Real life experience with mTOR-inhibitors after lung transplantation.

Mammalian target of rapamycin inhibitors (mTORi) are increasingly used after lung transplantation as part of a calcineurin inhibitor sparing regimen, aiming to preserve renal function. The aim of our study was to determine whether immunosuppressive therapy using mTORi in lung transplant recipients (LTR) is feasible in practice, or limited by intolerance and adverse events. Data were retrospectively assessed for all LTR transplanted between July 1991 and January 2020. Patients ever receiving mTORi (monotherapy or in combination with calcineurin inhibitor) as treatment of physicians' choice were included. 149/1184 (13%) of the LTR ever received mTORi. Main reasons to start were renal insufficiency (67%) and malignancy (21%). In 52% of the patients, mTORi was stopped due to side effects or drug toxicity after a median time of 159 days. Apart from death, main reasons for discontinuation were infection (19%) and edema (14%). Early discontinuation (<90 days) was mainly due to edema or gastrointestinal intolerance. As mTORi was stopped due to adverse events or drug intolerance in 52% of LTR, cautious consideration of advantages and disadvantages when starting mTORi is recommended.

The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation.

Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient survival was 92%. One patient died at 9 months due to aspergillosis, another at 12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early acute rejection (AR) developed in two (15%); late AR in three (23%); all were reversible. No chronic rejection (CR) occurred. No malignancies developed and estimated glomerular filtration rate remained stable post-Tx. At last follow-up (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11 survivors were total parenteral nutrition free with a Karnofsky score >90% in 8 recipients (follow-up >1 years). A high frequency of circulating CD4+ CD45RA- Foxp3hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx, KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a low-inflammatory/pro-regulatory environment activates Tregs at levels similar to tolerant-KTx, without causing sensitization. LIP limits rejection under reduced IS and thereby prolongs long-term survival to an extent not previously attained after ITx.

Popliteal Arteriovenous Fistula Following Total Knee Arthroplasty.

Postoperative popliteal arteriovenous fistula is a very rare complication. We report a unique asymptomatic fistula in a 77-year-old male patient, seven months after total knee replacement. The diagnosis was suspected by a clinical palpable thrill and confirmed with a typical doppler ultrasound signaling. This vascular malformation was successfully treated by surgical resection of the fistula. Referring to the literature, considering the management of popliteal aneurysms, we suggest to prefer an open procedure in patients who are in good general condition.

Combined or Serial Liver and Lung Transplantation for Epithelioid Hemangioendothelioma: A Case Series.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with variable biological and clinical behavior. There is increasing experience with liver transplantation (LiTx) for hepatic EHE, even in cases of extrahepatic disease localization. Until now, no cases of lung transplantation (LuTx) had been reported for pulmonary EHE. This report describes three cases of EHE with multifocal disease in patients who underwent either serial or combined LiTx and LuTx.

Preoperative arterial embolization facilitates multivisceral transplantation for portomesenteric thrombosis.

Multivisceral transplantation (MvTx) for diffuse venous portomesenteric thrombosis is a surgically and anesthesiologically challenging procedure, partly because of the risk of massive bleeding during visceral exenteration. Preoperative visceral artery embolization might reduce this risk. In three consecutive MvTx, the celiac trunk (CT) and superior mesenteric artery (SMA) were embolized immediately pretransplant. We analyzed demographics, serum D-lactate, pH, base excess, hemoglobin, blood pressure, transfused packed cell (PC) units, intervention time and outcome. Results are reported as median (range). All recipients were male (43, 22, 47 years old). Portomesenteric thrombosis followed antiphospholipid syndrome, neuroendocrine tumor and liver cirrhosis. A peritransplant D-lactate peak of 6.1 (5.1-7.6) mmol/L, lowest pH of 7.24 (7.18-7.36) and lowest base excess level of -9.5 (-7.6 to -11.5) were observed. Values normalized within 3 h posttransplant. Embolization and exenteration times were 80 (70-90) min and 140 (130-165) min, respectively, during which blood pressure remained stable, lowest hemoglobin was 6.1 (6.1-7.6) g/dL and three (2-4) PC were administered. All procedures were uneventful. Follow-up was 7 (4-9) months. The first patient died 4 months post-MvTx after an intracranial bleeding; the other patients are doing well. Our experience suggests that preoperative embolization of CT and SMA facilitates native organ resection in MvTx.

Combined liver and lung transplantation with extended normothermic lung preservation in a patient with end-stage emphysema complicated by drug-induced acute liver failure.

Isolated lung transplantation (LuTx) and liver transplantation are established treatments for irreversible lung and liver failure. Combined liver and lung transplantation (cLiLuTx) is a less common, but approved therapy of combined organ failure, mostly applied in patients suffering from progressive cystic fibrosis and advanced liver disease. We report a patient who was listed for LuTx due to end-stage chronic obstructive pulmonary disease and who developed drug-induced acute hepatic failure. The only therapeutic option was hyper-urgent cLiLuTx. To correct the poor coagulation in order to reduce the per-operative risk of bleeding, the liver was transplanted first. In anticipation of the longer lung preservation time, cold flushed lungs were preserved on a portable lung perfusion device for ex vivo normothermic perfusion for 11 h 15 min, transplanted sequentially off-pump, and reperfused after a total ex vivo time of 13 h 32 min and 16 h for the first and second lung, respectively. Ten months later, the patient is doing well and no rejection occurred. Normothermic ex vivo lung perfusion may help to prolong preservation time, facilitating long-distance transport and combined organ transplantation.

The therapeutic implications of an abdominal aortic aneurysm with coincident horseshoe kidney.

Two male patients were admitted to the department of vascular surgery for treatment of a large infrarenal abdominal aortic aneurysm (AAA) and an associated horseshoe kidney (HSK). Both patients were successfully treated by endovascular aneurysm repair (EVAR). Horseshoe kidney is a rare and complex congenital anomaly, which increases significantly the technical difficulty of conventional surgical repair of an associated AAA. Appropriate preoperative evaluation of the vascular supply of the HSK by CT- angiography and renal function is mandatory for optimal planning of the treatment strategy. EVAR is regarded as a valuable alternative to open surgical therapy, in the absence of renal failure and provided that accessory renal arteries are absent or small.

Ileocolic intussusception due to lipomatosis of the ileum: a common complication of a rare clinical entity.

We report a case of intestinal ileal lipomatosis in a 56-year-old Caucasian male complicated with small bowel obstruction due to ileocolic intussusception with a lipoma serving as lead point. This rare disease is often only discovered incidentally as a consequence of mechanical complications and not well reported in the international literature, compared to intussusception due to an isolated lipoma. Computed tomography is the imaging modality of choice to depict complications of this distinct clinicopathological entity. Density measurements can confirm the fatty content and homogeneity analysis of the lesions can guide the radiologist in the differential diagnosis.

Combined kidney and intestinal transplantation in patients with enteric hyperoxaluria secondary to short bowel syndrome.

Kidney transplantation is the treatment of choice for end-stage renal disease whereas indications for intestinal transplantation are currently restricted to patients with irreversible small bowel failure and severe complications of total parenteral nutrition (mostly shortage and infection of venous accesses, major electrolyte disturbances and liver failure). Enteric hyperoxaluria is secondary to certain intestinal diseases like intestinal resections, chronic inflammatory bowel disease and other malabsorption syndromes and can lead to end-stage renal disease requiring kidney transplantation. We report two patients suffering from renal failure due to enteric hyperoxaluria (secondary to extensive intestinal resection) in whom we elected to replace not only the kidney but also the intestine to prevent recurrence of hyperoxaluria in the transplanted kidney.

If you had less than a year to live, would you want to know? A seven-country European population survey of public preferences for disclosure of poor prognosis.

OBJECTIVE: With increasing European cancer deaths, clinicians must manage information regarding poor prognosis. This study aimed to determine European citizens' preferences, within a scenario of serious illness such as cancer with less than a year to live, for information disclosure regarding poor prognosis, the likely symptoms and problems, and the care options available, to measure variations between countries and to identify factors associated with preferences. METHODS: A population-based cross-national telephone survey using random digit dialling in seven countries was conducted. RESULTS: Among 9344 respondents, data revealed an international preference (73.9%) to always be informed in the scenario of having a serious illness such as cancer with less than a year to live. This varied from 67.6% in Italy to 80.7% in Flanders. A minority (21.1%) did not want such information unless they ask, or at all. People younger than 70 years (OR 0.72, 95% CI 0.62-0.83, p < 0.001), men (OR 1.23, 95% CI 1.10-1.37, p < 0.001), those with experience of illness (OR = 1.20. 95% CI 1.01-1.43, p < 0.05) and with more education (OR = 1.20, 95% CI 1.09-1.32, p < 0.001) were more likely to want to know of limited time left. CONCLUSIONS: The models confirmed the influence of four factors in more than one country (age, gender, education and most concerning problem) and added 11 country-specific factors to which national policies and clinical practice should respond. These findings confirm a majority public preference to be informed in a scenario of poor prognosis. Policy clinical practice should facilitate elucidation and delivery of preferences. Evidence for effective communication skills-building interventions for clinicians is required.

Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain.

BACKGROUND: Cancer end-of-life care (EoLC) policies assume people want to die at home. We aimed to examine variations in preferences for place of death cross-nationally. METHODS: A telephone survey of a random sample of individuals aged ≥16 in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain. We determined where people would prefer to die if they had a serious illness such as advanced cancer, facilitating circumstances, personal values and experiences of illness, death and dying. RESULTS: Of 9344 participants, between 51% (95% CI: 48% to 54%) in Portugal and 84% (95% CI: 82% to 86%) in the Netherlands would prefer to die at home. Cross-national analysis found there to be an influence of circumstances and values but not of experiences of illness, death and dying. Four factors were associated with a preference for home death in more than one country: younger age up to 70+ (Germany, the Netherlands, Portugal, Spain), increased importance of dying in the preferred place (England, Germany, Portugal, Spain), prioritizing keeping a positive attitude (Germany, Spain) and wanting to involve family in decisions if incapable (Flanders, Portugal). CONCLUSIONS: At least two-thirds of people prefer a home death in all but one country studied. The strong association with personal values suggests keeping home care at the heart of cancer EoLC.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

BACKGROUND: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. OBJECTIVES: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. METHODS: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. RESULTS: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. INTERPRETATION: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Proximal row carpectomy vs four corner fusion for scapholunate (Slac) or scaphoid nonunion advanced collapse (Snac) wrists: a systematic review of outcomes.

Proximal row carpectomy (PRC) and scaphoid excision with four-corner fusion (4CF) are common motion-preserving, salvage procedures for the treatment of wrists with scaphoid nonunion (SNAC) or scapholunate advanced collapse (SLAC). A systematic review was undertaken to clarify controversies regarding which of these procedures has the better outcome. We collated 52 articles that examine outcomes for SNAC or SLAC patients undergoing PRC or 4CF. Although the lack of unbiased trials must be acknowledged, this systematic review confirms that both procedures give improvements in pain and subjective outcome measures for patients with symptomatic and appropriately staged SLAC or SNAC wrists. PRC may provide better postoperative range of movement and lacks the potential complications specific to 4CF (nonunion, hardware issues and dorsal impingement). However, the risk of subsequent osteoarthritis is significantly higher in PRC patients despite the majority being asymptomatic at the time of review. Grip strength, pain relief and subjective outcomes are similar in both treatment groups.

An Epidemiologic Study of the Effects of Carbon Disulfide on the Peripheral Nerves.

Although the labor inspection had disclosed considerable exposure to carbon disulfide (CS&inf2;) in a Belgian viscose rayon factory, the company medical officer had not diagnosed any case of polyneuropathy in association with CS&inf2; exposure, although this finding had been extensively reported in the literature. Personal monitoring of CS&inf2; exposure was performed in 17 jobs. Because the working conditions in the factory had not changed since 1932, a CS&inf2; cumulative exposure index (CS&inf2; index) could be calculated for each individual. Examination of the exposed subjects (n = 111) included a self-administered questionnaire, a clinical neurologic examination, and electroneuromyography. Seventy-four workers from other plants, not exposed to CS&inf2; or to any other neurotoxic agent, served as referents. The average CS&inf2; exposures of the study group ranged from 4 to 112 mg/m(3). The data were analyzed with multiple regression methods, adjusting the effect of exposure for a number of possible confounders. Significant associations were found between the cumulative CS&inf2; index and symptoms consistent with polyneuropathy in the legs and with abnormal recruitment pattern and decrease of motor conduction velocities of the peroneal nerves. Exposures to CS&inf2; at levels below the present threshold limit value (31 mg/m(3)) were associated with significant decreases of motor conduction velocity.

Torsade de pointes as a complication of brainstem encephalitis.

A case of brainstem encephalitis complicated by torsade de pointes is described. The possible occurrence of ventricular arrhythmias may contribute to the mortality in this condition. We recommend the admission of patients with brainstem encephalitis to an intensive care unit, for a period of electrocardiographic monitoring.