Recent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients. This case–control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin). The primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13–0.87 and OR 0.43, 95% CI 0.23–0.79, respectively). Improved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results. ClinicalTrials.gov NCT03094494 . Registered 28 March 2017.

Introduction: Nosocomial pneumonia develops after ≥48 h of hospitalisation and is classified as ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP); the latter may require mechanical ventilation (V-HAP) or not (NV-HAP).Main findings: VAP and HAP affect a significant proportion of hospitalised patients and are characterised by poor clinical outcomes. Among them, V-HAP has the greatest 28-day mortality rate followed by VAP and NV-HAP (27.8%versus18%versus14.5%, respectively). However, no differences in terms of pathophysiology, underlying microbiological pathways and subsequent therapy have been identified. International guidelines suggest specific flow charts to help clinicians in the therapeutic management of such diseases; however, there are no specific recommendations beyond VAP and HAP classification. HAP subtypes are scarcely considered as different entities and the lack of data from the clinical scenario limits any final conclusion. Hopefully, recent understanding of the pathophysiology of such diseases, as well as the discovery of new therapies, will improve the outcome associated with such pulmonary infections.Conclusion: Nosocomial pneumonia is a multifaced disease with features of pivotal interest in critical care medicine. Due to the worrisome data on mortality of patients with nosocomial pneumonia, further prospective studies focused on this topic are urgently needed.

Diagnostic delay (DD) is associated with poor radiological and quality of life outcomes in axial spondyloarthritis (ax-SpA) and ankylosing spondylitis (AS). The female (F) population is often misdiagnosed, as classification criteria were previously studied mostly in males (M). We conducted a systematic review to investigate (i) the difference in DD between the sexes, the impact of HLA*B27 and clinical and social factors (work and education) on this gap, and (ii) the possible influence of the year of publication (before and after the 2009 ASAS classification criteria), geographical region (Europe and Israel vs. extra-European countries), sample sources (mono-center vs. multi-center studies), and world bank (WB) economic class on DD in both sexes. We searched, in PubMed and Embase, studies that reported the mean or median DD or the statistical difference in DD between sexes, adding a manual search. Starting from 399 publications, we selected 26 studies (17 from PubMed and Embase, 9 from manual search) that were successively evaluated with the modified Newcastle–Ottawa Scale (m-NOS). The mean DD of 16 high-quality (m-NOS > 4/8) studies, pooled with random-effects meta-analysis, produces results higher in F (1.48, 95% CI 0.83–2.14, p < 0.0001) but with significant results at the second analysis only in articles published before the 2009 ASAS classification criteria (0.95, 95% CI 0.05–1.85, p < 0.0001) and in extra-European countries (3.16, 95% CI 2.11–4.22, p < 0.05). With limited evidence, some studies suggest that DD in F might be positively influenced by HLA*B27 positivity, peripheral involvement, and social factors.

The potential role of the COVID-19 vaccine and infection to induce autoimmunity is currently underestimated despite the literature emphasizing arthralgia as a common adverse event. We aimed to study the impact of rheumatological complications post-COVID-19 (PC) and post-COVID-19 vaccine (PCV), comparing undifferentiated arthritis (UA) to Polymyalgia Rheumatica, Horton’s Arteritis (PMR-HA) and isolated arthritis to UA with “connective-like” accompanying symptoms. We retrospectively included 109 patients with at least 6 months of follow-up, analyzing serum biomarkers, joint ultrasound (US), lung HRCT, DLCO, and HLA haplotypes. There were 87 UA patients showing increased gastrointestinal and lung involvement (p = 0.021 and p = 0.012), higher anti-spike protein IgG levels (p = 0.003), and anti-SARS-CoV-2 IgG positivity (p = 0.003). Among them, 66 cases progressed to ACR-EULAR 2010 early arthritis after 3 months, whereas PMR-HA patients were more commonly PCV (81.8%, p = 0.008), demonstrating higher CRP (p = 0.007) and ESR (p = 0.006) levels, a lower rate of ANA positivity (p = 0.005), and a higher remission rate after six months (p = 0.050). In UA patients, the prevalent HLA was DRB1*11 and C*07 (36.8% and 42.1%). Serum calprotectin, interleukin-6, and C*07 (p = 0.021, 0.041, 0.018) seemed more specific for isolated UA. Conversely, “connective-like” arthritis showed poorer DLCO (p = 0.041) and more frequent US synovitis (p = 0.041). In conclusion, UA is a frequent common PC and PCV complication and may persist over time when compared to PMR-HA.

Super-refractory status epilepticus (SRSE) is a life-threatening condition characterized by the persistence or recurrence of seizures despite the use of first- and second-line antiepileptic drugs and the continuous infusion of anesthetics for more than 24 hours. This has always been a challenge for the physician, given the high mortality and morbidity related to this condition. Unfortunately, there are currently no definitive data to guide the therapy, since most of the therapeutic approaches regarding SRSE come from anecdotal evidence. Here, we present a case report of long-persisting new-onset SRSE treated with unconventional therapies recently reported to be successful such as ketamine, ketogenic diet, and tocilizumab, that could have played an important role in the management of this patient. A review of the literature regarding those is also included. SRSE has been reported to have long hospital length of stay, with a small percentage of patients returning to baseline functional status. Moreover, recent evidence showed that functional and cognitive outcome could depend on seizure duration, so prolonged duration of epileptic activity with abnormalities on the magnetic resonance imaging (MRI) could be seen as a reason to discontinue treatment. However, despite many weeks of seizures and a noncomforting MRI, our patient was discharged with a good functional status.