ABSTRACT
BACKGROUND: Sarcoidosis is a rare, multisystem, inflammatory condition associated with the formation of granulomas. Diagnosis can be challenging because of non-specific symptoms complicating epidemiological investigations of its aetiology. Despite research efforts, a review of the current state of the evidence is needed. AIMS: To assess the evidence for an association between occupational exposures and the development of sarcoidosis. To determine if workers in any occupation are at a greater risk of developing sarcoidosis. METHODS: This rapid review follows the methodology suggested by the World Health Organization. Two electronic databases were systematically searched until April 2022. The methodological quality of the studies was critically appraised, and a best-evidence approach was used to synthesize the results. RESULTS: Titles and abstracts of 2916 articles were screened, with 67 full-text articles reviewed for eligibility. Among the 13 studies eligible for this review, none were of high quality (i.e. low risk of bias). Six studies exploring the association between sarcoidosis and a range of occupations and exposures, and one previous systematic review were of low quality reporting inconsistent findings. Six studies examined the risk of sarcoidosis associated with occupational silica exposure, two of which were of acceptable quality. Overall, the study methodologies and results were inadequate to support causal relationships. CONCLUSIONS: There is limited evidence of acceptable methodological quality to assess the risk of sarcoidosis associated with occupational exposures. There is a growing body of research examining occupational exposure to silica and sarcoidosis. Additional high-quality confirmatory research is needed.
Subject(s)
Occupational Exposure , Sarcoidosis , Humans , Occupational Exposure/adverse effects , Sarcoidosis/etiology , Sarcoidosis/epidemiology , Occupational Diseases/epidemiology , Occupational Diseases/etiologyABSTRACT
BACKGROUND: Combining immune-checkpoint inhibitors with chemotherapy yielded an increased response rates in patients with metastatic triple-negative breast cancer (TNBC). Therefore, we evaluated the addition of durvalumab to standard neoadjuvant chemotherapy (NACT) in primary TNBC. PATIENTS AND METHODS: GeparNuevo is a randomised phase II double-blind placebo-controlled study randomising patients with TNBC to durvalumab or placebo given every 4 weeks in addition to nab-paclitaxel followed by standard EC. In the window-phase durvalumab/placebo alone was given 2 weeks before start of nab-paclitaxel. Randomisation was stratified by stromal tumour-infiltrating lymphocyte (sTILs). Patients with primary cT1b-cT4a-d disease, centrally confirmed TNBC and sTILs were included. Primary objective was pathological complete response (pCR) (ypT0 ypN0). RESULTS: A total of 174 patients were randomised, 117 participated in the window-phase. Median age was 49.5 years (range 23-76); 47 patients (27%) were younger than 40 years; 113 (65%) had stage ≥IIA disease, 25 (14%) high sTILs, 138 of 158 (87%) were PD-L1-positive. pCR rate with durvalumab was 53.4% (95% CI 42.5% to 61.4%) versus placebo 44.2% (95% CI 33.5% to 55.3%; unadjusted continuity corrected χ2P = 0.287), corresponding to OR = 1.45 (95% CI 0.80-2.63, unadjusted Wald P = 0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% versus 41.4%, OR = 2.22, 95% CI 1.06-4.64, P = 0.035; interaction P = 0.048). In both arms, significantly increased pCR (P < 0.01) were observed with higher sTILs. There was a trend for increased pCR rates in PD-L1-positive tumours, which was significant for PD-L1-tumour cell in durvalumab (P = 0.045) and for PD-L1-immune cell in placebo arm (P = 0.040). The most common immune-related adverse events were thyroid dysfunction any grade in 47%. CONCLUSIONS: Our results suggest that the addition of durvalumab to anthracycline-/taxane-based NACT increases pCR rate particularly in patients treated with durvalumab alone before start of chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02685059.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/analysis , Neoadjuvant Therapy/methods , Triple Negative Breast Neoplasms/therapy , Adult , Aged , Albumins/administration & dosage , Albumins/adverse effects , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/analysis , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Breast/pathology , Breast/surgery , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Double-Blind Method , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Humans , Hyperthyroidism/chemically induced , Hyperthyroidism/epidemiology , Hypothyroidism/chemically induced , Hypothyroidism/epidemiology , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Mastectomy , Middle Aged , Neoadjuvant Therapy/adverse effects , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Placebos/administration & dosage , Placebos/adverse effects , Prospective Studies , Receptor, ErbB-2/analysis , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Thyroid Gland/drug effects , Treatment Outcome , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/pathology , Young AdultABSTRACT
BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.
ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.
Subject(s)
Breast Neoplasms/surgery , Mammaplasty/methods , Mastectomy/methods , Breast Implants , Breast Neoplasms/radiotherapy , Clinical Decision-Making , Consensus , Evidence-Based Medicine , Female , Humans , Time FactorsABSTRACT
Background: In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods: Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results: A significantly better DFS (hazard ratio 0.56, 95% CI 0.34-0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26-5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17-1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23-1.04, P = 0.059). Conclusions: The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Recombinational DNA Repair/genetics , Triple Negative Breast Neoplasms/therapy , Anthracyclines/pharmacology , Anthracyclines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast/pathology , Breast/surgery , Bridged-Ring Compounds/pharmacology , Bridged-Ring Compounds/therapeutic use , Carboplatin/pharmacology , Disease-Free Survival , Doxorubicin/analogs & derivatives , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Drug Resistance, Neoplasm/genetics , Female , Follow-Up Studies , Humans , Mastectomy , Middle Aged , Mutation , Neoadjuvant Therapy/methods , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Polyethylene Glycols/pharmacology , Polyethylene Glycols/therapeutic use , Prognosis , Survival Analysis , Taxoids/pharmacology , Taxoids/therapeutic use , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathologyABSTRACT
Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.
Subject(s)
Breast Neoplasms/drug therapy , Letrozole/administration & dosage , Medication Adherence , Aged , Antineoplastic Agents/administration & dosage , Aromatase Inhibitors/administration & dosage , Breast Neoplasms/pathology , Breast Neoplasms/psychology , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Postmenopause , Prospective StudiesABSTRACT
BACKGROUND: The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracycline-taxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years. RESULTS: Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low. CONCLUSIONS: Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Breast Neoplasms/mortality , Capecitabine , Carcinoma, Ductal, Breast/mortality , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Neoadjuvant Therapy , Proportional Hazards Models , Taxoids/administration & dosage , Trastuzumab , Treatment OutcomeABSTRACT
BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Breast Neoplasms/drug therapy , Sirolimus/analogs & derivatives , Adult , Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Drug Therapy, Combination , Everolimus , Female , Humans , Middle Aged , Receptor, ErbB-2/metabolism , Sirolimus/administration & dosage , Sirolimus/therapeutic use , Survival AnalysisABSTRACT
BACKGROUND: We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC). PATIENTS AND METHODS: A total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0-3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded. RESULTS: Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice. CONCLUSION: RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/prevention & control , Antineoplastic Agents, Hormonal/economics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Cost-Benefit Analysis , Decision Making , Female , Humans , Lymphatic Metastasis , Markov Chains , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Staging , Patient Care Planning , Prospective Studies , Receptors, Estrogen/metabolism , Surveys and QuestionnairesABSTRACT
BACKGROUND: We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m(2); q3w) followed by four cycles docetaxel (100 mg/m(2); q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. RESULTS: TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. CONCLUSIONS: The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ductal, Breast/drug therapy , Triple Negative Breast Neoplasms/drug therapy , Adult , Aged , Anthracyclines/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/pathology , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Epirubicin/administration & dosage , Everolimus , Female , Humans , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Paclitaxel/administration & dosage , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , Treatment Outcome , Triple Negative Breast Neoplasms/diagnostic imaging , Triple Negative Breast Neoplasms/pathology , Tumor Burden/drug effects , Ultrasonography , Young AdultABSTRACT
BACKGROUND: Approximately 0.5-2% of upper respiratory tract infections in adults and 6-13% of viral upper respiratory tract infections in children are complicated by acute sinusitis. This study was aimed to evaluate the coadministration effect of fluticasone nasal spray (FNS) with amoxicillin for AS in children. MATERIALS AND METHODS: One hundred children 2 to 14 years of age with acute sinusitis referred to Shahid Mohammadi Pediatric Hospital in Bandar Abbas were randomly allocated into two equal intervention and control groups to receive amoxicillin with fluticasone nasal spray one puff twice daily for 14 days and amoxicillin 80 to 100 mg/kg/ day for 14 days respectively. RESULTS: Twenty one (42%) of children in intervention group were cured completely and 2 (4%) children in control group had complete recovery (p < 0.001). Symptom severity score was 22.98 ± 2.95 before treatment that reduced to 13.26 ± 3.20 after treatment (p < 0.001). CONCLUSIONS: Use of fluticasone can reduce the severity of symptoms of sinusitis in children.
Subject(s)
Amoxicillin/administration & dosage , Androstadienes/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Sinusitis/drug therapy , Acute Disease , Administration, Intranasal , Adolescent , Child , Child, Preschool , Female , Fluticasone , Humans , Male , Single-Blind MethodABSTRACT
BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.
Subject(s)
Antineoplastic Agents/adverse effects , Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Letrozole/adverse effects , Medication Adherence , Postmenopause , Aged , Breast Neoplasms/pathology , Female , Germany , Humans , Middle Aged , Prospective Studies , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Symptomatic candiduria often occurs in patients with indwelling bladder catheters or immunocompromised host. Isolation of Candida in urine in high-risk patients should primarily be considered as a marker for candidemia. Hematological and genitourinary malignancies are one of the main risk factors associated with Candida urinary tract infections (CUTI). Fluconazole is a choice for initial treatment of CUTI, but it is fluctuate depending on the patient's condition including renal failure, site of urinary infection and Candida species. Poor glomerular filtration is the main disadvantage echinocandins resulting in very low urinary concentrations. Therefore, echinocandins have prohibited their use in CUTI. Up to now, there are only 10 cases reported in the literatures with highly effective echinocandins in CUTI because of high concentrations in the tissue are needed to control invasive fungal disease. Herein, we report a candiduria followed by renal candidiasis caused by Candida albicans in a 6-year-old Iranian male with a history of Wilms tumor in left kidney. Direct examination of urine specimen revealed an infection due to budding yeast cells with numerous pseudohyphae and growths of C. albicans was reconfirmed by sequencing of ITS rDNA region. MICs in increasing order were as follows: caspofungin (0.016µg/ml), voriconazole (0.125µg/ml), amphotericin B (0.25µg/ml), itraconazole (0.5µg/ml) and fluconazole (2µg/ml). It seems that successful treatment with caspofungin owes achieved high renal tissue concentrations that are unrelated to glomerular filtration. In conclusion, predisposing factors for better outcome are more important than treatment of CUTI, therefore, management of UTI is essential for critically patients.
Subject(s)
Candidiasis/drug therapy , Echinocandins/therapeutic use , Kidney Neoplasms/drug therapy , Lipopeptides/therapeutic use , Urinary Tract Infections/drug therapy , Wilms Tumor/drug therapy , Antifungal Agents/therapeutic use , Candida/isolation & purification , Candidiasis/complications , Candidiasis/urine , Caspofungin , Child , Humans , Iran , Kidney Neoplasms/complications , Kidney Neoplasms/microbiology , Male , Treatment Outcome , Urinary Tract Infections/complications , Urinary Tract Infections/microbiology , Wilms Tumor/complications , Wilms Tumor/microbiologyABSTRACT
Large-scale genotyping studies have identified over 70 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge regarding genetic risk factors associated with the prognosis is limited. The aim of this study was therefore to investigate the prognostic effect of nine known breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant, randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1) , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) , rs6504950 (COX11) . Cox proportional hazards models were used to test the SNPs' association with overall survival (OS) and progression-free survival (PFS). Additional analyses were carried out for molecular subgroups. rs3817198 in LSP1 (lymphocyte-specific protein 1) was the only SNP that significantly influenced OS (p = 0.01) and PFS (p < 0.01) in the likelihood ratio test comparing the genetic survival model with the clinical survival model. In the molecular subgroups, triple-negative patients with two minor alleles in rs3817198 had a much better prognosis relative to OS (adjusted HR 0.03; 95% CI 0.002â-â0.279) and PFS (HR 0.09; 95% CI 0.02â-â0.36) than patients with the common alleles. The same effect on PFS was shown for patients with luminal A tumors (HR 0.19; 95% CI 0.05â-â0.84), whereas patients with luminal B tumors had a poorer PFS with two minor alleles (HR 2.13; 95% CI 1.02â-â4.40). The variant in rs3817198 has a prognostic effect particularly in the subgroup of patients with triple-negative BC, suggesting a possible link with immunomodulation and BC.
ABSTRACT
Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5â%, p < 0.001), as was leukopenia (64.1 vs. 58.5â%, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8â%, FEC-D: 36.3â%, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3â%, SGOT: 2â%), whereas neuropathy (1.2â%), arthralgia (1.6â%) and bone pain (2.6â%) were more common using FEC-D. Dose reductions > 20â% (4 vs. 2.4â%) and postponement of treatment cycles (0.9 vs. 0.4â%) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.
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BACKGROUND: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. PATIENTS AND METHODS: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. RESULTS: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. CONCLUSION: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/prevention & control , Bone Neoplasms/secondary , Breast Neoplasms/drug therapy , Diphosphonates/therapeutic use , Imidazoles/therapeutic use , Adult , Aged , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm, Residual , Zoledronic AcidABSTRACT
INTRODUCTION: Since kidney transplantation is the therapy of choice for children with end-stage renal disease (ESRD), we investigated the effects of mycophenolate mofetil (MMF) in pediatric renal transplantation. METHODS AND SUBJECTS: Two hundred sixteen children received renal transplants between 1985 and 2003: 100 patients received MMF with cyclosporine and prednisolone (cases), and 116 patients, azathioprine with cyclosporine and prednisolone (controls). RESULTS: The MMF group (100 patients) showed better graft survival and function than the AZA group (116 patients). Patients who received MMF immediately after transplantation experienced less graft loss and acute rejection episodes in the first 3 months after transplantation (P < .05). Patients who received MMF at the time of diagnosis of chronic rejection had stable renal function and remarkably better graft survival than those with chronic rejection who received AZA instead of MMF (P < .05). CONCLUSION: This study suggests that MMF may stop persistent graft dysfunction in chronic rejection, improving graft survival in the short and long terms posttransplantation.
Subject(s)
Graft Survival/immunology , Kidney Transplantation/physiology , Mycophenolic Acid/analogs & derivatives , Azathioprine/therapeutic use , Child , Chronic Disease , Graft Rejection/classification , Graft Rejection/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Mycophenolic Acid/therapeutic use , Retrospective StudiesABSTRACT
INTRODUCTION: Patients with end-stage renal disease and lower urinary tract abnormality are often considered high risk for renal transplantation. METHODS AND SUBJECTS: To examine the degree of risk, we studied patients who received renal transplants between 1985 and 2003. Forty eight patients had congenital lower urinary tract anomalies and 168 patients comprised a control group without these anomalies. RESULTS: Mean age and distribution of sex were not significantly different between the case and the control group. Among patients with anomalies, 8% had delayed graft function; 75%, acute rejection; and 39.5%, chronic rejection. Among the controls 2.3% had delayed graft function; 59%, acute rejection; and 35%, chronic rejection. None of these differences was significant. Mean survival time was 6 years in affected patients and 7.3 years in the control group (P = .7). Among patients with anomalies the rate of graft survival in the first year after transplantation was 90%; and those in the third, fifth, and seventh years, 76%, 65%, and 40%, respectively. For the controls, the graft survivals were 88% at 1 year; 73% at 3 years; 70% at 5 years; and 49% at 7 years after transplantation. CONCLUSION: This study showed that a history of lower urinary tract anomalies had no effect on graft function. Graft survival was not different among these patients compared with patients free of these anomalies.
Subject(s)
Kidney Transplantation/physiology , Urinary Tract/abnormalities , Acute Disease , Child , Chronic Disease , Creatinine/blood , Female , Graft Rejection/epidemiology , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Retrospective Studies , Treatment OutcomeABSTRACT
Aim: Breast reconstruction has become increasingly important for the body image of women with breast cancer. We conducted a study to investigate how patient characteristics correlate with surgical outcome after breast reconstruction with implant after mastectomy and to identify risk factors which could facilitate patient selection for reconstruction. Patients and Methods: For this case cohort analysis (n = 257 patients with 318 heterologous reconstructions), we analyzed BMI, smoking, pre-existing disease, chemotherapy and radiotherapy, one-stage/two-stage reconstruction, immediate/delayed reconstruction, antibiotic therapy and complications, partner interaction and adherence to the decision for reconstruction using a customized questionnaire. Results: 257 patients with 318 implant reconstructions (196 unilateral, 61 bilateral) were eligible for inclusion in the study. Median follow-up time was 3.1 years (range: 1 month to 10 years). Response rate to the questionnaire was 71.8â%. Median age was 49 years (range 24-79 years), median BMI was 22.44 (range 16.33-40.09). A BMI > 30 was inversely correlated with positive self-image (p = 0.004), and implant loss/rotation was more frequent in this group (p < 0.05). Smoking > 10 cigarettes/day had a negative impact on surgical outcome. A positive self-image had a positive impact on partner interaction (p < 0.001) and was correlated with a lower perception of pain. Aesthetic results did not vary with age (p = 0.054). Titanized polypropylene meshes were used to protect against implant rotation (p = 0.034). Rates of capsular fibrosis were low in our cohort (< 10â%), and implant loss rate was less than 2â%. Conclusions: This study offers a differentiated approach for the pre-surgical counselling of patients and shows that patients up to 80 years of age are highly satisfied with implant reconstruction. A high BMI and smoking > 10 cigarettes/day are unfavorable preconditions for implant reconstruction. The use of prophylactic antibiotics was confirmed as beneficial for surgical outcome. A positive self-image after reconstruction strongly influences partner interaction.
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INTRODUCTION: A paradigm shift in breast cancer was introduced by Sørlie's concept of intrinsic subtypes [1]. We validated this concept - which was originally based on 84 individuals - in a large cohort study of 1035 patients with oncoplastic surgery and analyzed if early and late recurrences are linked to a specific intrinsic tumor subtype or resection margins. MATERIALS AND METHODS: 1035 patients with oncoplastic surgery (2004-2009) were analyzed with regard to treatment characteristics and patterns of early (<5 years) and late recurrence (>5 years) and survival related to the intrinsic subtypes. Data was retrieved from patient's charts, customized patients questionnaires and cancer registries. RESULTS: 944 patients with primary, unilateral breast cancer, median age 58 years, were eligible for analysis. At a median FU of 5.2 years, LRR was 4.0%, 5-year-OS 94.5% and DFS 90.9%. Intrinsic subtypes, but not T-size, nodal-status, resections margins nor histopathology, governed local control and survival. There was no signal for prevelance of unclear margins in any of intrinsic subgroups and no preference of any oncoplastic technique attributed to them. TNBC and Her2 non-luminal breast cancer had highest recurrence and lowest survival rates. Although sentinel involvement (SLN+) was prevailing in the Luminal-B-Her 2 negative subtype at 34.3%, this did not translate into a higher axillary dissection rate. CONCLUSION: This study confirmed the intrinsic subtype concept on a large clinical basis and describes the patterns of early and late recurrence in oncoplastic surgery, concluding that bigger risk may not be overcome by bigger surgery.