Sterilising immunity that blocks infection for life, and thus prevents illness after infection, is the ultimate goal for vaccines. Neither influenza infection nor vaccination provide sterilising ...immunity. Mutations during influenza viral genome replication result in the emergence of viruses that evade immunity and cause reinfections. Waning of immunity also results in reinfections to homologous influenza viruses. However, immunity might limit the severity of disease after infection or vaccination (ie, immunoattenuation). We provide a comprehensive examination of experimental and observational peer reviewed evidence since 1933, when the first influenza virus was isolated, on whether immunity blocks subsequent infection or attenuates illness. Although an abundance of experimental evidence supports immunoattenuation, clinical evidence is rudimentary and conflicting. To the extent that immunoattenuation occurs, understanding the varied pathways to illness, pathogenesis, clinical manifestations, and correlates of attenuation can improve the design and evaluation of influenza vaccines. By elucidating the mechanisms of immunoattenuation and phenotypes of illness, we clarify ambiguities and identify unmet needs that, if addressed with priority, could strategically improve the design of vaccines for the prevention of influenza.
To test the hypothesis that relatively lower clot strength on thromboelastography maximum amplitude (MA) is associated with development of venous thromboembolism (VTE) in critically ill patients with ...COVID-19.
Prospective, observational cohort study.
Tertiary care, academic medical center in Nashville, TN.
Patients with acute respiratory failure from COVID-19 pneumonia admitted to the adult medical ICU without known VTE at enrollment.
None.
Ninety-eight consecutive critically ill adults with laboratory-confirmed COVID-19 were enrolled. Thromboelastography parameters and conventional coagulation parameters were measured on days 0 (within 48 hr of ICU admission), 3, 5, and 7 after enrollment. The primary outcome was diagnosis of VTE with confirmed deep venous thrombosis and/or pulmonary embolism by clinical imaging or autopsy. Twenty-six patients developed a VTE. Multivariable regression controlling for antiplatelet exposure and anticoagulation dose with death as a competing risk found that lower MA was associated with increased risk of VTE. Each 1 mm increase in enrollment and peak MA was associated with an 8% and 14% decrease in the risk of VTE, respectively (enrollment MA: subdistribution hazard ratio SHR, 0.92; 95% CI, 0.87-0.97;
= 0.003 and peak MA: SHR, 0.86; 95% CI, 0.81-0.91;
< 0.001). Lower enrollment platelet counts and fibrinogen levels were also associated with increased risk of VTE (
= 0.002 and
= 0.01, respectively). Platelet count and fibrinogen level were positively associated with MA (multivariable model: adjusted
= 0.51;
< 0.001).
When controlling for the competing risk of death, lower enrollment and peak MA were associated with increased risk of VTE. Lower platelet counts and fibrinogen levels at enrollment were associated with increased risk of VTE. The association of diminished MA, platelet counts, and fibrinogen with VTE may suggest a relative consumptive coagulopathy in critically ill patients with COVID-19.
To evaluate technical feasibility, complications, and clinical outcomes of endovascular thrombolysis for iliofemoral thrombosis at two tertiary-care children's hospitals.
Institutional review ...board-approved retrospective review from March 2003 through June 2013 showed that venous thrombolysis for iliofemoral thrombosis was performed in 57 children (64 limbs) with a median age of 16.1 years (mean age, 14.5 y; range, 1.0-17.8 y). Techniques included catheter-directed thrombolysis (CDT), percutaneous mechanical thrombectomy (PMT), and pharmacomechanical catheter-directed thrombolysis (PCDT) with adjunctive angioplasty and/or stent placement. Villalta and modified Villalta scales were applied retrospectively to follow-up data to assess postthrombotic syndrome (PTS).
Technical success (≥ 50% thrombolysis) rate was 93.7%: grade III (100%) in 19 limbs, grade II (50%-99%) in 41 limbs, and grade I (< 50%) in four limbs. Techniques included CDT with PCDT (32.8%) or PMT (35.9%), CDT alone (26.6%), PCDT alone (4.7%) or with adjunctive angioplasty (54.7%), and stent placement (6.3%). Mean duration of CDT was 36.5 hours (range, 2.9-89.6 h). There was one major complication (1.8%) of bleeding requiring transfusion. Minor complications (ie, bleeding) occurred in seven patients (12.2%). Median follow-up was 1.5 years (range, 30 d to 7 y). Seven patients underwent repeat thrombolysis for recurrent thrombosis. The PTS rate was 59.3% per modified Villalta scale but only 2.1% per Villalta scale.
Endovascular thrombolysis is technically feasible and safe for iliofemoral thrombosis in children. Variable results were seen with two scales to assess PTS, suggesting an acute need for standardization of outcome measurement in children.
Objective To evaluate rates of intussusception hospitalization among infants in Vietnam before the introduction of rotavirus vaccine. Study design Between 2009 and 2011, we identified intussusception ...hospitalizations among infants using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification code K56.1 at 2 large pediatric hospitals in Ho Chi Minh City, Vietnam that treat most of the intussusception cases in the city. We reviewed all medical records to confirm a Brighton level 1 case definition for intussusception. Results We identified a total of 869 intussusception cases in Ho Chi Minh City during the 3-year study period, for an annual rate of 296 per 100 000 infants. The mean age of intussusception was ∼37 weeks (8.6 months), with <2% of the cases occurring before age 15 weeks. Cases of intussusception were observed year-round in these hospitals with no evident seasonal pattern. Ultrasonography was used to diagnose most cases (97%), and reduction was performed by air enema in >95% of the cases, with only 1% of cases at 1 hospital and 5% at the other hospital requiring surgical intervention. Ultrasound diagnosis was confirmed by an independent radiologist in 94% of a randomly selected group of intussusception cases at 1 of the 2 hospitals. No mortality was reported. Conclusion Vietnam has a substantially higher rate of intussusception in children aged >15 weeks compared with most other regions of the world. Most of our cases were diagnosed by ultrasound, and only a small proportion required surgical intervention with no fatalities, suggesting that the higher rates may be related in part to better and earlier detection of intussusception.
Determine if thromboelastography parameters and platelet count on the day of ICU admission are associated with the development of venous thromboembolism in patients with coronavirus disease 2019.
...Prospective, observational cohort study.
Tertiary-care, academic medical center in Nashville, TN.
Patients with coronavirus disease 2019 pneumonia and acute respiratory failure admitted to the adult ICU without venous thromboembolism at the time of ICU admission.
None.
The primary outcome was development of venous thromboembolism during the index hospitalization. Venous thromboembolism was defined by clinical imaging or autopsy, demonstrating deep vein thrombosis or pulmonary embolism. Forty consecutive critically ill adults with laboratory-confirmed coronavirus disease 2019 were enrolled; 37 (92.5%) were hypercoagulable by at least one thromboelastography parameter at the time of ICU admission and 12 (30%) met the primary outcome of venous thromboembolism during the index hospitalization. Patients who developed venous thromboembolism had decreased measures of clotting (maximum amplitude, alpha angle, shear elastic modulus parameter, and clotting index) on ICU admission thromboelastography compared with patients who did not develop venous thromboembolism (
< 0.05 for all measures). For each individual thromboelastography parameter used to dichotomize patients as hypercoagulable, the rate of venous thromboembolism was not higher in those identified as hypercoagulable; in fact, the venous thromboembolism rate was higher in patients who were not hypercoagulable by thromboelastography for maximum amplitude (
= 0.04) and alpha angle (
= 0.001). Platelet count was positively correlated with maximum amplitude, alpha angle, G parameter, and clotting index, and significantly lower in patients who developed venous thromboembolism than those who did not (median 186 vs 278 10
/μL,
= 0.046). Venous thromboembolism was associated with inhospital mortality (odds ratio, 6.3; 95% CI, 1.4-29;
= 0.02).
Our data do not support the use of thromboelastography to risk stratify critically ill adults with coronavirus disease 2019 for the development of venous thromboembolism or to guide decisions about anticoagulation. Lower platelet count on ICU admission, which may reflect platelet aggregation, was associated with venous thromboembolism.
To evaluate the technical feasibility and safety of percutaneous endovascular thrombolysis for extremity deep venous thrombosis (DVT) in children < 24 months old.
A retrospective chart review of a ...clinical and imaging database was performed for pediatric patients who underwent endovascular therapy for DVT between January 2010 and July 2013. Indications, techniques, technical and clinical success, and complications were reviewed. Techniques for thrombolysis included catheter-directed therapy (CDT) using alteplase infusion via a multi-side hole catheter, mechanical thrombectomy, and angioplasty. Short-term outcomes were assessed using surgical and imaging follow-up examinations for patency of the targeted vessel. Patients included 11 children (mean age, 9 mo; range, 3 wk-23 mo) who consecutively underwent endovascular thrombolysis for upper extremity (n = 6) or lower extremity (n = 5) DVT. The most common indication was preservation of venous access for future cardiac surgery or medical therapy.
The most common risk factor was the presence of a central venous catheter (10 of 11 patients). All patients with upper extremity DVT had congenital heart disease. CDT and angioplasty were performed in all patients. Venous patency was established in all patients. A grade III (95%-100%) thrombolysis response was achieved in seven patients, and a grade II (50%-95%) thrombolysis response was achieved in four patients. A major complication of pulmonary embolism occurred in one patient with upper extremity thrombolysis and was managed by intravenous systemic alteplase and heparin. No recurrence of thrombosis was found on average follow-up of 11.8 months (range, 1-41 mo).
Percutaneous endovascular thrombolysis for extremity DVT is safe and technically feasible in children < 24 months old.
Abstract Background Sialorrhea is problematic for neurologically impaired children, and botulinum toxin A salivary gland injection has been reported as effective in reducing sialorrhea. This article ...assesses the success and safety of ultrasound-guided weight-based botulinum toxin A injection for the management of sialorrhea in children. Methods A total of 111 patients (63 males; 48 females; average age 7 years) with refractory sialorrhea were treated with ultrasound-guided botulinum toxin type A salivary gland injections (144 procedures) from July 1, 2004, to July 1, 2014, using a single weight-based protocol. Patient history, procedural records, and clinical follow-up documents were retrospectively reviewed. Clinical data were compared with reported effectiveness and complications using odds ratios. Results A total of 144 procedures were performed in 111 patients with refractory sialorrhea. Cerebral palsy was the most common underlying etiology for sialorrhea (29%), whereas others included encephalopathy (5%), anoxic brain injury (4%), and a variety of chromosomal anomalies (5%). There was a 100% technical success rate. Overall treatment effectiveness was 68%. Repeat injections were not associated with increased clinical success. No procedure-related deaths or major complications were identified; the minor complication rate was less than 2%. Conclusions The protocol used for ultrasound-guided injection of botulinum toxin A proved to be safe and effective in children suffering from sialorrhea. Image guidance technique may lead to a reduction in rates of adverse events reported in other series. Subsequent procedures do not improve upon initial efficacy.
Background:
Hindfoot and ankle fusions are mechanically limiting procedures for patients. However, patient-reported outcomes of these procedures have not been well studied. This study assessed ...outcomes of hindfoot and ankle fusions by using Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) Computer Adaptive Tests (CATs).
Methods:
Between 2014 and 2018, 102 patients were prospectively enrolled after presenting to a tertiary care facility for ankle and hindfoot fusions, including tibiotalar, tibiotalocalcaneal, subtalar, and triple arthrodeses. Study participants completed preoperative and 12-month postoperative PF and PI CATs. The differences between mean 12-month postoperative and preoperative PROMIS PF and PI T scores were analyzed with paired t tests. The relationship between the 12-month PF and PI differences for the overall sample and patient factors was examined using multiple regression modeling.
Results:
The sample had mean age of 57.69 years; 48% were male, and 55% were obese. Patients who underwent ankle and hindfoot arthrodesis had statistically significant improvements from preoperative to 12 months postoperative in mean PF (36.26±7.85 vs 39.38±6.46, P = .03) and PI (61.07±7.75 vs 56.62±9.81, P = .02). Triple arthrodesis saw the greatest increases in physical function (▵PF = 7.22±7.31, P = .01) and reductions in pain (▵PI = –9.17±8.31, P = .01), achieving minimal clinically important difference (MCID). Patients who underwent tibiotalar fusion had significant improvement in physical function (▵PF = 4.18±5.68, P = .04) and pain reduction that approached statistical significance (▵PI = –6.24±8.50, P = .09), achieving MCID. Older age (≥60 years ) was associated with greater improvements in PF (β = 0.20, P = .07) and PI (β = –0.29, P = .04). Preoperative PF and PI T scores were significantly associated with the 12-month change in PF and PI T scores, respectively (β = –0.74, P < .01; β = –0.61, P < .01).
Conclusion:
Hindfoot and ankle fusions are procedures with favorable patient outcomes leading to increased physical function and decreased pain at 12 months postoperation relative to preoperation.
Level of Evidence:
Level II, prospective comparative study.
Although deaths are often reported in the context of norovirus outbreaks, clinical and epidemiologic characteristics of the decedents prior to death are not well established. Through a literature ...review of published reports of deaths associated with norovirus infection, we identified and summarized 158 norovirus-associated deaths in 12 countries from 1988 to 2011.
To measure and compare individual staff radiation dose levels during interventional radiologic (IR) procedures with and without real-time feedback to evaluate whether it has any impact on staff ...radiation dose.
A prospective trial was performed in which individuals filling five different staff roles wore radiation dosimeters during all IR procedures during two phases: a 12-week "closed" phase (measurements recorded but display was off, so no feedback was provided) and a 17-week "open" phase (display was on and provided real-time feedback). Radiation dose rates were recorded and compared by Mann-Whitney U test.
There was no significant difference in median procedure time, fluoroscopy time, or patient dose (dose-area product normalized to fluoroscopy time) between the two phases. Overall, the median staff dose was lower in the open phase (0.56 µSv/min of fluoroscopy time) than in the closed phase (3.01 µSv/min; P < .05). The IR attending physician dose decreased significantly for procedures for which the physicians were close to the patient, but not for ones for which they were far away.
A radiation dose monitoring system that provides real-time feedback to the interventional staff can significantly reduce radiation exposure to the primary operator, most likely by increasing staff compliance with use of radiation protection equipment and dose reduction techniques.
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