ABSTRACT
INTRODUCTION: Invasive lobular carcinoma (ILC) accounts for 5-15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. METHODS: All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. RESULTS: A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001). A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). CONCLUSIONS: Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.
Subject(s)
Breast Neoplasms , Carcinoma, Lobular , Neoadjuvant Therapy , Humans , Female , Carcinoma, Lobular/pathology , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/mortality , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Middle Aged , Aged , Adult , Chemotherapy, Adjuvant , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/analysis , Receptors, Estrogen/metabolism , Receptors, Estrogen/analysis , Biomarkers, Tumor/analysis , Treatment Outcome , Retrospective Studies , Disease-Free Survival , Neoplasm GradingABSTRACT
BACKGROUND: Sexual assault (SA) poses a threat to all areas of contemporary society. Although older individuals represent a vulnerable demographic, a considerable gap exists in the literature regarding the context in which older individuals experience SA. This study aims to provide a comprehensive description of older individuals' attendances at the Sexual Assault Treatment Unit (SATU) network in the Republic of Ireland. METHODS: A 7-year national cross-sectional study was performed to analyse the attendances of older people (≥65 years old) to the SATU network, and to compare them with younger attendances (<65 years old), with a more in-depth subset analysis of Dublin SATU attendances. RESULTS: During the study period, there were 6478 attendances to the SATU network, of which 0.93 % (n = 60) were older people. These included 59 females and 1 male, with the average age of 76.05 years ± 8.16. Forensic examinations were performed in 81.7 %, with the majority seeking assistance within 7 days (80 %). Comparison of older (≥65 years) and younger (<65 years) attendees revealed older individuals were more uncertain whether a sexual assault had occurred (35.5 % vs. 14.4 %, p < 0.001) but more likely to report the incident to the police (78.3 % vs. 64.3 %, p = 0.02). Assault by a person in authority was significantly more common in older age groups (11.7 % vs. 1.8 %, p < 0.001). Older individuals were significantly more likely to be assaulted in their own home (33.3 % vs. 21.5 p < 0.03) or in 'other-indoors' settings (e.g. nursing home/hospital) (43.3 % vs. 23.4 % p < 0.001). They were less likely to be assaulted in the assailant's home (5.0 % vs. 22.9 %, p < 0.001) or outdoors (5.0 % vs. 19.7 %, p = 0.004). In our subset analysis of 19 cases, 73.7 % occurred in healthcare facilities, 63.2 % had dementia, and 42.1 % were care dependent. Genital injuries were present in 44.4 % of patients and extra-genital injuries in 22.2 %. CONCLUSION: Unique patterns are evident in sexual assault experienced by older people, underscoring the necessity for tailored interventions and effective support systems for reporting and addressing this vulnerable demographic. This is especially crucial in healthcare environments, where a notable proportion of cases occur, frequently involving individuals with dementia and requiring care assistance.
Subject(s)
Crime Victims , Sex Offenses , Humans , Female , Ireland/epidemiology , Male , Aged , Cross-Sectional Studies , Sex Offenses/statistics & numerical data , Middle Aged , Crime Victims/statistics & numerical data , Aged, 80 and over , Adult , Age Distribution , Elder Abuse/statistics & numerical dataABSTRACT
BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.
Subject(s)
Breast Neoplasms , Aged , Female , Humans , Anthracyclines/adverse effects , Breast Neoplasms/drug therapy , Stroke Volume , Trastuzumab , Ventricular Function, LeftABSTRACT
PURPOSE: Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021. METHODS: The Mann-Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp). RESULTS: 292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360-9.691, p = 0.010) and 2.445 (95% CI 1.131-5.288, p = 0.023), respectively. CONCLUSION: Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.
Subject(s)
Breast Density , Breast Neoplasms , Breast/diagnostic imaging , Breast/pathology , Breast/surgery , Breast Neoplasms/pathology , Female , Humans , Mammography , Neoadjuvant Therapy/adverse effectsABSTRACT
BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.
Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Humans , Lymphocytes , Lymphocytes, Tumor-Infiltrating , Prognosis , Receptor, ErbB-2/geneticsABSTRACT
PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of 4 million in treatment costs. Deducting assay costs, savings of 1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over 1,900,000.
Subject(s)
Breast Neoplasms , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Chemotherapy, Adjuvant , Cross-Sectional Studies , Female , Gene Expression Profiling , Humans , Ireland/epidemiology , Middle Aged , Neoplasm Recurrence, Local/genetics , Receptors, Estrogen/genetics , Retrospective StudiesABSTRACT
Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam energies from below-barrier to 25% above, for the reactions of ^{48}Ca, ^{50}Ti, and ^{54}Cr with ^{208}Pb. Moving from ^{48}Ca to ^{54}Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity P_{CN} (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for ^{50}Ti and 15 for ^{54}Cr in comparison to ^{48}Ca. The energy dependence of P_{CN} indicates that cold fusion reactions (involving ^{208}Pb) are not driven by a diffusion process.
ABSTRACT
Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P = 0.03). Grade ≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade ≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225.
Subject(s)
Albumins/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Maintenance Chemotherapy/methods , Paclitaxel/administration & dosage , Adult , Aged , Aged, 80 and over , Albumins/adverse effects , Antineoplastic Agents/adverse effects , Breast Neoplasms/mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Maintenance Chemotherapy/adverse effects , Middle Aged , Paclitaxel/adverse effects , Progression-Free Survival , Treatment OutcomeABSTRACT
Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.
Subject(s)
Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/adverse effects , Doxorubicin/adverse effects , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/epidemiology , Aged , Clinical Trials as Topic , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Echocardiography , Female , Follow-Up Studies , Humans , Middle Aged , Prospective Studies , Treatment Outcome , Ventricular Dysfunction, Left/chemically inducedSubject(s)
Adenosine Triphosphatases/genetics , Asymptomatic Diseases/psychology , Cation Transport Proteins/genetics , Hepatolenticular Degeneration , Treatment Refusal , Ceruloplasmin/analysis , Copper/analysis , Copper-Transporting ATPases , Female , Hepatolenticular Degeneration/blood , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/genetics , Hepatolenticular Degeneration/physiopathology , Homozygote , Humans , Liver/pathology , Middle Aged , Mutation , SiblingsABSTRACT
An analysis of 321 case notes of patients with Wilson's disease seen between 1955 and 2000 and one case seen in 1949 has revealed that 22 patients presented with a haemolytic crisis. This study was not a specific research project but a retrospective analysis of 321 patients with Wilson's disease seen between 1949 and 2000. All investigations were carried out in the best interests of diagnosis and management of patients referred to my clinic. The delay in diagnosis in 18 cases resulted in progression to severe hepatic disease in 14 cases and to neurological disease in 4 cases. One patient had no symptoms at the time her sister's illness was diagnosed as Wilson's disease. In a second patient, with liver disease, the diagnosis was also made when a sister was found to have Wilson's disease. There was a female to male ratio of 15:7. The average age of onset was 12.6 years and the incidence 6.9%. Delay in diagnosis resulted in nine deaths. Three patients, late in the series, were admitted in the acute phase, two female and one male; of these two responded to chelation therapy, the third required liver transplantation. Haemolysis appeared to be extravascular, and possible mechanisms of the haemolysis are discussed.
Subject(s)
Anemia, Hemolytic/etiology , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/diagnosis , Acute Disease , Adolescent , Chelating Agents/therapeutic use , Child , Delayed Diagnosis/adverse effects , Disease Progression , Female , Hepatolenticular Degeneration/mortality , Humans , Male , Retrospective Studies , Sex Factors , Young AdultABSTRACT
Tuberculosis is a multiorgan disease with varied clinical presentations and is reemerging due to increasing immigration and globalization. We present the case of an immigrant female patient who developed acute renal failure with clinical and biochemical features suggestive of lupus nephritis but with a timely renal biopsy showing caseating granulomata in the renal parenchyma consistent with renal tuberculosis. Despite treatment with antituberculosis treatment and resolution of TB on repeat renal biopsy, she remained haemodialysis dependent. We discuss the diagnostic challenges faced in this presentation and also explore possible differential diagnoses. This rare presentation highlights the importance of renal biopsy in the diagnosis and treatment of acute renal failure and the atypical presentation of tuberculosis.
ABSTRACT
BACKGROUND: The relationship between serum 'free' copper and urine copper in patients with Wilson disease has not been explored. AIM: The object of this study is to ascertain if there is a direct relationship between these two parameters. METHOD: The case notes of 320 patients with Wilson disease, seen between 1960 and 1987, have been reviewed. Eighty of these patients had received no treatment before referral and the results of serum 'free' copper and urine copper on admission and at one year of treatment have been analysed. RESULTS: Except for patients with acute haemolysis, the ratio between 'free' serum copper and urine copper before treatment, on average, is around 7:1, after treatment this falls to around 5:1. But results show a wide scatter and there is no direct linear relationship. CONCLUSION: The term 'free' copper is misleading and should be replaced by the more cumbersome but accurate term 'noncaeruloplasmin bound copper'. Most 'free' copper is complexed to albumin and is only available for excretion if there is significant protein loss by the kidneys.
Subject(s)
Copper/blood , Copper/urine , Hepatolenticular Degeneration/blood , Hepatolenticular Degeneration/urine , Adolescent , Adult , Ceruloplasmin/analysis , Chelating Agents/therapeutic use , Child , Child, Preschool , Hepatolenticular Degeneration/drug therapy , Humans , Penicillamine/therapeutic use , Trientine/therapeutic use , Young AdultABSTRACT
OBJECTIVE: To report the pregnancy outcomes in Irish female renal transplant recipients on modern maintenance immunosuppression. METHODS: The Republic of Ireland transplant database was accessed to identify the patient cohort in question. All female renal transplant recipients whose transplantation was in Ireland before or during their reproductive years were included. A questionnaire was sent to the identified women. A chart review was performed for those women who reported a pregnancy following renal transplantation. RESULTS: Two hundred and ten women met the inclusion criteria. There was a response rate of 70% (n = 148). Eighteen women reported 29 pregnancies. The live birth rate was 76%. The mean gestation of the live births was 36.2 weeks with a mean birth weight of 3.0 kg. There were six cases of pre-eclampsia. Twin pregnancies and those entering pregnancy with a creatinine greater than 135 µmol/l had particularly complicated clinical courses. Four women had not conceived post transplant despite actively trying for over 1 year. Two women utilised assisted fertility methods (in vitro fertilisation), one of whom became pregnant. CONCLUSIONS: A significant proportion of women who attempt to conceive following renal transplantation are successful, without the use of assisted fertility. Pregnancy in this setting warrants meticulous multidisciplinary care.
Subject(s)
Immunosuppressive Agents/adverse effects , Kidney Transplantation , Live Birth , Pregnancy Rate , Tacrolimus/adverse effects , Abortion, Spontaneous/etiology , Adult , Birth Weight , Female , Gestational Age , Humans , Immunosuppression Therapy/adverse effects , Ireland , Kidney Transplantation/adverse effects , Pre-Eclampsia/etiology , Pregnancy , Reproductive Techniques, Assisted , Young AdultABSTRACT
BACKGROUND: It is generally accepted that patients with Wilson's disease excrete excess copper in urine. However, there has been no study, on a large series of patients, as to whether there are differences in the rate of excretion at different stages of the disease or what changes may be expected after treatment. DESIGN: The present study follows from an analysis of the results of urinary copper excretion of 192 patients with Wilson's disease seen between 1955 and 2000. These patients were divided into three groups, pre-symptomatic, hepatic and neurological Wilson's disease. Patients were studied for basal pre-treatment, 24-h urinary copper excretion and for 6 h after a test dose of 500 mg penicillamine. The tests were repeated after approximately 1 and 2 years of chelation therapy with either penicillamine, or in a small minority of cases, trientine. RESULTS: The basal, pre-treatment copper excretion was the lowest in pre-symptomatic patients (207.93 µg/24 h) and the highest in the hepatic patients (465.75 µg/24 h). Those with neurological Wilson's disease gave an intermediate figure (305.58 µg/24 h). The response to penicillamine was the highest in the neurological patients and the lowest in the pre-symptomatic group. After 1 and 2 years of treatment all groups showed significant falls in both the basal and the after penicillamine rate of excretion of copper. The small subgroup treated with trientine, rather than penicillamine, showed similar results. CONCLUSIONS: The rate of copper excretion in patients with Wilson's disease shows wide variation from patient to patient, but in general patients with pre-symptomatic disease excrete less copper than those with symptomatic disease. All groups show a great increase when challenged with penicillamine. After 1 and 2 years of treatment, there is significant decrease in copper excretion in both basal and after penicillamine challenge. This presumably indicates a reduction in the body load of copper.
Subject(s)
Copper/urine , Hepatolenticular Degeneration/urine , Adolescent , Adult , Chelating Agents/therapeutic use , Chelation Therapy/methods , Child , Child, Preschool , Disease Progression , Hepatolenticular Degeneration/drug therapy , Humans , Penicillamine/therapeutic use , Young AdultABSTRACT
BACKGROUND: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. METHODS: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. RESULTS: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). CONCLUSIONS: This study confirms the higher bleeding risk associated with HD/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. SUMMARY: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A secondary finding was that INR variability was significantly higher in HD patients than non-HD patients on warfarin.
Subject(s)
Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , Blood Coagulation/drug effects , Brain Ischemia/prevention & control , Hemorrhage/chemically induced , Renal Dialysis/adverse effects , Stroke/prevention & control , Warfarin/adverse effects , Aged , Atrial Fibrillation/blood , Atrial Fibrillation/complications , Brain Ischemia/etiology , Erythrocyte Transfusion , Female , Hemorrhage/therapy , Hospitalization , Humans , International Normalized Ratio , Ireland , Length of Stay , Male , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/etiologyABSTRACT
BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, ≤ 5 mg/day, > 5 mg/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.