwent OLR in the PS segments between October 2011 and July 2016. Laparoscopic cases were case-matched with those who had an identical open procedure during the same period based on tumor location (same segment) and the Brisbane classification of the resection. Demographics, comorbid factors, perioperative outcomes, short-term outcomes, necessity of adjuvant chemotherapy, and the interval between surgery and initiation of adjuvant chemotherapy were compared between the two groups. Data were retrieved from a prospectively maintained electronic database. RESULTS Both groups were comparable for age, sex, ASA score, maximum tumor diameter, and number of patients with additional liver resections outside the posterior segments. Operative time was similar in both groups (median 140 min; p = 0.92). Blood loss was less in the LLR-group (median: 150 vs. 300 ml in OLR-group). Median hospital stay was 6 days in both groups. There was no significant difference in postoperative complications (OLR-group: 31.4% vs. LLR-group: 25.7%; p = 0.60). There was no significant difference in R0 resections (LLR: 97.2 vs. 100% in OLR; p = 1.00). Tumor-free margins were less in the LLR group (LLR: 5 vs. 9.5 mm in OLR; p = 0.012). Patients undergoing LLR were treated with chemotherapy sooner compared to those undergoing OLR (41 vs. 56 days, p = 0.02). CONCLUSION This study suggests that laparoscopic parenchymal preserving liver resections in the PS segments can be performed with comparable short-term outcomes as similar OLR. The shorter interval to chemotherapy might provide long-term oncologic benefits in patients who underwent LLR.


title: Challenges facing coronavirus disease 2019: Psychiatric services for patients with mental disorders.

text: As a Public Health Emergency of International Concern declared by WHO, the current outbreak of coronavirus disease (COVID-19) in China has captured the world's attention.1.


title: Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic.

text: Background: Cardiac injury and myocarditis have been described in adults with COVID-19. SARS-CoV-2 infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children (MIS-C) as defined by the US Centers for Disease Control. Methods: Over a two-month period contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range 2-16 years). Co-morbidities were present in 28% including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one third; 80% required inotropic support with 28% treated with ECMO. Inflammation markers were suggestive of cytokine storm (interleukin 6 median 135 pg/mL) and macrophage activation (D-dimer median 5284 ng/mL). Mean brain natriuretic peptide was elevated (5743 pg/mL). Thirty-one/35 (88%) patients tested positive for SARS-CoV-2 infection by PCR of nasopharyngeal swab or serology. All patients received intravenous immune globulin, with adjunctive steroid therapy used in one third. Left ventricular function was restored in the 25/35 of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned. Conclusion: Children may experience an acute cardiac decompensation due to severe inflammatory state following SARS-CoV-2 infection (multisystem inflammatory syndrome in children - MIS-C). Treatment with immune globulin appears to be associated with recovery of left ventricular systolic function.


title: Laryngeal injuries following endotracheal intubation in ENT surgery: predictive value of anatomical scores.

text: Endotracheal intubation has been associated with a threefold higher incidence of laryngopharyngeal complaints following anesthesia in comparison to laryngeal mask airway. Such complaints, including hoarseness and sore throat, have been reported in up to 90% of patients within 24 h of extubation. The purpose of this study was to determine which preoperatively documented clinical and anatomic parameters are predictive of laryngo-pharyngeal trauma resulting from elective endotracheal intubation. Fifty-three patients undergoing ENT procedures requiring general anesthesia with endotracheal intubation were recruited. Pre and postoperative laryngostroboscopic examination was performed and findings correlated to preoperative clinical and anatomic parameters. Readily assessed anatomic parameters including height (>180 cm) and weight (>80 kg) correlated significantly to the Eckerbom grade of intubation-associated acute laryngeal injury (rs = 0.374; p = 0.006 and rs = 0.278; p = 0.044, respectively). The mandibular protrusion test also correlated significantly to the Eckerbom grade (rs = 0.462, p = 0.001) while the upper-lip-bite test showed significant correlation to impaired vocal fold oscillation (rs = 0.288, p = 0.036), with injury prediction sensitivities of 37.5 and 39.4%, respectively. No parameters correlated to subjective complaints (n = 5, 9.2%). This study provides suggestions on how to improve the classification of intubation-associated laryngeal injuries as well as providing the basis for larger clinical trials in other surgical subspecialties.


title: Development of Snake Fungal Disease after Experimental Challenge with Ophidiomyces ophiodiicola in Cottonmouths (Agkistrodon piscivorous).

text: Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.


Outcomes of the 10th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.


title: Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L.

text: A novel small molecule thiocarbazate (PubChem SID 26681509), a potent inhibitor of human cathepsin L (EC 3.4.22.15) with an IC(50) of 56 nM, was developed after a 57,821-compound screen of the National Institutes of Health Molecular Libraries Small Molecule Repository. After a 4-h preincubation with cathepsin L, this compound became even more potent, demonstrating an IC(50) of 1.0 nM. The thiocarbazate was determined to be a slow-binding and slowly reversible competitive inhibitor. Through a transient kinetic analysis for single-step reversibility, inhibition rate constants were k(on) = 24,000 M(-1)s(-1) and k(off) = 2.2 x 10(-5) s(-1) (K(i) = 0.89 nM). Molecular docking studies were undertaken using the experimentally derived X-ray crystal structure of papain/CLIK-148 (1cvz. pdb). These studies revealed critical hydrogen bonding patterns of the thiocarbazate with key active site residues in papain. The thiocarbazate displayed 7- to 151-fold greater selectivity toward cathepsin L than papain and cathepsins B, K, V, and S with no activity against cathepsin G. The inhibitor demonstrated a lack of toxicity in human aortic endothelial cells and zebrafish. In addition, the thiocarbazate inhibited in vitro propagation of malaria parasite Plasmodium falciparum with an IC(50) of 15.4 microM and inhibited Leishmania major with an IC(50) of 12.5 microM.


title: Transcaval access for TAVR across a polyester aortic graft.

text: Transcaval access to the aorta allows transcatheter aortic valve replacement in patients without other good access options. The resulting aorto-caval fistula is closed with a nitinol cardiac occluder device. There is no experience traversing a synthetic aortic graft to perform transcaval access and closure. We describe a patient who underwent successful traversal of a polyester aortic graft using radiofrequency energy applied from the tip of a guidewire, to allow retrograde transcatheter aortic valve replacement from a femoral vein, along with details of our technique. The patient did well and was discharged home after 3 days. There was residual aorto-caval fistulous flow immediately after implantation of a polyester-seeded nitinol muscular ventricular septal defect occluder device, but this fistula spontaneously occluded within one month.