Effect of discontinuation of ticagrelor and switching-over to other P2Y12 agents in patients with acute coronary syndrome: a single-center real-world experience from India.

BACKGROUND: Dual antiplatelet therapy is the current standard of care after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). We intended to study the pattern of use of ticagrelor in patients with acute coronary syndrome undergoing PCI and the effect of switching over to other P2Y12 receptor inhibition on clinical outcomes. RESULTS: All patients aged > 18 years who had been admitted with acute coronary syndrome and had been provided ticagrelor as the second antiplatelet agent were included as study participants. The primary outcome of the study was the composite outcome of death, recurrent myocardial infarctions, re-intervention, and major bleeding. We studied 321 patients (54 female patients, 16.82%). The mean age of the patients was 56.65 ± 11.01 years. Ticagrelor was stopped in 76.7% on follow-up. It was stopped in 6.3%, 13.5%, 13.1%, 21.9%, and 45.1% of patients during the first month but after discharge, between first and third months, between 3 and 6 months, between 6 and 12 months, and after 12 months, respectively. In the majority of patients, ticagrelor was replaced by clopidogrel (97.9%). It was stopped according to the physician's discretion in 79.3% of patients, whereas it was the cost of the drug that made the patient to get swapped to another agent in 18.6%. No difference in the primary composite outcome was observed between the groups where ticagrelor was continued post 12 months and ticagrelor was continued and ticagrelor was switched-over to another agent. Similarly, no difference in death, recurrent myocardial infarctions, re-interventions, or major bleeding manifestations was observed between the two groups. CONCLUSION: In patients with acute coronary syndrome who undergo PCI, we observed that early discontinuation of ticagrelor and switching over to other P2Y12 inhibitors after discharge did not affect clinical outcomes.

A whole system approach to improving mortality associated with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is in the main managed by non-nephrologists, many who feel challenged by or lack awareness of the complexity that the renal element adds to their patients' care. National reports have raised major concerns about the quality of care and have predicted that mortality reductions of 30% are achievable with good medical practice. AIM: This quality improvement project evaluated whether a whole system approach could improve outcomes for patients with AKI. DESIGN AND METHODS: Quality improvement methodology was used to understand hospital patterns, processes and professional knowledge. Change concepts were developed which included management of patients at risk, staff education and awareness program, development of a patient specific electronic alert to prompt diagnosis, easy to remember care bundle (ABCDE-IT), dedicated outreach team and patient and family empowerment leaflet. RESULTS: Statistical process control analysis was used to verify outcomes over time. A shift in the in-hospital mortality rate corresponded to a relative 23.2% reduction in mortality and was sustained over the next 33 months (P < 0.0001). The favourable shift in mortality was temporally distinct from the improved AKI detection rate. This timeframe corresponded to lying below the 99.8% lower confidence limit in comparison with all English acute trusts for comparative AKI specific SHMI/HSMR mortality rates. Length of stay also reduced shortly after onset of the project by 14.1% or 2.6 day reduction (P < 0.0001). CONCLUSION: This project demonstrated that an integrated, whole-system approach is necessary to ensure sustained improvements in AKI mortality and length of stay.

Inequalities in outcomes of acute kidney injury in England.

BACKGROUND: Renal replacement is managed by renal specialists and is well documented in national registries. In contrast, nation-wide data on acute kidney injury (AKI) are difficult to capture as it presents in many different ways to all acute hospitals. This paucity impacts on the coordination of appropriate services. AIMS: We have set out to use all the information submitted by all hospitals in England to identify emergency patients in whom AKI was a major contributor to their hospital stay. We then examined workload in relation to specialist provision and outcomes of care. DESIGN AND METHODS: All English hospitals submit a sequential list of International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD 10) codes to describe the diagnosis of each admission. An algorithm was applied to all emergency admissions over a 2-year period to identify AKI. The level of renal specialist care available within each hospital trust was compared with patient outcomes, including 30-day mortality. RESULTS: The incidence of AKI was 1.34% of all emergency admissions. The numbers and types of AKI cases were similar in all trusts, regardless of the service available. Thirty-day mortality was 30.0%. More than half the acute hospitals did not have on-site renal specialists and their AKI mortality rates were significantly higher (P < 0.001). These differences persisted despite adjusting for multiple variables. CONCLUSION: The country has created specialist renal units in 45% of hospital trusts, but AKI presents as emergencies to all hospitals and there is an increased risk of mortality in the 55% of trusts without renal specialists.

Long-term experience of plasmapheresis in antibody-mediated rejection in renal transplantation.

BACKGROUND: Antibody-mediated rejection (AMR) continues to pose a serious challenge in renal transplantation with potentially devastating consequences. Treatment options for this condition include plasmapheresis, high-dose intravenous immunoglobulin (IVIG), plasmapheresis with low-dose IVIG, and the use of rituximab (anti-CD20 chimeric antibody). We previously reported on the short-term outcome of plasmapheresis as a rescue therapy for AMR in our centre. We now report on the long-term follow up. METHODS: Over a 2.5-year study period, 440 cadaveric transplants were performed. AMR developed in 20 (4.5%) patients. Treatment included plasmapheresis and intensification of their immunosuppressive therapy. RESULTS: Excluding two patients who had infarcted their grafts at diagnosis, 18 patients received plasmapheresis treatment for AMR. Of the 18 patients treated, 14 recovered function, two developed graft infarction within a fortnight of starting plasmapheresis, and two patients were withdrawn from treatment. In the 14 who recovered renal function, graft survival was 86% at 12 months. In this study we report on the 5-year follow-up of these AMR-treatment responders. Eleven patients have a functioning graft at 5 years; graft function was stable with a mean serum creatinine of 130 micromol/L at 5 years compared to 123 mumol/L at 1 year. At 5-years follow-up; graft survival was 78% and patient survival 93%. CONCLUSIONS: Little information is available in the literature regarding the long-term outcome of this therapy. This is the first report on the long-term (5-year) follow-up of plasmapheresis as a rescue therapy for AMR.

'Microalbuminuric anaemia'--the relationship between haemoglobin levels and albuminuria in diabetes.

BACKGROUND: There is an increasing incidence of anaemia in diabetes despite the absence of significant renal impairment. AIMS: This study set out to determine the prevalence of anaemia in a diabetic population and to explore the relationship between anaemia and urinary albumin excretion in diabetes mellitus. Also, to determine the difference between those with overt nephropathy, microalbuminuria and those without evidence of renal disease. METHODS: Five hundred and two consecutive diabetes patients were screened for anaemia. Anaemia was defined by World Health Organization criteria (<13 g/dl for men and <12 g/dl for women). Urinary albumin excretion was determined by urinary albumin creatinine ratio (ACR) from a single urine sample. RESULTS: Anaemia was present in 118 (23.5%) patients. There was a rise in the prevalence of anaemia from 19% in patients with a normal ACR to 29% in those with microalbuminuria and to 41% in macroalbuminuria. This increase in the prevalence of anaemia in microalbuminuria compared to normoalbuminuria was not explained by declining renal function as there was no significant difference in eGFR between the two groups. CONCLUSION: Anaemia was common in the study population. Early detection and correction of anaemia in diabetes is important for patients at risk of impaired quality of life and increased cardiovascular risk.

Revision using distal inflow for treatment of heart failure secondary to arteriovenous fistula for hemodialysis.

In patients on hemodialysis, cardiovascular disease can be precipitated or worsened by the presence of a high flow arteriovenous fistula. Fistula closure and banding are the traditional treatment methods of dialysis associated high output cardiac failure. We present a case of fistula-related high output cardiac failure treated by revision using distal inflow (RUDI).

Familial cardiac myxoma: Carney's complex.

We report a case of Carney's complex in a 12-year-old boy who had the characteristic features of multiple cutaneous tumors, pigmentation, and biatrial myxoma. His large right atrial myxoma almost occluded the tricuspid valve and presented a life-threatening emergency. Surgery saved his life, but recurrence of myxoma was noted on follow-up. The familial nature of the condition is highlighted by the case of the patient's 44-year-old mother, who also presented with features of Carney's complex: multiple cutaneous tumors and a tiny, asymptomatic, left atrial myxoma, which was detected during routine echocardiographic screening.

Left ventricular pseudoaneurysm caused by coronary spasm, myocardial infarction, and myocardial rupture.

We report a very rare case of a 47-year-old man who had coronary spasm that resulted in a silent myocardial infarction, a ruptured myocardial wall, and a nonruptured left ventricular pseudoaneurysm. The patient presented with a 6-month history of dyspnea on exertion, without evidence of fixed coronary artery stenosis. Coronary angiography showed severe coronary spasm of the left anterior descending and left circumflex arteries; the spasm was relieved promptly by nitroglycerin. Echocardiography and left ventricular angiography revealed the large left ventricular pseudoaneurysm posterolateral to the left ventricle. We performed surgical resection of the pseudoaneurysm and patch repair of the ruptured left ventricular wall, with excellent results. We present this case because of the highly unusual sequence of events. Early surgical intervention resulted in the patient's recovery.

Vancomycin-resistant peritonitis associated with peritoneal dialysis: a cause for concern.

BACKGROUND: Peritonitis resulting from peritoneal dialysis (PD) remains a serious cause of morbidity and even mortality among dialysis patients. AIM: To highlight the danger of antibiotic resistance in patients on dialysis who have received multiple courses of antibiotics. METHODS: Two cases are reported in which the patients developed peritonitis resistant to vancomycin. CONCLUSIONS: Multi-drug resistance is a growing danger. It is imperative to use the most appropriate antibiotics in the proper dosage. If infections persist, early removal of the catheters is essential. The use of antibiotics in PD patients needs to be limited. Sensitivity patterns of the cultured organisms must be monitored regularly as the lack of vigilance may help accelerate the development of the so-called 'super bug' resistant to all antibiotics.

The HELLP syndrome, a prospective study.

OBJECTIVE: We undertook this study to evaluate the incidence and outcome of HELLP in Irish patients. In addition, duration and trends of the abnormal laboratory results were studied. STUDY DESIGN: This prospective observational study screened 12068 pregnant women between January 1995 and March 1997. Any pregnant woman with hypertension, proteinuria, thrombocytopenia or anemia was monitored for hemolysis and elevated liver transaminases, from the time of recruitment till six weeks postpartum or resolution. RESULTS: Thirteen of 12068 pregnant women (0.11%) developed HELLP. All had hypertension and 84.6% had proteinuria. Delivery was the only factor found to terminate the syndrome. Acute renal dysfunction was noted in 53.8% but none required dialysis. Laboratory parameters stabilized by the sixth postpartum day. Fetal mortality was 1 out of 14. There were no maternal deaths. CONCLUSIONS: HELLP syndrome is a rare but potentially serious complication of pregnancy. Correlation with laboratory data and early intervention are vital in achieving a favorable outcome for both mother and fetus.

Influence of ribose on adenine salvage after intense muscle contractions.

The influence of ribose supplementation on skeletal muscle adenine salvage rates during recovery from intense contractions and subsequent muscle performance was evaluated using an adult rat perfused hindquarter preparation. Three minutes of tetanic contractions (60 tetani/min) decreased ATP content in the calf muscles by approximately 50% and produced an equimolar increase in IMP. Effective recovery of muscle ATP 1 h after contractions was due to reamination of IMP via the purine nucleotide cycle and was complete in the red gastrocnemius but incomplete in the white gastrocnemius muscle section. Adenine salvage rates in recovering muscle averaged 45 +/- 4, 49 +/- 5, and 30 +/- 3 nmol. h(-1). g(-1) for plantaris, red gastrocnemius, and white gastrocnemius muscle, respectively, which were not different from values in corresponding nonstimulated muscle sections. Adenine salvage rates increased five- to sevenfold by perfusion with approximately 4 mM ribose (212 +/- 17, 192 +/- 9, and 215 +/- 14 nmol. h(-1). g(-1) in resting muscle sections, respectively). These high rates were sustained in recovering muscle, except for a small (approximately 20%) but significant (P < 0.001) decrease in the white gastrocnemius muscle. Ribose supplementation did not affect subsequent muscle force production after 60 min of recovery. These data indicate that adenine salvage rates were essentially unaltered during recovery from intense contractions.

Successful transplantation of kidneys from a donor with HELLP syndrome-related death.

We report on the successful use of kidneys procured from a donor with HELLP syndrome. The use of organs from a donor with HELLP syndrome has not been reported previously, perhaps because of the renal complications associated with it. Both recipients have been doing well since renal transplantation, with immediate graft function and acceptable graft function at 2 years of follow-up. In view of the continuing shortage of cadaveric kidneys for transplantation, this report highlights how organs from "marginal" donors should not be discarded without worthy consideration.

A novel presentation of cryptococcal infection in a renal allograft recipient.

The population of immunosuppressed patients is growing rapidly because of the HIV epidemic and the rapid expansion in transplant medicine. These patients may present to a variety of clinical specialties with seemingly innocuous infections. We present here the first Irish case of primary cryptococcal cellulitis. The patient was a 62-year old renal transplant recipient and was immunosuppressed with Cyclosporine, Azathioprine and Prednisolone. He presented with an apparent bacterial cellulitis on the dorsum of the hand that had failed to respond to a 3-week course of oral antibiotics. There was no clinical evidence of systemic infection. There was tissue necrosis present and the area was debrided surgically. Histological examination of debrided tissue revealed necrotic granulomata and budding yeast-like organisms. Cryptococcus neoformans was cultured from this specimen. The patient was treated with oral fluconazole 400 mg daily for 6 weeks with complete healing of the infected area and no evidence of recurrence after 12 months of follow up. This case emphasises the need for a high index of suspicion for atypical infection in the immunocompromised patient.

Pregnancy in Irish renal transplant recipients in the cyclosporine era.

BACKGROUND: The effect of renal transplantation on pregnancy in Irish women not receiving CyA has been reported previously. AIM: To examine all pregnancies occurring in Irish female renal transplant recipients since the introduction of CyA. METHODS: Using a community based approach, we identified 29 pregnancies in 19 women, aged between 16 and 45, mean age 30.3 years. RESULTS: These pregnancies ended in four miscarriages (13%), two intra-uterine deaths (6.9%) and 23 live births (79.3%). Of these live births, 73.9% were premature (< or = 36 weeks) and 65.2% were of low birth weight (< 2500 g). Admission to the neonatal intensive care was necessary in 61%, and two babies (8.7%) died in the neonatal period. Mean gestational age was 34 weeks, and mean birth weight was 2190 g. There was no change in graft function during pregnancy, with a small rise in serum creatinine post-partum (+9.64 mumol/L). The renal graft failed in three women (15.8%) by the end of the follow-up period. Compared with the precyclosporine era, the live birth rate was higher (79.3% versus 58%) with a trend towards lower birth weight and shorter gestation. CONCLUSION: Renal transplantation with CyA use is not a contraindication to pregnancy, but it is associated with increased risk, especially when the serum creatinine is > 175 mumol/L.

Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus.

Hemolytic-uremic syndrome (HUS) is a well-recognized complication of cyclosporine (CyA) therapy. Transplant recipients with this complication are frequently switched to tacrolimus, although this drug has also been implicated. We report a case of a renal transplant recipient who developed severe graft dysfunction due to biopsy-proven HUS after receiving CyA. Renal function and hemolytic parameters improved with discontinuation of the drug, but they deteriorated again after commencement of tacrolimus 15 days later. A second transplant biopsy demonstrated fresh lesions diagnostic of HUS. Hemolytic parameters resolved with discontinuation of tacrolimus. This is the first report of metachronous HUS being caused in a renal transplant by both CyA and tacrolimus. We therefore believe that caution should be exercised when using tacrolimus as rescue therapy in patients with CyA-induced HUS.

Aortic valve disease and left dominant coronary system a significant association.

OBJECTIVES: To study the dominance of coronary artery distribution in patients with aortic valve disease. MATERIAL AND METHODS: The prevalence of left dominant coronary artery system in patients with aortic valve disease was compared with patients without aortic valve disease undergoing coronary angiography. Group 1 consisted of 237 patients with symptomatic aortic valve disease and Group 2 consisted of 241 consecutive patients without aortic valve disease undergoing cardiac catheterisation. RESULTS: Forty two patients in Group 1 and 20 patients in Group 2 (p < 0.01) showed a left dominant pattern of supply. Fifteen patients in Group 1 and eight patients in Group 2 showed a co-dominant pattern of supply (p = NS). Among patients in Group 1, there was no significant difference in the increased prevalence of left dominant system between patients with congenital or acquired aortic valve disease or between the different categories of aortic valve lesions. CONCLUSION: Patients with aortic valve disease show a statistically significant higher prevalence of left dominant pattern of blood supply. This higher prevalence of left dominance is seen in all categories of aortic valve lesions, namely, predominant aortic stenosis, predominant aortic regurgitation and in combined aortic stenotic and regurgitant lesions.

Percutaneous transvenous mitral commissurotomy for significant calcific mitral stenosis: utility of the stepwise balloon dilatation technique and follow-up results.

The present study examined the utility of the stepwise balloon dilatation technique in 41 patients with significant calcific mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Thirty-five patients (85.4%) had a successful procedure; one patient developed cardiac tamponade and underwent mitral valve replacement. The mitral valve area increased from 0.9 +/- 0.2 cm2 to 1.7 +/- 0.3 cm2 following PTMC. Increase in mitral regurgitation (MR) was seen in 11 patients (26.8%). All patients showed improvement in functional class of > or =1 level following PTMC, which was sustained in 34 patients at follow-up. At a mean follow-up period of 20 +/- 12 months (range 3-51 months) in 35 patients, 26 patients (74.3%) were in New York Heart Association (NYHA) functional Class I, 8 patients (22.9%) were in NYHA Class II, and 1 patient (2.8%) was in NYHA Class III. The cumulative 4-year cardiac event-free survival rate was 81.8%. However, patients with grade 4+ calcification had only 50% event-free survival rate. At follow-up, an increased incidence of cardiac events was seen in female patients as compared with male patients (83.3% versus 16.7%). Restenosis was seen in 3 patients (8.6%). One patient underwent repeat PTMC 37 months after the initial procedure. There was no incidence of death or mitral valve replacement at follow-up. We conclude that the stepwise balloon dilatation technique can be safely and effectively applied for patients with significant calcific mitral stenosis to achieve an optimal mitral valve area with low incidence of significant increase in MR. Favorable long-term benefits also accrue in the form of improved functional status and low incidence of repeat procedures (repeat PTMC or mitral valve replacement). The majority of patients (74.3%) were in NYHA functional class I without medication. Patients with grade 4+ calcification show less benefit from PTMC and may be considered for mitral valve replacement. Cardiac events occur more frequently in female patients than in male patients during follow-up.

Angioplasty and stenting of solitary supra-aortic artery and aortoplasty by kissing balloon technique.

A child presented with symptoms of compromise to cerebral blood flow and cardiac failure. On diagnostic angiography, he was found to have a discrete coarctation and related ostial stenosis of the left subclavian artery, which acted as the sole source of cerebral blood flow. The subclavian lesion was initially dilated with a 6 mm x 50 mm balloon. The discrete coarctation was then dilated with an 8 mm x 50 mm balloon. Since significant residual stenosis was present at the subclavian origin, it was stented with a 20 mm Palmaz-Schatz stent (Cordis Corporation, Miami Lakes, Florida). Since the coarcted segment required further dilatations, the kissing balloon technique was used, wherein the 6 mm balloon was placed extending from the left subclavian lesion distally to the related aortic lesion proximally, along with another 10 mm balloon in the aorta. The end result was acceptable and the patient's symptoms improved significantly after the procedure.