Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients.

OBJECTIVES: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. METHODS: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. RESULTS: All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4-3.3, P value = 0.79). CONCLUSIONS: These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.

[Long term follow-up evaluation of combined surgery for congenital tibial pseudarthrosis in children].

Objective: To explore the long-term effect of combined surgery for the treatment of congenital tibial pseudarthrosis in children. Methods: The clinical data of 44 children with congenital tibial pseudarthrosis who underwent combined surgery (tibial pseudarthrosis tissue resection, intramedullary rod fixation, Ilizarov external fixator fixation, wrapped autologous iliac bone graft) from August 2007 to October 2011 at the Department of Pediatric Orthopedics, Hunan Children's Hospital were collected retrospectively. There were 33 males and 11 females. The age at the time of surgery was (3.7±2.2)years (range:0.6 to 12.4 years), including 25 cases under 3 years old and 19 cases above 3 years old.Among them, 37 cases were complicated with neurofibromatosis type 1.The operation status, postoperative complications and follow-up results were recorded. Results: The follow-up time after surgery was (10.9±0.7)years (range:10 to 11 years).Thirty-nine out of 44 patients (88.6%) achieved initial healing of tibial pseudarthrosis, with an average healing time of (4.3±1.1)months (range:3 to 10months).In the last follow-up, 36 cases (81.8%) had unequal tibial length, 20 cases (45.4%) had refractures, 18 cases (40.9%) had ankle valgus, 9 cases (20.4%) had proximal tibial valgus, and 11 cases (25.0%) had high arched feet.Nine cases (20.4%) developed distal tibial epiphyseal plate bridging.17 cases (38.6%) had abnormal tibial mechanical axis.Seven cases (15.9%) developed needle infection, and one case (2.3%) developed tibial osteomyelitis. 21 patients (47.7%) had excessive growth of the affected femur.Five patients (11.3%) had ankle stiffness, and 34 patients (77.2%) had intramedullary rod displacement that was not in the center of the tibial medullary cavity.Among them, 8 cases (18.1%) protruded the tibial bone cortex and underwent intramedullary rod removal.18 children have reached skeletal maturity, while 26 children have not been followed up until skeletal maturity. Conclusion: Combined surgery for the treatment of congenital pseudarthrosis of the tibia in children has a high initial healing rate, but complications such as unequal tibia length, refracture, and ankle valgus occur during long-term follow-up, requiring multiple surgical treatments.

A prospective study on vulvovaginal candidiasis: multicentre molecular epidemiology of pathogenic yeasts in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is frequent in women of reproductive age, but very limited data are available on the epidemiology in cases of VVC in China. OBJECTIVES: The current study has been conducted to reveal the prevalence, species distribution of yeast causing VVC and molecular genetics of Candida albicans in China. METHODS: Vaginal swabs were collected from 543 VVC outpatients recruited in 12 hospitals in China between September 2017 and March 2018. They were preliminarily incubated on Sabouraud dextrose agar and then positive subjects of which were then transmitted to our institute for further identification. CHROMagar™ was used to isolate Candida species, and all isolates were finally identified by DNA sequencing. Multilocus sequence typing (MLST) was used to analyse phylogenetic relationships of the various C. albicans isolates. RESULTS: Eleven different yeast species were identified in 543 isolates, among which C. albicans (84.7%) was the most frequent, followed by C. glabrata (8.7%). We obtained 117 unique diploid sequence types from 451 clinical C. albicans isolates and 92 isolates (20.4%) belonged to a New Clade. All the strains appearing in the New Clade were from northern China and they were isolated from non-recurrent VVC. CONCLUSIONS: Our findings suggest that C. albicans are still the main cause of VVC in China and the majority of C. albicans isolates belongs to Clade 1 with DST 79 and DST 45 being two most common. Moreover, the New Clade revealed in our study seems to be specific to northern China.

Effect of Hypoxic-Ischemic Brain Injury in Neonatal Rats on Behavioral Parameters and Expression of CDK8 in the Brain Tissue.

Behavioral changes in newborn 3-day-old rats (n=44) with modeled hypoxic-ischemic brain injury (HIBI) were observed, and the expression of CDK8 in brain tissues was detected to clarify the significance of CDK8. In 30 min, 3 h, and 3 days after HIBI, the left (ischemic) hemisphere was taken for examination. In 3 days after HIBI, the rat pups were examined in the behavioral tests. In rat pups with HIBI, changes of CDK8 expression were detected by Western blotting and real-time PCR and changes in the righting reflex and forelimb grip strength test (p<0.05) were revealed in comparison with sham-operated animals. The expression of CDK8 increased 30 min after HIBI and decreased in 3 h and 3 days. Hypoxia and ischemia of the left brain may affect locomotion, but not sensation. Since CDK8 is involved in the immune response after cerebral hypoxia and ischemia, this kinase can be used as an early diagnostic index.

Editorial - Infectious-disease research during a pandemic: the importance of global unity.

The orthopaedic and trauma community have faced the threat of infection since the introduction of operative fracture fixation many decades ago. The parallel emergence and spread of antimicrobial resistance in clinically relevant pathogens has the potential to significantly complicate patient care. This editorial serves to provide a global context to the issue of antimicrobial resistance and how infectious disease research in general plays a crucial role both on a global scale as evidenced by the current pandemic, but also on a more personal scale for the daily management of orthopaedic trauma patients. The special issue on Orthopaedic Infection in the eCM journal provides a snapshot of the clinically relevant basic research that is being performed in this field.

Phagocytosis and macrophage polarization on bacterially contaminated dental implant materials and effects on tissue integration.

Bacterial contamination is hard to avoid during dental implant surgery. Macrophages and their polarisation play a decisive role in bacterial colonisation and tissue integration on bacterially contaminated dental implants. The present study investigated the role of macrophages in stimulating tissue coverage overgrowth of contaminating oral bacteria on polished titanium (Ti-P) and acid-etched zirconium dioxide (ZrO2-MA) dental implant materials. Different co-culture models were employed to determine phagocytosis rates of Streptococcus mitis or Staphylococcus aureus contaminating a dental implant surface and the influence of contaminating bacteria and osteoblasts (U2OS) on macrophage polarisation. S. aureus was phagocytized in higher numbers than S. mitis in bi-cultures on smooth Ti-P surfaces. Contaminating S. mitis stimulated near full polarisation of macrophages from a non-Ym1-expressing- to a Ym1-expressing-phenotype on smooth Ti-P, but on ZrO2-MA both phenotypes occurred. In tri-cultures with U2OS-cells on smooth Ti-P, a larger percentage of macrophages remained in their non-Ym1-expressing, "fighting" M1-like phenotype to clear Ti-P surfaces from contaminating bacteria. On ZrO2-MA surfaces, more macrophages tended towards their "fix- and-repair" M2-like phenotype than on Ti-P surfaces. Surface coverage of smooth, bacterially contaminated Ti-P surfaces by U2OS-cells was more effectively stimulated by fighting, M1-like macrophages than on ZrO2-MA surfaces. Comprehensive guidelines are provided for the development of infection-resistant, dental implant materials, including bacteria, tissue and immune cells. These guidelines point to more promising results for clinical application of Ti-P as compared with ZrO2-MA.

[Efficacy analysis of retroperitoneal laparoscopic selective renal artery branch occlusion and nephron sparing surgery for ≥ T1b stage renal carcinoma].

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m2. The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

[Relationship between inorganic elements in rhizosphere soil and rhizome radial striations in Ligusticum chuanxiong].

The study is aimed to reveal the fluctuation of the inorganic elements in the rhizosphere soil of Ligusticum chuanxiong during their whole growth period, and explore the relationship between that fluctuation and the formation of radial striations character in the rhizomes. During the cultivation period of L. chuanxiong, the rhizosphere soil samples were taken regularly, and the content of 26 inorganic elements were determined by X-ray fluorescence spectrometry(XRF). Then the difference between the radial striations and un-radial striations rhizomes were analyzed for their fluctuation of the inorganic elements. The results showed that there were different "key period" and "key elements" in the rhizosphere elements content of L. chuanxiong rhizome with radial and un-radial striations, and different element coordination and antagonistic relationship. The key fluctuation period of rhizosphere elements in un-radial striations group were in 0-60 and 60-150 days, of which 22 elements such as Na, Mg, Al were the key elements in 0-60 days, and 5 elements such as Sr, Hf, Pb, Co, Ce were the key elements in 60-150 days. The key fluctuation period of rhizosphere elements in radial striations group were in 0-60 and 210-270 days, of which four elements such as Na, Co, Ce, As are the key change elements in 0-60 days, and 18 elements such as Mg, Al, Si are the key change elements in 210-270 days. At the same time, the study showed that the fluctuation of inorganic elements in rhizosphere soil coincided with the growth and development process of L. chuanxiong and the key period of the formation of "radial striations rhizome". The key stage which the rapid growth of lateral buds of rhizome affected the formation of radial striations is 60-150 days after planting, while the increase of Sr and Co elements is likely to be an important reason for the expansion of lateral buds of rhizome and the failure to form typical "radial striations rhizome" in un-radial striations group.

Cervical carcinomas with a micropapillary component: a clinicopathological study of eight cases.

AIMS: Micropapillary carcinomas, or carcinomas with a micropapillary component, are well recognised in the breast and other anatomical sites. However, they have seldom been described in the cervix. In this article, we present a clinicopathological analysis of eight cervical tumours that showed at least a focal (≥5%) component of micropapillary carcinoma. METHODS AND RESULTS: The study group comprised eight cervical carcinomas (four adenocarcinomas and four adenosquamous carcinomas) with a micropapillary component. The median patient age was 41.5 years (range 27-65 years). At presentation, five patients were stage IB, two were stage IIB, and one was stage IV. The micropapillary component accounted for ≤25% of the tumour on initial biopsy or resection specimens in all but one case. Immunohistochemistry showed 'inside-out' (reverse polarity) mucin 1 staining along the cell membrane abutting the stroma. Four patients developed metastasis, all of whom showed a pure micropapillary pattern; this led to a misdiagnosis of an apparently independent peritoneal serous carcinoma in one case. All tumours showed diffuse p16 expression, and all three cases that were tested were positive for human papillomavirus (HPV) 18. Three of the six patients with at least 12 months of follow-up died of disease, and one is alive with distant metastasis. CONCLUSIONS: Usual-type (HPV-related) cervical carcinomas may show micropapillary differentiation, usually as a focal finding, and the cells show reverse polarity like similar tumours arising in other sites. Micropapillary cervical carcinoma appears to be a clinically aggressive malignancy, although this needs to be confirmed in larger studies.

Phylogeny of dermatophytes with genomic character evaluation of clinically distinct Trichophyton rubrum and T. violaceum.

Trichophyton rubrum and T. violaceum are prevalent agents of human dermatophyte infections, the former being found on glabrous skin and nail, while the latter is confined to the scalp. The two species are phenotypically different but are highly similar phylogenetically. The taxonomy of dermatophytes is currently being reconsidered on the basis of molecular phylogeny. Molecular species definitions do not always coincide with existing concepts which are guided by ecological and clinical principles. In this article, we aim to bring phylogenetic and ecological data together in an attempt to develop new species concepts for anthropophilic dermatophytes. Focus is on the T. rubrum complex with analysis of rDNA ITS supplemented with LSU, TUB2, TEF3 and ribosomal protein L10 gene sequences. In order to explore genomic differences between T. rubrum and T. violaceum, one representative for both species was whole genome sequenced. Draft sequences were compared with currently available dermatophyte genomes. Potential virulence factors of adhesins and secreted proteases were predicted and compared phylogenetically. General phylogeny showed clear gaps between geophilic species of Arthroderma, but multilocus distances between species were often very small in the derived anthropophilic and zoophilic genus Trichophyton. Significant genome conservation between T. rubrum and T. violaceum was observed, with a high similarity at the nucleic acid level of 99.38 % identity. Trichophyton violaceum contains more paralogs than T. rubrum. About 30 adhesion genes were predicted among dermatophytes. Seventeen adhesins were common between T. rubrum and T. violaceum, while four were specific for the former and eight for the latter. Phylogenetic analysis of secreted proteases reveals considerable expansion and conservation among the analyzed species. Multilocus phylogeny and genome comparison of T. rubrum and T. violaceum underlined their close affinity. The possibility that they represent a single species exhibiting different phenotypes due to different localizations on the human body is discussed.

Clinical and mutation analysis of 24 Chinese patients with ornithine transcarbamylase deficiency.

The principal aim of this study was to examine the clinical manifestations, biochemical features, and molecular genetic characteristics of Chinese patients with ornithine transcarbamylase deficiency (OTCD) at a single medical center. We retrospectively analyzed 24 patients (17 males and 7 females) diagnosed with OTCD between 2006 and 2015. Five male patients had a neonatal presentation; 12 male patients had late onset disease and 7 female patients presented as symptomatic. Patients with a neonatal presentation had the highest peak plasma ammonia and glutamine levels at diagnosis with a high mortality (80% vs 16% in late onset disease). Most of the male late onset disease cases displayed neurologic damage with a mild elevation in plasma ammonia, and a significant increase in serum glutamine, which was commonly misdiagnosed as intracranial infection. In the symptomatic female group, mortality was abnormally high in China with some patients dying at the time of presentation during the first episode of hyperammonemia. Refractory hyperammonemia, serious hepatic function damage, recurrent infection and lethal mutation are the main reasons for poor clinical outcomes of the symptomatic females. Molecular analyses identified 19 different mutations, including 3 novel mutations (c.103insA, c.591C>A and c.805G>A).

Influence of surface roughness on silicone rubber voice prostheses on in vitro biofilm formation and clinical lifetime in laryngectomised patients.

OBJECTIVES: Evaluation of the influence of a smooth surface moulding technique of silicone rubber indwelling voice prostheses on in vitro biofilm formation and analysis of the clinical in situ lifetime. DESIGN: Biofilm formation on smooth and Groningen ultra low resistance (URL) prostheses was studied in an artificial throat model. The clinical lifetime of smooth voice prostheses was compared to the previous lifetime of URL by counting the number of replacements in a consecutive 6-month period in the same patient. PARTICIPANTS: Eleven laryngectomised patients in follow-up who required frequent replacement of their voice prostheses. SETTINGS: Tertiary University Medical Center. RESULTS: Use of a smoother mould and less viscous silicone rubber yielded a decrease in surface roughness from 46 to 8 nm and was accompanied by a 40% reduction in the prevalence of bacteria and yeast in in vitro formed biofilms. Clinically, the lifetime was significantly (P<.005) increased by a factor of 2.1. CONCLUSIONS: This combined in vitro and clinical study suggests that the choice of material and in particular its surface finishing may be determining factors with respect to the clinical lifetime of silicone rubber implants and devices failing due to biofilm formation.

Visual detection technique for efficient screening and isolation of Salmonella based on a novel enrichment assay using chromatography membrane.

To detect Salmonella more efficiently and isolate strains more easily, a novel and simple detection method that uses an enrichment assay and two chromogenic reactions on a chromatography membrane was developed. Grade 3 chromatography paper is used as functionalized solid phase support (SPS), which contains specially optimized medium. One reaction for screening is based on the sulfate-reducing capacity of Salmonella. Hydrogen sulfide (H2S) generated by Salmonella reacts with ammonium ferric citrate to produce black colored ferrous sulfide. Another reaction is based on Salmonella C8 esterase that is unique for Enterobacteriaceae except Serratia and interacts with 4-methylumbelliferyl caprylate (MUCAP) to produce fluorescent umbelliferone, which is visible under ultraviolet light. A very low detection limit (10(1) CFU ml(-1)) for Salmonella was achieved on the background of 10(5) CFU ml(-1) Escherichia coli. More importantly, testing with more than 1,000 anal samples indicated that our method has a high positive detection rate and is relatively low cost, compared with the traditional culture-based method. It took only 1 day for the preliminary screening and 2 days to efficiently isolate the Salmonella cells, indicating that the new assay is specific, rapid, and simple for Salmonella detection. In contrast to the traditional culture-based method, this method can be easily used to screen and isolate targeted strains with the naked eye. The results of quantitative and comparative experiments showed that the visual detection technique is an efficient alternative method for the screening of Salmonella spp. in many applications of large-sized samples related to public health surveillance.

Biochemical analysis of the living human vitreous.

BACKGROUND: To date, our understanding of the biochemical composition of the living human vitreous relies on extrapolations from animal or human post-mortem studies. METHODS: This was a cross-sectional study of vitreous samples from 27 individuals scheduled for retinal surgery within a tertiary hospital. From each vitreous sample, the concentrations of sodium, potassium, chloride, calcium, magnesium, glucose, lactate, ß- hydroxybutyrate, copper, zinc, selenium, iron, ferritin and transferrin and osmolality were measured. Perioperative serum samples were also obtained for comparison. RESULTS: The following vitreous mean ± standard deviation (95% confidence interval of the mean) was observed for each analyte: sodium, 146.7 ± 3.3 (145.4-148.0) mmol/L; potassium, 5.73 ± 0.86 (5.39-6.08) mmol/L; chloride, 121.6 ± 2.6 (120.6-122.7) mmol/L; calcium, 1.128 ± 0.518 (0.923-1.333) mmol/L; magnesium, 0.900 ± 0.158 (0.838-0.962) mmol/L; glucose, 2.97 ± 0.98 (2.58-3.36) mmol/L; lactate, 3.97 ± 1.09 (3.54-4.40) mmol/L; osmolality, 289.5 ± 6.9 (286.6-292.5) mOsm/kg; BOHB, 0.0937 ± 0.0472 (0.0750-0.1124) mmol/L; copper, 0.519 ± 0.269 (0.412-0.625) µmol/L; zinc, 1.95 ± 1.09 (1.52-2.38) µmol/L; selenium, 0.1035 ± 0.0276 (0.0923-0.1146) µmol/L; iron, 3.11 ± 1.40 (2.56-3.66) µmol/L; ferritin, 19.5 ± 10.3 (15.5-23.6) µg/L; transferrin, 0.0878 ± 0.0526 (0.0670-0.1086) g/L. Vitreous biochemistry was not significantly different between male and female participants. Vitreous biochemistry was significantly different between non-diabetic and diabetic participants. Vitreous biochemistry was significantly different from the vitreous substitute BSS Plus (Alcon, USA). The vitreous extracted from living humans was markedly different from the commonly reported reference values obtained from animal studies. CONCLUSIONS: The current data provide hitherto unavailable information about the biochemical composition of the living human vitreous.

Effects of full-fat rice bran inclusion in diets on growth performance and meat quality of Sichuan goose.

This trial was conducted to study the effect of full-fat rice bran inclusion in diets on growth performance, carcass and meat quality and fatty acid composition in Sichuan goose. A total of 204 Sichuan white male geese (28-d-old, 984 ± 15 g) were used in the 42-d assay. Full-fat rice bran inclusion in diets was 0%, 6%, 12% and 18%, respectively. On d 70, two geese from each pen were randomly selected and killed for measuring the carcass and meat quality and the meat fatty acid composition. The results showed that full-fat rice bran inclusion had no effect on average daily gain during 28-56 d, but rice bran inclusion at 18% increased average daily gain during 57-70 d. In addition, the full-fat rice bran supplementation decreased the subcutaneous fat yield, and the inclusion of full-fat rice bran in amounts of 12% and 18% decreased the half-eviscerated carcass yield, eviscerated carcass yield and crude fat content in goose meat. Moreover, full-fat rice bran supplementation had no effect on the content of total saturated fatty acid (SFA), but decreased the content of total monounsaturated fatty acid (MUFA). The inclusion of full-fat rice bran in amounts of 12-18% increased the content of total polyunsaturated fatty acid (PUFA) and total n-6 in goose meat and in the amount of 18% increased n-3 fatty acids content in goose meat. The results indicated that the rice bran inclusion had a positive effect in geese by stimulating growth performance and improving meat quality and fatty acid composition of goose meat.

[The relationship of A Proliferation-Inducing Ligand expression with the clinical pathology and prognosis in colorectal carcinoma].

Objective: To investigate the protein expression of A Proliferation-Inducing Ligand (APRIL) in colorectal cancer (CRC) tissue, and its correlation with clinical pathology and prognosis. Methods: One hundred and twenty cases of CRC tissue and related clinical data were collected from the Department of Pathology of Affiliated Hospital of Nantong University. The specimens were made into tissue microarray. The protein expression of APRIL was detected by Envision immunohistochemistry. The relationship of the protein expression of APRIL with clinicopathological parameters and follow-up data were statistically analyzed. Results: APRIL protein expression positive rate of CRC tissue and cancer adjacent normal mucosal tissue were 83.33% (100/120) and 12.5% (15/120), with a statistical significance (P<0.001). The expression of APRIL was related to TNM staging (χ2=10.222, P=0.006) and the depth of tumor invasion (χ2=5.987, P=0.014). Kaplan-Meier survival curves showed that five years survival rate of high APRIL expression group was lower than that of low APRIL expression group. Univariate survival analysis showed that the expression of APRIL (P<0.001), the degree of tumor differentiation (P=0.033), TNM staging (P<0.001), depth of tumor invasion (P=0.011), lymph node metastasis (P<0.001) and serum CEA (P=0.003) time were associated with postoperative survival. Multivariate COX proportional hazard regression model analysis further revealed the expression of APRIL (P=0.001), the degree of tumor differentiation (P=0.005), TNM staging (P=0.001) and serum CEA (P=0.039) were the independent risk factors for prognosis. Conclusion: The expression of APRIL in CRC tumor tissue is closely related to TNM stage and depth of tumor invasion. The high expression of APRIL prompts bad prognosis. APRIL is one of the independent prognostic factors in patients with CRC, and could be a potential target for the therapy of CRC.

[Correlative study between X-ray type after healing of congenital pseudarthrosis of the tibia in children and postoperative refracture].

Objective: To investigate the relationship between postoperative X-ray type in 2 years after healing of congenital pseudarthrosis of the tibia(CPT) and refracture of CPT in children. Methods: A retrospective study was performed on 67 children patients with Crawford type Ⅳ CPT who were treated with combined surgeries from December 2007 to August 2012.There were 46 male and 21 female patients with 37 cases with left CPT and 30 cases with right CPT. There were 12 cases with proximal tibia dysplasia, 56 cases with neurofibromatosis type 1. The median age when operation was 2.8 years(from 0.6 to 11.2 years). The patients were divided into three groups, CPT with hypertrophic group, CPT with mediate group and CPT with atrophic group, on the basis of ratio of healing cross-sectional area and transition zone in pseudarthrosis.The incidence of refracture in the three groups were investigated. Results: The refracture rates of three groups were 13%(5/38), 14%(3/21), 5/8, respectively.The refracture rate difference between CPT with hypertrophic group and CPT with mediate group was not statistically significant(P=0.590). The refracture rate of CPT with atrophic group was statistically significant lower than that of CPT with hypertrophic group and CPT with mediate group(P=0.007, 0.019). In addition, the refracture-free cumulative survival rate of CPT with hypertrophic group or CPT with mediate group was higher than that of CPT with atrophic group with the statistically significant difference(both P<0.05). And the refracture-free cumulative survival rate in CPT with hypertrophic group was lower than that in CPT with mediate group, the difference was not significant(P>0.05). Conclusion: After the union of CPT, patients with hypertrophic, mediate type X ray characteristic showed lower incidence of refracture than those with atrophic type.

Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients.

The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Pharmacokinetic analysis was performed in mice, dosed at six different times (24-h period). Tissue samples were used for mRNA expression analysis of drug-metabolizing enzymes. In patients, a cross-over study was performed. During three 24-h periods, after tamoxifen dosing at 8 a.m., 1 p.m., and 8 p.m., for at least 4 weeks, blood samples were collected for pharmacokinetic measurements. Differences in tamoxifen pharmacokinetics between administration times were assessed. The mRNA expression of drug-metabolizing enzymes showed circadian variation in mouse tissues. Tamoxifen exposure seemed to be highest after administration at midnight. In humans, marginal differences were observed in pharmacokinetic parameters between morning and evening administration. Tamoxifen C(max )and area under the curve (AUC)0-8 h were 20 % higher (P < 0.001), and tamoxifen t(max) was shorter (2.1 vs. 8.1 h; P = 0.001), indicating variation in absorption. Systemic exposure (AUC0-24 h) to endoxifen was 15 % higher (P < 0.001) following morning administration. The results suggest that dosing time is of marginal influence on tamoxifen pharmacokinetics. Our study was not designed to detect potential changes in clinical outcome or toxicity, based on a difference in the time of administration. Circadian rhythm may be one of the many determinants of the interpatient and intrapatient pharmacokinetic variability of tamoxifen.

A biodegradable gentamicin-hydroxyapatite-coating for infection prophylaxis in cementless hip prostheses.

A degradable, poly (lactic-co-glycolic acid) (PLGA), gentamicin-loaded prophylactic coating for hydroxyapatite (HA)-coated cementless hip prostheses is developed with similar antibacterial efficacy as offered by gentamicin-loaded cements for fixing traditional, cemented prostheses in bone. We describe the development pathway, from in vitro investigation of antibiotic release and antibacterial properties of this PLGA-gentamicin-HA-coating in different in vitro models to an evaluation of its efficacy in preventing implant-related infection in rabbits. Bone in-growth in the absence and presence of the coating was investigated in a canine model. The PLGA-gentamicin-HA-coating showed high-burst release, with antibacterial efficacy in agar-assays completely disappearing after 4 days, minimising risk of inducing antibiotic resistance. Gentamicin-sensitive and gentamicin-resistant staphylococci were killed by the antibiotic-loaded coating, in a simulated prosthesis-related interfacial gap. PLGA-gentamicin-HA-coatings prevented growth of bioluminescent staphylococci around a miniature-stem mounted in bacterially contaminated agar, as observed using bio-optical imaging. PLGA-gentamicin-HA-coated pins inserted in bacterially contaminated medullary canals in rabbits caused a statistically significant reduction in infection rates compared to HA-coated pins without gentamicin. Bone ingrowth to PLGA-gentamicin-HA-coated pins, in condylar defects of Beagle dogs was not impaired by the presence of the degradable, gentamicin-loaded coating. In conclusion, the PLGA-gentamicin-HA-coating constitutes an effective strategy for infection prophylaxis in cementless prostheses.