Correction to: Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases -     

The Effects of Lysine Analogs During Pelvic Surgery: A Systematic Review and Meta-Analysis

Pelvic vasculature is complex and inconsistent while pelvic bones impede access to pelvic organs. These anatomical characteristics render pelvic surgery inherently difficult, and some of these procedures are frequently associated with blood loss that necessitates blood transfusion. The aim of this study was to review the literature on the use of lysine analogs to prevent bleeding and blood transfusion during pelvic surgery. The objective of this study was to assess the safety and efficacy of lysine analogs during pelvic surgery. A systematic literature search was performed using Medline, Cochrane Register of Clinical Trials, Embase, and the reference lists of relevant articles. Randomized controlled trials or observational cohort studies comparing a lysine analog to placebo or standard care were included. Outcomes collected were blood transfusion, blood loss, thromboembolic adverse events (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism), nonthromboembolic adverse events, and death. There were no language limitations. Fifty-six articles reported on 68 comparisons between a lysine analog and an inactive comparator, involving a total of 7244 patients published between 1961 and 2013. Thirty-nine studies evaluated urologic procedures, and 21 evaluated gynecologic procedures. Thirty-six studies (60%) were published before 1980. Of the 43 randomized comparisons, only 30 (44%) had a score of 3 or higher on Jadad's 5-point scale of methodological quality. Among randomized trials, lysine analogs reduced the risk of blood transfusion (pooled odds ratio [OR], 0.47; 95% confidence interval [CI], 0.35-0.64) and blood loss (pooled OR, 0.22; 95% CI, 0.18-0.27). There was a small statistically insignificant increased risk of thromboembolic events (pooled OR, 1.07; 95% CI, 0.72-1.59) and no-thrombotic serious adverse events (pooled OR, 1.11; 95% CI, 0.67-1.83). In the 17 randomized trials published since the year 2000, only 6 thrombotic events were reported, 4 of which occurred in the placebo arm. Lysine analogs did not increase risk of death (pooled OR, 0.91; 95% CI, 0.34-2.48). These results are significant as they indicate that lysine analogs significantly reduce blood loss and blood transfusion during pelvic surgery. Although there does not appear to be a large increase in the risk of thromboembolic and nonthrombotic adverse events, more data are required to definitively assess these outcomes. Based on this review, lysine analogs during pelvic surgery seem to reduce bleeding and blood transfusion requirements. Although there does not seem to be a significant risk of adverse effects, larger studies would help clarify risks, if any, associated with lysine analog use.     

Near full-length HIV type 1M genomic sequences from Cameroon : Evidence of early diverging under-sampled lineages in the country

Background: Cameroon is the country in which HIV-1 group M (HIV-1M) likely originated and is today a major hotspot of HIV-1M genetic diversity. It remains unclear, however, whether the highly divergent HIV-1M lineages found in this country arose during the earliest phases of the global HIV-1M epidemic, or whether they arose more recently as a result of recombination events between globally circulating HIV-1M lineages.Methodology: To differentiate between these two possibilities, we performed phylogenetic analyses of the near full genome sequences of nine newly sequenced divergent HIV-1M isolates and 15 previously identified, apparently unique recombinant forms (URFs) from Cameroon.Results: Although two of the new genome sequences were clearly classifiable within subtype G, the remaining seven were highly divergent and phylogenetically branched either outside of, or very near the bases of clades containing the well characterised globally circulating viral lineages that they were most closely related to. Recombination analyses further revealed that these divergent viruses were likely complex URFs. We show, however that substantial portions (>1 Kb) of three of the new genome sequences and 15 of the previously characterised Cameroonian URFs have apparently been derived from divergent parental viruses that branch phylogenetically near the bases of the major HIV-1M clades.Conclusions and implications: Our analyses indicate the presence in Cameroon of contemporary descendants of numerous early-diverging HIV-1M lineages. Further efforts to sample and sequence viruses from such lineages could be crucial both for retracing the earliest evolutionary steps during the emergence of HIV-1M in humans, and accurately reconstructing the ancestral sequences of the major globally circulating HIV-1M lineages.     

Anatomical basis for the intrahepatic glissonian approach during hepatectomies

Background

Anatomical liver resections are based on some basic technical principles such as vascular control, ischemic area delineation to be resected and maximum parenchymal preservation. These aspects are achieved by the intrahepatic glissonian approach, which consists in accessing the pedicles of hepatic segments within the hepatic parenchyma. Small incisions on well-defined anatomical landmarks are performed to approach the pedicles, making dissection of the hilar plate unnecessary.

Aim

Analyze parameters in liver anatomy related to intrahepatic surgical technique to glissonians pedicles, to set the normal anatomy related to the procedure and thereby facilitate the attainment of this technique.

Methods

Anatomical parameters related to the intrahepatic glissonian approach were studied in 37 cadavers. Measurements were performed with precision instruments. Data were expressed as mean±standard deviation. The subjects were divided into groups according to gender and liver weight and groups were compared statistically.

Results

Twenty-five cadavers were male and 12 female. No statistically significant difference was observed in virtually all parameters when groups were compared. This demonstrates the consistency of the anatomical parameters related to the intrahepatic glissonian approach.

Conclusion

The results obtained in this study made possible major technical advances in the realization of open and laparoscopic hepatectomies with intrahepatic glissonian approach, and can help surgeons to perform liver resections by this method.     

Concept of variable angle locking—evolution and mechanical evaluation of a recent technology

Applications for fracture‐adapted screw positioning offered by variable angle locking screws are increasing. The locking strength of the variable angle locking mechanism at different insertion angles was compared to conventional fixed angle locking screws. Stainless steel (S) and titanium (Ti) variable and fixed angle 2.4 mm locking screws, inserted at different inclinations (0°?15°), and locked at 0.8 Nm were subjected to a load‐to‐failure test. Ultimate failure moment at the screw‐head interface and failure mode of the screws were determined. Significant differences were detected by one‐way ANOVA (p < 0.05). Stainless steel and titanium variable angle locking screws inserted at 2°?10° inclination exhibited a failure moment comparable to the 0° position (S 1.67± 0.04 Nm; Ti 1.67 ± 0.14 Nm) and failed predominantly at the screw neck, with the head remaining fixed to the plate. Inserted at 15° inclination, screws revealed a lower failure moment (S 1.33 ± 0.06 Nm, Ti 1.58 ± 0.05Nm), and failed predominantly by breakout of the head thread. Fixed angle locking screws inserted at an inclination >2° did not lock properly in the plate hole, providing insufficient locking strength. Variable angle locking screws offer a stable head‐locking mechanism at different inclinations, comparable to the locking strength of orthogonal inserted fixed angle locking screws. Marginal inclinations >15° should be used with care. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:988–992, 2015.

     

Three-dimensional model of surfactant replacement therapy

Surfactant replacement therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. It is widely successful for treating surfactant deficiency in premature neonates who develop neonatal respiratory distress syndrome (NRDS). However, when applied to adults with acute respiratory distress syndrome (ARDS), early successes were followed by failures. This unexpected and puzzling situation is a vexing issue in the pulmonary community. A pressing question is whether the instilled surfactant mixture actually reaches the adult alveoli/acinus in therapeutic amounts. In this study, to our knowledge, we present the first mathematical model of SRT in a 3D lung structure to provide insight into answering this and other questions. The delivery is computed from fluid mechanical principals for 3D models of the lung airway tree for neonates and adults. A liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug deposits a coating film on the airway wall and then splits unevenly at the bifurcation due to gravity. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published procedural methods, we show the neonatal lung is a well-mixed compartment, whereas the adult lung is not. The earlier, successful adult SRT studies show comparatively good index values implying adequate delivery. The later, failed studies used different protocols resulting in very low values of both indexes, consistent with inadequate acinar delivery. Reasons for these differences and the evolution of failure from success are outlined and potential remedies discussed.Since the early 1980s, surfactant replacement therapy (SRT) has been successful in applications to prematurely born neonates to treat their lack of surfactant production, which normally initiates late in gestation (1). Because surfactant reduces the surface tension between the air and the lung’s liquid lining, its deficiency creates high surface tensions and collapsed, stiff lungs making them difficult to inflate. The resulting clinical entity of labored breathing and poor oxygenation is called neonatal respiratory distress syndrome (NRDS), or hyaline membrane disease, and is a risk of premature birth increasing with decreasing gestational age. The incidence is ∼1% of all births, equating to 40,000 cases annually in the United States (2). The mortality associated with NRDS dropped from 4,997 deaths in 1980 to 861 in 2005, and SRT played an important role in this success (3).SRT has also been tried in adults whose surfactant systems are compromised by acute respiratory distress syndrome (ARDS). ARDS results from overwhelming infections, mechanical injuries, and other insults either directly or indirectly to the lung. ARDS cases in the United States total 190,600 annually with a 39% mortality rate yielding 74,500 deaths (4). Although some early SRT large-animal and adult clinical trials were successful (5–8), subsequent studies were failures (9–11). The field is looking for direction, with concerns ranging from the delivered surfactant biochemistry to the persistence of the underlying ARDS disease to the adequacy of delivery (12). The model presented here addresses the delivery issue and shows that simulations of these adult SRT studies produce significantly different delivery distributions that can explain success vs. failure.Effective drug delivery is a major medical challenge. First mathematical models for i.v. (13), oral (14), and aerosol (15) modalities contributed to the development of those fields simulating drug uptake, distribution, metabolism, and elimination. The role of models is to interpret data mechanistically, predict outcomes, follow treatment courses, relate dose to response, establish safety criteria, design new drugs and delivery strategies, compare animal experiments to human applications, and tailor protocols to patient specific circumstances. To our knowledge, the work presented here is the first structural model of SRT with the same goals. It quantifies the physics of two-phase fluid flow, air and liquid, into a branching network of airways representing the lung (16–18). Our model provides a mechanistic foundation for SRT delivery, which turns out to be a highly nonlinear process. A working SRT model can have a significant impact on this field, moving it from a process of informed trial and error to one that harnesses the underlying fundamental mechanisms.In SRT, the instilled mixture can form a liquid plug in the trachea (19), which then propagates through the tracheobronchial tree by forced inspiratory airflow. As the liquid plug propagates distally, it coats the airway walls, losing some of its mass, and also splits at bifurcations. Our mathematical model considers these two important steps in sequence. For step A (airway), the propagating plug deposits some content onto the airway walls into a trailing film. This deposition, or coating, reduces efficiency because less surfactant mixture reaches the acinus. Our experimentally validated theory predicts the trailing film thickness as a function of plug viscosity, speed, surface tension, and tube radius from computational fluid dynamics results (17). Then, in step B (bifurcation), the plug splits at an airway bifurcation in an uneven manner due to gravity, favoring the steepest downhill daughter tube, so reduces distribution homogeneity. The larger the structure (adult lungs), the greater is this reduction. For this step, we compute the ratio of the split volumes from conservation of momentum and mass. This split ratio depends on the plug speed, viscosity, surface tension, bifurcation geometry, and orientation with gravity (20, 21). Each step is performed sequentially through a 3D tree construct with the geometrical features of the conducting airways (22, 23) (Materials and Methods). The time period for the flow is a single forced inspiration. A larger fluid velocity yields more even splitting, improving homogeneity, but leaves a thicker wall deposition layer, reducing efficiency. The resulting distribution of SRT depends on the competition between these two fluid mechanical phenomena.