Plasmapheresis Eliminates the Negative Impact of AAV Antibodies on Microdystrophin Gene Expression Following Vascular Delivery

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.     

Gallbladder Lesions Identified on Ultrasound. Lessons from the Last 10?Years

Background

Possible mass lesions identified on ultrasound (US) of the gallbladder may prompt an aggressive surgical intervention due to the possibility of a malignant neoplasm.

Aim

This study aims to utilize a large modern series of patients with gallbladder lesions identified on US to evaluate imaging characteristics consistent with malignancy.

Methods

A retrospective review was conducted of gallbladder ultrasound reports and clinicopathologic data of patients with a mass identified on US.

Results

Approximately 59,271 abdominal ultrasounds and 9,117 cholecystectomies were performed between February 2000 and February 2010. We identified 213 patients with a questionable gallbladder neoplasm on ultrasonography who underwent surgical exploration. Median age was 52?years (range?=?11?C87?years) and 147 (69%) were females. Final pathology demonstrated no neoplasm in 130 patients (61%), while 32 patients (15%) had a wall adenomyoma, 36 (17%) had a polyp (five of which were malignant), 14 (7%) had an adenocarcinoma not arising from a polyp, and one patient had a cystic papillary neoplasm. The smaller the lesion, the more likely it was to be a pseudo-mass. For lesions measuring <5?mm on US, 83% had no lesion found on final pathology. Significant predictors of malignancy were age >52?years (p?p?=?0.004), size >9?mm (p?p?5?mm (p?Conclusions Despite improvements in imaging, most apparent lesions measuring <5?mm on US are not identified in the surgical specimen. US size >9?mm, age >52?years, US suggestion of invasion at the liver interface, and wall thickening >5?mm, especially in the presence of gallstones, should raise the suspicion of malignancy.     

Electrochemical communication in biofilm of bacterial community

Electrochemical communication during biofilm formation has recently been identified. Bacteria within biofilm-adopt different strategies for electrochemical communication such as direct contact via membrane-bound molecules, diffusive electron transfer via soluble redox-active molecules, and ion channel-mediated long-range electrochemical signaling. Long-range electrical signals are important to communicate with distant members within the biofilm, which function through spatially propagating waves of potassium ion (K⁺) that depolarizes neighboring cells. During propagation, these waves coordinate between the metabolic states of interior and peripheral cells of the biofilm. The understanding of electrochemical communication within the biofilm may provide new strategies to control biofilm-mediated drug resistance. Here, we summarized the different mechanisms of electrochemical communication among bacterial populations and suggested its possible role in the development of high level of antibiotic resistance. Thus, electrochemical signaling opens a new avenue concerning the electrophysiology of bacterial biofilm and may help to control the biofilm-mediated infection by developing future antimicrobials.     

Imaging spectrum of abdominal manifestations of COVID-19

Coronavirus disease 2019 (COVID-19) has posed a serious threat to global public health with its rapid spread, high fatality, and severe burden on health care providers all over the world. Although COVID-19 has been established as a respiratory tract infection, it can manifest with gastrointestinal symptoms as a consequence of direct infection by the virus or due to inflammation-mediated cytotoxicity. It has been observed that COVID-19 patients presenting with gastrointestinal symptoms tend to progress to a severe form of disease with increased morbidity and mortality, thus indicating the need for timely management. COVID-19 manifests with a wide spectrum of radiologic findings on gastrointestinal tract imaging, encompassing bowel abnormalities, hepato-biliary and pancreatic involvement, vascular occlusion, and solid organ infarction. Early recognition of these imaging features can facilitate timely treatment of COVID-19 associated gastrointestinal tract complications and may prompt the diagnosis of COVID-19 in patients with atypical disease manifestations. The aim of this article is to provide an overview of the various gastrointestinal imaging manifestations that can be encountered in patients with COVID-19, with an emphasis on early diagnosis of the disease as well as treatment related complications.     

Lateral Ankle Sprain and Subsequent Ankle Sprain Risk: A Systematic Review

ObjectiveTo evaluate the evidence regarding the association between lateral ankle sprain (LAS) history and the subsequent LAS risk, as well as sex differences in the observed associations.Data SourcesPubMed, CINAHL, and SPORTDiscus were searched through July 2020 for articles on LAS history and incidence during the study period.Study SelectionStudies were included if they were prospective in nature and the authors reported the number of participants with and those without a history of LAS at study initiation as well as the number of participants in each group who sustained an LAS during the investigation.Data ExtractionData were study design parameters as well as the number of participants with and those without an LAS history and the number of subsequent LASs that occurred in both groups. Risk ratios (RRs) with 95% CIs compared the risk of LAS during the study period between those with and those without an LAS history for each investigation.Data SynthesisA total of 19 studies involving 6567 patients were included. The follow-up periods ranged from 14 weeks to 2 years. Assessment scores indicated the studies were of moderate to high quality. A significantly higher risk of LAS during the study period was observed among those with a history of LAS in 10 of 15 studies (RR range = 1.29–6.06). Similar associations were seen in 4 of 6 studies of all-male samples (RR range = 1.38–8.65) and 1 of 4 studies with an all-female sample (RR = 4.28).ConclusionsStrong evidence indicates that a previous LAS increased the risk of a subsequent LAS injury. Men with a history of LAS appeared to be at a higher risk of sustaining a subsequent LAS, but women were not. However, further data are needed to draw definitive conclusions from the limited number of sex-specific studies.     

Early,reliable, utilitarian predictive factors for fat embolism syndrome in polytrauma patients

Background:

Fat embolism is one of the apocalyptic pulmonary complications following high energy trauma situations. Since delay in diagnosis may have devastating consequences, early, easily accessible and relatively inexpensive investigations for risk stratification may prove useful, especially in developing nations.

Materials and Methods:

This prospective trial included a total of 67 young polytrauma patients, in whom the role of nine easily available, rapidly performable clinical or laboratory investigations (or observations noted at admission) in predicting the later occurrence of fat embolism syndrome were assessed. All the patients also underwent continuous monitoring of oxygen saturation with pulsoximetry.

Results:

The correlation between initial serum lactate (within 12 hours of injury) and hypoxia was statistically significant. There was a trend towards correlation with FES(by Gurd''s criteria) (P=0.07), Sensitivity of 24-hour monitoring of oxygen saturation in predicting later pulmonary deterioration approached 100%.

Conclusions:

The combination of three factors including polytrauma (with NISS >17), serum lactate >22 mmol/l at admission (within 12 hours of injury) fall in oxygen saturation (SaO₂ below 90% in the initial 24 hours) predict the development of post-traumatic pulmonary complications, especially the fat embolism syndrome.