Isolated Internuclear Ophthalmoplegia as an Embolic Complication of Transcatheter Aortic Valve Implantation.

An 83-year-old male developed horizontal diplopia immediately following elective transfemoral transcatheter aortic valve implantation (TAVI). On right gaze, left eye adduction was impaired while there was horizontal nystagmus of the abducting right eye, representative of internuclear ophthalmoplegia (INO). The remainder of the neurological examination was normal. Computer tomography (CT) imaging of the brain and CT angiogram of the head and neck were normal. Magnetic resonance imaging (MRI) of the brain showed five small foci of restricted diffusion affecting both the anterior and posterior circulation bilaterally. One such tiny infarct was seen in the left parasagittal upper pontine tegmentum and was attributed to his presentation. While all symptoms rapidly improved, minimal residual signs of INO were still detectable at the six-month follow-up. Isolated intra-nuclear ophthalmoplegia is a rare stroke syndrome and an unusual cardio-embolic complication of minimally invasive cardiac procedures. TAVI is an increasingly popular technique, although has been associated with a higher incidence of micro-embolic cerebrovascular events evident on MRI than surgical repairs. While the use of embolic protection devices has high-quality evidence in reducing the burden of these usually silent cerebrovascular events, their role in preventing long-term neurocognitive sequala has not been demonstrated.

SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.

Sepsis and the Microbiome: A Vicious Cycle.

Sepsis has been characterized as a dysregulated host response to infection, and the role of the microbiome as a key influencer of this response is emerging. Disruption of the microbiome while treating sepsis with antibiotics can itself result in immune dysregulation. Alterations in the gut microbiome resulting from sepsis and its treatment have been implicated in organ dysfunction typical of sepsis across multiple tissues including the lung, kidney, and brain. Multiple microbiota-directed interventions are currently under investigation in the setting of sepsis, including fecal transplant, the administration of dietary fiber, and the use of antibiotic scavengers that attenuate the effects of antibiotics on the gut microbiota while allowing them to concentrate at the primary sites of infection. The emerging evidence shows that the gut microbiome interacts with various elements of the septic response, and provides yet another reason to consider the judicious use of antibiotics via antibiotic stewardship programs.

SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.

Variation in Ventilator Allocation Guidelines by US State During the Coronavirus Disease 2019 Pandemic: A Systematic Review.

Importance: During the coronavirus disease 2019 pandemic, there may be too few ventilators to meet medical demands. It is unknown how many US states have ventilator allocation guidelines and how these state guidelines compare with one another. Objective: To evaluate the number of publicly available US state guidelines for ventilator allocation and the variation in state recommendations for how ventilator allocation decisions should occur and to assess whether unique criteria exist for pediatric patients. Evidence Review: This systematic review evaluated publicly available guidelines about ventilator allocation for all states in the US and in the District of Columbia using department of health websites for each state and internet searches. Documents with any discussion of a process to triage mechanical ventilatory support during a public health emergency were screened for inclusion. Articles were excluded if they did not include specific ventilator allocation recommendations, were in draft status, did not include their state department of health, or were not the most up-to-date guideline. All documents were individually assessed and reassessed by 2 independent reviewers from March 30 to April 2 and May 8 to 10, 2020. Findings: As of May 10, 2020, 26 states had publicly available ventilator guidelines, and 14 states had pediatric guidelines. Use of the Sequential Organ Failure Assessment score in the initial rank of adult patients was recommended in 15 state guidelines (58%), and assessment of limited life expectancy from underlying conditions or comorbidities was included in 6 state guidelines (23%). Priority was recommended for specific groups in the initial evaluation of patients in 6 states (23%) (ie, Illinois, Maryland, Massachusetts, Michigan, Pennsylvania, and Utah). Many states recommended exclusion criteria in adult (11 of 26 states [42%]) and pediatric (10 of 14 states [71%]) ventilator allocation. Withdrawal of mechanical ventilation from a patient to give to another if a shortage occurs was discussed in 22 of 26 adult guidelines (85%) and 9 of 14 pediatric guidelines (64%). Conclusions and Relevance: These findings suggest that although allocation guidelines for mechanical ventilatory support are essential in a public health emergency, only 26 US states provided public guidance on how this allocation should occur. Guidelines among states, including adjacent states, varied significantly and could cause inequity in the allocation of mechanical ventilatory support during a public health emergency, such as the coronavirus disease 2019 pandemic.

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

OBJECTIVE: We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH). METHODS: Two pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture. Capillary proliferation (CP) within the alveolar walls was measured by its distribution, extent (CP % involvement), and maximum number of layers (maximum CP). These measures were then evaluated to determine the strength of their association with right heart catheterization-proven PH. RESULTS: Using consensus measures, all measures of CP were significantly associated with PH. Maximum CP had the strongest association with PH (P = 0.013; C statistic 0.869). Maximum CP 2 or more layers and CP % involvement 10% or greater were the optimal thresholds that predicted PH, both with a sensitivity of 56% and specificity of 91%. The CP was typically multifocal rather than focal or diffuse and was associated with a background pattern of usual interstitial pneumonia. There was a significant but weaker relationship between the presence of abnormal small arteries and veins and PH. CONCLUSION: In the setting of advanced SSc-PF, the histopathologic feature of the pulmonary microcirculation best associated with PH was capillary proliferation in architecturally preserved lung areas.

Development of Pd/C-catalyzed cyanation of aryl halides.

A practical method for palladium-catalyzed cyanation of aryl halides using Pd/C is described. The new method can be applied to a variety of aryl bromide and active aryl chloride substrates to effect efficient conversions. The process features many advantages over existing cyanation conditions and the practical utility of the process has been demonstrated on scale.

Spine behavior caudal to instrumentation in King II and IV curves.

This retrospective review of children surgically treated for King Type II or IV curvature of the spine required a minimum lumbar Cobb angle of 40 degrees and a minimum lumbar inclination (the angle formed between a line through the spinous processes of the three most caudal lumbar vertebrae and a line perpendicular to the floor) of 10 degrees. Twenty children had combined anterior thoracolumbar and posterior instrumentations whereas 20 had only posterior instrumentation. Children who had combined surgery had significantly better corrections of their lumbar Cobb angles. They had a mean correction of 43.3 degrees compared with 26.7 degrees in children with posterior instrumentation only. These superior corrections of the lumbar Cobb angles did not result in significantly better improvements in the lumbar inclinations. Patients who had the combined procedures had a mean improvement of 10.1 degrees, whereas patients who had posterior instrumentation only had a mean improvement of 8.0 degrees in lumbar inclination. Instead of having superior corrections of the lumbar inclinations, the combined surgeries resulted in a significant worsening of the angle between the end plates of the last instrumented vertebra and the next most caudal end plate. In patients who had combined surgery this angle averaged 8.4 degrees, whereas in patients who had posterior instrumentation only this angle averaged 4.1 degrees.