Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

Combining Procalcitonin and Rapid Multiplex Respiratory Virus Testing for Antibiotic Stewardship in Older Adult Patients With Severe Acute Respiratory Infection.

OBJECTIVES: Virus infection is underevaluated in older adults with severe acute respiratory infections (SARIs). We aimed to evaluate the clinical impact of combining point-of-care molecular viral test and serum procalcitonin (PCT) level for antibiotic stewardship in the emergency department (ED). DESIGN: A prospective twin-center cohort study was conducted between January 2017 and March 2018. SETTING AND PARTICIPANTS: Older adult patients who presented to the ED with SARIs received a rapid molecular test for 17 respiratory viruses and a PCT test. MEASURES: To evaluate the clinical impact, we compared the outcomes of SARI patients between the experimental cohort and a propensity score-matched historical cohort. The primary outcome was the proportion of antibiotics discontinuation or de-escalation in the ED. The secondary outcomes included duration of intravenous antibiotics, length of hospital stay, and mortality. RESULTS: A total of 676 patients were included, of which 169 patients were in the experimental group and 507 patients were in the control group. More than one-fourth (27.9%) of the patients in the experimental group tested positive for virus. Compared with controls, the experimental group had a significantly higher proportion of antibiotics discontinuation or de-escalation in the ED (26.0% vs 16.1%, P = .007), neuraminidase inhibitor uses (8.9% vs 0.6%, P < .001), and shorter duration of intravenous antibiotics (10.0 vs 14.5 days, P < .001). CONCLUSIONS AND IMPLICATIONS: Combining rapid viral surveillance and PCT test is a useful strategy for early detection of potential viral epidemics and antibiotic stewardship. Clustered viral respiratory infections in a nursing home is common. Patients transferred from nursing homes to ED may benefit from this approach.

National retrospective cohort study to identify age-specific fatality risks of comorbidities among hospitalised patients with influenza-like illness in Taiwan.

OBJECTIVES: This study aimed to examine comprehensively the prognostic impact of underlying comorbidities among hospitalised patients with influenza-like illness (ILI) in different age groups and provide recommendations targeting the vulnerable patients. SETTING AND PARTICIPANTS: A retrospective cohort of 83 227 hospitalised cases with ILI were identified from Taiwan's National Health Insurance Research Database from January 2005 to December 2010. Cases were stratified into three different age groups: paediatric (0-17 years), adult (18-64 years) and elderly (≧65 years), and their age, sex, comorbidity and past healthcare utilisation were analysed for ILI-associated fatality. MAIN OUTCOME MEASURES: ORs for ILI-related fatality in different age groups were performed using multivariable analyses with generalised estimating equation models and adjusted by age, sex and underlying comorbidities. RESULTS: Hospitalised ILI-related fatality significantly increased with comorbidities of cancer with metastasis (adjusted OR (aOR)=3.49, 95% CI: 3.16 to 3.86), haematological malignancy (aOR=3.02, 95% CI: 2.43 to 3.74), cancer without metastasis (aOR=1.72, 95% CI: 1.54 to 1.91), cerebrovascular (aOR=1.24, 95% CI: 1.15 to 1.33) and heart diseases (aOR=1.19, 95% CI: 1.11 to 1.27) for all age groups. Adult patients with AIDS; adult and elderly patients with chronic kidney disease, tuberculosis and diabetes were significantly associated with elevated risk of death. Severe liver diseases and hypothyroidism among elderly, and dementia/epilepsy among elderly and paediatrics were distinctively associated with likelihood of ILI-related fatality. CONCLUSIONS: Different age-specific comorbidities were associated with increasing risk of death among hospitalised ILI patients. These findings may help update guidelines for influenza vaccination and other prevention strategies in high-risk groups for minimising worldwide ILI-related deaths.

Utility of a blood culture time to positivity-incorporated scoring model in predicting vascular infections in adults with nontyphoid Salmonella bacteremia.

BACKGROUND: Vascular infections (VI) are potentially catastrophic complications of nontyphoid Salmonella (NTS). We aimed to develop a scoring model incorporating information from blood culture time to positivity (TTP-NTSVI) and compared the prediction capability for VI among adults with NTS bacteremia between TTP-NTSVI and a previously published score (Chen-NTSVI). METHODS: This retrospective cohort study enrolled 217 adults with NTS bacteremia ≧ 50 years old. We developed a TTP-NTSVI score by multiple logistic regression modeling to identify independent predictors for imaging-confirmed VI and assigned a point value weighting by the corresponding natural logarithm of the odds ratio for each model predictor. Chen-NTSVI score includes hypertension, male sex, serogroup C1, coronary arterial disease (CAD) as positive predictors, and malignancy and immunosuppressive therapy as negative predictors. The prediction capability of the two scores was compared by area under the receiver operating characteristic curve (AUC). RESULTS: The mean age was 68.3 ± 11.2 years-old. Serogroup D was the predominant isolate (155/217, 71.4%). Seventeen (7.8%) patients had VI. Four independent predictors for VI were identified: male sex (24.9 [2.59-239.60]; 6) (odds ratio [95% confidence interval]; assigned score point), peripheral arterial occlusive disease (9.41 [2.21-40.02]; 4), CAD (4.0 [1.16-13.86]; 3), and TTP <10 h (4.67 [1.42-15.39]; 3). Youden's index showed best cutoff value of ≧7 with 70.6% sensitivity and 82.5% specificity. TTP-NTSVI score had higher AUC than Chen-NTSVI (0.851 vs 0.741, P = 0.039). CONCLUSION: While the previously reported scoring model performed well, a TTP-incorporated scoring model was associated with improved capability in predicting NTSVI.

Value of blood culture time to positivity in identifying complicated nontyphoidal Salmonella bacteremia.

Few studies analyzed the association between blood culture time to positivity (TTP) and risk of complicated nontyphoidal Salmonella (NTS) bacteremia. We conducted a retrospective study of 206 patients (aged 60.4 ± 17.4 years) with NTS bacteremia during a 30-month period. Complicated NTS bacteremia was defined as the presence of 30-day mortality, complicated infection requiring surgery or abscess drainage, or requirement of intensive care unit admission. Serogroup D (75.7%) was the predominant isolates. Malignancy (44.7%) was the most prevalent comorbidity. Patients with rapid TTP (<10 h) were more likely to have thrombocytopenia, septic shock, persistent bacteremia, complicated infection, and a higher intensive care unit admission rate. In multivariate logistic regression model, a TTP <10 h was an independent predictor for complicated NTS bacteremia (adjusted odd ratio, 5.683, 95% confidence interval, 2.396-13.482). Our study showed that blood culture TTP provides important diagnostic and prognostic information in the treatment of NTS bacteremia patients.

Queer consequence of cough: atrial myxoma embolization with acute occlusion of the abdominal aorta.

We introduce a rare case of sudden paraplegia preceded by vigorous coughing. This case demonstrates that detachment of a myxoma fragment can possibly be triggered by an abrupt increase in intrathoracic pressure. It is a potential complication that has never been reported in the literature. This case illustrates that clinicians should consider cardiac myxoma in a patient with an embolic event of ambiguous etiology, especially when the event is preceded by a forceful, valsalva maneuver-like action.

Mycotic aneurysm caused by gas-forming serotype K5 Klebsiella pneumoniae.

We describe the first documented case of mycotic aneurysm caused by gas-forming serotype K5, and rmpA and iuc positive Klebsiella pneumonia with a hypermucoviscosity phenotype in a diabetic patient. The patient received ceftriaxone for one month and underwent aorto-bi-iliac grafting and inferior mesenteric artery reimplantation and recovered well.

Epidemiology and prognostic determinants of patients with bacteremic cholecystitis or cholangitis.

OBJECTIVES: To compare mortalities in patients with sepsis due to biliary tract infections (BTIs) and due to infections from other sources, and to identify independent predictors of mortality in these patients. METHODS: This study was part of a community-acquired bloodstream infection (BSI) study that prospectively collected comprehensive clinical, laboratory, and outcome data from 937 consecutive patients with microbiologically documented BSI in the emergency department. BTI was the confirmed source of 145 of the 937 BSIs. We determined the independent prognostic factors by evaluating the correlation between 30-day mortality and various factors, for example, comorbidity, clinical severity, related hepatobiliary complication, and decompressive procedures. RESULTS: Patients with biliary sepsis had a high percentage of Gram-negative (88.3%), polymicrobial (26.9%), and anaerobic infections (6.9%). The 30-day overall mortality was 11.7%. Cox proportional hazard regression analysis disclosed five significant independent predictors: acute renal failure (hazard ratio, 95% confidence interval: 6.86, 6.02-25.5), septic shock (5.83, 4.36-15.64), malignant obstruction (4.35, 1.89-12.96), direct type hyperbilirubinemia (1.26, 1.1-1.42), and Charlson score > or =6 (1.57, 1.12-2.22). Compared with the remaining 792 patients in the source population, patients with bacteremic BTI had significantly better prognosis (log-rank test, P= 0.007). Adjusting for age, comorbidity, and clinical severity, BTI was still independently associated with better 30-day survival (0.25-0.76). CONCLUSIONS: Though the mortality rate in patients with bacteremic BTI is substantial, survival is better than in those with bacteremia from other sources. The main prognostic factors identified in this study may help clinicians recognize patients at high risk for early mortality so that they can give prompt, appropriate treatment.

Delayed fluid resuscitation in hemorrhagic shock induces proinflammatory cytokine response.

STUDY OBJECTIVE: This study is designed to determine the effects of delayed fluid resuscitation on the hemodynamic changes and cytokine responses in a rat model of hemorrhagic shock. METHODS: Wistar male rats (n=40; 8/group) were subjected to a volume-controlled hemorrhagic shock for 30 minutes and received lactated Ringer's solution resuscitation as follows: (1) immediate resuscitation, (2) delayed resuscitation begun 30 minutes after hemorrhage (delayed resuscitation 30), (3) delayed resuscitation begun 45 minutes after hemorrhage (delayed resuscitation 45), (4) delayed resuscitation begun 60 minutes after hemorrhage (delayed resuscitation 60), or (5) unresuscitated group, induction of hemorrhagic shock without resuscitation. Hemodynamic parameters were recorded and blood samples were collected at 0 minutes and at 30, 90, 150, 210, 270, and 330 minutes after hemorrhage for plasma levels of interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNF-alpha). Repeated-measurement analysis of variance was used for within- and between-groups comparisons. RESULTS: Final mean blood pressure, serum levels of lactate, and hematocrit levels after immediate resuscitation were not different from those in the delayed resuscitation groups. Comparing with the unresuscitated group, TNF-alpha and IL-6 concentrations were significantly higher, whereas IL-10 concentrations were significantly lower in the 4 resuscitation groups. Circulating concentrations of IL-6 were significantly higher in the delayed resuscitation 45 (P<.001) and delayed resuscitation 60 (P<.001) groups. Circulating concentrations of TNF-alpha and IL-10 in the 4 resuscitation groups were comparable throughout the experimental period. CONCLUSION: Delayed fluid resuscitation in hemorrhagic shock induces increased production of proinflammatory cytokines, and the release of cytokine was correlated with the time delayed for resuscitation.

Tension pneumoperitoneum following upper gastrointestinal endoscopy.

Tension pneumoperitoneum is a potentially lethal complication of numerous iatrogenic procedures, including upper gastrointestinal (UGI) endoscopy. We report a 69-year-old man with UGI bleeding who developed tension pneumoperitoneum and cardiac arrest after UGI endoscopy. He was successfully resuscitated with needle decompression. Emergency surgery revealed a perforated gastric ulcer, and subtotal gastrectomy with Billroth II anastomosis was performed. Recovery was smooth and he was discharged from the hospital 18 days later. Tension pneumoperitoneum should be suspected in all patients who develop circulatory collapse with acutely distended abdomen after UGI endoscopy. Early identification relies on a high index of suspicion. Prompt treatment with needle decompression should not be delayed for confirmatory radiography once the clinical diagnosis is made.

Community-acquired anaerobic bacteremia in adults: one-year experience in a medical center.

A prospective observational study was conducted to evaluate the clinical characteristics and outcome of community-acquired anaerobic bacteremia. From June 1 2001 through May 31 2002, 52 patients with community-acquired anaerobic bacteremia were enrolled at the emergency department in a teaching hospital. There were 19 patients (34%) with polymicrobial bacteremia and Escherichia coli was the most common copathogen (n = 6). Of 62 anaerobic isolates, species of the Bacteroides fragilis group were the most common isolates (n = 28, 45%), followed by Clostridium spp. (n = 11, 18%). Among the 52 patients enrolled, up to 27% had underlying malignancy and the gastrointestinal tract accounted for 48% of the sources of infection. Clinical manifestations suggesting anaerobic infections were common and three-quarters (n = 39) of 52 patients received adequate empirical antimicrobial treatment. Documentation of anaerobic bacteremia seldom influenced antimicrobial treatment. The 30-day mortality was 25%. Although univariate analysis revealed that underlying malignancy (p=0.003), leukopenia (p=0.044) and absence of fever (p=0.047) were associated with mortality, only malignancy (p=0.007) was an independent risk factor in the multivariate analysis.

Characteristics of community-acquired and health care-associated Staphylococcus aureus bacteremia in patients treated at the emergency department of a teaching hospital.

The changing epidemiology of Staphylococcus aureus bacteremia has been noted worldwide. This enhanced awareness appears to be closely associated with the evolution of health care systems. To further delineate this change and to clarify the prevalence of true community-acquired methicillin-resistant S. aureus (MRSA), reclassification for community-onset bacteremia was proposed. Exposure to health care system, such as nursing home residence, regular outpatient invasive interventions, and prior hospitalization within 1 year, was identified among the community-onset S. aureus bacteremia patients. During the 1-year study period, 102 episodes of S. aureus bacteremia from the emergency department patients of a teaching hospital were prospectively enrolled. Nine of the episodes were hospital-acquired, 56 episodes were associated with health care system exposure, and the remaining 37 episodes were classified as true community-acquired bacteremia. The characteristics of patients, primary site of infection, antimicrobial susceptibilities of S. aureus isolates, adequacy of initial antimicrobial therapy, and percentage of metastatic infections differed significantly between health care-associated and true community-acquired S. aureus bacteremias. Prevalence of MRSA infection in true community-acquired bacteremia was low in contrast to bacteremia with health care-associated exposure (2.7% versus 42.9%, P < 0.01). In conclusion, clinical characteristics and risk of contracting methicillin-resistant S. aureus bacteremia among community patients with and without exposure to health care system are distinct. Precise classification of patients is mandatory for the surveillance of antimicrobial resistance and selection of rationale empirical antibiotics.

Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome.

Although viral replication and overwhelming immune responses are believed to contribute to the progression of severe acute respiratory syndrome (SARS), little is known about the temporal relationship between viral load, ribavirin, proinflammatory cytokines, and clinical progression. We report that ribavirin was not effective in reducing the SARS coronavirus load in 3 of 8 probable cases studied and that elevated levels of interleukin (IL)-6 and IL-8 subsequent to the peak viral load were found in 8 and 6 cases, respectively. The nadir lymphocyte count during lymphopenia, the peak level of lactate dehydrogenase, and the peak density of pulmonary infiltrates lag further behind the peak viral load by a median of 4, 5, and 3.5 days, respectively. These findings provide important information for therapeutic strategies to treat SARS.

Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis.

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis.

Mesenteric adenitis caused by Salmonella enterica serovar Enteritidis.

Mesenteric adenitis is a self-limited condition characterized by fever, localized right lower quadrant abdominal pain, and frequent leukocytosis, making it difficult to differentiate from appendicitis. We report a case of mesenteric adenitis in an 8-year-old boy who presented at the emergency department with right lower quadrant abdominal pain, diarrhea, and fever up to 40 degrees C. Acute appendicitis was initially suspected, but further abdominal ultrasound and contrast enhanced computed tomography studies showed a normal appendix with marked mesenteric adenopathy. Symptomatic treatment was given and pain and fever subsided 2 days later. Follow-up sonography showed resolution of adenopathy, confirming the diagnosis of mesenteric adenitis. The admission stool cultures grew Salmonella enterica serovar Enteritidis (S. Enteritidis). Unlike previous reports in western countries where Yersinia species prevails and was thought to be self-limited, S. Enteritidis carries potential risk for serious systemic complications, such as meningitis or septic arthritis. The isolation of this unusual microbiological species thus has both therapeutic and epidemiological implications for mesenteric adenitis in Taiwan.

Validation of a novel severe acute respiratory syndrome scoring system.

STUDY OBJECTIVE: In a pilot study conducted during March 14 to April 2, 2003, 2 severe acute respiratory syndrome (SARS) screening scores were developed for predicting SARS among febrile patients presenting to the emergency department (ED). The objective of this study is to validate these scoring systems with a different set of patients. METHODS: All adult patients with documented fever, measured at home or at the hospital, and presenting to the ED of National Taiwan University Hospital, a 2,400-bed tertiary care teaching hospital in northern Taiwan, were prospectively enrolled. Two previously developed SARS screening scores were applied to all patients. The final diagnosis of SARS was made by the Expert Committee of the Center for Disease Control Taiwan, Republic of China, according to the criteria of Centers for Disease Control and Prevention, Atlanta, GA. RESULTS: A total of 239 adult patients, including 117 men and 122 women, were enrolled. Eighty-two patients were finally diagnosed with SARS. Compared with the SARS patients in the derivation cohort, those in the validation cohort were older (44.5+/-15.9 versus 33.9+/-15.9 years), more likely to acquire the disease locally (76.8% versus 37.5%), and more likely to have cough before or during fever. For the non-SARS patients, cases in the validation cohort presented with less cough and coryza but more diarrhea. For the 4-item symptom score, the sensitivity reached 96.3% (95% confidence interval [CI] 89.7% to 98.7%) and the specificity 51.6% (95% CI 43.8% to 59.3%). For the 6-item clinical score, the sensitivity reached 92.6% (95% CI 84.8% to 96.6%) and the specificity 71.2% (95% CI 63.6% to 77.7%). When the clinical score was applied to patients with a positive symptom score, the combined sensitivity reached 90.2% (95% CI 82.0% to 95.0%), and the combined specificity reached 80.1% (95% CI 73.2% to 85.6%). CONCLUSION: This prospective study validated the scoring system previously developed by using a different cohort. The scoring systems could be applied to settings where mass screening of SARS is needed during future outbreaks.

Sequential symptomatic analysis in probable severe acute respiratory syndrome cases.

STUDY OBJECTIVE: Previous reports on severe acute respiratory syndrome (SARS) described mainly its symptoms. However, the time sequence of symptom development was rarely discussed. The objective of this study is to chronologically document the time sequence of symptom development in probable SARS cases and compare that of the febrile non-SARS cases, thus providing valuable information for early recognition of the disease. METHODS: This prospective, descriptive, cohort study was conducted in an academic university hospital in Taipei, Taiwan, from March 14 through May 12, 2003. Patients presenting to the emergency department (ED) with a temperature of at least 38.0 degrees C (> or =100.3 degrees F) and exposure history were evaluated with a structured protocol. Detailed time sequences of individual symptoms were recorded, and chest radiography and laboratory test results were obtained. Probable SARS cases were determined by the Center of Disease Control Taiwan. Children younger than 15 years and suspected SARS patients with negative polymerase chain reaction results were excluded from final analysis. RESULTS: Seventy-nine SARS and 220 non-SARS cases were analyzed. The major clinical symptoms of SARS patients on ED presentation were myalgia, loose stool or diarrhea, nonproductive cough or dyspnea, headache, and chills. Upper airway symptoms, including rhinorrhea and sore throat, were rarely seen in the SARS patients but were common in the non-SARS group. Characteristic symptom sequence, consisting of initial fever accompanied by diarrhea and myalgia and then progressive respiratory symptoms, was identified in 55 SARS patients (69.6%; 95% confidence interval [CI] 0.60 to 0.80) but only 7 (3.2%; 95% CI 0.008 to 0.05) non-SARS patients. Chest radiographic abnormality may precede lower respiratory tract symptoms in some SARS patients. CONCLUSION: During an outbreak period, recognition of possible SARS cases depends on the heightened awareness of its clinical presentation. Aside from travel and contact history, the time sequence of the accompanying symptoms of SARS should help first-line physicians screen SARS patients at an early stage.