18F-FDG PET/CT对急性白血病骨髓移植术后髓内复发灶的诊断价值

目的 探讨18F-氟脱氧葡萄糖（FDG） PET/CT对急性白血病（AL）骨髓移植术后髓内复发灶的诊断价值,筛选可用于诊断其复发的半定量参数。 方法 回顾性分析2016年11月至2019年11月于河北燕达医院接受骨髓移植且疑为髓内复发的81例AL患者的18F-FDG PET/CT图像和病历资料,其中男性45例、女性36例,年龄3~55（25.14±15.07）岁。以骨髓活检的组织病理学检查结果为诊断复发的“金标准”,将患者分为复发组（41例）、无复发组（40例）,测量并计算所有可疑复发病灶的最大标准化摄取值（SUV_max）及肝脏本底SUV_max,计算附肢骨SUV_max/中轴骨SUV_max和骨髓SUV_max/肝脏SUV_max比值,并以其不同的临界值和受试者工作特征（ROC）曲线进行分析,计算曲线下面积（AUC）和诊断复发的效能。以视觉判读法为参照,分析并计算18F-FDG PET/CT不同半定量参数诊断AL髓内复发灶的效能。2组间半定量参数的比较采用独立样本t检验;计数资料的比较采用Pearson卡方检验。 结果 81例AL患者中,复发组的中轴骨SUV_max高于无复发组（3.10±1.65对1.99±1.26,t=3.367,P=0.001）;与无复发组比较,复发组的骨髓SUV_max /肝脏SUV_max比值（1.20±0.56对0.89±0.74）和附肢骨SUV_max /中轴骨SUV_max比值（1.58±1.38对0.79±0.37）均较高,且差异均有统计学意义（t=2.186、3.477,均P<0.05）。基于SUV_max的半定量指标的ROC曲线分析结果显示,以中轴骨SUV_max≥2.05作为判断髓内复发的标准时,其诊断AL复发的灵敏度、特异度和准确率分别为70.73%（29/41）、72.50%（29/40）和 71.60%（58/81）,AUC为0.770。视觉判读法结果显示,以多灶性摄取+弥漫性摄取18F-FDG为髓内复发的诊断标准时,其诊断AL复发的灵敏度、特异度和准确率分别为85.37%（35/41）、70.00%（28/40）和77.78%（63/81）。 结论 18F-FDG PET/CT视觉判读法是诊断AL复发简便、可靠的方法,具有较高的诊断效能,基于SUV_max的半定量参数分析是视觉判读法的重要补充。     

Effect of mycophenolate mofetil regimen on peripheral blood lymphocyte subsets in kidney transplant recipients

BACKGROUND AND AIMS: There is growing evidence of the effects of immunosuppressive agents on "immune targets" in renal transplantation. Immunological monitoring could indirectly measure the suppressive effect of these drugs and guide early preventive interventions in transplant recipients. Due to the selective antiproliferative effect of mycophenolate mofetil (MMF) on lymphocytes, our goal was to determine whether MMF modulates peripheral blood lymphocyte subsets (PBLS) in kidney allograft patients. METHODS: We assessed absolute CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD19(+), CD16(+)CD3(-) PBLS counts and CD4/CD8 ratios for 12 months in three groups of kidney allograft patients stratified according to maintenance immunosuppressive regimen: group A (n = 31), which started MMF with prednisone (P) + cyclosporine A (CyA), and two control groups, B (n = 19) and C (n = 15) on P + CyA + azathioprine (Aza) and P + CyA regimens, respectively. We compared intra- and intergroup lymphocyte counts and ratios. RESULTS: Intergroup comparisons showed a significant reduction in all PBLS in group A (CD19(+) from 3 months and other subsets from 6 months), whereas there were no significant changes in PBLS in the other group analyses or comparisons. CONCLUSIONS: Our findings suggest that (1) MMF modulates all PBLS in kidney allograft patients, causing a progressive reduction occurring earlier in CD19(+), and (2) we can rule out that these changes were caused by the "natural immunological evolution" of the transplantation. These results could offer a new method for immunological monitoring of transplant patients.     

Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties

Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll‐like receptor 5–deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross‐sectional geometry, implicating impaired bone tissue material properties. Small differences in whole‐bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole‐bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.     

Components of the Gut Microbiome That Influence Bone Tissue-Level Strength

Modifications to the constituents of the gut microbiome influence bone density and tissue-level strength, but the specific microbial components that influence tissue-level strength in bone are not known. Here, we selectively modify constituents of the gut microbiota using narrow-spectrum antibiotics to identify components of the microbiome associated with changes in bone mechanical and material properties. Male C57BL/6J mice (4 weeks) were divided into seven groups (n = 7–10/group) and had taxa within the gut microbiome removed through dosing with: (i) ampicillin; (ii) neomycin; (iii) vancomycin; (iv) metronidazole; (v) a cocktail of all four antibiotics together (with zero-calorie sweetener to ensure intake); (vi) zero-calorie sweetener only; or (vii) no additive (untreated) for 12 weeks. Individual antibiotics remove only some taxa from the gut, while the cocktail of all four removes almost all microbes. After accounting for differences in geometry, whole bone strength was reduced in animals with gut microbiome modified by neomycin (−28%, p = 0.002) and was increased in the group in which the gut microbiome was altered by sweetener alone (+39%, p < 0.001). Analysis of the fecal microbiota detected seven lower-ranked taxa differentially abundant in animals with impaired tissue-level strength and 14 differentially abundant taxa associated with increased tissue-level strength. Histological and serum markers of bone turnover and trabecular bone volume per tissue volume (BV/TV) did not differ among groups. These findings demonstrate that modifications to the taxonomic components of the gut microbiome have the potential to decrease or increase tissue-level strength of bone independent of bone quantity and without noticeable changes in bone turnover. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV‐seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12‐month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non‐CMV infection, graft loss, and all‐cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve‐month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS‐adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01–0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29–0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late‐onset disease.     

Anticonvulsant and neuroprotective effects of the novel calcium antagonist NP04634 on kainic acid‐induced seizures in rats

Kainic acid (KA)‐induced status epilepticus (SE) is a well‐characterized model of excitotoxic neuronal injury. Excitotoxicity results from activation of specific glutamate receptors, with resultant elevation of intracellular Ca²⁺. The CA1 and CA3 subregions of the hippocampus are especially vulnerable to KA, and this pattern of neuronal injury resembles that occurring in patients with temporal lobe epilepsy. Calcium plays an essential role in excitotoxicity, and accordingly calcium channel inhibitors have been shown to have protective effects in various experimental models of epilepsy and brain injury. Moreover, they also potentiate the antiseizure efficacy of conventional antiepileptic drugs. This study was undertaken to determine whether NP04634, a novel compound, reported as a non‐L‐type voltage‐sensitive calcium channel (VSCC) inhibitor, could prevent the entrance in SE and the neuronal loss evoked by intraperitoneal injection of KA. Our results show that intragastrical administration of NP04634 reduced the percentage of rats that entered SE after KA injection, increased the latency of SE entry, and significantly reduced the mortality of rats that entered SE. Also, NP04634 prevented the loss of hippocampal CA1 and CA3 pyramidal neurons and reduced the gliosis induced by KA. These results point to a potential anticonvulsant and neuroprotective role for NP04634. © 2009 Wiley‐Liss, Inc.     

Histological evaluation of an alternative method of neophalloplasty based on two lower abdominal skin flaps and simultaneous buccal mucosa graft in the ventral surface of the neophallus (two-stage urethroplasty): Experimental study in rabbits

ObjectiveTo evaluate, in an experimental study in rabbits, a new model of neophalloplasty based on two lower abdominal skin flaps and ventral buccal mucosa graft for planned two-stage urethroplasty procedure.Material and methodsSixteen rabbits were operated and divided into four equal groups which were sacrificed at 2, 4, 8 and 12 weeks. The inflammatory pattern, presence of sub-epithelial fibrosis and epithelial changes in the grafted area were evaluated histologically.ResultsThere were no deaths and no dehiscence of the wound was seen. One animal in the 2-week group developed an ulcer in the grafted area. We found minimal contracture of the neophallus, but this was not statistically significant between groups. Buccal mucosa graft showed good uptake in all groups, with vascular support from subcutaneous tissue of the flaps. The grafted area developed epithelial metaplasia, showing a decrease in cell layers with time, with disappearance of the sub-epithelial papillae and appearance of stratum granulosum and keratinization of the epithelial graft surface. A decrease in sub-epithelial fibrosis with replacement of immature by mature (eosinophilic) collagen was found. In the later groups was also observed an important decrease in inflammatory response, and the chorion of the grafted area presented a dilated capillary network, indicating that the process of neoangiogenesis was effective.ConclusionBuccal mucosa displayed histological integration in the abdominal flaps with epithelial metaplasia in all groups. The surgical aspect of the neophallus was cosmetically acceptable, with minimal contracture.     

Spatial distribution,blood feeding pattern,and role of <Emphasis Type="Italic">Anopheles funestus</Emphasis> complex in malaria transmission in central Kenya

Studies were conducted to determine the role of sibling species of Anopheles funestus complex in malaria transmission in three agro-ecosystems in central Kenya. Mosquitoes were sampled indoors and outdoors, and rDNA PCR was successfully used to identify 340 specimens. Anopheles parensis (91.8%), A. funestus (6.8%), and Anopheles leesoni (1.5%) were the three sibling species identified. A. parensis was the dominant species at all study sites, while 22 of 23 A. funestus were collected in the non-irrigated study site. None of the 362 specimens tested was positive for Plasmodium falciparum circumsporozoite proteins by enzyme-linked immunosorbent assay. The most common blood-meal sources (mixed blood meals included) for A. parensis were goat (54.0%), human (47.6%), and bovine (39.7%), while the few A. funestus s.s. samples had fed mostly on humans. The human blood index (HBI) for A. parensis (mixed blood meals included) in the non-irrigated agro-ecosystem was 0.93 and significantly higher than 0.33 in planned rice agro-ecosystem. The few samples of A. funestus s.s. and A. funestus s.l. also showed a trend of higher HBI in the non-irrigated agro-ecosystem. We conclude that agricultural practices have significant influence on distribution and blood feeding behavior of A. funestus complex. Although none of the species was implicated with malaria transmission, these results may partly explain why non-irrigated agro-ecosystems are associated with higher risk of malaria transmission by this species compared to irrigated agro-ecosystems.     

Spatial Working Memory Deficits in Autism

Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals with autism made more errors than a matched group of typically developing controls on this task, and were less likely to consistently use a specific organized search strategy to complete the task. Overall, these results demonstrate reduced spatial working memory abilities in autism, and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory.