Intrahepatic cholangiocarcinoma as a rare secondary malignancy after allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia: A case report

Secondary malignancies are a significant cause of non‐relapse mortality in patients who undergo allogeneic HCT. However, secondary liver cancer is rare, and ICC following HCT has never been reported in the literature. Secondary solid cancers typically have a long latency period, and cholangiocarcinoma is classically a malignancy occurring in older individuals. Here, we report the first case of secondary ICC, which presented just 3 years after HCT in a young adult with a history of childhood ALL. A 26‐year‐old male with history of precursor B‐cell ALL presented with asymptomatic elevated liver function tests 3 years after HCT. Laboratories were indicative of biliary obstruction. ERCP showed focal biliary stricturing of the common and left hepatic ducts. MRCP revealed left intrahepatic duct dilatation, suggestive of intrahepatic obstructing mass. Additional workup lead to a clinical diagnosis of ICC. The patient underwent left hepatectomy with extrahepatic bile duct resection and portal lymphadenectomy. Surgical pathology was consistent with moderately differentiated cholangiocarcinoma. Our case illustrates a rare SMN following HCT for ALL. It is the first case report of ICC occurring as a secondary cancer in this patient population. Although cholangiocarcinoma is characteristically diagnosed in the older population, it must remain on the differential for biliary obstruction in post‐HCT patients.     

Antimicrobial Activity and Biocompatibility of Antibiotic-Loaded Chitosan Hydrogels as a Potential Scaffold in Regenerative Endodontic Treatment

IntroductionThe objective of this study was to determine the effectiveness of several antibiotic-loaded hydrogel scaffolds against Enterococcus faecalis, as well as their ability to stimulate proliferation and mineralization of dental pulp stem cells.MethodsFibrin (Fg) or chitosan-fibrin hydrogels (Ch) were prepared using 12.5 mg/mL fibrinogen and 0.4% (w/v) chitosan. Triple antibiotics, clindamycin-modified triple antibiotic paste, or double antibiotics were loaded in gels (1 mg/mL). Antibacterial effect against E. faecalis biofilm was determined by using colony-forming units (CFUs) and confocal laser scanning microscope (CLSM). Cell viability and morphology were determined by loading cells into different gels at 7 and 14 days using the water-soluble tetrazolium salt-1 cell viability assay and Live & Dead cell analysis. Mineralization was detected by using alkaline phosphatase and alizarin red staining activity.ResultsAntibiotic-loaded Fg gel and Ch gel alone without antibiotics resulted in a significant reduction in CFUs compared with the positive control (P < .05). When antibiotics were loaded in Ch gel, there were no CFUs detected in any groups (P < .05). CLSM images showed dense red areas with mostly dead bacteria on the dentin surface in antibiotic-loaded Ch groups, which showed significantly less live bacteria compared with the other groups (P < .05). Triple antibiotic-loaded Fg and Ch gels resulted in a dramatic decrease in the mineralized nodule formation compared with all other gel groups (P < .05). Ch hydrogels resulted in round cell morphology up to 7 days. Ch alone or with double antibiotic paste showed more cell spreading with spindle-shaped morphology at 14 days and higher alkaline phosphatase activity compared with other antibiotic-loaded Ch groups (P > .05).ConclusionsDouble antibiotic-loaded Ch gel appears to enhance the antibacterial properties while maintaining higher cell viability, cell spreading, and mineralization activity, compared with all the other scaffolds investigated.     

浅低温不停循环优先重建弓部血管结合术中支架阻断技术与传统孙氏手术的对比研究

目的:采用浅低温不停循环优先重建弓部血管结合术中支架阻断技术治疗急性Stanford A型主动脉夹层,并与传统孙氏手术进行比较,评估其效果和安全性。方法:回顾性分析2017年1月至2018年12月山东省临沂市人民医院心脏血管外科手术治疗的40例急性A型主动脉夹层患者的资料,其中21例在浅低温不停循环下,采用优先重建弓部血管结合术中支架阻断技术进行改良的孙氏手术治疗,19例采用传统的孙氏手术治疗。统计分析患者术中、术后的相关指标及并发症情况。结果:与传统的孙氏手术相比,改良组在术中阻断时间[(218.63±27.86)min比(101.52±17.23)min]、停循环时间[(1174.74±183.65)s比(43.19±8.32)s]、体外循环时间[(218.63±27.86)min比(194.19±24.25)min]、术后并发症(14次比6次)、术后呼吸机辅助时间[(72.89±45.57)h比(29.86±32.3)h]及围术期输血量[(1332.63±301.55)ml比(991.90±323.23)ml]等方面存在明显优势,差异有统计学意义(P均<0.05)。手术后清醒时间方面,改良组优于传统组,但差异无统计学意义。结论:采用浅低温不停循环优先重建弓部血管结合术中支架阻断技术治疗急性A型主动脉夹层是安全、有效的,可以明显改善患者预后,减少并发症的发生。     

Comparison of fiber tract low frequency stimulation to focal and ANT stimulation in an acute rat model of focal cortical seizures

BackgroundCurrent implementations of direct brain stimulation for epilepsy in patients involve high-frequency (HFS) electrical current and targeting of grey matter. Studies have shown that low-frequency (LFS) fiber-tract stimulation may also prove effective. To compare the efficacy of high-frequency grey matter stimulation to the low-frequency fiber tract stimulation technique a well-controlled set of experiments using a single animal model of epilepsy is needed.ObjectiveThe goal of this study was to determine the relative efficacy of different direct brain stimulation techniques for suppressing seizures using an acute rat model of focal cortical seizures.Methods4-AP was injected into the S1 region of cortex in rodents over 3 h. LFPs were recorded from the seizure focus and mirror focus to monitor seizure frequency during the experiments. CC-LFS, HFS-ANT, Focal-HFS, or a transection of the CC was applied.ResultsStimulation of the CC yielded a 65% ±14% (p = 0.0014) reduction of seizures in the focus and a 97% ±15% (p = 0.0026) reduction in the mirror focus (n = 7). By comparison transection of the CC produced a 65% ±18% reduction in the focus and a non-statistically significant reduction of 57% ±18% (p = 0.1381) in the mirror focus (n = 5). All other methods of stimulation failed to have a statistically significant effect on seizure suppression.ConclusionsLFS of the CC is the only method of stimulation to significantly reduce seizure frequency in this model of focal cortical seizures. These results support the hypothesis that LFSof fiber tracts has significant potential for seizure control.     

Sleep and brain morphological changes in the eighth decade of life

ObjectiveSleep is important for brain health. We analysed associations between usual sleep habits and magnetic resonance imaging (MRI) markers of neurodegeneration (brain atrophy), vascular damage (white matter hyperintensities, WMH) and waste clearance (perivascular spaces, PVS) in older community-dwelling adults.MethodWe collected self-reported usual sleep duration, quality and medical histories from the Lothian Birth Cohort 1936 (LBC1936) age 76 years and performed brain MRI. We calculated sleep efficiency, measured WMH and brain volumes, quantified PVS, and assessed associations between sleep measures and brain markers in multivariate models adjusted for demographic and medical history variables.ResultsIn 457 subjects (53% males, mean age 76 ± 0.65 years), we found: brain and white matter loss with increased weekend daytime sleep (β = −0.114, P = 0.03; β = −0.122, P = 0.007 respectively), white matter loss with less efficient sleep (β = 0.132, P = 0.011) and PVS increased with interrupted sleep (OR 1.84 95% CI, P = 0.025).ConclusionCross-sectional associations of sleep parameters with brain atrophy and more PVS suggest adverse relationships between usual sleep habits and brain health in older people that should be evaluated longitudinally.     

急性髓系白血病异基因造血干细胞移植前微小残留病检测意义的Meta分析

目的:探讨急性髓系白血病(AML)异基因造血干细胞移植(allo-HSCT)前微小残留病(MRD)状态与预后之间的关系。方法:计算机检索PubMed数据库、Embase数据库、CNKI数据库、万方数据库，收集符合纳入标准的研究，检索时限均为2016年1月至2018年12月，由两位研究者独立进行文献筛选、资料提取和质量评价后，采用RevMan 5.3软件进行Meta分析。结果:Meta分析结果显示:allo-HSCT前MRD阳性与较低的总生存率(HR=2.72，95%CI:2.27~3.25，P<0.000 01)、无白血病生存率(HR=2.64，95%CI:1.93~3.60，P<0.000 01)及较高的累积复发率(HR=4.13，95%CI:3.15~5.40，P<0.000 01)和非复发死亡率(HR=1.64，95%CI:1.09~2.49，P=0.02)相关。结论:allo-HSCT前MRD阳性与移植后较差的预后具有明显的相关性。     

(Re)organisation of the somatosensory system after early brain lesion: A lateralization index fMRI study

ObjectiveTo evaluate the relationship between neural (re)organization of the somatosensory cortex and impairment of sensory function (2-point discrimination [2PD]) in individuals with unilateral cerebral palsy.MethodsWe included 21 individuals with unilateral cerebral palsy. 2PD thresholds were evaluated on thumb pads, and activation of the somatosensory cortex was recorded by functional MRI (fMRI) during passive movements of the affected hand. A lateralization index (LI) was calculated for the primary sensory (S1) and secondary sensory (S2) cortices and the correlation between the LI and 2PD thresholds was analysed.ResultsWe found a significant negative correlation between the 2PD thresholds and the S2 LI (r = −0.5, one-tailed P-value = 0.01) and a trend towards a negative correlation with the S1 LI (r = −0.4, one-tailed P-value = 0.05).ConclusionHigh levels of activation in the contralesional hemisphere were associated with high levels of sensory impairment in individuals with unilateral cerebral palsy. The interhemispheric (re)organization of the somatosensory system may not effectively compensate for somatosensory impairment.     

Mevalonic aciduria: Does stem cell transplant fully cure disease?

MA is a rare, autosomal recessive disorder characterized by episodes of inflammation and periodic fevers. In its most severe form, it can result in facial dysmorphism, growth inhibition, ataxia, liver dysfunction, intellectual disability, and at times can be fatal. A number of case reports exist stating that SCT is curative in these patients. We present the case of a patient diagnosed with MA at birth, who underwent SCT at the age of 14 months with intent to cure. She achieved complete engraftment and urine mevalonate became undetectable. However, 18 months following transplant, she developed frequent episodes of fevers, rashes, arthritis, and a rising urinary mevalonate. She was subsequently diagnosed with relapse. She now requires treatment with steroids and canakinumab to manage her disease. This case is the first report of disease relapse following transplant for MA. It runs contrary to prior reports that SCT is fully curative of MA and suggests that transplant may instead provide a means of decreasing disease severity without entirely eradicating the condition.