Prognostic value of serial (1,3)-ß-D-glucan measurements in ICU patients with invasive candidiasis.

BACKGROUND: To determine whether a decrease in serum (1,3)-ß-D-glucan (BDG) was associated with reduced mortality and to investigate the performance of BDG downslope in predicting clinical outcome in invasive candidiasis. METHODS: Observational cohort study in ICU patients over a ten-year period (2012-2022) in Italy. Proven invasive candidiasis with at least 2 BDG determinations were considered. RESULTS: In the study population of 103 patients (age 47 [35-62] years, SAPS II score 67 [52-77]) 68 bloodstream and 35 intrabdominal infections were recorded. Serial measurements showed that in 54 patients BDG decreased over time (BDG downslope group) while in 49 did not (N-BDG downslope group). Candida albicans was the pathogen most frequently isolated (61%) followed by C. parapsilosis (17%) and C. glabrata (12%), in absence of any inter-group difference. Invasive candidiasis related mortality was lower in BDG downslope than in N-BDG downslope group (17% vs 53%, p < 0.01). The multivariate Cox regression analysis showed the association of septic shock at infection occurrence and chronic liver disease with invasive candidiasis mortality (HR [95% CI] 3.24 [1.25-8.44] p = 0.02 and 7.27 [2.33-22.66] p < 0.01, respectively) while a BDG downslope was the only predictor of survival (HR [95% CI] 0.19 [0.09-0.43] p < 0.01). The area under the receiver operator characteristic curve for the performance of BDG downslope as predictor of good clinical outcome was 0.74 (p = 0.02) and our model showed that a BDG downslope > 70% predicted survival with both specificity and positive predictive value of 100%. CONCLUSIONS: A decrease in serum BDG was associated with reduced mortality and a steep downslope predicted survival with high specificity in invasive candidiasis.

Antimicrobial De-Escalation in Critically Ill Patients.

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations.

Update on vitamin D role in severe infections and sepsis.

Severe infections frequently require admission to the intensive care unit and cause life-threatening complications in critically ill patients. In this setting, severe infections are acknowledged as prerequisites for the development of sepsis, whose pathophysiology implies a dysregulated host response to pathogens, leading to disability and mortality worldwide.Vitamin D is a secosteroid hormone that plays a pivotal role to maintain immune system homeostasis, which is of paramount importance to resolve infection and modulate the burden of sepsis. Specifically, vitamin D deficiency has been widely reported in critically ill patients and represents a risk factor for the development of severe infections, sepsis and worse clinical outcomes. Several studies have demonstrated the feasibility, safety and effectiveness of vitamin D supplementation strategies to improve vitamin D body content, but conflictual results support its benefit in general populations of critically ill patients. In contrast, small randomised clinical trials reported that vitamin D supplementation may improve host-defence to pathogen invasion via the production of cathelicidin and specific cytokines. Nonetheless, no large scale investigations have been designed to specifically assess the impact of vitamin D supplementation on the outcome of critically ill septic patients admitted to the intensive care unit.

Intentional ingestion of elemental mercury requiring multi-step decontamination and prophylactic appendectomy: a case report and treatment proposal.

BACKGROUND: Ingestion of elemental mercury (Hg0) is considered non-toxic. After massive ingestion, local intestinal complications may develop: retention within appendix is quite frequent but treatment is debated. We describe a case of intentional ingestion of Hg0 requiring multi-step decontamination and prophylactic appendectomy. Case detail: A 19-year-old woman was admitted to ED for abdominal pain. History revealed ingestion of large amount of Hg0 as suicide attempt. To prevent absorption, facilitate elimination, and avoid complications a conservative approach was started. Due to inefficacy of initial maneuvers colonoscopy with irrigation/aspiration was performed, repeated whole bowel irrigation was continued and second colonoscopy was performed to clean residual metal. Abdominal plain films confirmed the presence of retained mercury within the appendix in asymptomatic patient. To reduce risk of appendicitis, potential perforation, and possibly systemic toxicity, a prophylactic laparoscopic appendectomy was performed at day 5 with removal of all retained mercury without peritoneal spillage. Highest mercury concentration was 22.7 mcg/L in serum (1-4.5 mcg/L) and 5.1 mcg/L in urine (0.1-5 mcg/L). CONCLUSIONS: After ingestion, metal retention in appendix is quite frequent. Evidence about optimal treatment are different and based on case reports. A multi-step approach with multidisciplinary evaluation tailored to the patient is suggested.

Changing trends in acute upper-GI bleeding: a population-based study.

BACKGROUND: Advances in medical practice in recent decades have influenced the etiology and management of acute upper-GI bleeding (UGIB), but their impact on the incidence and mortality is unclear. OBJECTIVE: To analyze the time trends of UGIB in 2 different management eras. DESIGN: Prospective observational study. SETTING: General university-affiliated hospital. PATIENTS AND INTERVENTIONS: A total of 587 patients who presented with UGIB during the 1983-to-1985 period were compared with 539 patient in the 2002-to-2004 period. RESULTS: The overall incidence of UGIB decreased from 112.5 to 89.8 per 100,000/y, which corresponds to a 35.5% decrease after adjustment for age (95% CI, 24.2%-46.8%). The age standardized incidence of ulcer bleeding decreased by 41.6% (95% CI, 27.2%-56%); the decrease occurred only in people younger than 70 years of age. The rate of history of peptic ulcer disease decreased from 32.7% in the 1983-to-1985 period versus 19.5% in the 2002-to-2004 period (P < .001). The mean age increased from 61.0 to 68.7 years (P < .001), and the male:female ratio decreased from 2.7 to 1.8 (P = .002). The comorbidities increased from 69% to 75% (P = .01), the use of nonsteroidal anti-inflammatory drugs from 40.0% to 46.4% (P = .03), and the cases of bleeding occurring during hospitalization from 10.4% to 17.1% (P < .001). In the 1983-to-1985 cohort, the endoscopy was solely diagnostic, and antisecretory therapy consisted of H2-antagonists drugs. In the second period, 39.3% of patients underwent endoscopic therapy, whereas proton pump inhibitors were administered in 47%. Rebleeding rates decreased from 32.5% to 7.4% (P < .001) and surgery from 10.2% to 2.0% (P < .001). Overall mortality decreased from 17.1 to 8.2 per 100,000/y, which corresponded to a 60.8% decrease after adjustment for age (95% CI, 46.5%-75.1%). The age standardized mortality rate for ulcer bleeding decreased by 56.5% (95% CI, 41.9%-71.1%). LIMITATIONS: A single-center study and a potential lack of generalizability. CONCLUSIONS: From the 1983-to-1985 period to the 2002-to-2004 period, major changes occurred in the incidence of UGIB, features of patients, management, and outcomes. The incidence and mortality of UGIB overall and ulcer bleeding decreased significantly, and the decline of incidence occurred only in patients younger than 70 years old.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.

BACKGROUND: The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain. METHODS: Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy. RESULTS: Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P= 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P= 0.32). Mean units of blood transfused were 1.7 +/- 2.1 in the intensive and 1.5 +/- 2.1 in the standard regimen group (P= 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P= 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died. CONCLUSIONS: Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).