Late Functional Recovery Research Articles

G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration

Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model – nerve transection and repair – in healthy and diabetic rats.In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed.In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment.In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it.G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery.

447 Late recovery of erectile function in men treated with robotic-assisted laparoscopic radical prostatectomy (RALP): A novel nomogram development and validation

447 Late recovery of erectile function in men treated with robotic-assisted laparoscopic radical prostatectomy (RALP): A novel nomogram development and validation

Antithrombotic treatment at onset of stroke with atrial fibrillation, functional outcome, and fatality: a systematic review and meta-analysis.

In atrial fibrillation-associated stroke, conflicting data exist regarding association between therapeutic vitamin K-antagonist anticoagulation (International Normalized Ratio 2-3) and early death and functional outcome, and few data exist relating to late outcome in ischemic and haemorrhagic atrial fibrillation-stroke. We performed a systematic review and meta-analysis of oral anticoagulation at stroke onset, death and functional outcome. We performed a systematic review, searching multiple sources. Studies were included if outcomes in atrial fibrillation-associated stroke were reported stratified by pre-stroke antithrombotic status, with documented International Normalized Ratio at onset. Outcomes were survival and good functional outcome (modified Rankin score 0-2) at discharge/30 days, and at one-year. Of eight studies (3552 patients) in ischemic stroke, International Normalized Ratio ≥ 2 compared with other treatments (International Normalized Ratio < 2, antiplatelet, or no antithrombotic) was associated with good outcome [pooled odds ratio 1·9 (95% confidence interval) 1·5-2·5, P < 0·001] and improved survival at 30 days discharge (pooled odds ratio for death 0·4, confidence interval 0·2-0·5, P < 0·001). The net benefit remained after inclusion of haemorrhagic stroke (odds ratio for good outcome 1·89, confidence interval 1·45-2·46, P < 0·001). At one-year, improved functional outcome for International Normalized Ratio ≥ 2 (pooled odds ratio 1·7, confidence interval 1·0-2·7, P = 0·04) and survival (odds ratio for death 0·5, confidence interval 0·4-0·8, P = 0·001) were also observed. Therapeutic International Normalized Ratio at stroke onset was associated with early and late improved survival and functional recovery suggesting sustained benefit for warfarin anticoagulation for stroke outcome in atrial fibrillation patients. Long-term outcome data following stroke in patients taking new oral anticoagulants is required.

The effect of functional electrical stimulation cycling on late functional improvement in patients with chronic incomplete spinal cord injury.

Prospective single-arm study. To investigate the effect of functional electrical stimulation (FES) cycling on late functional recovery, spasticity, gait parameters and oxygen consumption during walking in patients with chronic incomplete spinal cord injury (SCI). Turkish Armed Forces Rehabilitation Center, Ankara, Turkey. Ten patients with chronic (duration of more than 2 years) incomplete SCI who could ambulate at least 10 m independently or with the assistance of a cane or walker, but no hip-knee-ankle-foot orthosis. The subjects underwent 1-h FES cycling sessions three times a week for 16 weeks. Outcome measures including the total motor score, the Functional Independence Measure (FIM) score, the Modified Ashworth Scale for knee spasticity, temporal spatial gait parameters and oxygen consumption rate during walking were assessed at baseline, 3 and 6 months after the baseline. There were statistically significant improvements in total motor scores, the FIM scores and spasticity level at the 6-month follow-up (P<0.01). The changes in gait parameters reached no significant level (P>0.05). Oxygen consumption rate of the patients showed significant reduction at only 6 months compared with baseline (P<0.01). The results suggest that FES cycling may provide some functional improvements in the late period of SCI. The study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK).

Second-Toe Transfer for Traumatic Thumb Amputation in Children Under 5 Years

Posttraumatic thumb amputations in children under 5 years are uncommon. The final clinical long-term results have been reported shortly in literature. We report our clinical experience in children under 5 years with traumatic amputation of the thumb that were reconstructed using a second-toe transfer. There were 7 boys and 2 girls between the ages of 1 and 5 years. The follow-up was between 6 and 14 years. The average age at the time of transfer was 2.8 years, and the average follow-up was 10.7 years (range, between 6 and 14 y). The most frequent cause of amputation was avulsion (33.3%). All the transferred toes survived and achieved bone union and static 2-point discrimination was averaged at 5 mm. They acquired good prehensile pinch and grasp. All of the structures of the transferred toes showed substantial growth. Second-toe transfer for traumatic amputation of the thumb continues to be one of the best choices. Children require secondary procedures less often and in some cases late functional recovery can be expected. It is a safe procedure and there are fewer complications and a better success rate.

GW24-e0060 Predictive Value of Low Dose Adenosine Stress Echocardiography in Identifying Improvement of Left Ventricular Function after Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

ObjectivesWe studied the value of lowdose adenosine stress echocardiography (LDASE) in early prediction of left ventricular functional recovery (LVFR) after acute myocardial infarction (AMI) treated with successful percutaneous coronary intervention...

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Successful outcome of severe Amanita phalloides poisoning in children

Amanita phalloides intoxication can lead to FHF with high mortality, especially in children. There is still ongoing discussion about the optimal treatment and decision criteria for emergency liver transplantation (LTx). Here, we summarize our experience with outcomes in five children. Five children with severe A.phalloides intoxication were treated at our tertiary center from 1995 to 2010 and studied retrospectively with respect to clinical and laboratory aspects that might help to decide between LTx or conservative therapy only. The findings are discussed with regard to recommended treatment and transplantation criteria for adults. All patients survived, of whom two of five received emergency LTx. Three patients survived with conservative treatment consisting of intravenous silibinin, NAC, detoxification measures, and intensive care. Indications for LTx in two children were progressive brain edema and cardiovascular failure. Children with FHF due to A.phalloides intoxication should be considered early for emergency LTx but should be monitored closely for the necessity of definite LTx. Early detoxification with active charcoal as well as silibinin and NAC seems to improve the outcome. Late recovery of liver function after day 4 post-ingestion is possible.

Clinical Effects of CD34+ Cell Transplantation in Non-Ischemic Dilated Cardiomyopathy Correlate with Myocardial Cell Engraftment

Purpose In pre-clinical models of stem cell therapy, early myocardial cell engraftment predicted late cardiac functional recovery. We sought to analyze the effect of myocardial homing of CD34 + cells on clinical outcome in patients with non-ischemic dilated cardiomyopathy (DCM). Methods and Materials In 94 patients with non-ischemic DCM, stem cells were mobilized by daily subcutaneous injections of filgrastim. CD34 + cells were collected via apheresis and labeled with technetium. Cells were injected intracoronary in the artery supplying segments of reduced myocardial viability (n=53), or transendocardially in the target areas defined by electro-anatomical mapping (n=41). Nuclear imaging for quantitation of myocardial homing was performed 18 hours after the procedure.Good homing was predefined as measured activity greater than median value of general activity.Patients were followed for 1 year. Results At baseline, patients with good (>median, group A) and poor (≤median, group B) homing did not differ in age, gender, LVEF, or plasma levels of creatinine or NT-proBNP. The number of mobilized CD34 + cells used for injection was comparable in both groups (98±56 x 10 6 in group A vs. 101±38 x 10 6 in group B, P=0.73). Transendocardial cell injection was more frequent in group A (62%) than in group B (32%, P=0.01). At year 1, LVEF improved more in group A (+6.2±2.8 %) than group B (+2.7±1.7 %, P=0.01). The same was true for 6-minute walk test distance (+101±21 m in group A vs. +46±11 m in group B, P=0.01) and levels of NT-proBNP (−733±2411 pg/ml vs. −115±123 pg/ml, P=0.006). In both groups, we found no significant change in LVEDD (-0.08±0.16 cm in group A vs. -0.06±0.10 cm in group B, P=0.70). Conclusions In patients with non-ischemic DCM, higher myocardial CD34 + cell homing is associated with superior improvement in ventricular function, NT proBNP levels, and exercise capacity. This suggests that early myocardial cell engraftment translates into long-term clinical benefit in this patient cohort.

Peripheral Gangrene in Children With Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe clinical manifestation, frequent recurrence, and poor long-term prognosis. It is usually caused by abnormalities in complement regulation. We report 2 cases of children affected by a catastrophic extrarenal complication. A 4-year-old Indian girl developed gangrene of the finger tips 2 days after initial presentation of aHUS. Factor H autoantibodies were identified. Renal function continued to decline despite daily plasma exchanges, and she was started on peritoneal dialysis 5 days after admission. The distal tips of the left hand remained gangrenous with a line of demarcation. Three weeks later, she did not return for follow-up and died at home because of dialysis-related complications. An Arabic girl developed end-stage renal disease due to aHUS in the fourth month after birth. A de novo activating C3 mutation was found. At age 9 months, she suddenly developed ischemic changes in fingers of both hands and several toes. The lesions progressed, and several finger tips became gangrenous despite intense plasma exchange therapy. The decision was made to administer complement blocking therapy with the C5 antibody eculizumab. All nonnecrotic digits rapidly regained perfusion. The 3 already gangrenous fingers healed with loss of the end phalanges. During maintenance, eculizumab aHUS activity subsided completely and some late recovery of renal function was observed. aHUS may present by thrombotic macroangiopathy of small peripheral arteries. Eculizumab appears effective in preserving tissue viability if administered before gangrene occurs and should be considered as first-line rescue therapy in such cases.

Late recovery of renal function by rituximab in a patient with Wegener’s granulomatosis

Rituximab has proven effective in the treatment of complicated granulomatosis with polyangiitis (Wegener's, GPA). Two controlled trials in adults demonstrated beneficial effects of rituximab compared to cyclophosphamide in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis to induce remission and to treat relapses. Pediatric experience with rituximab in GPA is limited; the impact on renal function is unknown. We report a female adolescent with GPA and necrotizing glomerulonephritis that lead to end-stage renal disease (ESRD). After 22 months of peritoneal dialysis, she still experienced relapses and major treatment-associated adverse effects. After a single dose of rituximab, she rapidly achieved clinical remission and, unexpectedly, steadily recovered glomerular filtration rate, plateauing at 25 ml/min/1.73 m(2). Peritoneal dialysis could be discontinued for 16 months. This case documents a potent beneficial effect of rituximab on renal manifestation of GPA even in long-established ESRD.

Early Stem Cell Engraftment Predicts Late Cardiac Functional Recovery

Background— Human cardiac progenitor cells have demonstrated great potential for myocardial repair in small and large animals, but robust methods for longitudinal assessment of their engraftment in humans is not yet readily available. In this study, we sought to optimize and evaluate the use of positron emission tomography (PET) reporter gene imaging for monitoring human cardiac progenitor cell (hCPC) transplantation in a mouse model of myocardial infarction. Methods and Results— hCPCs were isolated and expanded from human myocardial samples and stably transduced with herpes simplex virus thymidine kinase (TK) PET reporter gene. Thymidine kinase-expressing hCPCs were characterized in vitro and transplanted into murine myocardial infarction models (n=57). Cardiac echocardiographic, magnetic resonance imaging and pressure-volume loop analyses revealed improvement in left ventricular contractile function 2 weeks after transplant (hCPC versus phosphate-buffered saline, P &lt;0.03). Noninvasive PET imaging was used to track hCPC fate over a 4-week time period, demonstrating a substantial decline in surviving cells. Importantly, early cell engraftment as assessed by PET was found to predict subsequent functional improvement, implying a “dose–effect” relationship. We isolated the transplanted cells from recipient myocardium by laser capture microdissection for in vivo transcriptome analysis. Our results provide direct evidence that hCPCs augment cardiac function after their transplantation into ischemic myocardium through paracrine secretion of growth factors. Conclusions— PET reporter gene imaging can provide important diagnostic and prognostic information regarding the ultimate success of hCPC treatment for myocardial infarction.

Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association?

This study investigated whether changes in thyroid hormone (TH) in plasma are associated with the recovery of cardiac function in patients with acute myocardial infarction (AMI). Previous experimental studies have provided evidence of potential implication of TH signaling in post-ischemic recovery of cardiac function. A total of 47 patients with AMI and early reperfusion therapy were included in this study. Myocardial injury was analyzed by peak creatinine kinase-MB (CKMB) and cardiac function was assessed by echocardiographic left ventricular ejection fraction (LVEF%). Recovery of function (ΔEF%) was estimated as the difference of LVEF% between 48 h and 6 months (6 mo) after AMI. Total triiodothyronine (T(3)), thyroxine (T(4)), and TSH were measured in plasma at different time points (24 h, 48 h, 5 d, and 6 mo). A significant correlation between LVEF% and T(3) (r=0.5, P=0.0004) was found early after AMI (48 h), whereas no correlation was observed between CKMB and T(3) (r=-0.04, P=0.81). A strong correlation was found between ΔEF% and total T(3) (r=0.64, P=10(-6)) at 6 mo after AMI. Furthermore, multivariate regression analysis revealed that T(3) at 6 mo (r=0.64, r(2)=0.41, P=10(-6)) was an independent determinant of ΔEF%. Changes in T(3) levels in plasma are closely correlated with the early and late recovery of cardiac function after AMI. T(3) levels at 6 mo appear to be an independent predictor of late functional recovery.

Outcome of protracted hypoparathyroidism after total thyroidectomy

Although the variables that influence the development of post-thyroidectomy hypocalcaemia are now better understood, the risk factors and long-term outcome of persistent hypoparathyroidism (HPP) are poorly defined. A retrospective review of a prospective protocol for the management of post-thyroidectomy hypocalcaemia was performed. Patients with a serum calcium level below 8 mg/dl (2 mmol/l) 24 h after total thyroidectomy were prescribed oral calcium with or without calcitriol and followed for at least 1 year. Protracted HPP was defined as an intact parathyroid hormone (iPTH) level below 13 pg/ml and need for calcium medication at 1 month after thyroidectomy. Of 442 patients (343 with goitre, 99 with carcinoma) undergoing total thyroidectomy, 222 (50.2 per cent) developed postoperative hypocalcaemia. Eleven patients were lost to follow-up. Parathyroid function recovered in 131 patients within 1 month and 80 developed protracted HPP, which was associated with lymphadenectomy, fewer than three glands left in situ and incidental parathyroidectomy. Parathyroid function recovered within 1 year in 78 per cent of patients with protracted HPP. Factors associated with late recovery of parathyroid function were higher serum calcium and low but detectable iPTH levels 1 month after surgery. These factors were associated with higher calcitriol and calcium dosages at hospital discharge. Parathyroid autotransplantation did not protect against permanent HPP. Higher serum calcium levels at 1 month after total thyroidectomy are associated with recovery of parathyroid function. It is hypothesized that intensive medical treatment of hypocalcaemia-'parathyroid splinting'-may improve the outcome of patients with protracted HPP.

Relationship between myocardial perfusion with myocardial contrast echocardiography and function early after acute myocardial infarction for the prediction of late recovery of function

Background Following ST elevation acute myocardial infarction (STEMI) and reperfusion therapy, there are often persistent wall thickening (WT) abnormalities and perfusion defects due to variable degree of myocardial stunning and necrosis. We hypothesised that following STEMI and reperfusion therapy, the extent of residual perfusion assessed by myocardial contrast echocardiography (MCE) and not the extent of WT abnormalities would predict subsequent global recovery of left ventricular (LV) function. Methods Accordingly, 112 patients with STEMI underwent simultaneous assessment of WT abnormality and perfusion using MCE 7 ± 2 days after AMI and reperfusion therapy. Both WT and perfusion were scored on a 16 segment LV model. Contrast perfusion index (CPI), and global LV function were calculated. Echocardiography was repeated 12 weeks after reperfusion to assess recovery of LV function. Results Of the 112 patients recruited, follow up echocardiography 12 weeks after reperfusion was available in 98 patients. CPI was significantly higher ( p < 0.0001) in the 66 patients, who showed late recovery of LV function (1.67 ± 0.27) compared to those who did not show recovery of function (1.25 ± 0.04). No significant difference was noted in the indices of baseline LV function in patients with (1.67 ± 0.32) and without (1.80 ± 0.36) recovery of LV function. The multivariable predictors of late recovery of function were MCE ( p = 0.02), absence of diabetes ( p = 0.02) and lower peak creatine kinase ( p = 0.01). Conclusion The extent of residual contrast perfusion and not WT abnormalities predicts late recovery of global LV function after acute myocardial infarction and reperfusion therapy.

Comparison of the Effects of Carbon Dioxide and Helium Pneumoperitoneum on Renal Function

Carbon dioxide pneumoperitoneum is associated with significant hypercarbia and acidosis. The aim of this study is to evaluate the effects of carbon dioxide and helium pneumoperitoneum on renal function. Thirty adult dogs were put randomly into one of three groups (n=10 animals each): group A--pneumoperitoneum not performed; group B--CO(2) pneumoperitoneum; and group C--helium pneumoperitoneum. The groups were analyzed with consideration given to body weight, hematologic values, hemodynamic parameters (heart rate, mean arterial pressure, central venous pressure, cardiac output, stroke volume, systemic vascular resistance, pulmonary vascular resistance, left cardiac work index, cardiac index, mean pulmonary artery pressure, and pulmonary capillary wedge pressure), and renal function (plasma renin activity, urinary output, creatinine clearance, and sodium excretory fraction). An accentuated decrease in urinary output was observed during pneumoperitoneum in groups B and C compared to the control group. In groups B and C, creatinine clearance declined significantly during pneumoperitoneum in comparison to group A, but after deflation a faster recovery of glomerular filtration was noticed for group C, and a significant increase in sodium excretory fraction was seen for group B. On the other hand, in comparison to the control group, group B had a significant increase in plasma renin activity, with late recovery of glomerular function. Helium ameliorates renal alterations when used for pneumoperitoneum, and it might be used for patients with compromised renal function who have to undergo laparoscopic surgery.

Early predictors of left ventricular function improvement late after myocardial infarction

Prognosis after acute myocardial infarction (AIM) depends on the extent of irreversibly damaged myocardium and viable tissue due to stunning or hibernation. The aim of the study was to assess the prognostic significance of early echocardiographic parameters of myocardial viability in prediction of late recovery of regional and global ventricular function. The study prospectively included 40 patients after the first, uncomplicated univessel AIM treated with percutaneous coronary intervention (PCI). Low dose dobutamine echocardiography (LDDE) was preformed 7-10 days after AIM and follow-up resting echocardiography from 7 to 12 months later. The sensitivity and specificity for the prediction of post revascularisation regional, dys synergy improvement were 61.29% and 94.59% respectively. The positive and negative predicative values were 90.48% and 74.47% re spectively. The number of viable segments (p = 0.01) and extent of contractile reserve (p = 0.01) were univariate, independent predictors of improvement in ejection fraction (EF). From the multivariate stepwise regression analysis contractile reserve was selected as most powerful predictor of late recovery of left ventricular contractile function (p = 0.007). Receiving-operator characteristic curve (ROC) analysis demonstrated that three or more recovered segments were necessary for an improvement of left ventricular ejection fraction (LVEF) > or = 5% after the revascularisation, with the highest sensitivity, 100% and specificity 56% (p = 0.01). Low-dose dobutamine echocardiography is a powerful predictor of the regional dys synergy recovery late after AIM treated with PTCA with implantation stent. Late full functional improvement of the left ventricle is related to the extent of contractile reserve and amount of viable tissue. At least three recovered segments are necessary for a significant recovery of the global left ventricular contractility.

Histological Features of Acute Tubular Necrosis in Native Kidneys and Long-Term Renal Function

There are few studies on the relationship between the morphology of acute tubular necrosis (ATN) in native kidneys and late functional recovery. Eighteen patients with acute renal failure (ARF) who had undergone renal biopsy were studied. All had the histological diagnosis of ATN and were followed for at least six months. Clinical characteristics of ARF were analyzed, and histological features were semi-quantitatively evaluated (tubular atrophy, interstitial inflammatory infiltrate, interstitial fibrosis, and ATN). According to the maximal GFR achieved during the follow-up, patients were divided into two groups: complete recovery (GFR ≥ 90 mL/min/1.73 m2) and partial recovery (GFR < 90 mL/min/1.73 m2). Only 39% of the patients achieved complete recovery. Patients with partial recovery achieved their maximal GFR (63 ± 9 mL/min/1.73 m2) 37 ± 14 months after ARF, a period of time similar to those patients with complete recovery (i.e., 54 ± 22 months). Patients with partial recovery had more severe ARF: oliguria was more frequent (90 versus 17%, p < 0.01), and they had higher peak creatinine (13.85 ± 1.12 versus 8.95 ± 1.30 mg/dL, p = 0.01), and longer hospitalization (45 ± 7 versus 20 ± 4 days, p = 0.03). No single histological parameter was associated with partial recovery, but the sum of all was when expressed as an injury index [4.00 (2.73–5.45) versus 2.00 (1.25–3.31), p < 0.05]. In conclusion, among patients with atypical ATN course, those with more severe ARF and tubule-interstitial lesions are more prone to partial recovery.

Deep brain stimulation promotes late functional recovery after traumatic brain injury

Deep brain stimulation promotes late functional recovery after traumatic brain injury

Prevalence, Predictors, Time Course, and Long-Term Clinical Implications of Left Ventricular Functional Recovery After Mechanical Reperfusion for Acute Myocardial Infarction

This study prospectively evaluated the prevalence, predictors, time course, and prognostic impact of left ventricular (LV) functional recovery after successful primary percutaneous coronary intervention in 228 consecutive patients with acute myocardial infarctions (AMIs) and LV dysfunction. Serial echocardiographic exams were performed within 24 hours (time 1) and at 1 month (time 2) and 6 months (time 3) after AMI. Overall, 133 patients (58%) showed significant LV functional recovery (> or =10% ejection fraction increase compared with time 1 or ejection fraction > or =50%) at time 3. Early (from time 1 to time 2) and late (from time 2 to time 3) functional recovery patterns were detected in 102 patients (45%) and 31 patients (14%), respectively. Independent predictors of LV functional recovery were enzymatic infarct size (p = 0.0001), time from symptom onset to reperfusion (p = 0.022), extent and severity of baseline LV wall motion abnormalities (p = 0.007), and female gender (p = 0.031). Six-month LV remodeling rates were 36% and 64% in patients with and without LV functional recovery (p = 0.0001). The five-year cardiac death rate was significantly lower in patients with LV functional recovery than in those without (8% vs 18%, respectively, p = 0.024). The time course of LV functional recovery during 6 months did not significantly affect long-term survival. In conclusion, after successful mechanical reperfusion of AMIs, nearly half of patients showed poor LV functional recovery. The presence of significant LV functional recovery 6 months after reperfused AMI, but not the specific time course of recovery, is clearly associated with a better long-term clinical outcome. Simple baseline variables can predict the improvement of cardiac function after reperfused AMI.