Care and outcomes of end-stage kidney disease patients in times of armed conflict: recommendations for action.

BACKGROUND: Conflicts can lead to significant disruption in the care of endstage kidney disease (ESKD) patients. The purpose of this paper is to review the available literature on the care of ESKD patients in times of armed conflict and make recommendations for action. METHOD: A review of all PubMed-published reports between 1965 and 2015 about the care of ESKD patients at the time of conflict. We excluded articles that reported on acute kidney injury and natural disasters. RESULTS: We found a total of 12 reports on dialysis care and/or kidney transplant care from five armed conflicts and resulting refugee crises. These conflicts led to significant shortage of staff and resources and caused several obstacles in providing adequate dialysis to ESKD patients. In one study, the mortality rate of patients on automated peritoneal dialysis was as high as 95%. The kidney transplantation rate decreased in all but one of the reports about kidney transplant care and patients had difficulties securing their immunosuppressive medications. CONCLUSIONS: ESKD patients, especially dialysis patients, comprise a severely vulnerable population during conflicts. Their care can be disrupted and altered leading to a substantial increase in their mortality rate. Efforts to improve their care during conflicts are needed.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

[Subacute lower back pain and acute kidney failure in a 47-year old man]. / Subakute lumbale Rückenschmerzen und akute Niereninsuffizienz bei einem 47-jährigen Mann.

A 47-year-old man presented with subacute, low back pain and increased creatinine levels. A CT scan showed an extrinsic, bilateral compression of the ureters by a retroperitoneal mass with pronounced uptake of 18F-fluorodeoxyglucose in positron emission tomography. Histological findings were consistent with the diagnosis of retroperitoneal fibrosis. Urological decompression was performed. The initiated corticosteroids led to a rapid clinical improvement and regression of the retroperitoneal mass. A relapse occurred after tapering of corticosteroids with a prompt response to increase of the dosage.

Clearance of circulating IgA immune complexes is mediated by a specific receptor on Kupffer cells in mice.

To characterize the physiology of circulating IgA immune complexes (IgA-IC), the dynamics of IgA-IC removal by the liver were examined. After intravenous injection, covalently cross-linked IgA antibodies to the dinitrophenyl determinant were rapidly removed from the circulation by the liver. Immunofluorescence microscopy and light and electron microscope autoradiography showed that the IgA-IC were associated with Kupffer cells. With increasing doses of injected IgA-IC the clearance velocity approached a maximum, thus prolonging the circulation of IgA-IC. All these observations indicated a receptor-mediated process. Saturating doses of various potential receptor-blocking agents, heat-aggregated mouse IgG, microaggregated human serum albumin, and purified dimeric IgA did not influence the clearance pattern and hepatic uptake of radiolabeled IgA-IC. Mouse livers were also perfused via the portal vein with 1 microgram of IgA-IC. In the presence or absence of serum proteins, 43% of the perfused IgA-IC were removed in a single passage. This liver uptake was not reduced with simultaneous perfusion of large doses of aggregated mouse IgG, aggregated human serum albumin, or purified free dimeric mouse IgA. In contrast, the liver uptake of radiolabeled IgA-IC was decreased by 88% with the addition of 1 mg unlabeled IgA-IC. These observations support the conclusion that removal of IgA-IC from circulation is mediated by a specific IgA receptor on Kupffer cells.

The N-glycans determine the differential blood clearance and hepatic uptake of human immunoglobulin (Ig)A1 and IgA2 isotypes.

Human immunoglobulin (Ig)A exists in blood as two isotypes, IgA1 and IgA2, with IgA2 present as three allotypes: IgA2m(1), IgA2m(2), and IgA2m(n). We now demonstrate that recombinant, chimeric IgA1 and IgA2 differ in their pharmacokinetic properties. The major pathway for the clearance of all IgA2 allotypes is the liver. Liver-mediated uptake is through the asialoglycoprotein receptor (ASGR), since clearance can be blocked by injection of excess galactose-Ficoll ligand and suppressed in ASGR-deficient mice. In contrast, only a small percentage of IgA1 is cleared through this pathway. The clearance of IgA1 lacking the hinge region with its associated O-linked carbohydrate was more rapid than that of wild-type IgA1. IgA1 and IgA2 that are not rapidly eliminated by the ASGR are both removed through an undefined ASGR-independent pathway with half-lives of 14 and 10 h, respectively. The rapid clearance of IgA2 but not IgA1 through the liver may in part explain why the serum levels of IgA1 are greater than those of IgA2. In addition, dysfunction of the ASGR or altered N-linked glycosylation, but not O-glycans, that affects recognition by this receptor may account for the elevated serum IgA seen in liver disease and IgA nephropathy.

Experimental IgA nephropathy.

An animal model for IgA immune complex nephritis was developed. IgA immune complexes formed in vitro with an IgA anti-dinitrophenyl (DNP) derived from MOPC-315 plasmacytoma, and dinitrophenylated bovine serum albumin (DNP-BSA) produced mild focal glomerulonephritis in mice. Similar, but more severe pathological changes were produced with complexes formed in vivo either in normal mice or MOPC-315 tumor-bearing mice. In contrast to the focal nature of the PAS-positive glomerular lesions observed by light microscopy, immunofluorescent examination revealed IgA deposits in all glomeruli. This discrepancy between immunofluorescent and histopathologic findings as well as the distribution of the immune complexes within the affected glomeruli, are some of the features which bear resemblance between this experimental model and human IgA nephropathy. Fixation of complements by DNP-BSA-IgA immune complexes, formed in vitro or in vivo, was shown to occur in the glomeruli of mice with IgA immune complex nephropathy. The pattern of C3 glomerular deposits was similar to that of IgA. However, complement proved to be nonessential for complex deposition. This conclusion is based on the observation that decomplemented mice, although showing no deposition of C3 in their glomerulus, developed glomerular immunohistological changes similar to those observed in experimental mice that were not decomplemented. Polymeric IgA was observed to be critical for renal deposition of complexes and induction of nephritic histological changes. In contrast, monomeric IgA immune complexes failed to produce glomerular deposits. This finding raises the possibility that secretory IgA, which is predominantly polymeric, may play a role in human IgA-associated glomerulonephritis.

IgA nephropathy: markers of progression and clues to pathogenesis.

The unpredictable progression of IgA nephropathy hinders its treatment. The correlation of renal dysfunction with the immunophenotype of leukocytic infiltrates revealed interstitial CD20(+) cells and tubular NKG7(+)(GMP-17(+))/CD8(+) intraepithelial cells as predictive markers of progression in early-phase IgA nephropathy. This suggests that adaptive and innate immune responses mediate progression.

Glycogen synthase kinase 3beta: a novel marker and modulator of inflammatory injury in chronic renal allograft disease.

One key cell-signaling event central to inflammation in kidney diseases, including chronic renal allograft dysfunction or disease (CRAD), is the activation of NF-kappaB, which controls transcription of numerous proinflammatory mediators. Glycogen synthase kinase (GSK) 3beta is an indispensable element of NF-kappaB activation, however, the exact role of GSK3beta in the pathogenesis of inflammatory kidney diseases like CRAD is uncertain and was examined. Immunohistochemistry staining of GSK3beta was weak in normal kidneys, but was markedly induced in inflamed allograft kidneys, with prominent cytoplasmic staining of tubular cells in areas of inflammation. Net GSK3beta activity is regulated by inhibitory phosphorylation of its serine 9 residue, and this occurred in CRAD. Thus, the magnitude of GSK3beta inactivation was inversely correlated with the degree of injury as assessed by Banff criteria. In vitro in cultured human tubular epithelial cells, GSK3beta overexpression augmented, while GSK3beta silencing diminished proinflammatory cellular responses to TNF-alpha stimulation, including NF-kappaB activation and expression of chemokines MCP-1 and RANTES. These inflammatory responses were obliterated by GSK3beta inhibitors. Collectively, GSK3beta plays an important role in mediating proinflammatory NF-kappaB activation and renal inflammation. Suppression of GSK3beta activity might represent a novel therapeutic strategy to treat CRAD.

Prognostic value of postoperative and post-ablative serum thyroglobulin levels in patients with differentiated thyroid cancer.

BACKGROUND: The study was designed to examine the value of post-operative and post-ablative serum thyroglobulin levels and diagnostic whole body scan in predicting remission in patients with differentiated thyroid carcinoma. METHODOLOGY: Serum TG levels and diagnostic iodine-123 whole body scans performed prior to and 6-12 months after 131I ablation for DTC were evaluated in 100 consecutive patients at King Faisal Specialist Hospital Riyadh. Patients were followed up for a period of 7.6 years (range 7-10 years). All patients underwent total thyroidectomypriorto 131I ablation. RESULTS: Patients with serum TG levels < 8 ng/ml post thyroidectomy (50 patients) also maintained low TG < 8 ng/ml after 131I ablation and had better outcome (60%) remission. On the other hand DTC subjects with higher TG > 8 ng/ml post thyroidectomy (50 patients) 40% remained in remission X2 = 4.00, p = 0.046. For the group with initial high post-operative TG, it became < 8 ng/ml in 34/50 (68%) patients after ablation with 131I and in this subgroup, remission was seen in 16/34 (47%) of patients in contrast to 4/16 (25%) remission rate in those who continue to have TG > 8 ng/ml after ablation. At the end of follow up, 123I-WBS was positive in 4% and 10% of patients with initial TG < 8 ng/ml and TG > 8 ng/ml respectively; X2 = 1.38, p= 0.24. CONCLUSION: Post-operative and post-ablative serum TG levels -but not follow up diagnostic WBS- have predictive values and permit selection of patients with higher risk for persistent/recurrent disease.

Influence of antigen on immune complex behavior in mice.

To explore the possibility that the behavior of immune complexes can, under some circumstances, be directed by the antigen, we have studied the behavior of complexes of identical size made with the glycoproteins, orosomucoid (OR), and ceruloplasmin: or with their desialylated derivatives, asialo-orosomucoid (ASOR) and asialo-ceruloplasmin. Such desialylated proteins are rapidly removed from the circulation by a hepatic cell receptor for galactose, the sugar exposed upon removal of sialic acid. Mixtures of 125I-goat anti-ASOR with either ASOR or OR and mixtures of 125I-rabbit anti-OR with either ASOR or OR form complexes identically. The complexes were separated by density gradient centrifugation and injected intravenously into C3H mice. Blood clearance and hepatic uptake of the OR complexes and ASOR complexes were markedly different. T 1/2 for the goat OR complexes exceeded 300 min, whereas that for the ASOR complexes was 15 min. More detailed studies using rabbit complexes of various sizes revealed that light rabbit complexes behaved similarly to the goat complexes. The light rabbit OR complexes were cleared slowly, with only 18% found in the liver at 60 min, whereas the light rabbit ASOR complexes were cleared much more rapidly, with 62% found within the liver by 30 min. This rapid clearance was completely suppressed by a prior injection of a blocking dose of ASOR, which implies uptake by a galactose-mediated mechanism on hepatocytes. As the size of the rabbit complexes increased, so did the rate of Fc receptor-mediated clearance. Heavy rabbit OR complexes were cleared more rapidly than light OR complexes but not so rapidly as heavy ASOR complexes. The clearance and hepatic uptake of the heavy OR complexes were markedly suppressed by a prior injection of heat-aggregated gamma globulin, a known Fc receptor-blocking agent (45% hepatic uptake without and 6% with aggregated gamma globulin). The heavy rabbit ASOR complexes exhibited inhibition of blood clearance and hepatic uptake by both galactose receptor-blocking and Fc receptor-blocking agents. A blocking dose of ASOR reduced the hepatic uptake at 30 min from 75 to 49%, and heat-aggregated gamma globulin reduced it from 75 to 39%, which suggests that these heavy complexes were removed from the circulation by receptors both for the immunoglobulin and for the antigen. Cell separation studies and autoradiographs confirmed that those complexes cleared primarily by galactose-mediated mechanism were within hepatocytes, and those cleared by Fc receptors were within the nonparenchymal cells of the liver. It seems probable, therefore, the some antigen-antibody complexes may be removed from the circulation via receptors not only for immunoglobulin but also for antigen.

One- to ten-year follow-up results of balloon angioplasty of native coarctation of the aorta in adolescents and adults.

OBJECTIVES: We attempted to evaluate the role of balloon angioplasty in the treatment of discrete coarctation of the aorta in adolescents and adults, with special emphasis on long-term results. BACKGROUND: Controversy persists over the use of balloon dilation for the treatment of native coarctation of the aorta. METHODS: Between July 1986 and January 1997, 43 consecutive adolescent and adult patients with discrete coarctation of the aorta underwent balloon angioplasty. One- to 10-year follow-up data of 37 patients, including results of cardiac catheterization and magnetic resonance imaging (MRI), form the basis of this study. RESULTS: No early or late deaths occurred. Balloon angioplasty produced a reduction in the peak to peak coarctation gradient from a mean +/- SD of 69 +/- 24 mm Hg (95% confidence interval [CI] 61 to 76) to 12 +/- 8 mm Hg (95% CI 10 to 14.8) (p < 0.001). Follow-up catheterization 12 months later (37 patients) revealed a residual gradient of 6.7 +/- 6 mm Hg (95% CI 4.6 to 8.9); 3 (7%) of 43 patients had suboptimal results with development of recoarctation, defined as peak gradient >20 mm Hg, with successful repeat angioplasty. A small aneurysm developed at the site of dilation in 3 (7%) of the 43 patients. MRI follow-up data 1 to 10.8 years (mean 5.2 +/- 2.7) after angioplasty (37 patients) revealed no new aneurysm or appreciable change in the size of the preexisting aneurysm in the three patients. The blood pressure had normalized without medication in 27 (73%) of 37 patients at follow-up examination. CONCLUSIONS: Balloon angioplasty is safe and effective and should be considered a viable alternative to operation for treatment of discrete coarctation of the aorta in adolescents and adults.

Duration of neuroleptic treatment and prevalence of tardive dyskinesia in late life.

BACKGROUND: Although increasing age is the most consistently cited risk factor for the development of tardive dyskinesia for patients in the second to sixth decades of life, this relationship may not hold within geriatric populations. METHODS: Consecutively admitted geropsychiatric inpatients were examined with the Abnormal Involuntary Movement Scale within 72 hours of admission; comprehensive demographic, diagnostic, and psychometric data were also obtained. RESULTS: Seventy-four (19.2%) of 386 patients received diagnoses of dyskinesia. Lifetime duration of neuroleptic use was strongly correlated with dyskinesia rates. After accounting for the effect of lifetime duration of neuroleptic use in a stepwise logistic regression, only associations with Global Assessment Scale score and presence of dental problems remained statistically significant. In comparison with the duration of neuroleptic use, however, the contribution of these factors was minor. Sixteen percent of patients with less than 3 months of neuroleptic use, 29% with 3 to 12 months of neuroleptic use, 30% with 1 to 10 years of neuroleptic use, and 41% with more than 10 years of neuroleptic use had dyskinesia. Compared with patients with no history of neuroleptic treatment, the relative risks for these durations of neuroleptic use were 1.62 (95% confidence limits [CL], 0.81, 3.24), 2.89 (95% CL, 1.50, 5.55), 3.08 (95% CL, 1.66, 5.70), and 4.11 (95% CL, 2.12, 7.96), respectively. CONCLUSIONS: Within elderly populations, duration of exposure to neuroleptics is the strongest predictor of risk for tardive dyskinesia, and this risk increases rapidly within the first year of total lifetime neuroleptic use.

Lingual thyroid. Diagnosis and treatment.

We describe four patients who presented with a lingual thyroid condition (three females and one male, aged between 7 and 22 years). Only the male patient was symptomatic with mild dysphagia and hemoptysis. The diagnosis was suspected in three patients, and was confirmed by iodine 123 or 131 scanning in all patients and by a computed tomographic scan in the one patient studied. The patient with dysphagia received a 10-mCl therapeutic dose of iodine 131 before thyroxine replacement was started. The diagnosis and management of lingual thyroid is discussed. All patients need lifelong thyroxine suppression. Unenhanced computed tomographic scans have a diagnostic appearance due to the iodine content of the ectopic thyroid tissue.

Maternal and perinatal outcome of pregnancies complicated by cardiac disease.

OBJECTIVE: The aim of this study was to assess the maternal and perinatal outcome of pregnancies complicated by cardiac disease in a tertiary care center in Egypt. METHODS: During a 1-year period, a total of 86 pregnant women with cardiac disease were admitted. Maternal and perinatal morbidity and mortality were calculated and compared with a control group. RESULTS: Seventy-seven (89.5%) patients were due to rheumatic affection, and 60 patients were classified as NYHA classes I-II. There was one case of maternal mortality (1.16%), and 10 other cases developed life-threatening complications. Two perinatal mortalities (2.32%) occurred in this series. Birth weight of babies born to mothers with functional classes III and IV were significantly lower than those of functional classes I-II and control group. CONCLUSION: Rheumatic heart disease with pregnancy is still predominant in Egypt. Maternal and perinatal morbidity and mortality are strongly correlated to maternal cardiac functional classification.

[Acute myocardial infarction: what is new?]. / Infarctus du myocarde et thrombolyse: actualités.

Current recommendations on the management of acute myocardial infarction and the use of thrombolysis are reviewed.