title: Effects of spinal anesthesia and sedation with dexmedetomidine or propofol on cerebral regional oxygen saturation and systemic oxygenation a period after spinal injection.

text: PURPOSE To evaluate changes in cerebral regional oxygen saturation (rSO2) after spinal anesthesia and compare the changes in rSO2 and systemic oxygenation between dexmedetomidine sedation and propofol sedation. METHODS Thirty-six patients scheduled to undergo transurethral surgery under spinal anesthesia were randomly assigned to the dexmedetomidine (n = 18) and propofol groups (n = 18). We used near-infrared spectroscopy sensors to measure rSO2, and obtained data from each side were averaged. After oxygen insufflation, baseline measurements of mean arterial blood pressure (MAP), heart rate, rSO2, pulse oximetry saturation (SpO2), bispectral index, and body temperature were made. After spinal anesthesia, we measured these parameters every 5 min. Twenty minutes after spinal injection, dexmedetomidine or propofol administration was started. We measured each parameter at 10, 25, and 40 min after the administration of dexmedetomidine or propofol. RESULTS The baseline rSO2 in the dexmedetomidine group was 71.3 ± 7.3%, and that in the propofol group was 71.8 ± 5.6%. After spinal anesthesia, rSO2 in both groups decreased significantly (dexmedetomidine group: 65.4 ± 6.9%; propofol group: 64.3 ± 7.4%). After administering sedatives, rSO2 was equivalent after spinal anesthesia. rSO2 was comparable between the two groups. MAP and SpO2 were significantly higher in the dexmedetomidine group than in the propofol group. CONCLUSION Spinal anesthesia decreased rSO2; however, the decline was not severe. Dexmedetomidine and propofol did not compromise cerebral oxygenation under spinal anesthesia. Nevertheless, MAP and SpO2 were more stable in dexmedetomidine sedation than in propofol sedation. Dexmedetomidine may be suitable for spinal anesthesia.


title: Comparison of laparoscopic, hand-assisted, and open surgical nephroureterectomy.

text: BACKGROUND AND OBJECTIVES The aim of this study was to compare oncologic outcomes after laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy for upper urinary tract urothelial cancer. METHODS Between April 1995 and August 2010, 189 patients underwent laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, or open nephroureterectomy for upper urinary tract urothelial cancer. Of these patients, 110 with no previous or concurrent bladder cancer or any metastatic disease were included in this study. Cancer-specific survival, recurrence-free survival, and intravesical recurrence-free survival rates were analyzed by the Kaplan-Meier method and compared with the log-rank test. The median follow-up period for the cohort was 70 months (range, 6-192 months). RESULTS The 3 groups were well matched for tumor stage, grade, and the presence of lymphovascular invasion and concomitant carcinoma in situ. The estimated 5-year cancer-specific survival rates were 81.1%, 65.6%, and 65.2% for laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy, respectively (P = .4179). The estimated 5-year recurrence-free survival rates were 33.8%, 10.0%, and 41.2% for laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy, respectively (P = .0245). The estimated 5-year intravesical recurrence-free survival rates were 64.8%, 10.0%, and 76.2% for laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy, respectively (P < .0001). CONCLUSION Although there was no significant difference in cancer-specific survival rate among the laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy groups, hand-assisted laparoscopic nephroureterectomy may be inferior to laparoscopic nephroureterectomy or open nephroureterectomy with regard to recurrence-free survival and intravesical recurrence-free survival rates.


title: Isolation of an NDM-5-producing ST16 Klebsiella pneumoniae from a Dutch patient without travel history abroad, August 2015.

text: A New Delhi Metallo-beta-lactamase-5 (NDM-5)-producing ST16 Klebsiella pneumoniae strain was isolated from a Dutch patient in a long-term care facility without recent travel history abroad. Core genome multilocus sequence typing (cgMLST) revealed that the Dutch isolate was clonally related to isolates detected in four patients in Denmark in 2014. Public health experts and clinicians need to be informed; repetitive screening may be needed in patients without known risk factors for carbapenemases-producing Enterobacteriaceae who have undergone antibiotic treatment.


title: Influence of needle gauge used for venipuncture on measures of hemostasis in cats.

text: OBJECTIVES The objective of this study was to evaluate the effect of different needle sizes used to obtain blood via jugular venipuncture in cats on routine measures of hemostasis. METHODS This was a prospective, observational, randomized, clinical study carried out at a university teaching hospital. Twenty healthy, client-owned cats were used. Each cat had blood collected via direct venipuncture from both jugular veins. Sampling of the right and left jugular vein was randomized to be collected with either a 22 G or a 25 G needle, respectively, and routine coagulation variables and platelet count were performed on all samples. Values were analyzed for differences in needle size, and site of sample collection. RESULTS There was no difference between the two needle gauges in activated partial thromboplastin time, platelet count, fibrinogen degradation products, or fibrinogen, or between sampling from the left and right jugular vein. Prothrombin time (PT) was significantly higher when drawn from a 25 G needle (11.7 s) compared with a 22 G needle (11.4 s) ( P = 0.01), but not different in left vs right jugular vein samples. Bland-Altman analysis of PT comparing for 25 G minus 22 G needle vs the average, calculated a mean bias (95% limits of agreement) of 0.49 s (-1.4 s to 2.4 s). CONCLUSIONS AND RELEVANCE This study of 20 healthy cats found that the use of either a 25 G or 22 G needle for jugular venipuncture did not introduce any clinically meaningful difference in routine coagulation variables or platelet count.


title: Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system.

text: Many viruses induce type I interferon responses by activating cytoplasmic RNA sensors, including the RIG-I-like receptors (RLRs). Although two members of the RLR family, RIG-I and MDA5, have been implicated in host control of virus infection, the relative role of each RLR in restricting pathogenesis in vivo remains unclear. Recent studies have demonstrated that MAVS, the adaptor central to RLR signaling, is required to trigger innate immune defenses and program adaptive immune responses, which together restrict West Nile virus (WNV) infection in vivo. In this study, we examined the specific contribution of MDA5 in controlling WNV in animals. MDA5(-/-) mice exhibited enhanced susceptibility, as characterized by reduced survival and elevated viral burden in the central nervous system (CNS) at late times after infection, even though small effects on systemic type I interferon response or viral replication were observed in peripheral tissues. Intracranial inoculation studies and infection experiments with primary neurons ex vivo revealed that an absence of MDA5 did not impact viral infection in neurons directly. Rather, subtle defects were observed in CNS-specific CD8(+) T cells in MDA5(-/-) mice. Adoptive transfer into recipient MDA5(+/+) mice established that a non-cell-autonomous deficiency of MDA5 was associated with functional defects in CD8(+) T cells, which resulted in a failure to clear WNV efficiently from CNS tissues. Our studies suggest that MDA5 in the immune priming environment shapes optimal CD8(+) T cell activation and subsequent clearance of WNV from the CNS.


title: Effect of opaque wraps for pulse oximeter sensors: randomised cross-over trial.

text: BACKGROUND Evidence is lacking as to whether ambient light or phototherapy light could interfere with pulse oximeter performance. METHODS In this randomised cross-over trial, we recruited neonates of gestation >24 weeks. Consented infants were randomly assigned to either pulse oximeter sensor with opaque wrap or without opaque wrap. Nellcor and Masimo sensors were applied simultaneously to different feet for 10 min of recording. Infants were crossed over to the other intervention for a further 10 min, totalling 20 min recording per infant. Primary outcome was faster acquisition of data with shielding of pulse oximeter sensor as compared with not shielding. RESULTS A total of 96 babies were recruited. There was no difference in primary outcome of time taken to display valid data between the two groups (opaque wrap: 12.73±3.1 s vs no opaque wrap: 13.16±3.3 s, p=0.27). There was no difference in any of the secondary outcomes (percentage of valid data points, percentage of time saturation below target, and so on) between the two groups in both pulse oximeters. Masimo sensor readings displayed a higher mean oxygen saturation (mean difference of 2.85, p=0.001) and lower percentage of time saturation below 94% (mean difference of -27.8, p=0.001) than Nellcor in both groups. There was no difference in any of the outcomes in babies receiving phototherapy (n=21). CONCLUSION In this study, shielding the pulse oximeter sensor from ambient light or phototherapy light did not yield faster data acquisition or better data quality. TRIAL REGISTRATION NUMBER ISRCTN10302534.


title: Laparoscopic Extralevator Abdominoperineal Excision of the Rectum with Primary Suturing: Short-Term Outcomes from Single-Institution Study.

text: AIMS This study evaluated the safety, feasibility, and short-term outcomes of laparoscopic extralevator abdominoperineal excision (laparoscopic-ELAPE) with primary suturing for low rectal cancer. MATERIALS AND METHODS Consecutive patients who underwent laparoscopic-ELAPE with primary suturing for low rectal cancer at our institution between September 2013 and January 2015 were retrospectively identified from a prospectively maintained database. Short-term outcomes, including intraoperative complications, postoperative morbidity, and oncologic adequacy of surgical specimens, were evaluated. RESULTS Laparoscopic-ELAPE was successful in all 33 included patients, with no patient requiring conversion to an open approach. Mean operation time was 200 minutes, and mean intraoperative blood loss was 90 mL. Except for bowel perforation in 2 patients (6.1%), there were no intraoperative complications. Two patients (6.1%) had positive circumferential resection margins. Median length of hospital stay was 7 days. The 30-day morbidity and mortality rates were 15.2% and 0%, respectively. Postoperative complications within 30 postoperative days included perineal wound infection (2 patients, 6.1%), respiratory infection (2 patients, 6.1%), and chylous fistula (1 patient, 3.0%). Complications at a median follow-up time of 12 months (range, 3-19 months) included local tumor recurrence (1 patient, 3.0%), perineal dehiscence (2 patients, 6.1%), perineal seroma (1 patient, 3.0%), bowel obstruction (1 patient, 3.0%), urinary retention (2 patients, 6.1%), and chronic perineal pain (2 patients, 6.1%). There were no instances of perineal hernia, persistent sinus, or peristomal hernia. CONCLUSIONS Laparoscopic-ELAPE with primary suturing appears to be a feasible and safe treatment approach for low rectal cancer, with acceptable short-term outcomes.


title: Receptor mimicry as novel therapeutic treatment for biothreat agents.

text: The specter of intentional release of pathogenic microbes and their toxins is a real threat. This article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. The minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the Galβ1-4GlcNAc structure. The botulinum toxin serotypes A-F bind to a low number of gangliosides (GT1b, GQ1b, GD1a and GD1b) hence it should be possible to determine the minimal structure for binding. The minimal disaccharide sequence of GalNAcβ1-4Gal found in the gangliosides asialo-GM1 and asialo-GM2 is required for adhesion for many respiratory pathogens. Although a number of adhesins have been identified in bacterial biothreat agents such as Yersinia pestis, Bacillus anthracis, Francisella tularensis, Brucella species and Burkholderia pseudomallei, specific information regarding their in vivo expression during pneumonic infection is lacking. Limited oligosaccharide inhibition studies indicate the potential of GalNAcβ1-4Gal, GalNAcβ-3Gal and the hydrophobic compound, para-nitrophenol as starting points for the rational design of generic anti-adhesion compounds. A cocktail of multivalent oligosaccharides based on the minimal binding structures of identified adhesins would offer the best candidates for anti-adhesion therapy.


title: Serum amylase and C-reactive protein in risk stratification of pancreas-specific complications after pancreaticoduodenectomy.

text: BACKGROUND Pancreas-specific complications (PSCs), comprising postoperative pancreatic fistula, haemorrhage and intra-abdominal collections, are drivers of morbidity and mortality after pancreaticoduodenectomy (PD). A serum amylase concentration of 130 units/l or more on postoperative day (POD) 0 has been shown to be an objective surrogate of pancreatic texture, a determinant of PSCs. This study evaluated serial measurements of C-reactive protein (CRP) to refine PSC risk stratification. METHODS Consecutive patients undergoing PD between 2008 and 2014, with vascular resection if required and without preoperative chemoradiotherapy, had serum investigations from the day before operation until discharge. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP with clinically relevant PSCs for up to 30 days after discharge as outcome measure. RESULTS Of 230 patients, 95 (41·3 per cent) experienced a clinically relevant PSC. A serum CRP level of 180 mg/l or higher on POD 2 was associated with PSCs, prolonged critical care stay and relaparotomy (all P < 0·050). Patients with a serum amylase concentration of 130 units/l or more on POD 0 who developed a serum CRP level of at least 180 mg/l on POD 2 had a higher incidence of morbidity. Patients were stratified into high-, intermediate- and low-risk groups using these markers. The low-risk category was associated with a negative predictive value of 86·5 per cent for development of clinically relevant PSCs. There were no deaths among 52 patients in the low-risk group, but seven deaths among 79 (9 per cent) in the high-risk group. CONCLUSION A serum amylase level below 130 units/l on POD 0 combined with a serum CRP level under 180 mg/l on POD 2 constitutes a low-risk profile following PD, and may help identify patients suitable for early discharge.


title: The management of the critically ill obstetric patient.

text: Hypertensive disorders, postpartum hemorrhage, and sepsis are the most common indications for intensive care unit admission among obstetric patients. In general, ICU mortality is low, and better than would be predicted using available mortality prediction tools. Provision of care to this special population requires an intimate understanding of physiologic changes that occur during pregnancy. Clinicians must be aware of the way various diagnostic and treatment choices can affect the mother and fetus. Most clinically necessary radiographic tests can be safely performed and fall under the maternal radiation exposure limit of less than 0.05 Gray (Gy). Careful attention must be paid to acid-base status, oxygenation, and ventilation when faced with respiratory failure necessitating intubation. Cesarean delivery can be justified after 4 minutes of cardiac arrest and may improve fetal and maternal outcomes. The treatment of obstetric patients in the ICU introduces complexities and challenges that may be unfamiliar to many critical care physicians; teamwork and communication with obstetricians is crucial.


title: Clinics in Diagnostic Imaging: COVID-19 atypical pneumonia.

text: A 53-year-old man presented with high fever and a non-productive cough but had no recent travel history. He deteriorated clinically very rapidly and was intubated. The endotracheal tube microbiological culture isolated Klebsiella pneumoniae. On chest computed tomography, the presence of mixed ground-glass airspace opacities, patchy consolidation and a ‘crazy paving’ appearance was atypical for Klebsiella infection. As there was also a lack of cavitating nodules, lymphadenopathy and pleural effusion, atypical pneumonia due to COVID-19 was diagnosed. The patient tested positive for COVID-19. He was isolated and subsequently recovered.


title: High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer.

text: BACKGROUND The progression of colorectal cancer (CRC) involves recurrent amplifications/mutations in the epidermal growth factor receptor (EGFR) and downstream signal transducers of the Ras pathway, KRAS and BRAF. Whether genetic events predicted to result in increased and constitutive signaling indeed lead to enhanced biological activity is often unclear and, due to technical challenges, unexplored. Here, we investigated proliferative signaling in CRC using a highly sensitive method for protein detection. The aim of the study was to determine whether multiple changes in proliferative signaling in CRC could be combined and exploited as a "complex biomarker" for diagnostic purposes. METHODS We used robotized capillary isoelectric focusing as well as conventional immunoblotting for the comprehensive analysis of epidermal growth factor receptor signaling pathways converging on extracellular regulated kinase 1/2 (ERK1/2), AKT, phospholipase Cγ1 (PLCγ1) and c-SRC in normal mucosa compared with CRC stage II and IV. Computational analyses were used to test different activity patterns for the analyzed signal transducers. RESULTS Signaling pathways implicated in cell proliferation were differently dysregulated in CRC and, unexpectedly, several were downregulated in disease. Thus, levels of activated ERK1 (pERK1), but not pERK2, decreased in stage II and IV while total ERK1/2 expression remained unaffected. In addition, c-SRC expression was lower in CRC compared with normal tissues and phosphorylation on the activating residue Y418 was not detected. In contrast, PLCγ1 and AKT expression levels were elevated in disease. Immunoblotting of the different signal transducers, run in parallel to capillary isoelectric focusing, showed higher variability and lower sensitivity and resolution. Computational analyses showed that, while individual signaling changes lacked predictive power, using the combination of changes in three signaling components to create a "complex biomarker" allowed with very high accuracy, the correct diagnosis of tissues as either normal or cancerous. CONCLUSIONS We present techniques that allow rapid and sensitive determination of cancer signaling that can be used to differentiate colorectal cancer from normal tissue.


title: Phylogenetic analysis of porcine epidemic diarrhea virus field strains prevailing recently in China.

text: Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED), which is characterized by severe diarrhea, dehydration and high mortality in the affected pigs. Recently, clinical outbreaks of diarrhea in suckling piglets emerged in pig-producing areas of China. In this study, molecular detection of PEDV was conducted using RT-PCR (targeting the M gene) on samples collected from piglets with watery diarrhea from 15 pig farms, and phylogenetic analysis of PEDV field strains was carried out based on their M and S genes. In addition, the complete genome sequence of a PEDV field strain was determined. PEDV was detected in 92.7 % of the samples (267/288). The 15 M genes that were amplified shared 99.6-100 % nucleotide identity and 99.1-100 % amino acid similarity with each other. The 15 S genes exhibited 98.6-99.9 % homology, both at the nucleotide level and at the deduced amino acid level. Phylogenetic analysis showed that all of the amplified M genes grouped in cluster 3, together with some Chinese, Korean and Thai strains, while all of the amplified S genes were in cluster 3 and were closely related to Korean strains. Compared with previous PEDV strains, all of the S genes have common characteristics, namely, a 4-aa (GENQ) insertion between positions 55 and 56, a 1-aa (N) insertion between positions 135 and 136, and a 2-aa (DG) deletion between positions 155 and 156, similar or identical to Korean KNU-serial strains reported in recent years. The genome of the sequenced PEDV field strain is 28,038 nucleotides in length, excluding the poly (A) tail. Our findings suggest that a novel PEDV with a characteristic variant S gene is responsible for recent outbreaks of clinical diarrhea in piglets in China.


title: Extended aortic arch replacement through the L-incision approach.

text: There are various methods for approaching the aortic arch, such as median sternotomy or lateral thoracotomy. However, accessing the site of distal anastomosis is problematic when the distal arch is extensively involved. We report a case of extended aortic arch replacement and coronary artery bypass through the L-incision approach.


title: Robot-assisted laparoscopic transperitoneal pelvic lymphadenectomy and metastasectomy for melanoma: initial report of two cases.

text: Robotic pelvic lymphadenectomy is a well established procedure in the urologic and gynecologic literature. To our knowledge robotic pelvic lymphadectomy for metastatic melanoma has yet to be described. Herein we present the first report of robot-assisted pelvic lymphadenectomy in malignant melanoma. After placement of six laparoscopic ports (12 mm camera, three 8-mm robotic ports, 12-mm and 5-mm assistant ports) the DaVinci S robot (Intuitive Surgical, CA, USA) was docked in standard fashion with the patient in low lithotomy. In both cases the patients had enlarged pelvic lymph nodes on computed tomography and complete excision of these masses was accomplished along with complete lymphadenectomy extending from Cooper's ligament to just below the hypogastric artery in case 1 and to level of the bifurcation of aorta in case 2. A PK Maryland Dissector and monopolar scissors were used for dissection. Both patients were discharged on postoperative day #1. Robotic pelvic lymphadenectomy can be safely used for management of patients with metastatic melanoma involving the pelvic lymph nodes. Compared with the standard open procedure, pelvic lymphadenectomy with robotic assistance is associated with excellent vision and minimum morbidity.


Getting a grip on touch receptors.


title: History repeating. The plague of 1630 in Milan and the COVID-19 pandemia.

text: In western democracies, individual behaviour will be crucial to control the spread of COVID-19, as well as government actions [1] that unfortunately, except China, South Korea and Italy, followed by others, seems to be generally unconvinced and, speculatively, late. Indeed human history has been marked by epidemics/pandemics which have affected, more or less, large geographical areas [2]. Italy, as well as the rest of Europe, has often been affected by these phenomena and, Lombardy, due to his position, was, as today by COVID-19, severely stroked in Italy that is, after China, the second most affected country [3]. This is also linked to the position of Lombardy and its capital, Milan, but this is beyond this brief comment. There are several differences between the past plagues and the actual COVID-19 pandemic and these must be sought in the increased ability to transmit diseases at-distance through the mobility of humans and goods [4], and in the catastrophic consequences of the breakdown of ecosystems, as told, a few years ago, by David Quammen in the book Spillover [5].


title: Global Epidemiology of Tuberculosis and Progress Toward Meeting Global Targets - Worldwide, 2018.

text: Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1), including among persons living with human immunodeficiency virus (HIV) infection (2). A World Health Organization (WHO) initiative, The End Tuberculosis Strategy, set ambitious targets for 2020-2035, including 20% reduction in TB incidence and 35% reduction in the absolute number of TB deaths by 2020 and 90% reduction in TB incidence and 95% reduction in TB deaths by 2035, compared with 2015 (3). This report evaluated global progress toward these targets based on data reported by WHO (1). Annual TB data routinely reported to WHO by 194 member states were used to estimate TB incidence and mortality overall and among persons with HIV infection, TB-preventive treatment (TPT) initiation, and drug-resistant TB for 2018 (1). In 2018, an estimated 10 million persons had incident TB, and 1.5 million TB-related deaths occurred, representing 2% and 5% declines from 2017, respectively. The number of persons with both incident and prevalent TB remained highest in the WHO South-East Asia and African regions. Decreases in the European region were on track to meet 2020 targets. Globally, among persons living with HIV, 862,000 incident TB cases occurred, and 1.8 million persons initiated TPT. Rifampicin-resistant or multidrug-resistant TB occurred among 3.4% of persons with new TB and 18% among persons who were previously treated for TB (overall, among 4.8% of persons with TB). The modest decreases in the number of persons with TB and the number of TB-related deaths were consistent with recent trends, and new and substantial progress was observed in increased TPT initiation among persons living with HIV. However, to meet the global targets for 2035, more intensive efforts are needed by public health partners to decrease TB incidence and deaths and increase the number of persons receiving TB curative and preventive treatment. Innovative approaches to case finding, scale-up of TB preventive treatment, use of newer TB treatment regimens, and prevention and control of HIV will contribute to decreasing TB.


title: Glycosylation of gp116 and gp64 envelope proteins of yellow head virus of Penaeus monodon shrimp.

text: Yellow head virus (YHV) is a highly virulent pathogen of Penaeus monodon shrimp that is classified in the genus Okavirus, family Roniviridae, in the order Nidovirales. Separation of virion proteins treated with peptide-N-glycosidase-F (PNGase-F) in SDS-polyacrylamide gels and the use of glycoprotein-specific staining methods indicated that the gp116 and gp64 envelope glycoproteins possess N-linked rather than O-linked glycans. Competitive binding inhibition of lectins with various oligosaccharide specificities indicated that glycans linked to gp64 are mannose-rich, whilst glycans linked to gp116 possess terminal N-acetylgalactosamine and N-acetylglucosamine in addition to terminal mannose-type sugars. Mass spectrometry analyses of peptides generated from YHV proteins before and after deglycosylation with PNGase-F, using combinations of the endoproteinases trypsin, Asp-N and Lys-C, confirmed occupancy of six of the seven potential N-linked glycosylation sites in gp116 and three of the four potential sites in gp64.


title: Fully Textile, PEDOT:PSS Based Electrodes for Wearable ECG Monitoring Systems.

text: GOAL To evaluate a novel kind of textile electrodes based on woven fabrics treated with PEDOT PSS, through an easy fabrication process, testing these electrodes for biopotential recordings. METHODS Fabrication is based on raw fabric soaking in PEDOT PSS using a second dopant, squeezing and annealing. The electrodes have been tested on human volunteers, in terms of both skin contact impedance and quality of the ECG signals recorded at rest and during physical activity (power spectral density, baseline wandering, QRS detectability, and broadband noise). RESULTS The electrodes are able to operate in both wet and dry conditions. Dry electrodes are more prone to noise artifacts, especially during physical exercise and mainly due to the unstable contact between the electrode and the skin. Wet (saline) electrodes present a stable and reproducible behavior, which is comparable or better than that of traditional disposable gelled Ag/AgCl electrodes. CONCLUSION The achieved results reveal the capability of this kind of electrodes to work without the electrolyte, providing a valuable interface with the skin, due to mixed electronic and ionic conductivity of PEDOT PSS. These electrodes can be effectively used for acquiring ECG signals. SIGNIFICANCE Textile electrodes based on PEDOT PSS represent an important milestone in wearable monitoring, as they present an easy and reproducible fabrication process, very good performance in wet and dry (at rest) conditions and a superior level of comfort with respect to textile electrodes proposed so far. This paves the way to their integration into smart garments.


title: Bridging complexity theory and resilience to develop surge capacity in health systems.

text: Purpose Health systems are periodically confronted by crises - think of Severe Acute Respiratory Syndrome, H1N1, and Ebola - during which they are called upon to manage exceptional situations without interrupting essential services to the population. The ability to accomplish this dual mandate is at the heart of resilience strategies, which in healthcare systems involve developing surge capacity to manage a sudden influx of patients. The paper aims to discuss these issues. Design/methodology/approach This paper relates insights from resilience research to the four "S" of surge capacity (staff, stuff, structures and systems) and proposes a framework based on complexity theory to better understand and assess resilience factors that enable the development of surge capacity in complex health systems. Findings Detailed and dynamic complexities manifest in different challenges during a crisis. Resilience factors are classified according to these types of complexity and along their temporal dimensions: proactive factors that improve preparedness to confront both usual and exceptional requirements, and passive factors that enable response to unexpected demands as they arise during a crisis. The framework is completed by further categorizing resilience factors according to their stabilizing or destabilizing impact, drawing on feedback processes described in complexity theory. Favorable order resilience factors create consistency and act as stabilizing forces in systems, while favorable disorder factors such as diversity and complementarity act as destabilizing forces. Originality/value The framework suggests a balanced and innovative process to integrate these factors in a pragmatic approach built around the fours "S" of surge capacity to increase health system resilience.


title: Robot-assisted urological surgery: Current status and future perspectives.

text: OBJECTIVES To discuss the current status of robot-assisted urological surgery. METHODS We searched PubMed for articles published from 2008 using the search terms 'advances', 'robotic surgery equipment' and 'instrumentation'. We also searched PubMed for articles describing the latest developments in reconstructive techniques for lower and upper urinary tract procedures. Finally, we searched PubMed for original articles containing the terms 'robotic surgery training' and 'credentialing'. RESULTS With each release of hardware or ancillary instrumentation, the reconstructive abilities of the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA) improve. Recent developments in reconstructive capabilities of robotic urological surgery include posterior reconstruction during robot-assisted radical prostatectomy, barbed sutures for urethrovesical anastomosis, sliding-clip renorrhaphy for robot-assisted partial nephrectomy, and repair of pelvic organ prolapse. The safe implementation of robotic surgery is aided by new guidelines in credentialing and proctoring, and the introduction of virtual reality simulators for training. CONCLUSION Robotic urological surgery is rapidly developing and expanding globally. To achieve the highest levels of safety for patients, surgeons must ensure that the implementation of robotic surgery is an integrative and effective process.


title: Complications of gastrointestinal surgery in companion animals.

text: The small animal surgeon creates wounds in the gastrointestinal (GI) tract for biopsy, for foreign body or neoplasm removal, or to relieve obstruction. Unlike a skin wound, dehiscence of a wound of the GI tract often leads to generalized bacterial peritonitis and potentially death. Technical failures and factors that negatively affect GI healing are of great clinical significance. Surgery of the GI tract must be considered clean-contaminated at best; as one progresses aborally down the GI tract, the bacterial population increases. Intraoperative spillage, wound dehiscence, or perforations that occur in the lower small intestine or colon tend to be associated with a relatively higher mortality rate.


title: Nasal Reconstruction Involving Multiple Subunit Defects.

text: The challenges of nasal reconstruction are readily apparent to any surgeon who has undertaken this task. Defects involving multiple subunits of the nose usually require adjacent tissue transferred to the wound typically in the form of a forehead flap or other local flaps. Herein, we describe current thought on the subunit principle and the application of local flaps and grafts in reconstructing larger superficial defects of the nose. Primary attention is paid to analysis and patient counseling.


title: Hartmann's procedure and laparoscopic reversal versus primary anastomosis and ileostomy closure for left colonic perforation.

text: PURPOSE Emergency surgical strategies for acute left-sided colonic perforation are evolving preferring primary anastomosis (PA) with ileostomy to Hartmann's procedure (HP) based on the morbidity and reversal rates. However, HP is still commonly performed. Hartmann's reversal is associated with considerable morbidity. It is of interest whether laparoscopic reversal results in a lower morbidity as retrospective data suggest. Here, we compared the combined morbidity rates for two surgical strategies: strategy A, HP followed by laparoscopic reversal, and strategy B, sigmoid resection with PA followed by ileostomy closure. METHODS Prospectively collected data of all consecutive patients undergoing HP for benign left-sided colonic perforation between 2010 and 2014 were retrospectively compared to data of patients undergoing PA. Groups were matched for age and Charlson comorbidity index. Additionally, patients were analyzed for American Society of Anesthesiologists score, body mass index, and peritonitis stage. End points were morbidity, operation time, reversal rate, time to reversal, and length of hospital stay. RESULTS The study included 32 patients for whom Hartmann's reversal was planned, along with 32 matched patients who underwent PA and diverting ileostomy. Median age was 75 and 72 years, Charlson score was 6 (4-9) and 6 (5-7), and patients classified by the American Society of Anesthesiologists (ASA) higher than III were 81 % in both groups. Combined major morbidity rates were 21 % for strategy A and 20 % for strategy B (p = 1.0). Combined comprehensive complication index was 16.4 ± 14.1 and 12.3 ± 19.1 (p = 0.08). HP reversal by laparoscopy was achieved in 71 %. The colostomy reversal rate was 75 % compared to ileostomy closure rate of 88 % (p = 0.34). CONCLUSIONS Laparoscopic Hartmann's reversal is achievable in a high proportion of patients. Strategy B tends to have lower overall morbidity; meanwhile, major morbidity seems to be similar. Yet, in critically ill patients and in the absence of expertise of the surgeon on call, HP followed by elective laparoscopic reversal represents a viable alternative.


title: Esophageal extracellular matrix hydrogel mitigates metaplastic change in a dog model of Barrett's esophagus.

text: Chronic inflammatory gastric reflux alters the esophageal microenvironment and induces metaplastic transformation of the epithelium, a precancerous condition termed Barrett's esophagus (BE). The microenvironmental niche, which includes the extracellular matrix (ECM), substantially influences cell phenotype. ECM harvested from normal porcine esophageal mucosa (eECM) was formulated as a mucoadhesive hydrogel, and shown to largely retain basement membrane and matrix-cell adhesion proteins. Dogs with BE were treated orally with eECM hydrogel and omeprazole (n = 6) or omeprazole alone (n = 2) for 30 days. eECM treatment resolved esophagitis, reverted metaplasia to a normal, squamous epithelium in four of six animals, and downregulated the pro-inflammatory tumor necrosis factor-α+ cell infiltrate compared to control animals. The metaplastic tissue in control animals (n = 2) did not regress. The results suggest that in vivo alteration of the microenvironment with a site-appropriate, mucoadhesive ECM hydrogel can mitigate the inflammatory and metaplastic response in a dog model of BE.


title: Comparison of the value of tissue-sealing devices for thoracoscopic pulmonary lobectomy in small children: a first report.

text: Accurate division and sealing of lung parenchyma particularly in cases of total or near total incomplete fissure are crucial for preventing air leakage following thoracoscopic pulmonary lobectomy (TPL). However, conventional endoscopic stapling devices cannot be used during TPL in small children because of limited space. Consequently, Ligasure (LS) and Enseal (ES) devices are being used instead. We are the first to compare LS and ES for efficacy and efficiency during TPL. Of 26 TPL (6 upper, 3 middle, and 17 lower) performed for congenital adenomatoid malformation (n = 16) and sequestration (n = 10), incomplete fissure was found in 14. TPL (LS = 11; ES = 15) was performed conventionally in the lateral decubitus position with single lung ventilation using four 5 mm trocars. All cases had a chest tube inserted intraoperatively that was left in situ. Patient demographics, location of pathology, incidence of incomplete fissure, mean age/weight at TPL, mean blood loss, and mean operative time were all similar. However, duration of chest tube insertion was significantly shorter in ES because there was less postoperative air leakage (1.3 vs. 3.9 days; p < 0.05). ES would appear to seal lung parenchyma more effectively during TPL based on the shorter duration of chest tube insertion.


title: Collateral lessons from recent acute ischemic stroke trials.

text: Numerous acute ischemic stroke trials have recently published detailed results, providing an opportunity to consider the role of collaterals in stroke pathophysiology and their influential effect on patient outcomes. Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS), the largest randomized controlled trial of device therapy to date, tested the potential augmentation of collateral perfusion. SYNTHESIS Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Interventional Management of Stroke (IMS) III chronicled the saga of endovascular therapy trialed against medical treatment for acute ischemic stroke. These recent randomized studies, however, largely neglect current device technology available for endovascular therapy as advanced by the TREVO2 and SOLITAIRE™(TM) FR With the Intention For Thrombectomy (SWIFT) studies. Such exhaustive efforts in recent trials have failed to introduce a new treatment for stroke that unequivocally improves patient outcomes. Collateral perfusion is widely recognized to vary across individuals in any population and exerts a dramatic effect on baseline variables including the time course of ischemic injury, stroke severity, imaging findings, and therapeutic opportunities. Similarly, collaterals have been recognized to influence recanalization, reperfusion, hemorrhagic transformation, and subsequent neurological outcomes after stroke. Collateral lessons may be gleaned from these trials, to expand consideration of overall study results and perhaps most importantly, alter ongoing and new trials in development. Detailed analyses of available information on collaterals from these trials demonstrate that collaterals may be more influential than the choice of treatment modality or intervention.


title: People experiencing homelessness urgently need to be recognised as a high risk group for COVID-19.

text: History shows that pandemics rarely impact on the population equally - the 14th century Black Death plague reduced the global population by a third, with the greatest number of deaths occurring among the poor.1 Fast forward six centuries, and the same pandemic inequities are prevailing due to COVID-19; with Smith and Judd articulating that "while COVID-19 has the potential to impact everyone in society, these impacts will be felt differentially… the most vulnerable will be hardest hit"2 in their recent Health Promotion Journal of Australia editorial.


title: Targeting human prostate cancer with 111In-labeled D2B IgG, F(ab')2 and Fab fragments in nude mice with PSMA-expressing xenografts.

text: D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab')2 and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing subcutaneous prostate cancer xenografts. The optimal time point for imaging was determined in biodistribution and microSPECT imaging studies with (111)In-D2B IgG, (111)In-capromab pendetide, (111)In-D2B F(ab')2 and (111)In-D2B Fab fragments in mice with PSMA-expressing LNCaP and PSMA-negative PC3 tumors at several time points after injection. All (111)In-labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of (111)In-D2B IgG and (111)In-capromab pendetide at 168 h p.i. (94.8 ± 19.2% injected dose per gram (ID/g) and 16.7 ± 2.2% ID/g, respectively), whereas uptake of (111)In-D2B F(ab')2 and (111)In-D2B Fab fragments peaked at 24 h p.i. (12.1 ± 3.0% ID/g and 15.1 ± 2.9% ID/g, respectively). Maximum LNCaP tumor-to-blood ratios were 13.0 ± 2.3 (168 h p.i.), 6.2 ± 0.7 (24 h p.i.), 23.0 ± 4.0 (24 h p.i.) and 4.5 ± 0.6 (168 h p.i.) for (111)In-D2B IgG, (111)In-F(ab')2, (111)In-Fab and (111)In-capromab pendetide, respectively. LNCaP tumors were clearly visualized with microSPECT with all antibody formats. This study demonstrates the feasibility of D2B IgG, F(ab')2 and Fab fragments for targeting PSMA-expressing prostate cancer xenografts.


title: Inspiratory Muscle Training with Isokinetic Device to Help Ventilatory Weaning in a Patient with Guillain-Barré Syndrome by Zika Virus.

text: Zika is an arbovirus infection mainly transmitted by the mosquito Aedes aegypti. In 2016, the burden of Zika epidemic in Brazil was significant. Patients affected by Zika virus can develop Guillain-Barré syndrome, evolving to muscle respiratory failure requiring mechanical ventilation. In this setting, delayed recovery of the muscle weakness can result in prolonged weaning, a condition that by itself is related to a high mortality rate. The study is reporting a case of a patient with Zika and Guillain-Barré syndrome who underwent an inspiratory muscle training program starting after twenty-five days of mechanical ventilation and guided by serial measurements of the timed inspiratory effort (TIE) index. The patient was successfully weaned in two weeks and discharged from the hospital 30 days after extubation.


title: Albumin-binding domain from Streptococcus zooepidemicus protein Zag as a novel strategy to improve the half-life of therapeutic proteins.

text: Recombinant antibody fragments belong to the promising class of biopharmaceuticals with high potential for future therapeutic applications. However, due to their small size they are rapidly cleared from circulation. Binding to serum proteins can be an effective approach to improve pharmacokinetic properties of short half-life molecules. Herein, we have investigated the Zag albumin-binding domain (ABD) derived from Streptococcus zooepidemicus as a novel strategy to improve the pharmacokinetic properties of therapeutic molecules. To validate our approach, the Zag ABD was fused with an anti-TNFα single-domain antibody (sdAb). Our results demonstrated that the sdAb-Zag fusion protein was highly expressed and specifically recognizes human, rat and mouse serum albumins with affinities in the nanomolar range. Moreover, data also demonstrated that the sdAb activity against the therapeutic target (TNFα) was not affected when fused with Zag ABD. Importantly, the Zag ABD increased the sdAb half-life ∼39-fold (47min for sdAb versus 31h for sdAb-Zag). These findings demonstrate that the Zag ABD fusion is a promising approach to increase the half-life of small recombinant antibodies molecules without affecting their therapeutic efficacy. Moreover, the present study strongly suggests that the Zag ABD fusion strategy can be potentially used as a universal method to improve the pharmokinetics properties of many others therapeutics proteins and peptides in order to improve their dosing schedule and clinical effects.


title: Emergency reconstructive endovascular management of intraoperative complications involving the internal carotid artery from trans-sphenoidal surgery.

text: PURPOSE To report our experience with intraoperative complications involving the internal carotid artery (ICA) during trans-sphenoidal surgery and their outcome with reconstructive endovascular management. METHODS A retrospective review was conducted of patients with an ICA injury related to trans-sphenoidal surgery from 2000 to 2012. Demographic data, clinical charts, indications for treatment, radiographic images, lesion characteristics, operative notes, endovascular procedure notes and post-procedure hospital course were reviewed. RESULTS Three men and one woman of mean age of 52 years (range 33-74) were identified. The lesions included two macroadenomas, one meningioma and one chondrosarcoma. Risk factors for ICA rupture included two patients with carotid dehiscence, one with sphenoid septal attachment to the ICA, two with revision surgery, one with prior radiation to the tumor, one with bromocriptine treatment and two with acromegaly. In three patients, covered stent placement achieved hemostasis at the site of injury within the ICA. One patient developed delayed bleeding 6 h after covered stent placement and underwent successful endovascular occlusion of the ICA but died 6 days after the injury. The fourth patient had an intraoperative ICA stroke requiring suction thrombectomy, thrombolysis, stent placement and evacuation of an epidural hematoma. At 1-year follow-up, two patients had a modified Rankin score (mRS) and National Institute of Health Stroke Scale (NIHSS) score of 0; in the patient who had a stroke the mRS score was 1 and the NIHSS score 2. CONCLUSIONS Endovascular management with arterial reconstruction is helpful in the treatment of ICA injuries during trans-sphenoidal surgery.


title: Hydrogel dressings for healing diabetic foot ulcers.

text: BACKGROUND Foot ulcers in people with diabetes are a prevalent and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from including hydrogel dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. OBJECTIVES To assess the effects of hydrogel wound dressings compared with alternative dressings or none on the healing of foot ulcers in people with diabetes. SEARCH METHODS For this first update, in April 2013, we searched the following databases the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of hydrogel with alternative wound dressings or no dressing in the treatment of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS We included five studies (446 participants) in this review. Meta analysis of three studies comparing hydrogel dressings with basic wound contract dressings found significantly greater healing with hydrogel: risk ratio (RR) 1.80, 95% confidence interval (CI) 1.27 to 2.56. The three pooled studies had different follow-up times (12 weeks, 16 weeks and 20 weeks) and also evaluated ulcers of different severities (grade 3 and 4; grade 2 and grade unspecified). One study compared a hydrogel dressing with larval therapy and found no statistically significant difference in the number of ulcers healed and another found no statistically significant difference in healing between hydrogel and platelet-derived growth factor. There was also no statistically significant difference in number of healed ulcers between two different brands of hydrogel dressing. All included studies were small and at unclear risk of bias and there was some clinical heterogeneity with studies including different ulcer grades. No included studies compared hydrogel with other advanced wound dressings. AUTHORS' CONCLUSIONS There is some evidence to suggest that hydrogel dressings are more effective in healing (lower grade) diabetic foot ulcers than basic wound contact dressings however this finding is uncertain due to risk of bias in the original studies. There is currently no research evidence to suggest that hydrogel is more effective than larval therapy or platelet-derived growth factors in healing diabetic foot ulcers, nor that one brand of hydrogel is more effective than another in ulcer healing. No RCTs comparing hydrogel dressings with other advanced dressing types were found.


title: COVID-19. Immunothrombosis and the gastrointestinal tract.

text: Mönkemüller et al. brilliantly describe the pathogenesis of SARS-CoV-2 (COVID-19) in the gastrointestinal tract. Their findings highlight the local and systemic inflammatory response generated by the coronavirus. After having the opportunity to observe three cases of severe colonic ischemia and elevation of D-dimer levels in patients with COVID-19 and severe acute respiratory distress syndrome (SARS) due to SARS-CoV-2, we would like to highlight the thromboembolic complications in COVID-19, which are related to those reported by Mönkemüller and which have been mentioned by other authors.


title: In silico evaluation of marine fish proteins as nutritional supplements for COVID-19 patients.

text: To date, no specific drug has been discovered for the treatment of COVID-19 and hence, people are in a state of anxiety. Thus, there is an urgent need to search for various possible strategies including nutritional supplementation. In this study, we have tried to provide a reference for protein supplementation. Specifically, 20 marine fish proteins were subjected to in silico hydrolysis by gastrointestinal enzymes, and a large number of active peptides were generated. Then, the binding abilities of these peptides to SARS-CoV-2 main protease and monoamine oxidase A were assessed. The results showed that NADH dehydrogenase could be a good protein source in generating potent binders to the two enzymes, followed by cytochrome b. In addition, some high-affinity oligopeptides (VIQY, ICIY, PISQF, VISAW, AIPAW, and PVSQF) were identified as dual binders to the two enzymes. In summary, the supplementation of some fish proteins can be helpful for COVID-19 patients; the identified oligopeptides can be used as the lead compounds to design potential inhibitors against COVID-19 and anxiety.


title: Pain characteristics after laparoscopic inguinal hernia repair.

text: BACKGROUND Previous studies have shown different pain characteristics in different types of laparoscopic operations, but pain pattern has not been studied in detail after laparoscopic inguinal hernia repair. To optimise preoperative patient information and postoperative analgesic treatment the present study investigated postoperative pain in terms of time course, pain intensity and individual pain components during the first 4 days after transabdominal preperitoneal hernia repair (TAPP). METHODS The study was a single-centre prospective trial including 50 consecutive male patients with primary or recurrent inguinal and/or femoral hernia undergoing elective repair. Several pain components (visceral pain, incisional pain and shoulder pain) were studied as well as pain at the three different trocar incisions. Pain was recorded before operation and on a daily basis during the first four postoperative days using a visual analogue and a verbal rating scale. We used 1 × 12 and 2 × 5 mm trocars for TAPP. RESULTS A total of 46 patients were available for analyses (age median 58 years, range 27-69 years). Visceral pain dominated significantly compared with incisional pain (P < 0.01), which again dominated over shoulder pain intensity and incidence (P < 0.01). Pain intensity did not significantly differ between different trocar incisions (5 and 12 mm) (P > 0.05). The overall pain intensity (a conglomerate of the different pain components) was most intense 3 h after TAPP and declined to preoperative levels on day 3 (P > 0.5). CONCLUSION Pain was most intense 3 h after the operation and declined to low levels within the first 3 days. Visceral pain was by far the dominating pain component compared with incisional and shoulder pain.


title: Epidemiology of Serotype 1 Invasive Pneumococcal Disease, South Africa, 2003-2013.

text: In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003-2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1-associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003-2004 and 2008-2012, but incidence decreased after 2011. Among children <5 years of age, those who had non-serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.


Hyperglycemia, Hypertriglyceridemia, and Acute Pancreatitis in COVID-19 Infection: Clinical Implications.


title: Joint estimation of the basic reproduction number and generation time parameters for infectious disease outbreaks.

text: The basic reproduction number is a key parameter determining whether an infectious disease will persist. Its counterpart over time, the effective reproduction number, is of value in assessing in real time whether interventions have brought an outbreak under control. In this paper, we use theoretical arguments and simulation to understand the relationship between estimation of the reproduction number based on a full continuous time epidemic model and 2 other recently developed estimators. All these methods make use of "epidemic curve" data and require assumptions about the generation time distribution. The 2 simplest estimators do not require information about the-often difficult to obtain-population size. The simplest estimator is shown to require further assumptions that are rarely valid in practical settings and to produce severely biased estimates compared to the others. Furthermore, we show that in general the parameters of the generation time distribution and the reproduction number are non-identified in the early stages of an incomplete outbreak. On the basis of these results, we recommend that, wherever possible, estimation of the basic and effective reproduction numbers should be based on a well-defined epidemic model; moreover, if external information is available then it should be incorporated in a Bayesian analysis.


title: Surgical Intervention for Refractory Donor-Site Seroma After Immediate Breast Reconstruction with Latissimus Dorsi Flap.

text: Donor-site seroma persisting for > 3 weeks is the most common complication of latissimus dorsi (LD) flaps for breast reconstruction after mastectomy. Conservative treatment is insufficient for refractory seroma resolution. We report the results of surgical intervention for refractory donor-site seroma. Between January 2012 and April 2018, 319 patients undergoing breast reconstruction using an LD flap at our hospital were treated with conservative therapy if seroma was found. Refractory seroma of > 3 months' duration was observed in five patients (1.6%). Before surgery, the precise location and extent of the capsule were determined using chest computed tomography, and surgical intervention was planned. An en bloc capsulectomy was performed after confirming the internal capsule. Simultaneously, a quilting suture, bolster suture, and fibrin sealant were applied to prevent recurrence. The mean age of the patients with refractory seroma was 45.4 ( ± 7.3) years, and their mean body mass index was 31.0 ( ± 6.2) kg/m2. All patients underwent breast reconstruction with an extended LD flap or extended LD flap with a silicone implant after total mastectomy. During the follow-up period of ≥ 10.4 months, a mean of 34.4 ( ± 10.4) needle aspiration procedures were performed, and a mean of 12.8 ( ± 2.2) cc of seroma fluid was removed each time. Intraoperatively, the formation of a capsule with a well-defined border was confirmed; all patients showed complete resolution of donor-site seroma within 4 weeks after surgical intervention. Refractory donor-site seroma occurrence was rare in the cases assessed. Surgical intervention was successful in cases of refractory donor-site seroma unsuccessfully treated with conservative therapy and is thus one of the most effective methods for complete resolution of refractory seroma.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


title: Histochemistry as an irreplaceable approach for investigating functional cytology and histology.

text: In agreement with the evolution of histochemistry over the last fifty years and thanks to the impressive advancements in microscopy sciences, the application of cytochemical techniques to light and electron microscopy is more and more addressed to elucidate the functional characteristics of cells and tissue under different physiological, pathological or experimental conditions. Simultaneously, the mere description of composition and morphological features has become increasingly sporadic in the histochemical literature. Since basic research on cell functional organization is essential for understanding the mechanisms responsible for major biological processes such as differentiation or growth control in normal and tumor tissues, histochemical Journals will continue to play a pivotal role in the field of cell and tissue biology in all its structural and functional aspects.


title: Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019.

text: Importance Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL). Conclusions and Relevance This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.


title: Validation and initial application of a semiautomatic aneurysm measurement software: a tool for assessing volumetric packing attenuation.

text: BACKGROUND AND PURPOSE Precise aneurysm measurements and volume embolization ratios are essential for long-term durability of endovascular coil embolization. We evaluated the accuracy of newly developed semiautomatic cerebral aneurysm measurement software, NeuroVision, and explored the value of volume embolization ratio in the prediction of re-treatment. MATERIALS AND METHODS We compared software-derived volume measurements of 4 silicone aneurysm models with those calculated with an approximation formula and ground truth values (validation study). We used NeuroVision to retrospectively evaluate outcomes of 100 unruptured aneurysms (97 patients) treated with embolization (clinical study). Aneurysm size (height, width, and neck), volume, and volume embolization ratios were calculated for 3 groups (stable, recanalization, and re-treatment) and were compared. RESULTS This validation study illustrated higher accuracy of NeuroVision in computing aneurysm volume compared with an approximation formula: percentage absolute errors were 4.50% ± 3.18% and 23.07% ± 17.60%, with maximal percentage absolute errors of 8.99% and 45.63%, respectively. Of 100 unruptured aneurysms, 20 recanalized and 12 were re-treated. Average volume embolization ratios of stable and re-treated aneurysms were 24.88% ± 5.91% and 20.50% ± 4.06%, respectively (P ≤ .01). The optimal volume embolization ratio cutoff point for re-treatment was < 19.15%, at which the Youden index was 0.50 (sensitivity, 58.33%; specificity, 87.50%; area under the receiver operating characteristic curve, 0.74). CONCLUSIONS The NeuroVision software provided accurate aneurysm volume measurements and may be a useful standardized tool to measure aneurysm size and volume, especially for multicenter clinical studies. Volume embolization ratio may be a valuable predictor of aneurysm occlusion changes.


title: Effects of mesenchymal stem cell and fibroblast coating on immunogenic potential of prosthetic meshes in vitro.

text: BACKGROUND The aim of this study was to reveal the effect of fibroblast or mesenchymal stem cell (MSC) coating on the mesh-induced production of IL-1β, IL-6, and VEGF by macrophages. METHODS Four commonly used surgical meshes were tested in this study, including Parietex, SoftMesh, TIGR, and Strattice. One-square-centimeter pieces of each mesh were placed on top of a monolayer of human fibroblasts or rat MSCs. The coating status was monitored with a light microscope. The human promonocytic cell line U937 was induced to differentiate into macrophages (MΦ). Three weeks later, meshes were transferred to new 24-well plates and cocultured with the MΦs for 72 h. Culture medium was collected and analyzed for IL-1β, IL-6, and VEGF production using standard ELISA essays. Parallel mesh samples were fixed with paraformaldehyde or glutaraldehyde for histology or transmission electronic microscopy (TEM) analyses, respectively. RESULTS Uncoated meshes induced increased production of all three cytokines compared with macrophages cultured alone. HF coating further increased the production of both IL-6 and VEGF but reduced IL-1β production. Except for the SoftMesh group, MSC coating significantly blunted release of all cytokines to levels even lower than with MΦs cultured alone. MΦs tended to deteriorate in the presence of MSCs. Both histology and TEM revealed intimate interactions between cell-coated meshes and MΦs. CONCLUSIONS Cytokine response to fibroblast coating varied, while MSC coating blunted the immunogenic effect of both synthetic and biologic meshes in vitro. Cell coating appears to affect mesh biocompatibility and may become a key process in mesh evolution.


title: Epidemiology and clinical associations of human parechovirus respiratory infections.

text: Infections with human parechoviruses (HPeVs) are prevalent in young children and have been associated with mild gastroenteritis and, less frequently, with meningitis and neonatal sepsis. To investigate the involvement of these viruses in respiratory disease, a highly sensitive nested PCR was used to screen a large archive of respiratory specimens, collected between January and December 2007. Respiratory samples had previously been tested for eight respiratory viruses, including respiratory syncytial virus and adenovirus, by PCR. HPeV was detected in 34 of 3,844 specimens, representing 27 of 2,220 study subjects (1.2%). HPeV types were identified by sequencing the VP3/VP1 junction amplified by PCR directly from clinical specimens. The assay could amplify all HPeV types examined with high sensitivity (types 1 and 3 to 6) and also identified HPeV types in all but one of the screen-positive study specimens (25 HPeV1 and eight HPeV6 specimens). Infections with both HPeV1 and HPeV6 were seasonal, with highest frequencies in July and August, and restricted to children aged between 6 months and 5 years. Other respiratory viruses were frequently codetected in HPeV-positive specimens, with significant overrepresentation of adenovirus coinfections (37%). Most HPeV-positive specimens were referred from emergency departments, although no association with specific respiratory symptoms or disease was found. In summary, the low frequency of detection and lack of clear disease associations indicate that HPeV1 and -6 are not major pathogens in individuals presenting with respiratory disease. However, the screening and typing methods developed will be of value in further HPeV testing, including testing for meningitis cases and other suspected HPeV-associated disease presentations.


title: Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets.

text: Qualitative risk assessment methods are often used as the first step to determining design space boundaries; however, quantitative assessments of risk with respect to the design space, i.e., calculating the probability of failure for a given severity, are needed to fully characterize design space boundaries. Quantitative risk assessment methods in design and operational spaces are a significant aid to evaluating proposed design space boundaries. The goal of this paper is to demonstrate a relatively simple strategy for design space definition using a simplified Bayesian Monte Carlo simulation. This paper builds on a previous paper that used failure mode and effects analysis (FMEA) qualitative risk assessment and Plackett-Burman design of experiments to identity the critical quality attributes. The results show that the sequential use of qualitative and quantitative risk assessments can focus the design of experiments on a reduced set of critical material and process parameters that determine a robust design space under conditions of limited laboratory experimentation. This approach provides a strategy by which the degree of risk associated with each known parameter can be calculated and allocates resources in a manner that manages risk to an acceptable level.


title: Clinical Evaluation of Synovial Alpha Defensin and Synovial C-Reactive Protein in the Diagnosis of Periprosthetic Joint Infection.

text: BACKGROUND Diagnosing periprosthetic joint infection after total joint arthroplasty is often challenging. The alpha defensin test has been recently reported as a promising diagnostic test for periprosthetic joint infection. The goal of this study was to determine the diagnostic accuracy of alpha defensin testing. METHODS One hundred and eighty-three synovial alpha defensin and synovial fluid C-reactive protein (CRP) tests performed in 183 patients undergoing evaluation for periprosthetic joint infection were reviewed. Results were compared with the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection. RESULTS Alpha defensin tests were performed prior to surgical treatment for infection, and 37 of these patients who had these tests were diagnosed by MSIS criteria as having infections. Among this group, the alpha defensin test had a sensitivity of 81.1% (95% confidence interval [CI], 64.8% to 92.0%) and a specificity of 95.9% (95% CI, 91.3% to 98.5%). There were 6 false-positive results, 4 of which were associated with metallosis. There were 7 false negatives, all of which were associated with either draining sinuses (n = 3) or low-virulence organisms (n = 4). A combined analysis of alpha defensin and synovial fluid CRP tests was performed in which a positive result was represented by a positive alpha defensin test and a positive synovial fluid CRP test (n = 28). Among this group, the sensitivity was calculated to be 73.0% (95% CI, 55.9% to 86.2%) and the specificity was calculated to be 99.3% (95% CI, 96.2% to 99.9%). An additional combined analysis was performed where a positive result was represented by a positive alpha defensin test or positive synovial fluid CRP test (n = 64). Among this group, the sensitivity was calculated to be 91.9% (95% CI, 78.1% to 98.3%) and the specificity was calculated to be 79.5% (95% CI, 72.0% to 85.7%). CONCLUSIONS Alpha defensin in combination with synovial fluid CRP demonstrates very high sensitivity for diagnosing periprosthetic joint infection, but may yield false-positive results in the presence of metallosis or false-negative results in the presence of low-virulence organisms. When both alpha defensin and synovial fluid CRP tests are positive, there is a very high specificity for diagnosing periprosthetic joint infection. LEVEL OF EVIDENCE Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.


title: Efficiency and risks of laparoscopic conversion of omega anastomosis gastric bypass to Roux-en-Y gastric bypass.

text: BACKGROUND There is a paucity on literature data related to conversion of Omega anastomosis gastric bypass (OAGB) to Roux-en-Y gastric bypass (RYGB). METHODS This is a retrospective study. Records of all patients who underwent this conversion were analyzed. Additionally, patients were contacted to answer a questionnaire on their current clinical condition. RESULTS Twenty-eight patients underwent laparoscopic conversion between September 2007 and June 2016. Indications were peritonitis in 7 patients (leaks after OAGB in 5, perforated marginal ulcer (MU) and blow-out remnant with concomitant leak in one patient each), anastomotic bleeding in one, bile reflux in 6, recalcitrant MU in 4, afferent loop syndrome in 6, postprandial vomiting in 2 (related to anastomotic stenosis and perianastomotic diverticulum, one each), and malnutrition and hypoglycemia both in 1. Thirty-day mortality was zero, complication rate (Clavien-Dindo grade III or more) 5% ((N = 1/20), abscess) when conversion was elective and 50.0% ((N = 4/8), all persisting leaks) when conversion was urgent. All 4 leaks persisting after conversion were successfully treated by endoscopic stenting, despite stent migration in 2 patients. Follow-up was available in 92.9%, for a mean time of 64.5 ± 30.1 months. Successful symptom relief (Likert score 4 or more) was noted for bile reflux and postprandial vomiting. Additionally, malnutrition was corrected. CONCLUSIONS When indicated, conversion of OAGB to RYGB is a safe treatment strategy. In case conversion is performed for leak after OAGB, persisting subclinical leaks are frequent but can be efficiently addressed by endoscopic stenting.


title: Respiratory effects of sulfur mustard exposure, similarities and differences with asthma and COPD.

text: CONTEXT Previous research has found relationships between sulfur mustard (SM) toxicity and its adverse effects. OBJECTIVE SM is highly toxic to the respiratory system, leading to hacking cough, rhinorrheachest tightness, acute pharyngitis and laryngitis, chronic bronchitis and lung fibrosis. In this review, based on the scientific literature, we provide an updated summary of information on SM exposures and their differences with asthma and COPD. METHOD Information of this review was obtained by searching Medline/PubMed, ScienceDirect, Scopus, Google Scholar, ISI Web of Knowledge and Chemical Abstracts. RESULTS SM exposure can decrease pulmonary function tests (PFTs) values. In addition, inflammatory cell accumulation in the respiratory tract and increased expression of some pro-inflammatory cytokines including tumor necrosis factor-α (TNFα), IL-1a, IL-1β, and reactive oxygen radicals due to SM exposure have been shown. Matrix metalloproteinase (MMP) which degrade extracellular matrix proteins, contributing to inflammatory cell recruitment, tissue injury and fibrosis are also up-regulated in the lung after SM exposure. In the lung, SM exposure also can cause serious pathological changes including airway inflammation, parenchymal tissue destruction and airway obstruction which can lead to asthma or chronic obstructive pulmonary disease (COPD). Following SM poisoning, DNA damage, apoptosis and autophagy are observed in the lung along with the increased expression of activated caspases and DNA repair enzymes. CONCLUSION In the present article, respiratory symptoms, changes in PFTs, lung pathology and lung inflammation due to SM exposure and the similarities and differences between them and those observed in asthma and COPD were reviewed.


title: Spatiotemporal study of elderly suicide in Korea by age cohort.

text: OBJECTIVES This study analyzed the spatiotemporal pattern and spatial diffusion of elderly suicide by age cohort, in Korea. STUDY DESIGN The research investigated the elderly suicide rates of the 232 municipal units in South Korea between 2001 and 2011. METHODS The Gi* score, which is a spatially weighted indicator of area attributes, was used to identify hot spots and the spatiotemporal pattern of elderly suicide in the nation during the last 10 years. The spatial Markov matrix and spatial dynamic panel data model were employed to identify and estimate the diffusion effect. RESULTS The suicide rate among elderly individuals 75 years and older was substantially higher than the rate for those between 65 and 74 years of age; however, the spatial patterns of the suicide clusters were similar between the two groups. From 2001 to 2011, the spatial distribution of elderly suicide hot spots differed each year. For both age cohorts, elderly suicide hot spots developed around the north area of South Korea in 2001 and moved to the mid-east area and the mid-western coastal area over 10 years. The spatial Markov matrix indicates that the change in the suicide rate of one area was affected by the suicide rates of neighbouring areas from the previous year, which suggests that suicide increase in one area inflates a neighbouring area's suicide rate over time. Using a spatial dynamic panel data model, elderly suicide diffusion effects were found to be statistically significant for both age cohorts even after economic and demographic indicators and a time variable are included. For individuals 75 years and older, the diffusion effect appeared to be larger. CONCLUSIONS This study demonstrates that elderly suicide can spread spatially over time in both age cohorts. Thus, it is necessary to design a place-based and age-differentiated intervention policy that precisely considers the spatial diffusion of elderly suicide.


title: Using sensitivity analysis to identify key factors for the propagation of a plant epidemic.

text: Identifying the key factors underlying the spread of a disease is an essential but challenging prerequisite to design management strategies. To tackle this issue, we propose an approach based on sensitivity analyses of a spatiotemporal stochastic model simulating the spread of a plant epidemic. This work is motivated by the spread of sharka, caused by plum pox virus, in a real landscape. We first carried out a broad-range sensitivity analysis, ignoring any prior information on six epidemiological parameters, to assess their intrinsic influence on model behaviour. A second analysis benefited from the available knowledge on sharka epidemiology and was thus restricted to more realistic values. The broad-range analysis revealed that the mean duration of the latent period is the most influential parameter of the model, whereas the sharka-specific analysis uncovered the strong impact of the connectivity of the first infected orchard. In addition to demonstrating the interest of sensitivity analyses for a stochastic model, this study highlights the impact of variation ranges of target parameters on the outcome of a sensitivity analysis. With regard to sharka management, our results suggest that sharka surveillance may benefit from paying closer attention to highly connected patches whose infection could trigger serious epidemics.


title: Development of a new system for guidewire-assisted tracheal intubation: manikin and cadaver evaluation.

text: Guided intubation using a tracheal tube and semi-rigid introducer is associated with technical difficulties, failure and traumatic complications. We describe the development of a new system of guidewire-assisted tracheal intubation that may circumvent these problems. A reinforced silicone tracheal tube was modified with a guide channel built inside its wall, and a nitinol non-kinking guidewire was matched to this channel. Both anterograde and retrograde tracheal intubation were evaluated in a test rig, an airway manikin and then in preserved and fresh cadavers. There was minimal resistance to passage of the guidewire through the guide channel when the modified tube was in an anatomical configuration, in contrast to moderate resistance when an Airway Exchange Catheter was passed through a PVC tracheal tube. Intubation using the new equipment required increased force in the manikin and preserved cadavers, but minimal force in fresh cadavers. Resistance to tracheal tube advancement in preserved cadavers was overcome by withdrawal followed by 90° rotation, but this manoeuvre was not required in fresh cadavers. We suggest that the combination of the modified tracheal tube and matching guidewire may allow easy and reliable single-step guided tracheal intubation when used in patients.


title: MEN2-related pheochromocytoma: current state of knowledge, specific characteristics in MEN2B, and perspectives.

text: Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome due to mutations of the proto-oncogene REarranged during Transfection (RET), defined by the association of medullary thyroid carcinoma (MTC) in almost 100% cases, and pheochromocytoma in roughly 50% (primary hyperparathyroidism can be seen in 10-20% of patients with MEN2A). Early thyroidectomy and the efficacy of novel tyrosine kinase inhibitors modified the natural history of MTC, with possibilities of cure or long-term control. The second main compound, pheochromocytoma, is reported with a variable penetrance, from 10 to 80% cases, depending on the mutation of RET. Pheochromocytoma constitutes the main disease to screen in patients with RET mutations. Pheochromocytoma clinical and biochemical diagnosis, as well as the way to treat it are thus crucial. This review will thus focus on the epidemiological specificities of MEN2-related pheochromocytoma, the genotype/phenotype relationship, the modern imaging modalities necessary to confirm the diagnosis in this hereditary context, as well as the optimal management and the possibilities of adrenal sparing surgery. Additional information will include the natural history of MEN2B-pheochromocytoma, the rare cases of malignant pheochromocytoma, and the factors that could modify the penetrance between individuals carrying the same mutation, especially in the same family.


title: Availability and quality of publicly available health workforce data sources in Australia: a scoping review protocol.

text: INTRODUCTION The health workforce is an integral component of the healthcare system. Comprehensive, high-quality data on the health workforce are essential to identifying gaps in health service provision, as well as informing future health workforce and health services planning, and health policy. While many data sources are used in Australia for these purposes, the quality of the data sources with respect to relevance, accessibility and accuracy is not clear. METHODS AND ANALYSIS This scoping review aims to identify and appraise publicly available data sources describing the Australian health workforce. The review will include any data source (eg, registry, administrative database and survey) or document reporting a data source (eg, journal article, report) on the Australian health workforce, which is publicly available and describes the characteristics of the workforce. The search will be conducted in 10 bibliographic databases and the grey literature using an iterative process. Screening of titles and abstracts will be undertaken by two investigators, independently, using Covidence software. Any disagreement between investigators will be resolved by a third investigator. Documents/data sources identified as potentially eligible will be retrieved in full text and reviewed following the same process. Data will be extracted using a customised data extraction tool. A customised appraisal tool will be used to assess the relevance, accessibility and accuracy of included data sources. ETHICS AND DISSEMINATION The scoping review is a secondary analysis of existing, publicly available data sources and does not require ethics approval. The findings of this scoping review will further our understanding of the quality and availability of data sources used for health workforce and health services planning in Australia. The results will be submitted for publication in peer-reviewed journals and presented at conferences targeted at health workforce and public health topics.


title: Diagnostics and laboratory role in outbreaks.

text: PURPOSE OF REVIEW The review describes the investigative benefits of traditional and novel molecular epidemiology techniques, while acknowledging the limitations faced by clinical laboratories seeking to implement these methods. RECENT FINDINGS Pulse-field gel electrophoresis and other traditional techniques remain powerful tools in outbreak investigations and continue to be used by multiple groups. Newer techniques such as matrix-assisted laser desorption/ionization-time of flight mass-spectrometry and whole genome sequencing show great promise. However, there is a lack of standardization regarding definitions for genetic relatedness, nor are there established criteria for accuracy and reproducibility. There are also challenges regarding availability of trained bioinformatics staff, and concerns regarding reimbursement. SUMMARY There are many tools available for molecular epidemiologic investigation. Epidemiologists and clinical laboratorians should work together to determine which testing methods are best for each institution.


title: COVID-19 Delays Cancer Screenings.

text: In recent months, the COVID-19 pandemic has caused many institutions to pause routine cancer screenings-delays that may not be problematic for patients but can create challenges for healthcare providers.


title: Single-port access in laparoscopic bilateral inguinal hernia repair: first clinical report of a novel technique.

text: PURPOSE To report the initial clinical case of single-port transabdominal preperitoneal (TAPP) bilateral inguinal hernia repair. METHODS One patient with symptomatic bilateral inguinal hernias underwent a single-port TAPP hernia repair using the Triport Single Port System (ASC, TriPort Laparoscopic Access Device, Wicklow, Ireland). The device was placed through a single supraumbilical incision. Hernia repair was performed with a typical TAPP technique with implantation of an Ultrapro Mesh (Ethicon, Norderstedt, Germany). RESULTS The procedure was technically successful without placement of additional trocars. Operative time was 120 min. No blood loss and no intraoperative complications were observed. The patient was discharged on the 2nd postoperative day and follow-up at 2 weeks demonstrated the patient to be without complaints with uncomplicated wound healing. CONCLUSION Single-port TAPP bilateral inguinal hernia repair is technically feasible and safe.


Oxygen and carbon dioxide targets during and after resuscitation of cardiac arrest patients.


title: A rational framework for selecting modes of ventilation.

text: Mechanical ventilation is a life-saving intervention for respiratory failure and thus has become the cornerstone of the practice of critical care medicine. A mechanical ventilation mode describes the predetermined pattern of patient-ventilator interaction. In recent years there has been a dizzying proliferation of mechanical ventilation modes, driven by technological advances and market pressures, rather than clinical data. The comparison of these modes is hampered by the sheer number of combinations that need to be tested against one another, as well as the lack of a coherent, logical nomenclature that accurately describes a mode. In this paper we propose a logical nomenclature for mechanical ventilation modes, akin to biological taxonomy. Accordingly, the control variable, breath sequence, and targeting schemes for the primary and secondary breaths represent the order, family, genus, and species, respectively, for the described mode. To distinguish unique operational algorithms, a fifth level of distinction, termed variety, is utilized. We posit that such coherent ordering would facilitate comparison and understanding of modes. Next we suggest that the clinical goals of mechanical ventilation may be simplified into 3 broad categories: provision of safe gas exchange; provision of comfort; and promotion of liberation from mechanical ventilation. Safety is achieved via optimization of ventilation-perfusion matching and pressure-volume relationship of the lungs. Comfort is provided by fostering patient-ventilator synchrony. Liberation is promoted by optimization of the weaning experience. Then we follow a paradigm that matches the technological capacity of a particular mode to achieving a specific clinical goal. Finally, we provide the reader with a comparison of existing modes based on these principles. The status quo in mechanical ventilation mode nomenclature impedes communication and comparison of existing mechanical ventilation modes. The proposed model, utilizing a systematic nomenclature, provides a useful framework to address this unmet need.


title: Role of infection in the development and exacerbation of asthma.

text: Respiratory infections are associated with wheezing illnesses in all ages and may also impact the development and severity of asthma. Respiratory tract infections caused by viruses, Chlamydophila or Mycoplasma have been hypothesized to have significant roles in the pathogenesis of asthma. Progress is being made toward establishing the mechanisms by which these agents can cause acute wheezing and impact the pathophysiology of asthma. Host factors probably contribute to the risk of asthma inception and exacerbation, and these contributions may also vary with respect to early- versus adult-onset disease. This review discusses these various associations as they pertain to the development and exacerbation of asthma.


How China is planning to go to Mars amid the coronavirus outbreak.


title: Robotically assisted laparoscopic repair of anterior vaginal wall and uterine prolapse by lateral suspension with mesh: initial experience and video.

text: INTRODUCTION AND HYPOTHESIS Sacral colpopexy/hysteropexy is a well-established approach to vaginal apex support and was the first technique used to treat pelvic organ prolapse (POP) with robotic assistance. However, dissection at the level of the promontory may be difficult, especially in obese patients, and associated with rare but potential serious morbidity such as life-threatening vascular injury. In an attempt to avoid this risk, we describe a new robotic approach for POP repair with lateral suspension. METHODS From March 2012 through June 2013, ten patients with symptomatic anterior vaginal wall and uterine prolapse were operated by a single surgeon. The video presents the different steps of robotically assisted laparoscopic repair of POP by lateral suspension with mesh and uterine conservation using da Vinci S or Si system. RESULTS POP repair was successfully completed in all ten patients without any perioperative or postoperative complication. CONCLUSION Robotically assisted laparoscopic repair of POP by lateral suspension with mesh is a novel and feasible technique with promising short-term results. It may have several theoretical advantages over sacral colpopexy/hysteropexy and may represent an alternative in cases of difficult dissection of the promontory.


title: Optimizing vaccine-induced CD8(+) T-cell immunity: focus on recombinant adenovirus vectors.

text: Recombinant adenoviruses have emerged as promising viral vectors for CD8(+) T-cell vaccines. Our studies have indicated that unlike most acute infections, the CD8(+) T-cell memory population elicited by recombinant human adenovirus serotype 5 (rHuAd5) displays a dominant effector memory phenotype. Persistent, low-level transgene expression from the rHuAd5 vector sustains the CD8(+) T-cell memory population and a nonhematopoietic cell compartment appears to be involved in long-term presentation of adenoviral antigens. Although we are beginning to learn more about the factors that control the maintenance and functionality of memory CD8(+) T cells, we do not yet fully understand what comprises a protective CD8(+) T-cell response. Results from upcoming Phase II clinical trials will be important for determining whether rHuAd5 T-cell vaccines are effective in humans and should help identify correlates of CD8(+) T-cell protection.


title: Changes in popliteal vein diameter and flow velocity with knee flexion and hyperextension.

text: OBJECTIVE To compare popliteal vein (PV) diameter and peak flow velocity generated by a calf compressor, when the knee is either flexed or hyperextended. METHOD Subjects lay supine on a couch with a calf compressor on each leg. Peak flow velocities in the PV were measured by duplex ultrasound during activation of the compressor, when the knee was either flexed or hyperextended. Hyperextension of the knee is seen when the heel is elevated to prevent heel pressure ulcers. RESULTS The results were analysed using the Wilcoxon signed rank test. This showed a significant increase in peak flow measurements related to narrowing of the PV when the knee was hyperextended. CONCLUSION There is a functional narrowing of the PV during hyperextension of the knee. We developed a model, which postulates an increase in the risk of deep vein thrombosis in patients whose knee is hyperextended. Based on this model, we suggest that the knee should be flexed slightly when patients are supine and anaesthetized.


title: Risk factors for bleeding evaluated using the Forrest classification in Japanese patients after endoscopic submucosal dissection for early gastric neoplasm.

text: BACKGROUND/AIMS Bleeding remains a serious complication after endoscopic submucosal dissection (ESD). Second-look endoscopy for hemostasis helps prevent post-ESD bleeding. We investigated the relationships between patient characteristics, tumor characteristics, and the Forrest classification for exposed vessels on artificial ulcers after ESD and evaluated whether hemostasis during second-look endoscopy was useful for preventing post-ESD bleeding. PATIENTS AND METHODS We analyzed 250 patients (265 lesions) who underwent ESD for gastric neoplasms. Vessels classified by Forrest classifications during scheduled second-look endoscopy were analyzed for associations with patient characteristics, tumor characteristics, and recurrent bleeding. RESULTS Two of 250 patients (0.8%) underwent emergency hemostatic endoscopy before scheduled second-look endoscopy. The remaining 248 patients (99.2%) underwent scheduled second-look endoscopy on the day after ESD. Patients with Forrest classification Ia, Ib, or IIa vessels had a significantly higher risk for recurrent bleeding after scheduled second-look endoscopy compared with patients with IIb or III vessels according to univariate analysis (P<0.05) and multivariate logistic regression analysis (odds ratio: 3.45; 95% confidence interval: 1.04-11.41; P=0.042). Univariate analysis indicated that hemodialysis correlated significantly with the presence of Ia, Ib, or IIa vessels compared with that of IIb or III vessels found during second-look endoscopy (P<0.05). Multivariate analysis indicated a significant relationship between hemodialysis and recurrent bleeding after second-look endoscopy (odds ratio: 10.05; 95% confidence interval: 1.97-51.26; P=0.006). CONCLUSION Hemodialysis is a risk factor for post-ESD bleeding. Proper classification of exposed vessels within post-ESD ulcers according to the Forrest classification using second-look endoscopy might help predict or prevent recurrent bleeding.


title: Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2.

text: Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics.Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication.Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen.Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects.Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.