Etiologies, risk factors and outcomes of dental pulp necrosis

Dental pulp necrosis is referred to the situation in which the teeth biologically die due to bacterial infection or without bacterial infection. Dental pulp necrosis can be due to a chronic progression of pulpitis, in which the tissue of soft pulp in the tooth dies due to several causes such as trauma or severe bacterial infection. Untreated cavities, multiple invasive treatments for the tooth, and pathological ischemia for dental pulp are among the most common causes for the necrosis process. Usually, the first symptom of dental pulp necrosis is the irritant pain in the tooth only or the surrounding area because of the inflammation. The grade of pain ranges from mild, moderate, to severe pain according to the size of the damage, followed by swelling and discomfort in chewing due to the pressure on the nerve root at the base of the tooth. We aim to review the different etiologies, risk factors, correlations, and clinical outcomes associated with pulp necrosis. To our knowledge, this article is going to be the first comprehensive review of dental pulp necrosis.

Interleukin 6 as a marker of severe bacterial infection in children with sickle cell disease and fever: a case–control study

Background Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods A prospective, case–control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7–7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively). Conclusion We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: An observational cohort study

Introduction Maternal and newborn infections are important causes of mortality but morbidity data from low- and middle-income countries is limited. We used telephone surveillance to estimate infection incidence and risk factors in women and newborns following hospital childbirth in Dar es Salaam. Methods We recruited postnatal women from two tertiary hospitals and conducted telephone interviews 7 and 28 days after delivery. Maternal infection (endometritis, caesarean or perineal wound, or urinary tract infection) and newborn infection (umbilical cord or possible severe bacterial infection) were identified using hospital case-notes at the time of birth and self-reported symptoms. Adjusted Cox regression models were used to assess the association between potential risk-factors and infection. Results We recruited 879 women and interviewed 791 (90%). From day 0–7, 6.7% (49/791) women and 6.2% (51/762) newborns developed infection. Using full follow-up data, the infection rate was higher in women with caesarean childbirth versus women with a vaginal delivery (aHR 1.93, 95%CI 1.11–3.36). Only 24% of women received pre-operative antibiotic prophylaxis before caesarean section. Infection was higher in newborns resuscitated at birth versus newborns who were not resuscitated (aHR 4.45, 95%CI 2.10–9.44). At interview, 66% (37/56) of women and 88% (72/82) of newborns with possible infection had sought health-facility care. Conclusions Telephone surveillance identified a substantial risk of postnatal infection, including cases likely to have been missed by hospital-based data-collection alone. Risk of maternal endometritis and newborn possible severe bacterial infection were consistent with other studies. Caesarean section was the most important risk-factor for maternal infection. Improved implementation of pre-operative antibiotic prophylaxis is urgently required to mitigate this risk.

Plasma from patients with bacterial sepsis or severe COVID-19 induces production of suppressive myeloid cells from human hematopoietic progenitor cells in vitro

Bacterial sepsis and severe COVID-19 share similar clinical manifestations and are both associated with dysregulation of the myeloid cell compartment. We previously reported an expanded CD14+ monocyte cell state, MS1, in patients with bacterial sepsis, and validated expansion of this cell subpopulation in 18 patients with sepsis using publicly available transcriptomics data. Here, using published scRNA-seq datasets, we show that the gene expression program associated with MS1 correlated with sepsis severity and was up-regulated in monocytes from patients with severe COVID-19. To examine the ontogeny and function of MS1 cells, we developed a cellular model for inducing CD14+ MS1 monocytes by treating human hematopoietic stem and progenitor cells (HSPCs) from healthy bone marrow donors in culture with plasma from patients with severe bacterial infection or SARS-CoV-2 infection. We demonstrated that plasma from patients with bacterial sepsis or COVID-19 induced myelopoiesis in HSPCs in vitro and expression of the MS1 gene program in monocytes and neutrophils that differentiated from these HSPCs. Furthermore, we found that plasma concentrations of IL-6, and to a lesser extent IL-10, correlated with increased myeloid cell output from HSPCs in vitro and enhanced expression of the MS1 gene program. We validated the requirement for these two cytokines to induce the MS1 gene program through CRISPR-Cas9 editing of their receptors in HSPCs. Using this cellular model system, we demonstrated that MS1 cells were broadly immunosuppressive and showed decreased responsiveness to stimulation with a synthetic RNA analog. Our in vitro study suggests a potential role for systemic cytokines in inducing myelopoiesis during severe bacterial infection or SARS-CoV-2 infection.

Interleukin 6 as a Marker of Severe Bacterial Infection in Children with Sickle Cell Disease and Fever: A Case-Control Study

BackgroundEtiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI).MethodsA prospective, case-control study of febrile and steady-state SCD children was carried out during 3 years. Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed.ResultsA total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI) and 33 no proven infection (NPI). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences, respectively).ConclusionWe found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

The Significance of Clinical and Laboratory Findings in Predicting Serious Bacterial Infections in Children With Acute Fever Without a Focus

Objective: Fever is among most common causes of admission to hospital in childhood. In 20% of febrile infants and children, no focus can be identified by physical examination and this group is defined as “acute fever without a focus” (AFWF). Bacteremia (5%), and serious bacterial infection (15%) is determined in of children with AFWF. Clinical scales and laboratory tests are used to detect the risk of occult bacteremia and serious bacterial infection in children with AFWF This study aimed to determine relation between biochemical indicators and YALE Observation Scale, besides, rates of clinical scales and biochemical indicators predicting serious bacterial infections, in 3-36 months children with AFWF. Material and Methods: This study was performed prospectively, in 77 cases, between 3-36 months of AFWF. Low risk criteria was evaluated by performing YALE Observation Scale in children. Complete blood count, absolute neutrophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin 6, procalcitonin, urine analysis, chest x-ray, cerebrospinal fluid (CSF) examination; blood, urine and CSF cultures were obtained. Results: The mean age of the patients was 11.0 (4-36) months, 64.9% (n= 50) were boys. Most commonly AFWF recovered in patients (35.0%), and urinary tract infection was diagnosed (32.5%). Severe bacterial infection was determined in 44.2%. When patient groups with and without severe bacterial infection were compared, white blood count, ESH, CRP, and procalcitonin were significantly higher in severe bacterial infection (p< 0.05). Erythrocyte sedimentation rate had highest specificity (87.5%) in discriminating between groups with and without severe bacterial infection. Conclusion: In conclusion, AFWF mostly recovered in children at 3-36 months, and urinary tract infection was common cause. White cell count, ESR, CRP and procalcitonin were found valuable in predicting serious bacterial infection. Further studies are needed to predict interleukin-6 value relevant to serious bacterial infection.