Late Toxicity and Long-Term Local Control in Patients With Ultra-Central Lung Tumours Treated by Intensity-Modulated Radiotherapy-Based Stereotactic Ablative Body Radiotherapy With Homogenous Dose Prescription.

AIMS: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes. RESULTS: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm3 and 57.4 (range 7.7-426.6) cm3, respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED3 for 4 cm3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively. CONCLUSION: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment.

Public Awareness of Knowledge, Belief, and Attitude Regarding Organ Donation and Organ Transplantation: A National Survey From the United Arab Emirates.

BACKGROUND: Organ donation in the United Arab Emirates (UAE) was restricted until recently to living donation. This survey was conducted to explore the public knowledge, belief, and attitude regarding donation during life and after death. METHODOLOGY: A 31-item survey was distributed among 900 participants (UAE residents) of whom 495 completed the forms and were considered for further analysis. RESULTS: Among the participants, 293 (59.2%) were women and 202 (40.1%) were men. With 8 items as the highest possible score, the mean score of knowledge was 4.42 (SD = 1.54) and 436 (88%) of the participants knew about a brain-dead condition. However, their awareness on organ donation and transplantation legislation in the UAE was not consistent, and less than 198 (40%) had correct knowledge in this regard. Religious belief regarding organ donation was scored at 80 and the mean of the beliefs score obtained was 56.56 (SD = 6.39). Together, 369 (74.6%) of the participants had positive religious sentiments regarding the issue. Participants' attitude toward organ donation and transplantation was scored at 14.7 out of 20 possible score (SD = 2.46) with 396 (80%) acknowledging the fact that organ donation and transplantation prolongs and improves recipient's quality of life. LIMITATIONS: The small number of respondents (n = 495) in the survey was a limitation of the study. CONCLUSIONS: The population of the UAE was moderately well informed and motivated about organ donation and transplantation. Although a knowledge gap about the current legislation prevailed, the majority of the participants were knowledgeable, they nurtured positive beliefs, and had compassionate attitude regarding lawful organ transplantation.

Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina.

There is much debate on the adeno-associated virus (AAV) serotype that best targets specific retinal cell types and the route of surgical delivery-intravitreal or subretinal. This study compared three of the most efficacious AAV vectors known to date in a mouse model of retinal degeneration (rd1 mouse) and macaque and human retinal explants. Green fluorescent protein (GFP) driven by a ubiquitous promoter was packaged into three AAV capsids: AAV2/8(Y733F), AAV2/2(quad Y-F) and AAV2/2(7m8). Overall, AAV2/2(7m8) transduced the largest area of retina and resulted in the highest level of GFP expression, followed by AAV2/2(quad Y-F) and AAV2/8(Y733F). AAV2/2(7m8) and AAV2/2(quad Y-F) both resulted in similar patterns of transduction whether they were injected intravitreally or subretinally. AAV2/8(Y733F) transduced a significantly smaller area of retina when injected intravitreally compared with subretinally. Retinal ganglion cells, horizontal cells and retinal pigment epithelium expressed relatively high levels of GFP in the mouse retina, whereas amacrine cells expressed low levels of GFP and bipolar cells were infrequently transduced. Cone cells were the most frequently transduced cell type in macaque retina explants, whereas Müller cells were the predominant transduced cell type in human retinal explants. Of the AAV serotypes tested, AAV2/2(7m8) was the most effective at transducing a range of cell types in degenerate mouse retina and macaque and human retinal explants.

Voltage-controlled interlayer coupling in perpendicularly magnetized magnetic tunnel junctions.

Magnetic interlayer coupling is one of the central phenomena in spintronics. It has been predicted that the sign of interlayer coupling can be manipulated by electric fields, instead of electric currents, thereby offering a promising low energy magnetization switching mechanism. Here we present the experimental demonstration of voltage-controlled interlayer coupling in a new perpendicular magnetic tunnel junction system with a GdOx tunnel barrier, where a large perpendicular magnetic anisotropy and a sizable tunnelling magnetoresistance have been achieved at room temperature. Owing to the interfacial nature of the magnetism, the ability to move oxygen vacancies within the barrier, and a large proximity-induced magnetization of GdOx, both the magnitude and the sign of the interlayer coupling in these junctions can be directly controlled by voltage. These results pave a new path towards achieving energy-efficient magnetization switching by controlling interlayer coupling.

Bulk dentine replacement versus incrementally placed resin composite: A randomised controlled clinical trial.

OBJECTIVE: This randomized controlled clinical trial compared two techniques and materials for restoring carious teeth-Bulk dentine replacement versus incremental placement of a hybrid posterior resin composite material in terms of patient comfort (post operative sensitivity and tenderness on biting). MATERIAL AND METHODS: Seventy-two carious teeth were randomized to one of two treatment groups: Group A-were restored with a bulk dentine replacement material or Group B-restored with incrementally placed hybrid composite. Patients were followed up by way of a structured phone call at day 2 and day 7 post-operatively. Patients reporting discomfort at day 7 were subsequently followed up on days 14, and 30. RESULTS: All patients were followed up. At day 2, 18/72 restored teeth had post-operative sensitivity; this figure fell to 10/72 at day 7. A Chi squared test revealed that at day 2 a greater level of sensitivity was reported by patients in Group A (P=0.029). However, at day 7 there was no statistically significant difference between the two groups in terms of sensitivity (P=0.453). 8/72 and 6 /72 teeth had tenderness to biting at days 2 and 7 respectively. A Chi squared test revealed no statistically significant difference between the two groups in terms of tenderness on biting at any time period (P=0.722). Interestingly, Class I cavities were found to be more tender on biting than Class II cavities. At day 30 2/72 teeth exhibited sensitivity and none of the teeth exhibiting tenderness on biting. CONCLUSION: At day 7 there was no significant difference between the two groups in terms of postoperative sensitivity and tenderness on biting.

Mental illness self-management: a randomised controlled trial of the Wellness Recovery Action Planning intervention for inpatients and outpatients with psychiatric illness.

OBJECTIVE: Wellness Recovery Action Planning (WRAP) is a cross-diagnostic, patient-centred, self-management intervention for psychiatric illness. WRAP utilises an individualised Wellness Toolbox, a six part structured monitoring and response system, and a crisis and post-crisis plan to promote recovery. The objective of this study was to evaluate the effect of WRAP on personal recovery, quality of life, and self-reported psychiatric symptoms. METHOD: A prospective randomised controlled trial, based on the CONSORT principles was conducted using a sample of 36 inpatients and outpatients with a diagnosis of a mental disorder. Participants were randomly allocated to Experimental Group or Waiting List Control Group conditions in a 1:1 ratio. Measures of personal recovery, personal recovery life areas, quality of life, anxiety, and depression were administered at three time points: (i) pre-intervention, (ii) post-Experimental Group intervention delivery, and (iii) 6-month follow-up. Data was analysed by available case analysis using univariate and bivariate methodologies. RESULTS: WRAP had a significant effect on two personal recovery life areas measured by the Mental Health Recovery Star: (i) addictive behaviour and (ii) identity and self-esteem. WRAP did not have a significant effect on personal recovery (measured by the Mental Health Recovery Measure), quality of life, or psychiatric symptoms. CONCLUSIONS: Findings indicate that WRAP improves personal recovery in the areas of (i) addictive behaviour and (ii) identity and self-esteem. Further research is required to confirm WRAP efficacy in other outcome domains. Efforts to integrate WRAP into recovery-orientated mental health services should be encouraged and evaluated.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

Autotransplantation of a single functioning kidney following rupture of renal artery aneurysm.

Renal artery aneurysms (RAA) are the second most common visceral artery aneurysm. In cases of rupture they pose a significant and emergent surgical challenge. Extracorporeal arterial reconstruction and autotransplantation is often necessary in certain complex cases that are not amenable to aneurysm repair in vivo. We report a case of a 35 year old female with a RAA in a solitary functioning kidney, requiring ex vivo reconstruction and autotransplantation to the iliac vessels.

Organ donation following the circulatory determination of death (DCD): an audit of donation and outcomes following renal transplantation.

Organ Donation following the Circulatory determination of Death was introduced in Beaumont Hospital during 2011. The Intensive Care Society of Ireland formally endorsed a national DCD clinical practice guideline in 2012. This retrospective audit covers a 2-year period during which eleven patients were considered suitable for DCD and where consent was obtained. Nine patients died within the ninety-minute period following the withdrawal of life sustaining therapies and subsequently donated organs (82%). Eighteen kidneys were recovered and seventeen patients received renal transplants--one patient received a nephron-dosing dual renal transplant. Lungs were recovered on two occasions and one patient received a lung transplant. Heart valves were recovered on one occasion. To date sixteen of seventeen recipient patients have functioning renal transplants (94%). In conclusion, this model of deceased donation has proven acceptable to families, nursing and medical staff and the outcomes reported are consistent with international best practice.

Incidence and long-term outcomes of squamous cell bladder cancer after deceased donor renal transplantation.

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.

Mediators of antiretroviral adherence: a multisite international study.

The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare provider (eHCP) and whether this differed by international site. Data were obtained from a cross-sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand, and US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC, and eHCP with adherence (3 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus, the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest, while enriched by a sample obtained from international sites, may not have the same relationships in each country.

Twenty-year survivors of kidney transplantation.

There have been few studies of patients with renal allografts functioning for more than 20 years. We sought to identify clinical factors associated with ultra long-term (>20 year) renal allograft survival and to describe the clinical features of these patients. We performed a retrospective analysis of the Irish Renal Transplant Database and included 1174 transplants in 1002 patients. There were 255 (21.74%) patients with graft function for 20 years or more. Multivariate analysis identified recipient age (HR 1.01, CI 1.01-1.02), gender (male HR 1.25, CI 1.08-1.45), acute rejection (HR 1.26, CI 1.09-1.45) and transplant type (living related donor vs. deceased donor) (HR 0.52, CI 0.40-0.66) as significantly associated with long-term graft loss. Median serum creatinine was 115 µmol/L. The 5-year graft survival in 20-year survivors was 74.7%. The mean age at death was 62.7 years (±10.6). The most common causes of death were cardiovascular disease and malignancy. The two major causes of graft loss were death (with function) and interstitial fibrosis/tubular atrophy. Comorbidities included skin cancer (36.1%), coronary heart disease (17.3%) and other malignancies (14.5%). This study identifies factors associated with long-term allograft survival and a high rate of morbidity and early mortality in long-term transplant recipients.

Two-wavelength fundus autofluorescence and macular pigment optical density imaging in diabetic macular oedema.

PURPOSE: To evaluate the application of 488 and 514 nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features. PATIENTS AND METHODS: A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514 nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference. RESULTS: Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488 nm FAF, 0.63 for 514 nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488 nm FAF; 55.2 and 94.8% for 514 nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488 nm FAF and MPOD imaging, DMO was better visualised in comparison with 514 nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts. CONCLUSION: MPOD imaging, and particularly its combination with 488 nm and 514 nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.

Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections.

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

Successful pregnancy after simultaneous pancreas-kidney transplantation.

The effect of pregnancy on simultaneous pancreas-kidney transplant recipients has previously been described, but experience is limited. We describe the case of a thirty-five-year-old female who previously underwent simultaneous pancreas-kidney transplant for type 1 diabetes mellitus-complicated nephropathy. An integrated multidisciplinary team including the transplant team, nephrologist, endocrinologist, and obstetrician closely followed progress during pregnancy. Blood glucose levels and HbA1c remained within normal limits, and she did not require insulin treatment at any point. She experienced deterioration in renal indices and underwent an uncomplicated, elective Caesarean section at thirty-week gestation. She delivered a male infant of 1.18 kg, appropriate for gestational age, who had hypothermia and respiratory distress, which required intubation and ventilation and an eleven-week stay in the special care baby unit. At eighteen-month followup the infant shows normal development, and there has been no deterioration in either grafts' function.

Analysis of waiting times on Irish renal transplant list.

INTRODUCTION: A number of recipient variables have been identified which influence waiting list times for a renal allograft. The aim of this study was to evaluate these factors in the Irish population. METHODS: We examined patients accepted onto the transplant list from January 1, 2000 until December 31, 2005. Inclusion criteria were adults listed for kidney only, deceased donor transplants. We included patients previously transplanted. Patients were censored, but still included in the analysis, if they died while on the list, permanently withdrew from the list or if they were not transplanted at the time of the study. RESULTS: There were a total of 984 patients accepted onto the waiting list during the study period, of which 745 of these were transplanted. Factors significantly associated with longer waiting times included age above 50 yr, blood group O and high peak panel reactive antibodies level. Gender and patient body mass index were not associated with longer waiting times. CONCLUSION: We have identified factors associated with a longer waiting time on the Irish cadaveric renal transplant list. This information can help our patients make informed decisions regarding likely waiting times and the merits of living related transplantation.

Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2-13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14-20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5-27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5-77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

An assessment of the long-term health outcome of renal transplant recipients in Ireland.

BACKGROUND: Renal transplantation remains the preferred method of renal replacement therapy in terms of patient survival, quality of life and cost. However, patients have a high risk of complications ranging from rejection episodes, infection and cancer, amongst others. AIMS AND METHODS: In this study, we sought to determine the long-term health outcomes and preventive health measures undertaken for the 1,536 living renal transplant patients in Ireland using a self-reported questionnaire. Outcomes were divided into categories, namely, general health information, allograft-related information, immunosuppression-related complications and preventive health measures. RESULTS: The results demonstrate a high rate of cardiovascular, neoplastic and infectious complications in our transplant patients. Moreover, preventive health measures are often not undertaken by patients and lifestyle choices can be poor. CONCLUSIONS: This study highlights the work needed by the transplantation community to improve patient education, adjust immunosuppression where necessary and aggressively manage patient risk factors.