A peptidoglycan storm caused by β-lactam antibiotic’s action on host microbiota drives Candida albicans infection

AbstractThe commensal fungus Candida albicans often causes life-threatening infections in patients who are immunocompromised with high mortality. A prominent but poorly understood risk factor for the C. albicans commensal‒pathogen transition is the use of broad-spectrum antibiotics. Here, we report that β-lactam antibiotics cause bacteria to release significant quantities of peptidoglycan fragments that potently induce the invasive hyphal growth of C. albicans. We identify several active peptidoglycan subunits, including tracheal cytotoxin, a molecule produced by many Gram-negative bacteria, and fragments purified from the cell wall of Gram-positive Staphylococcus aureus. Feeding mice with β-lactam antibiotics causes a peptidoglycan storm that transforms the gut from a niche usually restraining C. albicans in the commensal state to promoting invasive growth, leading to systemic dissemination. Our findings reveal a mechanism underlying a significant risk factor for C. albicans infection, which could inform clinicians regarding future antibiotic selection to minimize this deadly disease incidence.

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Association Between Elevated Hemolysis at Diagnosis and Early Mortality and Risk of Thrombosis In Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients with Cytopenia

Blood ◽

10.1182/blood.v116.21.4241.4241 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4241-4241 ◽

Cited By ~ 1

Author(s):

Jin Seok Kim ◽

Jong Wook Lee ◽

Sung-Soo Yoon ◽

Je-Hwan Lee ◽

Deog-Yeon Jo ◽

...

Keyword(s):

Quality Of Life ◽

Risk Factor ◽

Abdominal Pain ◽

Conflicts Of Interest ◽

Significant Risk ◽

Significant Risk Factor ◽

Poor Quality ◽

Severe Fatigue ◽

Life Threatening

Abstract Abstract 4241 Introduction: PNH is a rare, progressive and life threatening disease driven by chronic hemolysis leading to thrombosis, renal impairment, pain, severe fatigue, poor quality of life and premature death. Thrombosis is the leading cause of death (accounting for 40–67% of PNH-related deaths) and was recently identified as a significant risk factor for mortality in Asian PNH patients. Abdominal pain is a common and distressing symptom in PNH and has also been found to be risk factor for thrombosis and mortality in PNH patients. In PNH patients with concomitant aplasia/cytopenias (PNH-cytopenia), the symptoms associated with hemolytic PNH (i.e., severe fatigue and anemia) may be attributed to a hypocellular marrow, potentially masking the life threatening risk of hemolysis-mediated thrombosis and abdominal pain. Here we evaluate the correlation of clinical risk factors with hemolytic symptoms in cytopenic PNH patients. Methods: We retrospectively analyzed medical charts of 286 PNH patients from the National Data Registry in South Korea to identify aplastic PNH patients with evidence of hemolytic symptoms at the time of diagnosis. We defined PNH-cytopenia patients with evidence of at least 2 of the following hematological values at diagnosis: Hgb <10 g/dL; ANC <1.5×109/L; thrombocytopenia <100×109/L. Hemolysis was defined as LDH °Ã1.5 fold above the upper limit of normal (ULN). Results: The median patient age was 37 years (range: 8 to 88 years) and median PNH duration was 7.8 years. At diagnosis, median PNH granulocyte clone was 49% and LDH was 3.9-fold above ULN. Median platelet count was 99×109/L and median ANC was 1.2×109/L, 21% with ANC <1.0×109/L. PNH-cytopenia was identified at diagnosis in 42% of PNH patients. PNH-cytopenic patients experienced a similar prevalence of hemolytic symptoms and mortality compared to PNH patients with no evidence of cytopenia (PNH) (see table below). Thrombosis was equally prevalent in PNH-cytopenia compared to PNH (12% vs18%; P=0.175). Abdominal pain was equally prevalent in PNH-cytopenia and PNH (52% vs 42%; P=0.112) and there was similar mortality between the 2 groups (13% vs 11%; P=0.631). There was a significantly higher prevalence of mortality (14% vs 4%; p=0.048), thrombosis (22% vs 4%; p=0.003) and abdominal pain (53% vs 32%; p=0.007) in patients with elevated hemolysis (°Ã LDH 1.5 above ULN) compared to patients without hemolysis. We found that 69% of PNH-cytopenia patients demonstrated elevated hemolysis at diagnosis. Thrombosis was identified in 17% of PNH-cytopenia patients with elevated hemolysis compared to 3% with no evidence of elevated LDH (p=0.051); abdominal pain (59% vs 32%; p= 0.012) and death (16% vs 3%; p=0.070) were higher in PNH-cytopenia patients with hemolysis compared to PNH-cytopenia patients without hemolysis. CONCULSION: These data demonstrate that the presence of hemolysis at diagnosis is associated with of life-threatening thrombosis, poor quality of life, and mortality in PNH patients. Despite the evidence of hypoplasia, PNH-cytopenia patients with hemolysis demonstrate a higher risk of life-threatening thrombosis, pain, and mortality. These data indicate that hemolysis is a potential risk factor for life- threatening complications independent of the presence of cytopenia in patients with PNH. Treatment for PNH patients with cytopenias should focus on both controlling hemolysis as well as improving hypoplasia. Disclosures: No relevant conflicts of interest to declare.

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Prevalence of Gastroesophageal Reflux in Infants with Recurrent Brief Apneic Episodes

Canadian Respiratory Journal ◽

10.1155/1999/546420 ◽

1999 ◽

Vol 6 (5) ◽

pp. 401-404 ◽

Cited By ~ 16

Author(s):

Shahid Sheikh ◽

Thomas C Stephen ◽

Barbara Sisson

Keyword(s):

Risk Factor ◽

Gastroesophageal Reflux ◽

Medical Records ◽

Significant Risk ◽

Significant Risk Factor ◽

Acid Reflux ◽

Diagnostic Dilemma ◽

Esophageal Ph ◽

Life Threatening ◽

The Relationship

BACKGROUND: Apnea in an infant can be a diagnostic dilemma for the treating pediatrician. It is suggested that in some infants, gastroesophageal reflux (GER) might be a factor in the pathogenesis of apnea, although its role as a cause of apnea is still controversial.OBJECTIVE: To evaluate the prevalence of GER in infants presenting with recurrent brief apneic periods.PATIENTS AND METHODS: A retrospective review of the medical records of all the infants who underwent prolonged esophageal pH studies for brief apneic episodes (n=105) at the Kosair Children’s Hospital in the six years from January 1992 to December 1997 was performed. Infants presenting with apparent life-threatening episodes were excluded.RESULTS: Of 105 infants, 72 (68.6%) were younger than two months of age and 22 (21%) were born preterm. Fifty of 105 infants (47.6%) had positive esophageal pH studies for acid reflux. Among infants with positive pH studies, only 21 (42%) had associated gastrointestinal or feeding complaints.CONCLUSION: GER is present in a large number of infants presenting with brief apneic episodes. Though the relationship between the two is still not fully established, GER may be a significant risk factor for such apneic episodes in infants.

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Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽

10.1027/0227-5910/a000271 ◽

2014 ◽

Vol 35 (5) ◽

pp. 330-337 ◽

Cited By ~ 14

Author(s):

Cun-Xian Jia ◽

Lin-Lin Wang ◽

Ai-Qiang Xu ◽

Ai-Ying Dai ◽

Ping Qin

Keyword(s):

Risk Factor ◽

Family Income ◽

Rural China ◽

Significant Risk ◽

Significant Risk Factor ◽

Health Condition ◽

Physical Illness ◽

Rural Residents ◽

Increased Risk ◽

Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

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Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

Scientific Reports ◽

10.1038/s41598-021-91800-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting-Chun Huang ◽

Po-Tseng Lee ◽

Mu-Shiang Huang ◽

Pei-Fang Su ◽

Ping-Yen Liu

Keyword(s):

Risk Factor ◽

Dose Response ◽

Cox Model ◽

Significant Risk ◽

Significant Risk Factor ◽

Cardiovascular Death ◽

Specific Model ◽

Distribution Model ◽

All Cause Mortality ◽

Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

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DIGEORGE SYNDROME IS A SIGNIFICANT RISK FACTOR FOR THE DEVELOPMENT OF INFECTIOUS ENDOCARDITIS FOLLOWING TRANSCATHETER PULMONARY VALVE REPLACEMENT WITH THE MELODY VALVE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)01805-2 ◽

2021 ◽

Vol 77 (18) ◽

pp. 446

Author(s):

Graham Stockdale ◽

Joseph Graziano ◽

Wayne Franklin ◽

Jordan Awerbach ◽

Byron Garn ◽

...

Keyword(s):

Risk Factor ◽

Valve Replacement ◽

Digeorge Syndrome ◽

Pulmonary Valve ◽

Significant Risk ◽

Significant Risk Factor ◽

Pulmonary Valve Replacement ◽

Infectious Endocarditis ◽

Melody Valve ◽

Transcatheter Pulmonary Valve Replacement

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Comorbidity and severity-of-illness risk adjustment for hospital-onset Clostridioides difficile infection using data from the electronic medical record

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1344 ◽

2020 ◽

pp. 1-7

Author(s):

Stephanie M. Cabral ◽

Katherine E. Goodman ◽

Natalia Blanco ◽

Surbhi Leekha ◽

Larry S. Magder ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Risk Adjustment ◽

Community Hospital ◽

Significant Risk ◽

Significant Risk Factor ◽

Bivariate Analysis ◽

Patient Admissions ◽

Clostridioides Difficile ◽

Risk Adjustment Model

Abstract Objective: To determine whether electronically available comorbidities and laboratory values on admission are risk factors for hospital-onset Clostridioides difficile infection (HO-CDI) across multiple institutions and whether they could be used to improve risk adjustment. Patients: All patients at least 18 years of age admitted to 3 hospitals in Maryland between January 1, 2016, and January 1, 2018. Methods: Comorbid conditions were assigned using the Elixhauser comorbidity index. Multivariable log-binomial regression was conducted for each hospital using significant covariates (P < .10) in a bivariate analysis. Standardized infection ratios (SIRs) were computed using current Centers for Disease Control and Prevention (CDC) risk adjustment methodology and with the addition of Elixhauser score and individual comorbidities. Results: At hospital 1, 314 of 48,057 patient admissions (0.65%) had a HO-CDI; 41 of 8,791 patient admissions (0.47%) at community hospital 2 had a HO-CDI; and 75 of 29,211 patient admissions (0.26%) at community hospital 3 had a HO-CDI. In multivariable regression, Elixhauser score was a significant risk factor for HO-CDI at all hospitals when controlling for age, antibiotic use, and antacid use. Abnormal leukocyte level at hospital admission was a significant risk factor at hospital 1 and hospital 2. When Elixhauser score was included in the risk adjustment model, it was statistically significant (P < .01). Compared with the current CDC SIR methodology, the SIR of hospital 1 decreased by 2%, whereas the SIRs of hospitals 2 and 3 increased by 2% and 6%, respectively, but the rankings did not change. Conclusions: Electronically available patient comorbidities are important risk factors for HO-CDI and may improve risk-adjustment methodology.

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Intoxication is a Significant Risk Factor for Severe Craniomaxillofacial Injuries in Standing Electric Scooter Accidents

Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.joms.2020.09.026 ◽

2020 ◽

Author(s):

Kyle Shiffler ◽

Khal Mancini ◽

Melissa Wilson ◽

Allen Huang ◽

Eric Mejia ◽

...

Keyword(s):

Risk Factor ◽

Significant Risk ◽

Significant Risk Factor ◽

Electric Scooter

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Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection

Microorganisms ◽

10.3390/microorganisms9061211 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1211

Author(s):

Mahnaz Norouzi ◽

Shaghayegh Norouzi ◽

Alistaire Ruggiero ◽

Mohammad S. Khan ◽

Stephen Myers ◽

...

Keyword(s):

Type 2 Diabetes ◽

Risk Factor ◽

Inflammatory Responses ◽

Significant Risk ◽

Significant Risk Factor ◽

Diabetic Patients ◽

Angiotensin Converting Enzyme 2 ◽

Immune System Dysfunction ◽

Current Outbreak

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

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