Sublingual administration of tacrolimus in a renal transplant patient

Tacrolimus is used in renal and other organ transplantations for immunossupression therapy. Bioavailability of enterally administered tacrolimus is poor, and further reduced by gastrointestinal failure or enteral nutrition. In these situations, intravenous administration is necessary to prevent treatment failure. However, intravenous administration should be done in a continuous manner and it has been implicated in anaphylaxis, torsades de pointes, cardiac arrhythmia and other serious adverse events. Also it is more expensive than other routes of administration. Sublingual administration of tacrolimus has been used in some cases, and literature reports show that it provides therapeutic tacrolimus levels in lung and liver transplant recipients. Here, we report a first case of sublingual administration of tacrolimus in kidney transplantation.     

High venous pressure in the main renal vein causing development of peritransplant venous collaterals in renal transplant patients: a rare finding

We will show the sonographic appearance of peritransplant venous collaterals in renal transplants with renal venous hypertension. Three cases of renal transplants with pericapsular vessels were identified at our institution. Two cases were related to renal vein thrombosis. The third case had pericapsular vessels secondary to venous hypertension from arterialization of the transplant renal vein by a preexisting right thigh arteriovenous graft. The development of high venous pressures in renal transplants leading to the collaterals' venous drainage has been rarely described. This finding should be recognized as a rare complication of renal transplants but does not necessarily lead to transplant failure.     

Recombinant activated factor VII in a patient with intracranial hemorrhage and severe thrombocytopenia

Hemorrhage in patients with hematologic malignancies is often difficult to manage as many of these patients also have coagulopathy and thrombocytopenia of varying severity. Recombinant factor VIIa is a FDA‐approved agent for management of bleeding in hemophilia patients with inhibitors. Use of recombinant FVIIa has also been used as a last resort in various clinical settings such as trauma, alveolar hemorrhage, gastrointestinal bleeding, and intracranial hemorrhage for control of bleeding with variable outcomes. This paper presents a case of recombinant FVIIa administration in a patient with multiple myeloma and profound transfusion refractory thrombocytopenia suffering from traumatic subdural hematoma.     

Laparoscopic Roux-en-Y gastric bypass in a morbidly obese patient with renal transplant: a case report

Renal transplant is the only curative treatment for end-stage renal disease. As diabetes and obesity are the major causes of graft failure and post-transplant complication, it is important to manage obesity in patients with renal transplant. Herein, we report a case of a morbidly obese renal-transplant patient with poorly controlled diabetes who received bariatric surgery. A 34-year-old obese Taiwanese man with type 2 diabetes had end-stage renal disease that had progressed since 2008, when he had commenced hemodialysis (January 2008) and had a renal transplant (July 2008). Because of persistent obesity and poorly controlled diabetes, he received LRYGB at Chiayi Christian hospital on 18 August 2010. In the month that followed, he lost 10 kg. His serum creatinine decreased to 1.11 mg/dL (1.4 mg/dL, preoperative) and his hemoglobin A1c decreased to 8.5% (10.4%, preoperative). These results indicate that, in obese renal transplant patients, LRYGB may be employed to treat obesity, control diabetes and stabilize or improve the renal function.     

Estimation of the area under the curve for mycophenolic acid in adult renal transplant patients with concomitant tacrolimus using a limited sampling strategy

Objectives: The aim of this study was to develop a limited sampling strategy (LSS) for monitoring the use of mycophenolic acid (MPA) in maintenance therapy with tacrolimus (TCL) in renal transplant patients. Methods: Eighteen adult patients receiving a first transplant were investigated. All patients were treated with a combination of TCL, steroid and mycophenolate mofetil (MMF). Besides the predose trough concentration (C₀), whole blood samples were taken for measurement of the MPA concentration at 0·5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 h for a 14‐point 12‐h pharmacokinetic (PK) profile. Using stepwise linear regression analysis, an abbreviated area under the concentration time curve (AUC) was calculated using all 14, and any combination of sampling points to give an estimating equation with up to three predictors. Results: The equation derived from C₂, C₇ and C_12, for AUC estimation: AUC = (2·05 × C₂) + (8·51 ×C₇) + (2·29 × C₁₂) + 4·24. was found to be optimal. Using this formula, there was an excellent correlation between the estimated 3‐point AUC and AUC_{0–12 h}. To assess the agreement between the abbreviated methods and the full PK profile, we plotted the average AUC of the abbreviated estimates and the full PK profile. This Bland‐Altman analysis indicated good agreement to within ±2 SD and a prediction variability of 7·56 μg × h/mL. Conclusion: Our proposed three‐sampling‐point estimate of AUCs is clinically acceptable. However, the sampling times are inconvenient for outpatients, and is recommended only for monitoring MMF treatment of inpatients with suspected toxicity or at high risk of organ rejection.     

Extraocular sebaceous carcinoma in a renal transplant patient: A case report

The high risk of skin cancer after organ transplantation is a major clinical challenge. We describe a case of a patient presenting with sebaceous carcinoma (SC) after a kidney transplant. Although it is exceedingly rare, SC should always be considered in the presence of any skin lesion occurring after a transplant.     

Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients

BACKGROUND AND OBJECTIVES: Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration-time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. METHODS: The associations between tacrolimus trough concentrations (C(0)), non-trough concentrations (C(1), C(2), C(4), C(6/8)), and AUC(0-12) and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. RESULTS AND DISCUSSION: The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C(0), C(1), C(2), C(4), C(6/8) or AUC(0-12) and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects. CONCLUSIONS: Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range.     

Congenital coagulation factor V deficiency with intracranial hemorrhage

BackgroundCongenital coagulation factor V (FV) deficiency is a very rare hemorrhagic disease with an incidence of approximately one in a million. The common clinical manifestations of FV deficiency include ecchymosis and mucosal bleeding. Life‐threatening intracranial bleeding is rare. It has been reported in several cases. However, the molecular basis has been established in only a few cases.MethodsWe reported a 2‐month‐old girl with congenital FV deficiency and intracranial hemorrhage. Coagulation screening combined with clinical manifestations was performed to diagnose congenital FV deficiency. Genetic testing was performed to identify the pathogenic genes. A literature review was included to emphasize the clinical manifestation, diagnosis, and treatment for congenital FV deficiency with intracranial bleeding.ResultsThe coagulation tests revealed a significantly prolonged prothrombin time (PT) of 51 s and an activated partial thromboplastin time (APTT) of 73.7 s. The patient had a plasma FV activity of 0.9%. Genetic testing showed compound heterozygous mutations of the patient''s FV gene. A literature review showed that patients with homozygous or compound heterozygous variants of the FV gene were often associated with a severe bleeding phenotype.ConclusionOur study provides a direction for the rapid and accurate diagnosis and treatment for FV deficiency to avoid life‐threatening bleeding. Infants with spontaneous cranial hematoma and intracranial hemorrhage should be investigated for underlying hemostatic defects. Congenital coagulation factor deficiency should be considered. Once congenital FV deficiency is diagnosed, fresh frozen plasma (FFP) should be given on a regular basis. Liver transplantation may be performed in severe cases.     

不典型新生儿颅内出血的临床特征

目的探讨不典型新生儿颅内出血的临床特征,提高早期诊断的准确率.方法2000～2005年间,我科共有152例新生儿颅内出血病例住院治疗,其中不典型颅内出血65例.对所有的病例资料作回顾性分析,对比典型与不典型新生儿颅内出血的临床表现和预后情况.结果65例不典型病例多表现为意识、肌张力、原始反射等方面轻度异常,伴蛛网膜下腔出血者最多（46例）.其分娩方式和产伤人数与典型病例组无显著性差异（P＞0.05）;早产儿比例显著较高（P＜0.05）;窒息程度较轻（P＜0.05）;治愈52例,预后较好（P＜0.05）.结论不典型新生儿颅内出血多见于早产儿,早期病情相对较轻,临床表现不明显,易导致误诊漏诊,临床医师应给予足够重视.     

Low levels of lymphocyte MDR1 gene expression during early renal transplantation in patients treated with tacrolimus

P-glycoprotein (P-gp) is a membrane efflux pump increasing the transport of drugs such as tacrolimus out of the cells. The aim of the study was to determine the kinetics of lymphocyte P-gp expression in patients treated with tacrolimus during the first 3 months following renal transplantation. Lymphocyte MDR1 gene expression was measured by semi-quantitative RT-PCR a few hours before transplantation, 3 weeks and 3 months after the graft. Lymphocyte MDR1 gene expression was low in all the 10 patients compared to 10 healthy volunteers: 0.30 +/- 0.07 arbitrary units (patients) vs. 1.74 +/- 0. 55 (healthy volunteers) (P = 0.0002). MDR1 gene expression decreased among the patients during the study: 0.28 +/- 0.12 (3 weeks later) and 0.12 +/- 0.09 (3 months later) (P = 0.006). We can conclude that lymphocyte MDR1 gene expression among patients before renal transplantation is low and remains low during the first 3 months following the graft.     

新生儿颅内出血的相关因素分析

目的分析新生儿颅内出血的相关因素,并探讨相关预防对策。方法回顾性分析2011年8月至2019年8月我院120例新生儿颅内出血的临床资料,另外收集同期120例非新生儿颅内出血的相关资料进行对照观察。分析新生儿颅内出血的相关因素,并探讨相关预防对策。结果宫内窘迫、妊娠高血压、早产、难产、窒息、新生儿生后用多巴胺、APTT是新生儿颅内出血的危险因素,而新生儿体重为新生儿颅内出血的保护因素(P<0.05)。结论新生儿颅内出血的影响因素复杂,临床应完善产妇孕期保健,避免孕期合并症的发生,从而降低新生儿颅内出血的发生率与死亡率,提高人口质量。     

Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.     

Transplant with a twist: A pitfall in sonographic diagnosis of renal transplant torsion

Torsion is an uncommon cause of impaired function in a renal transplant. We present a case of intraperitoneal transplant torsion secondary to adhesions to the left fallopian tube and ovary. Inability to confirm renal venous flow with Doppler misled to the erroneous sonographic diagnosis of renal vein thrombosis, although end diastolic flow was absent rather than reversed. The correct diagnosis was made with CT. The combination of abnormal orientation of the graft on ultrasonography, acutely impaired renal function, and abnormal Doppler study should have led to a diagnosis of transplant torsion. The case is also unusual in that the lead point was adnexal pathology. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45 :528–530, 2017     

早产儿颅内出血的超声与MRI对比研究

摘要：目的 应用超声与MIR对早产儿颅内出血进行同期对照检查,比较两种方法对早产儿颅内出血的诊断价值。方法 对335例临床高度疑似颅内出血的早产儿,同时进行颅脑超声及MRI检查,对两种诊断结果进行分析比较。结果335例颅内出血中,超声诊断符合315例,不符合20例;MRI诊断符合323例,不符合12例。两种检查方法在诊断Ⅰ级脑室出血、硬模下腔出血、蛛网膜下腔出血中均有统计学意义（P≤0.05）,对于其他类型脑出血均无统计学意义（P＞0.05）。灵敏度、特异度、准确性方面：Ⅰ级脑室出血超声检查均为100%,MRI检查分别为94%、100%、94%;硬模下腔出血超声检查分别为78%、100%、80%,MRI检查均为100%;蛛网膜下腔出血超声检查分别为77%、100%、79%,MRI检查均为100%。结论 超声与MRI对诊断不同的早产儿颅内出血各有利弊,临床对高危新生儿,特别是早产儿可先行超声检查,需进一步明确诊断时,再行MRI检查。     

Fatal intracranial hemorrhage associated with phenylpropanolamine, pentazocine, and tripelennamine overdose

Hemorrhagic cerebrovascular accident is an uncommon but serious complication of drug overdose. A case of fatal intracranial hemorrhage following overdose with phenylpropanolamine, pentazocine, and tripelennamine is presented. The pharmacology, pathophysiology, clinical presentation, and management of poisoning by these agents are discussed.