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1.
Ann Oncol ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39147364

ABSTRACT

BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. RESULTS: Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

2.
Intern Med J ; 54(6): 871-881, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38247402

ABSTRACT

BACKGROUND: Endobronchial valve (EBV) insertion for lung volume reduction is a management option for patients with severe emphysema. One-way valves cause lobar deflation and improve lung function, exercise capacity and quality of life. AIMS: To retrospectively analyse and compare the outcomes of the first 57 patients treated with EBVs between 2015 and 2021 at the Royal Adelaide Hospital to international standards. METHODS: Clinical outcomes of forced expiratory volume in 1 s (FEV1), residual volume (RV), treated lobe volume reduction (TLVR) and 6-min walk distance (6MWD) at 3, 6 and 12 months after valve insertion were reviewed against established minimally clinically important differences (MCIDs). Complications and subjective breathlessness measured by Borg scores were also reviewed. RESULTS: Fifty-seven patients were included. At 12 months, 77.2% achieved TLVR. FEV1 improved by 170 mL (95% confidence interval (CI): 100-250, P < 0.001), 80 mL (95% CI: 10-150, P = 0.019) and 40 mL (95% CI: -60 to 130, P 0.66) at 3, 6 and 12 months respectively. RV improved by -610 mL (95% CI: -330 to -900, P < 0.0001) at 3 months, -640 mL (95% CI: -360 to -920, P < 0.0001) at 6 months and -360 mL (95% CI: -60 to -680, P = 0.017) at 12 months. 6MWD improved by 57.34 m (95% CI: 36.23-78.45, P < 0.0001) and 44.93 m (95% CI: 7.19-82.67, P = 0.02) at 3 and 6 months. Borg score improved by -0.53 (95% CI: 0.11 to -1.2, P = 0.11) and -0.49 (95% CI: 0.17 to -1.15, P = 0.16) at 3 and 6 months. Complication rates aligned with international standards with mucous/infection (26.3%) and pneumothorax (17.5%) as the most common. Subgroup analysis signalled improved outcomes in patients with heterogeneous emphysema. CONCLUSION: Our study represents the first publicly funded Australian analysis of EBVs. The results align with international prospective trials demonstrating improved lung function and exercise capacity. Australians with severe emphysema and gas trapping should be referred to a multidisciplinary centre for consideration of EBVs.


Subject(s)
Pneumonectomy , Pulmonary Emphysema , Humans , Male , Female , Pulmonary Emphysema/surgery , Pulmonary Emphysema/physiopathology , Retrospective Studies , Middle Aged , Aged , Australia , Forced Expiratory Volume , Treatment Outcome , Quality of Life , Exercise Tolerance , Walk Test , Bronchoscopy/methods , Severity of Illness Index , Prostheses and Implants
3.
Malays J Pathol ; 45(2): 275-283, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37658537

ABSTRACT

Thyroid carcinoma is uncommon. Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid carcinoma and is a recognised complication of prior exposure to ionizing radiation. Even more uncommon is the synchronous occurrence of PTC with Hodgkin lymphoma (HL) as multiple primary malignancies. We report a 33-year-old mother of three who developed asymptomatic thyroid nodule for four years, and neck swelling for the recent ten months. She denied constitutional symptoms or B symptoms, and thyroid profiles were normal. Initially, metastatic thyroid cancer was suspected based on ultrasound scan findings of enlarged left thyroid gland and enlarged supraclavicular lymph nodes (LN). However, fine needle aspiration examinations of the thyroid nodule were inconclusive, and the supraclavicular LN was suspicious of HL. Computerised tomography scan detected a large mass at the thyroid glands and lymphadenopathies in the mediastinal, hilar, subcarinal and axilla with dimensions up to 6 cm. Left hemi-thyroidectomy with left supraclavicular LN biopsy revealed PTC in the left thyroid lobe measuring 38 x 25 x 18 mm, and the left supraclavicular LN was not definitive of HL. Completion thyroidectomy on the right side, bilateral central neck dissection and excision biopsy of the right supraclavicular LN revealed the presence of HL in the right supraclavicular LN, and both HL and metastatic PTC in right central LN. After multidisciplinary discussions, the patient received chemotherapy at four weeks postoperatively and achieved complete remission. This report highlights the importance of patient-centered approach and multidisciplinary consensus within lack of established guidelines, given rarity of the case.


Subject(s)
Hodgkin Disease , Thyroid Neoplasms , Thyroid Nodule , Female , Humans , Adult , Thyroid Cancer, Papillary , Biopsy, Fine-Needle
4.
Support Care Cancer ; 28(8): 3801-3812, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31832822

ABSTRACT

PURPOSE: To compare febrile neutropenia (FN) incidence and hospitalization among breast cancer patients on docetaxel with no granulocyte colony-stimulating factors (GCSF) primary prophylaxis (PP), 4/5-day PP, or 7-day PP. METHODS: We identified 3916 breast cancer patients using docetaxel-cyclophosphamide (TC), doxorubicin-cyclophosphamide then docetaxel (AC-T), fluorouracil-epirubicin-cyclophosphamide then docetaxel (FEC-T), docetaxel-carboplatin-trastuzumab (TJH), or docetaxel-doxorubicin-cyclophosphamide (TAC) from a hospital pharmacy dispensing database in Hong Kong between 2014 and 2016. Patients were offered GCSF within 5 days since administering docetaxel. Outcomes included FN incidence, time to first hospitalization, hospitalization rate, and duration. RESULTS: In TC regimen, FN incidence (with odds ratio, OR) of patients with no PP, 4/5-day PP, and 7-day PP was 21.69%, 7.95% (OR 0.31, p < 0.001), and 5.33% (OR 0.20, p < 0.001), respectively. In TJH regimen, FN incidence of patients with no PP, 4/5-day PP, and 7-day PP was 38.26%, 8.33% (OR 0.15, p < 0.001), and 8.57% (OR 0.15, p < 0.001), respectively. FN incidence of patients on AC-T regimen with no PP and 4/5-day PP was 20.93% and 6.84%, respectively (OR 0.28, p = 0.005); with FEC-T regimen, the incidence was 9.91% and 4.77%, respectively (OR 0.46, p = 0.035). Only 3.27% FN cases were not hospitalized. Mean (±standard deviation, SD) time to first hospitalization was 8.21 ± 2.44 days. Mean (±SD) duration of hospitalization for patients with no PP, 4/5-day PP, and 7-day PP was 4.66 ± 2.60, 4.37 ± 2.85, and 5.12 ± 2.97 days, respectively. CONCLUSION: GCSF prophylaxis in breast cancer patients on docetaxel could reduce FN incidence and hospitalization. 4/5-day PP demonstrated similar efficacy to 7-day PP with superior saving benefits on healthcare expenditure.


Subject(s)
Antineoplastic Agents/adverse effects , Breast Neoplasms/complications , Docetaxel/adverse effects , Febrile Neutropenia/etiology , Granulocyte Colony-Stimulating Factor/therapeutic use , Breast Neoplasms/drug therapy , Female , Hospitalization , Humans , Middle Aged , Retrospective Studies
5.
Ann Oncol ; 29(6): 1417-1422, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29659668

ABSTRACT

Background: PD-L1 immunohistochemistry (IHC) testing is usually carried out on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay. Methods: A total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as <1%, 1%-49% and ≥50% tumor cells. A total of 100 viable tumor cells were required for adequacy. Results: Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P = 0.04), and 29% of surgical resections (P = 0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS ≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001). Conclusion: Our results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.


Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Squamous Cell/diagnosis , Cytodiagnosis/methods , Immunohistochemistry/methods , Lung Neoplasms/diagnosis , Adenocarcinoma/surgery , Biopsy , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/surgery , Humans , Lung Neoplasms/surgery , Prognosis
7.
J Clin Pharm Ther ; 42(1): 111-114, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27790727

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Human herpesvirus-8 (HHV-8)-positive, HIV-negative multicentric Castleman's disease is a rare lymphoproliferative disorder with no standardized treatment. Concurrent Kaposi's sarcoma, another HHV-8-related disease, is uncommon in HIV-negative patients. The role of antiviral therapy and rituximab in HIV-negative patients is not well established. CASE DESCRIPTION: We report a case of a 5-year, durable remission of HHV-8-positive, HIV-negative comorbid multicentric Castleman's disease and Kaposi's sarcoma treated with long-term valganciclovir, following initial rituximab and liposomal doxorubicin. WHAT IS NEW AND CONCLUSION: Currently, there is no defined role for antiviral therapy in the treatment of HIV-negative HHV-8-positive multicentric Castleman's disease and Kaposi's sarcoma. Ganciclovir followed by indefinite, continuous valganciclovir is thought to have contributed significantly to the durable response in this case.


Subject(s)
Antineoplastic Agents/therapeutic use , Castleman Disease/drug therapy , Doxorubicin/analogs & derivatives , Ganciclovir/analogs & derivatives , Rituximab/therapeutic use , Sarcoma, Kaposi/drug therapy , Antiviral Agents/therapeutic use , Castleman Disease/virology , Doxorubicin/therapeutic use , Ganciclovir/therapeutic use , HIV Infections/drug therapy , Herpesviridae Infections/drug therapy , Humans , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Sarcoma, Kaposi/virology , Valganciclovir
8.
J Clin Microbiol ; 54(2): 428-31, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26659218

ABSTRACT

Testing cerebrospinal fluid (CSF) for the presence of galactomannan (GM) antigen may help in diagnosing cerebral aspergillosis (CA). However, the use of the CSF GM test as a diagnostic test has been little studied. We evaluated its diagnostic performance by comparing the CSF GM optical density indexes (ODI) at different cutoffs in patients with probable and proven CA to those in patients without CA. Patients from 2 tertiary referral hospitals with suspected CA between 2004 and 2014 and in whom CSF GM ODI had been determined were selected. European Organization for Research and Treatment of Cancer/Invasive Infectious Diseases Study Mycoses Group (EORTC/MSG) definitions of invasive aspergillosis and CA were used, but with the exclusion of the test to be validated (i.e., the CSF GM test) as a microbiological EORTC/MSG criterion. The study population consisted of 44 patients (4 with proven CA, 13 with probable CA, and 27 with no CA). Of the 17 patients with CA, 15 had a CSF GM ODI of ≥2.0. Of 27 patients without CA, 26 had a CSF GM ODI of <0.5 and 1 had a CSF GM ODI of 8.2. When a GM CSF ODI cutoff of 1.0 was used, the sensitivity, specificity, and positive and negative predictive values were 88.2%, 96.3%, 93.8%, and 92.9%, respectively. The same results were found when a CSF GM ODI cutoff of 0.5 or 2.0 was used. Testing GM in CSF has a high diagnostic performance for diagnosing CA and may be useful to diagnose or virtually rule out the infection without the need for a cerebral biopsy.


Subject(s)
Antigens, Fungal/cerebrospinal fluid , Antigens, Fungal/immunology , Mannans/cerebrospinal fluid , Mannans/immunology , Neuroaspergillosis/diagnosis , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Galactose/analogs & derivatives , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Young Adult
9.
J Antimicrob Chemother ; 71(12): 3528-3535, 2016 12.
Article in English | MEDLINE | ID: mdl-27530755

ABSTRACT

OBJECTIVES: In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius® multiplex real-time PCR assay identifies clinically relevant Aspergillus species and four resistance-associated mutations (RAMs; TR34/L98H/T289A/Y121F) in the Cyp51A gene. This multicentre study evaluated the diagnostic performance of this assay on bronchoalveolar lavage (BAL) fluid and correlated the presence of RAMs with azole treatment failure and mortality. METHODS: Stored BAL samples from patients with haematological diseases with suspected IA were used. BAL samples that were galactomannan/culture positive were considered positive controls for the presence of Aspergillus. Azole treatment failure and 6 week mortality were compared in patients with and without RAMs that had received ≥5 days of voriconazole monotherapy. RESULTS: Two hundred and one patients each contributed one BAL sample, of which 88 were positive controls and 113 were negative controls. The optimal cycle threshold cut-off value for the Aspergillus species PCR was <38. With this cut-off, the PCR was positive in 74/88 positive controls. The sensitivity, specificity, positive predictive value and negative predictive value were 84%, 80%, 76% and 87%, respectively. 32/74 BAL samples were culture negative. Azole treatment failure was observed in 6/8 patients with a RAM compared with 12/45 patients without RAMs (P = 0.01). Six week mortality was 2.7 times higher in patients with RAMs (50.0% versus 18.6%; P = 0.07). CONCLUSIONS: The AsperGenius® assay had a good diagnostic performance on BAL and differentiated WT from Aspergillus fumigatus with RAMs, including in culture-negative BAL samples. Most importantly, detection of RAMs was associated with azole treatment failure.


Subject(s)
Aspergillus fumigatus/genetics , Bronchoalveolar Lavage Fluid/microbiology , Cytochrome P-450 Enzyme System/genetics , Drug Resistance, Fungal , Fungal Proteins/genetics , Invasive Pulmonary Aspergillosis/diagnosis , Polymerase Chain Reaction/methods , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/isolation & purification , Azoles/pharmacology , Azoles/therapeutic use , Female , Genotyping Techniques/methods , Hematologic Diseases/complications , Humans , Invasive Pulmonary Aspergillosis/microbiology , Male , Middle Aged , Mutation , Retrospective Studies , Survival Analysis , Treatment Failure , Young Adult
10.
Clin Genet ; 87(6): 536-42, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25318681

ABSTRACT

We identified an MSH6 mutation (c.10C>T, p.Gln4*) causing Lynch syndrome (LS) in 11 French Canadian (FC) families from the Canadian province of Quebec. We aimed to investigate the molecular and clinical implications of this mutation among FC carriers and to assess its putative founder origin. We studied 11 probands and 27 family members. Additionally 6433 newborns, 187 colorectal cancer (CRC) cases, 381 endometrial cancer (EC) cases and 179 additional controls, all of them from Quebec, were used. Found in approximately 1 of 400 newborns, the mutation is one of the most common LS mutations described. We have found that this mutation confers a greater risk for EC than for CRC, both in the 11 studied families and in the unselected cases: EC [odds ratio (OR) = 7.5, p < 0.0001] and CRC (OR = 2.2, p = 0.46). Haplotype analyses showed that the mutation arose in a common ancestor, probably around 430-656 years ago, coinciding with the arrival of the first French settlers. Application of the results of this study could significantly improve the molecular testing and clinical management of LS families in Quebec.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA-Binding Proteins/genetics , Ethnicity/genetics , Founder Effect , Mutation , Adolescent , Adult , Aged , Canada/epidemiology , Child , Child, Preschool , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/genetics , Family , Female , Genetic Association Studies , Genetic Predisposition to Disease , Haplotypes , Heterozygote , Humans , Loss of Heterozygosity , Male , Middle Aged , Quebec , Risk , Young Adult
11.
Eur J Gynaecol Oncol ; 36(6): 750-4, 2015.
Article in English | MEDLINE | ID: mdl-26775367

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. Extragastrointestinal stromal tumors (EGISTs) are extremely rare tumors that show the features of GISTs outside the GI tract. Their most common locations are the omentum, mesentery, and retroperitoneum. The authors report herein a case of a 54-year-old woman with GIST in rectovaginal septum. The patient underwent low anterior resection of the rectum, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial resection of the posterior vagina. She received adjuvant therapy with an oral tyrosine-kinase inhibitor. She is presently healthy without any evidence of recurrence at 26 months after surgery. For GISTs arising in the rectovaginal septum, it is difficult to ascertain whether the tumor origin site is the rectum, rectovaginal septum, or vagina. In other words, it is difficult to classify these tumors as GISTs or EGISTs. More consideration for the exact origin should be given to the GIST in the rectovaginal septum for the precise diagnosis (GIST or EGIST) and risk classification in future.


Subject(s)
Gastrointestinal Stromal Tumors/therapy , Rectal Neoplasms/therapy , Vaginal Neoplasms/therapy , Female , Gastrointestinal Stromal Tumors/diagnosis , Humans , Middle Aged , Prognosis , Rectal Neoplasms/diagnosis , Vaginal Neoplasms/diagnosis
12.
Eur J Gynaecol Oncol ; 36(5): 560-3, 2015.
Article in English | MEDLINE | ID: mdl-26513883

ABSTRACT

OBJECTIVE: Ovarian cancer is the seventh most common cancer in women worldwide, with nearly a quarter of a million women diagnosed every year. The serum tumor markers cancer antigens CA 125, CA 19-9, and carcinoembryonic antigen (CEA) are potentially of clinical value for the diagnosis of ovarian cancer. A diagnostic tool that is noninvasive, simple to perform, and specific is needed to predict primary ovarian cancer. The purpose of this study was to evaluate the diagnostic sensivitity and specificity of vaginal-washing tumor markers CA 125, CA 19-9, and CEA for diagnosis of primary ovarian cancer. MATERIALS AND METHODS: In the current prospective study, 30 patients with advanced primary ovarian cancer and 30 patients with benign ovarian cysts were enrolled. The vaginal-washing fluid samples were obtained the day before surgery and were immediately centrifuged and stored at -80 degrees C until analysis. Measurements of CA 125, CA 19-9, and CEA were determined using fully-automated chemiluminescent microparticle immunoassays. RESULTS: The vaginal fluid concentrations of CA 125, CA 19-9, and CEA in patients with primary ovarian carcinoma were significantly higher (p < 0.001) compared to those in patients with benign adnexal masses (p < 0.001). In the ROC curve analysis, the optimal cut-off values for the detection of primary ovarian cancer were >295 for CA 125 (p < 0.001), > 101 for CA 19-9 (p < 0.001), and >135 for CEA (p < 0.001). CONCLUSION: Vaginal-washing tumor markers CA 125, CA 19-9, and CEA are simple, noninvasive, and reliable diagnostic tests for the detection of primary ovarian cancer.


Subject(s)
Biomarkers, Tumor/analysis , Ovarian Neoplasms/diagnosis , Vagina/chemistry , CA-125 Antigen/analysis , CA-19-9 Antigen/analysis , Carcinoembryonic Antigen/analysis , Female , Humans , Luminescent Measurements , Middle Aged , Prospective Studies
13.
Curr Oncol ; 22(5): 317-25, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26628864

ABSTRACT

BACKGROUND: Sarcomas in adults can be associated with hereditary cancer syndromes characterized by early-onset predisposition to numerous types of cancer. Because of variability in familial presentation and the largely unexplained genetic basis of sarcomas, ascertainment of patients for whom a genetics evaluation is most indicated poses challenges. We assessed the utility of a Sarcoma Clinic Genetic Screening (scgs) questionnaire in facilitating that task. METHODS: Between 2008 and 2012, 169 patients (median age: 53 years; range: 17-88 years) completed a self-administered scgs questionnaire. A retrospective chart review was completed for all respondents, and descriptive statistics were reported. Probands were divided into two groups depending on whether they did or did not report a family history of Li-Fraumeni syndrome-type cancers. RESULTS: A family history of cancer (as far as 3rd-degree relatives) was reported in 113 of 163 sarcoma patients (69%). Eeles Li-Fraumeni-like (lfl) criteria were fulfilled in 46 probands (28%), Chompret lfl in 21 (13%), Birch lfl in 8 (5%), and classic Li-Fraumeni in none. In the 10 probands tested for TP53 mutations, 1 pathogenic mutation was found. Further investigation of selected families led to the discovery of germline mutations in MLH1, MSH2, and APC genes in 3 individuals. CONCLUSIONS: The scgs questionnaire was useful for ascertaining probands with sarcoma who could benefit from a genetic assessment. The tool allowed us to identify high-risk families fitting the criteria for lfl and, surprisingly, other hereditary cancer syndromes. Similar questionnaires could be used in other cancer-specific clinics to increase awareness of the genetic component of these cancers.

14.
J Hosp Infect ; 146: 31-36, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38286238

ABSTRACT

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast which can cause severe infection in hospitalized patients. Since its first detection in 2009, C. auris has spread globally. The control and elimination of this pathogen in a hospital setting is particularly challenging because of its ability to form biofilms, allowing for long-term patient colonization and persistence in the environment. Identification of C. auris from cultures is difficult due to the morphologic similarities to other yeasts, its slow growth, and the low culture sensitivity when using standard agars and temperatures. AIM: We have developed a screening protocol for C. auris colonization using an in-house-developed polymerase chain reaction (PCR), combined with confirmatory culture in optimized conditions. METHODS: C. auris-specific primers and probe were developed, targeting the internal transcribed spacer (ITS) region, and specificity was confirmed in silico using the BLAST tool. The PCR was validated using a panel of 12 C. auris isolates and 103 isolates from 22 other Candida species and was shown to be 100% accurate. The limit of detection of the assay was determined at approximately four cells per PCR. FINDINGS: C. auris screening was introduced on February 15th, 2023, and was used for patients who had been admitted to a healthcare facility abroad in the two months prior to admission to our hospital. The screening protocol included swabs from nose, throat, rectum, axilla, and groin. In the first eight months, 199 patients were screened and seven were found positive (4%). CONCLUSION: Our proposed screening protocol may contribute to control C. auris in hospitals.


Subject(s)
Candidiasis , Humans , Candidiasis/diagnosis , Candida auris , Candida/genetics , Yeasts , Antifungal Agents , Microbial Sensitivity Tests
15.
Eur J Gynaecol Oncol ; 34(2): 128-31, 2013.
Article in English | MEDLINE | ID: mdl-23781582

ABSTRACT

PURPOSE: To evaluate the correlation between immunohistochemical expression of synuclein-gamma, glucose transporter-1, and survival outcomes in endometrioid endometrial carcinoma. MATERIALS AND METHODS: A tissue microarray was constructed using formalinfixed, paraffin-embedded tissue that included 23 early and 18 advanced cases. The intensity and area of the immunohistochemical reactions were evaluated using the semi-quantitative scoring system. RESULTS: Synuclein-y expression was higher in the advanced stage, although it was not statistically significant (p = 0.51). Glucose transporter-1 was overexpressed in the advanced stage (p = 0.01). Synuclein-gamma (score = 0 vs > 0) and glucose transporter-1 (score < or = 7 vs > 7) did not show any differences in overall survival (p = 0.54, p = 0.48) and disease-free survival (p = 0.61, p = 0.14). CONCLUSION: In this study the expression of synuclein-y and glucose transporter-1 were not considered to be a prognostic factor and were not related with survival outcomes in endometrioid endometrial carcinoma.


Subject(s)
Carcinoma, Endometrioid/mortality , Endometrial Neoplasms/mortality , Glucose Transporter Type 1/analysis , Neoplasm Proteins/analysis , gamma-Synuclein/analysis , Adult , Aged , Carcinoma, Endometrioid/chemistry , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/chemistry , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasm Staging , Tissue Array Analysis
16.
Br J Cancer ; 107(11): 1864-8, 2012 Nov 20.
Article in English | MEDLINE | ID: mdl-23093229

ABSTRACT

BACKGROUND: There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N. METHODS: Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis. RESULTS: The EGFR was present in over 90% of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19. CONCLUSION: The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.


Subject(s)
Anus Neoplasms/genetics , Carcinoma, Squamous Cell/genetics , Chemoradiotherapy , ErbB Receptors/genetics , Mutation , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adult , Aged , Aged, 80 and over , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , ErbB Receptors/analysis , ErbB Receptors/antagonists & inhibitors , Exons , Female , Head and Neck Neoplasms , Humans , Immunohistochemistry , Male , Middle Aged , Proto-Oncogene Proteins p21(ras) , Squamous Cell Carcinoma of Head and Neck
18.
Clin Genet ; 79(6): 512-22, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21155762

ABSTRACT

Founder mutations are an important cause of Lynch syndrome and facilitate genetic testing in specific ethnic populations. Two putative founder mutations in MSH6 were analyzed in 2685 colorectal cancer (CRC) cases, 337 endometrial cancer (EnCa) cases and 3310 healthy controls of Ashkenazi Jewish (AJ) descent from population-based and hospital-based case­control studies in Israel, Canada and the United States. The carriers were haplotyped and the age of the mutations was estimated. MSH6*c.3984_3987dupGTCA was found in 8/2685 CRC cases, 2/337 EnCa cases, and 1/3310 controls, consistent with a high risk of CRC (odds ratio (OR) = 9.9, 95% confidence interval (CI) = 1.2­78.9, p = 0.0079) and a very high risk of EnCa (OR = 19.6, 95% CI = 1.8­217.2, p = 0.0006). MSH6*c.3959_3962delCAAG was identified in 3/2685 CRC cases, 2/337 EnCa cases and no controls. Each mutation was observed on separate conserved haplotypes. MSH6*c.3984_3987dupGTCA and MSH6*c.3959_3962delCAAG probably arose around 585 CE and 685 CE, respectively. No carriers were identified in Sephardi Jews (450 cases and 490 controls). Truncating mutations MSH6*c.3984_3987dupGTCA and MSH6*c.3959_3962delCAAG cause Lynch syndrome and are founder mutations in Ashkenazi Jews. Together with other AJ founder mutations, they contribute substantially to the incidence of CRC and EnCa and are important tools for the early diagnosis and appropriate management of AJ Lynch syndrome patients.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA-Binding Proteins/genetics , Founder Effect , INDEL Mutation , Jews , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Colorectal Neoplasms, Hereditary Nonpolyposis/ethnology , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/genetics , Female , Genetic Association Studies , Genetic Markers , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Young Adult
19.
Community Dent Health ; 28(3): 243-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21916362

ABSTRACT

UNLABELLED: In New South Wales (NSW), Australia, the responsibility to implement water fluoridation rests with local government Councils, partly accounting for the hindrance in its statewide implementation. Since 2003, the NSW Health Department has been actively promoting water fluoridation to the remaining unfluoridated rural communities. OBJECTIVES: To describe the community education and consultation strategies which led to the implementation of fluoridation in two rural NSW towns. METHODS: In February 2005, the Mid-Western Regional Council and the NSW Health Department undertook a comprehensive community education process followed by a consultation process. The education process included the organization of public forums; distribution of fluoridation information packs; building rapport with the local media; and the use of local disease and treatment data to demonstrate oral health disparities with neighbouring fluoridated towns. The consultation process to determine support for fluoridation included seeking written submissions from the community and conducting interviews on a random sample of households by an independent research organization. RESULTS: A total of 502 (N = 1,012) interviews to determine support for fluoridation were completed, achieving a response rate of 49.6%. 54% of respondents wanted their water supplies fluoridated, 25% did not and the remaining 21% were unsure. In June 2005, the Mid-Western Regional Council resolved to implement water fluoridation and fluoride was added to the towns' water supplies in November 2007. CONCLUSIONS: This case study demonstrates that it is possible to garner community support for water fluoridation with the use of a multifaceted approach in educating and consulting communities and stakeholders.


Subject(s)
Community Networks , Fluoridation , Health Education, Dental , Health Promotion/organization & administration , Organizational Case Studies , Community Participation , Humans , Information Dissemination , Interviews as Topic , Local Government , New South Wales
20.
Sci Rep ; 11(1): 12769, 2021 06 17.
Article in English | MEDLINE | ID: mdl-34140571

ABSTRACT

Reputed to be the driest desert in the world, the Atacama Desert in the Central Andes of Northern Chile is an extreme environment with high UV radiation, wide temperature variation, and minimum precipitation. Scarce lagoons associated with salt flats (salars) in this desert are the surface expression of shallow groundwater; these ponds serve as refugia for life and often host microbial communities associated with evaporitic mineral deposition. Results based on multidisciplinary field campaigns and associated laboratory examination of samples collected from the Puquios of the Salar de Llamara in the Atacama Desert during austral summer provide unprecedented detail regarding the spatial heterogeneity of physical, chemical, and biological characteristics of these salar environments. Four main lagoons ('Puquios') and more than 400 smaller ponds occur within an area less than 5 km2, and are characterized by high variability in electrical conductivity, benthic and planktonic biota, microbiota, lagoon bottom type, and style of mineral deposition. Results suggest that electrical conductivity is a driving force of system heterogeneity. Such spatial heterogeneity within the Puquios is likely to be expanded with temporal observations incorporating expected seasonal changes in electrical conductivity. The complexity of these Andean ecosystems may be key to their ability to persist in extreme environments at the edge of habitability.

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