Intrauterine restriction (IUGR)

Perinatal mortality and morbidity is markedly increased in intrauterine growth restricted (IUGR) fetuses. Prenatal identification of IUGR is the first step in clinical management. For that purpose a uniform definition and criteria are required. The etiology of IUGR is multifactorial and whenever possible it should be assessed. When the cause is of placental origin, it is possible to identify the affected fetuses. The major complication is chronic fetal hypoxemia. By monitoring the changes of fetal vital functions it is thus possible to improve both management and outcome. The timing of delivery is crucial but the optimal management scheme has not yet been identified. When IUGR is identified at very early gestational ages, serial assessments of the risk of continuing the in utero fetal life under adverse conditions versus the risks of the prematurity should be performed. Delivery of IUGR fetuses should take place in centers where appropriate neonatal assistance can be provided. Careful monitoring of the IUGR fetus during labor is crucial as the IUGR fetus can quickly decompensate once uterine contractions have started.     

Prophylactic endovascular management of peripheral artery disease in elderly candidates prior to cardiac surgery

Background and objectives Peripheral vascular disease (PVD) is a major risk factor in candidates for cardiac surgery and can impact morbidity and mortality in the perioperative and follow-up period. Elderly patients with PVD may benefit from endovascular treatment prior to cardiac surgery. We sought to assess the common clinical settings requiring prophylactic endovascular treatment before coronary surgery in elderly patients, the results, and the mid-term impact on subsequent revascularization. Methods Between November 2002 and June 2006, 37 patients (25 males, mean age 79.9±8.3 years, mean serum creatinine 1.9±0.6 mg/dl) underwent endovascular repair of PVD before cardiac surgery. For each patient, diagnostic methods, indications for intervention, types of interventions, procedural success, and complications were recorded. Results Four clinical settings were identified: renal artery stenting prior to coronary surgery (7 patients), iliac artery angioplasty and stenting (10 patients) in order to facilitate aortic balloon pump insertion after surgery, subclavian artery angioplasty and stenting prior to utilization of ipsilateral arterial conduits bypass surgery (5 patients), and carotid artery stenting before coronary surgery (15 patients). Technical success was achieved in all patients (100%); complications included brachial artery occlusion (1 patient), minor stroke (2 patients), contrast nephropathy (1 patient), and minor bleeding at the puncture site (3 patients). All patients underwent successful coronary or valvular surgery; no patients died in the perioperative period. After a mean follow-up of 26.6±3.1 months, all patients are alive and free from anginal symptoms or valvular dysfunction without clinical or Doppler ultrasonography evidence of restenosis of the implanted peripheral vascular stents. Conclusions It is not unusual for elderly patients who are candidates for cardiac surgery to require endovascular intervention for significant PVD prior to coronary bypass or valvular surgery. The results showed a low complication rate. The cardiologists have a fundamental role, not only in the diagnosis of peripheral vascular stenosis, which was seen frequently in patients with significant CAD, but also in the appropriate endovascular management of these high-risk patients.     

Improving pancreas graft utilization through importation

Background

We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation.

Methods

This is an observational retrospective cohort of 26 recipients who received either a locally procured (n = 16) or an imported pancreas graft (n = 10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data were also reviewed to analyze the cost‐effectiveness of this strategy.

Results

Imported pancreas grafts had significantly increased cold ischemia times (CIT) and peak lipase (PL) levels compared to locally procured grafts (CIT 827 vs 497 minutes; P = .001, PL 563 vs 157 u/L; P = .023, respectively). There were no differences in graft or patient survival. The median wait time was significantly lower for simultaneous kidney‐pancreas transplants at our center (518 days, n = 21) compared to Region 9 (1001 days, n = 65) P = .038. Despite financial concerns, the cost of transport for imported grafts was offset by lower standard acquisition costs.

Conclusions

Imported pancreas grafts may be a cost‐effective strategy to increase organ utilization and shorten wait times in regions with longer waiting times.     

Coronary thrombi neovascularization in patients with ST-elevation myocardial infarction - clinical and angiographic implications

Introduction

Coronary artery thrombosis in ST-elevation myocardial infarction (STEMI) is a dynamic process often preceded by episodes of silent plaque rupture and subocclusive thrombosis. Thrombus organization is achieved by ingrowth of endothelial and smooth muscle cells. Clinical significance and impact of thrombus neovascularization on primary percutaneous coronary intervention (pPCI) outcome remain unclear. Therefore we investigated composition and neovascularization of thrombi aspirated during pPCI and their association with clinical and angiographic parameters of STEMI patients.

Methods

Aspirated thrombi retrieved from 84 STEMI patients were classified as fresh (< 1 day), lytic (1-5 days) or organized (> 5 days). Thrombus neovascularization was evaluated immunohistochemically using CD34, CD31 and VEGF antibodies. CD34 and CD31 immunopositive (CD34/CD31 +) cells were organized as single, clusters and microvessels. VEGF positivity was graded as low or high, based on thrombus surface immunopositive area.

Results

CD34/CD31 + cells were present in 67% of all aspirated thrombi. Thrombus CD34/CD31 positivity was associated with previous history of angina pectoris (χ² = 6.142, p = 0.013) and lower myocardial blush grade (MBG < 3, χ² = 12.602, p < 0.001). Organization of CD34/CD31 + cells showed inverse association with the extent of VEGF positivity (χ² = 10.607, p = 0.005). Fresh thrombi were associated with shorter ischemic time (U = 237.5, p = 0.002) and MBG 3 (χ² = 6.379, p = 0.012).

Conclusions

Older thrombus age and neovascularization are associated with suboptimal myocardial perfusion in STEMI patients. Thrombus VEGF expression is inversely associated with degree of CD34 + cell organization. Therefore, neovascularization of aspirated thrombi may indicate the duration of thrombosis, coronary microcirculation status and outcome in STEMI patients.     

Hearing results of surgery for tympanosclerosis

Between January 1990 and December 2003, 117 patients were surgically treated for tympanosclerosis at a tertiary referral center. The objective of our study was to review the hearing results in this cohort. The patients were divided into three groups: predominant involvement of tympanic membrane (33 cases), predominant fixation of malleus or/and incus (72 cases), and stapedial fixation (12 cases). Preoperative and postoperative air–bone gap (ABG), and pure tone average (PTA) were compared after short-term and long-term follow-up, and statistical significance was determined. After surgery, air–bone gap was improved by 11.7 dB after short-term, and by 10.9 dB after long-term observation period. The improvement of ABG was not significantly different between the groups. Pure tone average (PTA) was improved by 15.2 dB in short-term period, with decrease of results in the long-term follow-up to 10.3 dB. Successful hearing result as judged by ABG was obtained in 66.7% with affected tympanic membrane, in 65.3% with malleus or/and incus fixation, and in 50.0% with stapedial fixation. Statistical analysis confirmed significant improvement of hearing for all groups. Highly significant difference was noted for low frequency ABG (0.5, 1, and 2 kHz). Hearing improvement on ABG was preserved after long-term observation. No significant sensorineural hearing loss was seen in this series. Surgery for tympanosclerosis results in significant improvement of ABG and PTA. Most of the improvement is obtained in lower frequencies. Long-term results are comparable to short-term results, with slight hearing deterioration in stapedial fixation.     

E-selectin ligand–1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-β

The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-β signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-β signaling is tightly controlled by numerous mechanisms at the extracellular level and downstream of ligand-receptor interactions. However, TGF-β is synthesized as an inactive precursor that is cleaved to become mature in the Golgi apparatus, and the regulation of this posttranslational intracellular processing and trafficking is much less defined. Here, we report that a cysteine-rich protein, E-selectin ligand–1 (ESL-1), acts as a negative regulator of TGF-β production by binding TGF-β precursors in the Golgi apparatus in a cell-autonomous fashion, inhibiting their maturation. Furthermore, ESL-1 inhibited the processing of proTGF-β by a furin-like protease, leading to reduced secretion of mature TGF-β by primary mouse chondrocytes and HEK293 cells. In vivo loss of Esl1 in mice led to increased TGF-β/SMAD signaling in the growth plate that was associated with reduced chondrocyte proliferation and delayed terminal differentiation. Gain-of-function and rescue studies of the Xenopus ESL-1 ortholog in the context of early embryogenesis showed that this regulation of TGF-β/Nodal signaling was evolutionarily conserved. This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-β during skeletal development and homeostasis.     

Noninvasive finding of local repolarization changes in the heart using dipole models and simplified torso geometry

Two inverse methods using dipole models for noninvasive assessment of local repolarization changes were investigated and compared in the simulation study. Lesions with changed repolarization were modeled by shortening of the action potential durations in ventricular regions typically influenced by occlusion of coronary arteries. Corresponding body surface potentials were computed using a multiple dipole model of the cardiac generator and an inhomogeneous torso model. Position of each lesion was then estimated by an inverse solution to a single dipole and to a group of five neighbouring dipoles. For both methods the lesion localization error was evaluated and its dependence on the lesion size and the noise in input data was studied. When no noise was present in the input data, the use of the inverse method to a group of dipoles instead of a single dipole resulted in an unsubstantial reduction of the mean localization error of small lesions from 0.6 to 0.5 cm. For medium and especially for large lesions the mean localization errors decreased significantly from 1.1 to 0.6 cm and from 2.3 to 1.0 cm, respectively. The inverse solution to a group of five dipoles was more sensitive to noise. However, for large lesions it still gave better results than the solution to a single dipole if the signal to noise ratio was higher than 30 dB.