Treatment of a broncho-esophageal fistula complicated by severe ARDS.

INTRODUCTION: Broncho-esophageal fistula formation is a rare complication of tuberculosis, most often seen in immunocompromised patients. METHODS AND RESULTS: In this paper, we report the case of a young non-immunocompromised refugee from Somalia diagnosed with open pulmonary tuberculosis complicated by extensive osseous involvement and a broncho-esophageal fistula with consecutive aspiration of gastric contents. The patient rapidly developed a severe acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (ECMO) therapy for nearly 2 months. The fistula was initially treated by standard antituberculous combination therapy and implantation of an esophageal and a bronchial stent. Long-term antibiotic treatment was instituted for pneumonia and mediastinitis. 7 months later, discontinuity resection of the esophagus was performed and the bronchial fistula covered by an intercostal muscle flap. DISCUSSION: This case illustrates that tuberculosis should always be suspected in patients from high-incidence countries in case of lung involvement and that an interdisciplinary approach including long-term intensive care management can enable successful treatment of tuberculosis with severe, near-fatal complications.

Atrial fibrillation and survival on a medical intensive care unit.

BACKGROUND: Atrial fibrillation (AF) is common among patients in the intensive care unit (ICU) and can be triggered by severe illness or preexisting conditions. It is debated if AF is an independent predictor of poor outcome. METHODS: Data derives from a single center retrospective registry including all patients with a stay on the medical ICU for >24 h. The primary endpoint was ICU survival. Secondary endpoints included receiving mechanical support (renal, respiratory or circulatory), hemodynamic parameters during AF, rate and rhythm control strategies, anticoagulation, and documentation. RESULTS: A total of 616 patients (male gender 62.3%, median age 75 years) were included in our analysis. New-onset AF was diagnosed in 87 patients (14.1%), 136 (22.1%) presented with preexisting AF, and 393 (63.8%) did not develop AF. Initial episodes of new-onset AF exhibited higher hemodynamic instability than episodes in preexisting cases, with elevated heart rates and increased catecholamine doses (both p < 0.001). ICU survival in new-onset AF was 80.5% (70/87) compared to 92.4% (363/393) in patients without AF (OR 0.340, CI 0.182-0.658, p < 0.001). Likewise, ICU survival in preexisting AF was 86.8% (118/136) was significantly lower compared to no AF (OR 0.542, CI 0.290-0.986, p = 0.050*). Independent predictors of ICU survival for patients were atrial fibrillation (p = 0.016), resuscitation before or during ICU stay (p < 0.001), and receiving acute dialysis on ICU (p = 0.002). CONCLUSIONS: ICU survival is noticeably lower in patients with new-onset or preexisting atrial fibrillation compared to those without. Patients who develop new-onset AF during their ICU stay warrant special attention for both short-term and long-term care strategies.

Myocardial infarction type 1 is frequent in refractory out-of-hospital cardiac arrest (OHCA) treated with extracorporeal cardiopulmonary resuscitation (ECPR).

Extracorporeal cardiopulmonary resuscitation (ECPR) is a last resort treatment option for refractory cardiac arrest performed in specialized centers. Following consensus recommendations, ECPR is mostly offered to younger patients with witnessed collapse but without return of spontaneous circulation (ROSC). We report findings from a large single-center registry with 252 all-comers who received ECPR from 2011-2019. It took a median of 52 min to establish stable circulation by ECPR. Eighty-five percent of 112 patients with out-of-hospital cardiac arrest (OHCA) underwent coronary angiography, revealing myocardial infarction (MI) type 1 with atherothrombotic vessel obstruction in 70 patients (63% of all OHCA patients, 74% of OHCA patients undergoing coronary angiography). Sixty-six percent of 140 patients with intra-hospital cardiac arrest (IHCA) underwent coronary angiography, which showed MI type 1 in 77 patients (55% of all IHCA patients, 83% of IHCA patients undergoing coronary angiography). These results suggest that MI type 1 is a frequent finding and - most likely - cause of cardiac arrest (CA) in patients without ROSC, especially in OHCA. Hospital survival rates were 30% and 29% in patients with OHCA and IHCA, respectively. According to these findings, rapid coronary angiography may be advisable in patients with OHCA receiving ECPR without obvious non-cardiac cause of arrest, irrespective of electrocardiogram analysis. Almost every third patient treated with ECPR survived to hospital discharge, supporting previous data suggesting that ECPR may be beneficial in CA without ROSC. In conclusion, interventional cardiology is of paramount importance for ECPR programs.

Counter modulation of adipocyte mitochondrial processes by insulin and S-oxalylglutathione.

Oxalyl thiolesters, a group of putative intracellular regulators, have been shown to be in vitro inhibitors of some cytosolic enzymes which are stimulated by insulin. In this study, the effects of insulin and oxalyl thiolesters on pyruvate dehydrogenase, beta-oxidation, and acyl-CoA hydrolase activities in mitochondria from rat epididymal adipocytes are compared. Using glutathione, CoASH, cysteine, and cysteamine as thiol sources, oxalyl thioesters were synthesized, purified, and quantitated. Mitochondria were isolated from rat epididymal adipocytes, some of which were incubated with or without insulin. Mitochondrial activities were determined by radioisotopic assay subsequent to control, insulin, or oxalyl thiolester incubation. Under the conditions used in this study, pyruvate dehydrogenase activity was increased 28% subsequent to 10-min incubation of adipocytes with 400 microU/ml insulin; in contrast, preincubation of adipocyte mitochondria with S-oxalylglutathione resulted in a dose-dependent 11-19% inhibition of pyruvate dehydrogenase. S-oxalylglutathione also attenuated the spermine-induced activation of pyruvate dehydrogenase. Insulin treatment resulted in a small but significant increase in beta-oxidation of palmitic acid while 100 microM S-oxalylglutathione mediated a 40% decrease in palmitate oxidation. Palmitoyl-CoA hydrolase activity was decreased 14% by insulin treatment; however, S-oxalylglutathione caused a 14-50% increase in hydrolase activity. The other oxalyl thiolesters were not as effective or as consistent as S-oxalylglutathione in modulation of the mitochondrial activities; free thiols and oxalic acid did not modulate the activities. In summary, pyruvate dehydrogenase, palmitate beta-oxidation, and palmitoyl-CoA hydrolase activities in adipocyte mitochondria were modulated in approximately equal but opposite directions by insulin and S-oxalylglutathione. These findings support the suggestion that oxalyl thiolesters may function as an intracellular signal recruited to return insulin to normal levels.

Tyrphostin 47 nonenzymatically decarboxylates [1-14C]-pyruvate.

Tyrphostins inhibit tyrosine kinases and have little effect on the activity of serine/threonine kinases. Pyruvate dehydrogenase kinase inactivates pyruvate dehydrogenase by phosphorylating serine residues within the multienzyme complex. This serine/theronine kinase represents a new family of protein kinases, and one (tyrphostin 47) of two tyrphostins tested appeared to activate the pyruvate dehydrogenase kinase as determined by [1-14C]-lactate oxidation to 14CO2. Experiments designed to determine if the tyrphostins altered pyruvate dehydrogenase activity in mitochondria prepared from rat epididymal adipocytes using [1-14C]-pyruvate as the substrate demonstrated a dose dependent increase in enzyme activity in the presence of tyrphostin 47, but not in tyrphostin 23. This apparent stimulation of pyruvate dehydrogenase activity was attributed to tyrphostin 47's ability to nonenzymatically decarboxylate [1-14C]-pyruvate, the substrate for the pyruvate dehydrogenase assay. Neither tyrphostin directly altered pyruvate dehydrogenase kinase activity. Therefore, assays utilizing [1-14C]-pyruvate and tyrphostin 47 are subject to analytical interference.