Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction

INTRODUCTION: Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response. PATIENTS AND METHODS: One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection). RESULTS: PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12). PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann–Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP. CONCLUSIONS: PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters

Mitochondrial DNA reveals genetic structuring of <i>Pinna nobilis</i> across the Mediterranean Sea

Pinna nobilis is the largest endemic Mediterranean marine bivalve. During past centuries, various human activities have promoted the regression of its populations. As a consequence of stringent standards of protection, demographic expansions are currently reported in many sites. The aim of this study was to provide the first large broad-scale insight into the genetic variability of P. nobilis in the area that encompasses the western Mediterranean, Ionian Sea, and Adriatic Sea marine ecoregions. To accomplish this objective twenty-five populations from this area were surveyed using two mitochondrial DNA markers (COI and 16S). Our dataset was then merged with those obtained in other studies for the Aegean and Tunisian populations (eastern Mediterranean), and statistical analyses (Bayesian model-based clustering, median-joining network, AMOVA, mismatch distribution, Tajima’s and Fu’s neutrality tests and Bayesian skyline plots) were performed. The results revealed genetic divergence among three distinguishable areas: (1) western Mediterranean and Ionian Sea; (2) Adriatic Sea; and (3) Aegean Sea and Tunisian coastal areas. From a conservational point of view, populations from the three genetically divergent groups found may be considered as different management units

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy

IMPORTANCE Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. OBJECTIVE To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. EXPOSURES COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). MAIN OUTCOMES AND MEASURES The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. RESULTS Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] agewas 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dosewas 0.03 (95% CI, 0.03-0.04; P &lt;.001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P &lt;.001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P &lt;.001), primarily male individuals (110 patients [ 79.1%] vs 252 patients [60.9%]; P &lt;.001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P &lt;.001) and had higher ratio of arterial partial pressure of oxygen (PaO2) and fraction of inspiratory oxygen (FiO(2)) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P =.007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower PaO2/FiO(2) at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. CONCLUSIONS AND RELEVANCE In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status.These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units

Purpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods: In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients