The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short-and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T-and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (Luminex (R)), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed "de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome

Objective To evaluate the changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization in the ICU and their relation to outcome. Design Prospective observational study. Setting ICU of a veterinary university medical center. Animals Thirty dogs with severe sepsis or septic shock caused by pyometra who underwent surgery and were admitted to the ICU. Measurements and Main Results Severe sepsis was defined as the presence of sepsis and sepsis-induced dysfunction of one or more organs. Septic shock was defined as the presence of severe sepsis plus hypotension not reversed with fluid resuscitation. After the presumptive diagnosis of sepsis secondary to pyometra, blood samples were collected and clinical findings were recorded. Volume resuscitation with 0.9% saline solution and antimicrobial therapy were initiated. Following abdominal ultrasonography and confirmation of increased uterine volume, dogs underwent corrective surgery. After surgery, the animals were admitted to the ICU, where resuscitation was guided by the clinical parameters, central venous oxygen saturation (ScvO2), lactate, and base deficit. Between survivors and nonsurvivors it was observed that the ScvO2, lactate, and base deficit on ICU admission were each related independently to death (P = 0.001, P = 0.030, and P < 0.001, respectively). ScvO2 and base deficit were found to be the best discriminators between survivors and nonsurvivors as assessed via receiver operator characteristic curve analysis. Conclusion Our study suggests that ScvO2 and base deficit are useful in predicting the prognosis of dogs with severe sepsis and septic shock; animals with a higher ScvO2 and lower base deficit at admission to the ICU have a lower probability of death.

Does administering albumin to postoperative gastroschisis patients improve outcome?

OBJECTIVES: Newborns who undergo surgery for gastroschisis correction may present with oliguria, anasarca, prolonged postoperative ileus, and infection. New postoperative therapeutic procedures were tested with the objective of improving postoperative outcome. PATIENTS AND METHODS: One hundred thirty-six newborns participated in one of two phases. Newborns in the first phase received infusions of large volumes of crystalloid solution and integral enteral formula, and newborns in the second phase received crystalloid solutions in smaller volumes, with albumin solution infusion when necessary and the late introduction of a semi-elemental diet. The studied variables were serum sodium and albumin levels, the need for albumin solution expansion, the occurrence of anasarca, the length of time on parenteral nutrition, the length of time before initiating an enteral diet and reaching a full enteral diet, orotracheal intubation time, length of hospitalization, and survival rates. RESULTS: Serum sodium levels were higher in newborns in the second phase. There was a correlation between low serum sodium levels and orotracheal intubation time; additionally, low serum albumin levels correlated with the length of time before the initiation of an oral diet and the time until a full enteral diet was reached. However, the discharge weights of newborns in the second phase were higher than in the first phase. The other studied variables, including survival rates (83.4% and 92.0%, respectively), were similar for both phases. CONCLUSIONS: The administration of an albumin solution to newborns in the early postoperative period following gastroschisis repair increased their low serum sodium levels but did not improve the final outcome. The introduction of a semi-elemental diet promoted an increase in body weight at the time of discharge.

Prediction and probability of neonatal outcome in isolated congenital diaphragmatic hernia using multiple ultrasound parameters

Objectives To evaluate the accuracy and probabilities of different fetal ultrasound parameters to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). Methods Between January 2004 and December 2010, we evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right-sided). The following parameters were evaluated: gestational age at diagnosis, side of the diaphragmatic defect, presence of polyhydramnios, presence of liver herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung volume/fetal weight ratio (US-FLW), observed/expected contralateral and main pulmonary artery diameter (o/e-ContPA and o/eMPA) ratios and the contralateral vascularization index (Cont-VI). The outcomes were neonatal death and severe postnatal pulmonary arterial hypertension (PAH). Results Neonatal mortality was 64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/eLHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/eContPA, o/e-MPA and Cont-VI were associated with both neonatal death and severe postnatal PAH (P < 0.001). Receiver-operating characteristics curves indicated that measuring total lung volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI was the most accurate ultrasound parameter to predict neonatal death and severe PAH (P < 0.001). Conclusions Evaluating total lung volumes is more accurate than is measuring only the contralateral lung size. Evaluating pulmonary vascularization (Cont-VI) is the most accurate predictor of neonatal outcome. Estimating the probability of survival and severe PAH allows classification of cases according to prognosis. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial

Abstract Introduction Noninvasive ventilation (NIV), as a weaning-facilitating strategy in predominantly chronic obstructive pulmonary disease (COPD) mechanically ventilated patients, is associated with reduced ventilator-associated pneumonia, total duration of mechanical ventilation, length of intensive care unit (ICU) and hospital stay, and mortality. However, this benefit after planned extubation in patients with acute respiratory failure of various etiologies remains to be elucidated. The aim of this study was to determine the efficacy of NIV applied immediately after planned extubation in contrast to oxygen mask (OM) in patients with acute respiratory failure (ARF). Methods A randomized, prospective, controlled, unblinded clinical study in a single center of a 24-bed adult general ICU in a university hospital was carried out in a 12-month period. Included patients met extubation criteria with at least 72 hours of mechanical ventilation due to acute respiratory failure, after following the ICU weaning protocol. Patients were randomized immediately before elective extubation, being randomly allocated to one of the study groups: NIV or OM. We compared both groups regarding gas exchange 15 minutes, 2 hours, and 24 hours after extubation, reintubation rate after 48 hours, duration of mechanical ventilation, ICU length of stay, and hospital mortality. Results Forty patients were randomized to receive NIV (20 patients) or OM (20 patients) after the following extubation criteria were met: pressure support (PSV) of 7 cm H2O, positive end-expiratory pressure (PEEP) of 5 cm H2O, oxygen inspiratory fraction (FiO2) ≤ 40%, arterial oxygen saturation (SaO2) ≥ 90%, and ratio of respiratory rate and tidal volume in liters (f/TV) < 105. Comparing the 20 patients (NIV) with the 18 patients (OM) that finished the study 48 hours after extubation, the rate of reintubation in NIV group was 5% and 39% in OM group (P = 0.016). Relative risk for reintubation was 0.13 (CI = 0.017 to 0.946). Absolute risk reduction for reintubation showed a decrease of 33.9%, and analysis of the number needed to treat was three. No difference was found in the length of ICU stay (P = 0.681). Hospital mortality was zero in NIV group and 22.2% in OM group (P = 0.041). Conclusions In this study population, NIV prevented 48 hours reintubation if applied immediately after elective extubation in patients with more than 3 days of ARF when compared with the OM group. Trial Registration number ISRCTN: 41524441.

Minimal and mild endometriosis negatively impact on pregnancy outcome

Endometriosis, a highly prevalent gynecological disease, can lead to infertility in moderate to severe cases. Whether minimal stages are associated with infertility is still unclear. The purpose of this systematic review is to present studies regarding the association between pregnancy rates and the presence of early stages of endometriosis. Studies regarding infertility, minimal (stage I, American Society of Reproductive Medicine [ASRM]) and mild (stage II, ASRM) endometriosis were identified by searching on the MEDLINE database from 1985 to September 2011 using the following MESH terms: endometriosis; infertility; minimal; mild endometriosis; pregnancy rate. 1188 articles published between January of 1985 and November of 2011 were retrieved; based on their titles, 1038 citations were excluded. Finally, after inclusion and exclusion criteria, 16 articles were selected to be part of this systematic review. Several reasons have been discussed in the literature to explain the impact of minimal endometriosis on fertility outcome, such as: ovulatory dysfunction, impaired folliculogenesis, defective implantation, decrease embryo quality, abnormal immunological peritoneal environment, and luteal phase problems. Despite the controversy involving the topic, the largest randomized control trial, published by Marcoux et al. in 1997 found a statistically different pregnancy rate after resection of superficial endometrial lesions. Earlier stages of endometriosis play a critical role in infertility, and most likely negatively impact pregnancy outcomes. Further studies into stage I endometriosis, especially randomized controlled trials, still need to be conducted.

Treatment of knee articular cartilage defects: surgical strategies, results and analysis of factors determining the clinical outcome

Articular cartilage lesions, with their inherent limited healing potential, are hard to treat and remain a challenging problem for orthopedic surgeons. Despite the development of several treatment strategies, the real potential of each procedure in terms of clinical benefit and effects on the joint degeneration processes is not clear. Aim of this PhD project was to evaluate the results, both in terms of clinical and imaging improvement, of new promising procedures developed to address the challenging cartilage pathology. Several studies have been followed in parallel and completed over the 3-year PhD, and are reported in detail in the following pages. In particular, the studies have been focused on the evaluation of the treatment indications of a scaffold based autologous chondrocyte implantation procedure, documenting its results for the classic indication of focal traumatic lesions, as well as its use for the treatment of more challenging patients, older, with degenerative lesions, or even as salvage procedure for more advanced stages of articular degeneration. The second field of study involved the analysis of the results obtained treating lesions of the articular surface with a new biomimetic osteochondral scaffold, which showed promise for the treatment of defects where the entire osteochondral unit is involved. Finally, a new minimally invasive procedure based on the use of growth factors derived from autologous platelets has been explored, showing results and underlining indicatios for the treatment of cartilage lesions and different stages of joint degeneration. These studies shed some light on the potential of the evaluated procedures, underlining good results as well as limits, they give some indications on the most appropriate candidates for their application, and document the current knowledge on cartilage treatment procedures suggesting the limitations that need to be addressed by future studies to improve the management of cartilage lesions.

The "Orthoplastic" combined surgical approach to open tibia fractures: a multicentric prospective outcome study

Introduction: Open fractures of the leg represent a severe trauma. The combined approach, shared between plastic and orthopaedic surgeons, is considered to be important, although this multidisciplinary treatment is not routinely performed. Aim of this study was to verify whether the orthoplastic treatment is of any advantage over the traditional simply orthopedic treatment, through a multicentric inclusion of these unfrequent injuries into a prospective study. Material and methods: The following trauma centres were involved: Rizzoli Orthopaedic Institute/University of Bologna (leading centre) and Maggiore Hospital (Bologna, Italy), Frenchay Hospital (Bristol, United Kingdom), Jinnah Hospital (Lahore, Pakistan). All patients consecutively hospitalized in the mentioned centres between January 2012 and December 2013 due to tibial open fractures were included in the study and prospectively followed up to December 2014. Demographics and other clinical features were recorded, including the type of treatment (orthopaedic or orthoplastic). The considered outcome measures included duration of hospitalization, time for bone union and soft tissue closure, Enneking score at 3, 6 and 12 months, the incidence of osteomyelitis and other complications. Results: A total of 164 patients were included in the study. Out of them 68% were treated with an orthoplastic approach, whereas 32% received a purely orthopedic treatment. All considered outcome measures showed to be improved by the orthoplastic approach, compared to the orthopaedic one: time for soft tissue closure (2 versus 25 weeks), duration of hospital stay (22 versus 55 days), time for bone union (6 versus 8.5 months) , number of additional operations (0.6 versus 1.2) and functional recovery of the limb at 12 months (27 versus 19, Enneking’s score). All results were statistically significant. Conclusion: The combined orthoplastic approach to the treatment of open tibia fractures, in particular for high grade injuries (Gustilo 3B), is proven to improve the outcome of these severe injuries.

Antiepileptic drugs and pregnancy. Population based pharmaco-epidemiological study on prescription patterns, pregnancy outcome and foetal health

Aims of the study: To assess the prevalence of Antiepileptic Drug (AED) exposure in pregnant women with or without epilepsy and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirth, major congenital malformations (MCMs) and foetal growth retardation (FGR) following intrauterine AED exposure in the Emilia Romagna region (RER), Northern Italy (4 million inhabitants). Methods: Data were obtained from official regional registries: Certificate of Delivery Assistance, Hospital Discharge Card, reimbursed prescription databases and Registry of Congenital Malformations. We identified all the deliveries, hospitalized abortions and MCMs occurred between January 2009 and December 2011. Results: We identified 145,243 pregnancies: 111,284 deliveries (112,845 live births and 279 stillbirths), 16408 spontaneous abortions and 17551 TOPs. Six hundred and eleven pregnancies (0.42% 95% Cl: 0.39-0.46) were exposed to AEDs. Twenty-one per cent of pregnancies ended in TOP in the AED group vs 12% in the non-exposed (OR:2.24; CI 1.41-3.56). The rate of spontaneous abortions and stillbirth was comparable in the two groups. Three hundred fifty-three babies (0.31%, 95% CI: 0.28-0.35) were exposed to AEDs during the first trimester. The rate of MCMs was 2.3% in the AED group (2.2% in babies exposed to monotherapy and 3.1% in babies exposed to polytherapy) vs 2.0% in the non-exposed. The risk of FGR was 12.7 % in the exposed group compared to 10% in the non-exposed. Discussion and Conclusion: The prevalence of AED exposure in pregnancy in the RER was 0.42%. The rate of MCMs in children exposed to AEDs in utero was almost superimposable to the one of the non-exposed, however polytherapy carried a slightly increased risk . The rate of TOPs was significantly higher in the exposed women. Further studies are needed to clarify whether this high rate reflects a higher rate of MCMs detected prenatally or other more elusive reasons.

Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient-reported outcome at 4 weeks

Objective improvement following intradetrusor injections of botulinum neurotoxin type A (BoNTA) is well documented. Although patient-related outcome measures are highly recommended for monitoring overactive bladder symptoms, no study before has dealt with the question of patient-reported complete continence after BoNTA treatment using validated questionnaires.

Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency

INTRODUCTION: N-Acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder, which may present in the neonatal period with severe hyperammonemia and marked neurological impairment. CASE REPORT: We report on a Turkish family with a patient who died due to hyperammonemia in the neonatal period. Reduced activity of NAGS and carbamyl phosphate synthetase were found at autopsy. A second child who developed hyperammonemia on the second day of life was immediately treated with arginine hydrochloride, sodium benzoate and protein restriction. After NAGS deficiency was suspected by enzyme analysis, sodium benzoate was replaced by N-carbamylglutamate (NCG). A third child who developed slight hyperammonemia on the third day of life was treated with NCG before enzyme analysis confirmed reduced NAGS activity. Neither of the patients developed hyperammonemia in the following years. After the human NAGS gene was identified, mutation analysis revealed that the older sibling on NCG therapy was homozygous for a 971G>A (W324X) mutation. The parents and the younger sibling were heterozygous. Therapy was continued in the older sibling until now without any adverse effects and favourable neurodevelopment outcome. In the younger sibling, therapy was stopped without any deterioration of urea cycle function. CONCLUSION: NAGS deficiency can be successfully treated with NCG and arginine hydrochloride with favourable outcome. Molecular diagnostic rather than enzyme analysis should be used in patients with suspected NAGS deficiency.

Dental arch relationship in children with complete unilateral cleft lip and palate following one-stage and three-stage surgical protocols

The objective of this study is to compare dental arch relationship following one-stage and three-stage surgical protocols of unilateral cleft lip and palate. Dental casts of 61 children (mean age, 11.2 years; SD, 1.7), consecutively treated in one center with one-stage closure of the complete cleft at 9.2 months (SD, 2.0), were compared with a sample of 97 patients (mean age, 8.7 years; SD, 0.9), consecutively treated with a three-stage protocol including delayed hard palate closure in another center. The dental casts were assigned random numbers to blind their origin. Four raters graded dental arch relationship and palatal morphology using the EUROCRAN index. The strength of agreement of rating was assessed with kappa statistics. Independent t tests were run to compare the EUROCRAN scores between one-stage and three-stage samples, and Fisher's exact tests were performed to evaluate differences of distribution of the EUROCRAN grades. The intra- and inter-rater agreement was moderate to very good. Dental arch relationship in the one-stage sample was less favorable than in three-stage group (mean scores, 2.58 and 1.97 for one-stage and three-stage samples, respectively; p?following one-stage repair was less favorable than the outcome of three-stage repair. The palatal morphology following one-stage repair, however, was more favorable than the outcome of three-stage repair.

Healing of two and three wall intrabony periodontal defects following treatment with an enamel matrix derivative combined with autogenous bone

BACKGROUND: There are still limited data on the outcomes of regenerative periodontal surgery using a combination of an enamel matrix protein derivative (EMD) and autogenous bone (AB). AIM: To evaluate the healing of deep intrabony defects treated with either a combination EMD+AB or EMD alone. MATERIALS AND METHODS: Forty patients with advanced chronic periodontitis, with one deep intrabony defect, were randomly treated with either EMD+AB (test) or EMD (control). Clinical assessments were performed at baseline and at 1 year after treatment. The primary outcome variable was relative attachment level (RAL). RESULTS: Healing was uneventful in all patients. The test sites showed a reduction in the mean probing pocket depth (PPD) of 5.6 +/- 0.9 mm (p<0.001), a gain in the mean RAL of 4.2 +/- 1.1 mm (p<0.001) and a gain in the mean probing bone level (PBL) of 3.9 +/- 1.0 mm (p<0.001). The control group displayed a mean PPD reduction of 4.6 +/- 0.4 mm (p<0.001), a mean RAL gain of 3.4 +/- 0.8 mm (p<0.001) and a mean PBL gain of 2.8 +/- 0.8 mm (p<0.001). RAL gains of > or =4 mm were measured in 90% of the test defects and in 55% of the controls. PBL gains of > or =4 mm were obtained in 85% of the test defects and in 25% of the control ones. The test treatment resulted in statistically higher PPD reductions, RAL gains and PBL gains compared with the control (p<0.01). CONCLUSIONS: Within their limits, the present results indicate that: (i) at 1 year after surgery, both therapies resulted in statistically significant clinical improvements compared with baseline and (ii) although the combination of EMD+AB resulted in statistically significant higher soft and hard tissue improvements compared with treatment with EMD, the clinical relevance of this finding is unclear.

Prolonged inflammation following critical illness may impair long-term survival: a hypothesis with potential therapeutic implications

Despite successful intensive care a substantial portion of critically ill patients dies after discharge from the intensive care unit or hospital. Observational studies investigating long-term survival of critically ill patients reported that most deaths occur during the first months or year after discharge. Only limited data on the causes of impaired quality of life and post-intensive care unit deaths exist in the current literature. In this manuscript we hypothesize that the acute inflammatory response which characteristically accompanies critical illness is ensued by a prolonged imbalance or activation of the immune system. Such a chronic low-grade inflammatory response to critical illness may be sub-clinical and persist for a variable period of time after discharge from the intensive care unit and hospital. Chronic inflammation is a well-recognized risk factor for long-term morbidity and mortality, particularly from cardiovascular causes, and may thus partly contribute to the impaired quality of life as well as increased morbidity and mortality following intensive care unit and hospital discharge of critically ill patients. Assuming that critical illness is indeed followed by a prolonged inflammatory response, important implications for treatment would arise. An interesting and potentially beneficial therapy could be the administration of immune-modulating drugs during the time after intensive care unit or hospital discharge until chronic inflammation has subsided. Statins are well-investigated and effective drugs to attenuate chronic inflammation and could potentially also improve long-term outcome of critically ill patients after intensive care unit or hospital discharge. Future studies evaluating the course of inflammation during and after critical illness as well as its response to statin therapy are required.

Lipid profiles and outcome in patients treated by intravenous thrombolysis for cerebral ischemia

OBJECTIVE:To determine whether low low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) and triglyceride concentrations are associated with worse outcome in a large cohort of ischemic stroke patients treated with IV thrombolysis. METHODS:Observational multicenter post hoc analysis of prospectively collected data in stroke thrombolysis registries. Because of collinearity between total cholesterol (TC) and LDL-C, we used 2 different models with TC (model 1) and with LDL-C (model 2). RESULTS:Of the 2,485 consecutive patients, 1,847 (74%) had detailed lipid profiles available. Independent predictors of 3-month mortality were lower serum HDL-C (adjusted odds ratio [(adj)OR] 0.531, 95% confidence interval [CI] 0.321-0.877 in model 1; (adj)OR 0.570, 95% CI 0.348-0.933 in model 2), lower serum triglyceride levels ((adj)OR 0.549, 95% CI 0.341-0.883 in model 1; (adj)OR 0.560, 95% CI 0.353-0.888 in model 2), symptomatic ICH, and increasing NIH Stroke Scale score, age, C-reactive protein, and serum creatinine. TC, LDL-C, HDL-C, and triglycerides were not independently associated with symptomatic ICH. Increased HDL-C was associated with an excellent outcome (modified Rankin Scale score 0-1) in model 1 ((adj)OR 1.390, 95% CI 1.040-1.860). CONCLUSION:Lower HDL-C and triglycerides were independently associated with mortality. These findings were not due to an association of lipid concentrations with symptomatic ICH and may reflect differences in baseline comorbidities, nutritional state, or a protective effect of triglycerides and HDL-C on mortality following acute ischemic stroke.