Impact of Retrograde Cerebral Perfusion on Ascending Aortic and Arch Aneurysm Repair

Purpose. The effect of retrograde cerebral perfusion on the incidence of stroke and death among patients undergoing repair of aneurysms of the ascending aorta and transverse arch was determined.

Material and Methods. Between January 1991 and March 1995, 161 patients were operated on for aneurysms of the ascending aorta and transverse arch. Thirty-three of the patients (20%) had an aneurysm of the ascending aorta only and 128 (80%) had aneurysms of both the ascending aorta and the transverse arch. All the patients underwent cardiopulmonary bypass, profound hypothermia, and circulatory arrest, and 120 (74%) also underwent retrograde cerebral perfusion. Median pump time was 143 minutes (range, 21 to 461 minutes). Median circulatory arrest time was 42 minutes (range, 8 to 111 minutes), and median myocardial ischemic time was 71 minutes (range, 14 to 306 minutes).

Results. The overall 30-day mortality rate was 6% (9 patients) and the incidence of stroke was 4% (7 patients). The use of retrograde cerebral perfusion demonstrated a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%; odds ratio, 0.24; confidence interval, 0.06 to 0.99; p < 0.049). This was most significant in patients more than 70 years of age; none of the 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p < 0.003). Only pump time was associated with an increased risk of stroke (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.005). Pump time also was associated with increased mortality (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.008).

Conclusion. Retrograde cerebral perfusion decreased the incidence of stroke in patients undergoing repair of aneurysms of the ascending aorta and transverse arch.     

Cardiac function predicts mortality following thoracoabdominal and descending thoracic aortic aneurysm repair.

OBJECTIVE: Previous studies have identified age, renal failure and aneurysm extent as predictors of mortality following thoracoabdominal and descending thoracic aortic aneurysm (TAA) repair. We studied the impact of coronary artery disease (CAD) and cardiac function on 30-day mortality following TAA repair. METHODS: Between February 1991 and May 2001, we performed 854 TAA repairs. Two hundred ninety-one patients (34%) had a history of coronary artery disease. One hundred forty-one/291 (49%) had undergone coronary artery bypass surgery (CAB) prior to TAA repair. We conducted multivariable analyses of known risk factors along with the left ventricular ejection fraction (EF) and prior CAB to determine the adjusted effect of CAD on outcome. RESULTS: Mortality in patients with CAD was 54/291 (18%) compared to 75/563 (13%) without CAD (P<0.05). In patients who had prior CAB, mortality was 31/141 (22%) compared to 98/713 (14%) patients without prior CAB, (P<0.02). In multivariable analysis, the effects of CAD and CAB on mortality were eliminated by consideration of a low EF (defined as less than 50%). CONCLUSION: Impaired left ventricular function appears to be the strongest cardiac predictor of mortality for TAA repair, independent of the presence of coronary artery disease or coronary artery bypass revascularization.     

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims

Background: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the sudden infant death syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and the duration of sleep apnea were analyzed. The brain-stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. Results: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla in the medulla oblongata and the frequency and duration of sleep apnea. Conclusions: No significant association between the pathological data and the physiological data refers to TH-positive neurons in the medulla oblongata in SIDS victims.     

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims

Background: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G_o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.     

Differentiation of Campylobacter jejuni Serotype O19 Strains from Non-O19 Strains by PCR

Guillain-Barré syndrome (GBS), a neurologic disease characterized by acute paralysis, is frequently preceded by Campylobacter jejuni infection. Serotype O19 strains are overrepresented among GBS-associated C. jejuni isolates. We previously showed that all O19 strains tested were closely related to one another by randomly amplified polymorphic DNA (RAPD) and restriction fragment length polymorphism analyses. RAPD analysis demonstrated a 1.4-kb band in all O19 strains tested but in no non-O19 strains. We cloned this O19-specific band; nucleotide sequence analysis revealed a truncated open reading frame with significant homology to DNA gyrase subunit B (gyrB) of Helicobacter pylori. PCR using the random primer and a primer specific for gyrB showed that in non-O19 strains, the random primer did not recognize the downstream gyrB binding site. The regions flanking each of the random primer binding sites were amplified by degenerate PCR for further sequencing. Although the random primer had several mismatches with the downstream gyrB binding site, a single nucleotide polymorphism 6 bp upstream from the 3′ terminus was found to distinguish O19 and non-O19 strains. PCR using 3′-mismatched primers based on this polymorphism was designed to differentiate O19 strains from non-O19 strains. When a total of 42 (18 O19 and 24 non-O19) strains from five different countries were examined, O19 strains were distinguishable from non-O19 strains in each case. This PCR method should permit identification of O19 C. jejuni strains.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Evaluation of Surveyor nuclease for rapid identification of FKS genes mutations in Candida glabrata

IntroductionInfections with Candida glabrata have recently gained worldwide attention owing to its association with long hospitalizations and high mortality rates. This problem is highlighted when the infection is associated with echinocandin resistance, which is used for first-line therapy. Echinocandin resistance is exclusively attributed to functional mutations in FKS genes, and especially in hot spot (HS) regions. Unfortunately, few studies have focused on the rapid identification of FKS mutations associated with echinocandin resistance in C. glabrata. This study was intended to evaluate and validate the use of Surveyor nuclease assay (SN) for detection of FKS gene mutations.MethodsSN was evaluated against three segments of FKS1 and FKS2 genes including whole gene, regions including all HSs, and the region including only HS1.ResultsOur results showed that SN results are basically dependent on the type of gene as well as the segment type. Interestingly, SN can detect mutations in the region containing HS1 in both FKS1 and FKS2 genes. Furthermore, SN can detect mutations in the segment containing all HS regions for FKS1 but not FKS2. SN was unable to detect mutations in the whole FKS1 and FKS2 genes.ConclusionsAs far as we know, this is the first study to validate SN for rapid identification of FKS gene mutations. This assay could be used as a sample for rapid identification of mutations associated with HS1 region in FKS genes, which have a predominant role for echinocandin resistance induction in C. glabrata.