IDH1/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction-a retrospective propensity score analysis.

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to leukemia gene mutations and associates with an increased risk for coronary artery disease and poor prognosis in ischemic cardiomyopathy. Two recurrently mutated genes in CHIP and adult acute myeloid leukemia (AML) encode for isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). Global expression of mutant IDH2 in transgenic mice-induced dilated cardiomyopathy and muscular dystrophy. In this retrospective observational study, we investigated whether mutant IDH1/2 predisposes to cardiovascular disease in AML patients. Among 363 AML patients, IDH1 and IDH2 mutations were detected in 26 (7.2%) and 39 patients (10.7%), respectively. Mutant IDH1 patients exhibited a significantly higher prevalence of coronary artery disease (26.1% vs. 6.4%, p = 0.002). Applying inverse probability-weighting analysis, patients with IDH1/2 mutations had a higher risk for a declining cardiac function during AML treatment compared to IDH1/2 wild type patients [left ventricular ejection fraction pretreatment compared to 10 months after diagnosis: 59.2% to 41.9% (p < 0.001) vs 58.5% to 55.4% (p = 0.27), respectively]. Mechanistically, RNA sequencing and immunostaining in hiPS-derived cardiomyocytes indicated that the oncometabolite R-2HG exacerbated doxorubicin mediated cardiotoxicity. Evaluation of IDH1/2 mutation status may therefore help identifying AML patients at risk for cardiovascular complications during cytotoxic treatment.

Induction of cardiomyocyte proliferation and angiogenesis protects neonatal mice from pressure overload-associated maladaptation.

Cardiac pressure overload (for example due to aortic stenosis) induces irreversible myocardial dysfunction, cardiomyocyte hypertrophy and interstitial fibrosis in patients. In contrast to adult, neonatal mice can efficiently regenerate the heart after injury in the first week after birth. To decipher whether insufficient cardiac regeneration contributes to the progression of pressure overload dependent disease, we established a transverse aortic constriction protocol in neonatal mice (nTAC). nTAC in the non-regenerative stage (at postnatal day P7) induced cardiac dysfunction, myocardial fibrosis and cardiomyocyte hypertrophy. In contrast, nTAC in the regenerative stage (at P1) largely prevented these maladaptive responses and was in particular associated with enhanced myocardial angiogenesis and increased cardiomyocyte proliferation, which both supported adaptation during nTAC. A comparative transcriptomic analysis between hearts after regenerative versus non-regenerative nTAC suggested the transcription factor GATA4 as master regulator of the regenerative gene-program. Indeed, cardiomyocyte specific deletion of GATA4 converted the regenerative nTAC into a non-regenerative, maladaptive response. Our new nTAC model can be used to identify mediators of adaptation during pressure overload and to discover novel potential therapeutic strategies.

Internal jugular catheter malposition in a patient with end stage renal disease: a case report.

A 30-year-old female with end-stage renal disease was a candidate for dual lumen catheter placement. After catheter insertion, O2 saturation measurement of the aspirated blood from the catheter was similar to that of arterial blood. They referred the patient to our hospital after 48 hours. Diagnostic procedures revealed that the tip of the catheter had entered the pleural cavity. Catheter removal in the CPR room resulted in hemorrhagic shock. The patient was resuscitated and stabilized and sent to the operating room. A laceration found at the junction of right jugular and right subclavian veins and was surgically repaired. The patient was discharged after ten days without any complication.

The role of routine chest radiography for detecting complications after central venous catheter insertion.

Chest radiographs are obtained routinely after central venous catheter (CVC) insertion in many institutions, although it consumes time and money. The purpose of this study was to evaluate the role of post-procedural chest X-ray in detecting complications of CVC insertion; we performed CVC insertion without using ultrasonography guidance. A total of 454 patients who required an emergency vascular access for hemodialysis between February 2008 and March 2010 were included in this study. In cases where three to five unsuccessful attempts were encountered to place the CVC or pierce the artery, we used another site for CVC placement or we placed the CVC under ultrasonographic guidance. Both the internal jugular and the subclavian veins were used as routes for catheter insertion. All the catheters were dual lumen and were inserted by the same vascular access surgeon. All the catheters were inserted using the same protocol. This protocol consists of five stages including position, percutaneous anesthesia, puncture, pull out and placement. Chest radiography was obtained after the procedure and patients were interviewed for the presence of any unusual symptoms. The X-rays were reviewed by a radiologist who was unaware of the patients' symptoms. Complications occurred in two patients who had unusual symptoms after the placement of the catheter. Although immediate postprocedural chest radiography is recommended for tip position confirmation, it should not be considered a reliable procedure for detecting complications in the absence of clinical symptoms. It is recommended to monitor patients after catheter insertion and perform delayed chest X-ray in the presence of any unusual symptoms.

Brachial artery-jugular vein jump graft: a salvage procedure for vascular access.

A prospective analysis was made on 11 patients who received a brachial artery-external/internal jugular polytetrafluoroethylene jump graft for hemodialysis access. The procedure was chosen because of exhaustion of the veins in the upper extremity owing to previous multiple failed fistulas or grafts. In two patients, the procedure failed after several months. Six patients retained functioning grafts for >18 months after shunt construction. Three patients are still under observation and have a functional graft after 3 months. We believe that the brachial artery-external/internal jugular vein jump graft is a salvage procedure that can be used for vascular access when all upper extremity veins, including the subclavian or axillary veins, cannot be used.