[Pathogenetic analysis of transfusion-related acute lung injury caused by human leukocytes antigen antibody against human leukocyte antigen].

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that　HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient's HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K.　Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

Comparing the efficacy of endovascular treatment for iliac vein compression syndrome with or without acute deep venous thrombosis: A single-center retrospective study.

BACKGROUND: To compare the efficacy of endovascular treatment for iliac vein compression syndrome (IVCS) with or without acute deep venous thrombosis of lower extremity. METHODS: This study retrospectively analyzed the clinical data of 300 IVCS patients, who received endovascular treatment between January 2013 and December 2017. According to whether IVCS was complicated by deep venous thrombosis or not, these patients were divided into non-thrombotic iliac vein lesion group (NIVL group, n = 127) and post-thrombotic iliac vein lesion group (PIVL group, n = 173). After endovascular treatment, all patients were followed up to assess the symptoms improvement and to evaluate the patency of iliac vein. RESULTS: The technical success rate was 98% (294/300), and percutaneous transluminal angioplasty with stenting was adopted in 294 cases. The incidence of perioperative complications was 36.33% (109/300), but no severe complications occurred. During a mean follow-up of 22.3 months (range 6-30 months), 9(6.82%, 9/132) patients in PIVL group had recurrence of deep venous thrombosis, but nobody had deep venous thrombosis and varicose veins recurrence in NIVL group. The effective rate of endovascular treatment in NIVL group and PIVL group was 96.88% and 90.15% (P = 0.050), while the cumulative primary patency of iliac vein in NIVL group was significantly higher than that in PIVL group (P = 0.008). CONCLUSIONS: The endovascular treatment is an effective, feasible, safe method for treating IVCS. There is no difference in the efficacy of IVCS patients with or without deep venous thrombosis, but the medium and long-term patency of patients with deep venous thrombosis is lower than that in patients without deep venous thrombosis.

[Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell].

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 µmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 µmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 µmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 µmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

[Prognostic factors for failure of transvaginal repair of vesicovaginal fistula: A nested case-control study].

OBJECTIVE: To analyze the prognostic factors affecting the failure of transvaginal repair of vesicovaginal fistula (VVF). METHODS: A retrospective nested case-control study was conducted. A total of 15 patients who underwent unsuccessful transvaginal vesicovaginal fistula repair in the Department of Urology, Peking University First Hospital from January 2014 to December 2020 were enrolled as the case group. A total of 60 patients receiving transvaginal vesicovaginal fistula repair by the same surgeon within the same time range, were selected as the control group. The age, body mass index (BMI), etiology of vesicovaginal fistula, associated genitourinary malformation, frequency of repair, characteristics of fistula, surgical procedure, postoperative recovery and other factors were compared between the case group and the control group, and the influencing factors of failure were analyzed. RESULTS: The BMI of the case group was (26.3±3.9) kg/m2, the diameter of vaginal fistula was (1.5±0.8) cm, and the operative time of transvaginal repair was (111.8±19.8) min. The proportion of the patients with genitourinary malformations was 4/15, the proportion of the patients with multiple vaginal repairs was 13/15, the proportion of the patients with concurrent ureteral reimplantation was 6/15, and the proportion of the patients with postoperative fever was 5/15. In the control group, the BMI was (23.9±3.0) kg/m2, the diameter of vaginal fistula was (0.8±0.5) cm, the operative time of transvaginal repair was (99.9±19.7) min, the rate of associated genitourinary malformation was 2/60, the rate of multiple transvaginal repair was 18/60, the rate of concurrent ureteral reimplantation was 5/60, and no postoperative fever was found. Compared with the control group, the case group had higher BMI (P=0.013), bigger vaginal fistula (P=0.002), longer time of operation (P=0.027), higher proportion of genitourinary malformations (P=0.013), higher proportion of repeated transvaginal repair (P < 0.001), higher proportion of ureter reimplantation (P=0.006), and higher proportion of postoperative fever (P < 0.001). Multivariate analysis showed that fistula diameter ≥1 cm (OR=10.45, 95%CI=1.90-57.56, P=0.007) and repeated transvaginal repair (OR=16.97, 95%CI=3.17-90.91, P=0.001) were independent prognostic factors for VVF failure in transvaginal repair. CONCLUSION: Fistula diameter ≥1 cm and repeated transvaginal repair are independent prognostic factors of failure in transvaginal repair.

[Evaluating continence recovery time after robot-assisted radical prostatectomy].

OBJECTIVE: To evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP). METHODS: From January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated. RESULTS: In total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 µg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group. CONCLUSION: RARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.

[A survey of risk factors and quality of life in female medical staff with urinary incontinence].

OBJECTIVE: To explore risk factors of urinary incontinence (UI) and influences of UI on quality of life in female medical staff from Beijing. METHODS: One hundred and forty-six female medical personnel were included in the present study through the convenient sampling method in Peking University First Hospital. The questionnaires contained the following information: demographic information, daily urination condition, the severity of UI [international consultation on incontinence questionnaire short form (ICI-Q-SF)], and the influences of UI on quality of life (QOL). We excluded the subjects who were in pregnancy or had urinary infection, neurogenic bladder, or urethral stricture. We used SPSS 21.0 software (IBM Corp, Armonk, NY) for statistical analysis. The Kolmogorov-Smirnov test determined the normality of the continuous variables. Means and standard deviation presented continuous variables in normality. Median and range presented continuous variables without normality. Frequency and percentile were used to present categorical or ranked variables. RESULTS: There were 63 out of 146 (43.2%) female medical staff suffering from UI. The mean age and body mass index of the whole study cohort were (39.4±9.9) years and (22.3±3.4) kg/m2. The median delivery times of all the subjects were 1 time (range: 0-3 times). Fifty out of 146 (34.2%) subjects had transvaginal delivery history. Chronic constipation was diagnosed in 32 subjects (21.9%). No significant difference in daytime micturition and nocturia times were found between the UI and non-UI subjects. According to the multivariate analysis, chronic constipation (OR=4.95, 95%CI=1.81-13.53, P=0.002) and transvaginal delivery history (OR=3.50, 95%CI=1.49-8.21, P=0.004) were independent risk factors for UI. The non-UI subjects had superior quality of life than the UI subjects in terms of incontinence quality of life (I-QOL) total scores and all sub-scores of avoidance and limiting behaviors, psychosocial impacts, and social embarrassment (P<0.001). In addition, avoidance and limiting behaviors (r=-0.449, P<0.001), psychosocial impacts (r=-0.538, P<0.001), and social embarrassment (r=-0.454, P<0.001) of the 63 UI subjects were equally influenced by the incontinence symptom. CONCLUSION: UI is not uncommon in female medical staff. The quality of life of medical faculty is influenced by UI in terms of avoidance and limiting behaviors, psychosocial impacts, and social embarrassment. Chronic constipation and transvaginal delivery history were independent risk factors for UI.

Association between rs12252 and influenza susceptibility and severity: an updated meta-analysis.

In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03-1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39-33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08-1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08-2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36-5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.

The roles of autophagy and hypoxia in human inflammatory periapical lesions.

AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues, were examined. Enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-1ß cytokine; immunohistochemical (IHC) and Western blot (WB) analyses were employed to examine autophagy-related and hypoxia-related proteins. Transmission electron microscopy (TEM) was used to explore the ultrastructural morphology of autophagy in periapical lesions. Nonparametric Kruskal-Wallis tests and Mann-Whitney U-tests were used for statistical analyses. RESULTS: ELISA revealed a significantly higher (P < 0.001) IL-1ß expression in periapical lesions than in normal pulp tissue. Immunoscores of IHC expressions of pAMPK, HIF-1α, BNIP3, BECN-1 and Atg5-12 proteins in periapical lesions were significantly higher (P < 0.001) (except BECN-1) than those in normal pulp tissue. The results of IHC studies were largely compatible with those of WB analyses, where significantly higher (P < 0.05) expressions of hypoxia-related and autophagy-related proteins (except BECN-1, p62 and LC3II in WB analyses) in periapical lesions were noted as compared to normal pulp tissue. Upon TEM, ultrastructural double-membrane autophagosomes and autolysosomes were observed in PGs and RCs. CONCLUSIONS: Autophagy associated with hypoxia may play a potential causative role in the development and maintenance of inflamed periapical lesions.

[Developing a Chinese PI-RADS v2-based nomogram for predicting clinically significant prostate cancer in patients with a prior negative biopsy].

Objective: To develop a nomogram based on prostate imaging reporting and data system version 2 (PI-RADS v2) to predict clinically significant prostate cancer in patients with a prior negative prostate biopsy. Methods: The clinical and pathological data of 231 patients who underwent repeat prostate biopsy and multiparametric MRI (mpMRI) were reviewed. Based on PI-RADS v2, the mpMRI results were assigned as PI-RADS grade from 0 to 2. A Logistic regression nomogram for predicting the probabilities of clinically significant prostate cancer were constructed. The performances of the nomogram were assessed using area under the receiver operating characteristic (ROC) curve, calibrations and decision curve analysis. Results: Of the total 231 repeat prostate biopsy patients, clinically significant prostate cancer was detected in 59 cases(25.5%). In multivariate Logistic regression analysis, age, prostate specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) and mpMRI results were significant independent predictors of the diagnosis of clinically significant prostate cancer (P<0.05). The nomogram with super predictive accuracy were constructed (AUC=0.927, P<0.001), and exhibited excellent calibration. Decision curve analysis also demonstrated a high net benefit across a wide range of threshold probabilities . Conclusions: PI-RADS v2 combined with age, PSA, PV and DRE can predict the probability of clinically significant prostate cancer in patients with negative initial biopsies. The nomogram generated may help the decision-making process in patients with prior benign histology before the performance of repeat biopsy.

[Development of a Chinese nomogram based on muti-parametric magnetic resonance for predicting the probability of prostate cancer in patients after initial negative biopsy].

Objective: To develop a predictive nomogram based on multi-parametric magnetic resonance imaging (mpMRI) information to identify men more likely to have a cancer diagnosed on repeat prostate biopsy. Methods: The clinical data of 237 patients who received repeat prostate biopsy after initial negative biopsy from Department of Urology of Peking University First Hospital between January 2001 and August 2016 was reviewed. Patient age, body mass index (BMI), serum total prostate-specific antigen (PSA), percent free PSA (f/t), prostate volume (PV), PSA density (PSAD), PSA velocity (PSAV), digital rectal examination (DRE), transrectal ultrasound (TRUS)and mpMRI results were included in the univariate and multivariate analysis. A nomogram was developed using selected variables and the area under the receiver operating characteristic (ROC) curve was calculated as a measure of discrimination. Results: A total of 76 patients (32.07%) had prostate cancer (PCa) detected on repeat biopsy. Based on univariate and multivariate logistic regression analysis, the patient age, PSA, PV, DRE and mpMRI results were independent predictors for the diagnosis of PCa on repeat biopsy. The current nomogram performed well (AUC=0.910) and showed excellent calibration. Conclusions: Multi-parametric magnetic resonance imaging combined with age, PSA, PV and DRE can predict the probability of PCa in patients with initial negative biopsy. The nomogram might help in decision-making for men with prior benign histology before the performance of repeat biopsy.

[Changes of macrophages in colitis-associated colonic carcinogenesis].

OBJECTIVE: To investigate the changes of quantity and phenotype of macrophages during the progress of colitis-associated carcinogenesis, and to identify the chemokines mediating macrophage recruitment. METHODS: Colitis-associated cancer was induced by azoxymethane (AOM) combined with dextran sulfate sodium (DSS) in C57BL/6 mice. The three sequential developmental stages of colitis associated cancer in the mice were named AD1, AD2 and AD3, respectively. Colon tissues were collected and digested into single-cell suspension. The percentage and phenotype of macrophages in the colon tissues were determined by fluorescence activated cell sorter (FACS). Protein array and real-time polymerase chain reaction (PCR) were used to predict potential chemotatic factors of macrophages. RESULTS: Colitis-associated cancer was effectively induced in C57BL/6 mice using AOM combined with DSS. The percentage of macrophages was gradually elevated in the AD1, AD2 and AD3 groups [(9.93±1.28)%, (15.42±1.15)%, (21.25±0.62)%], respectively, significantly higher than that of the control group [(2.39±0.54)%, P<0.01]. The macrophages infiltrating the colonic mucosa exhibited mainly a pro-inflammatory phenotype as CD206(-)CD86(+) MHCII(-). The positive rates of CD206 in the AD1, AD2 and AD3 groups were (15.03±1.54)%, (8.11±3.70)%, and (9.06±1.16)%, respectively, significantly lower than that of the control group [(19.43±7.31)%, P<0.01]. The positive rates of CD86 in the AD2 and AD3 groups were (46.73±6.58)% and (76.90±14.32)%, respectively, significantly higher than that of the control group [(19.37±9.69)%, P<0.01)]. The positive rates of MHCⅡ in the AD1, AD2 and AD3 groups were (31.10±2.69)%, (33.93±14.08)%, and (29.93±1.41)%, respectively, significantly lower than that of the control group [(50.30±6.58)%, P<0.01]. Protein array analysis and real-time PCR data revealed that G-CSF was the potential chemokine to recruit macrophages in the AOM-DSS mouse model. CONCLUSION: Macrophages infiltrate increasingly during the carcinogenesis and development of colitis-associated cancer, which mostly express CD206(-)CD86(+) MHCII(-) and might be potentially recruited by G-CSF.

Risk of diabetes mellitus among patients with myasthenia gravis.

OBJECTIVES: To determine the risk of diabetes mellitus (DM) in patients with myasthenia gravis (MG) in a large cohort representing 99% of the Taiwan population. METHODS: Data from the Taiwan National Health Insurance Database were used to conduct retrospective cohort analyses. The study cohort comprised 1520 patients with MG who were four-fold frequency matched to those without MG by age and sex, and assigned the same index year. Cox proportional hazard regression analysis was conducted to estimate the risk of DM. RESULTS: The MG cohort had a 1.26-fold increased risk of developing DM compared with the comparison cohort (HR=1.26, 95% CI=1.04-1.53). MG patients without corticosteroids use had no increased risk of developing DM (HR=1.05, 95% CI=0.79-1.40), and MG patients with corticosteroids use had a 1.46-fold increased risk of developing DM (HR=1.46, 95%=1.15-1.86). In addition, patients with MG received aggressive treatment, associated thyroid diseases, and male patients had higher risk of DM. CONCLUSION: This population-based retrospective cohort study demonstrates that MG is associated with a high risk of DM, which might be related to the adverse effect of corticosteroid and aggressive therapy.

Association between GSTM1 polymorphisms and lung cancer: an updated meta-analysis.

The relationship between glutathione S-transferase M1 (GSTM1) genetic polymorphisms and lung cancer has been reported previously. However, the results are not consistent. Therefore, to clarify the association between GSTM1 polymorphisms and lung cancer, we performed a meta-analysis based on published studies. We used the Revman 5.0 software to perform literature retrieval, article selection, data collection, and statistical analysis. We utilized a random-effect model to pool the odds ratios (ORs) and 95% confidence intervals (CIs). A total of 38 eligible studies including 5737 lung cancer patients and 6843 cancer-free control subjects were analyzed. We found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.15, 95%CI = 0.98-1.36, P = 0.08). Including only Chinese individuals, we found no association between GSTM1 genetic polymorphisms and lung cancer risk (OR = 1.13, 95%CI = 0.97-1.32, P = 0.13). In conclusion, we found that GSTM1 polymorphisms are not associated with lung cancer risk.

Influence of CYP3A5 genotypes on tacrolimus dose requirement: age and its pharmacological interaction with ABCB1 genetics in the Chinese paediatric liver transplantation.

AIM: The purpose of the study was to evaluate the impact of single nucleotide polymorphisms (SNPs) of Cytochrome P450 (CYP) 3A5 and adenosine triphosphate-binding cassette B1 (ABCB1) genotypes on TAC pharmacokinetics in Chinese paediatric patients. METHOD: A total of 136 Chinese paediatric liver recipients (R) and their donors (D) were divided into groups according to their CYP3A5 genotypes [expression of *1 allele: expressor (EX) or non-expressor (NEX)]. RESULT: Both recipient and donor CYP3A5*1 alleles had impacts on the TAC pharmacokinetics after liver transplantation. EX-R/EX-D recipients required a significantly higher TAC daily dose compared with NEX-R/NEX-D (0.24 ± 0.08 vs. 0.14 ± 0.06 mg/kg/day, p < 0.01). Age was also an independent factor on TAC requirement. Compared with EX-R/EX-D, non-expressor infants or recipients over 3-years old needed < 0.2 mg/kg/day. None of the ABCB1 SNPs (1236C>T, 2677G>A/T, 3435C>T) had an impact on TAC pharmacokinetics. However, EX-R/EX-D recipients bearing the ABCB1 1236-CC genotype required a much higher TAC dose than those without this genotype (0.23 vs. 0.18 mg/kg/day, p < 0.01), who required a similar TAC dose to that of NEX-R/NEX-D children. Furthermore, EX-R/EX-D with ABCB1 1236-CC recipients exhibited an markedly higher incidence of acute rejection and transplant-related infections clinically. CONCLUSION: CYP3A5 and ABCB1-1236 genotyping, in addition to recipient age, are necessary for establishing a more accurate TAC dosage regimen in paediatric liver recipients. We should be cautious regarding the treatment of paediatric recipients with both CYP3A5-expressor and ABCB1 1236-CC genotypes with TAC, as these patients are more susceptible to acute rejection and infection.

Pontine microbleeds and depression in stroke.

OBJECTIVES: Depression is the most common affective disorder following stroke yet the neuroanatomical model of poststroke depression (PSD) remains unclear. This study examined the association between PSD and cerebral microbleeds (CMBs) and hypothesized that CMBs in specific regions would be associated with PSD. METHODS: Of the 4766 patients with first ever or recurrent acute ischemic stroke admitted to the Acute Stroke Unit of the Prince of Wales Hospital between June 2004 and October 2010, 229 met the entry criteria and formed the study sample. Patients with a Geriatric Depression Scale score of 7 or above were classified as having PSD. The presence and location of CMBs were evaluated with magnetic resonance imaging. RESULTS: Compared to the non-PSD group, patients with PSD were more likely to have pontine CMBs (32.0% vs 18.2%; P = .019). The presence of pontine CMBs remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 2.2 (P = .016). CONCLUSION: The results suggest that pontine CMBs are associated with a higher risk of developing PSD.

Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study.

BACKGROUND: This study examined the risk of cancer in patients with Hashimoto's thyroiditis (HT). METHODS: The Taiwanese National Health Insurance Research Database (NHIRD) was used to identify 1521 newly diagnosed HT patients from 1998-2010, and 6084 frequency-matched non-HT patients. The risk of developing cancer for HT patients was measured using the Cox proportional hazard model. RESULTS: The incidence of developing cancer in the HT cohort was 5.07 per 1000 person-years, which was 1.68-fold higher than that in the comparison cohort (P<0.001). Compared with patients aged 20-34 years, patients in older age groups had a higher risk of developing cancer (35-55 years: hazard ratio (HR)=5.96; >55 years: HR=9.66). After adjusting for sex, age, and comorbidities, the HT cohort had HRs of 4.76 and 11.8 for developing colorectal cancer and thyroid cancer, respectively, compared with non-HT cohort. Furthermore, the HT cohort to non-HT cohort incidence rate ratio (IRR) of thyroid cancer was higher in the first 3 years (48.4, 95% confidence interval (CI)=35.0-66.3), with an adjusted HR of 49.4 (95% CI=6.39-382.4). CONCLUSION: Hashimoto's thyroiditis patients have a higher risk of thyroid cancer and colorectal cancer. The thyroid cancer prevention effort should start soon after HT is diagnosed, while being cautious of colorectal cancer increases with time.

Location of infarcts and apathy in ischemic stroke.

BACKGROUND: Apathy is common in stroke survivors. Unlike poststroke depression, apathy after stroke has not been extensively investigated and the significance of the location of infarcts in the development of apathy following a stroke is unknown. This study examined the association between poststroke apathy (PSA) and the location of infarcts. METHODS: A cohort of 185 patients with acute ischemic stroke admitted to the Stroke Unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a psychiatrist administered the Apathy Evaluation Scale (AES). PSA was defined as an AES score of 37 or above. The presence and location of infarcts were evaluated with magnetic resonance imaging. RESULTS: Altogether 185 patients met the entry criteria and formed the study sample; 20 (10.8%) had PSA. PSA patients were older and had higher stroke severity and more depressive symptoms. The PSA group also had lower levels of physical and cognitive functioning. Compared with the non-PSA group, PSA patients were more likely to have acute pontine infarcts (35.0% vs. 11.5%; p = 0.011). They had a higher mean number (0.5 ± 0.7 vs. 0.1 ± 0.3; p = 0.003) and larger volume (0.6 ± 1.4 vs. 0.1 ± 0.3 ml; p = 0.002) of acute pontine infarcts. Six variables were entered into the predictive regression model: age, the presence, number and volume of acute pontine infarcts, the number of old infarcts and periventricular white matter hyperintensities scores. The volume of infarcts remained an independent predictor of PSA in the multivariate analysis, with an odds ratio of 3.9 (p = 0.007). The Geriatric Depression Scale, National Institutes of Health Stroke Scale, Barthel Index and Mini-Mental State Examination scores were also entered into the subsequent associative regression model; the volume of acute pontine infarcts remained a significant predictor (odds ratio = 3.8). CONCLUSIONS: This is the first report of an association between pontine infarcts and the risk of PSA. The results suggest that pontine infarcts may play a role in the development of PSA. The importance of acute pontine infarcts in the pathogenesis of PSA warrants further investigation.

White matter hyperintensities and quality of life in acute lacunar stroke.

White matter hyperintensities (WMH) are common in stroke. The influence of WMH on health-related quality of life (HRQoL) following a lacunar stroke is unknown. This study evaluated the impact of WMH on HRQoL in acute lacunar stroke. A cohort of 160 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a research assistant administered the Short Form-36 (SF-36) to assess HRQoL. The severity of WMH was evaluated with magnetic resonance imaging (MRI). In univariate analysis, the severity of deep WMH (DWMH) negatively correlated with patients' vitality (VT; p < 0.05), social function (SF; p < 0.001), role-emotional (RE; p < 0.01), mental health (MH; p < 0.01), and mental component summary (MCS; p < 0.001) scores of HRQoL. DWMH was independently associated with all of the above five SF-36 scores (p < 0.05) in linear regression analysis. These findings suggest that DWMH has a significant impact on the HRQoL of stroke survivors. The importance of DWMH in the long-term HRQoL in lacunar stroke warrants further investigation.

Hemodynamic changes in patients with SARS-CoV-2 infection presenting for cesarean delivery under spinal anesthesia: a retrospective case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with adverse maternal and neonatal outcomes. Early studies suggested that COVID-19 was associated with a higher incidence of hypotension following neuraxial anesthesia in parturients. We explored the hemodynamic response to spinal anesthesia for cesarean delivery in pregnant severe respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) positive patients, using a retrospective case-control design. METHODS: We searched our electronic medical records for patients who received spinal anesthesia for cesarean delivery, and were SARS-CoV-2 positive or recovered at delivery, and used historical and SARS-CoV-2 negative controls from two tertiary care hospitals. We compared the demographic, clinical, and hemodynamic variables between patients who were SARS-CoV-2 positive at delivery, those who were positive during pregnancy and recovered before delivery, and controls. Analyses were stratified by normotensive versus hypertensive status of the patients at delivery. RESULTS: We identified 22 SARS-CoV-2 positive, 73 SARS-CoV-2 recovered, and 1517 controls. The SARS-CoV-2 positive, and recovered pregnant patients, had on average 5.6 and 2.2 mmHg, respectively, higher post-spinal mean arterial pressures (MAPs) than control patients, adjusting for covariates. Additionally, the lowest post-spinal MAP was negatively correlated with the number of daysbetween the onset of COVID-19 symptoms and delivery in patients with hypertension (correlation -0.55, 95% CI -0.81 to -0.09). CONCLUSIONS: Patients with SARS-CoV-2 infection during pregnancy exhibit less spinal hypotension than non-infected patients. While the clinical significance of this finding is unknown, it points to important cardiovascular effects of the virus.

Linear phase-and-frequency-modulated photonic links using optical discriminators.

We report our experimental results for linear analog optical links that use phase or frequency modulation and optical discrimination. The discriminators are based on two architectures: a cascaded MZI FIR lattice filter and a ring assisted MZI (RAMZI) IIR filter. For both types of discriminators, we demonstrate > 6 dB improvement in the link's third-order output intercept point (OIP3) over a MZM link. We show that the links have low second-order distortion when using balanced detection. Using high optical power, we demonstrate an OIP3 of 39.2 dBm. We also demonstrate 4.3dB improvement in signal compression.