[Clinical analysis of 3 cases of mucormycosis in children with acute lymphoblastic leukemia and literature review].

Objective: To investigate the clinical features, diagnosis,treatment and prognosis of children with acute lymphoblastic leukemia complicated with mucormycosis, and to improve the understanding of the disease. Methods: The clinical data of 3 children with acute lymphoblastic leukemia (ALL) complicated with mucormycosis treated at the First Affiliated Hospital of Zhengzhou University between October 2020 and January 2021 were analyzed retrospectively. Literature search and review covered the China national knowledge infrastructure, Wanfang database and Pubmed using the keywords of "acute lymphoblastic leukemia" and "mucormycosis" up to June 2021. Results: Case 1, a 12-year-old boy, was diagnosed with ALL, developed fever and chest pain during induction therapy. The Metagenomic next-generation sequencing (mNGS) testing of alveolar perfusion fluid suggested infection with Rhizopus oryzae. Amphotericin B combined with posaconazole was applied and amphotericin B was removed after improvement. Bone destruction was indicated by CT. Amphotericin B was applied again. Case 2, a 4-year-old boy, with a history of pallor and tetter, was diagnosed with ALL. He developed cough and fever during induction therapy. mNGS of blood suggested infection with Rhizomucor pusillus. Amphotericin B combined with voriconazole was applied, but the situation was not significantly improved. The disseminated infection occurred. Amphotericin B combined with posaconazole was applied and vacuum sealing drainage was performed. Case 3, a 2-year-old girl, was diagnosed with ALL, developed fever and cough during induction therapy. Rhizomucor pusillus was indicated by mNGS. Amphotericin B combined with posaconazole was used, and posaconazole was stopped after improvement. Follow-up until June 2021, the condition of the 3 children improved. There was no recurrent Mucor infection, and the primary hematopathy was in complete remission. According to the literature, 7 reports were found in Chinese journals, while 17 reports were found in English literature, 25 cases have been reported. Among a total of 28 children, 11 cases rhino-orbito-cerebral mucormycosis, four pulmonary mucormycosis, 2 cutaneous mucormycosis, 2 gastrointestinal mucormycosis and 9 disseminated mucormycosis. There were 17 cases developed infection during induction chemotherapy, 8 cases during maintenance therapy, 3 cases after hematopoietic stem cell transplantation. Voriconazole was used in 15 cases; 19 cases were treated with combined surgery, 7 cases were treated with drugs only, 2 cases were untreated; 21 cases showed improvement after treatment. Death occurred in seven cases. Conclusions: ALL complicated with mucormycosis often occurs in the stage of induction therapy. The clinical features lacked specificity, mNGS can help find the pathogen and provide evidence for diagnosis. Surgical treatment also could be combined when necessary, which is helpful to improve the prognosis.

Comparison of molecular diagnosis with serum markers and synovial fluid analysis in patients with prosthetic joint infection.

AIMS: The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). PATIENTS AND METHODS: Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. RESULTS: A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). CONCLUSION: Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345-51.

[The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

OBJECTIVE: To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. METHODS: This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. RESULTS: Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). CONCLUSIONS: The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without correction, than emmetropia. Wearing spectacles may improve the threshold and sensitivity of accommodations, and the accommodative accuracy at near-work distances (<30 cm) to some extent. The poor accommodative accuracy at near-work distances may be not related to early-onset myopia, but the value of FCC (20 cm) is related to early-onset myopia. The higher the FCC value is, the higher the diopter is. (Chin J Ophthalmol, 2016, 52: 520-524).

Locomotory abilities and habitat of the Cretaceous bird Gansus yumenensis inferred from limb length proportions.

The relative length proportions of the three bony elements of the pelvic (femur, tibiotarsus and tarsometatarsus) and pectoral (humerus, ulna and manus) limbs of the early Cretaceous bird Gansus yumenensis, a well-represented basal ornithuromorph from China, are investigated and compared to those of extant taxa. Ternary plots show that the pectoral limb length proportions of Gansus are most similar to Apodiformes (swifts and hummingbirds), which plot away from all other extant birds. In contrast, the pelvic limb length proportions of Gansus fall within the extant bird cluster and show similarities with the neornithine families Podicipedidae (grebes), Diomedeidae (albatross) and Phalacrocoracidae (cormorants). Although it does have some of the pelvic limb features of grebes and cormorants, the femur of Gansus is more gracile and is thus more consistent with an albatross-like shallow-diving mode of life than a strong foot-propelled diving movement pattern. The position of Gansus in pectoral limb ternary morphospace is largely due to its elongated manus. In contrast to apodiformes, where the humerus and ulna are short and robust, an adaptation, which provides a stiff wing for their demanding fast agile and hovering flight (respectively), the wing-bones of Gansus are slender, indicating a less vigorous flapping flight style. The suite of characters exhibited by Gansus mean it is difficult to completely interpret its likely ecology. Nevertheless, our analyses suggest that it is probable that this bird was both volant and capable of diving to some degree using either foot-propelled or, perhaps, both its wings and its feet for underwater locomotion.

HMBS mutations in Chinese patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by partial deficiency of hydroxymethylbilane synthase (HMBS) affecting heme biosynthesis. Patients with AIP are characterized by recurrent abdominal pain, port-wine urine, and motor paresis. The disease can be provoked by changes in hormone levels, drugs and fasting. Molecular analysis for twenty-four unrelated Chinese AIP patients from Taiwan identified twenty-five HMBS mutations. There were 10 missense (40%), four nonsense (16%), five frame-shift (20%) and six splice site (24%) mutations. More than a half (15/25, 60%) of these mutations are predicted to produce a truncated protein. Four (c.33 + 5C>A, Arg26Cys, Arg26His, Arg325X) occurred more than once among the 24 families and one individual carried two mutations in the same allele, a missense (Gly221Asp) and a splice site mutation (c.652-1G>A). Of the 25 mutations, eleven were novel (Arg149Pro, Gly218Arg, Asn322X, Gly221Asp, Pro313X, c.88-4_-16delAAGTCTCTACCCG, c.1008_1019delCAGCCTGGCCAA, c.113delT, c.88-4_-16delAAGTCTCTACCCGinsCA, c.160delA, c.902_909delTCCCTGCC). No correlation between genetic defect and phenotype (both clinical and biochemical) was observed in this study.

Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma.

OBJECTIVE: Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC. MATERIAL AND METHODS: Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (< or = 3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve. RESULTS: Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p = 0.0001). The IGF-II levels in LC patients were lower than those in controls (p = 0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15-9.55; p = 0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; p = 0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%). CONCLUSIONS: Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC.

Serum insulin-like growth factor-II and alpha-fetoprotein as tumor markers of hepatocellular carcinoma.

To evaluate the diagnostic application of serum insulin-like growth factor-II (IGF-II) and alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), IGF-II and AFP were determined in 100 cirrhotic patients with HCC, 100 sex- and age-matched patients with cirrhosis alone and 50 healthy controls. The results indicated that IGF-II and AFP levels in patients with HCC were higher than in those with cirrhosis alone (p = 0.0001). There is an inverse correlation between IGF-II and (log)AFP (r = -0.410, p = 0.0001) in patients with HCC. Multivariate analysis indicated that IGF-II and AFP were closely associated, in a dose-related fashion, with the presence of HCC. Receiver operating characteristic curves were used to determine the optimal cutoff values of IGF-II (4.5 mg/g prealbumin) and AFP (100 ng/ml), respectively. Both IGF-II and AFP show a high specificity and positive likelihood ratio. The sensitivity was 42.0% for IGF-II and 73.0% for AFP. Determination of both markers in parallel significantly increased the diagnostic accuracy (96.5%) and sensitivity (97.9%), with a high specificity (95.1%) and positive likelihood ratio (19.9). In conclusion, IGF-II and AFP may be used as complementary tumor markers to discriminate HCC from cirrhosis.

A juvenile ankylosaur from China.

Juvenile ankylosaur specimens are very rare. A new ankylosaur, Liaoningosaurus paradoxus gen. et sp. nov., is described based on a beautifully preserved juvenile ankylosaur specimen from the famous Yixian Formation of Liaoning, China. Liaoningosaurus has a large bony plate (somewhat shell-like) shielding the abdomen. This discovery represents the first record of such a structure among dinosaurs. Although it has a number of distinct features seen in the family Ankylosauridae, a cladistic analysis placed Liaoningosaurus in the sister-family Nodosauridae. The 'intermediate' status of this taxon between the two ankylosaur families further supports the monophyly of Ankylosauria. This finding also documents the smallest known ankylosaur specimen and first complete nodosaurid specimen from Asia.

Epidermal growth factor receptor-binding growth factors in the urine of patients with cancers of the digestive tract.

We aimed to assess the diagnostic application of urinary epidermal growth factor receptor (EGFR)-binding growth factors in cancers of the digestive tract. By radioreceptor assay and radioimmunoassay, we determined these growth factors in 115 patients with various cancers of the digestive tract, 30 patients with benign disease, and 40 healthy controls. The receiver operating characteristic (ROC) curve and likelihood ratio were employed to determine the best diagnostic efficiency. Urinary EGFR-binding growth factors in each cancer group were significantly higher than those in the non-cancer groups. Multivariate analysis indicated that the growth factors, determined by both the radioreceptor assay (odds ratio, 1.184; 95% confidence interval,1.077-1.302; P = 0.001) and radioimmunoassay (odds ratio,1.055; 95% confidence interval, 1.002-1.111; P = 0.039), were associated, in a dose-related fashion, with the presence of cancers. By ROC curve analysis, the optimal cutoff values for EGFR-binding growth factors were 25.5 microg/g creatinine (radioreceptor assay) and 33.6 microg/g creatinine (radioimmunoassay). The resulting sensitivity, specificity, diagnostic accuracy, and positive and negative likelihood ratios were 84.4%. 87.5%, 85.2%, 6.75 and 0.18 (for radioreceptor assay) and 86.1%, 67.5%, 81.3%, 2.64 and 0.21 (for radioimmunoassay), respectively. Except for pancreatic cancer the growth factors showed moderate diagnostic efficiency for the other digestive tract cancers. In conclusion, urinary EGFR-binding growth factors were increased in cancers of the digestive tract. They may be used as diagnostic tumor markers.