Abstract Introduction Thrombotic microangiopathy (TMA) is characterized by endothelial cell injury and formation of fibrin thrombi within capillary and arterioles. In renal allograft recipients, TMA ...mainly presents as hemolytic uremic syndrome. Its occurrence is rare, and diagnosis requires a high degree of suspicion. Drug toxicity, in particular from calcineurin inhibitors (CNIs) and mTOR inhibitors (mTORi), is the most common cause posttransplant and has recently been emphasized in the setting of lung transplantation. Objective The goal of this study was to investigate the role of mTORi as an added risk factor in the development of TMA to propose strategies for modulation of immunosuppressive (IS) therapy. Patients and Methods From a database of 496 renal graft recipients, we analyzed 350 renal graft biopsy specimens gathered at our center from 1998 to 2012. In patients undergoing combined therapy with mTORi and CNI, we compared drugs levels in TMA-affected and TMA-free groups, using mTORi and CNI TLC and the summation of everolimus TLC + (cyclosporine C2/100) (Σ) as a surrogate marker of combined exposition to 2 drugs. Receiver-operating characteristic analysis of association of EVL TLC + (C2/100) was performed for patients exposed to mTORi. Results Histologic features of TMA were found in 36 patients (prevalence of 7.3%). The caseload was divided into 2 groups: not drug-related TMA (n = 19) and drug-related TMA (n = 17). Despite the prevalence of TMA in patients exposed to mTORi being greater (8 of 153; prevalence, 5.3%) compared with therapies without mTORi (9 of 324; prevalence, 2.8%), statistical difference was not reached. Patients treated with mTORi who developed de novo drug-related TMA had higher blood levels of IS drugs compared with those who did not develop TMA. Receiver-operating characteristic analysis found a significant threshold of 12.5 ng/mL (area under the curve, 0.803; P = .006). Conclusions Results confirm the pivotal role of IS drugs in the onset of de novo TMA. On the basis of literature, we could speculate a sequence of endothelial damage by CNI, on which everolimus fits hindering the repair of endothelial injury. Therefore, high blood levels of CNI and mTORi seem to predispose patients to posttransplant TMA. Combined monitoring of these 2 drugs might be used to prevent the complication. Σ everolimus TLC + (cyclosporine C2/100) >12.5 ng/mL should be avoided as a surrogate risk factor for adverse effects.
Abstract Background In Human immunodeficiency virus (HIV)-positive patients undergoing kidney transplantation, outcomes and immunosuppression (IS) protocol are not yet established due to infectious ...and neoplastic risks as well as to pharmacokinetic interactions with antiretroviral therapy (TARV). Methods We report a retrospective, 1-center study on 18 HIV+ patients undergoing, between October 2007 and September 2015, kidney transplantation (13 cases) or combined kidney-liver transplant (5 cases). Inclusion criteria for transplant were based on the Italian National Transplant Center protocol. IS regimen was based on quick tapering of steroids and the use of mTOR inhibitors (mTORi) with low dose of calcineurin inhibitors (CNI). In the early post-transplant period, TARV was based on enfuvirtide, raltegravir, plus 1 or more nucleoside analogues. Results In a mean follow-up of 3.1 years, patient survival rate at 1 and 3 years was, respectively, 86.6% and 84.6%, whereas graft survival was 81.2% and 78.6%. Cumulative rejection rate was 20.0% and 26.6% (1- and 3-year results). Median eGFR (MDRD) was 58.8 mL/min and 51.9 mL/min at 1 and 3 years. We had 9 cases of clinically relevant infections (2 Pneumocystis jirovecii pneumonia, 1 pulmonary aspergillosis, 2 severe sepsis, and 4 HCV reactivation) as well as 1 case (5.5%) of HIV reactivation. Conclusions IS therapy based on mTORi and low CNI dose ensures good graft survival, low rate of acute rejection, limited drug toxicity, and control of HIV disease. TARV has no significant interaction with IS therapy.
Objectives
Pain control after thoracotomies prevents complications (infections, atelectasies, etc.) and improves respiratory function. The gold standard for post-thoracotomy analgesia is ...administration of drugs through an epidural catheter preoperatively placed by the anaesthesiologist. The aim of this study is to prospectively compare that technique with drugs administration through a paravertebral catheter.
Methods
From November 2011 to June 2012, 42 patients submitted to thoracotomy have been randomized into two groups for the administration of analgesic drugs, through an epidural in group A or a paravertebral catheter in group B. The last one was placed by the same team of surgeons tunnelling parietal pleura and entering the paravertebral space before thoracotomy closure. The following parameters have been recorded on scheduled postoperative days: a) pain control using the Visual Analogue Scale; b) respiratory function using FEV1 and ambient air saturation; c) blood cortisol values as index of systemic reaction to pain. Records have been analyzed with the Mann-Whitney or Student's tests for independent variables.
Results
Significant differences have been found in favour of group B concerning both cough and rest pain control (P = 0.002 and 0.002) and respiratory function in terms of FEV1 and ambient air saturation (P = 0.023 and 0.001). No significant differences have been found in blood cortisol trends comparing the two groups (P > 0.05). No complications after placement were recorded in both groups. Collateral effects such as vomit, nausea, low pressure or urinary retention have been observed in 18 of 21 patients belonging to group A. Instead there were no recorded collateral effects in the paravertebral group.
Conclusions
According to our data paravertebral catheter after thoracotomy is more effective than epidural and has no collateral effects. Moreover, its intraoperative placement is easy and without contraindications (spine anomalies and coagulation deficits). Therefore, paravertebral should be always considered as an alternative to epidural catheter.
Disclosure
All authors have declared no conflicts of interest.
Objective: To compare post-operative course, lung function and survival of lung cancer patients with a forced expiratory volume in 1 s (FEV1) more or less than 80% of predicted submitted to ...lobectomy. Methods: The data of patients undergoing lobectomy for non small cell carcinoma at the Thoracic Surgery Unit of the Ospedale Maggiore Policlinico of Milan, Italy, were prospectively collected. Inclusion criteria were a radical resectable tumor with size less than 2.5 cm, negative mediastinal nodes, capability to complete pulmonary function tests, Exclusion criteria were FEV1 ≪40% of predicted, pre- or post-operative chemo or radiotherapy, lobe to be resected receiving more than 30% of the perfusion, incapacity to quit smoking. Results: Eighty-eight patients entered the study and were divided into two groups according to their FEV1%: 45 patients were included in control group (mean FEV1: 92.2%) and 42 in chronic obstructive pulmonary disease group (mean FEV1: 64.2%). Post-operative complications, operative mortality and actuarial survival were the same in the 2 groups. Six months after lobectomy, the mean changes in FEV1 were −14.9% for first group and −3.2% for second group (P≪0.001). Conclusion: Lobectomy for cancer can be performed successfully also in selected patients with chronic obstructive pulmonary disease. Post-operative course and survival of these patients is not different from that of patients with normal FEV1, on the contrary, patients with low FEV1 may lose less pulmonary function or even mend it.
Acquired fistulas between the trachea and the esophagus (TEFs) are unusual, serious and still challenging clinical entities. Between 1980 and 1997, 31 patients with acquired benign TEF were evaluated ...and treated in our department. The definitive treatment was undertaken when patients were weaned from the ventilator. Dissection of the fistula and closure of the tracheal and esophageal defect was performed in 26 patients. Esophagogastroplasty plus closure of the tracheal defect and omental interposition was performed in two patients. Tracheal resection and reconstruction plus of the sternocleidomastoid muscle interposition was carried out in one patient with circumferential tracheal damage. In two patients, no surgical treatment was carried out. One patient died after surgical treatment. In 23 patients, long‐term follow‐up was excellent, with normal post‐operative function of both the esophagus and the airway. Two failures of treatment occurred which required definitive tracheostomy plus T‐tube. Management of TEFs can be safely carried out after weaning patients from the ventilator.
Hemangiomas are tumors of vascular origin and represent less than 3% of benign neoplasm of the esophagus. We herein report a case of a 55‐year‐old man, who presented transitory dysphagia and weight ...loss. A malignancy could not be excluded by a complete work‐up, including esophagogram, endoscopic biopsies, CT scan, esophageal endoscopic ultrasonography, PET and thoracoscopic biopsies. Only after partial esophagectomy with laparoscopic gastric mobilization was histological diagnosis obtained. In fact, on microscopic observation of the specimen, the neoplasm appeared to be a cavernous hemangioma of the esophageal submucosa with transparietal extension.
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