Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. METHODS: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. RESULTS: One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. INTERPRETATION: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Acute-Onset Panhypopituitarism Nearly Missed by Initial Cosyntropin Testing.

INTRODUCTION: Diagnosis of adrenal crisis and panhypopituitarism in patients with septic shock is difficult but crucial for outcome. CASE: A 66-year-old woman with metastasized breast cancer presented to the ED with respiratory insufficiency and septic shock after a 2-day history of the flu. After transfer to the ICU, corticosteroids were started in addition to antibiotics, as the patient was vasopressor-nonresponsive. Diabetes insipidus was diagnosed due to polyuria and treated with 4 mg desmopressin. Thereafter, norepinephrine could be tapered rapidly. On day 2, basal cortisol was 136 nmol/L with an increase to 579 nmol/L in low-dose cosyntropin testing. Polyuria had not developed again. Therefore, corticosteroids were stopped. On day 3, the patient developed again nausea, vomiting, and polyuria. Adrenal crisis and diabetes insipidus were postulated. Corticosteroids and desmopressin were restarted. Further testing confirmed panhypopituitarism. MRI showed a new sellar metastasis. After 2 weeks, stimulated cortisol in cosyntropin testing reached only 219 nmol/l, confirming adrenal insufficiency. DISCUSSION: The time course showed that the adrenal glands took 2 weeks to atrophy after loss of pituitary ACTH secretion. Therefore, a misleading result of the cosyntropin test in the initial phase with low basal cortisol and allegedly normal response to exogenous ACTH may be seen. Cosyntropin testing in the critically ill should be interpreted with caution and in the corresponding clinical setting.

A fatal tick bite occurring during the course of tick-borne encephalitis vaccination.

In Western Europe tick-borne encephalitis virus infections with fatal outcome are rare, especially in children. We report the case of an adolescent who died of meningoencephalitis after a tick bite that occurred between the first 2 tick-borne encephalitis vaccinations. The case demonstrates the difficulty of differentiating possible adverse events associated with the immunization from symptoms of simultaneous infection with tick-borne encephalitis virus.

Hepatic veno-occlusive disease associated with immunosuppressive cyclophosphamide dosing and roxithromycin.

OBJECTIVE: To report on a patient developing hepatic veno-occlusive disease while being treated with immunosuppressive doses of cyclophosphamide (< or =2 mg/kg). CASE SUMMARY: A 66-year-old woman with autoimmune hemolytic anemia developed hepatic veno-occlusive disease while being treated with immunosuppressive cyclophosphamide 100 mg/day in combination with roxithromycin (total dose 600 mg/day). After all drugs were stopped, the patient recovered within 2 weeks. The Naranjo probability scale indicated a probable relationship between veno-occlusive disease and treatment with cyclophosphamide in this patient. DISCUSSION: Since roxithromycin inhibits CYP3A4, which is involved with cyclophosphamide metabolism, a drug-drug interaction could have been responsible. In addition, roxithromycin is an inhibitor of the drug transporter P-glycoprotein, possibly leading to accumulation of cyclophosphamide in endothelial cells. Alternatively, since cyclophosphamide has been reported to induce apoptosis, roxithromycin could have rendered endothelial cells more vulnerable for apoptosis. CONCLUSIONS: In specific patients, cyclophosphamide can be associated with hepatic veno-occlusive disease at immunosuppressive doses.

Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: A randomized trial of prophylaxis with low--molecular weight heparin.

PURPOSE: The risk of deep vein thrombosis (DVT) in patients undergoing arthroscopic knee surgery is not well known. The purpose of this study was to determine the incidence of DVT, to demonstrate the efficacy of a perioperative and postoperative prophylaxis against thromboembolism with use of low--molecular weight heparin (LMWH), and to show the safety and feasibility of LMWH administration. TYPE OF STUDY: Prospective, single-blind, randomized clinical trial. METHODS: There were 218 consecutive outpatients scheduled for ambulatory arthroscopic knee surgery eligible. Of these, 130 patients were randomized to a treatment group with LMWH (dalteparin: 2,500 IU less-than-or-equal70 kg and 5,000 IU >70 kg, started perioperatively and given once daily for 4 weeks; n = 66) and a control group (n = 64) with no prophylaxis. To detect DVT, all patients underwent bilateral compression ultrasonography before and 12 and 31 days after surgery. RESULTS: Among the 130 patients studied, thromboembolism was significantly lower in the treatment than in the control group: 1 of 66 (1.5%) versus 10 of 64 (15.6%); 95% confidence interval, 7.8% to 26.8%; P =.004. Eighty percent of DVT occurred within the first 14 postoperative days. No severe side effects of LMWH were observed. Only 5% of patients refused continued subcutaneous LMWH injections. CONCLUSIONS: In patients undergoing ambulatory arthroscopic knee surgery without antithrombotic prophylaxis, the risk of DVT is high. Perioperative and postoperative prophylaxis with dalteparin is an effective and safe means of reducing this risk.