title: Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

text: UNLABELLED The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity. METHODS C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys). At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a) global transcriptional variations in kidney tissues, (b) morphological changes in the kidneys, (c) changes in white and red blood cell count as well as blood levels of urea, and (d) changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy. RESULTS In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months. CONCLUSION Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these genes as markers of radiation damage in kidney tissue.


title: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020.

text: Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.


title: Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.

text: BACKGROUND AND OBJECTIVE The risk factors associated to long-term survival were assessed in patients with liver metastases of colorectal carcinoma undergoing ablative therapies. PATIENTS AND METHODS Single-centre cohort study, retrospectively analysed and prospectively collected consecutive patients with unresectable metastatic liver disease of colorectal carcinoma treated with ablative therapies between 1996 and 2013. Factors associated with survival time were identified using Cox's proportional hazard model with time-dependent covariates. A forward variable selection based on Akaike information criterion was performed. Relative risk and 95% confidence intervals for each factor were calculated. Statistical significance was set as P<.05. RESULTS Seventy-five patients with liver metastases of colorectal cancer, with a mean age of 65.6 (10.3) underwent 106 treatments. Variables selected were good quality of life (RR 0.308, 95% CI 0.150-0.632) and tumour extension (RR 3.070, 95% CI 1.776-5.308). The median overall survival was 18.5 months (95% CI 17.4-24.4). The survival prognosis in median was 13.5 vs. 23.4 months for patients with and without tumour extension, and 23.0 vs. 12.8 months for patients with good and fair or poor quality of life, respectively. CONCLUSIONS Good quality of life and tumour extension were the only statistically significant predictors of long-term survival in patients of colorectal carcinoma with liver metastatic disease undergoing ablative treatment with ultrasound.


title: Enzyme-Activatable Cell-Penetrating Peptides through a Minimal Side Chain Modification.

text: Activatable cell-penetrating peptides are of great interest in drug delivery because of their enhanced selectivity which can be controlled by the external stimuli that trigger their activation. The use of a specific enzymatic reaction to trigger uptake of an inert peptide offers a relevant targeting strategy because the activation process takes place in a short time and only in areas where the specific cell surface enzyme is present. To this aim, the lysine side chain of Tat peptides was modified with an enzyme-cleavable domain of minimal size. This yielded blocked Tat-peptides which were inactive but that could be activated by coincubation with the selected enzymes.


title: Post-ictal Modulation of Baroreflex Sensitivity in Patients With Intractable Epilepsy.

text: Objective: Seizure-related autonomic dysregulation occurs in epilepsy patients and may contribute to Sudden Unexpected Death in Epilepsy (SUDEP). We tested how different types of seizures affect baroreflex sensitivity (BRS) and heart rate variability (HRV). We hypothesized that BRS and HRV would be reduced after bilateral convulsive seizures (BCS). Methods: We recorded blood pressure (BP), electrocardiogram (ECG) and oxygen saturation continuously in patients (n = 18) with intractable epilepsy undergoing video-EEG monitoring. A total of 23 seizures, either focal seizures (FS, n = 14) or BCS (n = 9), were analyzed from these patients. We used 5 different HRV measurements in both the time and frequency domains to study HRV in pre- and post-ictal states. We used the average frequency domain gain, computed as the average of the magnitude ratio between the systolic BP (BPsys) and the RR-interval time series, in the low-frequency (LF) band as frequency domain index of BRS in addition to the instantaneous slope between systolic BP and RR-interval satisfying spontaneous BRS criteria as a time domain index of BRS. Results: Overall, the post-ictal modulation of HRV varied across the subjects but not specifically by the type of seizures. Comparing pre- to post-ictal epochs, the LF power of BRS decreased in 8 of 9 seizures for patients with BCS; whereas following 12 of 14 FS, BRS increased. Similarly, spontaneous BRS decreased following 7 of 9 BCS. The presence or absence of oxygen desaturation was not consistent with the changes in BRS following seizures, and the HRV does not appear to be correlated with the BRS changes. These data suggest that a transient decrease in BRS and temporary loss of cardiovascular homeostatic control can follow BCS but is unlikely following FS. Significance: These findings indicate significant post-ictal autonomic dysregulation in patients with epilepsy following BCS. Further, reduced BRS following BCS, if confirmed in future studies on SUDEP cases, may indicate one quantifiable risk marker of SUDEP.


title: A standardized neurointerventional thrombectomy protocol leads to faster recanalization times.

text: BACKGROUND AND PURPOSE Intra-arterial therapy (IAT) is most effective when performed rapidly after ischemic stroke onset. However, there are limited performance benchmarks in IAT and there is a scarcity of information on how to structure an effective IAT protocol and its impact on time to treatment. The objective of our study was to detail a standardized IAT protocol, and to assess its influence on time to treatment in ischemic stroke. METHODS This was a retrospective observational study over 4 years at a comprehensive stroke center. A standardized IAT protocol was implemented in June 2013 that included pre-notifying the stroke team before hospital arrival, defining clinician roles, processing tasks in parallel, and standardizing IAT procedures. Three time metrics were examined and reported as median (IQR) minutes: arrival to CT imaging, CT to groin puncture, and puncture to recanalization. We compared these metrics in patients admitted before implementation (January 2012-May 2013) to patients admitted after (June 2013-December 2015) using Wilcoxon Mann-Whitney tests. RESULTS 380 patients were included. After the protocol was implemented, there were significant reductions in time from arrival to CT (17 (14-21) vs 13 (11-19) min, p<0.001), CT to puncture (46 (30-82) vs 31 (23-54) min, p<0.001), and puncture to recanalization (65 (33-90) vs 37 (22-65) min, p<0.001). 60% of time was saved during puncture to recanalization. Significant reductions in time were observed during both normal working hours and off-hours. CONCLUSIONS Implementation of a standardized protocol resulted in a significant reduction in time to recanalization for patients with an ischemic stroke. A standardized IAT protocol decreases time to recanalization when team roles are clearly defined, tasks are processed in parallel, and procedures are standardized.


title: [Treatment of brain AVMS (TOBAS): A randomized controlled trial and registry].

text: OBJECTIVE The management of unruptured and ruptured brain arteriovenous malformations (AVMs) remains controversial. The Treatment of Brain AVM Study (TOBAS) was designed to assess curative treatments in the management of AVMs. The purpose of our study is to provide a care trial context to brain AVM patients. METHODS TOBAS is a pragmatic, prospective study including 2 randomized controlled trials and a registry. All AVM patients can be recruited. The preferred management modality will be predetermined prior to randomization by the team based on clinical judgment. Patients eligible for both conservative and interventional management will be randomly allocated conservative or curative treatment. Randomization will be stratified by a treatment modality (surgery, radiosurgery or embolization) and minimized according to a history of previous rupture and Spetzler-Martin grade. A second randomization will allocate eligible patients to embolization/no embolization prior to surgery or radiosurgery. The primary outcome of the study is death (any cause) or disabling stroke (mRS>2) at 10 years. All patients managed according to clinical judgment alone will be included in the registry. The study is registered under: wwwTrials.gov, ID: NCT02098252. EXPECTED RESULTS A minimum recruitment of 540 patients is required to show that treatment can reduce the primary outcome by 10 % (from 25 to 15 %); 440 patients will be needed to show a 10 % increase in angiographic occlusion for a good clinical outcome with pre-embolization. CONCLUSION The trial is designed to offer optimal and verifiable care to patients with brain AVMs in spite of the uncertainty. We are currently seeking the participation of multiple centers.


title: Use of Barbed Sutures in Laparoscopic Gastrointestinal Single-Layer Sutures.

text: BACKGROUND AND OBJECTIVES Laparoscopic anastomotic methods are not commonly used because of the cumbersome laparoscopic intracorporeal sutures and tying involved. The barbed suture is one of the various devices developed to simplify the placement of intracorporeal sutures. However, barbed sutures are not commonly used during reconstruction after radical gastrectomy in cancer patients or for single-layer entire-thickness running suturing for intestinal anastomoses. We describe the procedure for using barbed sutures and report on the short-term surgical outcomes. METHODS Between August 2012 and March 2014, 15-cm-long barbed sutures (V-Loc 180; Covidien, Mansfield, MA, USA) were used for laparoscopic intestinal anastomoses, including intestinal hole closure for esophagojejunal and gastrojejunal anastomoses after mechanical anastomoses and gastric wall closure after partial resection. RESULTS In total, 38 patients underwent 40 laparoscopic anastomoses (esophagojejunostomies, 26; gastrojejunostomies, 7; and simple closure of gastric defect, 7); no cases required conversion to open surgery. Two cases exhibited positive air leak test results during surgery (1 case of esophagojejunostomy and 1 case of simple closure of gastric defect). Two cases of intestinal obstruction were noted; of those, one patient with postoperative intestinal paresis (grade II) was managed conservatively, and the other underwent repeat laparoscopic surgery (grade IIIb) for internal herniation unrelated to V-Loc use. No postoperative complications at the anastomosis site and no surgery-related deaths were noted. CONCLUSION Single-layer entire-thickness running suturing with the V-Loc 180 barbed suture after stapled side-to-side intestinal anastomosis was found to be safe and feasible in the reported cases.


title: The Doctor's Dilemma: lessons from GB Shaw in a modern pandemic COVID-19.

text: In the current COVID 19 pandemic, the only treatments are supportive as no definitive pharmacological intervention is available. The heterogeneity of the immune response in different patient groups is clear with less severe illness in children. Understanding these disparities is particularly important as severely affected patients with COVID19 cannot always be predicted before they experience a cytokine storm and multiorgan dysfunction. Over 100 years ago, the concept of individualised immunotherapy was introduced by Sir Almroth Wright and immortalised in GB Shaw's play The Doctor's Dilemma. Shaw's play The Doctor's Dilemma explores the issues of private medical practice, equality of health care delivery, rationing of scarce resources (intensive care) and high-risk therapies. The play also describes the dilemma of rationing of resources and selecting the correct patient for new experimental therapies. Immunological theories of the time are now reflected in current understanding of inflammatory responses in sepsis and immunomodulation during the COVID19 pandemic.


title: Predictive factors for complications of anatomical pulmonary segmentectomies.

text: OBJECTIVES The role of anatomical pulmonary segmentectomy is increasing, but there are few data about its complication rate. We have analysed the postoperative morbidity, mortality and risk factors in a consecutive series of 228 segmentectomies performed in our department. METHODS Between January 2007 and December 2011, 221 patients underwent 228 segmentectomies. There were 99 women (45%) and 122 men (55%). The mean age was 61 years (range 18-86 years). The mean forced expiratory volume in 1 s (FEV1) was 87%, and 30 patients had an FEV1 of ≤60%. Fifty-seven patients had a previous history of pulmonary resection. Indications for segmentectomy were: primary lung cancer (111 cases), metastases (71 cases), benign non-infectious (25 cases) and benign infectious diseases (21 cases). The approach was a posterolateral thoracotomy (Group PLT) in 146 patients (64%) and a thoracoscopy (Group TS) in 82 (36%). The two groups were homogenous in terms of age, gender, indications of surgery and type of segmentectomy. RESULTS The mortality rate at 3 months was 1.3% (3 patients). The overall complication rate was 34%. Ten patients were reoperated for the following reasons: haemothorax (4 cases), ischaemia of the remaining segment (3 cases), active bleeding (1 case), prolonged air leak (1 case) and dehiscence of thoracotomy (1 case). The average duration of drainage was 5 days (range 1-34 days) and the average length of stay was 9 days (range 3-126 days). On univariate analysis, FEV1, male gender and thoracotomy were statistically significant risk factors for complications. On multivariate analysis, the same three predictive factors of complications independently of age were found statistically significant: preoperative FEV1 < 60% [odds ratio (OR) = 5.9, 95% CI (2.5-13.7), P < 0.001] male gender [OR = 2.04, 95% CI (1.2-3.6), P < 0.013] and thoracotomy [OR = 2.14, 95% CI (1.33-3.46), P = 0.001]. CONCLUSIONS Pulmonary anatomical segmentectomies have an acceptable morbidity rate. Postoperative complications are more likely to develop in male gender patients, with FEV1 ≤ 60% and operated by open surgery.


title: Local surgical, ablative, and radiation treatment of metastases.

text: Because local therapies directed toward a specific tumor mass are known to be effective for treating early-stage cancers, it should be no surprise that there has been considerable historical experience using local therapies for metastatic disease. In more recent years, increasing interest in the use of local therapy for metastases likely has arisen from improvements in systemic therapy. In the absence of effective systemic therapies, such local treatments were often considered futile given both the difficulty in eliminating all sites of identifiable metastatic disease as well as realities regarding the rapid natural history of uncontrolled tumor dissemination. However, with a higher likelihood of patients surviving longer after effective systemic therapy, even if not cured, the goal of the eradication of residual metastases via potent local therapies can be rationalized. However, this rationalization should be evidence-based so as to avoid harming patients for no established benefit. Although surgical metastectomy remains the most common and first-line standard among local therapies, nonsurgical alternatives, including thermal ablation and stereotactic body radiotherapy, have become increasingly popular because they are generally less invasive than surgery and have demonstrated considerable promise in eradicating macroscopic tumor. Rather than eliminating the need for local therapies, improvements in systemic therapies appear to be increasing the prudent utilization of modern local therapies in patients presenting with more advanced cancer.


Understanding Observational Treatment Comparisons in the Setting of Coronavirus Disease 2019 (COVID-19).


title: Safety and efficacy using a detachable tip microcatheter in the embolization of pediatric arteriovenous malformations.

text: PURPOSE The treatment of deep-seeded pediatric brain arteriovenous malformations (AVMs) remains a challenging task. We describe our experience using a new detachable tip microcatheter in the embolization of brain arteriovenous malformations, pial arteriovenous fistulas, and vein of Galen malformations. We describe the safety and efficacy using a new detachable tip microcatheter in the treatment of pediatric deep brain arteriovenous malformations, pial malformations, and vein of Galen malformations. METHODS During a period of 9 months from March 2013 through January 2014, 11 pediatric patients in 14 procedures with 27 total injections were selected for treatment with a detachable tip under Food and Drug Administration (FDA) compassionate use exemption and were admitted to our department for treatment of their brain AVM using a liquid embolic agent and a detachable tip microcatheter. The ages of the patients ranged from 3 months to 18 years old. RESULTS Of the 27 total injections done, the tip detached in seven cases. For the 16 n-BCA injections, the tip detached six times (37.5 %), and for the 11 Onyx injections, the tip detached one time (9 %). There were no cases of premature microcatheter detachment during normal vessel navigation. CONCLUSIONS The introduction of these detachable tip microcatheters allows for a safe and relaxed injection that permits a true circumferential occlusion, and may further permit filling a larger amount of angioarchitecture without the risk of distal migration, or vessel damage during the usual rapid removal of non detachable micocatheters.


Emerging and re-emerging infectious diseases: a continuous challenge for Europe.


title: Two-port laparoscopic appendectomy assisted with needle grasper comparison with conventional laparoscopic appendectomy.

text: PURPOSE The 2-port laparoscopic appendectomy technique (TLA) is between the conventional 3-port and single-port laparoscopic appendectomy surgeries. We compared postoperative pain and cosmetic results after TLA with conventional laparoscopic appendectomy (CLA) by a 3-port device. METHODS Patients undergoing TLA were matched with patients undergoing CLA between February 2015 and November 2015 at the same institution. Thirty-two patients underwent TLA with a needle grasper. The appendix was secured by a percutaneous organ-holding device (needle grasper), then removed through a puncture at McBurney's point. Another 38 patients underwent CLA. Patient demographics, operative details, and postoperative outcomes were collected and evaluated. RESULTS One patient in the TLA group developed a wound infection and 1 patient in the CLA group developed a postoperative intra-abdominal abscess and 3 wound infections. There was no significant difference between the groups when comparing the length of hospital stay, time until oral intake, and other complications. The pain score in the first 12 hours after surgery was significanly higher in CLA group than the TLA group (P < 0.001). Operative time was significantly shorter in the CLA group compared to the TLA group (P < 0.001). CONCLUSION TLA using a needle grasper was associated with a significantly lower pain score 12 hours after surgery, better cosmetic results, and lower cost, than the CLA 3-port procedure because of the fewer number of ports.


title: Sharp transection of the suspensory ligament as an alternative to digital strumming during canine ovariohysterectomy.

text: OBJECTIVE To compare time efficiency and nociceptive input between digital strumming (DS) and sharp transection (ST) of the suspensory ligament during ovariohysterectomy (OVH). STUDY DESIGN Randomized controlled trial. ANIMALS 30 adult female dogs. METHODS Dogs were randomly assigned to ST or DS procedures. Measures of nociception were assessed through measurements of preoperative and intraoperative heart rate during manipulation of the suspensory ligament. Measures of pain were assessed through preoperative and postoperative pain scores by using the short form Glasgow Composite Pain Scale. Time efficiency was measured through total surgical time and the time to release each suspensory ligament. RESULTS After body weight was accounted for, the total surgical time was 1.1 minutes (P = .06) faster for ST than for DS, and each additional kilogram of body weight increased total surgical time by 0.1 minutes (P = .02). Digital strumming had 30.6-fold greater odds of taking greater than 1 minute compared with ST (P = .001). The heart rate from baseline to peak was 7.4 beats per minute lower in the ST group than in the DS group (P = .06). No complications were observed, and there was no difference in postoperative pain scores between treatments. CONCLUSION Sharp transection was faster and generated less intraoperative acceleration in heart rate but did not differ in postoperative outcomes compared with DS. CLINICAL SIGNIFICANCE Sharp transection is a viable alternative to DS for breakdown of the suspensory ligament during canine OVH. Sharp transection may improve surgical efficiency, especially when performing large volumes in the spay/neuter setting and could influence veterinary student training.


title: Robotic assistance improves intracorporeal suturing performance and safety in the operating room while decreasing operator workload.

text: BACKGROUND Intracorporeal suturing is one of the most difficult laparoscopic tasks. The purpose of this study was to assess the impact of robotic assistance on novice suturing performance, safety, and workload in the operating room. METHODS Medical students (n = 34), without prior laparoscopic suturing experience, were enrolled in an Institutional Review Board-approved, randomized protocol. After viewing an instructional video, subjects were tested in intracorporeal suturing on two identical, live, porcine Nissen fundoplication models; they placed three gastro-gastric sutures using conventional laparoscopic instruments in one model and using robotic assistance (da Vinci) in the other, in random order. Each knot was objectively scored based on time, accuracy, and security. Injuries to surrounding structures were recorded. Workload was assessed using the validated National Aeronautics and Space Administration (NASA) task load index (TLX) questionnaire, which measures the subjects' self-reported performance, effort, frustration, and mental, physical, and temporal demands of the task. Analysis was by paired t-test; p < 0.05 was considered significant. RESULTS Compared with laparoscopy, robotic assistance enabled subjects to suture faster (595 +/- 22 s versus 459 +/- 137 s, respectively; p < 0.001), achieve higher overall scores (0 +/- 1 versus 95 +/- 128, respectively; p < 0.001), and commit fewer errors per knot (1.15 +/- 1.35 versus 0.05 +/- 0.26, respectively; p < 0.001). Subjects' overall score did not improve between the first and third attempt for laparoscopic suturing (0 +/- 0 versus 0 +/- 0; p = NS) but improved significantly for robotic suturing (49 +/- 100 versus 141 +/- 152; p < 0.001). Moreover, subjects indicated on the NASA-TLX scale that the task was more difficult to perform with laparoscopic instruments compared with robotic assistance (99 +/- 15 versus 57 +/- 23; p < 0.001). CONCLUSIONS Compared with standard laparoscopy, robotic assistance significantly improved intracorporeal suturing performance and safety of novices in the operating room while decreasing their workload. Moreover, the robot significantly shortened the learning curve of this difficult task. Further study is needed to assess the value of robotic assistance for experienced surgeons, and validated robotic training curricula need to be developed.


title: Convalescent plasma: new evidence for an old therapeutic tool?

text: Passive immunisation for the prevention and treatment of human infectious diseases can be traced back to the 20(th) century. The recent Ebola virus outbreak in West Africa has turned the spotlight onto the possible use of convalescent whole blood and convalescent plasma in the treatment of infectious diseases because they are the only therapeutic strategy available in some cases, given the unavailability of vaccines, drugs or other specific treatments. Convalescent blood products could be a valid option in the treatment/prophylaxis of several infectious diseases both in association with other drugs/preventive measures and as the only therapy when a specific treatment is not available. However, there are still some issues to consider in determining the advisability of implementing a large-scale convalescent plasma transfusion programme.


title: Incorporating Geographic Information Science and Technology in Response to the COVID-19 Pandemic.

text: Incorporating geographic information science and technology (GIS&T) into COVID-19 pandemic surveillance, modeling, and response enhances understanding and control of the disease. Applications of GIS&T include 1) developing spatial data infrastructures for surveillance and data sharing, 2) incorporating mobility data in infectious disease forecasting, 3) using geospatial technologies for digital contact tracing, 4) integrating geographic data in COVID-19 modeling, 5) investigating geographic social vulnerabilities and health disparities, and 6) communicating the status of the disease or status of facilities for return-to-normal operations. Locations and availability of personal protective equipment, ventilators, hospital beds, and other items can be optimized with the use of GIS&T. Challenges include protection of individual privacy and civil liberties and closer collaboration among the fields of geography, medicine, public health, and public policy.


title: Changes of EEG phase synchronization and EOG signals along the use of steady state visually evoked potential-based brain computer interface.

text: The steady-state visual evoked potential (SSVEP)-based brain computer interface (BCI) has demonstrated relatively high performance with little user training, and thus becomes a popular BCI paradigm. However, due to the performance deterioration over time, its robustness and reliability appear not sufficient to allow a non-expert to use outside laboratory. It would be thus helpful to study what happens behind the decreasing tendency of the BCI performance. This paper explores the changes of brain networks and electrooculography (EOG) signals to investigate the cognitive capability changes along the use of the SSVEP-based BCI. The EOG signals are characterized by the blink amplitudes and the speeds of saccades, and the brain networks are estimated by the instantaneous phase synchronizations of electroencephalography (EEG) signals. Experimental results revealed that the characteristics derived from EOG and brain networks have similar trends which contain two stages. At the beginning, the blink amplitudes and the saccade speeds start to reduce. Meanwhile, the global synchronizations of the brain networks are formed quickly. These observations implies that the cognitive decline along the use of the SSVEP-based BCI. Then, the EOG and the brain networks related characteristics demonstrate a slow recovery or relatively stable trend. This study could be helpful for a better understanding about the depreciation of the BCI performance as well as its relationship with the brain networks and the EOG along the use of the SSVEP-based BCI.


Knowledge gaps about Tamiflu and Relenza for pandemic flu are blamed on research failure.


title: Effect of controlled hypotension on regional cerebral oxygen saturation during rhinoplasty: a prospective study.

text: The aim of this study was to investigate the effect of controlled hypotension on cerebral oxygen saturation (rSO2) using near infrared spectroscopy (NIRS) and evaluation of postoperative cognitive function in patients undergoing rhinoplasty. Fifty adult patients who were scheduled for elective rhinoplasty surgery and required controlled hypotension were enrolled in this prospective study. Controlled hypotension was provided using a combination of propofol and remifentanil infusion supplemented with nitroglycerin infusion as necessary. rSO2 was evaluated during controlled hypotension by NIRS. Cerebral desaturation was observed in 5 out of 50 patients (10 %) during hypotensive anesthesia. The greatest decrease from baseline was 28 % when MAP was 57 mmHg. In both non-desaturated and desaturated patients, postoperative MMSE scores were significantly lower than preoperative scores. There was a 4 % decrease in the non-desaturated patients and a 7 % decrease in the desaturated patients when preoperative and postoperative MMSE scores were compared. A decline in cognitive function 1 day after surgery was observed in 23 patients (46 %) and in all patients with intraoperative cerebral desaturation. The current study showed that even if SpO2 is in the normal range, there might be a decrease of more than 20 % in cerebral oxygen saturation during controlled hypotension.


title: Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms.

text: Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(Z)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics.


title: The Story of #GetMePPE and GetUsPPE.org - Rapidly Deploying Digital Tools for Better Healthcare.

text: UNSTRUCTURED Physicians, nurses, and other healthcare providers initiated the #GetMePPE movement on Twitter to spread awareness of the shortage of personal protective equipment (PPE) during the COVID-19 pandemic. Dwindling supplies, such as face masks, gowns and goggles, and inadequate production to meet increasing demands, has left healthcare workers and patients at risk. The momentum of this Twitter hashtag resulted in a petition to urge public officials to address the PPE shortage through increased funding and production. Simultaneously, GetUsPPE.org was launched by a collaborative of physicians and software engineers to develop a digital platform for the donation, request, and distribution of multi-modal sources of PPE. GetUsPPE.org and #GetMePPE merged in an attempt to combine public engagement and advocacy on social media with the coordination of PPE donation and distribution. Within ten days, over 1800 hospitals and PPE suppliers were registered in a database that allowed for the rapid coordination and distribution of scarce and in-demand materials. One month after its launch, the organization has distributed hundreds of thousands of items of PPE and built a database of over 6,000 PPE requesters[1] The call for action on social media and the rapid development of this digital tool created a productive channel for the public to contribute to the healthcare response to COVID-19 in meaningful ways. #GetMePPE and GetUsPPE.org were able to mobilize individuals and organizations outside of the healthcare system to address the unmet needs of the medical community. The success of GetUsPPE.org demonstrates the potential of digital tools as a platform for larger healthcare institutions (table 1) to rapidly address urgent issues in healthcare. In this manuscript, we outline this process and discuss key factors determining success.


title: Robotic-assisted Roux-en-Y gastric bypass performed in a community hospital setting: the future of bariatric surgery?

text: INTRODUCTION Since receiving Food and Drug Administration approval in 2000, surgery utilizing a robot has been successfully performed in numerous procedures including gastric bypass. However, despite the proven safety profile, reported lower complication rates, and technical benefits of robotic surgery, only a few centers in the USA have consistently applied this technology to bariatric surgery. In addition, there are limited studies with relatively small sample sizes comparing robotic-assisted Roux-en-Y gastric bypass (RRYGB) with laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS Through a retrospective analysis of our database, we compared outcomes of RRYGB versus LRYGB in the treatment of morbid obesity. All patients who underwent RRYGB and LRYGB through the Comprehensive Weight Management Program of the Queen's Medical Center (Honolulu, HI) from January 2007 to December 2009 were included. Outcomes data included weight loss, operative times, and hospital length of stay. All complications were reported. RESULTS 105 patients who underwent RRYGB were compared with 195 patients who received LRYGB. Excess weight loss, estimated blood loss, and length of hospital stay were similar in both groups. There were no mortalities in either group. The RRYGB group experienced a 9.5% complication rate versus 9.7% in LRYGB patients. Operative time was the only statistically significant difference, being approximately 17 min in favor of LRYGB. However, there was a steady decrease in RRYGB operative time with increasing experience. CONCLUSION Our study demonstrates a favorable safety profile with nearly equivalent outcomes and some previously unidentified qualitative benefits of the RRYGB approach to bariatric surgery in a community setting. These results are despite our early experience with the robotic surgery platform and confirm noninferiority of RRYGB versus LRYGB. While the RRYGB operative time was longer than LRYGB, the demonstrated decrease in operative time commensurate with increase in operative experience holds tremendous promise for the future.


title: Interplay between Myeloid Cells and Humoral Innate Immunity.

text: The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation. Therefore, soluble PRMs are part of the immune response and retain antibody-like effector functions. Here, we will review the expression and general function of soluble PRMs, focusing our attention on the long pentraxin PTX3.


title: Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong.

text: BACKGROUND We sought to determine the virologically confirmed hospitalization rates associated with influenza virus infection among Hong Kong children. METHODS Patients <18 years of age who lived on Hong Kong Island (a separate island within Hong Kong) and were admitted to either of the only 2 public hospitals on the island for a febrile acute respiratory infection on 1 fixed day of the week in each hospital from October 2003 through September 2006 were prospectively recruited. These 2 hospitals together accounted for 72.5% of all general pediatric admissions in Hong Kong Island with a known population denominator. Nasopharyngeal aspirates were obtained from all recruited patients and were tested for influenza A and influenza B viruses by direct antigen detection and culture. RESULTS All cases of influenza A during 2003-2004 were caused by H3N2 virus, whereas 85.7% of cases during 2004-2005 were due to H3N2 virus, and 93.5% during 2005-2006 were due to H1N1 virus. During 2004-2005, infants <1 year of age had the highest rate of hospitalization for influenza A (103.8 cases per 10,000 population), whereas children 1 year of age had the highest rate of hospitalization during the other 2 seasons (95.5 and 54.6 cases per 10,000 population during 2003-2004 and 2005-2006, respectively). A protection rate of 25%, presumably attributable to maternal antibodies, was seen in infants <1 year of age who were hospitalized during 2003-2004 with infection due to an H3N2 virus that had been in circulation. The hospitalization rates for influenza B were highest among children 2-4 years of age. CONCLUSIONS This population-based study of hospitalizations due to virologically confirmed influenza demonstrated a very high burden of disease among young children in Hong Kong. The morbidity varied with virus type, subtype, and antigenic variants.


title: Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

text: BACKGROUND Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). METHODS Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 105 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. RESULTS We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p < 0.05). IgG leakage, tight junction protein loss, and inflammatory cytokines IL-1β, IL-6, and TNF-α reduced in mesenchymal stem cell-treated mice compared to the control group following ischemia (p < 0.05). After transplantation, MMP-9 was decreased in protein and activity levels as compared with controls (p < 0.05). Furthermore, myeloperoxidase-positive cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p < 0.05). CONCLUSION The results showed that mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.


title: Gene signatures of SARS-CoV/SARS-CoV-2-infected ferret lungs in short- and long-term models.

text: Coronaviruses (CoVs) consist of six strains, and the severe acute respiratory syndrome coronavirus (SARS-CoV), newly found coronavirus (SARS-CoV-2) has rapidly spread leading to a global outbreak. The ferret (Mustela putorius furo) serves as a useful animal model for studying SARS-CoV/SARS-CoV-2 infection and developing therapeutic strategies. A holistic approach for distinguishing differences in gene signatures during disease progression is lacking. The present study discovered gene expression profiles of short-term (3 days) and long-term (14 days) ferret models after SARS-CoV/SARS-CoV-2 infection using a bioinformatics approach. Through Gene Ontology (GO) and MetaCore analyses, we found that the development of stemness signaling was related to short-term SARS-CoV/SARS-CoV-2 infection. In contrast, pathways involving extracellular matrix and immune responses were associated with long-term SARS-CoV/SARS-CoV-2 infection. Some highly expressed genes in both short- and long-term models played a crucial role in the progression of SARS-CoV/SARS-CoV-2 infection, including DPP4, BMP2, NFIA, AXIN2, DAAM1, ZNF608, ME1, MGLL, LGR4, ABHD6, and ACADM. Meanwhile, we revealed that metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term infection models. The present study showed alterations in gene expressions from short-term to long-term SARS-CoV/SARS-CoV-2 infection. The current result provides an explanation of the pathophysiology for post-infectious sequelae and potential targets for treatment.


title: Soft Tissue Conduction: Review, Mechanisms, and Implications.

text: Soft tissue conduction (STC) is a recently explored mode of auditory stimulation, complementing air (AC) and bone (BC) conduction stimulation. STC can be defined as the hearing induced when vibratory stimuli reach skin and soft tissue sites not directly overlying skull bone such as the head, neck, thorax, and body. Examples of STC include the delivery of vibrations to the skin of parts of the body by a clinical bone vibrator, hearing underwater sounds and free field air sounds, while AC hearing is attenuated by earplugs. The vibrations induced in the soft tissues are apparently transmitted along soft tissues, reaching, and exciting the ear. Further research is required to determine whether the mechanism of the final stage of STC hearing involves the excitation of the ear by eliciting inner ear fluid pressures that activate the hair cells directly, by the induction of skull bone vibrations, or by a combination of both mechanisms, depending on the magnitude of each mechanism.


title: [Application of convalescent plasma therapy on novel coronavirus infection].

text: Coronavirus Disease 2019(COVID-19) caused by 2019-nCoV was in an outbreak globally. A large number of severe cases lead to strong clinical pressure even treated actively. Convalescent plasma (CP) therapy refers to a therapy infusing plasma from recovered donors into other infected individuals. It has played an important role in conquering variety of epidemics over a century with some limitations. Considering the absence of specific treatments, CP has been used for treating COVID-19 and achieved some efficacies. This article provides a reference for clinical application of CP therapy in COVID-19, by discussing the history, mechanism and application of CP therapy in viral diseases such as SARS.


title: THE EFFICACY OF NALBUPHINE, MEDETOMIDINE, AND AZAPERONE IN IMMOBILIZING AMERICAN BISON (BISON BISON).

text: We evaluated a combination of nalbuphine, medetomidine, and azaperone (NalMed-A) in 12 American bison ( Bison bison ) during 13 sedation handling events. The mean (SE) dosage was 0.4 (0.02) mg/kg nalbuphine, 0.08 (0.003) mg/kg medetomidine, and 0.08 (0.003) mg/kg azaperone contained in an average delivery volume of 0.8 mL/100 kg. Two animals required a supplemental dose for safe handling (additive dose used in calculating means) and a third animal was not adequately sedated despite a supplemental dose. Bison immobilized with NalMed-A showed good sedation in 12 of 13 handling attempts. Advantages of this drug combination included a relatively low delivery volume, rapid antagonism, and minimal regulatory burden for component drugs. The most consistent disadvantage was hypoxemia, and oxygen supplementation is recommended when using this sedative combination in bison.


title: The Use of Flow Diversion for the Treatment of Intracranial Aneurysms: Expansion of Indications.

text: Flow diversion is a novel concept for treating anatomically challenging intracranial aneurysms and has gained increasing acceptance. Flow diverter stents, such as the Pipeline Embolization Device (PED) (ev3-Covidien, Irvine, CA, USA), are approved for treating unruptured large and giant aneurysms from the internal carotid artery between the superior hypophyseal and cavernous segments. However, technological advances and recent clinical results suggest that flow diversion can be safely and effectively used in treating ruptured aneurysms, posterior circulation aneurysms, and distal anterior circulation aneurysms. In this brief review, we aim to investigate the recent evidence on the utilization of PEDs in these controversial vascular territories and to discuss whether the indications for flow diversion can be expanded.


title: Role of esophageal manometry and 24-h pH testing in patients with refractory reflux symptoms.

text: BACKGROUND A proportion of patients with gastroesophageal reflux disease (GERD) do not respond to proton pump inhibitor (PPI) therapy. AIM OF THE STUDY To determine the findings on high-resolution esophageal manometry (HREM) and 24-h pH recording in patients with typical GERD symptoms, refractory to PPI treatment. METHODS Retrospective analysis of prospectively maintained database of patients referred for HREM and 24-h pH recording was done. We selected patients who were referred for evaluation of refractory GERD symptoms despite > 8 weeks of at least once-daily PPI treatment. Details noted were demographic profile, upper gastrointestinal endoscopy report, HREM findings and 24-h pH findings. RESULTS Ninety-six patients had symptoms of GERD that were refractory to PPI therapy. Seven patients (7.1%) were diagnosed having diseases mimicking GERD: eosinophilic esophagitis (n=2), supragastric belching (n=4) and rumination (n=1). After excluding these patients and those with insufficient data, the final study cohort included 82 cases. Fifty patients (61%) had normal motility. Major motility disorders were detected in 8 (9.75%) patients: achalasia cardia (6) and distal esophageal spasm (2). Ineffective esophageal motility was noted in 24 patients. A total of 74 patients underwent 24-h pH testing. Significant acid reflux with good symptom correlation was noted in 56 patients. Eighteen patients did not have significant acid reflux (Johnson-DeMeester score < 14.7): hypersensitive esophagus (12) and functional heartburn (6). CONCLUSION Fifty-six patients (68.3%) had definite diagnosis of GERD and 31.7% (26) had non-GERD conditions like motility disorders, functional heartburn and hypersensitive esophagus.


title: The Early Results of the Laparoscopic Mini-Gastric Bypass/One Anastomosis Gastric Bypass on Patients with Different Body Mass Index.

text: Introduction. Obesity is among the newest health matters that human beings are struggling with. Length of bypassed intestine is important in achievement of most weight loss and least nutritional and absorptive disorders. This study has aimed to assess short-term metabolic and nutritional effects of laparoscopic mini-gastric bypass/one anastomosis gastric bypass (MGB/OAGB) with a loop bypass length of 180 centimeters (cm) and compare these factors among patients with a body mass index (BMI) of 40-45 and 45-50 kilograms per square meter (kg/m2). Methods 25 patients were put in group 1 (BMI = 40-45 kg/m2) and 25 patients in group 2 (BMI = 45-50 kg/m2). Patients' BMI, postoperative weight, excess weight loss, and laboratory tests including fasting blood sugar (FBS), lipid profile, serum iron (Fe), ferritin, total iron-binding capacity (TIBC), 25-OH vitamin D, vitamin B12, liver function tests, and albumin were recorded preoperatively and within 3- and 6-month follow-up. Results Weight loss and BMI reduction was significantly more in patients with higher BMI level (P=0.007), and excess weight loss was higher in patients with lower preoperative BMI level (P=0.007), and excess weight loss was higher in patients with lower preoperative BMI level (P=0.007), and excess weight loss was higher in patients with lower preoperative BMI level (. Conclusion Based on this study, 180-cm intestinal bypassed length works for patients with a BMI level of 40-45 and 45-50 kg/m2, according to their significant decrease in weight, BMI, and improving glycolipid profile.


Wearable Technology and Long-term Weight Loss-Reply.


The Social, Economic and Sanitary Impact of COVID-19 Pandemic.


title: Does a more extensive mucosal excision prevent haemorrhoidal recurrence after stapled haemorrhoidopexy? Long-term outcome of a randomized controlled trial.

text: AIM The study aimed in a multicentric randomized controlled trial to define the role of a more extensive mucosal resection on recurrence of mucosal prolapse in patients with Stage III haemorrhoids undergoing stapled haemorrhoidopexy. METHOD In all, 135 patients were randomized to treatment with a PPH-01/03 (Ethicon EndoSurgery) or an EEA (Covidien) stapler. They were reviewed after a minimum follow-up of 4 years to determine the rate of recurrent mucosal prolapse and general condition (wellness evaluation score). Postoperative bowel dysfunction was assessed using the Rome III criteria. RESULTS Eighty-seven (65%) of the 135 patients (48 in the EEA stapler group and 37 in the PPH group) were available for long-term follow-up. The two groups were comparable for age, gender and duration of follow-up (mean 49.3 ± 5.4 months and 49.0 ± 5.3 months respectively). In the EEA group, 11 (23%) patients had some degree of recurrent prolapse compared with 12 (32%) in the PPH group (P = 0.409). Persistence of anal bleeding was significantly higher in the PPH group (P = 0.04) while the postoperative Haemorrhoid Symptom Score was significantly better in the EEA group (1.73 ± 1.65 vs 3.17 ± 1.94, P < 0.001). The wellness evaluation score was significantly better in the EEA group (1.2 ± 1.27 vs 0.6 ± 1.0, P = 0.028). Furthermore, 7 (15%) of the patients in the EEA group complained of some evacuation disturbance compared with 13 (36%) in the PPH group (P = 0.021). CONCLUSION The study failed to demonstrate any significant difference in the long-term recurrence rate of Stage III haemorrhoids using EEA or PPH. Nevertheless, use of the larger volume EEA provides better symptom resolution compared with PPH.


title: Mental Health Nurses locked out while Australia locks down.

text: Australia is currently in lockdown, it's State, and National borders closed, gatherings of more than two people in public are banned, and a raft of other unprecedented measures have been implemented in response to the COVID-19 pandemic. This comes on the back of apocalyptic fires, floods and cyclones. Those that have been involved in recovery efforts in any of these events will have been witness to the resilience of the Australian community. These adventitious crises tend to bring communities together. This pandemic poses quite a different existential, psychological and social threat to Australians.


title: Activity of a phenolic dibenzylsulfide against New World arenavirus infections.

text: BACKGROUND Junín virus (JUNV) and several other clade B New World arenaviruses cause human disease ranging from mild febrile illness to severe viral haemorrhagic fever. These viruses pose a significant threat to national security and safe and effective therapies are limited except in Argentina, where immune plasma is the standard of care for treating JUNV infection in cases of Argentine haemorrhagic fever. METHODS An in vitro screen of the Chemtura library identified several compounds with activity against Tacaribe virus (TCRV), a clade B arenavirus closely related to JUNV. Of these compounds, D746, a phenolic dibenzylsulfide, was further pursued for additional in vitro studies and evaluated in the AG129 mouse TCRV infection model. RESULTS D746 was found to act during an early to intermediate stage of the TCRV replication cycle and μM range activity was confirmed by virus yield reduction assays with both TCRV and JUNV. Although intraperitoneal twice daily treatment regimens were found to be highly effective when started 2 h prior to TCRV challenge in AG129 mice, post-exposure treatment initiated 3 days after infection was not efficacious. Interestingly, despite the pre-exposure treatment success, D746 did not reduce serum or tissue virus titres during the acute infection. Moreover, D746 elicited ascites fluid accumulation in mice during, as well as independent of, infection. CONCLUSIONS Our findings suggest that D746 may be altering the host response to TCRV infection in AG129 mice in a way that limits pathogenesis and thereby protects mice from otherwise lethal infection in the absence of measurable reductions in viral burden.


title: The Function of TrophomiRs and Other MicroRNAs in the Human Placenta.

text: In eutherian organisms, the placenta interfaces the fetal and maternal environments. Located at the placental villous surface, in direct contact with maternal blood, is the trophoblast layer, which mediates the crucial maternal-fetal exchange of gases, nutrients, and waste products, produces hormones that support the pregnancy, and provides immunologic defense. Discovery of microRNAs (miRNAs) and their role in development, differentiation, and homeostatic resilience has increased our understanding of genomic and epigenomic networks that regulate placental function. Moreover, unique miRNA species, which are expressed by human trophoblasts and are termed "trophomiRs," may show specialized functions during normal and pathological pregnancies. Placental miRNAs, packaged within exosomes and other vesicles or bound in protein complexes, are capable of communicating distinctive signals to maternal and/or fetal tissues. Additional research may usher in the use of circulating miRNAs as pregnancy-related disease biomarkers, providing new diagnostic and therapeutic options during pregnancy.


title: Systematic review of the effects of iodised salt and iodine supplements on prenatal and postnatal growth: study protocol.

text: INTRODUCTION Iodine is an essential micronutrient and component of the thyroid hormones. Sufficient ingestion of iodine is necessary for normal growth and development. If iodine requirements are not met, growth can be impaired. Salt iodisation and supplementation with iodine can prevent iodine deficiency disorders and stunted growth. No systematic review has yet collated the evidence linking iodine to growth. With an increased emphasis on stunting within the WHO Global Nutrition Targets for 2025, we propose a systematic review to address this question. METHODS AND ANALYSIS We will undertake a systematic review, and if appropriate, meta-analyses, evaluating the effects of iodised salt or iodine supplements on prenatal and postnatal somatic growth, until age 18. We will search a number of databases, including MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, the Cochrane Library, including the CENTRAL register of Controlled Trials and also the WHO library and ICTRP (International Clinical Trials Registry Platform), which includes the Clinicaltrials.gov repository. We will also search Wanfang Data and the China Knowledge Resource Integrated Database. Included studies must have compared exposure to iodised salt, iodine supplements or iodised oil, to placebo, non-iodised salt or no intervention. Primary outcomes will be continuous and categorical markers of prenatal and postnatal somatic growth. Secondary outcomes will cover further measures of growth, including growth rates and indirect markers of growth such as insulin-like growth factor-1 (IGF-1). ETHICS AND DISSEMINATION The systematic review will be published in a peer-reviewed journal, and will be sent directly to the WHO, United Nations Children's Fund, International Council for the Control of Iodine Deficiency Disorders and other stakeholders. The results generated from this systematic review will provide evidence to support future programme recommendations regarding iodine fortification or supplementation and child growth. TRIAL REGISTRATION NUMBER PROSPERO CRD42014012940.


title: COVID in NYC: What We Could Do Better.

text: New York City hospitals expanded resources to an unprecedented extent in response to the COVID pandemic. Thousands of beds, ICU beds, staff members, and ventilators were rapidly incorporated into hospital systems. Nonetheless, this historic public health disaster still created scarcities and the need for formal crisis standards of care. These were not available to NY clinicians because of the state's failure to implement, with or without revision, long-standing guidance documents intended for just such a pandemic. The authors argue that public health plans for disasters should be well-funded and based on available research and expertise. Communities should insist that political representatives demonstrate responsible leadership by implementing and updating as needed, crisis standards of care. Finally, surge requirements should address the needs of both those expected to survive and those who will not, by expanding palliative care and other resources for the dying.


Comments on: Tool kit for survival: How to run and manage ophthalmic practices during the difficult time of COVID-19 crisis.


title: Genomic evidence of homologous recombination in spring viremia of carp virus: a negatively single stranded RNA virus.

text: A new strain of spring viraemia of carp virus, denominated SVCV-265, was isolated from an ornamental common carp (Cyprinus carpio) in Shanghai, China, 2013. The isolate could produce obvious cytopathic effects on EPC cells, while was shown to be of low virulence for juvenile koi. Complete genome sequencing revealed the genome of the SVCV-265 strain is 11,029 nucleotides in length and phylogenetic analysis showed the isolate was clustered within Asia clade but was divergent from Chinese A1, A2 and BJ0505-2 strains. Previous report indicated that the G and P gene of SVCV shared similar topologies of evolutionary trees. In this study, phylogenetic analysis based on the P gene sequences showed the SVCV-265 was clustered into Iai subgroup and divergent from Chinese isolates A1, A2 and BJ0505-2, which were clustered into Iaii group. However, sequence alignment of the G gene showed the SVCV-265 has a close relationship with A1, A2 and BJ0505-2 isolates. Recombination analysis of all the whole sequences of SVCV available revealed isolates A2 and BJ0505-2 were likely the homologous recombination descendants of the A1 and SVCV-265. The crossover regions were located between 3845-6387nt for A2 and 3573-6444 nt for BJ0505-2, respectively. Phylogenetic analysis of the crossover region further confirmed these findings. This current study describes the molecular characterization of the new isolate SVCV-265 from China and is the first report of homologous recombination in SVCV.


title: RETROSPECTIVE ANALYSIS OF THE EPIDEMIOLOGIC LITERATURE, 1990-2015, ON WILDLIFE-ASSOCIATED DISEASES FROM THE REPUBLIC OF KOREA.

text: To assess the status of research on wildlife diseases in the Republic of Korea (ROK) and to identify trends, knowledge gaps, and directions for future research, we reviewed epidemiologic publications on wildlife-associated diseases in the ROK. We identified a relatively small but rapidly increasing body of literature. The majority of publications were focused on public or livestock health and relatively few addressed wildlife health. Most studies that focused on human and livestock health were cross-sectional whereas wildlife health studies were mostly case reports. Fifteen diseases notifiable to the World Organisation for Animal Health were identified and 21 diseases were identified as notifiable to either the Korea Ministry of Health and Welfare or the Korea Ministry of Agriculture, Food and Rural Affairs. Two diseases were reported as occurring as epidemics; highly pathogenic avian influenza (HPAI) and virulent Newcastle disease. Six diseases or disease agents were described in the literature as emerging including HPAI, rabies, Babesia microti , avian coronaviruses, scrub typhus, and severe fever thrombocytopenia syndrome virus. The diseases for which there were the largest number of publications were HPAI and rabies. The majority of wildlife-associated zoonotic disease publications focused on food-borne parasitic infections or rodent-associated diseases. Several publications focused on the potential of wildlife as reservoirs of livestock diseases; in particular, Korean water deer ( Hydropotes inermis argyropus ) and wild boar ( Sus scrofa ). In contrast, there were few publications on diseases of concern for wildlife populations or research to understand the impacts of these diseases for wildlife management. Increased focus on prospective studies would enhance understanding of disease dynamics in wildlife populations. For the high-consequence diseases that impact multiple sectors, a One Health approach, with coordination among the public health, agricultural, and environmental sectors, would be important. This type of review can provide useful information for countries or regions planning or implementing national wildlife health programs.


Adverse drug reaction and causality assessment scales.


title: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis.

text: Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.


title: The use of erythromycin and colistin-loaded cement in total knee arthroplasty does not reduce the incidence of infection: a prospective randomized study in 3000 knees.

text: BACKGROUND The use of antibiotic-loaded cement is believed to prevent infection in primary total knee arthroplasty, but there is a lack of randomized studies to support this concept. The aim of this study was to evaluate the use of an antibiotic-loaded cement to reduce the infection rate in primary total knee arthroplasty. METHODS This is a prospective randomized study with 2948 cemented total knee arthroplasties, in which bone cement without antibiotic was used in 1465 knees (the control group) and a bone cement loaded with erythromycin and colistin was used in 1483 knees (the study group). All patients received the same systemic prophylactic antibiotics. The patients were followed for a minimum of twelve months. The rate of infection was analyzed according to the criteria of the Centers for Disease Control and Prevention. RESULTS The rate of deep infection (1.4% in the control group and 1.35% in the study group; p = 0.96) and the rate of superficial infection (1.2% and 1.8%, respectively; p = 0.53) were similar in both groups. The factors related to a higher rate of deep infection in a multivariate analysis were male sex and an operating time of >125 minutes. CONCLUSIONS The use of erythromycin and colistin-loaded bone cement in total knee arthroplasty did not lead to a decrease in the rate of infection when systemic prophylactic antibiotics were used, a finding that suggests that the use of antibiotic-loaded bone cement would not be indicated in the general population. Further research is needed to assess whether its use is recommended for patients with a higher risk of infection.


Combating COVID-19: East meets West.


title: Determination of Lung Volume and Hemodynamic Changes During High-Frequency Ventilation Recruitment in Preterm Neonates With Respiratory Distress Syndrome.

text: OBJECTIVES To evaluate the changes in end-expiratory lung volume during an oxygenation-guided stepwise recruitment procedure in elective high-frequency ventilation. We hypothesized that high continuous distending pressure impedes pulmonary blood flow as evidenced by reduced lung volume measurements using respiratory inductive plethysmography. Changes in oxygenation, ventilation, and peripheral perfusion were evaluated as secondary outcomes. DESIGN A prospective, single center, observational, nonrandomized study. SETTING The study was conducted in a neonatal ICU in Italy. PATIENTS High-frequency ventilated preterm infants with respiratory distress syndrome. INTERVENTIONS During the recruitment procedure, end-expiratory lung volume measured by respiratory inductive plethysmography, oxygen saturation, perfusion index, regional cerebral and perirenal tissue oxygenation, heart rate, transcutaneous PCO2, and tidal volume were simultaneously recorded at each airway pressure step. MEASUREMENTS AND MAIN RESULTS In 12 preterm newborns (gestational age, 27.4 ± 0.2 wk; birth weight, 979 ± 198 g), high-frequency ventilation was initiated at a continuous distending pressure of 10 cm H2O and incrementally increased by 1-2 cm H2O every 2-5 minutes until FIO2 was less than or equal to 0.25. End-expiratory lung volume progressively increased during the initial recruitment, but decreased at the maximum airway pressure in nine patients, indicative of a reduction in pulmonary perfusion. At the end of recruitment, tidal volume was significantly higher (p = 0.002) and oxygenation was significantly improved (p = 0.002); however, mean perfusion index, postductal saturation, and mean renal tissue oxygenation values were significantly reduced (p < 0.05) compared with baseline. Mean cerebral tissue oxygenation and mean transcutaneous PCO2 values were reduced but failed to reach significance. CONCLUSIONS High distending lung pressures increased oxygenation but decreased peripheral perfusion with no adverse cerebral side effects. Coupled with the reduction in respiratory inductive plethysmography-derived lung volume, high continuous distending pressure had adverse cardiopulmonary effects. Incorporation of lung volume and hemodynamic and oxygenation variables may guide optimum lung volume determination during high-frequency ventilation recruitment procedure while preventing adverse effects on the pulmonary circulation.


title: [Biosimilars and the nocebo effect].

text: Biosimilars have been approved for use in Germany for many years and in the meantime also in rheumatology but only a few years ago. Biosimilars, which are biotechnologically manufactured products the same as reference biologicals, have actually now achieved a substantial proportion of the market in some regions but there are still doubters among patients and physicians who fear a loss of quality even if there is no evidence for this. A part of this problem can be explained by the nocebo effect but which furthermore also has a substantial medical importance. This effect is described and explained in this article. Psychosocial and context-related factors, such as the relationship between patient and physician, previous experience with treatment and treatment expectations can either improve or impair the efficacy of treatment interventions. These phenomena are commonly known as placebo and nocebo effects. As placebo and nocebo effects can influence the development of symptoms, the frequency of undesired events and the efficacy of treatment, it is decisive to know these effects and to develop strategies for prevention in order to optimize the treatment results. Although in recent years experimental studies have achieved substantial progress in the clarification of the psychosocial and neurobiological mechanisms of placebo effects, detailed mechanisms of nocebo effects are still widely unexplored. An improved understanding of these mechanisms promises the development of user-friendly strategies for the clinical care to improve treatment results and patient satisfaction.


title: Prevalence of dementia in elderly patients with hip fracture.

text: Hip fractures occur commonly and are a cause of disability for older adults and lead to increased dependence and requirements for social support. Dementia is one of the possible risk factors for falling and hip fracture, a potential source for complications during surgery and during the postoperative period, difficulties in rehabilitation and a risk factor for hip fracture reccurence. However, in previous studies of hip fracture patients, cognitive status has not been formally assessed during the inpatient stay and diagnosis was based only on previous history. Additionally, no previous studies have compared prevalence of dementia between elderly patients with hip fracture and patients with other surgical pathology. Our aim was to define whether dementia was more prevalent in older subjects with hip fracture than in other elderly patients undergoing surgery. In this study, we prospectively assessed all patients aged 68 and older admitted to our hospital for hip fracture surgery during a one year period and compared them with age and gender matched patients attending other surgical departments. 80 hip fracture patients and 80 controls were assessed for dementia. Dementia was common in both groups, presumably reflecting the advanced mean age of both groups and cognitive deterioration due to hospitalization-status. Dementia was significantly higher in the hip fracture group (85%) compared to the control group (61.5%; p=0.002). Dementia is very common in older patients admitted for surgery to a general hospital and extremely common in those with hip fracture. It seems that dementia is under diagnosed in elderly hospitalised patients. Our data confirm that dementia is a major risk factor for hip fracture in the elderly.


title: Surface-expressed viral proteins in feline infectious peritonitis virus-infected monocytes are internalized through a clathrin- and caveolae-independent pathway.

text: Infection with feline infectious peritonitis virus (FIPV), a feline coronavirus, frequently leads to death in spite of a strong humoral immune response. In previous work, we reported that infected monocytes, the in vivo target cells of FIPV, express viral proteins in their plasma membranes. These proteins are quickly internalized upon binding of antibodies. As the cell surface is cleared from viral proteins, internalization might offer protection against antibody-dependent cell lysis. Here, the internalization and subsequent trafficking of the antigen-antibody complexes were characterized using biochemical, cell biological and genetic approaches. Internalization occurred through a clathrin- and caveolae-independent pathway that did not require dynamin, rafts, actin or rho-GTPases. These findings indicate that the viral antigen-antibody complexes were not internalized through any of the previously described pathways. Further characterization showed that this internalization process was independent from phosphatases and tyrosine kinases but did depend on serine/threonine kinases. After internalization, the viral antigen-antibody complexes passed through the early endosomes, where they resided only briefly, and accumulated in the late endosomes. Between 30 and 60 min after antibody addition, the complexes left the late endosomes but were not degraded in the lysosomes. This study reveals what is probably a new internalization pathway into primary monocytes, confirming once more the complexity of endocytic processes.


title: Systemic Immunosuppressive Therapy for Inflammatory Skin Diseases in Children: Expert-Consensus-Based Guidance for Clinical Decision Making During the COVID-19 Pandemic.

text: BACKGROUND/OBJECTIVES The COVID-19 pandemic has raised questions about the approach to management of systemic immunosuppressive therapies for dermatologic indications in children. Given the absence of data to address concerns related to SARS-CoV-2 infection while on these agents in an evidence-based manner, a Pediatric Dermatology COVID-19 Response Task Force (PDCRTF) was assembled to offer time-sensitive guidance for clinicians. METHODS A survey was distributed to an expert panel of 37 pediatric dermatologists on the PDCRTF to assess expert opinion and current practice related to three primary domains of systemic therapy: initiation, continuation, and laboratory monitoring. RESULTS Nearly all respondents (97%) reported that the COVID-19 pandemic had impacted their decision to initiate immunosuppressive medications. The majority of pediatric dermatologists (87%) reported that they were pausing or reducing the frequency of laboratory monitoring for certain immunosuppressive medications. In asymptomatic patients, continuing therapy was the most popular choice across all medications queried. The majority agreed that patients on immunosuppressive medications who have a household exposure to COVID-19 or test positive for acute infection should temporarily discontinue systemic and biologic medications, with the exception of systemic steroids, which may require tapering. CONCLUSIONS The ultimate decision regarding initiation, continuation and laboratory monitoring of immunosuppressive therapy during the pandemic requires careful deliberation, consideration of the little evidence available, and discussion with families. Consideration of an individual's adherence to COVID-19 preventive measures, risk of exposure, and the potential severity if infected must be weighed against the dermatological disease, medication, and risks to the patient of tapering or discontinuing therapies.


title: Extraperitoneal Robot-Assisted Radical Prostatectomy: Indications, Technique and Outcomes.

text: PURPOSE OF REVIEW Extraperitoneal robot-assisted radical prostatectomy (eRARP) is an alternative to the more commonly employed transperitoneal RARP (tRARP) for treatment of clinically localized prostate cancer. The purpose of this review is to discuss indications in which eRARP would be a more favorable approach in comparison to tRARP. In addition, we will discuss the safety and technique of eRARP. RECENT FINDINGS Recently published work has highlighted the outcomes and safety of eRARP in comparison to tRARP; specifically that eRARP is not inferior to tRARP. In addition, eRARP may be preferred in certain circumstances. For example, Ludwig et al. recently discussed the concomitant repair of inguinal hernia during eRARP. Extraperitoneal RARP is a safe and effective alternative to tRARP. With previous knowledge and experience with tRARP, urologists can adapt the extraperitoneal approach without difficulty. This approach is useful for specific situations in which tRARP may be challenging.


title: SARS CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus.

text: Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to find other more specific antiviral strategies.


title: Utility of Adjunctive Digital Subtraction Venography for the Treatment of Saphenous Vein Insufficiency.

text: PURPOSE To report the use of adjunctive venography for the treatment of superficial venous reflux. METHODS Two hundred consecutive patients (mean age 60.9 years, range 33-86; 128 women) with chronic venous disease underwent saphenous or perforator vein ablation in 268 limbs (305 venous trunks) guided by adjunctive venography and fluoroscopy in addition to ultrasound between October 2010 and May 2016. Intraprocedural venograms were independently evaluated by 2 vascular specialists to identify the presence of venous anomalies and the need for fluoroscopy-guided maneuvers to successfully complete venous ablation. Intraprocedural venography results were compared with preoperative venous duplex scan reports to ascertain if the duplex study could be of value in identifying preoperatively any anatomical variants that may pose a technical challenge to the operator. RESULTS In this cohort, 542 venograms (2.0/limb) were performed with a mean duration of 4.9±9.1 minutes (range 1-48). Two thirds of patients (132, 66%) had anomalies or abnormalities within the target vein; more than a third (88, 44%) required an endovascular maneuver to successfully complete the ablation and 17% (34) of cases were impossible to complete without adjunctive fluoroscopic guidance. Per-patient comparison of intraprocedural venography with preoperative venous duplex reports identified 21 (11%) patients with abnormalities detected on ultrasound (23 anomalies) compared with 123 (64%) on venography (193 anomalies). This gave ultrasound a 17.1% sensitivity, 100% specificity and positive predictive value, and 40.7% negative predictive value. CONCLUSION Venography is a valuable addition to ultrasound to facilitate complete ablation of insufficient saphenous veins in selected patients with complex anatomy.


Bridging the distance: continuing psycho-oncological care via video-consults during the COVID-19 pandemic.


title: Inpatient outcomes after elective versus nonelective ventral hernia repair.

text: BACKGROUND Patients who present emergently with hernia-related concerns may experience increased morbidity with repair when compared with those repaired electively. We sought to characterize the outcomes of patients who undergo elective and nonelective ventral hernia (VH) repair using a large population-based data set. MATERIALS AND METHODS The Nationwide Inpatient Sample was queried for primary International Classification of Diseases, Ninth Revision codes associated with VH repair (years 2008-2011). Outcomes were inhospital mortality and the occurrence of a preidentified complication. Multivariable analysis was performed to determine the risk factors for complications and mortality after both elective and nonelective VH repair. RESULTS We identified 74,151 VH repairs performed during the study interval. Of these procedures, 67.3% were elective and 21.6% were performed laparoscopically. Nonelective repair was associated with a significantly higher rate of morbidity (22.5% versus 18.8%, P < 0.01) and mortality (1.8% versus 0.52, P < 0.01) than elective repair. Elective repairs were more likely to occur in younger patients, Caucasians, and were more likely to be performed laparoscopically. Logistic modeling revealed that female gender, Caucasian race, elective case status, and laparoscopic approach were independently associated with a lower probability of complications and mortality. Minority status and Medicaid payer status were associated with increased probability of nonelective admission. CONCLUSIONS Patients undergoing elective VH repair in the United States tend to be younger, Caucasian, and more likely to have a laparoscopic repair. Nonelective VH is associated with a substantial increase in morbidity and mortality. We recommend that patients consider elective repair of VHs because of the increased morbidity and mortality associated with nonelective repair.


title: Maternal folic acid supplementation and infant birthweight in low- and middle-income countries: A systematic review.

text: The relationship between maternal folic acid supplementation in pregnancy and infant birthweight has not been well described in low- and middle-income countries. We conducted a systematic review and meta-analysis of the current evidence of the association between folic acid supplementation in pregnancy on three primary outcomes: the incidence of low birthweight, small for gestational age, and mean birthweight. Seventeen studies were identified, which satisfied the inclusion criteria, covering a total of 275,421 women from 13 cohort studies and four randomized controlled trials. For the primary outcome of mean birthweight (n = 9), the pooled mean difference between folic acid and control groups was 0.37 kg (95% confidence interval [CI]: 0.24 to 0.50), and this effect was larger in the randomized controlled trials (0.56, 95% CI: 0.15 to 0.97, n = 3). The pooled odds ratio was 0.59 for low birthweight (95% CI: 0.47 to 0.74, n = 10) among folic acid supplementation versus control. The pooled odds ratio for the association with small for gestational age was 0.63 (95% CI: 0.39 to 1.01, n = 5). Maternal folic acid supplementation in low- and middle-income countries was associated with an increased mean birthweight of infants and decreases in the incidence of low birthweight and small for gestational age.


title: Permanent mesh results in long-term symptom improvement and patient satisfaction without increasing adverse outcomes in hiatal hernia repair.

text: BACKGROUND The purpose of this study is to evaluate symptom relief, patient satisfaction, and safety of permanent mesh following Nissen fundoplication and hiatal hernia repair. METHODS Patients who underwent Nissen fundoplication and hiatal hernia repair with permanent mesh (Crurasoft; Davol, Inc, Bard, Warwick, RI) between 2005 and 2011 were identified. A retrospective chart review was conducted. Long-term follow-up data were obtained via telephone interviews using a modified 5-point Likert scale. RESULTS Forty-one patients were identified. Twenty-six patients (63%) had complete follow-up data. Mean follow-up period was 65 months (14 to 96 months). Symptomatic improvement occurred in 23 patients (88%). Twenty-three patients (88%) reported overall satisfaction with the procedure as either excellent or good, and 23 of 26 patients (89%) would undergo surgery again. Three patients (12%) reported hernia recurrence. There were no mesh erosions. CONCLUSION The use of permanent (Crurasoft; Davol, Inc) mesh resulted in symptom improvement as well as patient satisfaction, and no mesh erosions were seen.


Immune dysregulation.


title: Hospitalizations for severe lower respiratory tract infections.

text: BACKGROUND Hospitalization for lower respiratory tract infections (LRTIs) among children have been well characterized. We characterized hospitalizations for severe LRTI among children. METHODS We analyzed claims data from commercial and Medicaid insurance enrollees (MarketScan) ages 0 to 18 years from 2007 to 2011. LRTI hospitalizations were identified by the first 2 listed International Classification of Diseases, Ninth Revision discharge codes; those with ICU admission and/or receiving mechanical ventilation were defined as severe LRTI. Underlying conditions were determined from out- and inpatient discharge codes in the preceding year. We report insurance specific and combined rates that used both commercial and Medicaid rates and adjusted for age and insurance status. RESULTS During 2007-2011, we identified 16797 and 12053 severe LRTI hospitalizations among commercial and Medicaid enrollees, respectively. The rates of severe LRTI hospitalizations per 100000 person-years were highest in children aged <1 year (commercial: 244; Medicaid: 372, respectively), and decreased with age. Among commercial enrollees, ≥ 1 condition increased the risk for severe LRTI (1 condition: adjusted relative risk, 2.68; 95% confidence interval, 2.58-2.78; 3 conditions: adjusted relative risk, 4.85; 95% confidence interval, 4.65-5.07) compared with children with no medical conditions. Using commercial/Medicaid combined rates, an estimated 31289 hospitalizations for severe LRTI occurred each year in children in the United States. CONCLUSIONS Among children, the burden of hospitalization for severe LRTI is greatest among children aged <1 year. Children with underlying medical conditions are at greatest risk for severe LRTI hospitalization.


title: Efficacy and Safety of Radiofrequency Ablation for Benign Thyroid Nodules: A Prospective Multicenter Study.

text: Objective To assess the efficacy and safety of thyroid radiofrequency (RF) ablation for benign thyroid nodules by trained radiologists according to a unified protocol in a multi-center study. Materials and Methods From 2010 to 2011, 345 nodules from 345 patients (M:F = 43:302; mean age ± SD = 46.0 ± 12.7 years, range = 15-79) who met eligibility criteria were enrolled from five institutions. At pre-ablation, the mean volume was 14.2 ± 13.2 mL (1.1-80.8 mL). For 12 months or longer after treatment, 276 lesions, consisting of 248 solid and 28 predominantly cystic nodules, were followed. All operators performed RF ablation with a cool-tip RF system and two standard techniques (a transisthmic approach and the moving-shot technique). Volume reduction at 12 months after RF ablation (the primary outcome), therapeutic success, improvement of symptoms as well as of cosmetic problems, and complications were evaluated. Multiple linear regression analysis was applied to identify factors that were independently predictive of volume reduction. Results The mean volume reduction at 12 months was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n = 198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed significant improvements (p < 0.001). The rate of major complications was 1.0% (3/276). Solidity and applied energy were independent factors that predicted volume reduction. Conclusion Radiofrequency ablation performed by trained radiologists from multiple institutions using a unified protocol and similar devices was effective and safe for treating benign thyroid nodules.


title: Paediatric musculoskeletal interventional radiology.

text: Interventional radiology technique is now well established and widely used in the adult population. Through minimally invasive procedures, it increasingly replaces surgical interventions that involve higher percentages of invasiveness and, consequently, of morbidity and mortality. For these advantageous reasons, interventional radiology in recent years has spread to the paediatric age as well. The aim of this study was to review the literature on the development, use and perspectives of these procedures in the paediatric musculoskeletal field. Several topics are covered: osteomuscle neoplastic malignant and benign pathologies treated with invasive diagnostic and/or therapeutic procedures such as radiofrequency ablation in the osteoid osteoma; invasive and non-invasive procedures in vascular malformations; treatment of aneurysmal bone cysts; and role of interventional radiology in paediatric inflammatory and rheumatic inflammations. The positive results that have been generated with interventional radiology procedures in the paediatric field highly encourage both the development of new ad hoc materials, obviously adapted to young patients, as well as the improvement of such techniques, in consideration of the fact that childrens' pathologies do not always correspond to those of adults. In conclusion, as these interventional procedures have proven to be less invasive, with lower morbidity and mortality rates as well, they are becoming a viable and valid alternative to surgery in the paediatric population.


title: Stroke lesion volumes and outcome are not different in hemispheric stroke side treated with intravenous thrombolysis based on magnetic resonance imaging criteria.

text: BACKGROUND AND PURPOSE Patients with right hemispheric stroke (RHS) have been reported to have fewer good outcomes after thrombolysis. We aimed at evaluating outcome after stroke thrombolysis with regards to the affected hemisphere controlling for stroke lesion volume as a potential confounder. METHODS We retrospectively analyzed data from a prospective study of patients with acute stroke treated with intravenous tissue-type plasminogen activator, based on magnetic resonance imaging criteria within 6 hours of symptom onset. Neurological deficit was assessed by the National Institutes of Health Stroke Scale. Lesion volume on acute perfusion imaging, diffusion-weighted imaging (DWI) and perfusion imaging/DWI mismatch were measured. Clinical outcome was assessed after 90 days using the modified Rankin Scale, and relation to affected hemisphere was studied by multivariate analysis. RESULTS Of 173 patients, 55 (32%) presented with RHS, whereas 118 (68%) had left HS. Baseline National Institutes of Health Stroke Scale was lower in RHS (11.7 versus 13.6; P=0.031). There were no differences in DWI lesion volume (11.0 versus 17.8 mL; P=0.519), perfusion imaging lesion volume (98.9 versus 118.3 mL; P=0.395), perfusion imaging/DWI mismatch (60 versus 85.05 mL; P=0.283). Clinical outcome was also comparable for both groups (modified Rankin Scale, 0-1; P=0.327). In multivariate analysis, DWI lesion volume (P<0.001) and age were associated with modified Rankin Scale at day 90, whereas affected hemisphere was not. CONCLUSIONS We did not find differences between RHS and left HS with regards to stroke lesions volumes or outcome after thrombolysis. Previously reported hemisphere-related differences in stroke outcome may partly results from imbalances in stroke lesion volume between RHS and left HS.


title: Amputation-Free Survival after Crural Percutaneous Transluminal Angioplasty for Critical Limb Ischemia.

text: BACKGROUND AND AIM To evaluate the amputation-free survival after below the knee percutaneous transluminal angioplasty in a consecutive group of patients with critical ischemia of the lower extremity. MATERIALS AND METHODS A total of 70 consecutive patients with critical ischemia were treated with below the knee percutaneous transluminal angioplasty at the vascular center at Rigshospitalet with the purpose of limb salvage. All patients were deemed unfit for major surgery due to anatomical limitations or severe co-morbidity, and no prior attempts of revascularization were performed. Follow-up clinical examinations were performed within 6 weeks and after 1 year. All medical records were crosschecked with the national vascular registry ensuring a valid 1-year status in 97% of the patients. RESULTS A total of 15 major amputations were performed during follow-up, with 11 amputations performed within the first year. Complications after percutaneous transluminal angioplasty were rare. Cumulative mortality after 1 and 2 years was 22% and 34%, respectively. Amputation-free survival at 1 and 2 years of follow-up was 68% and 58%, respectively. There were no association between known risk factors such as diabetes, ischemic ulcers, cardiac disease, history of smoking, major amputation, or overall amputation. CONCLUSION Below the knee percutaneous transluminal angioplasty in patients with end-stage peripheral arterial disease and critical limb ischemia is a safe procedure in relieving critical ischemia, reducing the short-term rate of a major amputation as opposed to best medical treatment alone.


title: Antiviral applications of Toll-like receptor agonists.

text: In the past, antiviral research has focused mainly on viral targets. As the search for effective and differentiated antiviral therapies continues, cellular targets are becoming more common, bringing with them a variety of challenges and concerns. Toll-like receptors (TLRs) provide a unique mechanism to induce an antiviral state in the host. In this review we introduce TLRs as targets for the pharmaceutical industry, including how they signal and thereby induce an antiviral state through the production of type I interferons. We examine how TLRs are being therapeutically targeted and discuss several clinically precedented agents for which efficacy and safety data are available. We describe some of the chemistries that have been applied to both small molecule and large molecule leads to tune agonist potency, and offer a differentiated safety profile through targeting certain compartments such as the gut or the lung, thereby limiting systemic drug exposure and affecting systemic cytokine levels. The application of low-dose agonists of TLRs as vaccine adjuvants or immunoprotective agents is also presented. Some of the challenges presented by this approach are then discussed, including viral evasion strategies and mechanism-linked inflammatory cytokine induction.


Diabetes and the COVID-19 Pandemic: How Insights from Recent Experience Might Guide Future Management.