Liver Transplantation Following Life-threatening Abdominal Trauma: A Case Series of 5 Patients at a Single Institution

Managing traumatic liver injury (TLI) is always challenging and demands precise clinical judgment. Currently, treatment of TLI in most circumstances is non-operative; however, surgical therapy might be required for severe TLI, particularly those that result in extensive blood loss. In the current institutional study carried out from June 1995 to April 2017, we describe our experience with 5 patients who received an orthotopic liver transplant for severe TLI. One patient passed away postoperatively from cerebral edema; 1 patient died of renal failure 4 years after the liver transplantation, and 3 patients are still alive. Based on our experience, we conclude that in patients with TLI, especially those with uncontrollable bleeding or those who develop liver failure, liver transplantation should be taken into consideration.     

Multifocal pheochromocytoma-paraganglioma in a 29-year-old woman with cyanotic congenital heart disease

Background

Multifocal pheochromocytoma/paraganglioma presenting at an early age is commonly associated with a hereditary syndrome.

Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings

ObjectivesDescribe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA).MethodsClinical seizures from eight patients (mean follow-up of 10.1 years) were analyzed pre- and post-treatment. Chronic ambulatory electrocorticograms (ECoGs) recorded from PVNHs, hippocampus and neocortex were evaluated to identify the earliest electrographic seizure onset type, pattern of spread, and interictal characteristics.ResultsMean reduction in disabling seizures was 85.7 % (n = 8); seven patients had >50% seizure reduction and two were seizure-free in the final year of analysis. Seizure rate showed a progressive reduction over the course of the study with the highest rate of improvement in the first two to three years after implantation. Four of seven patients with one PVNH lead and a second lead in the hippocampus or neocortex had some electrographic seizures first recorded at either lead location, suggesting two foci or seizure propagation patterns. Low voltage fast type activity was the prominent seizure onset pattern. Interictal ECoG power was lower in PVNH than hippocampus.ConclusionsRNS® System treatment substantially reduced clinical seizure frequency in patients with PVNH. Analysis of ictal ECoG records suggests PVNH may be involved in seizure generation.SignificanceChronic ECoG recordings suggest PVNH tissue can actively participate in epileptogenic networks. Direct brain-responsive neurostimulation is a safe and effective treatment option in such patients, progressively reducing seizure rate over a period of years.     

TP53 and therapy-related myeloid neoplasms

Therapy-related myeloid neoplasms (t-MNs) are the most serious late complications in patients treated with traditional cytotoxic chemotherapy and/or radiation. T-MNs are aggressive and chemorefractory hematologic malignancies, with a median survival of less than 6 months. TP53 mutations are highly enriched in t-MN patients, though the mechanism for this selective enrichment has only come to light over the past several years. In this review, we discuss the history and function of p53, and the role of TP53 mutations in the origin and progression of t-MNs. Emerging data has begun to elucidate who may be at highest risk of developing t-MNs, which ideally will enable us to develop preventative strategies for this devastating disease. As t-MNs may not be avoidable, novel therapies are urgently needed for this patient group and are underway as exemplified by recent investigation in restoring wild-type p53 function as well as directly targeting TP53 mutant variants. With better prevention and treatment, outcomes will hopefully begin to improve in the near future.     

中国肾移植患者红细胞内嘌呤类药物活性代谢物6-硫鸟嘌呤核苷酸浓度监测及影响因素分析

目的：研究服用硫唑嘌呤（AZA）中国肾移植患者红细胞（RBC）内活性代谢物6-硫鸟嘌呤核苷酸（6-TGNs）分布特征及影响因素，为临床合理应用嘌呤类药物提供依据。方法：以89例中国肾移植患者为研究对象，关联分析年龄、性别、体质量、AZA剂量和TPMT活性对RBC内6-TGNs浓度的影响，并应用SPSS v20.0软件进行多元线性回归分析。结果：89例中国肾移植患者RBC内6-TGNs浓度呈非正态分布（P<0.000 1），6-TGNs浓度中位数为167.60（四分位间距，108.10~300.80） pmol/8×10⁸ RBC，个体间差异约24.3倍。关联分析显示患者年龄、性别、体质量、TPMT活性对6-TGNs浓度均无显著影响（P>0.05）；而AZA剂量与6-TGNs浓度间呈显著正相关性（r_s=0.307 1，P<0.01）。多元线性回归分析显示，RBC内6-TGNs浓度与AZA剂量间呈显著正相关（P<0.001），与TPMT活性呈显著负相关（P<0.05）。结论：AZA剂量和RBC内TPMT活性协同影响嘌呤类药物活性代谢物6-TGNs浓度，进而影响该类药物临床疗效和毒性反应。     

Does choice of antiretroviral drugs matter for inflammation?

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut.

Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies.

Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.     

TGF‐β1‐activated type 2 dendritic cells promote wound healing and induce fibroblasts to express tenascin c following corneal full‐thickness hydrogel transplantation

We showed previously that 1‐ethyl‐3‐(3‐dimethylamino‐propyl)‐carbodiimide hydrochloride (EDC) cross‐linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4 years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers—bulky, aromatic N‐cyclohexyl‐N0‐(2‐morpholinoethyl)‐carbodiimide (CMC), and nonbulky EDC—in a mouse corneal graft model. Murine corneas undergoing full‐thickness implantation with these gels became opaque due to dense retro‐corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c⁺ dendritic cells (DC) were found, suggesting a hydrogel‐specific innate immune response. More DC infiltrated the stroma surrounding EDC‐N‐hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis‐associated tenascin c expression. The opposite was true for CMC‐NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor β1 (TGF‐β1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF‐β1 neutralisation. Furthermore, tenascin c staining was found in 40‐ to 50μm long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF‐β1 alternatively activated (tolerising) DC regulate fibroblast‐mediated tenascin c secretion, possibly via local production of TGF‐β1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries.