title: A Comparison of Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Fine-Needle Biopsy in the Diagnosis of Solid Pancreatic Lesions.

text: Background and Aims Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) is the method of choice for sampling pancreatic lesions. This study compares the diagnostic accuracy and safety of FNB using a novel core needle to FNA in solid pancreatic lesions. Methods A retrospective review of patients in whom EUS FNA or FNB was performed for solid pancreatic lesions was conducted. Diagnostic performance was calculated based upon a dual classification system: classification 1, only malignant pathology considered a true positive, versus classification 2, atypical, suspicious, and malignant pathology considered a true positive. Results 43 patients underwent FNB compared with 51 FNA. Using classification 1, sensitivity was 74.0% versus 80.0%, specificity 100% versus 100%, and diagnostic accuracy 77.0% versus 80.0% for FNB versus FNA, respectively (all p > 0.05). Using classification 2, sensitivity was 97% versus 94.0%, specificity 100% versus 100%, and diagnostic accuracy 98.0% versus 94.0% for FNB versus FNA, respectively (all p > 0.05). FNB required significantly fewer needle passes (median = 2) compared to FNA (median = 3; p < 0.001). Adverse events occurred in two (4.5%) FNB patients compared with none in the FNA group (p > 0.05). Conclusion FNA and FNB have comparable sensitivity and diagnostic accuracy. FNB required fewer passes.


title: Duration of rhinovirus shedding in the upper respiratory tract in the first year of life.

text: BACKGROUND Current molecular diagnostic methods have detected rhinovirus RNA in a high proportion of asymptomatic infants and children, raising the question of the clinical significance of these findings. This study investigates the prevalence of prolonged rhinovirus RNA presence in the upper respiratory tract of infants during the first year of life. METHODS In a longitudinal study, infants were followed from birth up to 12 months. Nasopharyngeal specimens were collected monthly (months 1-6 and month 9) and during an upper respiratory infection. Rhinoviruses were detected by quantitative reverse-transcription polymerase chain reaction. Presence of repeated rhinovirus RNA was evaluated by nucleotide sequence analysis. RESULTS A total of 2153 specimens from 362 infants were studied; 341 distinct rhinovirus infections in 216 infants were identified. Follow-up specimens were available within 30 days for 179 infections, creating the sample set to assess prolonged rhinovirus presence. Of the 179 infections, 46 involved the detection of the same rhinovirus strain in repeated specimens, including 8 events of prolonged presence of the same strain (detected in specimens collected >30 days apart), representing 4.5% of the evaluable rhinovirus infections. There were 26 events in which a rhinovirus strain was replaced by a different strain within a 30-day interval, representing 14.5% of the 179 infections. CONCLUSIONS Although rhinovirus infections are common in healthy infants, prolonged presence of rhinovirus RNA in the respiratory tract after an upper respiratory infection was uncommon (<5%). Detection of rhinovirus RNA in an infant most likely represents an infection within a 30-day period.


title: Robot-assisted simple prostatectomy for treatment of lower urinary tract symptoms secondary to benign prostatic enlargement: surgical technique and outcomes in a high-volume robotic centre.

text: BACKGROUND Robot-assisted simple prostatectomy (RASP) is a minimally invasive procedure for treatment of patients with lower urinary tract symptoms (LUTS) due to large benign prostatic enlargement (BPE). OBJECTIVE To present the perioperative and short-term functional outcomes of RASP in a large series of patients with LUTS due to BPE treated in a high-volume referral center. DESIGN, SETTING, AND PARTICIPANTS We retrospectively collected data for 67 consecutive patients who underwent RASP from October 2008 to August 2014. SURGICAL PROCEDURE RASP was performed using a Da Vinci S or Si system with a transvesical approach. MEASUREMENTS Complications were graded according to the Clavien-Dindo system. Continuous variables are reported as median and interquartile range (IQR). Comparison of preoperative and postoperative outcomes was assessed by Wilcoxon test. A two-sided value of p<0.05 was considered statistically significant. RESULTS AND LIMITATIONS The median preoperative prostate volume was 129ml (IQR 104-180). For the 45 patients who did not have an indwelling catheter, the median preoperative International Prostate Symptom Score (IPSS) was 25 (20.5-28), the median maximum flow rate (Qmax) was 7ml/s (IQR 5-11), and the median post-void residual volume (PVRV) was 73ml (IQR 40-116). The median operative time was 97min (IQR 80-127) and the median estimated blood loss was 200ml (IQR 115-360). The postoperative complication rate was 30%, including three cases (4.5%) with grade 3b complications (major bleeding requiring cystoscopy and coagulation). The median catheterization time was 3 d (IQR 2-4) and the median length of stay was 4 d (IQR 3-5). The median follow-up was 6 mo (IQR 2-12). At follow-up, the median IPSS was 3 (IQR 0-8), the median Qmax was 23ml/s (IQR 16-35), and the median PVRV was 0ml (IQR 0-36) (all p<0.001 vs baseline values). The retrospective design is the major study limitation. CONCLUSIONS Our data indicate good perioperative outcomes, an acceptable risk profile, and excellent improvements in patient symptoms and flow scores at short-term follow-up following RASP. PATIENT SUMMARY We analyzed the perioperative and functional outcomes of robot-assisted simple prostatectomy in the treatment of male patients with lower urinary tract symptoms due to large prostatic adenoma. The procedure was associated with a relatively low risk of complications and excellent functional outcomes, including considerable improvements in symptoms and flow performance. We can conclude that the procedure is a valuable option in the treatment of such patients. However, comparative studies evaluating the efficacy of the procedure in comparison with endoscopic treatment of large prostatic adenomas are needed.


Developing an Algorithm to Guide Resumption of Operative Activity in the COVID-19 Pandemic and Beyond.


title: Safety of intracorporeal circular stapling esophagojejunostomy using trans-orally inserted anvil (OrVil) following laparoscopic total or proximal gastrectomy - comparison with extracorporeal anastomosis.

text: BACKGROUND There have been several attempts to develop a unique and easier way to perform esophagojejunostomy during laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy. The OrVil system (Covidien, Mansfield, MA, USA) is one of those methods, but its technical and oncologic feasibility have not been proven and need to be observed. METHODS Among 87 patients who underwent laparoscopy-assisted total gastrectomy (LATG; 79 cases) and laparoscopy-assisted proximal gastrectomy with double tract anastomosis (LAPG_DT; 8 cases) from April 2004, 47 patients underwent the conventional extracorporeal method (Group I; 2004-2008) were compared with 40 patients treated with the intracorporeal OrVil system (Group II; 2009-2012). RESULTS There was no significant difference in clinicopathologic characteristics between the two groups except tumor location; more cardia lesions were involved in group II (p = 0.012). The mean time for esophagojejunostomy (E-J), defined as the time from anvil insertion to closure of the jejunal entry site has no significant difference (Group I vs II: 22.2 ± 3.2 min vs 18.6 ± 3.5 min, p = 0.623). In terms of anastomotic complication, there was no significant difference in E-J leakage and stricture. E-J leakage occurred in 2 out of 47 (4.3%) cases in group I and 2 out of 40 (5%) in group II (p = 0.628); half of them were treated conservatively in each group and the others underwent reoperation. E-J stricture occurred in 2 (4.3%) cases in group I and 1 (2.5%) in group II (p = 0.561), which required postoperative gastrofiberscopic balloon dilatation. CONCLUSIONS Esophagojejunostomy using the OrVil system was a feasible and safe technique compared with the conventional extracorporeal method through mini-laparotomy in terms of anastomotic complications. Moreover, it can help to reduce surgeon's stress regarding esophagojejunostomy because it needs no purse-string procedure and serves a secure operation view laparoscopically.


Large Pantaloon Hernia in a Five-months-old Infant.


title: Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue.

text: Although povidone-iodine (PVP-I) has been used as a gargle since 1956, its effectiveness and material safety have been remained controversial. The aim of this study was to investigate the toxicity of PVP-I to epithelial cells in a concentration range significantly lower than that used clinically. Study design was in vitro laboratory investigations and in vivo histological and immunologic analysis. We examined the effects of PVP-I at concentrations of 1 × 10(-2) to 1 × 10(3) μM and 1 × 10(-4) to 1 × 10 μM on HeLa cells as a model of epithelial cells and rat oral mucosa, respectively, after 1 or 2 days of exposure. Annexin V/FLUOS was used to distinguish live, apoptotic and necrotic cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was also used to observe whether apoptotic epithelial cells exist in rat oral mucosa after 1 day of exposure of PVP-I. HeLa cells developed concentration-dependent cytotoxicity, and epithelium of rat oral mucosa was thinned in a concentration-dependent manner. HeLa cell apoptosis increased after 1 × 10(0) μM of PVP-I exposure for 2 days. In the TUNEL method, many apoptotic epithelial cells were observed in the rat oral mucosa after 1 day of exposure to diluted 1 × 10(-2) μM of PVP-I, but minimal apoptotic epithelial cells were observed using 1 × 10(-3) μM of PVP-I. Our findings suggest that exposure to PVP-I, of which concentrations are even lower than those used clinically, causes toxicity in epithelial cells. This knowledge would help us better understand the risk of the use of PVP-I against mucosa.


title: Thymosin α1 modifies podosome architecture and promptly stimulates the expression of podosomal markers in mature macrophages.

text: BACKGROUND AND AIMS The immunomodulatory activity of thymosin α1 (Tα1) on innate immunity has been extensively described, but its mechanism of action is not completely understood. We explored the possibility that Tα1-stimulation could affect the formation of podosomes, the highly dynamic, actin-rich, adhesion structures involved in macrophage adhesion/chemotaxis. METHODS The following methods were used: optical and scanning electron microscopy for analyzing morphology of human monocyte-derived macrophages (MDMs); time-lapse imaging for visualizing the time-dependent modifications induced at early times by Tα1 treatment; confocal microscopy and Western blot for analyzing localization and expression of podosome components; and Matrigel Migration Assay and zymography for testing MDM invasive ability and metalloproteinase secretion. RESULTS We obtained data to support that Tα1 could affect MDM motility, invasion and chemotaxis by promptly stimulating assembly and disassembly of podosomal structures. At very early times after its addition to cell culture medium and within 1 h of treatment, Tα1 induces modifications in MDM morphology and in podosomal components that are suggestive of increased podosome turnover. CONCLUSIONS Since impairment of podosome formation leads to reduced innate immunity and is associated with several immunodeficiency disorders, we confirm the validity of Tα1 as a potent activator of innate immunity and suggest possible new clinical application of this thymic peptide.


A response to "Major complications associated with xenograft biologic mesh implantation in abdominal wall reconstruction" (Harth KC, Rosen MJ. Surg Innov. 2009;16:324-329) and discussion of the MAUDE (manufacturer and user facility device experience) database, FDA regulation of biologic implants, an


title: Comparison of Two Specialized Histology Needles for Endoscopic Ultrasound (EUS)-Guided Liver Biopsy: A Pilot Study.

text: BACKGROUND EUS-guided liver biopsy (EUS-LB) has been shown to be a safe and effective alternative to percutaneous liver biopsy. The optimal needle device and technique for EUS-LB is still evolving. The aim of this study was to compare the efficacy of two second-generation 19G fine-needle biopsy (FNB) (Franseen- and Fork-tip) devices for EUS-LB. METHODS This is a repeated-measure crossover study with a prospectively maintained cohort of patients. We performed EUS-LB with a one-pass and single-actuation method using two 19G FNB needles in 22 consecutive patients between 10/2018 and 9/2019. Patients were randomized to left vs right liver lobes to be biopsied as well as the needle sequence. The specimens obtained were evaluated for adequacy for histologic diagnosis. The primary outcome was number of complete portal tracts (CPTs), post-fix aggregate, and longest specimen length. Secondary outcomes were prefix aggregate specimen length and the specimen adequacy judged by two expert pathologists. RESULTS A total of 44 liver biopsies were performed in 22 patients. The CPTs were higher in the Franseen-tip needle group compared to the Fork-tip needle group (14.4 vs 9.5, p = 0.043). Post-fix aggregate specimen length (44.9 mm vs 34.6 mm, p = 0.097), the post-fix longest specimen length (19.9 mm vs 13.7 mm, p = 0.175), and prefix aggregate specimen length (51.7 mm vs 45 mm, p = 0.265) were not significantly different. Both needles showed similarly high histologic adequacy (100% vs 95.5%, p = 0.312). Interestingly, the right of the liver showed higher yield of CPTs with both needles (Franseen, 16.2 vs. 12.8, p = 0.003, the Fork-tip, 12.8 vs. 7.0, p < 0.0001). CONCLUSION EUS-guided liver biopsy using the 19G Franseen-tip needle may provide more CPTs than 19G Fork-tip needle on a single-pass, single-actuation comparison.


title: Optimal radiation dosing in concurrent neoadjuvant chemoradiation for resectable esophageal cancer: a meta-analysis.

text: Background This is the first meta-analysis to study optimal radiation dose in the setting of concurrent neoadjuvant chemoradiotherapy (cnCRT) for esophageal cancer (EC). We sought to compare outcomes between high dose radiotherapy (HDRT) [>48.85 Gy biologically effective dose (BED)] group and low dose radiotherapy (LDRT) (≤48.85 Gy BED) for patients with EC receiving cnCRT. Methods Medline, Embase, and Cochrane databases were searched independently by two members of our team on August 07, 2017. Articles were screened using Covidence. Study quality was assessed via CONSORT. Eligible studies had to be randomized controlled trials (RCT) comparing cnCRT vs. surgery alone in full-text English. Those with induction or sequential chemoradiotherapy were excluded. We captured data points including radiation dose, hazard ratios (HRs) for overall survival (OS), and treatment-related mortality (TRM). We analyzed HRs for OS and risk ratio (RR) for TRM and corresponding 95% confidence interval (CI) as the summary statistic. We used both fixed- and random-effects models in the presence of heterogeneity. The primary outcome was OS; secondary endpoint was treatment related mortality (TRM). We compared outcomes by HDRT vs. LDRT. To minimize chemotherapy heterogeneity, we performed a pre-planned analysis excluding the CROSS trial. Results The eleven included studies contained a total of 1,697 patients. Eight hundred forty-eight were randomized into the cnCRT. Of these 848 patients, 287 received HDRT and 561 received LDRT. HR for OS was not statistically different between LDRT (HR 0.67; 95% CI, 0.55-0.8) and HDRT (HR 0.68; 95% CI, 0.45-0.91). Excluding the CROSS trial, there was still no difference in outcomes between LDRT and HDRT. TRM was similar between LDRT and HDRT. Conclusions With no difference in OS or TRM between LDRT and HDRT, 48.85 Gy BED cnCRT may be a sufficient radiation dose for cnCRT for patients with EC fit for surgery.


title: Gastrobronchial fistula following minimally invasive esophagectomy for esophageal cancer in a patient with myotonic dystrophy: Case report.

text: INTRODUCTION Myotonic dystrophies are inherited multisystemic diseases characterized by musculopathy, cardiac arrythmias and cognitive disorders. These patients are at increased risk for fatal post-surgical complications from pulmonary hypoventilation. We present a case with myotonic dystrophy and esophageal cancer who had a minimally invasive esophagectomy complicated with gastrobronchial fistulisation. PRESENTATION OF CASE A 44-year-old male with myotonic dystrophy type 1 and esophageal cancer had a minimally invasive esophagectomy performed instead of open surgery in order to reduce the risk for pulmonary complications. At day 15 respiratory failure occurred from a gastrobronchial fistula between the right intermediary bronchus (defect 7-8mm) and the esophagogastric anastomosis (defect 10mm). In order to minimize large leakage of air into the gastric conduit the anastomosis was stented and ventilation maintained at low airway pressures. His general condition improved and allowed extubation at day 29 and stent removal at day 35. Bronchoscopy confirmed that the fistula was healed. The patient was discharged from hospital at day 37 without further complications. DISCUSSION The fistula was probably caused by bronchial necrosis from thermal injury during close dissection using the Ligasure instrument. Fistula treatment by non-surgical intervention was considered safer than surgery which could be followed by potentially life-threatening respiratory complications. Indications for stenting of gastrobronchial fistulas will be discussed. CONCLUSIONS Minimally invasive esophagectomy was performed instead of open surgery in a myotonic dystrophy patient as these patients are particularly vulnerable to respiratory complications. Gastrobronchial fistula, a major complication, was safely treated by stenting and low airway pressure ventilation.


title: Mid-term outcomes after biologic mesh use: Does their performance meet our expectations?

text: INTRODUCTION The indications for use of biological mesh prostheses are very limited because of their high cost, but include parietal repair in a contaminated setting. Their efficacy has been questioned by several recent studies. We therefore studied the results of all of our patients who received a biological prosthesis, including hernia recurrence and infectious complications. PATIENTS AND METHODS We retrospectively reviewed the outcomes of 68 patients who underwent biological prosthesis placement from 2009 to 2015 in a single center. RESULTS The site of implantation was on the anterior abdominal wall in 49 (72%) of cases, in the pelvis in 19 (28%). The median follow-up was 19 months. In the early post-operative period, 22 (32.3%) of patients presented with wall abscess; eight (11.7%) underwent surgical revision and seven (10.2%) underwent interventional radiological drainage. In the medium term, 41/56 (73%) had a late complication; 32 (57%) of the patients developed recurrent herniation and 15 (26.7%) of them were re-operated. In addition, nine (16%) of patients developed a late surgical site infection and eight (14.2%) a chronic residual infection. In multivariate analysis, the risk factors for recurrence were parastomal hernia (P=0.007) and a history of recurrent hernia (P=0.002). CONCLUSION A majority of patients developed recurrent incisional herniation in the medium term. This puts the use of biological prostheses into question. These results need to be compared to those of semi-absorbable prostheses.


title: Operating Protocols of a Community Treatment Center for Isolation of Patients with Coronavirus Disease, South Korea.

text: Most persons with confirmed coronavirus disease (COVID-19) have no or mild symptoms. During the COVID-19 pandemic, communities need efficient methods to monitor asymptomatic patients to reduce transmission. We describe the structure and operating protocols of a community treatment center (CTC) run by Seoul National University Hospital (SNUH) in South Korea. SNUH converted an existing facility into a CTC to isolate patients who had confirmed COVID-19 but mild or no symptoms. Patients reported self-measured vital signs and symptoms twice a day by using a smartphone application. Medical staff in a remote monitoring center at SNUH reviewed patient vital signs and provided video consultation to patients twice daily. The CTC required few medical staff to perform medical tests, monitor patients, and respond to emergencies. During March 5-26, 2020, we admitted and treated 113 patients at this center. CTCs could be an alternative to hospital admission for isolating patients and preventing community transmission.


title: Treatment of TASC C and D Femoropoliteal Lesions with Paclitaxel eluting Stents: 12 month Results of the STELLA-PTX Registry.

text: OBJECTIVE The aim was to evaluate the safety and the efficacy of primary stenting with paclitaxel eluting stents for TASC C and D femoropopliteal lesions. METHODS Patients with TASC C/D de novo femoropopliteal lesions were treated by implanting paclitaxel eluting stents. Patients were included in a single center registry and prospectively followed by clinical and ultrasound evaluation. X-ray of the stented zone was systematically performed 12 months after implantation. The primary endpoint was primary sustained clinical improvement after 12 months. RESULTS A total of 45 patients (48 limbs) suffering from claudication (25 limbs) or CLI (23 limbs) were enrolled. Lesions were either TASC C (28 limbs) or TASC D (20 limbs). The mean length of the treated segment was 252 ± 90 mm. The mean number of stents was 2.9 ± 1 (2-5). Mean follow up was 12.7 months. No patient was lost to follow up. At 1 year post procedure, primary and secondary sustained clinical improvements were 56.3 ± 7.4% and 80.1 ± 5.9% respectively. Freedom from target lesion and target extremity revascularization were 63.6% and 90.1%, respectively. Primary and secondary patency rates were 52.5% and 79.6%. One year primary sustained clinical improvement rates for TASC C/D were 63.3 ± 9.2% and 45.6 ± 11.7%, respectively (p = .34). One year primary sustained clinical improvement rates for claudication/CLI patients were 68 ± 9.3% and 41.6 ± 11.1%, respectively (p = .13). The incidence of in stent re-stenosis and in stent thrombosis were 25% and 14%, respectively. The incidence of stent fracture was 12.5% on a limb basis and 9% on a per stent basis. CONCLUSIONS The paclitaxel eluting stent did not achieve its goal in terms of prevention of in stent re-stenosis for TASC C/D femoropopliteal lesions. It requires frequent re-interventions during the first year to maintain satisfactory clinical results.


title: The Potential Health Care Costs And Resource Use Associated With COVID-19 In The United States.

text: With the coronavirus disease 2019 (COVID-19) pandemic, one of the major concerns is the burden COVID-19 will impose on the United States (U.S.) health care system. We developed a Monte Carlo simulation model representing the U.S. population and what can happen to each person who gets infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We estimate resource use and direct medical costs per infection and at the national level, with various "attack rates" (infection rates) to understand the potential economic benefits of reducing the burden of the disease. A single symptomatic COVID-19 infection would cost a median of $3,045 in direct medical costs incurred only during the course of the infection. Eighty percent of the U.S. population getting infected could result in a median of 44.6 million hospitalizations, 10.7 million ICU admissions, 6.5 million ventilators used, and 249.5 million hospital bed days, costing $654.0 billion in direct costs over the course of the pandemic. If 20% were to become infected, there would be a median of 11.2 million hospitalizations, 62.3 million hospital bed days, and 1.6 million ventilators used, costing $163.4 billion. [Editor's Note: This fast-track Ahead-of-Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].


QnAs with Leslie B. Vosshall.


title: Montelukast's ability to fight COVID-19 infection.

text: Montelukast can be effective in the treatment of SARS-CoV-2 infection.


title: Resting and active motor thresholds versus stimulus-response curves to determine transcranial magnetic stimulation intensity in quadriceps femoris.

text: BACKGROUND Transcranial magnetic stimulation (TMS) is a widely-used investigative technique in motor cortical evaluation. Recently, there has been a surge in TMS studies evaluating lower-limb fatigue. TMS intensity of 120-130% resting motor threshold (RMT) and 120% active motor threshold (AMT) and TMS intensity determined using stimulus-response curves during muscular contraction have been used in these studies. With the expansion of fatigue research in locomotion, the quadriceps femoris is increasingly of interest. It is important to select a stimulus intensity appropriate to evaluate the variables, including voluntary activation, being measured in this functionally important muscle group. This study assessed whether selected quadriceps TMS stimulus intensity determined by frequently employed methods is similar between methods and muscles. METHODS Stimulus intensity in vastus lateralis, rectus femoris and vastus medialis muscles was determined by RMT, AMT (i.e. during brief voluntary contractions at 10% maximal voluntary force, MVC) and maximal motor-evoked potential (MEP) amplitude from stimulus-response curves during brief voluntary contractions at 10, 20 and 50% MVC at different stimulus intensities. RESULTS Stimulus intensity determined from a 10% MVC stimulus-response curve and at 120 and 130% RMT was higher than stimulus intensity at 120% AMT (lowest) and from a 50% MVC stimulus-response curve (p < 0.05). Stimulus intensity from a 20% MVC stimulus-response curve was similar to 120% RMT and 50% MVC stimulus-response curve. Mean stimulus intensity for stimulus-response curves at 10, 20 and 50% MVC corresponded to approximately 135, 115 and 100% RMT and 180, 155 and 130% AMT, respectively. Selected stimulus intensity was similar between muscles for all methods (p > 0.05). CONCLUSIONS Similar optimal stimulus intensity and maximal MEP amplitudes at 20 and 50% MVC and the minimal risk of residual fatigue at 20% MVC suggest that a 20% MVC stimulus-response curve is appropriate for determining TMS stimulus intensity in the quadriceps femoris. The higher selected stimulus intensities at 120-130% RMT have the potential to cause increased coactivation and discomfort and the lower stimulus intensity at 120% AMT may underestimate evoked responses. One muscle may also act as a surrogate in determining optimal quadriceps femoris stimulation intensity.


title: Molecular characterization of a respiratory syncytial virus outbreak in a hematology unit in Heidelberg, Germany.

text: In 2011 and 2012, a large outbreak of respiratory syncytial virus (RSV) infections affecting 57 laboratory-confirmed patients occurred in an adult hematology unit in Heidelberg, Germany. During the outbreak investigation, we performed molecular genotyping of RSV strains to differentiate between single versus multiple introductions of the virus into the unit. Furthermore, we assessed the time of viral shedding of consecutive samples from the patients in order to better understand the possible impact of prolonged shedding for outbreak control management. We used subtype-specific reverse transcription-PCR on nasopharyngeal and bronchoalveolar specimens for routine diagnostics and for measuring the viral shedding period. Samples of 47 RSV-infected patients involved in the outbreak were genotyped by sequence analysis and compared to samples from RSV-infected hospitalized children representing the timing of the annual RSV epidemic in the community. Molecular investigation of the virus strains from clinical samples revealed a unique cluster with identical nucleotide sequences of RSV type A (RSV A outbreak strain) for 41 patients, while 3 patients were infected with different RSV A (nonoutbreak) strains and three other patients with RSV type B. Outbreak strains were identified in samples from November 2011 until January 2012, while nonoutbreak strains were from samples coinciding with the community epidemic in February and March 2012. Median duration of viral shedding time was 24.5 days (range, 1 to 168 days) with no difference between outbreak and nonoutbreak strains (P = 0.45). Our investigation suggests a single introduction of the RSV A outbreak strain into the unit that spread among the immunocompromised patients. Prolonged viral shedding may have contributed to nosocomial transmission and should be taken into account in the infection control management of RSV outbreaks in settings with heavily immunosuppressed patients.


title: Differences in alarm events between disposable and reusable electrocardiography lead wires.

text: BACKGROUND Disposable electrocardiographic lead wires (ECG-LWs) may not be as durable as reusable ones. OBJECTIVE To examine differences in alarm events between disposable and reusable ECG-LWs. METHOD Two cardiac telemetry units were randomized to reusable ECG-LWs, and 2 units alternated between disposable and reusable ECG-LWs for 4 months. A remote monitoring team, blinded to ECG-LW type, assessed frequency and type of alarm events by using total counts and rates per 100 patient days. Event rates were compared by using generalized linear mixed-effect models for differences and noninferiority between wire types. RESULTS In 1611 patients and 9385.5 patient days of ECG monitoring, patient characteristics were similar between groups. Rates of alarms for no telemetry, leads fail, or leads off were lower in disposable ECG-LWs (adjusted relative risk [95% CI], 0.71 [0.53-0.96]; noninferiority P < .001; superiority P = .03) and monitoring (artifact) alarms were significantly noninferior (adjusted relative risk [95% CI]: 0.88, [0.62-1.24], P = .02; superiority P = .44). No between-group differences existed in false or true crisis alarms. Disposable ECG-LWs were noninferior to reusable ECG-LWs for all false-alarm events (N [rate per 100 patient days], disposable 2029 [79.1] vs reusable 6673 [97.9]; adjusted relative risk [95% CI]: 0.81 [0.63-1.06], P = .002; superiority P = .12.) CONCLUSIONS Disposable ECG-LWs with patented push-button design had superior performance in reducing alarms created by no telemetry, leads fail, or leads off and significant noninferiority in all false-alarm rates compared with reusable ECG-LWs. Fewer ECG alarms may save nurses time, decrease alarm fatigue, and improve patient safety.


title: Toileting Disability in Older People Residing in Long-term Care or Assisted Living Facilities: A Scoping Review of the Literature.

text: For purposes of this review, we defined toileting disability as a result of practices, procedures, or conditions that result in an individual requiring assistance using the bathroom. This scoping review synthesizes existing knowledge of extrinsic and/or intrinsic factors that might lead to or be associated with toileting disability and identified knowledge gaps related to toileting disability in older adults residing in long-term care or assisted living facilities. A search of 9 electronic databases and the gray literature identified 3613 articles. After exclusions and screening of the full text of 71 articles, 7 remaining eligible articles mapped research activity and identified knowledge gaps in this area. Only 1 study used toileting disability as the primary outcome; it was present in 15% of older adults without dementia living in long term-care facilities (a subgroup that comprised 34% of all residents). The other 6 articles examined factors and treatment of overall activities of daily living (ADL) performance as their primary outcome; in these, toileting disability was added to other difficulties, yielding a summary ADL outcome score. No study reported the incidence, distribution, or factors that affect toileting disability in long-term care; findings of this scoping review suggest a rich research agenda for future investigation.


title: A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis.

text: Chikungunya virus (CHIKV) is a medically important human viral pathogen that causes Chikungunya fever accompanied with debilitating and persistent joint pain. Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential mediators of CHIKV clearance. Therefore, this study aimed to generate and characterize a panel of mAbs for their neutralization efficacy against CHIKV infection in a cell-based and murine model. To evaluate their antigenicity and neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and a plaque reduction neutralization test were performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b neutralization were generated, and reverse genetics techniques were then used to create an infectious CHIKV clone with a single mutation. 3E7b was also administered to neonate mice prior or after CHIKV infection. The survival rate, CHIKV burden in tissues and histopathology of the limb muscles were evaluated. Both IgM 3E7b and 8A2c bind strongly to native CHIKV surface and potently neutralize CHIKV replication. Further analyses of 3E7b binding and neutralization of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV attachment to permissive cells, possibly by binding to the surface-accessible E2-N218 residue. Prophylactic administration of 3E7b to neonate mice markedly reduced viremia and protected against CHIKV pathogenesis in various mice tissues. Given therapeutically at 4 h post-infection, 3E7b conferred 100% survival rate and similarly reduced CHIKV load in most mice tissues except the limb muscles. Collectively, these findings highlight the usefulness of 3E7b for future prophylactic or epitope-based vaccine design.


title: Peripheral blood eosinophils and other non-invasive biomarkers can monitor treatment response in eosinophilic oesophagitis.

text: BACKGROUND Monitoring of the treatment response in eosinophilic oesophagitis (EoE) requires structured endoscopical and histological examination of the oesophagus. Less invasive methods would be highly desirable. AIM To evaluate the utility of several EoE-associated blood and serum markers in order to non-invasively monitor the response to treatment with swallowed topical corticosteroids in adult EoE patients. METHODS In a randomised, controlled double-blind trial blood samples of EoE patients (n = 69) were collected at baseline and after 14 days of treatment with budesonide (n = 51) or placebo (n = 18) respectively. Absolute blood eosinophil count (AEC) as well as serum levels of CCL-17, CCL-18, CCL-26, eosinophil-cationic-protein (ECP) and mast cell tryptase (MCT) were determined and correlated with oesophageal eosinophil density and with symptom and endoscopy scores. RESULTS Histological remission, defined as mean number of <16 eos/mm(2) hpf at end-of-treatment, was achieved in 98% of the budesonide and 0% of the placebo recipients. AEC [380.2 vs. 214.7/mm(3) (P = 0.0001)], serum-CCL-17 [294.3 vs. 257.9 pg/mL (P = 0.0019)], -CCL-26 [26.7 vs. 16.2 pg/mL (P = 0.0058)], -ECP [45.5 ± 44.7 vs. 27.5 ± 25.0 μg/L (P = 0.0016)] and -MCT [5.3 ± 2.9 vs. 4.5 ± 2.6 μg/L (P = 0.0019)] significantly decreased under budesonide but not under placebo. AEC significantly correlated with oesophageal eosinophil density before (r = 0.28, P = 0.0236) and after (r = 0.42, P = 0.0004) budesonide treatment. In ROC-AUC analyses post-treatment values of AEC were significantly associated with histological remission (ROC-AUC 0.754; 95% CI: 0.617-0.891; P = 0.0003). CONCLUSIONS The budesonide-induced treatment response in EoE is mirrored by several blood and serum markers, and the absolute blood eosinophil count is the most valuable as it shows correlation with the oesophageal eosinophil density.


title: The Relationship Between Humeral Torsion and Arm Injury in Baseball Players: A Systematic Review and Meta-analysis.

text: CONTEXT Humeral torsion (HT) has been linked to various injuries and benefits. However, the exact interplay between HT, shoulder range of motion (ROM), competition level differences, and injury risk is unclear. OBJECTIVE To determine the relationship between HT, ROM, and injury risk in baseball players. Secondarily, to determine HT based on competition level. DATA SOURCES PubMed, Embase, Web of Science, CINAHL, and Cochrane databases were searched from inception until November 4, 2018. STUDY SELECTION Inclusion criteria consisted of (1) HT measurements and (2) arm injury or shoulder ROM. STUDY DESIGN Systematic review. LEVEL OF EVIDENCE Level 3. DATA EXTRACTION Two reviewers recorded patient demographics, competition level, HT, shoulder ROM, and injury data. RESULTS A total of 32 studies were included. There was no difference between baseball players with shoulder and elbow injuries and noninjured players (side-to-side HT difference: mean difference [MD], 1.75 [95% CI, -1.83 to 2.18]; dominant arm: MD, 0.17 [95% CI, -1.83 to 2.18]). Meta-regression determined that for every 1° increase in shoulder internal rotation (IR), there was a subsequent increase of 0.65° in HT (95% CI, 0.28 to 1.02). HT did not explain external rotation (ER ROM: 0.19 [95% CI, -0.24 to 0.61]) or horizontal adduction (HA ROM: 0.18 [95% CI, -0.46 to 0.82]). There were no differences between HT at the high school, college, or professional levels. CONCLUSION No relationship was found between HT and injury risk. However, HT explained 65% of IR ROM but did not explain ER ROM or HA ROM. There were no differences in HT pertaining to competition level. The majority of IR may be nonmodifiable. Treatment to restore and maintain clinical IR may be important, especially in players with naturally greater torsion. HT adaptation may occur prior to high school, which can assist in decisions regarding adolescent baseball participation.


title: Treatment and Survival of Elderly Patients with Stage I-II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium.

text: BACKGROUND Elderly patients with pancreatic cancer are underrepresented in clinical trials, resulting in a lack of evidence. OBJECTIVE The aim of this study was to compare treatment and overall survival (OS) of patients aged ≥ 70 years with stage I-II pancreatic cancer in the EURECCA Pancreas Consortium. METHODS This was an observational cohort study of the Belgian (BE), Dutch (NL), and Norwegian (NOR) cancer registries. The primary outcome was OS, while secondary outcomes were resection, 90-day mortality after resection, and (neo)adjuvant and palliative chemotherapy. RESULTS In total, 3624 patients were included. Resection (BE: 50.2%; NL: 36.2%; NOR: 41.3%; p < 0.001), use of (neo)adjuvant chemotherapy (BE: 55.9%; NL: 41.9%; NOR: 13.8%; p < 0.001), palliative chemotherapy (BE: 39.5%; NL: 6.0%; NOR: 15.7%; p < 0.001), and 90-day mortality differed (BE: 11.7%; NL: 8.0%; NOR: 5.2%; p < 0.001). Furthermore, median OS in patients with (BE: 17.4; NL: 15.9; NOR: 25.4 months; p < 0.001) and without resection (BE: 7.0; NL: 3.9; NOR: 6.5 months; p < 0.001) also differed. CONCLUSIONS Differences were observed in treatment and OS in patients aged ≥ 70 years with stage I-II pancreatic cancer, between the population-based cancer registries. Future studies should focus on selection criteria for (non)surgical treatment in older patients so that clinicians can tailor treatment.


title: Transvenous approach for the treatment of direct carotid cavernous fistula following Pipeline embolization of cavernous carotid aneurysm: a report of two cases and review of the literature.

text: Flow diverters are increasingly used for the endovascular treatment of cerebral aneurysms. A rare complication from flow diversion is delayed aneurysm rupture, which can lead to carotid-cavernous fistula (CCF) in the setting of cavernous carotid aneurysms (CCAs). Direct CCFs pose unique management challenges, given the lack of transarterial access to the fistula. We present two cases of direct CCFs following treatment of CCAs with the Pipeline embolization device (PED). Case 1 was a middle-aged patient with a symptomatic 10 mm wide-necked left CCA. Six weeks after PED treatment the patient developed diplopia secondary to direct CCF. Case 2 was a middle-aged patient with a symptomatic 17 mm left CCA treated with PED. One-month follow-up angiography demonstrated a direct CCF. Both patients underwent successful coil embolization of the CCF through a transvenous approach. Direct CCF formation following PED deployment for CCA is a rare complication. Parent vessel sacrifice may be avoided with transvenous occlusion of the fistula.


title: The Timing of Tracheostomy and Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Analysis.

text: BACKGROUND The goal of this study was to investigate the association of tracheostomy timing with outcomes after aneurysmal subarachnoid hemorrhage (SAH) in a national population. METHODS Poor-grade aneurysmal SAH patients were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable linear regression was used to analyze predictors of tracheostomy timing and multivariable logistic regression was used to evaluate the association of timing of intervention with mortality, complications, and discharge to institutional care. Covariates included patient demographics, comorbidities, severity of subarachnoid hemorrhage (measured using the NIS-SAH severity scale), hospital characteristics, and other complications and length of stay. RESULTS The median time to tracheostomy among 1380 poor-grade SAH admissions was 11 (interquartile range: 7-15) days after intubation. The mean number of days from intubation to tracheostomy in SAH patients at the hospital (p < 0.001) was the strongest predictor of tracheostomy timing for a patient, while comorbidities and SAH severity were not significant predictors. Mortality, neurologic complications, and discharge disposition did not differ significantly by tracheostomy time. However, later tracheostomy (when evaluated continuously) was associated with greater odds of pulmonary complications (p = 0.004), venous thromboembolism (p = 0.04), and pneumonia (p = 0.02), as well as a longer hospitalization (p < 0.001). Subgroup analysis only found these associations between tracheostomy timing and medical complications in patients with moderately poor grade (NIS-SAH severity scale 7-9), while there were no significant differences by timing of intervention in very poor-grade patients (NIS-SAH severity scale > 9). CONCLUSIONS In this analysis of a large, national data set, variation in hospital practices was the strongest predictor of tracheostomy timing for an individual. In patients with moderately poor grade, later tracheostomy was independently associated with pulmonary complications, venous thromboembolism, pneumonia, and a longer hospitalization, but not with mortality, neurological complications, or discharge disposition. However, tracheostomy timing was not significantly associated with outcomes in very poor-grade patients.


title: Experimental Adaptive Evolution of Simian Immunodeficiency Virus SIVcpz to Pandemic Human Immunodeficiency Virus Type 1 by Using a Humanized Mouse Model.

text: Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, originated from simian immunodeficiency virus from chimpanzees (SIVcpz), the precursor of the human virus, approximately 100 years ago. This indicates that HIV-1 has emerged through the cross-species transmission of SIVcpz from chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into pandemic HIV-1 in humans. To address this question, we inoculated three SIVcpz strains (MB897, EK505, and MT145), four pandemic HIV-1 strains (NL4-3, NLCSFV3, JRCSF, and AD8), and two nonpandemic HIV-1 strains (YBF30 and DJO0131). Humanized mice infected with SIVcpz strain MB897, a virus phylogenetically similar to pandemic HIV-1, exhibited a peak viral load comparable to that of mice infected with pandemic HIV-1, while peak viral loads of mice infected with SIVcpz strain EK505 or MT145 as well as nonpandemic HIV-1 strains were significantly lower. These results suggest that SIVcpz strain MB897 is preadapted to humans, unlike the other SIVcpz strains. Moreover, viral RNA sequencing of MB897-infected humanized mice identified a nonsynonymous mutation in env, a G413R substitution in gp120. The infectivity of the gp120 G413R mutant of MB897 was significantly higher than that of parental MB897. Furthermore, we demonstrated that the gp120 G413R mutant of MB897 augments the capacity for viral replication in both in vitro cell cultures and humanized mice. Taken together, this is the first experimental investigation to use an animal model to demonstrate a gain-of-function evolution of SIVcpz into pandemic HIV-1.IMPORTANCE From the mid-20th century, humans have been exposed to the menace of infectious viral diseases, such as severe acute respiratory syndrome coronavirus, Ebola virus, and Zika virus. These outbreaks of emerging/reemerging viruses can be triggered by cross-species viral transmission from wild animals to humans, or zoonoses. HIV-1, the causative agent of AIDS, emerged by the cross-species transmission of SIVcpz, the HIV-1 precursor in chimpanzees, around 100 years ago. However, the process by which SIVcpz evolved to become HIV-1 in humans remains unclear. Here, by using a hematopoietic stem cell-transplanted humanized-mouse model, we experimentally recapitulate the evolutionary process of SIVcpz to become HIV-1. We provide evidence suggesting that a strain of SIVcpz, MB897, preadapted to infect humans over other SIVcpz strains. We further demonstrate a gain-of-function evolution of SIVcpz in infected humanized mice. Our study reveals that pandemic HIV-1 has emerged through at least two steps: preadaptation and subsequent gain-of-function mutations.


title: Identifying Target Risk Factors Using Population Attributable Risks of Ischemic Stroke by Age and Sex.

text: BACKGROUND AND PURPOSE Estimating age- and sex-specific population attributable risks (PARs) of major risk factors for stroke may be a useful strategy to identify risk factors for targeting preventive strategies. METHODS For this case-control matched study, consecutive patients aged 18-90 years and admitted to nine nationwide hospitals with acute ischemic stroke between December 2008 and June 2010, were enrolled as cases. Controls, individually matched by age and sex, were chosen from the 4th Korean National Health & Nutrition Examination Survey (2008-2010). Based on odds ratios and prevalence, standardized according to the age and sex structure of the Korean population, PARs of major risk factors were estimated according to age (young, ≤ 45; middle-aged, 46-65; and elderly, ≥ 66 years) and sex subgroups. RESULTS In 4,743 matched case-control sets, smoking (PAR, 45.1%) was the greatest contributing risk factor in young men, followed by hypertension (28.5%). In middle-aged men, the greatest contributing factors were smoking (37.4%), hypertension (22.7%), and diabetes (14.6%), whereas in women the greatest factors were hypertension (22.7%) and stroke history (10.6%). In the elderly, hypertension was the leading factor in men (23.7%) and women (23.4%). Other noticeable factors were stroke history (men, 19.7%; women, 17.3%) and diabetes (men, 12.5%; women, 15.1%). In young women, risk factors with a PAR greater than 10% were not found. CONCLUSIONS Smoking cessation in young people and hypertension and diabetes control in older people may be effective in reducing the burden of stroke on the population. In the elderly, secondary prevention could also be emphasized.


title: Complications following decompression of Chiari malformation Type I in children: dural graft or sealant?

text: OBJECT Posterior fossa decompression with duraplasty for Chiari malformation Type I (CM-I) is a common pediatric neurosurgery procedure. Published series report a complication rate ranging from 3% to 40% for this procedure. Historically, many dural substitutes have been used, including bovine grafts, human cadaveric pericardium, synthetic dura, and autologous pericranium. The authors hypothesized that a recently observed increase in complications was dependent on the graft used. METHODS Between January 2004 and January 2008, 114 consecutive patients ≤ 18 years old underwent primary CM-I decompression using duraplasty. Records were retrospectively reviewed for short- and intermediate-term complications and operative technique, focusing on the choice of duraplasty graft with or without application of a tissue sealant. RESULTS The average age of the patients was 8.6 years. The dural graft used was variable: 15 were treated with cadaveric pericardium, 12 with Durepair, and 87 with EnDura. Tisseel was used in 75 patients, DuraSeal in 12, and no tissue sealant was used in 27 patients. The overall complication rate was 21.1%. The most common complications included aseptic meningitis, symptomatic pseudomeningocele, or a CSF leak requiring reoperation. The overall complication rates were as follows: cadaveric pericardium 26.7%, Durepair 41.7%, and EnDura 17.2%; reoperation rates were 13%, 25%, and 8.1%, respectively. Prior to adopting a different graft product, the overall complication rate was 18.1%; following the change the rate increased to 35%. Complication rates for tissue sealants were 14.8% for no sealant, 18.7% for Tisseel, and 50% for DuraSeal. Nine patients were treated with the combination of Durepair and DuraSeal and this subgroup had a 56% complication rate. CONCLUSIONS Complication rates after CM-I decompression may be dependent on the dural graft with or without the addition of tissue sealant. The complication rate at the authors' institution approximately doubled following the adoption of a different graft product. Tissue sealants used in combination with a dural substitute to augment a duraplasty may increase the risk of aseptic meningitis and/or CSF leak. The mechanism of the apparent increased inflammation with this combination remains under investigation.


title: Interferon-stimulated genes and their role in controlling hepatitis C virus.

text: Infections with the hepatitis C virus (HCV) are a major cause of chronic liver disease. While the acute phase of infection is mostly asymptomatic, this virus has the high propensity to establish persistence and in the course of one to several decades liver disease can develop. HCV is a paradigm for the complex interplay between the interferon (IFN) system and viral countermeasures. The virus induces an IFN response within the infected cell and is rather sensitive against the antiviral state triggered by IFNs, yet in most cases HCV persists. Numerous IFN-stimulated genes (ISGs) have been reported to suppress HCV replication, but in only a few cases we begin to understand the molecular mechanisms underlying antiviral activity. It is becoming increasingly clear that blockage of viral replication is mediated by the concerted action of multiple ISGs that target different steps of the HCV replication cycle. This review briefly summarizes the activation of the IFN system by HCV and then focuses on ISGs targeting the HCV replication cycle and their possible mode of action.


title: Surgical safety and personal costs in morbidly obese, multimorbid patients diagnosed with early-stage endometrial cancer having a hysterectomy.

text: BACKGROUND Many women who develop endometrial cancer (EC) or endometrial hyperplasia with atypia are obese and therefore at high risk of surgical complications. Recently clinical trials have been initiated offering non-surgical treatment to these women, but not all may agree to participate in such trials. This paper aims to describe the patient characteristics, and surgical outcomes of women with suspected early stage endometrial cancer and body mass index (BMI) of 30 or greater, who declined enrolment in the feMMe trial, which offers non-surgical hormonal treatment, hormonal plus metformin or hormonal plus weight loss as primary treatment. METHODS Consecutive case series from a tertiary gynaecological oncology unit. Over the course of the first 2 years of the feMMe trial, 27 patients met the initial eligibility screening, but declined enrolment in the feMMe trial and opted for upfront surgery. The main surgical outcome measures were type of surgical approach, need for conversion from laparoscopic to open approach, length of stay in hospital and adverse events. RESULTS Patients' median age was 63 years (range 40 to 86); median BMI was 37.3 kg/m2 (range 30.7 to 54.7); median medical co-morbidities were six (range 3-10). Of the 26/27 surgeries planned to be undertaken laparoscopically, 2/26 patients had to be converted (7 %). Overall, the average hospital stay was 4.5 days, and 11/27 (41 %) of the patients developed one or more adverse events grade 2+ rated according to the Common Toxicity Criteria Version 3. CONCLUSIONS Adverse surgical outcomes are common in multi-morbid, obese or morbidly obese patients diagnosed with early stage EC or endometrial hyperplasia with atypia and who have a hysterectomy.


title: How dermatology will change in the POST CORONA era.

text: COVID19 has forced a sea change in the practice of dermatology across the world in 2020. Some changes enforced upon us will be long standing after the horrific pandemic and current deployment of many dermatologists to internal medicine. Whilst attention is currently focussed upon managing the pandemic and its immediate impact of COVID19 upon dermatology departments,1 it is instructive to consider the ways in which dermatology (and medicine more broadly) will change in the POST CORONA era.


title: Totally laparoscopic versus laparoscopic-assisted left colectomy for cancer: a retrospective review.

text: BACKGROUND Laparoscopic left colectomy (LLC) became the standard of care for treating distal transverse and descending colon cancer in many centers. Most centers use laparoscopic-assisted colectomy with extracorporeal anastomosis (LAC/EA). A totally laparoscopic colectomy with intracorporeal anastomosis (TLC/IA) has been proposed. The purpose of our study is to compare these two techniques. METHODS A series of 52 patients undergoing LLC for left-sided colon cancer was retrospectively evaluated. Thirty-three patients underwent TLC/IA, and 19 underwent LAC/EA. The following data were collected: gender, age, body mass index, American Society of Anesthesiologists risk class, operation duration, conversion to laparotomy, intraoperative complications, postoperative complications, postoperative course (duration of stay, time to first flatus), number of excised lymph nodes, readmission, and reoperation rates. Data were prospectively recorded in a colorectal cancer database and retrospectively analyzed. RESULTS The only demographic parameter that differed significantly between the groups was age (64.2 ± 12.4 years for the TLC/IA group, vs. 72.7 ± 2.1 years for LAC/EA, p = 0.0116). The mini-laparotomy incision was significantly shorter in the TLC/IA than in the LAC/EA group (5.8 ± 0.9 vs. 8.2 ± 0.9 cm, respectively, p < 0.00001). Hospital stay duration was shorter in the TLC/IA group (4.2 ± 1.2 vs. 6.3 ± 1.9, p = 0.0001). The average number of harvested lymph nodes did not differ significantly between the groups (12.9 ± 5.7 in TLC/IA vs. 11.2 ± 4.2 in LAC/EA, p = 0.2546). No significant differences between the groups were observed in any other perioperative or surgical outcome parameters. CONCLUSIONS TLC/IA in LLC for the treatment of left colon cancer is technically feasible and can be performed with a low complication rate, favorable cosmetics, and possibly shorter hospital stay, without significantly lengthening operative duration or compromising oncologic radicality principles. Although further prospective randomized studies are needed to determine its role and limitations, we encourage using it as an alternative to LAC/EA in LLC.


China's HIV/AIDS epidemic: continuing challenges.


title: Implementing an emotional support and mental health response plan for healthcare workers during the COVID-19 pandemic.

text: Institutions across the world are working to develop initiatives aimed at supporting the well-being of healthcare workers (HCWs) facing the psychological impacts of the novel coronavirus (COVID-19) pandemic. This Commentary identifies risks that HCWs are experiencing, reviews sources of fear and stress, and describes the implementation of a three-tiered model for the provision of emotional support and mental health services for clinical and nonclinical HCWs. The model recognizes the fluid, ever-evolving nature of the COVID-19 pandemic and includes proactive, visible, and easy-to-access supportive psychological services that expand the safety net and help address immediate and future mental health challenges of HCWs. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Quercetin reduces susceptibility to influenza infection following stressful exercise.

text: Exercise stress is associated with increased risk for upper respiratory tract infection. We have shown that exercise stress can increase susceptibility to infection. Quercetin, a flavonoid present in a wide variety of fruits and vegetables, has been reported to inhibit infectivity and replication of a broad spectrum of viruses and may offset the increase in susceptibility to infection associated with stressful exercise. This study examined the effects of quercetin feedings on susceptibility to the influenza virus A/Puerto Rico/8/34 (H1N1) following stressful exercise. Mice were randomly assigned to one of four treatment groups: exercise-placebo, exercise-quercetin, control-placebo, or control-quercetin. Exercise consisted of a run to fatigue (approximately 140 min) on a treadmill for 3 consecutive days. Quercetin (12.5 mg/kg) was administered via gavage for 7 days before viral challenge. At 30 min after the last bout of exercise or rest, mice (n=23-30) were intranasally inoculated with a standardized dose of influenza virus (0.04 hemagglutinating units). Mice were monitored daily for morbidity (time to sickness), symptom severity, and mortality (time to death) for 21 days. Exercise stress was associated with an increased susceptibility to infection [morbidity, mortality, and symptom severity on days 5-7 (P<0.05)]; quercetin offset the increase in susceptibility to infection [morbidity, mortality, and symptom severity on days 5-7 (P<0.05)] that was associated with stressful exercise. These data suggest that short-term quercetin feedings may prove to be an effective strategy to lessen the impact of stressful exercise on susceptibility to respiratory infection.


title: Efficacy of the omental roll-up technique in pancreaticojejunostomy as a strategy to prevent pancreatic fistula after pancreaticoduodenectomy.

text: BACKGROUND Most morbidity and mortality are caused by a pancreatic fistula after pancreaticoduodenectomy (PD), and its prevention is the major concern. We applied the omental roll-up technique around pancreaticojejunostomy and investigated the effectiveness of this technique to prevent a pancreatic fistula. DESIGN Retrospective study. SETTING Tertiary hepatobiliary and pancreas surgery clinic, Korea University Guro Hospital, Seoul. PATIENTS Between March 1, 2009, and March 31, 2011, 68 patients underwent PD. The patients were divided into 2 groups according to the surgical application of the omental roll-up technique around the PJ site: group 1 (those who did not undergo the omental roll-up technique) compared with group 2 (those who did undergo the omental roll-up technique). MAIN OUTCOME MEASURE The occurrence of a pancreatic fistula. RESULTS No differences were noted in the clinical characteristics, including patients' demographics and operation-related factors, between the 2 groups. A pancreatic fistula occurred in 23 of 39 patients in group 1 (59%) and in 6 of 29 patients in group 2 (20.7%). Group 2 had a significantly lower incidence of pancreatic fistula (P = .002), and these fistulas were classified as being grade A using the International Study Group on Pancreatic Fistula Definition showing a transient high amylase level in the drainage fluid without significantly affecting the patient's recovery. Drain removal was performed earlier in group 2 (P < .001). Mean postoperative hospital stay was 23.4 days in group 1 compared with 15.9 days in group 2 (P = .009). Overall mortality was 1.5%; however, no deaths were related to a pancreatic fistula. CONCLUSIONS The omental roll-up technique for the PJ site definitely reduced the occurrence of a pancreatic fistula. Therefore, the omental roll-up technique is a simple and effective strategy to prevent a pancreatic fistula.


title: Glycan array: a powerful tool for glycomics studies.

text: Glycan arrays have become a powerful tool for the high-throughput elucidation of interactions of different carbohydrate structures with a wide variety of biological targets, including antibodies, proteins, viruses and cells. This technique is especially suitable for glycomics studies, because arrays present carbohydrate ligands in a manner that mimics interactions at cell-cell interfaces. This review assesses the recent advances involving glycan arrays, including new methods for glycan-array fabrication, new platforms for novel biological information, and new perceptions of glycomics for improving the understanding of disease-related glycobiology. Furthermore, this review attempts to forecast trends in the development of glycan arrays and possible solutions for some remaining challenges to improve this new technology.


Pandemic preparedness and response--lessons from the H1N1 influenza of 2009.


China's rapid urbanization.


title: Psychosocial interventions for stroke survivors, carers and survivor-carer dyads: a systematic review and meta-analysis.

text: Objective: To evaluate the effectiveness of psychosocial interventions on depressive symptoms, anxiety symptoms, quality of life, self-efficacy, coping, carer strain and carer satisfaction among stroke survivors, carers and survivor-carer dyads. Data sources: MEDLINE, CINAHL, PsycINFO, SocINDEX, Cochrane Library, Web of Science and Scopus databases and the grey literature were searched up to September 2018. Methods: A systematic review and meta-analysis of randomized controlled trials of psychosocial interventions for stroke survivors, carers and survivor-carer dyads, compared to usual care. Outcomes measured were depressive symptoms, anxiety symptoms, quality of life, coping, self-efficacy, carer strain, and carer satisfaction. Results: Thirty-one randomized controlled trials (n = 5715) were included in the systematic review which found improvements in depressive symptoms, anxiety symptoms, quality of life and coping, though the number of trials assessing each outcome varied. A meta-analysis (11 trials; n = 1280) on depressive symptoms found that in seven trials psychosocial interventions reduced depressive symptoms in stroke survivors (SMD: -0.36, 95% CI -0.73 to 0.00; p = .05) and in six trials reduced depressive symptoms in carers (SMD: -0.20, 95% CI -.40 to 0.00; p = .05). Conclusion: Psychosocial interventions reduced depressive symptoms in stroke survivors and their carers. There was limited evidence that such interventions reduced anxiety symptoms, or improved quality of life and coping for stroke survivors and carers and no evidence that they improved self-efficacy, carer strain or carer satisfaction.


title: Diversity and clonal selection in the human T-cell repertoire.

text: T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults. Naïve repertoire richness modestly declined two- to fivefold in healthy elderly. Repertoire richness contraction with age was even less pronounced for memory CD4 and CD8 T cells. In contrast, age had a major impact on the inequality of clonal sizes, as estimated by a modified Gini-Simpson index clonality score. In particular, large naïve T-cell clones that were distinct from memory clones were found in the repertoires of elderly individuals, indicating uneven homeostatic proliferation without development of a memory cell phenotype. Our results suggest that a highly diverse repertoire is maintained despite thymic involution; however, peripheral fitness selection of T cells leads to repertoire perturbations that can influence the immune response in the elderly.


Implications of Reduced Health Care Services for Cancer Patients in India and Similar Resource-Limited Health Care Systems During COVID-19 Pandemic.


title: Improving attrition rates in Ebola virus drug discovery.

text: INTRODUCTION The Ebola 2014/2015 outbreak has had devastating effects on the people living in West Africa. The spread of the disease in endemic countries and the potential introduction of sporadic cases in other continents points out the global health threat of Ebola virus disease (EVD). Despite the urgent need for treating EVD, there are no approved treatments. Given the lack of treatments available, alternative therapeutic strategies have had to be used. AREAS COVERED This article summarizes the unregistered therapeutics that were used to treat patients during the Ebola 2014/2015 outbreak, in addition to approaches used for the selection of candidate drugs. The article also proposes potential theoretical criterion for use in virtual screening of molecular libraries for candidate Ebola drugs. EXPERT OPINION In the absence of approved therapeutics for EVD, experimental drugs have had to be used. The repurposing of approved drugs for the treatment of EVD, as an alternative therapeutic strategy, has also been suggested. Screening in vitro- and in silico-approved drugs revealed several promising candidates but further testing is required to test their efficacy. All these therapeutic approaches are, however, only short-term solutions and there is still an urgent need for the development of specific drugs for the current and future outbreaks.


Covid-19: Test and trace programmes are important but no silver bullet, say scientists.


title: Acute stroke from tumor embolus in a patient with cardiac sarcoma: Aspiration thrombectomy with Penumbra catheter.

text: The most common primary malignant cardiac tumor is the cardiac sarcoma, which is mesenchymal in origin. This case report describes a patient with hyperacute stroke caused by cardiac sarcoma who underwent rapid recanalization through mechanical aspiration thrombectomy with Penumbra catheter.


title: Antigen replacement of domains D2 and D3 in flagellin promotes mucosal IgA production and attenuates flagellin-induced inflammatory response after intranasal immunization.

text: Targeting early infection in mucosal sites is one of the primary goals for mucosal vaccines so as to prevent pathogen mucosal transmission and infection. The TLR5 agonist flagellin was deemed to be a mucosal adjuvant candidate for clinical usage. However, the high antigenicity of flagellin and the possible inflammatory injury induced by flagellin might restrict its clinical usage. Here HIV-1 p24 protein was selected as an antigen model and we replaced the main antigenicity region domains D2 and D3 of non-pathogenic E.coli-derived flagellin (KF). The derived soluble protein KFD-p24 3D was then compared with KF-p24, which fused p24 directly to the C-terminal of KF. In vitro and ex vivo experiments showed that KFD-p24 3D has lower TLR5 agonist efficacy and less immunocyte-activating efficacy. Interestingly, the production of KF- specific antibody was highly reduced, and KFD-p24 3D induced IgA-biased antibody responses in mucosal sites. Moreover, KFD-p24 3D induced far fewer systemic inflammatory responses and abrogated detectable inflammatory side effects on mice, even at the high dose. The properties of enhanced IgA generation and attenuated inflammatory responses broaden the safe-dose range of KFD-p24 3D flagellin, creating a potentially promising mucosal adjuvant.


title: Elastography Study of Hamstring Behaviors during Passive Stretching.

text: INTRODUCTION The mechanical properties of hamstring muscles are usually inferred from global passive torque/angle relationships, in combination with adjoining tissues crossing the joint investigated. Shear modulus measurement provides an estimate of changes in muscle-tendon stiffness and passive tension. This study aimed to assess the passive individual behavior of each hamstring muscle in different stretching positions using shear wave elastography. METHODS/RESULTS The muscle shear modulus of each hamstring muscle was measured during a standardized slow passive knee extension (PKE, 80% of maximal range of motion) on eighteen healthy male volunteers. Firstly, we assessed the reliability of the measurements. Results were good for semitendinosus (ST, CV: 8.9%-13.4%), semimembranosus (SM, CV: 10.3%-11.2%) and biceps femoris long-head (BF-lh, CV: 8.6%-13.3%), but not for biceps femoris short-head (BF-sh, CV: 20.3%-44.9%). Secondly, we investigated each reliable muscle in three stretch positions: 70°, 90° and 110° of hip flexion. The results showed different values of shear modulus for the same amount of perceived stretch, with the highest measurements in the high-flexed hip situation. Moreover, individual muscles displayed different values, with values increasing or BF-lh, SM and ST, respectively. The inter-subject variability was 35.3% for ST, 27.4% for SM and 30.2% for BF-lh. CONCLUSION This study showed that the hip needs to be high-flexed to efficiently tension the hamstrings, and reports a higher muscle-tendon stress tolerance at 110° of hip angle. In addition muscles have different passive behaviors, and future works will clarify if it can be linked with rate of injury.


Airport screening for Ebola: current thermal scanning procedures are unreliable.


title: Trigeminocardiac reflex caused by selective angiography of the middle meningeal artery.

text: We describe an interesting case of trigeminocardiac reflex (TCR) caused by selective angiography of the middle meningeal artery (MMA). A 28-year-old woman presented with a symptomatic meningioma. Preoperative tumour embolisation was performed. In the procedure, when selective MMA angiography was done with Omnipaque 300 mg I/mL for 3 mL by manual injection, the patient complained of flashing lights in her eye followed by vomiting and bradycardia down to 40 bpm without increased intracranial pressure signs. On selective MMA angiography, the choroidal crescent and arteries of the periorbital region were opacified by anastomosis from the MMA via the meningo-ophthalmic artery. We diagnosed that her symptoms were caused by selective MMA angiography leading to high pressure stimulation towards the ophthalmic nerve innervation around the orbit as a TCR. We suggest that the operator should be prepared to manage TCR during treatment with expected selective MMA angiography, and gentle low pressure contrast injection should be attempted.


title: HiJAKing SARS-CoV-2? The potential role of JAK inhibitors in the management of COVID-19.

text: JAK kinase inhibitors are being investigated as a way of managing cytokine storm in severe COVID-19 patients.


title: Prehospital triage for endovascular clot removal in acute stroke patients.

text: Aim To establish prehospital triage in accordance with the new guidelines for endovascular therapy, we retrospectively analyzed the monitoring data of the city-wide transportation system using the Maria Prehospital Stroke Scale (MPSS), a novel prehospital stroke scale for emergency medical technicians (EMTs) to predict the likelihood of thrombolytic therapy after transportation. Methods Kawasaki City, Japan, has six comprehensive stroke centers (CSCs) and six primary stroke centers (PSCs). In CSCs, endovascular therapy can be carried out 24 h a day, 7 days a week, but not in PSCs. There is no "drip and ship" protocol for further endovascular therapy from PSCs to CSCs. We determined the predictive value of MPSS scoring by the EMTs for the performance of endovascular therapy after transportation. Results There were 2031 patients (mean age, 71.1 ± 13.3 years) registered from April 2012 to March 2015. Multivariate logistic regression analysis indicated that the MPSS score and type of stroke center were independent predictors for performance of endovascular therapy. In particular, the odds ratio (OR) for endovascular therapy was significant for MPSS score 3 (OR, 2.914; 95% confidence interval (CI), 1.152-7.372; P = 0.024), MPSS score 4 (OR, 5.474; 95%CI, 2.300-13.029; P = 0.000), and MPSS score 5 (OR, 11.459; 95%CI, 4.334-30.296; P = 0.000) when MPSS score 1 was set as a reference. The diagnostic accuracy of the MPSS score evaluated by EMTs was 0.689 (95%CI, 0.627-0.751). Conclusions Prehospital triage using MPSS scores evaluated by EMTs can predict the likelihood of performance of endovascular therapy after transportation, and may become a tool offering a flexible solution for designing a new transportation protocol.


title: Predicting postoperative complications after bariatric surgery: the Bariatric Surgery Index for Complications, BASIC.

text: BACKGROUND Around 20% of bariatric surgery patients develop a short- or long-term complication. OBJECTIVE Aim of this study was to develop a risk model predicting complications: the Bariatric Surgery Index for Complications (BASIC). SETTING The Obesity Center Amsterdam, located in a large teaching hospital, in Amsterdam, The Netherlands. METHODS A prospective consecutive database including patients operated between November 2007 and February 2015 was used. For the BASIC, analysis according to the TRIPOD statement was performed to identify risk factors for complications. Class I included patients with zero to one risk factor, class II patients with two risk factors, and class III patients with three or more risk factors. RESULTS Of 1709 analyzed patients, mean age was 45 years (±SD 10.7), 1393 (81.5%) were female; mean body mass index was 44.5 kg/m2 (6.8). Overall, 271 (15.9%) patients developed a complication of which 197 (72.5%) occurred within 30 days. Predictors in multivariable analysis were use of anticoagulants (odd's ratio (OR) 1.5); chronic obstructive pulmonary disease (OR 2.3); dyslipidemia (OR 1.4); gender (OR 1.4); psychiatric history (OR 1.3); and revisional surgery (OR 1.5). In class I, 13.5% (181 out of 1338) experienced complications, in class II 58 (21.6%) of the 269 patients and in class III 32 (31.4%) of the 102 patients, respectively. There was a significant difference (p < 0.001) in both overall and 30 day complications. CONCLUSION The BASIC uses six preoperative variables to classify patients in a low-, intermediate-, or high-risk group for postoperative complications after bariatric surgery.


Is cardiac stress testing appropriate in asymptomatic adults at low risk?


title: [Feasibility study about the single-port in gynecologic oncology surgery].

text: OBJECTIVES To describe our single-port experience in gynecologic oncology surgery, and emphasize the feasibility to use the single-port in this surgery. PATIENTS AND METHODS It is a retrospective, feasibility study, monocentric. All patients who were operated by the single-port, between 1st January 2010 to 1st November 2011, were included. RESULTS We note that 107 patients were included. We made different interventions: uni- and bilateral salpingo-ovariectomy, hysterectomy, pelvic and para-aortic lymph node sampling or lymphadenectomy in gynecologic malignancies. The median age of the population and the body mass index were respectively 52 and 22.6 kg/m(2). In total, six interventions will be converted. The median hospital stay of patients, all procedures combined, was 2 days. We find low rate of postoperative complications. CONCLUSION Gynecological cancer surgery appears feasible for single-port. However, we need other studies to confirm a benefit of using the single-port compared to conventional laparoscopy.


title: Psychosocial considerations for mass decontamination.

text: Mass exposure to explosions, infectious agents, foodborne illnesses, chemicals or radiological materials may require mass decontamination that have critical psychosocial implications for the public and for both traditional and non-traditional responders in terms of impact and of response. Five main issues are common to mass decontamination events: (i) perception, (ii) somatisation, (iii) media role and communication, (iv) information sharing, (v) behavioural guidance and (vi) organisational issues. Empirical evidence is drawn from a number of cases, including Chernobyl; Goiania, Brazil; the sarin gas attack in Tokyo; the anthrax attacks in the USA; Three Mile Island; and by features of the 2003 severe acute respiratory syndrome pandemic. In this paper, a common platform for mass casualty management is explored and suggestions for mass interventions are proposed across the complete event timeline, from pre-event threat and warning stages through to the impact and reconstruction phases. Implication for responders, healthcare and emergency infrastructure, public behaviour, screening processes, risk communication and media management are described.


title: Extraperitoneal colostomy in laparoscopic abdominoperineal resection using a laparoscopic retractor.

text: Although extraperitoneal colostomy is often performed to prevent postoperative parastomal hernia formation following an open abdominoperineal resection of lower rectal cancer, it has not been widely employed laparoscopically because of the difficulty associated with the extraperitoneal route. This paper describes a laparoscopic extraperitoneal sigmoid colostomy using the Endo Retract™ Maxi instrument. This surgical technique is easy, and helps to prevent the development of parastomal hernias.


title: Resource husbandry in challenging times.

text: Coronavirus disease 2019 (COVID-19) pandemic has put a huge pressure on healthcare systems across the globe, more so in developing countries. Not only patients of acute febrile illness and respiratory problems but also patients with other acute and chronic diseases are facing challenges while seeking healthcare, getting laboratory investigations done and obtaining medications. Healthcare workers have their challenges including limited resources, lack of personal protective equipments, and fear of contracting COVID-19. Resource husbandry, which refers to the judicious use of available stocks, is a vital concept that needs to be promoted during such challenging times to combat the shortage of medical resources while simultaneously providing effective treatment to the patients. Some easily implementable concepts of resource husbandry can have a significant impact and result in minimising trouble for many patients during a challenging time.


title: Basigin: a multifunctional membrane protein with an emerging role in infections by malaria parasites.

text: INTRODUCTION Malaria is one of the most serious infectious diseases at the beginning of the twenty-first century. Various membrane proteins are present in Plasmodium falciparum, the principal malaria pathogen. Among them, P. falciparum reticulocyte-binding protein homolog 5 (PfRh5) is indispensable for erythrocyte invasion, and has become a promising vaccine target. Basigin (CD147, EMMPRIN) has been identified as the erythrocyte receptor of PfRh5, and shown to be essential for the invasion of multiple strains of the pathogen. AREAS COVERED Fundamental information on basigin is fully described, including structure as a member of the immunoglobulin superfamily and function based on its interactions with external molecules and with proteins within the same membrane. The involvement of basigin in many diseases such as cancer and inflammatory diseases is also described, the implication being that anti-basigin therapy might be helpful to treat certain illnesses. Finally, PfRh5 as a vaccine candidate is covered, and its interaction with basigin is evaluated. EXPERT OPINION The identification of basigin, a well-characterized membrane protein, as a receptor essential for malaria infection will contribute significantly to prevention and treatment of malaria. As an example, anti-basigin therapy can be considered an alternative approach to the treatment of drug-resistant malaria.


title: Hysterectomy via transvaginal natural orifice transluminal endoscopic surgery for nonprolapsed uteri.

text: BACKGROUND Natural orifice transluminal endoscopic surgery has shown its prospection as a minimally invasive endoscopic surgery. This study aimed to examine the safety and feasibility of transvaginal natural orifice transluminal endoscopic hysterectomy (tVNOTEH) for nonprolapsed uteri in the management of benign gynecological diseases. METHODS Records were reviewed for the 147 consecutive tVNOTEH procedures between April 2011 and October 2013. Age, body mass index, number of vaginal delivery, and specimen weight were used to select comparable patient who had undergone laparoscopically assisted vaginal hysterectomy (LAVH). RESULTS A total of 512 patients were recruited in this study (147 tVNOTEHs and 365 LAVHs, respectively). These patients were stratified into six subgroups according to the uterine weight and type of hysterectomy. There was no incidence of switching to abdominal laparatomy. Length of operation, estimated blood loss (EBL), requirement of blood transfusion, and length of postoperative stay were significantly greater in the LAVH group than in the tVNOTEH group but total hospital charges were higher in the tVNOTEH group (p < 0.001). There was no difference in overall incidence of operative complications between the two groups but more complications in LAVH for uterine weight more than 500 g (4.3 vs. 0 %, p < 0.001); this likely reflects higher hospital charges in this subgroup. Significant linear correlations of uterine weight with operating time and EBL existed in both groups. CONCLUSION tVNOTEH can be safely performed for large and nonprolapsed uterus. Besides, as uterine weight increased, the operative efficiency of tVNOTEH increases compared with LAVH.


title: Tendencias temporales de las concentraciones de citocinas Th1 y Th2 en esputo inducido de pacientes asmáticos durante infecciones víricas agudas de las vías respiratorias superiores

text: Resumen Fundamento Muchas de las exacerbaciones del asma se deben a infecciones víricas de las vías respiratorias que inducen una interacción de respuestas inmunitarias entre Th1 y Th2. Sin embargo, las tendencias temporales de estas respuestas durante estos fenómenos no se han estudiado con detalle. Objetivo Identificar los posibles mecanismos subyacentes de la relación entre las infecciones víricas respiratorias y las exacerbaciones del asma. Pacientes y métodos Seleccionamos 40 adultos, de 21–58 años de edad, en 4 grupos: A, sanos; B, sanos con infección vírica; C, con asma leve o moderada, y D, igual que C pero con infección vírica. Durante el curso de una infección vírica aguda de las vías respiratorias superiores se monitorizaron las citocinas Th1 y Th2 en muestras de esputo inducido en individuos por lo demás sanos y en pacientes asmáticos. La interleucina (IL) 4, la IL-5 y el interferón gamma (IFN-γ) se analizaron mediante un método ELISA. Se monitorizaron las puntuaciones de los síntomas de infección vírica y de gravedad del asma. Las tendencias temporales se analizaron mediante la utilización de modelos mixtos lineales. Resultados En los grupos C y D los valores de IL-4 e IL-5 fueron mayores que en los grupos A y B. En el grupo B, los valores de IFN-γ y las puntuaciones de síntomas de infección vírica fueron máximos en el día 2 y disminuyeron rápidamente en el día 7, mientras que en el grupo D los valores de IFN-γ y las puntuaciones de síntomas de infección vírica y de asma alcanzaron un máximo mucho más tarde (días 3–5) y disminuyeron lentamente. En el grupo D, los cocientes IL-4 e IL-5:IFN-γ fueron significativamente más altos que en el grupo C. Conclusiones Las exacerbaciones del asma inducidas por las infecciones pueden deberse a un deterioro de las respuestas inmunitarias antivíricas Th1. Parece identificarse un intervalo decisivo de 3–5 días para instaurar una intervención terapéutica. Abstract Fundamentals Many asthma exacerbations are caused by respiratory viral infections that induce the interplay between Th1 and Th2 immune responses. However, the time trends for Th1 and Th2 immune responses during these phenomena have not been well studied. Objective To identify possible mechanisms underlying the link between respiratory viral infections and asthma exacerbations. Patients and methods We recruited 40 adults aged 21–58 years for 4 groups. A. Healthy, B. Healthy with viral infection, C. Mild to moderate asthma and D. Same as C, but with viral infection. Th1 and Th2 cytokines in induced sputum samples during the course of acute upper respiratory viral infections in otherwise healthy and asthmatic subjects were monitored. IL-4, IL-5 and IFN-γ were assayed by ELISA. Viral infection symptoms and asthma severity scores were monitored. Time trends were analyzed using linear mixed models. Results IL-4 and IL-5 levels in groups C and D were higher than in groups A and B. IFN-γ levels and viral infection symptoms scores in group B spiked by day 2 and rapidly declined by day 7, while in group D, IFN-γ and symptoms scores for viral infection and asthma peaked much later (days 3–5) and slowly declined. The ratios of IL-4 and IL-5 to IFN-γ in group D were significantly higher than in group C. Conclusions Infection-induced asthma exacerbations may be due to impaired anti-viral Th1-immune responses. There appears to be a critical window of 3–5 days for therapeutic intervention.


The Impact of the COVID-19 pandemic on a stroke center in Latin America.


title: Outcomes of Prophylactic Pantoprazole in Adult Intensive Care Unit Patients Receiving Dialysis: Results of a Randomized Trial.

text: BACKGROUND Intensive care unit (ICU) patients with acute kidney injury requiring renal replacement therapy (RRT) are considered at high risk of gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP) is often prescribed. We aimed to assess the incidence of GI bleeding and effects of SUP in these patients. METHODS We assessed GI bleeding in ICU patients receiving RRT at baseline (and at any time in the ICU) and effects of prophylactic pantoprazole versus placebo in the international SUP in the ICU (SUP-ICU) trial. All analyses were conducted according to a published protocol and statistical analysis plan. RESULTS Data of 3,291 acutely admitted adult ICU patients with one or more risk factors for GI bleeding randomized to pantoprazole or placebo intravenously once daily during ICU stay (until ICU discharge, death, or a maximum of 90 days) were analyzed. Some 20 out of 258 (7.8%, 95% CI 4.5-11.1%) and 52 out of 568 (9.2%, 95% CI 6.8-11.6%) of the patients receiving RRT at baseline and at any time in ICU, respectively, developed clinically important GI bleeding in the ICU. We did not observe statistically significant differences in the intervention effect (pantoprazole vs. placebo) in the proportion of patients with clinically important GI bleeding, clinically important events, infectious adverse events, use of interventions to stop GI bleeding, or 90-day mortality in patients with versus without RRT at baseline. CONCLUSIONS In adult ICU patients receiving RRT at baseline, we observed high incidences of clinically important GI bleeding, but did not observe effects of pantoprazole versus placebo in this subgroup.


title: Vaccine Design: Replication-Defective Adenovirus Vectors.

text: Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies.


title: Pharmacokinetics of golimumab in moderate to severe ulcerative colitis: the GO-KINETIC study.

text: Background: Golimumab (GLM) is approved for the treatment of moderate to severe ulcerative colitis (UC). Higher serum concentrations of anti-tumor necrosis factor (TNF) agents are associated with improved clinical and endoscopic outcomes. Correlations between GLM serum concentrations and clinical and endoscopic outcomes were investigated during induction and maintenance treatment. In addition, a population pharmacokinetic model was developed to identify factors associated with the pharmacokinetics of GLM in UC. Methods: A prospective observational trial (GO-KINETIC) was conducted in patients with moderate to severe UC receiving induction and maintenance treatment with GLM. Clinical and endoscopic outcomes were evaluated, fecal GLM concentrations were measured and pharmacokinetic data were analyzed. Results: A total of 20 patients were enrolled. At week 8 (after induction treatment), 12 out of 20 patients (60%) showed an endoscopic response (≥1 point reduction in endoscopic Mayo score). Patients with endoscopic response at week 8 had numerically higher median GLM serum concentrations at week 2 compared to endoscopic non-responders: 9.1 µg/ml [5.9-12.3] vs. 7.1 µg/mL [5.2-9.0]; p = .384, respectively. At week 52, 3/20 patients (15%) achieved endoscopic remission (endoscopic Mayo score ≤1) and continued GLM treatment. Population pharmacokinetic analysis showed an inverse association between albumin concentrations and GLM clearance. GLM concentrations were undetectable in fecal samples. Conclusions: After induction therapy, 60% of the patients showed endoscopic response. During maintenance therapy, about one third of patients discontinued GLM treatment because of loss of response. These patients might benefit from dose optimization.


title: Garlic for the common cold.

text: Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four.Objectives To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.Search methods We searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966 to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August 2014).Selection criteria Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment.Data collection and analysis Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data.Main results In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria.This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily)for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. Authors' conclusions There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.


title: Non-invasive positive pressure ventilation to facilitate the post-operative respiratory outcome of spine surgery in neuromuscular children.

text: PURPOSE Scoliosis surgery may be associated with a high morbidity and even mortality in children with non-idiopathic scoliosis. The aim of the study was to report our experience with a pre-operative training to non-invasive positive pressure ventilation (NPPV) and a mechanical insufflator-exsufflator (MI-E) device to improve the post-operative respiratory outcome of children scheduled for scoliosis surgery. METHODS Consecutive patients with non-idiopathic scoliosis undergoing posterior arthrodesis were trained to NPPV and MI-E before intervention. NPPV and MI-E were performed immediately after extubation. Length of intubation and intensive care unit (ICU) stay, duration of NPPV, and respiratory complications were assessed. RESULTS Thirteen patients participated in the training (mean age 13.9 ± 2.6, mean vital capacity 52.3 ± 15.4% predicted). The patients had severe respiratory muscle weakness with a mean sniff oesophageal pressure of 35.8 ± 14.2 cmH2O (50% predicted) and a mean gastric pressure during a cough of 31.9 ± 7.8 cmH2O (30% predicted). The mean length of intubation was 19.9 ± 12.3 h with a mean length of ICU stay of 2.5 ± 2.5 days. NPPV was used during a mean of 2.7 ± 1.9 days after surgery. No respiratory complication was observed. One patient died 3 months after surgery from multi-organ failure of non-respiratory origin. CONCLUSIONS No respiratory complications were observed after scoliosis correction surgery in children with non-idiopathic scoliosis after pre-operative training and post-operative use of NPPV and MI-E, underlying the interest of this management in these high-risk patients.


title: Minimally invasive unilateral arytenoid lateralization in dogs: A cadaveric study.

text: The aim of this study was to develop a minimally invasive thyroarytenoid lateralization technique (MITAL). Eleven unilateral MITAL procedures were performed on 11 canine cadavers. Two hypodermic needles were passed through the skin into the lumen of the larynx, penetrating the thyroid and arytenoid cartilages. Suture material was passed through the needles to lateralize the arytenoid cartilage. A rigid endoscope was used to visualize needle insertion and suture material placement. A key-hole approach to the larynx was performed and the suture material was knotted on the lateral aspect of the thyroid cartilage. The change in the rima glottidis area was recorded as were the duration of the procedure and complications encountered. The landmarks for needle insertion were easily palpated, and a significant increase in the area of the rima glottidis was documented after performing unilateral MITAL. In conclusion, unilateral MITAL is a quick, minimally invasive procedure which increases the area of the rima glottidis in cadaveric dogs.


title: Ischemic conditioning of the gastric conduit prior to esophagectomy improves mucosal oxygen saturation.

text: BACKGROUND Ischemic conditioning of the gastric conduit is considered as a possible approach to improve perfusion of the gastric tube after esophagectomy. The aim of this study was to assess the impact of ischemic conditioning on gastric microcirculation in a clinical setting. METHODS Nineteen patients with an esophageal carcinoma were included. In a first laparoscopic procedure, the stomach was devascularized by complete gastric mobilization including ligation of the left gastric artery ("laparoscopic gastrolysis"). After a delay of 4 to 5 days, all patients underwent a transthoracic esophagectomy and reconstruction with the prepared gastric conduit (Ivor-Lewis). Mucosal oxygen saturation (MOS, sulfur dioxide in %) was quantitatively measured from the endoluminal side in well-defined areas of the antrum, corpus, and fundus using a tissue spectrometer located at the tip of a microprobe (LEA, Medizintechnik, Giessen, Germany). Under general anesthesia, sulfur dioxide measurement I was taken before, and measurement II after laparoscopic gastric mobilization; measurement III was done before esophagectomy and reconstruction 4 to 5 days later. RESULTS Before laparoscopic mobilization of the stomach the median MOS of the fundus was 72% (range, 49% to 86%). The MOS significantly decreased after devascularization of the stomach (median MOS, 38%; range, 9% to 86%). After 4 to 5 days, MOS almost recovered to values observed before gastric mobilization (median MOS, 62%; range, 48% to 85%). Compared with the fundus, no significant sulphur dioxide changes were detected in the corpus and antrum. CONCLUSIONS This study demonstrates that ischemic conditioning influences microcirculation of the gastric conduit and improves MOS in the anastomotic region at the time of reconstruction.