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1.
Clin Park Relat Disord ; 10: 100235, 2024.
Article in English | MEDLINE | ID: mdl-38292814

ABSTRACT

Objective: To assess the incidence of Impulse control and related behavioral disorders (ICRD) in Chinese Idiopathic Parkinson Disease (IPD) patients treated with different dopamine agonists (DA), and their clinical characteristics and associated risk factors. Methods: This was an observational cohort study based on clinical interviews and medical records of IPD patients treated with DA for >6 months in three hospitals in Hong Kong. The short version of Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP-S) was used to screen for ICRD. ICRD incidence among different DA, clinical characteristics and risk factors were examined. Results: Incidence of ICRD was analyzed in 311 patients taking their first, single DA. 43 patients (13.8 %) developed ICRD. The mean duration of IPD was 8.5 ± 5.6 years and median HY stage was 2.5. Bromocriptine and rotigotine users had lower ICRD incidence rate. Both pramipexole [adjusted HR 7.28 (2.46-21.54), p < 0.001] and ropinirole [adjusted HR 6.53 (2.67-15.99), p < 0.001] were independently associated with higher risk of ICRD compared to bromocriptine in multivariate analysis. Similarly, pramipexole and ropinirole appeared to carry higher risk compared to rotigotine but did not reach statistical significance. Male [adjusted HR 2.24 (1.07-4.72), p = 0.033], younger IPD onset [adjusted HR 2.99 (1.44-6.19) for onset < 50 year, p = 0.003] and history of psychiatric disorders [adjusted HR 2.80 (1.39-5.62), p = 0.004] were other independent risk factors. Conclusion: Bromocriptine and probably rotigotine carried a lower ICRD risk compared to pramipexole and ropinirole.

2.
Cell Rep ; 42(10): 113176, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37773750

ABSTRACT

MCL-1 is a high-priority target due to its dominant role in the pathogenesis and chemoresistance of cancer, yet clinical trials of MCL-1 inhibitors are revealing toxic side effects. MCL-1 biology is complex, extending beyond apoptotic regulation and confounded by its multiple isoforms, its domains of unresolved structure and function, and challenges in distinguishing noncanonical activities from the apoptotic response. We find that, in the presence or absence of an intact mitochondrial apoptotic pathway, genetic deletion or pharmacologic targeting of MCL-1 induces DNA damage and retards cell proliferation. Indeed, the cancer cell susceptibility profile of MCL-1 inhibitors better matches that of anti-proliferative than pro-apoptotic drugs, expanding their potential therapeutic applications, including synergistic combinations, but heightening therapeutic window concerns. Proteomic profiling provides a resource for mechanistic dissection and reveals the minichromosome maintenance DNA helicase as an interacting nuclear protein complex that links MCL-1 to the regulation of DNA integrity and cell-cycle progression.


Subject(s)
Antineoplastic Agents , Proto-Oncogene Proteins c-bcl-2 , Proto-Oncogene Proteins c-bcl-2/metabolism , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Apoptosis , Proteomics , Antineoplastic Agents/pharmacology , DNA Damage , Cell Line, Tumor
3.
Orphanet J Rare Dis ; 18(1): 186, 2023 07 10.
Article in English | MEDLINE | ID: mdl-37430370

ABSTRACT

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from mutations of α-galactosidase A gene, and has been emphasized as one of the etiologies of young stroke and leukoencephalopathy. Vertebrobasilar dolichoectasia (VBD) is a highlighted finding in FD. We aim to examine the utility of VBD in Chinese FD by comparing the differences in basilar artery (BA) diameter of Chinese FD patients against age-matched controls with and without stroke. METHODS: This was a matched case-control study involving 37 Chinese FD patients. The BA diameters were evaluated on axial T2-weighted magnetic resonance imaging and compared to two age-and-gender matched control groups, one with stroke and one without. The association between BA diameter and stroke occurrences and white matter hyperintensities (WMH) were analyzed among all FD patients. RESULTS: Patients with FD had significantly increased BA diameter compared to controls with and without stroke (p < 0.001). A BA diameter of 4.16 mm could distinguish FD from controls in the stroke subgroup (ROC AUC 0.870, p = 0.001, sensitivity 80% specificity 100%), and with a cut-off of 3.21 mm in the non-stroke subgroup (ROC AUC 0.846, p < 0.001, sensitivity 77.8% specificity 88.9%). Larger BA diameter had more stroke occurrences and was moderately associated with heavier WMH load in terms of higher total FAZEKAS scores. (Spearman's rho = 0.423, p = 0.011). CONCLUSION: VBD was also present in Chinese FD patients. BA diameter has high diagnostic utility in identifying FD from a mixed cohort of stroke and normal controls, and carried predictive value in evaluating neurological complications of FD.


Subject(s)
Fabry Disease , Stroke , Vertebrobasilar Insufficiency , Humans , Fabry Disease/diagnostic imaging , Basilar Artery/diagnostic imaging , Case-Control Studies , East Asian People , Stroke/diagnostic imaging , Vertebrobasilar Insufficiency/diagnostic imaging , Biomarkers , Neuroimaging
4.
iScience ; 26(2): 106070, 2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36824269

ABSTRACT

PTEN encodes a tumor suppressor with lipid and protein phosphatase activities whose dysfunction has been implicated in melanomagenesis; less is known about how its phosphatases regulate melanoma metastasis. We demonstrate that PTEN expression negatively correlates with metastatic progression in human melanoma samples and a PTEN-deficient mouse melanoma model. Wildtype PTEN expression inhibited melanoma cell invasiveness and metastasis in a dose-dependent manner, behaviors that specifically required PTEN protein phosphatase activity. PTEN phosphatase activity regulated metastasis through Entpd5. Entpd5 knockdown reduced metastasis and IGF1R levels while promoting ER stress. In contrast, Entpd5 overexpression promoted metastasis and enhanced IGF1R levels while reducing ER stress. Moreover, Entpd5 expression was regulated by the ER stress sensor ATF6. Altogether, our data indicate that PTEN phosphatase activity inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6, thereby identifying novel candidate therapeutic targets for the treatment of PTEN mutant melanoma.

5.
Front Pediatr ; 10: 1004890, 2022.
Article in English | MEDLINE | ID: mdl-36340731

ABSTRACT

Background/objectives: Maternal illicit drug use is associated with negative physical and developmental outcomes for their born children. We aim to find out the incidence of different developmental problems in a cohort of Chinese children born to drug-abusing mothers, compare the physical health and developmental outcomes of the subjects recruited in the Integrated Program to the Comprehensive Child Development Service (CCDS), and to study the potential factors on their associations. Methods: A retrospective longitudinal cohort study with frequent clinical assessments of the children's physical and developmental outcomes in a HKSAR's regional hospital from birth until 5 years old. 123 Children in Integrated Program were compared with 214 children in CCDS between 1 January 2008 and 28 February 2019. Cox regression analysis was performed to determine the possible factors associated with the developmental outcomes. Results: Developmental delay was detected in 129 children (38.9%). CCDS group has significantly higher incidence of cognitive delay (p = < 0.001), language delay (p = < 0.001), motor delay (p = < 0.001), social delay (p = 0.002), and global delay (p = 0.002). On Cox multivariable regression analysis, integrated program (HRadj 0.53, 95% C. I. 0.34-0.84), social support (HRadj 0.45, 95% C.I. 0.25-0.80), and maternal abstinence from drug use up to 2-year post-delivery (HRadj 0.62, 95% C.I. 0.40-0.95) were significant protective factors, while male gender (HRadj 1.73, 95% C.I. 1.18-2.54) was a significant risk factor. Conclusion: CCDS achieves early engagement of drug-abusing expectant mothers during pregnancy, and an early integrated program with multidisciplinary collaboration was an independent factor in improving the developmental outcomes of these vulnerable children.

6.
Eur J Obstet Gynecol Reprod Biol ; 277: 101-109, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36067607

ABSTRACT

OBJECTIVES: The purpose of our study is to evaluate clinical outcomes of CO2 laser vaporization in patients with high-grade vaginal intraepithelial neoplasia (VAIN), and analyze potential risk factors for unfavourable outcome. STUDY DESIGN: A retrospective cohort study was carried out on all patients with high-grade VAIN treated by laser vaporization from Jan 2001 to Dec 2020 in a gynae-oncology training centre in Hong Kong. RESULTS: A total of 116 women underwent laser therapy for high-grade VAIN during the study period and the median follow-up time was 49.5 months. Disease regression was achieved in 75% of patients after first laser treatment. However, 23% of them had disease recurrence after initial regression. Regression rate declined significantly at subsequent laser treatment for disease persistence or recurrence, from 75% after the first laser, to 52.9% after the second laser and 26.5% after the third or more laser (p < 0.001). Eleven patients (9.4%) had disease progression to cancer during subsequent follow-ups. VAIN 3 was the only independent risk factor for unfavourable outcome after multivariable logistic regression (OR = 2.86, 95% CI 1.16-7.06, p = 0.023). CONCLUSION: CO2 laser vaporization is a safe and effective treatment modality for high-grade VAIN, but with high recurrence rate. Patients should be carefully counselled about treatment failure, recurrence risk, and the need for long-term surveillance for any progression to cancer. Alternative treatment modalities should be considered in patients who failed to regress after two episodes of laser treatment.


Subject(s)
Carcinoma in Situ , Laser Therapy , Vaginal Neoplasms , Carbon Dioxide , Carcinoma in Situ/surgery , Female , Humans , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Vaginal Neoplasms/surgery
7.
J Am Soc Nephrol ; 33(6): 1193-1207, 2022 06.
Article in English | MEDLINE | ID: mdl-35354600

ABSTRACT

BACKGROUND: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. METHODS: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. RESULTS: A total of 346 children (age, 9.8 years; IQR, 6.6-13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3-7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. CONCLUSIONS: Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.


Subject(s)
Agammaglobulinemia , Nephrosis, Lipoid , Nephrotic Syndrome , Neutropenia , Agammaglobulinemia/chemically induced , Agammaglobulinemia/drug therapy , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Nephrosis, Lipoid/drug therapy , Nephrotic Syndrome/drug therapy , Neutropenia/chemically induced , Neutropenia/drug therapy , Recurrence , Retrospective Studies , Rituximab/adverse effects , Steroids/therapeutic use , Treatment Outcome
8.
J Med Imaging Radiat Oncol ; 66(6): 853-865, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35302281

ABSTRACT

INTRODUCTION: T4 nasopharyngeal carcinoma (NPC) with close proximity to critical organs at risk (OARs) is usually underdosed during radiotherapy in order to respect radiation constraints. N3 disease has high risk of distant metastasis. Induction chemotherapy (IC) provides advantages of sparing of OARs during subsequent chemoradiotherapy (CCRT) and early eradication of micrometastasis. However, factors predicting successes of IC in this patient group are not well-studied. METHODS: 104 T4 or N3 NPC patients were retrospectively reviewed during 2007-2018. They were planned for IC followed by CCRT using intensity-modulated radiotherapy. RESULTS: In the whole group, five-year failure-free survival (FFS), locoregional failure-free survival (LRFS), distant failure-free survival (DFFS) and overall survival (OS) were 40.9%, 45.7%, 46.9% and 53.6% respectively. Isolated marginal failure rate was 5% (4/80) among patients with primary tumours located close to critical OARs. Pre-IC gross tumour volume primary (GTVp) total volume > 110 cm3 correlated with worse five-year LRFS (OR 6.37, P = 0.008), DFFS (OR 8.89, P = 0.003) and OS (OR 50.12, P < 0.001). In the T4 subgroup, IC improved D100% GTVp from 61.39 Gy to 64.71 Gy (P < 0.001) and V100% GTVp from 98.78% to 99.28% (P < 0.001). CONCLUSION: Our study demonstrated improved dosimetric parameters and low isolated marginal failure rate. It supported the use of IC and CCRT for tumours located close to critical OARs. Further research is warranted to compare predictive roles of pre- and post-IC tumour volumes. For high-risk patients being defined by pre-IC volume or other prognostic models, treatment escalation should be considered.


Subject(s)
Induction Chemotherapy , Nasopharyngeal Neoplasms , Chemoradiotherapy/methods , Humans , Induction Chemotherapy/adverse effects , Induction Chemotherapy/methods , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/radiotherapy , Retrospective Studies
9.
J Cardiothorac Surg ; 16(1): 24, 2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33731180

ABSTRACT

BACKGROUND: In spontaneous pneumothorax, clamping the chest drain before its removal may avoid reinsertion in case of early recurrence, but may be unsafe and may prolong hospital stay. The objective of this study was to examine the incidence of early recurrence in both clamped and unclamped pneumothorax episodes, and factors associated with it. METHODS: Retrospective chart review of primary and secondary spontaneous pneumothorax episodes in which chest drain was inserted during the period April 2012 to March 2014. RESULTS: Data of 122 episodes were analysed. There were 36 primary pneumothorax and 86 secondary pneumothorax episodes. Mean age was 59 years with 92% males. Clamping of the chest drain was done in 68 episodes (55.7%), and not done in 54. The clamping group was significantly younger, had more primary pneumothorax, and had shorter time from cessation of air leak to clamp/removal. Recurrence within 24 h were seen in 12 (17.6%) clamped episodes and 4 (7.4%) non-clamped episodes, although in only eight episodes were reinsertion of chest drain saved. Significantly more previous pneumothorax episodes were seen in the early recurrence group. We observed no new onset of tension pneumothorax or subcutaneous emphysema associated with clamping. CONCLUSION: The practice of clamping the chest drain before removal in spontaneous pneumothorax appear safe. Clamping saved chest drain reinsertion in 11.8% of cases, and has the potential to save more if clamped for up to 24 h. However, clamping may result in more early recurrences. Prospective randomised studies are needed.


Subject(s)
Chest Tubes , Device Removal/methods , Drainage/methods , Pneumothorax/surgery , Female , Humans , Male , Middle Aged , Pneumothorax/etiology , Recurrence , Retrospective Studies
10.
Br J Haematol ; 192(1): 171-178, 2021 01.
Article in English | MEDLINE | ID: mdl-33095929

ABSTRACT

Haemoglobin H (HbH) disease is a type of non-transfusion-dependent thalassaemia. This cross-sectional study aimed at determining the prevalence and severity of liver iron overload and liver fibrosis in patients with HbH disease. Risk factors for advanced liver fibrosis were also identified. A total of 80 patients were evaluated [median (range) age 53 (24-79) years, male 34%, non-deletional HbH disease 24%]. Patients underwent 'observed' T2-weighted magnetic resonance imaging examination for liver iron concentration (LIC) quantification, and transient elastography for liver stiffness measurement (LSM) and fibrosis staging. In all, 25 patients (31%) had moderate-to-severe liver iron overload (LIC ≥7 mg/g dry weight). The median LIC was higher in non-deletional than in deletional HbH disease (7·8 vs. 2.9 mg/g dry weight, P = 0·002). In all, 16 patients (20%) had advanced liver fibrosis (LSM >7.9 kPa) and seven (9%) out of them had probable cirrhosis (LSM >11.9 kPa). LSM positively correlated with age (R = 0·24, P = 0·03), serum ferritin (R = 0·36, P = 0·001) and LIC (R = 0·28, P = 0·01). In multivariable regression, age ≥65 years [odds ratio (OR) 4·97, 95% confidence interval (CI) 1·52-17·50; P = 0·047] and moderate-to-severe liver iron overload (OR 3·47, 95% CI 1·01-12·14; P = 0·01) were independently associated with advanced liver fibrosis. The findings suggest that regular screening for liver complications should be considered in the management of HbH disease.


Subject(s)
Liver Diseases/etiology , alpha-Thalassemia/complications , Adult , Aged , Cross-Sectional Studies , Female , Humans , Iron/analysis , Iron Overload/etiology , Iron Overload/pathology , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Diseases/pathology , Male , Middle Aged , Young Adult , alpha-Thalassemia/pathology
11.
Int J Chron Obstruct Pulmon Dis ; 15: 2869-2877, 2020.
Article in English | MEDLINE | ID: mdl-33204083

ABSTRACT

Purpose: Blood eosinophil is a readily available biomarker to reflect the eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) patients, yet its association with exacerbation is inconclusive. It is uncertain which measurement, eosinophil percentage or absolute eosinophil count, should be used and what is the optimal cutoff for exacerbation prediction. Patients and Methods: A total of 247 COPD patients were included in this retrospective cohort study. Blood eosinophil during stable disease state, baseline demographics, and clinical characteristics in 12 months after the index complete blood count (CBC) were recorded. Exacerbation frequencies were compared between patients with high and low blood eosinophil percentage using 2% as cut-off. Logistic regression and receiver operating characteristics (ROC) curve analyses were conducted. Results: Patients with blood eosinophil ≥2% were associated with more frequent exacerbations than patients with eosinophil <2% in the 12 months after the index CBC (mean exacerbation 1.07 vs 0.34, p < 0.001). Higher blood eosinophil percentage conferred a higher risk of exacerbation. Adjusted odds ratio for exacerbation in 12 months after the index CBC for blood eosinophil ≥2% was 2.98 (95% confidence interval = 1.42-6.25). The area under the ROC curve of eosinophil percentage was significantly higher than that of absolute eosinophil count (0.678 vs 0.640, p = 0.010). The optimal cutoff of blood eosinophil percentage for exacerbation prediction was 2.8%. Conclusion: Blood eosinophilia was associated with higher exacerbation risk in COPD patients. Further studies are required to elucidate the mechanism of eosinophilic inflammation in COPD and determine the optimal treatment strategy to reduce exacerbations.


Subject(s)
Eosinophils , Pulmonary Disease, Chronic Obstructive , Cohort Studies , Disease Progression , Humans , Leukocyte Count , Pulmonary Disease, Chronic Obstructive/diagnosis , Retrospective Studies
12.
Kidney Int ; 97(2): 393-401, 2020 02.
Article in English | MEDLINE | ID: mdl-31874801

ABSTRACT

Rituximab is an effective treatment for steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) in children. However, the optimal rituximab regimen remains unknown. To help determine this we conducted an international, multicenter retrospective study at 11 tertiary pediatric nephrology centers in Asia, Europe and North America of children 1-18 years of age with complicated SDFRNS receiving rituximab between 2005-2016 for 18 or more months follow-up. The effect of rituximab prescribed at three dosing levels: low (375mg/m2), medium (750mg/m2) and high (1125-1500mg/m2), with or without maintenance immunosuppression (defined as concurrent use of corticosteroids, mycophenolate motile or calcineurin inhibition at first relapse or for at least six months following the rituximab treatment) was examined. Among the 511 children (median age 11.5 year, 67% boys), 191, 208 and 112 received low, medium and high dose rituximab, respectively. Within this total cohort of 511 children, 283 (55%) received maintenance immunosuppression. Renal biopsies were performed in 317 children indicating the predominant histology was minimal change disease (74%). Without maintenance immunosuppression, low-dose rituximab had a shorter relapse-free period and a higher relapse risk (8.5 months) than medium (12.7 months; adjusted hazard ratio, 0.62) and high dose (14.3 months; adjusted hazard ratio, 0.50; all significant). With maintenance immunosuppression, the relapse-free survival in low-dose rituximab (14 months) was similar to medium (10.9 months; adjusted hazard ratio, 1.23) and high dose (12.0 months; adjusted hazard ratio, 0.92; all non-significant). Most adverse events were mild. Thus, children receiving low-dose rituximab without maintenance immunosuppression had the shortest relapse-free survival. Hence, both rituximab dose and maintenance immunosuppression have important effects on the treatment outcomes.


Subject(s)
Nephrotic Syndrome , Asia , Child , Europe , Female , Humans , Immunosuppression Therapy , Immunosuppressive Agents/adverse effects , Male , Nephrotic Syndrome/drug therapy , North America , Recurrence , Retrospective Studies , Rituximab/adverse effects , Steroids , Treatment Outcome
13.
Maturitas ; 128: 29-35, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31561819

ABSTRACT

OBJECTIVES: Limited data are available on the effect of the time interval of vaginal ring pessary replacement for pelvic organ prolapse (POP). This study investigated the effect of different replacement intervals on complications and patient satisfaction. STUDY DESIGN: A double-blinded, randomized controlled trial was conducted in a tertiary urogynecology center. Women with a vaginal ring pessary for POP (stage I to IV) were randomly allocated to two groups: 3-monthly or 6-monthly ring pessary replacement. All women were blinded to the replacement interval. Investigators were blinded during outcome assessment. Subjects were followed up for 6 months. MAIN OUTCOME MEASURES: The primary outcomes were the complication rates and patient satisfaction scores at 6 months. Secondary outcomes were the change in patient-reported symptoms and staging of POP. RESULTS: Of 101 women were screened from June 2016 to November 2017, 60 were recruited and randomly allocated: 30 to the 3-monthly replacement group and 30 to the 6-monthly replacement group. The overall complication rate in the 6-monthly group was higher than that in the 3-monthly group at the third visit (9 [30%] vs. 3[10.3%]; OR 3.71; 95%CI 0.89-15.58), but the difference was not statistically significant (p = 0.061). There were no statistically significant differences between groups in patient satisfaction scores, other prolapse-related symptoms or staging of POP. CONCLUSIONS: We provide evidence on the effect of replacement interval for a vaginal pessary on complications and patient satisfaction. A higher complication rate was found in the 6-monthly group than in the 3-monthly group, although the difference was not statistically significant. Patient satisfaction scores were similar in both groups.


Subject(s)
Patient Satisfaction , Pelvic Organ Prolapse/therapy , Pessaries , Aged , Double-Blind Method , Female , Humans , Middle Aged , Time Factors , Treatment Outcome , Vagina
14.
Int J Gynecol Cancer ; 29(4): 772-778, 2019 05.
Article in English | MEDLINE | ID: mdl-30829579

ABSTRACT

OBJECTIVE: Intra-operative frozen section (IFS) can provide an instinct guide for treatment of ovarian tumors intra-operatively, though limitations exist. This study intended to evaluate the diagnostic performance of IFS and possible clinicopathological factors influencing the diagnostic accuracy of IFS. METHODS: A retrospective review of IFS of ovarian lesions from 2006 to 2016 was done. The diagnostic performance of benign, borderline, and malignant IFS diagnosis was evaluated. Logistic regression analysis was used to assess the influence of clinicopathological parameters on the likelihood of underdiagnosis. RESULTS: There were 1143 consecutive cases during the study period. The overall accuracy was 93.7%. For benign diagnoses, the IFS diagnostic accuracy, sensitivity, and specificity were 97.20%, 100%, and 92.51%, respectively. If borderline and malignant diagnoses were considered as a single group, the IFS diagnostic accuracy was 97.20%, with 92.51% sensitivity and 100% specificity. At univariate regression analysis, intact capsules at time of delivery (ORunadj = 1.9), stage I lesions (ORunadj = 3.76) and ultrasound (USG) score 0 (ORunadj = 2.52) were positively associated with underdiagnosis. Further multivariate analysis showed that only stage I lesions (OR = 3.62) and USG score 0 (OR = 2.32) were positively associated with underdiagnosis. For the cases with underdiagnosed IFS, 54% (34/63) received incomplete primary staging surgery. CONCLUSIONS: The study demonstrated that IFS provided excellent specificity to differentiate borderline or malignant tumors from benign lesions. IFS in early-stage ovarian cancers needs to be interpreted with caution, though IFS is most important for this group of lesions. A reliable IFS diagnosis often requires efficient communication between surgeons and pathologists.


Subject(s)
Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Adult , Cohort Studies , Female , Frozen Sections/methods , Frozen Sections/standards , Hong Kong , Humans , Intraoperative Care/methods , Intraoperative Care/standards , Reproducibility of Results
15.
Oncogene ; 37(17): 2225-2236, 2018 04.
Article in English | MEDLINE | ID: mdl-29391600

ABSTRACT

PI3K/AKT pathway activation is thought to be a driving force in metastatic melanomas. Members of the pleckstrin homology (PH) domain leucine-rich repeat protein Ser/Thr specific phosphatase family (PHLPP1 and PHLPP2) can regulate AKT activation. By dephosphorylating specific serine residues in the hydrophobic motif, PHLPP1 and PHLPP2 restrain AKT signalings, thereby regulating cell proliferation and survival. We here show that PHLPP1 expression was significantly downregulated or lost and correlated with metastatic potential in melanoma. Forcing expression of either PHLPP1 or PHLPP2 in melanoma cells inhibited cell proliferation, migration, and colony formation in soft agar; but PHLPP1 had the most profound inhibitory effect on metastasis. Moreover, expression of PH mutant forms of PHLPP1 continued to inhibit metastasis, whereas a phosphatase-dead C-terminal mutant did not. The introduction of activated PHLPP1-specific targets AKT2 or AKT3 also promoted melanoma metastasis, while the non-PHLPP1 target AKT1 did not. AKT2 and AKT3 could even rescue the PHLPP1-mediated inhibition of metastasis. An AKT inhibitor blocked the activity of AKT2 and inhibited AKT2-mediated tumor growth and metastasis in a preclinical mouse model. Our data demonstrate that PHLPP1 functions as a metastasis suppressor through its phosphatase activity, and suggest that PHLPP1 represents a novel diagnostic and therapeutic marker for metastatic melanoma.


Subject(s)
Melanoma/pathology , Nuclear Proteins/physiology , Phosphoprotein Phosphatases/physiology , Proto-Oncogene Proteins c-akt/metabolism , Animals , Biomarkers, Tumor/genetics , Cells, Cultured , Down-Regulation/genetics , Enzyme Activation/genetics , Genes, Tumor Suppressor/physiology , Humans , Melanoma/genetics , Melanoma/metabolism , Mice , Mice, Inbred C57BL , Mice, Nude , Mice, SCID , Neoplasm Metastasis
16.
Nat Microbiol ; 2: 17059, 2017 Apr 18.
Article in English | MEDLINE | ID: mdl-28418382

ABSTRACT

Many prokaryotic cells are encapsulated by a surface layer (S-layer) consisting of repeating units of S-layer proteins. S-layer proteins are a diverse class of molecules found in Gram-positive and Gram-negative bacteria and most archaea1-5. S-layers protect cells from the outside, provide mechanical stability and also play roles in pathogenicity. In situ structural information about this highly abundant class of proteins is scarce, so atomic details of how S-layers are arranged on the surface of cells have remained elusive. Here, using purified Caulobacter crescentus' sole S-layer protein RsaA, we obtained a 2.7 Å X-ray structure that shows the hexameric S-layer lattice. We also solved a 7.4 Šstructure of the S-layer through electron cryotomography and sub-tomogram averaging of cell stalks. The X-ray structure was docked unambiguously into the electron cryotomography map, resulting in a pseudo-atomic-level description of the in vivo S-layer, which agrees completely with the atomic X-ray lattice model. The cellular S-layer atomic structure shows that the S-layer is porous, with a largest gap dimension of 27 Å, and is stabilized by multiple Ca2+ ions bound near the interfaces. This study spans different spatial scales from atoms to cells by combining X-ray crystallography with electron cryotomography and sub-nanometre-resolution sub-tomogram averaging.


Subject(s)
Bacterial Outer Membrane Proteins/chemistry , Caulobacter crescentus/chemistry , Membrane Glycoproteins/chemistry , Bacterial Proteins/chemistry , Crystallography, X-Ray , Electron Microscope Tomography , Membrane Glycoproteins/isolation & purification , Membrane Glycoproteins/ultrastructure , Surface Properties
17.
Medicine (Baltimore) ; 95(23): e3761, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27281074

ABSTRACT

In China, Community Health Centers (CHCs) are major providers of primary care services, but their potential in empowering patients' self-management capacity has not been assessed. This study aims to describe self-care practice patterns amongst CHC attendees in urban China.In this cross-sectional quantitative study, 3360 CHC patients from 6 cities within the Pearl Delta Region were sampled using multistage cluster sampling.Thirty-seven per cent had used with over-the-counter Chinese herbal medicines (OTC CHMs) in the past year and majority of respondents found OTC CHMs effective. OTC CHMs were more popular amongst those who needed to pay out of pocket for CHC services. Less than 10% used vitamins and minerals, and those with a lower socioeconomic background have a higher propensity to consume. Although doubts on their usefulness are expressed, their use by the vulnerable population may reflect barriers to access to conventional health care, cultural affinity, or a defense against negative consequences of illnesses. About 25% performed physical exercise, but the prevalence is lower amongst women and older people. Taiji seems to be an alternative for these populations with promising effectiveness, but overall only 6% of CHC attendees participated.These results suggest that CHCs should start initiatives in fostering appropriate use of OTC CHM, vitamins, and minerals. Engaging community pharmacists in guiding safe and effective use of OTC CHM amongst the uninsured is essential given their low accessibility to CHC services. Prescription of Taiji instead of physical exercises to women and older people could be more culturally appropriate, and the possibility of including this as part of the CHC services worth further exploration.


Subject(s)
Attitude to Health , Community Health Centers , Complementary Therapies/standards , Guidelines as Topic , Population Surveillance , Self Care/standards , Urban Population , Aged , China , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Middle Aged , Primary Health Care/organization & administration , Rivers , Surveys and Questionnaires
18.
Medicine (Baltimore) ; 95(17): e3316, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27124021

ABSTRACT

This study aims to examine the level of empathy perceived by patients receiving care from herbalists, acupuncturists and massage therapists and to investigate the factors that influence levels of perceived empathy.Participants who were 18 years or above; able to provide written informed consent; and able to read and write in Chinese without assistance were included. A total of 514 participants sampled from charity and semipublic Chinese medicine (CM) clinics in Hong Kong were recruited to assess levels of empathy perceived during various length of consultations (1-20 minutes) by the Chinese Consultation and Relational Empathy Measure (Chinese CARE). Multiple linear regressions were conducted to evaluate the associations between perceived levels of empathy and the type of CM practitioner consulted and participants' demographic and health characteristics.The average Chinese CARE total score for participants consulting CM practitioners was 34.3 of a maximum of 50. After adjusting for participants' health and demographic characteristics, acupuncturists received the highest ratings (P < 0.001), whereas massage therapists (P < 0.001) scored the lowest of the 3 modalities. Participants receiving social benefits (P = 0.013), those with longer waiting times (P = 0.002), and those with shorter consultation durations (P = 0.020) scored significantly lower on the Chinese CARE.The level of empathy perceived by participants using CM was similar to results found for those in conventional care, in contrast to findings in other geographical settings, where a high level of perceived empathy was a major motivator for participants to choose complementary medicine.


Subject(s)
Asian People/psychology , Empathy , Medicine, Chinese Traditional/psychology , Professional-Patient Relations , Social Perception , Adult , Aged , Cross-Sectional Studies , Female , Hong Kong , Humans , Male , Middle Aged , Surveys and Questionnaires , Young Adult
19.
Sci Rep ; 5: 18853, 2015 Dec 21.
Article in English | MEDLINE | ID: mdl-26686267

ABSTRACT

Chinese medicine (CM) is major form of traditional and complementary medicine used by Chinese populations. Evaluation on patients' experience on CM service is essential for improving service quality. This cross sectional study aims (i) to assess how CM clinics with different administrative model differ in terms of quality from patients' perspective; and (ii) to investigate how quality varies with patients' demographic and health characteristics. Five hundred and sixteen patients were sampled from charity and semi-public CM clinics in Hong Kong, and were invited to assess their experience using the Primary Care Assessment Tool (PCAT). Results indicated that overall mean PCAT scoring is satisfactory, achieving 70.7% (91.26/129) of total score. Ratings were lower in areas of "coordination of patient information", "continuity of care", and "range of service provided". Impact of administrative models, including involvement of tax-funded healthcare system and outreach delivery, were minimal after adjusting for patient characteristics. Demographic and health characteristics of patients did not contribute to substantial variations in scoring. To improve patient experience, policy makers should consider strengthening care coordination, continuity and comprehensiveness in CM primary care services. Sharing of electronic records and establishing referral system are potential solutions for linking CM and conventional healthcare services.


Subject(s)
Medicine, Chinese Traditional , Primary Health Care , Adolescent , Adult , Aged , Continuity of Patient Care , Cross-Sectional Studies , Female , Hong Kong , Humans , Male , Middle Aged , Surveys and Questionnaires
20.
Alcohol Alcohol ; 48(6): 720-8, 2013.
Article in English | MEDLINE | ID: mdl-23825091

ABSTRACT

AIM: In an effort to promote Hong Kong as a global wine hub, the government eliminated duties on wine and beer in 2008. The changes in alcohol consumption patterns are examined. METHODS: Anonymous, cross-sectional telephone surveys on a random sample of Chinese male and female residents aged 18-70 were carried out in 2011 (n = 4800) and 2012 (n = 1001). These data were compared with those of a 2006 (n = 9896) baseline survey conducted before the excise tax elimination. RESULTS: Prevalence of those ever drinking alcohol significantly increased from the 2006 baseline level of 66.6% to 82.0% in 2011 and to 85.2% in 2012. Of note, 10.2% of ever drinkers within the 2012 sample reported consuming alcohol for the first time in or after 2008. Younger, more educated or more affluent parts of the population are more likely to be ever drinkers. Unexpectedly, prevalence of binge drinking in the population decreased slightly from the 2006 baseline of 9.0% to 7.1% in 2011 and to 7.3% in 2012. Quantity of alcohol reportedly consumed by individuals did not change, while alcohol abuse and alcohol dependence levels decreased. However, binge drinking prevalence among the unemployed has increased. Logistic regression showed that those with lower educational achievement and the unemployed have higher likelihood of binge drinking. CONCLUSION: The government appears to have achieved its objective of making Hong Kong a world center for alcohol trade. However, the resulting access locally to cheaper alcohol has been associated with an increase in the numbers of those drinking alcohol. There has been a trend toward more adults drinking alcohol and greater risk of harm to some disadvantaged groups.


Subject(s)
Alcohol Drinking/epidemiology , Alcoholic Beverages/economics , Taxes/statistics & numerical data , Adolescent , Adult , Aged , Alcohol Drinking/psychology , Alcoholism/epidemiology , Attitude to Health , Beer , Binge Drinking/epidemiology , Data Interpretation, Statistical , Educational Status , Employment/statistics & numerical data , Female , Health Policy , Hong Kong/epidemiology , Humans , Male , Marital Status , Middle Aged , Prevalence , Socioeconomic Factors , Wine , Young Adult
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