Sepsis: Pathophysiology, Diagnosis and Therapy

Lead pacemaker infection is a complication on the rise. An infected oscillating mass attached to the leads (ILV) is a common finding in this setting. Percutaneous extraction of the leads and of the device is the best curative option. However, extraction of leads with large masses can be complicated by pulmonary embolism. The aim of this study was to understand the factors associated with large ILV using a sophisticated ultrasound technique to visualize the masses, namely intracardiac echocardiography (ICE), and investigate whether larger masses induce more complications during and after extraction. Percutaneous lead extraction and peri-procedural ICE were done in 36 patients (pts) (75 ± 11 years old, 74% males). Vegetations (max dimension = 8.2 ± 4.1 mm) in the right cavity were found in 26 of them, mostly adhering to the leads. We subdivided the patients into 2 groups: with vegetation size < 1 cm (18 pts) and vegetation size ≥ 1 cm (8 pts). By univariate analysis, we found that patients in group 1 were more often taking anticoagulation therapy (p = 0.03, Phi (Phi coefficient) = −0.5, OR [odds ratio] 0.071) and had signs of local pocket infection (p = 0.02, Phi = −0.52, OR 0.059) while significantly more patients in group 2 had diabetes (p = 0.08, Phi = 0.566, OR 15); moreover the patients in group 2 showed a trend toward a more frequent positive blood culture (p = 0.08, Phi = 0.39, OR 5.8) and infection with coagulase negative staphylococci (p = 0.06, Phi = 0.46, OR 8.3). At multivariate analysis, only 3 factors (diabetes, younger age and anticoagulation therapy) were independently associated with ILV size: diabetes, associated with larger vegetations (group 2), showed the largest beta value (0.44, p = 0.008); age was inversely correlated with ILV size (beta value = −32, p = 0.038), and anticoagulation therapy (beta value = −029, p = 0.048) was more commonly associated with smaller vegetations (group 1). Larger ILV were not associated with more complications or death during or after the extraction. Conclusion: diabetes, anticoagulation therapy and age are independent predictors of lead vegetation size. The embolic potential of large ILV during extraction was modest, so ILVs >1cm are not a contraindication to percutaneous extraction of infected leads. Full article

Sepsis is a life-threatening condition that accounts for numerous deaths worldwide, usually complications of common community infections (i.e., pneumonia, etc), or infections acquired during the hospital stay. Sepsis and septic shock, its most severe evolution, involve the whole organism, recruiting and producing a lot of molecules, mostly proteins. Proteins are dynamic entities, and a large number of techniques and studies have been devoted to elucidating the relationship between the conformations adopted by proteins and what is their function. Although molecular dynamics has a key role in understanding these relationships, the number of protein structures available in the databases is so high that it is currently possible to build data sets obtained from experimentally determined structures. Techniques for dimensionality reduction and clustering can be applied in exploratory data analysis in order to obtain information on the function of these molecules, and this may be very useful in immunology to better understand the structure-activity relationship of the numerous proteins involved in host defense, moreover in septic patients. The large number of degrees of freedom that characterize the biomolecules requires special techniques which are able to analyze this kind of data sets (with a small number of entries respect to the number of degrees of freedom). In this work we analyzed the ability of two different types of algorithms to provide information on the structures present in three data sets built using the experimental structures of allosteric proteins involved in sepsis. The results obtained by means of a principal component analysis algorithm and those obtained by a random projection algorithm are largely comparable, proving the effectiveness of random projection methods in structural bioinformatics. The usefulness of random projection in exploratory data analysis is discussed, including validation of the obtained clusters. We have chosen these proteins because of their involvement in sepsis and septic shock, aimed to highlight the potentiality of bioinformatics to point out new diagnostic and prognostic tools for the patients. Full article

Background: Malnutrition-inflammation complex syndrome (MICS) is a common and usually concurrent condition occurring in patients undergoing hemodialysis (HD), with a pathogenesis linked to biological and in situ environmental traditional risk factors. Periodontitis, one of the major types of infection-driven inflammation, often co-occurs in the in the hemodialysis population and correlates with markers of malnutrition and inflammation, such as albumin, creatinine, and C-reactive protein. Aim: The present study aimed to determine whether the periodontal inflammatory status parameters correlate with the albumin, creatinine, and C-reactive protein serum concentrations in HD patients, and investigate whether periodontal treatment improves these markers of nutritional and systemic inflammation. Materials and Methods: The serum creatinine, albumin, and C-reactive Protein (CRP) levels were measured at baseline and after non-surgical periodontal treatment, at 3 months and 6 months. Results: At 3 months, a significant correlation between plaque index and C-reactive protein (p = 0.012), bleeding on probing and C-reactive protein (p < 0.0019), and clinical attachment level and C-reactive protein (p = 0.022) was found. No significant correlation was found between clinical periodontal parameters and nutrition markers at each time. Conclusions: Our results confirmed the association between C-reactive protein serum concentration and periodontal inflammatory status, but further research is necessary to identify the contributing role of periodontitis on the onset and progression of MICS. Full article

Aims: There are many reasons for the increase in post-operative mortality and morbidity in patients undergoing surgery. In fact, an activated inflammatory state before cardiac surgery, can potentially worsen the patient’s prognosis and the effects of this preoperative inflammatory state in the medium-term remains unknown. Methods: There were 470 consecutive patients who underwent cardiac surgery, and were divided in three groups according to the median values of preoperative C-reactive protein (CRP) and fibrinogen (FBG): The first group was the low inflammatory status group (LIS) with 161 patients (CRP < 0.39 mg/dL and FBG < 366 mg/dL); the second was the medium inflammatory status group (MIS) with 150 patients (CRP < 0.39 mg/dL and FBG ≥ 366 mg/dL or CRP ≥ 0.39 mg/dL and FBG < 366 mg/dL,); and the third was the high inflammatory status group (HIS) with 159 patients (CRP ≥ 0.39 mg/dL and FBG ≥ 366 mg/dL,). Results: The parameters to be considered for the patients before surgery were similar between the three groups except, however, for age, left ventricular ejection fraction (LVEF) and the presence of arterial hypertension. The operative mortality was not significantly different between the groups (LIS = 2.5%, MIS = 6%, HIS = 6.9%, p = 0.16) while mortality for sepsis was significantly different (LIS = 0%, MIS = 1.3%, HIS = 3.7%, p = 0.03). The infections were more frequent in the HIS group (p = 0.0002). The HIS group resulted in an independent risk factor for infections (relative risk (RR) = 3.1, confidence interval (CI) = 1.2–7.9, p = 0.02). During the 48-months follow-up, survival was lower for the HIS patients. This HIS group (RR = 2.39, CI = 1.03–5.53, p = 0.05) and LVEF (RR = 0.96, CI = 0.92–0.99, p = 0.04) resulted in independent risk factors for mortality during the follow-up. Conclusions: The patients undergoing cardiac surgery with a preoperative highly activated inflammatory status are at a higher risk of post-operative infections. Furthermore, during the intermediate follow-up, the preoperative highly activated inflammatory status and LVEF resulted in independent risk factors for mortality. Full article

Sepsis is a condition that requires appropriate antibiotic treatment at the emergency department (ED). Most previous studies conducted on inappropriate antibiotic use at the ED were conducted in developed countries with a low percentage of sepsis. This study aimed to find additional clinical predictors for appropriate antibiotic use in bacteremia patients presenting at the ED from a developing country, in which there is a higher proportion of patients with sepsis. We included adult patients who presented at the ED with clinical suspicion of infection and bacteremia. Patients allocated to the appropriate antibiotic group were those in whom the prescribed antibiotic was sensitive to the pathogen. Predictors and outcomes of appropriate antibiotic use were analyzed. A total of 3133 patients who met the study criteria presented at the ED during the study period. Of those, 271 patients were diagnosed with bacteremia, 48 of whom (17.71%) received inappropriate antibiotic prescriptions. Only pulse rate was an independent factor for appropriate antibiotic treatment, with an adjusted odds ratio of 1.019 (95% CI of 1.001, 1.036). In terms of clinical outcomes, the inappropriate antibiotic group had higher proportions of 28-day mortality (29.17% vs. 25.25%; p-value = 0.022) and longer hospitalization (14 vs. 9 days; p-value = 0.003). This study found that inappropriate antibiotics were prescribed in 17% of bacteremia patients presenting at the ED and that high pulse rate was an indicator for appropriate antibiotic prescription. Patients with inappropriate antibiotic administration had longer hospitalization and higher 28-day mortality than those who received appropriate antibiotic treatment. Full article

Immune suppressed renal transplant patients are more prone to developing oral tissue alterations due to medications associated with a pleiotropic set of side effects involving the oral cavity. Drug-induced gingival overgrowth (DIGO) is the most commonly encountered side effect resulting from administration of calcineurin inhibitors such as cyclosporine-A (CsA), the standard first-line treatment for graft rejection prevention in transplant patients. Pathogenesis of gingival overgrowth (GO) is determined by the interrelation between medications and a pre-existing inflammatory periodontal condition, the main modifiable risk factor. Severity of gingival hyperplasia clinical manifestation is also related to calcium channel blocker association, frequently provided in addition to pharmacological therapy of transplant recipients. Specifically, nifedipine-induced enlargements have a higher prevalence rate compared to amlodipine-induced enlargements; 47.8% and 3.3% respectively. Available epidemiological data show a gender difference in prevalence, whereby males are generally more frequently affected than females. The impact of GO on the well-being of an individual is significant, often leading to complications related to masticatory function and phonation, a side effect that may necessitate switching to the tacrolimus drug that, under a similar regimen, is associated with a low incidence of gingival lesion. Early detection and management of GO is imperative to allow patients to continue life-prolonging therapy with minimal morbidity. The purpose of this study was threefold: firstly, to determine the prevalence and incidence of GO under the administration of CsA and Tacrolimus; secondly, to assess the correlation between periodontal status before and after periodontal therapy and medications on progression or recurrence of DIGO; and finally, to analyse the effect of immunosuppressant in association to the channel blocker agents on the onset and progression of gingival enlargement. We compared seventy-two renal transplant patients, including 33 patients who were receiving CsA, of which 25% were also receiving nifedipine and 9.72% also receiving amlodipine, and 39 patients who were receiving tacrolimus, of which 37.5% were also receiving nifedipine and 5.55% also receiving amlodipine, aged between 35 and 60 years. Medical and pharmacological data were recorded for all patients. Clinical periodontal examination, in order to establish the inflammatory status and degree of gingival enlargement, was performed at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). All patients were subjected to periodontal treatment. Statistically significant correlation between the reduction of the mean value of periodontal indices and degree of gingival hyperplasia at the three times was revealed. The prevalence of GO in patients taking cyclosporine was higher (33.3%) in comparison with those taking tacrolimus (14.7%). In accordance with previous studies, this trial highlighted the clinical significance of the pathological substrate on stimulating drug-induced gingival lesion, confirming the key role of periodontal inflammation in pathogenesis of gingival enlargement, but did not confirm the additional effect of calcium-channel blocker drugs in inducing gingival enlargement. Full article

Sepsis is a leading cause of morbidity and mortality worldwide. It is defined as the presence of a Systemic Inflammatory Response Syndrome, and it represents a significant burden for the healthcare system. This is particularly true when it is diagnosed in the setting of nosocomial infections, which are usually a matter of concern with regard to medical liability being correlated with increasing economic costs and people’s loss of trust in healthcare. Hence, the Italian governance promotes the clinical risk management with the aim of improving the quality and safety of healthcare services. In this context, the role of medico-legal experts working in a hospital setting is fundamental for performing autopsy to diagnose sepsis and link it with possible nosocomial infections. On the other hand, medico-legal experts are party to the clinical risk management assessment, and deal with malpractice cases and therefore contribute to formulating clinical guidelines and procedures for improving patient safety and healthcare providers’ work practices. Due to this scenario, the authors here discuss the role of medico-legal experts in Italy, focusing on sepsis and nosocomial infections. Full article

In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (2016), revolutionizes precedent criteria, overcoming the concept of SIRS and clearly distinguishing the infection with the patient’s physiological response from the symptoms of sepsis. Another fundamental change concerns the recognition method: The use of SOFA (Sequential-Sepsis Related-Organ Failure Assessment Score) as reference score for organ damage assessment. Also, the use of the qSOFA is based on the use of three objective parameters: Altered level of consciousness (GCS <15 or AVPU), systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22/min. If patients have at least two of these altered parameters in association with an infection, then there is the suspicion of sepsis. In these patients the risk of death is higher, and it is necessary to implement the appropriate management protocols, indeed the hospital mortality rate of these patients exceeds 40%. Patients with septic shock can be identified by the association of the clinical symptoms of sepsis with persistent hypotension, which requires vasopressors to maintain a MAP of 65 mmHg, and serum lactate levels >18 mg/dL in despite of an adequate volume resuscitation. Then, patient first management is mainly based on: (1) Recognition of the potentially septic patient (sepsis protocol-qSOFA); (2) Laboratory investigations; (3) Empirical antibiotic therapy in patients with sepsis and septic shock. With this in mind, the authors discuss the most important aspects of the sepsis in both adults and infants, and also consider the possible treatment according current guidelines. In addition, the possible role of some nutraceuticals as supportive therapy in septic patient is also discussed. Full article