Comparison between Capillary and Serum Lactate Levels in Predicting Short-Term Mortality of Septic Patients at the Emergency Department.

Sepsis is a time-dependent and life-threating condition related to macro- and micro-circulatory impairment leading to anaerobic metabolism and lactate increase. We assessed the prognostic accuracy of capillary lactates (CLs) vs. serum ones (SLs) on 48-h and 7-day mortality in patients with suspected sepsis. This observational, prospective, single-centre study was conducted between October 2021 and May 2022. Inclusion criteria were: (i) suspect of infection; (ii) qSOFA ≥ 2; (iii) age ≥ 18 years; (iv) signed informed consent. CLs were assessed with LactateProTM2®. 203 patients were included: 19 (9.3%) died within 48 h from admission to the Emergency Department, while 28 (13.8%) within 7 days. Patients deceased within 48 h (vs. survived) had higher CLs (19.3 vs. 5 mmol/L, p < 0.001) and SLs (6.5 vs. 1.1 mmol/L, p = 0.001). The best CLs predictive cut-off for 48-h mortality was 16.8 mmol/L (72.22% sensitivity, 94.02% specificity). Patients within 7 days had higher CLs (11.5 vs. 5 mmol/L, p = 0.020) than SLs (2.75 vs. 1.1 mmol/L, p < 0.001). The multivariate analysis confirmed CLs and SLs as independent predictors of 48-h and 7-day mortality. CLs can be a reliable tool for their inexpensiveness, rapidity and reliability in identifying septic patients at high risk of short-term mortality.

A 2-year retrospective analysis of the prognostic value of MqSOFA compared to lactate, NEWS and qSOFA in patients with sepsis.

PURPOSE: Sepsis is a life-threating organ dysfunction caused by a dysregulated host response to infection. Being a time-dependent condition, the present study aims to compare a recently established score, i.e., modified quick SOFA (MqSOFA), with other existing tools commonly applied to predict in-hospital mortality. METHODS: All cases of sepsis and septic shock consecutively observed at St. Anna University Hospital of Ferrara, Italy, from January 2017 to December 2018 were included in this study. Each patient was evaluated with MqSOFA, lactate assay, NEWS and qSOFA. Accurate statistical and logistic regression analyses were applied to our database. RESULTS: A total of 1001 consecutive patients with sepsis/septic shock were retrieved. Among them, 444 were excluded for incomplete details about vital parameters; thus, 556 patients were eligible for the study. Data analysis showed that MqSOFA, NEWS and lactate assay provided a better predictive ability than qSOFA in terms of in-hospital mortality (p < 0.001). Aetiology-based stratification in 5 subgroups demonstrated the superiority of NEWS vs. other tools in predicting fatal outcomes (p = 0.030 respiratory, p = 0.036 urinary, p = 0.044 abdominal, p = 0.047 miscellaneous and p = 0.041 for indeterminate causes). After Bonferroni's correction, MqSOFA was superior to qSOFA over respiratory (p < 0.001) and urinary (p < 0.001) aetiologies. Age was an independent factor for negative outcomes (p < 0.001). CONCLUSIONS: MqSOFA, NEWS and lactate assay better predicted in-hospital mortality compared to qSOFA. Since sepsis needs a time-dependent assessment, an easier and non-invasive score, i.e., MqSOFA, could be used to establish patients' outcome in the emergency setting.

Predictive Factors of Surgical Site Infection in Prosthetic Joint Surgery: A Prospective Study on 760 Arthroplasties.

Purpose: The success of total joint arthroplasty (TJA) has led to consistent growth in the use of arthroplasty in progressively younger patients. However, more than 10 percent of patients require revision surgery due to implant failure caused by aseptic or septic inflammation. Among the latter, surgical site infection (SSI) represents one of the worst complications of TJA, potentially resulting in the removal of the prosthesis. The aim of our study was to identify potential risk factors for SSIs in a population of patients undergoing TJA. Methods: TJA were prospectively recruited at Casa di Cura Santa Maria Maddalena from February 2019 to April 2020. Age, sex, major comorbidities, American Society of Anesthesiologists (ASA) class, length of surgery, type of surgical suture, total hospital length of stay, and clinical laboratory data were collected. The study population was then divided into two groups: Group A, normal postoperative course, and Group B, patients who developed SSI at follow-up (17-25 days). Results: 25/760 (3.3%) patients developed SSIs at follow-up. Clinical and demographic parameters were not different between the two groups. Total leucocyte and neutrophil values at discharge resulted to be significatively higher in Group B compared to Group A (p = 0.025 and p = 0.016, respectively). Values of 7860/µL for total leucocyte and 5185/µL for neutrophil count at discharge significantly predicted the future development of SSI (AUC 0.623 and AUC 0.641, respectively; p < 0.05) independently from confounding factors (total leukocytes: O.R. = 3, 69 [95% C.I. 1,63-8,32]; neutrophils: O.R. = 3, 98 [95% C.I. 1,76-8,97]). Deep SSIs has been diagnosed significantly before superficial SSIs (p = 0,008), with a median advance of 9 days. Conclusion: Total leukocytes and neutrophils at discharge seem useful to identify a population at risk for the development of septic inflammation at the surgical site following TJA. Further studies with larger populations are needed to develop a predictive SSIs risk score that should include those variables.

Irrelevance of Panton-Valentine leukocidin in hidradenitis suppurativa: results from a pilot, observational study.

Panton-Valentine leukocidin (PVL) appears to be a virulence factor which, among others, can exacerbate the pathogenicity of Staphylococcus aureus infections, especially inducing severe necrotic, deep-seated skin infections, abscesses, and recurrences. These peculiarities have some overlaps with hidradenitis suppurativa (HS). Our main aim was to assess if S. aureus producing PVL could have some role in influencing clinical features and/or course of HS, specifically in the suppuration and recurrence of lesions. This pilot, mono-centric, observational study included all adult subjects affected with HS consecutively referring to our HS clinic over a 3-month period. Clinically evident suppuration and at least 2 weeks wash out from any antibiotic were the main inclusion criteria. Purulent material from HS skin lesions was collected with swabs in order to isolate micro-organisms, with specific regard to S. aureus. Detection of PVL was performed by real-time quantitative PCR (RT-qPCR). We also analyzed purulent material from suppurative skin lesions other than HS, as a control. Thirty HS patients were included; 29 purulent lesions (96.7%) harbored at least one bacterial species. Five (16.7%) swab samples were positive for S. aureus, none of which was positive for PVL genes. Among the 30 purulent disorders included as controls, 8 (26.3%) were positive for S. aureus; of these, 4 strains (50%) expressed LPV. The study results seem to exclude the pathogenetic involvement of S. aureus producing PVL in HS; as a result, PVL does not seem to represent a potential target in the future development of HS treatments.

Predicting in-hospital mortality for sepsis: a comparison between qSOFA and modified qSOFA in a 2-year single-centre retrospective analysis.

Sepsis is a life-threating organ dysfunction caused by a dysregulated host response to infection. This study proposed a new tool, i.e. modified qSOFA, for the early prognostic assessment of septic patients. All cases of sepsis/septic shock consecutively observed in 2 years (January 2017-December 2018), at St. Anna University Hospital of Ferrara, Italy, were included. Each patient was evaluated with qSOFA and a modified qSOFA (MqSOFA), i.e. adding a SpO2/FiO2 ratio to qSOFA. Logistic regression and survival analyses were applied to compare the two scores. A total number of 1137 consecutive cases of sepsis and septic shock were considered. Among them 136 were excluded for incomplete report of vital parameters. A total number of 668 patients (66.7%) were discharged, whereas 333 (33.3%) died because of sepsis-related complications. Data analysis showed that MqSOFA (AUC 0.805, 95% C.I. 0.776-0.833) had a greater ability to detect in-hospital mortality than qSOFA (AUC 0.712, 95% C.I. 0.678-0.746) (p < 0.001). Eighty-five patients (8.5%) were reclassified as high-risk (qSOFA< 2 and MqSOFA≥ 2) resulting in an improvement of sensitivity with a minor reduction in specificity. A significant difference of in-hospital mortality was observed between low-risk and reclassified high-risk (p < 0.001) and low-risk vs. high-risk groups (p < 0.001). We demonstrated that MqSOFA provided a better predictive score than qSOFA regarding patient's outcome. Since sepsis is an underhanded and time-dependent disease, physicians may rely upon the herein proposed simple score, i.e. MqSOFA, to establish patients' severity and outcome.

Droplet-digital PCR assay to detect Merkel cell polyomavirus sequences in chorionic villi from spontaneous abortion affected females.

Droplet-digital polymerase chain reaction (ddPCR) technique was set up to detect/quantify Merkel cell polyomavirus (MCPyV) DNA in clinical specimens, including chorionic villi and peripheral blood mononuclear cells (PBMCs) from spontaneous abortion (SA)-affected females. This ddPCR assay showed high accuracy, sensitivity, and specificity in detecting MCPyV DNA cloned in a recombinant plasmid vector, the control. ddPCR was extended to MCPyV DNA to investigate/quantify its sequences in clinical samples. Overall, 400 samples were analyzed, that is, 100 chorionic villi and 100 PBMCs, from SA females (n = 100), the cases, and 100 chorionic villi and 100 PBMCs from females who underwent voluntary pregnancy interruption (VI, n = 100), the control. MCPyV DNA was detected in 4/100 (4%) and 5/100 (5%) of SA and VI chorionic villi, respectively. The mean viral DNA load was 1.99 ( ± 0.94 standard mean deviation [SD]) copy/104 cells in SA and 3.02 ( ± 1.86 [SD]) copy/104 cells in VI. In PBMCs, MCPyV DNA was revealed in 9/100 (9%) and 14/100 (14%) of SA and VI, with a mean of 2.09 ( ± 1.17 [SD]) copy/104 cells and 4.09 ( ± 4.26 [SD]) copy/104 cells in SA and VI, respectively. MCPyV gene expression analysis by quantitative PCR for the large T antigen (LT) and viral capsid protein 1 (VP1) showed their mRNAs in 2/4 (50%) SA- and 2/5 (40%) VI-MCPyV-positive samples. MCPyV DNA was detected/quantified using the ddPCR technique, in chorionic villi and PBMCs from SA and VI. In our experimental conditions, ddPCR provided a powerful tool to detect/quantify MCPyV DNA sequences in clinical samples.

A comparison between different anti-retroviral therapy regimes on soluble inflammation markers: a pilot study.

BACKGROUND: Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and immune activation. The use of certain antiretroviral drugs can contribute to this process. METHODS: We investigated 26 potential biomarkers in serum samples from HIV-1 infected patients virologically suppressed under ART. The main objective of our study was to evaluate if virological suppression achieved with a triple drug regimen containing tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC) as backbone, could correlate with a better immunological and inflammatory profile in relation to the third class of antiretroviral drug administered. The eligible patients were then divided into 3 groups in relation to the third drug associated with TDF/FTC: nucleoside reverse transcriptase inhibitors (NNRTI) (Group 1, n = 16), protease inhibitors (PI) (Group 2, n = 17) and integrase inhibitors (INI) (Group 3, n = 16). RESULTS: Inflammatory cytokines and chemokines were more represented in Group 2 than in Group 3 (IL-1Ra, p = 0.013; IL-12p70 p = 0.039; TNF-α p = 0.041; IL-8, p = 0.027; MIP1 ß, p = 0.033). Eotaxin showed lower levels in Group 1 compared to Group 2 (p = 0.010), while IP-10 was significantly lower in Group 1 compared to both Group 2 and Group 3 (p = 0.003 and p = 0.007, respectively). CONCLUSIONS: Our results seem to discourage the administration of PI as a third drug in a virologically effective antiretroviral regimen, as its use is linked to the detection of higher levels of pro-inflammatory mediators in comparison with INI and NNRTI.

Investigation on silent bacterial infections in specimens from pregnant women affected by spontaneous miscarriage.

Miscarriage is one of the main complications occurring in pregnancy. The association between adverse pregnancy outcomes and silent bacterial infections has been poorly investigated. Ureaplasma parvum and urealiticum, Mycoplasma genitalium and hominis and Chlamydia trachomatis DNA sequences have been investigated by polymerase chain reaction (PCR) methods in chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from females with spontaneous abortion (SA, n = 100) and females who underwent voluntary interruption of pregnancy (VI, n = 100). U. parvum DNA was detected in 14% and 15% of SA and VI, respectively, with a mean of bacterial DNA load of 1.3 × 10-1 copy/cell in SA and 2.8 × 10 -3 copy/cell in VI; U. urealiticum DNA was detected in 3% and 2% of SA and VI specimens, respectively, with a mean DNA load of 3.3 × 10-3 copy/cell in SA and 1.6 × 10-3 copy/cell in VI; M. hominis DNA was detected in 5% of SA specimens with a DNA load of 1.3 × 10-4 copy/cell and in 6% of VI specimens with a DNA load of 1.4 × 10-4 copy/cell; C. trachomatis DNA was detected in 3% of SA specimens with a DNA load of 1.5 × 10-4 copy/cell and in 4% of VI specimens with a mean DNA load of 1.4 × 10-4 copy/cell. In PBMCs from the SA and VI groups, Ureaplasma spp, Mycoplasma spp and C. trachomatis DNAs were detected with a prevalence of 1%-3%. Bacteria were investigated, for the first time, by quantitative real-time PCR (qPCR) in chorionic villi tissues and PBMCs from women affected by SA and VI. These data may help to understand the role and our knowledge of the silent infections in SA.

Subclinical Leishmania infection in patients with rheumatic diseases under biological drugs.

PURPOSE: Climate changes and immunosuppression are influencing the spread of leishmaniasis and re-emergence in Northern Italy, respectively. We evaluated the prevalence of subclinical leishmaniasis in patients from a Northern Italian region with chronic inflammatory rheumatism (CIRD) receiving biological drugs (BD) and correlated it to the area of residence. METHODS: DNA from PBMC of patients affected by CIRD treated with either BD for at least 5 years (Group A) or other immunosuppressive drugs (Group B) was investigated by a qPCR for Leishmania infantum kDNA and compared to healthy subjects (Group C). Variables such as sex and age, rural areas, dog ownership, type of BD administered and association between BD and steroids, were evaluated by statistical analysis. RESULTS: A higher proportion of L. infantum DNA positivity was found in Group A than in Group C (p < 0.05), while no parasite DNA was detected in Group B. In Group A, 18/50 patients (36%) had higher rates of parasite DNA (from 1 to 136 to 1.000.000 copies/ml) than Group C (from 1 to 10 copies/ml). 14/18 (77.7%) of positive patients from Group A lived in rural areas, but no statistical differences occurred in relation to dog ownership or BD type (p < 0.0003). CONCLUSIONS: We can speculate that exposure to rural areas appears to be a factor closely linked with the risk of developing Leishmania subclinical infection. A screening with molecular methods in patients with CIRD treated with BD living in these areas and monitoring Leishmania DNA during such therapies, would be mandatory to prevent delay in diagnosis should VL symptoms appear.

Entheseal involvement in asymptomatic human immunodeficiency virus infected patients: preliminary results of a clinical and ultrasonographic study.

OBJECTIVES: As a strong association between human immunodeficiency virus (HIV) infection and spondyloarthritis (SpA) has been hypothesised, our main objective was to explore by power Doppler ultrasonography (PDUS) the presence of subclinical enthesitis in asymptomatic HIV patients. The presence of subclinical synovitis was also evaluated. METHODS: Consecutive asymptomatic HIV patients were studied and compared with asymptomatic HCV patients and healthy controls (HC). All subjects underwent a clinical and PDUS bilateral examination of the following entheses and joints: epicondyle, quadriceps, patellar, Achilles and plantar fascia; wrists, II and III metacarpo-phalangeal, knee and ankle. RESULTS: Twenty-nine HIV, 32 HCV and 25 HC were recruited; 1.032 entheses and 860 joints were examined. Clinical diagnosis of enthesitis was made in 10.3% HIV patients, 6.2% HCV patients (p=0.66) and none HC (p=0.24). PDUS enthesitis was found in 72.4% HIV, 28.1% HCV (p=0.0008) and 12% HC (p<0.0001). Clinical diagnosis of synovitis was made in 3.4% HIV patients, 9.3% HCV patients (p=0.61) and none HC (p=1). PDUS abnormalities were documented in 24.1% HIV patients, 71.8% HCV patients (p=0.0003) and none HC (p=0.0001). In detecting enthesitis and synovitis, PDUS was more sensitive than clinical examination both in HIV and HCV patients. CONCLUSIONS: Our preliminary study shows the high frequency of PDUS enthesitis in asymptomatic HIV patients, which highlights the close link between HIV and SpA. Further studies are desirable on a larger number of HIV patients to confirm these results. PDUS proved to be more sensitive than clinical examination in detecting subclinical involvement of entheses and joints.

SVR 24 Achievement Two Weeks After a Tripled Dose of Daclatasvir in an HCV Genotype 3 Patient.

Directly-acting antivirals (DAA) have changed the chronic hepatitis C virus (HCV) infection therapeutic scenario allowing virus eradication in more than 95% of patients, independently from the genotype, with 12 to 24-week treatment regimens. We describe a 51-year-old Pakistani man with a chronic HCV-genotype 3 (GT3a) infection with moderate liver fibrosis, who achieved sustained virological response (SVR) 24 after a tripled dose of Daclatasvir (DCV) taken erroneously associated to Sofosbuvir (SOF). The patient had a concomitant intestinal TB infection whose treatment had been delayed in order to firstly eradicate HCV to reduce the liver toxicity of anti-mycobacterial drugs. Thanks to the cultural mediator support, we explained to the patient the correct posology of each drug to take during the day consisting of 12 week SOF (400 mg daily) plus DCV (60 mg daily) regimen. He returned 13 days after for a programmed visit and we were surprised to learn that he had taken 3 pills of DCV (180 mg/daily) instead of one, thus ending DCV assumption after only 9 days while SOF was taken correctly. He complained no symptoms. We immediately performed blood test that showed alteration of lactate dehydrogenase, creatine phosphokinase, and creatin kinase MB activity. At day 15 we stopped SOF closely monitoring the patient. Blood test alterations returned normal after one week of treatment suspension, HCV viremia remained suppressed after 4, 12 and 24 weeks proving HCV eradication. If confirmed, these data could suggest that higher doses of DCV, if tolerated, might be employed in short-time HCV-GT3 treatment.

Bipolar Disorder With Psychotic Features and Ocular Toxoplasmosis: A Possible Pathogenetic Role of the Parasite?

Recent evidence suggests the involvement of Toxoplasma gondii infection in the emergence of psychotic and affective disorders. In this report, we describe the case of a young Brazilian woman affected by recurrent ocular toxoplasmosis and presenting with a manic episode with psychotic features in the context of a diagnosis of Bipolar Disorder (BD), type I. We observed a relationship between ocular manifestations and the clinical course of bipolar illness, confirmed by molecular analyses (nested-PCR), as well as by the high level of T. gondii specific IgG. This case report is the first showing the presence of circulating parasite DNA at the time of occurrence of psychiatric symptoms, thus providing further support for a possible role of the parasite in the pathogenesis of some cases of BD.

Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic Fluid Concentrations.

Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.). Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563.

Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies.

BACKGROUND: The purpose of this study was to investigate intrathecal production and affinity distributions of Epstein-Barr virus (EBV)-specific antibodies in multiple sclerosis (MS) and controls. METHODS: Cerebrospinal fluid (CSF) and serum concentrations, quantitative intrathecal synthesis, oligoclonal bands (OCB) patterns and affinity distributions of anti-Epstein Barr virus (EBV) antibodies were evaluated in 100 relapsing-remitting MS (RRMS) patients and 200 age- and sex-matched controls with other inflammatory neurological disorders (OIND) and other noninflammatory neurological disorders (NIND). RESULTS: Levels of anti-EBNA-1 and anti-viral capsid antigen (VCA) IgG were different in both the CSF (P <0.0001 and P <0.01, respectively) and serum (P <0.001 and P <0.05, respectively) among the RRMS, OIND and NIND. An intrathecal synthesis of anti-EBNA-1 IgG and anti-VCA IgG, as indicated by the antibody index, was underrepresented in the RRMS, OIND and NIND (range 1 to 7%). EBV-specific OCB were detected in 24% of the RRMS patients and absent in the controls. High-affinity antibodies were more elevated in the RRMS and in the OIND than in the NIND for CSF anti-EBNA-1 IgG (P <0.0001) and anti-VCA IgG (P <0.0001). After treatment with increasing concentrations of sodium thiocyanate, the EBV-specific IgG OCB had low affinity in all 24 RRMS patients analyzed. CONCLUSIONS: Our findings do not support the potential role of an EBV persistent brain chronic infection in MS and suggest that an EBV-specific intrathecal oligoclonal IgG production can occur in a subset of MS patients as part of humoral polyreactivity driven by chronic brain inflammation.

Vaginal lactoferrin administration before genetic amniocentesis decreases amniotic interleukin-6 levels.

AIM: To verify the eventual efficacy of lactoferrin (LF), an iron-binding glycoprotein, to decrease the amniotic concentration of interleukin-6 (IL-6). METHODS: We prospectively enrolled 60 Caucasian patients at the 16th week of their singleton physiological gestation. A vaginal compound containing 300 mg of LF was administered randomly 4 or 12 h prior to amniocentesis, as to obtain 3 groups: A, 20 untreated patients; B, 20 treated 4 h before amniocentesis; C, 20 treated 12 h before amniocentesis. RESULTS: A normal karyotype was registered in all cases. The comparison of the distribution of IL-6 among the 3 groups showed a highly significant difference (p = 0.001). The difference between mean values of group B and both groups C and A was shown to be highly significant (p = 0.006 and p = 0.03, respectively). In contrast, there was no significant difference between mean values of groups A and C. CONCLUSION: Vaginal LF administration decreases amniotic IL-6 concentration. We therefore suggest that the glycoprotein may exert a protective role against ominous pregnancy complications linked to an increased level of the cytokine, such as abortion secondary to amniocentesis.

About Chlamydia trachomatis. Reply to Garcia-Teillard et al. Trachoma and the Importance of Sexual Infective Route in Developed Countries. Comment on "Gallenga et al. Why the SAFE-S Strategy for Trachoma? Are Musca sorbens or Scatophaga stercoraria Really the Culprit?-A Brief Historical Review from an Italian Point of View. Pathogens 2023, 12, 1419".

The confirmatory comment of Garcia-Teillard et al [...].

Active myeloperoxidase: a promising biomarker to differentiate "acute" and "low-grade" peri-prosthetic joint infections from aseptic failures.

Introduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI. Methods: Synovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant. Results: Active MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78-0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11-83.81%, positive likelihood ratio 5.88, 95% CI: 2.31-14.98 and negative likelihood ratio 0.35, 95%CI: 0.24-0.51). No difference in MPO levels was found between acute and chronic low-grade PJI. Conclusion: The proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines.

Historical account of clinical observations on leprosy and related manifestations in the Comacchio area, Italy, in the XIX century.

Known before Christ and in ancient Egypt, leprosy was believed to be a mysterious disease of supernatural origin. It covered the body with lumps and sores, dulled the senses, produced altered facial features and mutilation of the limbs. By the 6th century AD, the disease had certainly made its appearance in Western Europe and continued to occur in the following centuries. It was also thought to be attributable to poverty and poor sanitation. Leprosy was not considered an infectious disease until 1873, when physician G. H. A. Hansen first identified Mycobacterium leprae, calling it Hansen's bacillus, and the disease was named Hansen's disease. This paper analyses clinical reports on leprosy observed in Northern Italy, in the Comacchio area near Ferrara (Po Delta), in the 19th century, taking into consideration documents and manuscripts of the time. The scholars who made the greatest contribution to the description of the disease in and around Comacchio area were Antonio Campana, Andrea Verga, Alessandro Colla, Clodoveo Biagi, Ottone Schrön, Giacomo Sangalli, Raffaele Cavalieri, and local physicians Cristoforo Belloli, and Francesco Ballotta. Observations on the manifestations of the disease and attempts to cure it, including milk diet, are reported. In particular, this morbid form, which was not found in neighboring territories, was called "Mal di formica" because of its benignity at onset, its slowness and its slow progress. Tubercular Leprosy or Mal di fegato, a form of incurable leprosy was nothing more than the leprosy or elephantiasis described by the Greeks and Hebrews. The people most affected were women, who accounted for two-thirds of the sick. According to some authors, the causes of leprosy could be attributed to overuse of certain rotten or salted fish. Campana was the first to think that a lazaret should be erected for the sick.

Special Issue: Advances in SARS-CoV-2 Infection.

Coronavirus Disease 2019 (COVID-19) is a life-threatening disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus which was first reported in late 2019 in China, from where it then spread worldwide [...].