IgG4-related hypertrophic pachymeningitis (IgG4-HP) may coexist with autoimmune diseases, malignancies, or infectious diseases. We describe a case of a patient with both possible IgG4-HP and anti-N-methyl-D-aspartate receptor (NMDAR) disease. A 67-year-old woman was admitted to the emergency department due to persistent speech difficulties. An MRI scan of her brain showed diffuse T1-isointense contrast enhancement. High IgG4 concentrations were found in the serum and CSF, and NMDAR antibodies were detected in the CSF. A dura biopsy showed lymphoplasmacytic infiltration of IgG4-positive plasma cells. She was treated with intravenous corticosteroid therapy for five days but was referred to us again approximately one month later due to psychosis and behavioral changes. Corticosteroid therapy was started again, improving her condition. The implications of the coexistence of possible IgG4-HP and anti-NMDAR disease are unclear. An accurate diagnosis of both conditions is needed to avoid suboptimal control of the clinical course. Close collaboration between the involved professionals is warranted.

Objectives:Monocyte Distribution Width (MDW) is the standard deviation of the mean volume of monocytes and may indicate innate immune activation. We investigated the possible association between MDW values and late HIV diagnosis in consecutive patients. Methods:We retrospectively enrolled newly diagnosed HIV patients admitted to our clinical center. Demographic and clinical characteristics were analyzed. Results:A total of 97 patients were enrolled. Of these, 63% were late presenters and 43% fulfilled the criteria for advanced HIV disease. Continuous measures showed a significant inverse correlation between CD4 T-cell count and MDW. Multivariate analysis showed that MDW≥21.1 (OR:7.45, 2.13-30.54), HIV viral load >5 log (10) c/mL (OR:3.62, 1.04-13.30), blood lymphocytes<2 x103/μL (OR:14.82, 3.19-111.8) and HIV testing without symptoms (OR:0.21, 0.05-0.82) were independently associated with late presentation. Similarly, adjusted ORs for MDW≥22.5 (OR:4.03, 1.28-13.17), blood lymphocytes<1 x103/μL (OR:9.67, 2.19-57.57), age (OR:1.05, 1.00-1.10) and HIV testing without symptoms (OR:0.16, 0.04-0.52) were significantly associated with advanced HIV disease. Conclusions:Our results suggest that MDW may be a potential flagging parameter of innate immune activation in HIV infection. Continuous measurements of MDW showed a significant inverse correlation with CD4 T-cell count.Patients with increased MDW values were more likely to be diagnosed late.

Many cases of encephalitis are caused by an autoimmune response, and some are associated with underlying malignancies. Here we present the case of a 17-year-old female patient who was admitted to the pediatric ward with acute gastroenteritis, seizures, and behavioral changes. A brain computed tomography (CT) scan ruled out acute infarction, haemorrhage, mass lesions, and other intracranial injuries, while the initial EEG showed no epileptic discharges. In the absence of a definitive diagnosis, midazolam was administered to treat tonic-clonic seizures, while ceftriaxone and acyclovir were started for suspected infection. However, her condition deteriorated further and she was transferred to the ICU, where she was intubated. A Cell-Based Assay (CBA) revealed the presence of anti-NMDAR antibodies and a contrast-enhanced brain MRI showed leptomeningeal enhancement without limbic involvement. She was subsequently treated with intravenous immunoglobulins and high-dose corticosteroids. A subsequent transabdominal ultrasound scan revealed an oval, fluid-filled ovarian cyst. Based on these findings, her right ovary was removed, resulting in a gradual improvement in her condition. This case highlights that paraneoplastic autoimmune encephalitis may be misclassified due to persistent psychiatric symptoms with negative EEG and CSF findings. When clinical suspicion remains high despite negative initial instrumental and laboratory findings, it is essential to repeat these investigations. In such cases, neuroantibody testing may play a crucial role in establishing the diagnosis.

Background:Neuromyelitis optica spectrum disorders (NMOSDs) are degenerative diseases frequently associated with severe recurrences and high risk of progressive disability. In this report, we describe an unusual case of a patient with the coexistence between NMOSD and mixed connective tissue disease (MCTD). Case Description:A 58-year-old Caucasian man was admitted to the Emergency Department (ED) with low back pain and walking inability. He had an unsteady gait, paraesthesia of the lower limbs and pain in the left lumbar area of the spine. He previously manifested repeated episodes of Raynaud's phenomenon. The neurological examination revealed pyramidal signs with asymmetric and progressive paraparesis associated with hypoesthesia and bladder dysfunction. A spine magnetic resonance imaging (MRI) revealed the presence of a long extensive cervico-dorsal myelitis. Among laboratory analyses, serum immunometric examinations came back positive for anti-RNP (272 U/mL) and anti-SSA (20 U/mL) antibodies, whereas a recombinant immunofluorescence assay revealed the presence of immunoglobulin G (IgG) antibodies against AQP4. Consequently, he was treated with high-doses of corticosteroids, with progressive resolution of symptoms. To date, his last cervico-dorsal spine MRI showed negative results. Conclusions:Only a few anecdotal cases of the coexistence between NMOSD and MCTD have so far been described, and many clinical aspects of this association are not yet fully known. Missed diagnosis of rheumatologic or neurologic diseases may lead to treatment delay and, potentially, irreversible disability. Closer collaboration between neurologists and rheumatologists is needed for the early diagnosis of both diseases.

We planned a systemic review and meta-analysis to evaluate the diagnostic accuracy of Monocyte Distribution Width (MDW) in aiding the diagnosis of sepsis in the Emergency Department (ED) and Intensive Care Unit (ICU). A systematic literature search was performed in PubMed, Scopus, and OVID to retrieve studies published up to 29 January 2024. We examined results using mean difference and conducted a diagnostic test accuracy (DTA) meta-analysis using a bivariate random effects model. Pooled results showed that MDW was significantly higher in sepsis patients admitted to the ED (MD = 5.59, 95%CI: 4.14-7.05) or to the ICU (MD = 8.30, 95%CI: 2.98-13.62). Nine studies conducted in the ED were included in the DTA review. The overall sensitivity was 0.80 (95%CI: 0.75-0.85), the specificity was 0.76 (95%CI: 0.66-0.83), and the false-positive rate (FPR) was 0.24 (95%CI: 0.17-0.34). Three studies were conducted in the ICU, but only two were included in the DTA meta-analysis. Of the 662 patients admitted to the ICU, 175 developed sepsis, showing higher MDW values than non-septic patients. However, significant heterogeneity was noted among the studies. MDW is a helpful biomarker for sepsis in adult patients admitted to the ED and ICU. In the ED, MDW could aid clinicians in ruling out sepsis.

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11-2.02), SAPS II (OR: 1.05, CI: 1.01-1.1), SOFA score (OR: 1.37, CI: 1.06-1.76), lymphocytopenia (OR: 32.5, CI: 3.45-306.4), viral reactivation (OR: 9.75, CI: 1.72-55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8-271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98-2.05), lymphocytopenia (OR: 18.2, CI: 0.87-371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77-123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients' care.

Background: Dalbavancin is a long-acting lipoglycopeptide, approved for treatment of skin and skin structure infections. Its PK/PD profile and safety allow for short hospital stays even in the case of difficult-to-treat infections requiring long courses of therapy, e.g., osteomyelitis, cardiovascular, and prosthetic infections. Objectives: We aimed to evaluate the safety and efficacy of dalbavancin in real life settings for both in-label and off-label indications. Methods: retrospective evaluation of all consecutive patients treated with dalbavancin at our site between May 2017 and September 2021. Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson Comorbidity Index CCI = 2.7, 28% inpatients) were included with the following indications: acute bacterial skin and skin structure infections (22%), bone and prosthetic infections (57%), and cardiovascular infections (19%). Infections were caused by MSSA (30%), MRSA (5%), MR-CoNS (20%), and Streptococcus spp. (8%). In 32 cases, no isolate was obtained. The average number of infusions was 5 (s.d. = 3). Neither ensuing alteration of renal function nor neutropenia or thrombocytopenia were observed during treatment and follow-up. Two self-limiting skin rashes occurred. The overall clinical success rate was 84%-91% for registered and 82% for unregistered indications. The prescription of higher loading doses was the only predictor independently associated with better outcomes in multivariate models (OR: 5.2, 95%CI: 1.5-17.9, p < 0.01). Conclusions: Dalbavancin proved to be effective for skin and skin structure infections, as well as for difficult-to-treat infections in highly comorbid patients. Regarding tolerability, our results support the use of dalbavancin for long-lasting treatments of deep-seated infections.

Varicella is a benign, self-limiting disease, but both primary VZV infection and VZV reactivation can be life-threatening in immunocompromised children, due to CNS and systemic dissemination of the virus. Reactivation of the vaccine-type VZV (vOka) has been reported sporadically, although SARS COV2 infection may have recently played a role in facilitating VZV reactivation. Here we report on the case of a young boy with Acute Lymphocytic Leukemia, in remission after induction chemotherapy, and recent SARS COV 2 infection. He developed VZV encephalitis due to massive reactivation of VZV virus, complicated by PRES, diagnosed with brain MRI, and Super Refractory Status Epilepticus, lasting until substantial suppression of VZV replication in the CNS. We also report and discuss the role of the remarkably augmented renal clearance persistently observed in our patient, complicating CNS involvement and making both antiviral and antiepileptic treatments more difficult to manage. Effective neuroprotection was completed by physical hypothermia and infusion of IVIG and steroids. The patient obtained complete functional recovery, with reversion of MRI signs of occipital involvement at presentation, at 6-month follow-up. Intense and daily interplay of intensivists, neurologists, hematologists and infectious disease experts likely made his uneventful recovery possible, combining all skills necessary to manage his unusual and complex clinical picture.

INTRODUCTION: The spectrum of cancer therapy-related cardiovascular toxicity (CTR-CVT) is one of the major complications of cancer therapies and causes increased morbidity and mortality in oncologic patients. Anthracyclines, Anti-HER2 drugs, fluoropyrimidines, VEGF and TK1 inhibitors, and immune-checkpoint inhibitors are known to increase the risk of premature onset of cardiac diseases. Therefore, these patients have to be strictly monitored regarding their heart functionality, also after the therapies ending since the toxic effect of these agents can also occur after years. Aim of this study was to review the guidelines written so far for the management of CTR-CVT.EVIDENCE ACQUISITION: The literature research was performed by using the PRISMA Statement. It was conducted on August 30th, 2022 on the PubMed library, using the following keywords: “Cardiotoxicity guidelines” and “Cardiooncology guidelines.” Other guidelines known by the authors and judged relevant to the aim of this study were also considered.EVIDENCE SYNTHESIS: The selection process of the studies is schematically showed by the PRISMA flow-chart. A total of 603 articles (601 from PubMed and two from other sources) were identified. After the removal of 77 duplicates, 526 studies were retrieved. Five hundred and thirteen articles were excluded since they did not match the inclusion criteria. Therefore, 13 studies were included.CONCLUSIONS: Currently, guidelines recommended a careful monitoring for patients receiving potentially cardiotoxic treatment and they are fairly uniform about the approaches. Before the onset of the anticancer therapy, the oncologic patients should be stratified for the risk to develop cardiovascular complications. Risk assessment should include measurement of cardiac function. Strategies for screening and detection of cardiotoxicity include cardiac imaging (echocardiography, nuclear imaging, cardiac magnetic resonance) and cardiac biomarkers (troponin, natriuretic peptides). Although echocardiography is the method of choice, other imaging methods are recommended to improve reproducibility. Cardiac biomarkers, albeit not common used in clinical practice, are a reliable diagnostic tool for the early identification and monitoring of cardiotoxicity. A combined approach based on cardiac imaging and biomarkers looks promising. Identifying early cancer therapy-related cardiac dysfunction before a significant decline in LVEF may allow clinicians to promptly start cardioprotective treatments. Therefore, in patients with asymptomatic CTR-CVT (LVEF ≥50% with a significant new global longitudinal strain (GLS) reduction and/or cardiac biomarker increase), a cardioprotective therapy with (ACE-I/ARB and/or beta-blockers) should be considered. Currently, there are no evidence-based guidelines on how often or how long cardiac function should be monitored during and after cancer treatment. The timing of surveillance depends greatly on the cardiovascular risk of cancer patients and treatment protocol so that further research needs to establish the optimal protocol.

Background: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. Methods: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. Results: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%–1.4%,) and 6.5% (95% CI: 4.7–8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5–54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. Conclusions: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

The assessment of biological variability (BV) of tumour markers is of particular interest to laboratory medicine professionals who are frequently consulted for their opinion or interpretation of a result compared to one or more previous values. In the database maintained by Ricos et al. were reported intra-subject biological variability (CVI) values of several tumour markers which had been often obtained with outdated instrumentation and reported in articles dated and of limited impact. For example, the CVI values of the tumour markers most frequently requested in clinical laboratories in the data-base maintained by Ricos et al. and available on Westgard‘s website through 2018 were obtained from sixteen articles (ten for CEA, five for CA 15-3, four for CA 125, three for PSA and two for CA 19-9); five of these references were conference abstracts, one was a dissertation, and only four had been published after 2000. The limits of the data-base had been pointed out and correctives such as checklists were proposed to standardize the evaluation of articles and multicenter studies were planned that would comply with them and allow for calculating more correctly CVI in order to generate a new BV data-base. The European Federation of Clinical Chemistry and Laboratory Medicine made this very challenging commitment in 2014. It must be acknowledged (and known) that as of 2015 the work done has been truly relevant and laboratory medicine professionals from our country have played a significant role. A real open-air mine of what has been unearthed and what is still being excavated is now available. This review aims to document which aspects have been clarified and corrected and which ones remain undefined (for example, the comparability of CVI in the healthy subject and that in the subject with cancer and other severe non-neoplastic disease). Finally, the main points related to the state of the art on the BV and indicators of neoplasia have been summarized.

BackgroundUndesired intrathecal injections represent an important subset of medical errors, albeit rare. Clinical effects depend on the type and concentration of drug(s) injected. Here we report on the case of a healthy woman with persistent low back pain, treated with a paravertebral injection of lidocaine, thiocolchicoside, and l-acetylcarnitine at an orthopedic practice.Case reportA 42-year-old Caucasian woman, with no relevant past medical history, received a lumbar paravertebral injection of lidocaine, thiocolchicoside, and l-acetylcarnitine for persistent low back pain. Approximately 30 minutes after injection, she experienced quick neurological worsening. Upon arrival at the Emergency Department, she was comatose, with fixed bilateral mydriasis, trismus, and mixed acidosis; seizures ensued in the first hours; slow progressive amelioration was observed by day 6; retrograde amnesia was the only clinical relevant remaining symptom by 6 months.ConclusionsTo our knowledge, this is the first reported case of inadvertent intrathecal thiocolchicoside injection in an adult patient, as well as the first in the neurosurgical literature. Our experience suggests that injection therapy for low back pain should be administered in adequate settings, where possible complications may be promptly treated.

We investigated the possible role of the immune profile at ICU admission, among other well characterized clinical and laboratory predictors of unfavorable outcome in COVID-19 patients assisted in ICU. Retrospective analysis of clinical and laboratory data collected for all consecutive patients admitted to the ICUs of the General Hospital of Pescara (Abruzzo, Italy), between 1st March 2020 and 30th April 2021, with a confirmed diagnosis of COVID-19 respiratory failure. Logistic regressions were used to identify independent predictors of bacteremia and mortality. Out of 431 patients included in the study, bacteremia was present in N = 191 (44.3

Abstract Background Monocyte Distribution Width (MDW), a simple cellular marker of innate monocyte activation, can be used for the early recognition of sepsis. We performed an observational prospective monocentric study to assess the predictive role of MDW in detecting sepsis in a sample of consecutive patients presenting at the Emergency Department. Methods Prospective observational study using demographic and clinical characteristics, past medical history and other laboratory measurements to predict confirmed sepsis using multivariate logistic regression. Results A total of 2724 patients were included in the study, of which 272 (10%) had sepsis or septic shock. After adjusting for known and potential risk factors, logistic regression found the following independent predictors of sepsis: SIRS equal to 1 (OR: 2.32, 1.16–4.89) and 2 or more (OR: 27.8, 14.8–56.4), MDW > 22 (OR: 3.73, 2.46–5.70), smoking (OR: 3.0, 1.22–7.31), end stage renal function (OR: 2.3, 1.25–4.22), neurodegenerative disease (OR: 2.2, 1.31–3.68), Neutrophils ≥ 8.9 × 103/µL (OR: 2.73, 1.82–4.11), Lymphocytes < 1.3 × 103/µL (OR: 1.72, 1.17–2.53) and CRP ≥ 19.1 mg/L (OR: 2.57, 1.63–4.08). A risk score derived from predictive models achieved high accuracy by using an optimal threshold (AUC: 95%; 93–97%). Conclusions The study suggests that incorporating MDW in the clinical decision process may improve the early identification of sepsis, with minimal additional effort on the standard procedures adopted during emergency care.

BACKGROUND:The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms.CASE PRESENTATION:A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure.CONCLUSIONS:Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.

Abstract Background The hospital management of patients diagnosed with COVID-19 can be hampered by heterogeneous characteristics at entry into the emergency department. We aimed to identify demographic, clinical and laboratory parameters associated with higher risks of hospitalisation, oxygen support, admission to intensive care and death, to build a risk score for clinical decision making at presentation to the emergency department. Methods We carried out a retrospective study using linked administrative data and laboratory parameters available in the initial phase of the pandemic at the emergency department of the regional reference hospital of Pescara, Abruzzo, Italy, March–June 2020. Logistic regression and Cox modelling were used to identify independent predictors for risk stratification. Validation was carried out collecting data from an extended timeframe covering other variants of concern, including Alpha (December 2020–January 2021) and Delta/Omicron (January–March 2022). Results Several clinical and laboratory parameters were significantly associated to the outcomes of interest, independently from age and gender. The strongest predictors were: for hospitalisation, monocyte distribution width ≥ 22 (4.09; 2.21–7.72) and diabetes (OR = 3.04; 1.09–9.84); for oxygen support: saturation < 95% (OR = 11.01; 3.75–41.14), lactate dehydrogenase≥237 U/L (OR = 5.93; 2.40–15.39) and lymphocytes< 1.2 × 103/μL (OR = 4.49; 1.84–11.53); for intensive care, end stage renal disease (OR = 59.42; 2.43–2230.60), lactate dehydrogenase≥334 U/L (OR = 5.59; 2.46–13.84), D-dimer≥2.37 mg/L (OR = 5.18; 1.14–26.36), monocyte distribution width ≥ 25 (OR = 3.32; 1.39–8.50); for death, procalcitonin≥0.2 ng/mL (HR = 2.86; 1.95–4.19) and saturation < 96% (HR = 2.74; 1.76–4.28). Risk scores derived from predictive models using optimal thresholds achieved values of the area under the curve between 81 and 91%. Validation of the scoring algorithm for the evolving virus achieved accuracy between 65 and 84%. Conclusions A set of parameters that are normally available at emergency departments of any hospital can be used to stratify patients with COVID-19 at risk of severe conditions. The method shall be calibrated to support timely clinical decision during the first hours of admission with different variants of concern.

Abstract Background Monocyte Distribution Width (MDW), a simple proxy marker of innate monocyte activation, can be used for the early recognition of sepsis along with Procalcitonin. This study explored the added value of MDW as an early predictor of ensuing sepsis in patients hospitalised in an Intensive Care Unit. Methods We performed an observational prospective monocentric study to estimate the analytical performance of MDW in detecting ensuing sepsis in a sample of consecutive patients assisted in an Intensive Care Unit for > 48 h for any reason. Demographic and clinical characteristics, past medical history and other laboratory measurements were included as potential predictors of confirmed sepsis in multivariate logistic regression. Results A total of 211 patients were observed, 129 of whom were included in the final sample due to the suspect of ensuing sepsis; of these, 74 (57%) had a confirmed diagnosis of sepsis, which was best predicted with the combination of MDW > 23.0 and PCT > 0.5 ng/mL (Positive Predictive Value, PPV: 92.6, 95% CI: 82.1–97.9). The best MDW cut-off to rule out sepsis was ≤20.0 (Negative Predictive Value, NPV: 86.4, 95% CI: 65.1–97.1). Multivariate analyses using both MDW and PCT found a significant association for MDW > 23 only (OR:17.64, 95% CI: 5.53–67.91). Conclusion We found that values of MDW > 23 were associated with a high PPV for sepsis, whereas values of MDW ≤ 20 were associated with a high NPV. Our findings suggest that MDW may help clinicians to monitor ICU patients at risk of sepsis, with minimal additional efforts over standard of care.

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and β-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.