Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer.

BACKGROUND: ESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients. METHODS: ESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study. Samples collected at baseline (n = 51) and at cycle 2 (n = 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses. RESULTS: PFS at six months was 86% (18/21) in patients with an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6-8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3-9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6-33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3-36.9] for ESR1 wildtype patients [p = 0.27]. Patients with ≥ two ESR1 mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different between ESR1 and other mutations. CONCLUSIONS: Presence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.

Efficacy and safety of ultrasound-guided high-intensity focused ultrasound for uterine fibroids: a preliminary experience.

The objective of this prospective cohort study was to evaluate the therapeutic efficacy and safety of ultrasound-guided high-intensity focussed ultrasound (HIFU) in the treatment of uterine fibroids. Twenty premenopausal women with symptomatic fibroids underwent ultrasound-guided HIFU therapy. Twenty-two fibroids with a median baseline volume of 127.0 cm3 (range 18.5-481.2 cm3) were treated. The percentages fibroid volume reduction were 46.9 (range -8.8-73.1) at 1-month, 57.4 (-51.5-95.2) at 3-month, 60.1 (-18.9-97.8) at 6-month and 75.9 (-33.7-99.3) at 12-month, after treatment. The modified Uterine Fibroid Symptom and Quality of Life (UFS-QOL) scores were reduced by 40.7% (0-59.3%) at 3-month, 45.5% (0-70.4%) at 6-month and 44.9% (0-71.4%) at 12-month after treatment. Three patients required subsequent surgical interventions. No significant complications were encountered. Ultrasound-guided HIFU appears to be effective and safe for the treatment of symptomatic uterine fibroids in selected patients. Impact statement What is already known on this subject? Ultrasound-guided high-intensity focussed ultrasound (HIFU) is a relatively new uterine-sparing treatment for fibroids. Most clinical reports are from China, which suggest that this treatment is a safe and effective modality. However, in many other countries, HIFU treatment for fibroids, especially using ultrasound as image guidance, is still considered novel with limited clinical experience. What do the results of this study add? This preliminary report adds to our limited local experience on HIFU and provides reassurance on our continual utilisation of this treatment modality for fibroids. With the increasing demand of uterine-sparing alternatives, experiences shared among different countries are important to make this treatment modality generalisable and universally acceptable. What are the implications of these findings for clinical practice and/or further research?Ultrasound-guided HIFU (USgHIFU) can potential be offered as an alternative treatment modality for women with fibroids.

Risk factors associated with Clostridium difficile infection in kidney transplant recipients.

BACKGROUND: Solid organ transplant recipients are especially vulnerable to Clostridium difficile infection (CDI) due to cumulative risk factors including increased exposure to healthcare settings, persistent immunosuppression, and higher rates of antimicrobial exposure. We aimed to identify risk factors associated with CDI development in kidney transplant recipients including implications of immunosuppressive therapies and acid-suppressing agents. METHODS: This was a single-center, non-interventional, retrospective case-control study of adult subjects between June 1, 2009 and June 30, 2013. During this time, 728 patients underwent kidney transplantation. Overall, 22 developed CDI (cases) and were matched 1:3 with 66 controls. Cases and controls were also matched for induction agent, kidney allograft type (living or deceased), and time from transplant to CDI result (±60 days). RESULTS: The majority of subjects received a deceased donor kidney (77.3%) and basiliximab induction therapy (86.4%). The overall CDI incidence was 3%. Factors independently associated with CDI were average tacrolimus trough (AOR = 1.25, 95% CI = 1.00-1.56, P = .048) and antibiotic exposure for urinary tract infections (UTI) (AOR = 4.17, 95% CI = 1.12-15.54, P = .034). Proton pump inhibitor use was not associated with CDI (OR = 0.81, 95% CI = 0.29-2.29, P = .691). CONCLUSION: Maintaining a clinically appropriate tacrolimus trough and judicious antibiotic use and selection for UTI treatment could potentially reduce CDI in the kidney transplant population.

Impact of antimicrobial stewardship and rapid microarray testing on patients with Gram-negative bacteremia.

A rapid microarray assay, Nanosphere Verigene® Gram-negative blood culture test (BC-GN), detects four Gram-negative species, four Gram-negative genera, and six resistance genes directly from positive blood culture samples, shortening the time from Gram stain to pathogen and resistance-gene identification. The purpose of this study was to determine the impact of the BC-GN paired with an antimicrobial stewardship intervention on antimicrobial and clinical outcomes. Patients with Gram-negative bacteremia were compared before (n = 456) and after (n = 421) BC-GN implementation. The primary objective was to compare time from Gram stain to antimicrobial switch pre- and post-implementation. Time from Gram stain to effective treatment, in-hospital mortality, and hospital length of stay were also compared. The number and type of antimicrobial switches were similar between groups. Median (IQR) time from Gram stain to antimicrobial switch was significantly decreased in the post group, 28.6 (8.6-56.9) h vs 44.1 (18.9-64.6) h, p = 0.004. In patients on ineffective antimicrobial therapy at the time of result, median time to effective therapy was lower in the post group, 8.8 (5.5-18.4) h vs 24.5 (4.9-44.3) h, p = 0.034. Median (IQR) hospital length of stay was also decreased in the post group, 7 (5-15) days vs 9 (4.5-21) days, p = 0.001. The rate of in-hospital mortality was similar between groups, 11.6% (pre) vs 11.4% (post), p = 0.87. Rapid microarray testing on blood cultures combined with active antimicrobial stewardship intervention was associated with decreased time to antimicrobial switch, time to effective therapy, and hospital length of stay.

Remifentanil tolerance and hyperalgesia: short-term gain, long-term pain?

The unique pharmacology of remifentanil makes it a popular intra-operative analgesic. Short-acting opioids like remifentanil have been associated with acute opioid tolerance and/or opioid-induced hyperalgesia, two phenomena which have different mechanisms and are pharmacologically distinct. Clinical studies show heterogeneity of remifentanil infusion regimens, durations of infusion, maintenance of anaesthesia, cumulative dose of remifentanil and pain measures, which makes it difficult to draw conclusions about the incidence of acute tolerance or hyperalgesia. However, it appears that intra-operative remifentanil infusion rates of above 0.25 µg.kg-1 .min-1 are associated with higher postoperative opioid consumption, suggesting tolerance. Infusion rates greater than 0.2 µg.kg-1 .min-1 are characterised by lower mechanical/pressure/cold/pain thresholds, which suggests hyperalgesia. The use of concurrent multimodal analgesia, especially N-methyl-D-aspartate receptor antagonists, may be an effective preventive strategy. The clinical significance and long-term consequences of these entities is still uncertain.

MoCA-assessed cognitive function and excellent outcome after aneurysmal subarachnoid hemorrhage at 1 year.

BACKGROUND AND PURPOSE: After aneurysmal subarachnoid hemorrhage (aSAH), cognitive impairment, even mild and relatively isolated, can be devastating, especially in working-age persons. The Montreal Cognitive Assessment (MoCA) is accepted as a valid screening tool for mild cognitive impairment due to cerebral ischaemia. Whether MoCA is independently associated with excellent outcome [a score of 0 on the modified Rankin Scale (mRS) or 18/18 on the Lawton Instrumental Activities of Daily Living (IADL) scale] 1 year after aSAH was assessed. METHODS: Hong Kong Chinese aSAH patients were assessed prospectively by means of the MoCA, Mini-Mental State Examination (MMSE), mRS and IADL scale at 1 year. This multicenter prospective observational study is registered at ClinicalTrials.gov of the US National Institutes of Health (NCT01038193). RESULTS: In all, 194 patients completed the assessments at 1 year. After adjustment for age, both excellent IADL and mRS outcomes were associated with MoCA (OR 1.2, 95% CI 1.1-1.3, P < 0.001, and OR 1.1, 95% CI 1.0-1.2, P = 0.001, respectively). CONCLUSIONS: MoCA-assessed cognitive function is an important determinant for excellent outcomes after aSAH.

Spatial and temporal variations of coastal microplastic pollution in Hong Kong.

Further to our 2015-16 investigation, this study revealed the repeated presence of microplastics (MPs) in the coastal environment (Deep Bay, Tolo Harbour, Tsing Yi and Victoria Harbour) of Hong Kong from July 2016 to March 2017. The highest level of MPs in coastal surface water (17,182 particles/100 m3) was detected in Tsing Yi. Microplastic abundance in sediments of different sites (59 to 225 plastic particles/kg), however, did not vary significantly. MPs in the size of ≤1 mm were predominated in surface waters (53.3% to 98.6%) and sediments (79.1% to 96.8%). MPs in the shape of pellets and fragments were prevalent in surface waters and sediments respectively. Seasonal pattern of microplastic pollution was consistently observed in Victoria Harbour and Tsing Yi, where the number of MPs was always higher in dry season than in wet season for two consecutive years.

Phacoemulsification versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma with cataracts.

OBJECTIVE: To compare phacoemulsification alone versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma (CACG) with coexisting cataract. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Fifty-one medically uncontrolled CACG eyes with coexisting cataract of 51 patients. INTERVENTION: Recruited patients were randomized into group 1 (phacoemulsification alone) or group 2 (combined phacotrabeculectomy with adjunctive mitomycin C). Postoperatively, patients were reviewed every 3 months for 2 years. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and requirement for topical glaucoma drugs. RESULTS: Twenty-seven CACG eyes were randomized into group 1, and 24 CACG eyes were randomized into group 2. Combined phacotrabeculectomy resulted in lower mean postoperative IOP than phacoemulsification alone at 3 months (14.0 vs. 17.0 mmHg, P = 0.01), 15 months (13.2 vs. 15.4 mmHg, P = 0.02), and 18 months (13.6 vs. 15.9 mmHg, P = 0.01). Combined phacotrabeculectomy resulted in 1.25 fewer topical glaucoma drugs (P<0.001) in the 24-month postoperative period, compared with phacoemulsification alone. Combined surgery was associated with more postoperative complications (P<0.001) and more progression of optic neuropathy (P = 0.03), compared with phacoemulsification alone. CONCLUSIONS: Combined phacotrabeculectomy with adjunctive mitomycin C is more effective than phacoemulsification alone in controlling IOP in medically uncontrolled CACG eyes with coexisting cataract. Combined phacotrabeculectomy is associated with more postoperative complications.

Phacoemulsification versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma with cataract.

OBJECTIVE: To compare phacoemulsification alone versus combined phacotrabeculectomy in medically controlled chronic angle closure glaucoma (CACG) with coexisting cataract. DESIGN: Randomized clinical trial. PARTICIPANTS: Seventy-two medically controlled CACG eyes with coexisting cataract. INTERVENTION: Recruited patients were randomized into group 1 (phacoemulsification alone) or group 2 (combined phacotrabeculectomy with adjunctive mitomycin C). Postoperatively, patients were reviewed every 3 months for 2 years. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and requirement for topical glaucoma drugs. RESULTS: Thirty-five CACG eyes were randomized into group 1, and 37 CACG eyes were randomized into group 2. There were no statistically significant differences (P>0.05) in mean IOP between the 2 treatment groups preoperatively and postoperatively, except at 1 month (P = 0.001) and 3 months (P = 0.008). Combined phacotrabeculectomy with adjunctive mitomycin C resulted in 0.80 less topical glaucoma drugs (P<0.001) in the 24-month postoperative period compared with phacoemulsification alone. The differences in IOP control were, however, not associated with differences in glaucomatous progression. Combined surgery was associated with more postoperative (P<0.001) complications compared with phacoemulsification alone. CONCLUSIONS: Combined phacotrabeculectomy with adjunctive mitomycin C may be marginally more effective than phacoemulsification alone in controlling IOP in medically controlled CACG eyes with coexisting cataract. Combined surgery may be associated with more complications and additional surgery in the postoperative period. Further study is needed to determine whether the marginally better IOP control of combined surgery justifies the potential additional risks of complications and further surgery. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Gastric feed intolerance is not increased in critically ill patients with type II diabetes mellitus.

OBJECTIVE: To examine the occurrence of feed intolerance in critically ill patients with previously diagnosed type II diabetes mellitus (DM) who received prolonged gastric feeding. DESIGN AND SETTING: Retrospective study in a level 3 mixed ICU. PATIENTS: All mechanically ventilated, enterally fed patients (n = 649), with (n = 118) and without type II DM (n = 531) admitted between January 2003 and July 2005. INTERVENTIONS: Patients with at least 72 h of gastric feeding were identified by review of case notes and ICU charts. The proportion that developed feed intolerance was determined. All patient received insulin therapy. RESULTS: The proportion of patients requiring gastric feeding for at least 72 h was similar between patients with and without DM (42%, 50/118, vs. 42%, 222/531). Data from patients with DM were also compared with a group of 50 patients matched for age, sex and APACHE II score, selected from the total non-diabetic group. The occurrence of feed intolerance (DM 52% vs. matched non-DM 50% vs. unselected non-diabetic 58%) and the time taken to develop feed intolerance (DM 62.6 +/- 43.8 h vs. matched non-DM 45.3 +/- 54.6 vs. unselected non-diabetic 50.6 +/- 59.5) were similar amongst the three groups. Feed intolerance was associated with a greater use of morphine/midazolam and vasopressor support, a lower feeding rate and a longer ICU length of stay. CONCLUSIONS: In critically ill patients who require prolonged enteral nutrition, a prior history of DM type II does not appear to be a further risk factor for feed intolerance.

Microplastic pollution in the marine waters and sediments of Hong Kong.

The presence of plastic waste with a diameter of less than 5mm ("microplastics") in marine environments has prompted increasing concern in recent years, both locally and globally. We conducted seasonal surveys of microplastic pollution in the surface waters and sediments from Deep Bay, Tolo Harbor, Tsing Yi, and Victoria Harbor in Hong Kong between June 2015 and March 2016. The average concentrations of microplastics in local coastal waters and sediments respectively ranged from 51 to 27,909particles per 100m3 and 49 to 279particles per kilogram. Microplastics of different shapes (mainly fragments, lines, fibers, and pellets) were identified as polypropylene, low-density polyethylene, high-density polyethylene, a blend of polypropylene and ethylene propylene, and styrene acrylonitrile by means of Attenuated Total Reflectance - Fourier Transform Infrared Spectroscopy. This is the first comprehensive study to assess the spatial and temporal variations of microplastic pollution in Hong Kong coastal regions.

The role of pharmacogenetics in capecitabine efficacy and toxicity.

Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) and approved for treatment of various malignancies. Hereditary genetic variants may affect a drug's pharmacokinetics or pharmacodynamics and account for differences in treatment response and adverse events among patients. In this review we present the current knowledge on genetic variants, commonly single-nucleotide polymorphisms (SNPs), tested in cohorts of cancer patients and possibly useful for prediction of capecitabine efficacy or toxicity. Capecitabine is activated to 5-FU by CES, CDA and TYMP, of which SNPs in CDA and CES2 were found to be associated with efficacy and toxicity. In addition, variants in genes of the 5-FU metabolic pathway, including TYMS, MTHFR and DPYD also influenced capecitabine efficacy and toxicity. In particular, well-known SNPs in TYMS and DPYD as well as putative DPYD SNPs had an association with clinical outcome as well as adverse events. Inconsistent findings may be attributable to factors related to ethnic differences, sample size, study design, study endpoints, dosing schedule and the use of multiple agents. Of the SNPs described in this review, dose reduction of fluoropyrimidines based on the presence of DPYD variants *2A (rs3918290), *13 (rs55886062), -2846A>T (rs67376798) and -1236G>A/HapB3 (rs56038477) has already been recommended. Other variants merit further validation to establish their definite role in explanation of interindividual differences in the outcome of capecitabine-based therapy.

Validation of a base deficit-based trauma prediction model and comparison with TRISS and ASCOT.

BACKGROUND: Base deficit provides a more objective indicator of physiological stress following injury as compared with vital signs constituting the revised trauma score (RTS). We have previously developed a base deficit-based trauma survival prediction model [base deficit and injury severity score model (BISS)], in which RTS was replaced by base deficit as a measurement of physiological imbalance. PURPOSE: To externally validate BISS in a large cohort of trauma patients and to compare its performance with established trauma survival prediction models including trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT). Moreover, we examined whether the predictive accuracy of BISS model could be improved by replacement of injury severity score (ISS) by new injury severity score (NISS) in the BISS model (BNISS). METHODS: In this retrospective, observational study, clinical data of 3737 trauma patients (age ≥15 years) admitted consecutively from 2003 to 2007 were obtained from a prospective trauma registry to calculate BISS, TRISS, and ASCOT models. The models were evaluated in terms of discrimination [area under curve (AUC)] and calibration. RESULTS: The in-hospital mortality rate was 8.1 %. The discriminative performance of BISS to predict survival was similar to that of TRISS and ASCOT [AUCs of 0.883, 95 % confidence interval (CI) 0.865-0.901 for BISS, 0.902, 95 % CI 0.858-0.946 for TRISS and 0.864, 95 % CI 0.816-0.913 for ASCOT]. Calibration tended to be optimistic in all three models. The updated BNISS had an AUC of 0.918 indicating that substitution of ISS with NISS improved model performance. CONCLUSIONS: The BISS model, a base deficit-based trauma model for survival prediction, showed equivalent performance as compared with that of TRISS and ASCOT and may offer a more simplified calculation method and a more objective assessment. Calibration of BISS model was, however, less good than that of other models. Replacing ISS by NISS can considerably improve model accuracy, but further confirmation is needed.

Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration.

Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose.

Genetic polymorphisms and paclitaxel- or docetaxel-induced toxicities: A systematic review.

BACKGROUND: Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite clinical response. OBJECTIVE: Pharmacogenetic studies were reviewed for identification of genetic variants possibly underlying individual susceptibility to adverse events. METHOD: We conducted a systematic search in Pubmed and Embase for pharmacogenetic reports with focus on commonly reported taxane-related gastrointestinal, hematological and neurological toxicities in adult patients with solid tumors. The findings from a total of 51 eligible studies are presented in a comprehensive way. RESULTS: Most frequently investigated single nucleotide polymorphisms (SNPs) were located in genes encoding proteins affecting pharmacokinetics, such as drug transporters and genes of the cytochrome P450 family. Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8. Interest is also dedicated towards genes involved in pharmacodynamics, such as detoxification of reactive oxygen species, DNA repair, neuronal processes and microtubule function. Recent studies include variants in TUBB2A, EPHA5 and EPHA6 for a possible association with neurotoxicity. Variations in methodological approach, sample size, study design, treatment schedule and end-point of toxicity affect consistency of results. CONCLUSION: This review illustrates the complexity to well design pharmacogenetic studies for validation of SNPs that may clarify differences in taxane-induced toxicities among individuals. Novel genes encoding cellular targets of taxanes deserve further analysis by means of robust patient cohorts and definition of objective end-points.

Factors associated with adherence to antiretroviral medication in HIV-infected patients.

The aim of the study was to assess adherence with antiretroviral medication in a sample of HIV patients in Hong Kong and identify predictors of adherence. The study used a cross-sectional correlational design. Adherence behaviour was assessed with the use of self-reports. Other scales assessed knowledge with HIV medication, coping, health locus of control, anxiety, depression and fatigue. A blood sample was also obtained to assess CD4+ counts and viral load. Sociodemographic characteristics and medical information were obtained from the medical records. A high adherence rate was found in this sample of 136 predominantly Chinese patients. There were only 13.7% of the patients being classified as non-adherent. Predictors of adherence included high self-efficacy in terms of being certain that the medication schedule will be followed all or most of the time as directed, low tension-anxiety scores, and low intensity of nausea and vomiting (R2=0.304). An expanded regression model revealed additional factors influencing adherence, including coping variables, pain and numbness in the hands and feet, age, disease stage, internal locus of control, fatigue, family support and taking medication twice daily. This model explained 49% of the variance in adherence. The results suggest that adherence is a multidimensional concept. Every effort should be made to assess in individuals those variables found to affect adherence and alter them whenever possible. Continuous support of patients and individualized medication programmes that will help patients adjust their treatment to their lifestyle are recommended.

A pilot study of the effects of cognitive-behavioral group therapy and peer support/counseling in decreasing psychologic distress and improving quality of life in Chinese patients with symptomatic HIV disease.

Forty-six Chinese patients with symptomatic human immunodeficiency virus (HIV) participated in a comparative study assessing the effectiveness of cognitive-behavioral group therapy (CBT) and peer support/counseling group therapy (PSC) in relation to improving mood and quality of life and decreasing uncertainty in illness as compared to a group receiving routine treatment with no formal psychosocial intervention. The CBT group consisted of 10 subjects, the PSC group of 10 subjects, and the comparison group of 26 subjects. There was a 24% attrition rate. The intervention groups received 12 weekly sessions of therapy over 3 months. Assessment of mood states was carried out before randomization (baseline data), immediately postintervention (3-month time point) and followed-up 3 months later (6-month time point). Assessment of quality of life and uncertainty in illness was carried out before randomization and at the 6-month follow-up time point. Results indicated that the mood of the participants in the CBT group improved in terms of anger, tension-anxiety, depression, confusion, and overall mood. The quality of life in this group was significantly improved compared to the other two groups, as was uncertainty in illness. In the PSC group a worsening of psychologic functioning was observed immediately postintervention, but this picture dramatically improved at the follow-up assessment with improvements of up to 34%. Quality of life also improved over time in this group by almost 5%, but results did not reach statistical significance. This study demonstrated that psychologic interventions could decrease psychologic distress and improve quality of life in symptomatic HIV patients, indicating their use should be incorporated in the management of care of people living with HIV/AIDS.

Endophotocoagulation to retinal pigment epithelium as an adjuvant therapy in the management of retinal detachment caused by a highly myopic macular hole.

Retinal detachment secondary to a highly myopic macular hole remains a particular surgical challenge. Pars plana vitrectomy, endophotocoagulation at the base of a macular hole in conjunction with fluid-gas exchange was performed in 4 consecutive patients with a mean refraction of -13.8D (range, -8D-(-)18D). Mean axial length was 27.5 mm (range, 26.0-29.0 mm). Mild atrophy of the retinal pigment epithelium was present in 3 patients while 1 patient had moderate atrophy. The mean follow-up period was 12 months (range, 6-18 months). The overall primary anatomical success rate was 75%. All 3 eyes with mild retinal pigment epithelium atrophy had retinal reattachment after one operation.

Breast cancer classification by proteomic technologies: current state of knowledge.

Breast cancer is traditionally considered as a heterogeneous disease. Molecular profiling of breast cancer by gene expression studies has provided us an important tool to discriminate a number of subtypes. These breast cancer subtypes have been shown to be associated with clinical outcome and treatment response. In order to elucidate the functional consequences of altered gene expressions related to each breast cancer subtype, proteomic technologies can provide further insight by identifying quantitative differences at the protein level. In recent years, proteomic technologies have matured to an extent that they can provide proteome-wide expressions in different clinical materials. This technology can be applied for the identification of proteins or protein profiles to further refine breast cancer subtypes or for discovery of novel protein biomarkers pointing towards metastatic potential or therapy resistance in a specific subtype. In this review, we summarize the current state of knowledge of proteomic research on molecular breast cancer classification and discuss important aspects of the potential usefulness of proteomics for discovery of breast cancer-associated protein biomarkers in the clinic.