High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

BACKGROUND: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. METHODS: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DISCUSSION: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer.

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) < 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions.

Emergency Department Visits among Cancer Patients during SARS-CoV-2 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has had a global impact. Patients with cancer, their caregivers, and physicians need to balance the challenges associated with COVID-19 while ensuring cancer care. Nevertheless, emotional distress and hospital departmental reorganization could have led to a decrease in ED admissions even among oncological patients. Methods: We compared the 72 days of the pandemic in 2020 with the same calendar days in 2019 and 2021, defining a 20% decrease in ED visits as clinically significant. We studied the cause for visit, its severity, outcome (admission vs. discharge vs. death vs. hospice/palliative care), the tumor site, and method of arrival to the ED for the 3 time periods. Results: A significant decrease in ED oncological visits was found in 2020 compared to 2019, before returning to similar numbers in 2021. Fear, anxiety, and worry, in addition to hospital departmental reorganization, surely had an important role in the delay of ED visits, which resulted in irreparable consequences.

Predictors and outcomes of delirium in the emergency department during the first wave of the COVID-19 pandemic in Milan.

BACKGROUND: Respiratory infections can be complicated by acute brain failure. We assessed delirium prevalence, predictors and outcomes in COVID-19 ED patients. METHODS: This was a retrospective observational study conducted at the San Raffaele ED (Italy). Patients age >18 years attending the ED between 26 February 2020 and 30 May 2020 and who had a positive molecular nasopharyngeal swab for SARS-CoV-2 were included. The Chart-Based Delirium Identification Instrument (CHART-DEL) was used to retrospectively assess delirium. Univariable and multivariable logistic regression analyses were used to evaluate delirium predictors. Univariable binary logistic regression analyses, linear regression analyses and Cox regression analyses were used to assess the association between delirium and clinical outcomes. Age-adjusted and sex-adjusted models were then run for the significant predictors of the univariable models. RESULTS: Among the 826 included patients, 123 cases (14.9%) of delirium were retrospectively detected through the CHART-DEL method. Patients with delirium were older (76.9±13.15 vs 61.3±14.27 years, p<0.001) and more frequently living in a long-term health facility (32 (26%) vs 22 (3.1%), p<0.001). Age (OR 1.06, 95% CI 1.04 to 1.09, p<0.001), dementia (OR 17.5, 95% CI 7.27 to 42.16, p<0.001), epilepsy (OR 6.96, 95% CI 2.48 to 19.51, p<0.001) and the number of chronic medications (OR 1.09, 95% CI 1.01 to 1.17, p=0.03) were significant predictors of delirium in multivariable analyses. Delirium was associated with increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.55 to 3.03, p<0.001) and with a reduced probability of being discharged home compared with being institutionalised (adjusted OR 0.39, 95% CI 0.25 to 0.61, p<0.001). CONCLUSIONS: Chart review frequently identified ED delirium in patients with COVID-19. Age, dementia, epilepsy and polypharmacy were significant predictors of ED delirium. Delirium was associated with an increased in-hospital mortality and with a reduced probability of being discharged home after hospitalisation. The findings of this single-centre retrospective study require validation in future studies.

COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan.

BACKGROUND: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital. METHODS: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes. RESULTS: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%. DISCUSSION: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization. CONCLUSIONS: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

A radiological predictor for pneumomediastinum/pneumothorax in COVID-19 ARDS patients.

PURPOSE: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020-December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. RESULTS: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1-18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6-96.9), a specificity of 95.6% (95% CI: 90.6-98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3-92.3), a negative PV of 97.1% (95% CI: 74.6-96.9) and an accuracy of 94.2% (95% CI: 89.6-97.2) in predicting PMD/PNX (AUC:0.924). CONCLUSIONS: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.