Mortality of Haemodialysis Patients With and Without Chronic Itch: A Follow-up Study of the German Epidemiological Hemodialysis Itch Study (GEHIS).

The GEHIS (German Epidemiological Hemodialysis Itch Study) is a representative cohort study started in 2013 with 860 haemodialysis (HD) patients in 25 German dialysis units. Chronic itch (CI) has been reported to be a poor prognostic marker for patients on HD; however, this has not been investigated in a representative patient cohort. In 2017, all HD patients were contacted again to investigate mortality in those with and without CI and to identify its determinants. Patients' characteristics, study instruments and CI were assessed, as in 2013. The response rate was 84.2% (n = 724). One-year mortality was 15.3%. Mortality was significantly higher in those with secondary scratch lesions compared with those with non-affected skin. This was also true after controlling for age and sex in a multivariate model. This study demonstrates a high mortality in HD patients; however, mortality depends on itch intensity, not on the occurrence of CI itself.

Treatment outcomes for unresectable intrahepatic cholangiocarcinoma: Nationwide, population-based, cohort study based on propensity score matching with the Mahalanobis metric.

PURPOSE: No prospective randomized trials have been conducted to date to evaluate the efficacy of palliation of pain or jaundice without treatment, definitive concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiotherapy (CTRT), or chemotherapy (CT) alone for treating unresectable intrahepatic cholangiocarcinoma (ICC). We designed a nationwide, population-based, cohort study to determine the effects of different treatments on patients with unresectable ICC using propensity score matching (PSM) with the Mahalanobis metric. PATIENTS AND METHODS: We classified patients with unresectable ICC from the Taiwan Cancer Registry database into the following 4 treatment groups: group 1, definitive CCRT; group 2, sequential CTRT; group 3, no treatment (palliative therapy for relief of pain, pruritus, or jaundice); and group 4, CT alone. Confounding factors among the 4 treatment groups were minimized through propensity score matching (PSM). RESULTS: After PSM, the final cohort consisted of 844 patients (211 patients in each of the 4 groups). In both univariable and multivariable Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) derived for groups 1 and 2 compared with group 4 were 0.65 (0.59-0.71) and 0.95 (0.83-1.48), respectively. Furthermore, an aHR (95% CI) of 2.25 (1.89-2.67) was derived for significant independent prognostic risk factors for poor overall survival for group 3 compared with group 4. CONCLUSIONS: Definitive CCRT is the optimal therapy for patients with unresectable ICC without distant metastasis.

Prognostic importance and determinants of uremic pruritus in patients receiving peritoneal dialysis: A prospective cohort study.

BACKGROUND: Uremic pruritus is a common and frustrating symptom among patients receiving peritoneal dialysis (PD). This study aimed to examine the prognostic importance of uremic pruritus and to identify the determinants for higher pruritus intensity in PD patients. METHODS: We conducted a prospective cohort study of patients receiving maintenance PD. A visual analogue scale (VAS) score was used to measure the intensity of uremic pruritus. The composite endpoint of PD technique failure or all-cause death was assessed using a multivariable Cox proportional hazards model. The determinants for the VAS score of uremic pruritus was assessed using a multivariable linear regression model. RESULTS: Among the 85 PD patients, 24 (28%) had uremic pruritus. During a median follow-up of 28.0 months, 12 patients experienced technique failure, and 7 died. We found that a higher VAS score of pruritus intensity was an independent risk factor for technique failure or death (hazard ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P = 0.003) after adjusting for a variety of confounding factors. We also found that a weekly total Kt/V of less than 1.88, a longer duration of dialysis, a higher dietary protein intake, and higher blood levels of intact parathyroid hormone and high-sensitivity C-reactive protein were independent determinants of higher VAS scores of pruritus intensity. CONCLUSIONS: Our results show that uremic pruritus is an independent risk factor of technique failure and death in patients receiving PD. We also found that a weekly total Kt/V < 1.88 is associated with higher intensity of uremic pruritus in PD patients.

Uremic Pruritus is Associated with Two-Year Cardiovascular Mortality in Long Term Hemodialysis Patients.

BACKGROUND/AIMS: Uremic pruritus (UP) is an unpleasant complication in patients undergoing maintenance dialysis. Cardiovascular and infection related deaths are the major causes of mortality in patients undergoing dialysis. Studies on the correlation between cardiovascular or infection related mortality and UP are limited. METHODS: We analyze 866 maintenance hemodialysis (MHD) patients in our hemodialysis centers. Clinical parameters and 24-month cardiovascular and infection-related mortality are recorded. RESULTS: The associations between all-cause, cardiovascular and infection related mortality with clinical data including UP are analyzed. Multivariate Cox regression demonstrated that UP is a significantly predictor for 24-month cardiovascular mortality in the MHD patients (Hazard ratio: 3.164; 95% confidence interval, 1.743-5.744; p < 0.001). CONCLUSION: Uremic pruritus is one of the predictor of 24-month cardiovascular mortality in MHD patients.

Skin manifestations of chronic kidney disease / Manifestaciones Cutáneas de la Enfermedad Renal Crónica Skin manifestations of Chronic Kidney Disease

Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions

Las manifestaciones cutáneas asociadas a enfermedad renal crónica son muy comunes. La mayoría de estas enfermedades se presentan en la etapa terminal y pueden afectar la calidad de vida del paciente. El conocimiento de estas condiciones puede ser útil para establecer un diagnóstico y pronóstico preciso. El prurito renal severo está asociado a un incremento en la mortalidad y a un pobre pronóstico. La exploración ungueal puede proveer datos acerca del nivel plasmático de albumina y urea. La fibrosis sistémica nefrogénica es una enfermedad prevenible asociada a contrastes con gadolinio. Comorbilidades como la diabetes mellitus y el hiperparatiroidismo secundario, pueden causar dermatosis perforante adquirida y calcifilaxis, respectivamente. Existen tratamientos efectivos e innovadores para todos estos padecimientos

Food-induced anaphylaxis: mast cells as modulators of anaphylactic severity.

A food-induced anaphylactic reaction can occur within seconds to a few hours following exposure to the causal food allergen and often affects multiple organ systems including gastrointestinal, cutaneous, respiratory, and cardiovascular. A conundrum in the allergy field is that consumption of the same allergen can cause reactions of vastly different severity in separate individuals; one patient may experience a mild non-life-threatening reaction characterized by pruritis of lips or urticaria whereas another may experience a life-threatening reaction that involves respiratory and cardiovascular compromise leading to loss of consciousness and sometimes death. While there are tests available to determine the predictive risk value of a positive food challenge test or clinical reactivity, there is currently no reliable method to distinguish between individuals who are at risk of mild non-life-threatening versus life-threatening reaction. Recent research has significantly advanced our understanding of the involvement of immune pathways in the effector phase of food-induced anaphylaxis; a void remains regarding our understanding of the contribution of these pathways to severity of disease. In this review, we discuss mild non-life-threatening versus life-threatening food-induced anaphylaxis and factors (co-morbidities and immune activation) that predispose individuals to more severe disease. Furthermore, we summarize recent advancements in our understanding of the involvement of underlying immune pathways in systemic and food-induced anaphylaxis in mouse systems and discuss how these pathways may contribute to more severe disease phenotype.

Lumbar intrathecal administration of the quaternary lidocaine derivative, QX-314, produces irritation and death in mice.

BACKGROUND: We recently found that peripheral administration of the quaternary lidocaine derivative, QX-314, produces long-lasting sensory and motor blockade in animals. The goal of this study was to test whether intrathecal QX-314 has similar properties. METHODS: We conducted a randomized, double-controlled, blinded study with female CD-1 mice. Animals in the treatment group received lumbar intrathecal QX-314 (0.5-10 mM; volume, 2 microl; each concentration, n = 6). Normal saline and lidocaine (70 mM) served as negative and positive controls (each group, n = 12), respectively. Animals were tested for up to 3 h for lumbosacral neural blockade and observed for adverse effects. RESULTS: No animal injected with saline and 11 of 12 (92%) animals injected with lidocaine displayed reversible lumbosacral motor blockade (P < 0.001). QX-314 (5 mM) produced motor blockade in four of the six (67%) and sensory blockade in five of the six animals (83%; P < 0.05 vs. saline). However, six of the six mice (100%) at 5 mM QX-314 and five of the six (83%) at 10 mM exhibited marked irritation; one of the six animals at 5 mM (17%) and two of the six at 10 mM (33%) died. We observed no neural blockade without adverse effects in any animal injected with QX-314. All animals injected with saline and 11 of the 12 (92%) animals injected with lidocaine demonstrated normal behavior. CONCLUSION: Lumbar intrathecal QX-314 concentration-dependently produced irritation and death in mice, at lower concentrations than those associated with robust motor blockade. Although QX-314 did produce long-lasting neural blockade, these findings indicate that QX-314 is unlikely to be a suitable candidate for spinal anesthesia in humans.

Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality.

BACKGROUND: Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown. METHODS: This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) were used to evaluate inflammation. The patients were followed-up for 30 months. RESULTS: Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-α levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) × (moderate/severe uremic pruritus) (all P < 0.05). CONCLUSION: In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population.

Itchy skin--a clinical problem for haemodialysis patients.

BACKGROUND: Uraemic pruritus affects many patients receiving chronic dialysis therapy for end-stage renal disease. It is a distressing symptom which has a negative impact on quality of life (QoL) of the patients. The condition is also very frustrating for both patients and physicians since no effective treatment for relief of the itch has been demonstrated. The pathophysiological mechanisms of pruritus are mainly unknown despite several hypotheses presented. Recent concepts refer to changes in the opioidergic system and derangements of the immune system. METHODS: In the Dialysis Outcomes and Practice Pattern Study (DOPPS I, 1996-2001) pruritus was assessed by a self-reported questionnaire. The relationship of pruritus to morbidity, mortality, QoL, sleep quality and patient biochemical laboratory data was studied in >200 randomly selected haemodialysis (HD) facilities in seven countries. Pruritus data were collected from >6000 HD patients. Analyses were adjusted for age, gender, race, Kt/V, haemoglobin, serum albumin, serum calcium, serum phosphorus, 13 comorbidities, depression, years on dialysis, country and facility clustering effects. RESULTS: Moderate-to-extreme itch was observed in 46% of prevalent HD patients. Differences in pruritus prevalence were found between countries (ranging from 38% in France to 55% in Italy) and facilities (5-75%). Pruritus was more common in patients on HD >3 months than in patients starting HD. A number of patients' serum characteristics, including high calcium, phosphorous and calcium x phosphorous product levels, were significantly associated with pruritus. Patients with moderate-to-severe pruritus were more likely to feel washed out and to have poor sleep quality, physician-diagnosed depression and a reduced QoL than patients with no or mild pruritus. A significant 15% higher mortality risk was observed in pruritic HD patients but this significance was not seen after adjusting the data for sleep quality measures. CONCLUSIONS: The self-reported prevalence of pruritus in HD patients is relatively high, 40-50%. Pruritus is associated with poor outcomes and a higher mortality risk, probably attributed to poor sleep quality. Better therapeutic treatments are needed for relief of distressing uraemic itching in HD patients.

Toxicological study of the extracts of anti-malarial medicinal plant Enantia chlorantha.

Acute and sub-acute toxicity studies of the medicinal plant Enantia chlorantha were carried out in mice. The oral and s.c. routes of administration of both the aqueous and ethanolic extracts were employed. All the animals reacted to the medicinal plant, when given by both routes, with itching leading to body scratching lasting about 10 minutes. Fatality was not recorded in mice given 0.2g kg-1 s.c. and 20.0g kg-1 orally of both the ethanolic and aqueous extracts of E. chlorantha but larger concentration of both extracts resulted in deaths. Mean lethal dose (LD50) of 0.7g kg-1 was recorded for ethanolic, while 43.65g kg-1 was for aqueous preparations. In the sub-acute toxicity in which the animals were given 3 x 10(3)-5 x 10(-3)g kg-1 of the aqueous extract to drink at will for five weeks, no fatality was recorded and no significant damage to the body organs was observed. These data indicate that the plant drug when taken is safe in diseased states.

Mechanism of pruritus and peracute death in mice induced by pseudorabies virus (PRV) infection.

Mechanisms of postinfectious pruritus and peracute death in mice by pseudorabies virus (PRV) were investigated by inoculating the Yamagata-S81 strain of PRV peripherally or intracerebrally into 4-week-old ICR and BALB/c mice. Clinical signs developed most rapidly in mice inoculated intracerebrally, with intermediate speed in mice inoculated intraocularly, and slowly in mice inoculated subcutaneously. Since intraocularly inoculated mice showed an acute reaction and this is considered a peripheral route, the distribution of viral antigens in the nervous system of intraocularly inoculated mice was examined immunohistologically. Viral antigens were mainly detected along the trigeminal and the oculomotor nerves, but neither necrosis nor an inflammatory response was observed in these areas. The infectious virus was efficiently recovered from the viral antigen-positive tissues. In the pruritic skin lesions, viral antigens were not observed. These findings indicate that the main route of viral spread in intraocularly inoculated mice is the trigeminal and oculomotor nerves and that the virus in the trigeminal nerve may trigger pruritus.