Quantification of 1,3-ß-d-glucan by Wako ß-glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study.

OBJECTIVES: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available ß-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. METHODS: BDG results by Wako ß-glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. RESULTS: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1-3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut-offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). CONCLUSIONS: The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

Intensive multidisciplinary management in critical care patients affected by severe necrotizing soft tissue infections: a cooperative method to improve the efficacy of treatment.

To illustrate the effectiveness of our intensive multidisciplinary management (IMM) in the treatment of severely ill patients with necrotizing soft tissue infections (NSTIs). A retrospective observational study was conducted in a general ICU. Thirty-two consecutive patients undergoing IMM were carefully compared with 30 consecutive patients receiving a standard management (SM). IMM combined intensive care management, early surgical debridement followed by daily inspection of surgical wounds, close microbiological surveillance, and targeted high-dose antibiotics. IMM was associated with the better decrease of daily SOFA score (p = 0.04). Also, IMM caused + 12% increase in the overall number of surgical procedures (p = 0.022) and a higher number of tissue biopsies/per day (median 0.63 versus 0.32; p = 0.025), leading to a more targeted antimicrobial changes (89.6% vs 51.6%; p < 0.00001). High-dose daptomycin (75% vs 36.7%; p = 0.002) and extended/continuous infusion of beta-lactams (75% vs 43.3%; p = 0.011) were more frequently utilized. A specific efficiency score correlated with the decrease of SOFA score (efficacy) in IMM patients only (p = 0.027). Finally, IMM was associated with a significant lower ICU mortality rate (15.6% vs 40%; p = 0.032). IMM was more effective than SM as it allowed the earlier control of infection and the faster reduction of multiple organ-dysfunction.

Promoting resilience in the acute phase of the COVID-19 pandemic: Psychological interventions for intensive care unit (ICU) clinicians and family members.

This contribution draws from the experience of intensive care unit psychologists at 2 frontline hospitals in Milan, Italy, during the acute phase of the COVID-19 pandemic. In this contribution, we describe the main psychological needs observed in clinicians and in the families of COVID-19 patients and illustrate some psychological interventions implemented to respond to these needs. Containing emotions and promoting resilience were the aims of our interventions. In the future, psychological interventions should focus on the elaboration of traumatic experiences and losses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

In vivo acquisition and risk of inter-species spread of bla KPC-3-plasmid from Klebsiella pneumoniae to Serratia marcescens in the lower respiratory tract.

In recent years, Serratia marcescens has emerged as an important agent of hospital-acquired infections, such as pneumonia, urinary tract infection, septicaemia and meningitis, particularly in vulnerable patients. Compared to Klebsiella pneumoniae and Escherichia coli, S. marcescens is less commonly associated with bla KPC genes, yet few cases of plasmid transmission at the gastrointestinal level from K. pneumoniae carbapenemase (KPC)-producing Enterobacterales to S. marcescens have been described. Here we report a case of in vivo acquisition, during a 3-month period of hospitalization in the intensive care unit, of a bla KPC-3 gene carried by a pKpQIL-IT plasmid, and its probable transmission at the bronchial level among different species of Enterobacterales, including K. pneumoniae and S. marcescens. By using whole genome sequence analyses we were able provide insight into the dynamics of carbapenem-resistance determinants acquisition in the lower respiratory tract, a novel anatomical region for such plasmid transmission events, that usually involve the gastrointestinal tract. The co-presence at the same time of both wild-type and resistant Enterobacterales could have been the critical factor leading to the spread of plasmids harbouring carbapenem-resistance genes, of particular importance during surveillance screenings. The possibility of such an event may have significant consequences in terms of antimicrobial treatment, with a potential limitation of therapeutic options, thereby further complicating the clinical management of high-risk critically ill patients.

Hemophagocytic lymphohistiocytosis complicated by multiorgan failure: A case report.

RATIONALE: We present a case of hemophagocytic lymphohistiocytosis (HLH) with severe pulmonary complication and acute respiratory distress syndrome (ARDS) hospitalized in our intensive care unit (ICU) in 2014; distinctive trait of this case has been the challenging diagnosis, with a bone marrow biopsy always negative, the severe pulmonary complication with ARDS and severe pulmonary hypertension, and the ferritin temporal kinetics that precisely followed the clinical course of disease. PATIENT CONCERNS: A 32-year-old woman from the Philippines first diagnosed with upper airway infection, was subsequently hospitalized in infectious disease department and treated for community acquired pneumonia. DIAGNOSES: After clinical picture worsened with a profound respiratory insufficiency, the patient was intubated and transferred to our ICU. During this hospitalization, the clinical picture of fever, cutaneous rashes, lymphadenitis, hepatitis, leukopenia, anemia, hyperferritinemia, hypertriglyceridemia, high level of auto-antibodies, and low NK activity suggested an hemophagocytic lymphohistiocytosis syndrome, even if bone marrow biopsy was negative for hemophagocytosis. INTERVENTIONS: Immunosuppressive therapy with dexamethasone and etoposide was started, and the patient was discharged from ICU 4 months after admission. LESSONS: HLH is a rare disorder of the mononuclear phagocytic system, characterized by systemic proliferation of non- neoplastic histiocytes. The diagnosis is often challenging and not all of the diagnostic criteria may be present at the same time; this case shows how complex the diagnosis could be, how hematic ferritin levels could help in following the course of the disease, and the possibility of severe pulmonary complication either due to the disease itself and to possible sovra infections.

Combined totally mini-invasive approach in necrotizing pancreatitis: a case report and systematic literature review.

BACKGROUND: Currently, both the step-up approach, combining percutaneous drainage (PD) and video-assisted retroperitoneal debridement (VARD), and endoscopic transgastric necrosectomy (ETN) are mini-invasive techniques for infected necrosis in severe acute pancreatitis. A combination of these approaches could maximize the management of necrotizing pancreatitis, conjugating the benefits from both the experiences. However, reporting of this combined strategy is anecdotal. This is the first reported case of severe necrotizing pancreatitis complicated by biliary fistula treated by a combination of ETN, PD, VARD, and endoscopic biliary stenting. Moreover, a systematic literature review of comparative studies on minimally invasive techniques in necrotizing pancreatitis has been provided. CASE PRESENTATION: A 59-year-old patient was referred to our center for acute necrotizing pancreatitis associated with multi-organ failure. No invasive procedures were attempted in the first month from the onset: enteral feeding by a naso-duodenal tube was started, and antibiotics were administered to control sepsis. After 4 weeks, CT scans showed a central walled-off pancreatic necrosis (WOPN) of pancreatic head communicating bilateral retroperitoneal collections. ETN was performed, and bile leakage was found at the right margin of the WOPN. Endoscopic retrograde cholangiopancreatography confirmed the presence of a choledocal fistula within the WOPN, and a biliary stent was placed. An ultrasound-guided PD was performed on the left retroperitoneal collection. Due to the subsequent repeated onset of septic shocks and the evidence of size increase of the right retroperitoneal collection, a VARD was decided. The CT scans documented the resolution of all the collections, and the patient promptly recovered from sepsis. After 6 months, the patient is in good clinical condition. CONCLUSIONS: No mini-invasive technique has demonstrated significantly better outcomes over the others, and each technique has specific indications, advantages, and pitfalls. Indeed, ETN could be suitable for central WOPNs, while VARD or PD could be suggested for lateral collections. A combination of different approaches is feasible and could significantly optimize the clinical management in critically ill patients affected by complicated necrotizing pancreatitis.

Septic shock due to NSTI caused by Actinomyces Turicensis: the role of clinical pharmacology. Case report and review of the literature.

Critical septic patients affected by necrotizing soft tissue infections (NSTI) require an early, aggressive and multidisciplinary treatment. Pharmacokinetic alterations in antibiotic therapy are peculiar in these infections. Clinical pharmacology represents a first step in this setting. We report a case of septic shock due to NSTI in which clinical pharmacology is taken into account.

LAMA2 gene analysis in congenital muscular dystrophy: new mutations, prenatal diagnosis, and founder effect.

OBJECTIVE: To determine if laminin-alpha2 deficiency is due to mutations in the LAMA2 gene or secondary to mutations in other congenital muscular dystrophy genes. METHODS: We performed molecular analysis of LAMA2, by single-strand conformation polymorphism and sequencing, in 15 patients with undetectable or greatly reduced laminin-alpha2 expression. We also performed 4 prenatal diagnoses and investigated a founder effect. RESULTS: We found 1 known and 9 previously undescribed LAMA2 mutations spanning all protein domains. These were nonsense or frameshifts causing laminin-alpha2 absence or, in 1 case, a homozygous missense mutation producing partial protein expression and milder phenotype. LAMA2 mutations were undetected in 5 patients, in 2 of whom FKRP mutations explained the phenotype. In 3 prenatal cases, the fetus was heterozygous for the mutation of interest and pregnancy continued; in 1 case, the fetus was affected and aborted. In 2 patients, the Cys967Stop mutation and identical haplotypes flanking the LAMA2 gene indicated a founder effect. CONCLUSIONS: The clinical phenotype was severe in most patients with LAMA2 mutations and associated with undetectable protein expression. One case with no protein and another with partial expression had milder phenotypes. Typical white matter alterations on magnetic resonance imaging were found in all patients with LAMA2 mutations, supporting the utility of magnetic resonance imaging in differential diagnosis. The founder mutation (Cys967Stop) probably originated in Albania. Genetic characterization of affected families is mainly of use for prenatal diagnosis.

Endotoxin activity level and septic shock: a possible role for specific anti-endotoxin therapy?

Endotoxin activity (EA) plays an essential role in sepsis syndrome pathogenesis. There has been considerable interest in measuring and removing EA to predict and improve the morbidity and mortality of patients with sepsis. We performed a prospective study to assess the prevalence of EA in critically ill patients and its association with organ dysfunction and outcome, as well as in septic shock. EA (EAA(TM)) was measured within 24 h from onset of refractory septic shock in an intensive care unit. Our study demonstrated that EA level is independent from the type or the source of infection, but reflects the severity of illness in critically ill septic shock patients. Extracorporeal EA removal (PMX-HP) was assessed following our ICU clinical practice. PMX-HP seems to have better outcome, but further studies are required to verify this hypothesis.