Complex trauma, PTSD and complex PTSD in African refugees.

Background: The introduction of the diagnosis of complex posttraumatic stress disorder (CPTSD) by ICD-11 is a turning point in the field of traumatic stress studies. It's therefore important to examine the validity of CPTSD in refugee groups exposed to complex trauma (CT) defined as a repeated, prolonged, interpersonal traumatic event. Objective: The objective of this study was to compare DSM-5 and ICD-11 post-traumatic stress disorder diagnoses and to evaluate the discriminant validity of ICD-11 PTSD and CPTSD constructs in a sample of treatment-seeking refugees living in Italy. Method: The study sample included 120 treatment-seeking African refugees living in Italy. All participants were survivors of at least one CT. PTSD and CPTSD diagnoses were assessed according to both DSM-5 and ICD-11 criteria. Results: Findings revealed that 79% of the participants met the DSM-5 criteria for PTSD, 38% for ICD-11 PTSD and 30% for ICD-11 CPTSD. Generally, ICD-11 CPTSD items evidenced strong sensitivity and negative predictive power, low specificity and positive predictive power. Latent class analysis results identified two distinct groups: (1) a PTSD class, (2) a CPTSD class. None of the demographic and trauma-related variables analysed was significantly associated with diagnostic group. On the other hand, the months spent in Italy were significantly associated with PCL-5 score. Conclusions: Findings extend the current evidence base to support the discriminant validity of PTSD and CPTSD amongst refugees exposed to torture and other gross violations of human rights. The results suggest also that, in the post-traumatic phase, the time spent in a 'safe place' condition contributes to improve the severity of post-traumatic symptomatology, but neither this variable nor other socio-demographic factors seem to contribute to the emergence of complex PTSD. Further investigations are needed to clarify which specific vulnerability factors influence the development of PTSD or CPTSD in refugees exposed to complex trauma.

Antecedentes: La introducción del diagnóstico del trastorno de estrés postraumático complejo (TEPT-C) por la CIE-11 es un punto de inflexión en el campo de los estudios del estrés traumático. Por lo tanto, es importante examinar la validez del TEPT-C en los grupos de refugiados expuestos a un trauma complejo (TC) definido como un evento traumático interpersonal prolongado y repetido.Objetivo: El objetivo de este estudio fue comparar los diagnósticos de trastorno de estrés postraumático del DSM-5 y la CIE-11 y evaluar la validez discriminante de los constructos del TEPT y TEPT-C de la CIE-11 en una muestra de refugiados en busca de tratamiento que viven en Italia.Método: La muestra del estudio incluyó a 120 refugiados africanos que buscan tratamiento y que viven en Italia. Todos los participantes fueron sobrevivientes de al menos un TC. Los diagnósticos de TEPT y TEPT-C se evaluaron de acuerdo con los criterios del DSM-5 y de la CIE-11.Resultados: Los hallazgos muestran que el 79% de los participantes cumplieron con los criterios del DSM-5 para el TEPT, el 38% para el TEPT de la CIE-11 y el 30% para el TEPT-C de la CIE-11. En general, los ítems de TEPT-C de la CIE-11 evidenciaron una fuerte sensibilidad y poder predictivo negativo, baja especificidad y poder predictivo positivo. Los resultados del análisis de clase latente identificaron dos grupos distintos: (1) grupo de TEPT, (2) grupo de TEPT-C. Ninguna de las variables demográficas y relacionadas con el trauma analizadas se asoció significativamente con el grupo de diagnóstico. Por otro lado, los meses pasados en Italia se asociaron significativamente con la puntuación de PCL-5.Conclusiones: Los hallazgos amplían la base de evidencia actual para apoyar la validez discriminante del TEPT y el TEPT-C entre los refugiados expuestos a tortura y otras violaciones graves de los derechos humanos. Los resultados sugieren también que, en la fase postraumática, el tiempo pasado en una condición de "lugar seguro" contribuye a mejorar la gravedad de la sintomatología postraumática, pero ni esta variable ni otros factores sociodemográficos parecen contribuir a la aparición del TEPT-C. Se necesitan más investigaciones para aclarar qué factores de vulnerabilidad específicos influyen en el desarrollo de TEPT o TEPT-C en los refugiados expuestos a trauma complejo.

Regression of left ventricular hypertrophy in kidney transplant recipients: the potential role for inhibition of mammalian target of rapamycin.

Left ventricular hypertrophy (LVH) contributes to elevated cardiac mortality with graft function in renal transplant recipients. Antihypertensive therapy, and especially angiotensin-converting enzyme (ACE) inhibitors, proved to be effective in regressing the LVH of renal transplant recipients, at least in part by interacting with immunosuppressive agents, thus raising the possibility that immunosuppressive therapy might affect changes in the left ventricular mass (LVM) of recipients. This review mainly focuses on the potential role of mammalian target of rapamycin (mTOR) inhibition to regress cardiac hypertrophy in both experimental models and in the clinical setting. We comment on the results of experimental studies conducted on animal models, which showed regression of cardiac hypertrophy by sirolimus (SRL). We also discuss clinical studies that show that conversion from calcineurin inhibitors to SRL is effective to achieve regression of LVH in both kidney and cardiac transplant recipients, mainly by reducing the true left ventricular wall hypertrophy.

Reducing the risk of left ventricular hypertrophy in kidney transplant recipients: the potential role of mammalian target of rapamycin.

Persistence of left ventricular hypertrophy (LVH) following renal transplantation is associated with unfavorable outcomes in renal transplant recipients. This review presents clinical data on LVH after renal transplantation and the role of antihypertensive therapy, especially ACE inhibitors, to reduce left ventricular mass, as well as the effects of interactions between antihypertensive medications acting on the renin-angiotensin system and immunosuppressive agents to regress LVH among renal transplant recipients. The effectiveness of sirolimus (SRL) to reduce posttransplantation LVH is also discussed in light of both animal model studies and 2 clinical trials in transplant recipients that showed the efficacy of this immunosuppressive agent to treat LVH in both kidney and heart transplant recipients.

[Left ventricular hypertrophy in chronic kidney disease]. / L'ipertrofia ventricolare sinistra nella malattia renale cronica.

Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk. Left ventricular (LV) hypertrophy (LVH), together with coronary artery disease, has been considered the main target of intervention. LVH is highly prevalent in CKD even in early stages, as compared to general non-selected population. This is mainly due to the multifactorial pathogenesis of LVH in renal patients where both haemodynamic and non-haemodynamic stimuli synergically act inducing either an increase in left ventricular mass or an LV dilation. Anaemia and arterial hypertension seem to be the most important factors. Interventional studies have shown that partial correction of anaemia through epoetin, together with an arterial hypertension successful therapy through renin-angiotensin system acting drugs, such as ACE-inhibitors, were able to induce a LVH regression in CKD. Indeed, the unfavourable outcome in patients with both CKD and LVH, whose survival is reduced and incidence of fatal and non-fatal CV events increased, can be reversed if LVH is regressed by therapy. The most promising strategy in CKD seems to be LVH early diagnosis through echocardiography, the correct screening of risk factors, a LVM longitudinal monitoring through echo, as well as starting treatment in the early stages of CKD, with the aim of improving general and CV prognosis for these patients.

Alport syndrome: HLA association and kidney graft outcome.

Alport syndrome (AS) is a genetic disease of type IV collagen involving non-homogeneous patterns of inheritance characterized clinically by the presence of progressive haematuric nephritis leading to end-stage renal disease (ESRD), hearing loss and/or ophthalmologic abnormalities. The aim of this study was to investigate, in a cohort of AS patients who had undergone a kidney graft (KG) or who were still on a waiting list for a KG, (a) whether there is a correlation between AS and HLA antigen expression, and (b) long-term graft outcome in transplant patients. The AS cohort was represented by 34 ESRD patients, of whom 25 received a KG and the remaining nine were still on a waiting list. AS transplant patients represented 2.78% of 899 first KGs performed at our centre (Transplantation Department at S. Martino Hospital, Genoa) between 1983 and 2002. Grafts were procured from cadaveric donors in 18 cases and from living, related donors in seven cases. All AS transplant patients had a post-transplant follow-up period of at least 12 months. Results showed that: (i) the frequency of the HLA-DRB1*16 antigen was significantly increased in the whole AS cohort as compared to 128 healthy subjects (HS) (corrected P-value 0.0026; relative risk 7.20) as well as to 232 non-AS ESRD patients on a waiting list for KG (corrected P-values 0.0156; relative risk 4.67); (ii) 5- and 10-year graft survivals in the AS transplant patients were 80 and 73%, respectively, and did not differ from those of a control group represented by 25 non-AS KG recipients matched for sex, age, number of HLA mismatches and immunosuppressive treatment. Increased frequency of HLA-DRB1*16 in AS patients may reflect a linkage disequilibrium with genes coding for collagen synthesis.

Arterial hypertension and left ventricular hypertrophy in hemodialysis patients.

The high prevalence of left ventricular hypertrophy (LVH) among hemodialysis patients may be a consequence of inadequate diagnosis and treatment of arterial hypertension (AH). AH is not adaquately controlled in hemodialysis patients probably due to an underestimation of the effective BP load due to the unreliability of clinical BP readings in this population. Furthermore, BP reduction induced by dialysis ultrafiltration is not an acceptable criterion for discontinuing antihypertensive therapy, particularly when LVH coexists. Indeed, the few available interventional studies have demonstrated that strict BP control, together with anemia correction and dialysis adequacy improvement, can induce significant regression of the LVH of hemodialysis patients. Moreover, the decrease of SBP, particularly as a result of ACE-inhibitor therapy, is the most important predictor of LVH regression. Finally the use of ABPM and of echocardiography are recommended for correctly detecting an underlying AH and for tailoring and monitoring the effectiveness of antihypertensive therapy in dialysis patients with LVH.

Derangement of acid-base balance in uremia and under hemodialysis.

Uremic acidosis is due to impaired excretion of ammonium ions in the presence of unchanged acid production. However, the degree of acidosis is quite variable among uremic patients and pre-dialytic bicarbonate levels are mainly independent of dialytic base supply. These observations strengthen the suggestion that extra-renal mechanisms may play a significant role in controlling acid-base balance in uremic patients. The possible effects of diet, intestine, bone, intermediate metabolism, and the global acid-base balance are discussed. The metabolic and clinical effects of mild uremic acidosis are not well defined. In fact, no long-term clinical study have produced clear evidence for increased protein catabolism in humans. Some data provide evidence for reduced bone mineral content and osteomalacic lesions in uremic patients with severe acidosis. Overall, the impact of the present dialytic techniques on acid-base control is quite small, since no major difference is observed in uremic patients treated with different dialytic schedules. Furthermore, the base supply by dialysis does not seem to represent the main mechanism for acid-base correction by dialysis. In conclusion, at present time, metabolic acidosis of uremic patients is often mild and not accompanied by major symptoms. Probably, more attention needs to be paid to the possible noxious effect of over-correction of acidosis.

Abnormal arachidonic acid content of red blood cell membranes and main lithogenic factors in stone formers.

BACKGROUND: Increased arachidonic acid content in red blood cell membranes of stone formers (SF) has recently been reported and is hypothesized as representing the underlying causal factor for both hyperoxaluria and hypercalciuria. We performed the present study to see whether we could confirm this finding and to test whether any relationship exists between the fatty acid composition of red blood cell membranes and the main metabolic factors involved in stone formation. METHODS: In 21 SF and 40 healthy controls subjects the fatty acid composition of red blood cell membranes was assessed. In addition, the following parameters were evaluated in SF: daily and fasting urinary calcium excretion, fractional intestinal calcium absorption, 1,25-dihydroxy-vitamin D, intact parathyroid hormone, hydroxyproline in fasting urine, daily urinary excretion of oxalate, citrate, urate, electrolytes, urea, sulphate, relative supersaturation for calcium oxalate monohydrate. RESULTS: The red blood cell membrane of SF had a lower content of arachidonic acid, linoleic acid, and docosahexaenoic acid than that of control subjects. Arachidonic acid content was not correlated with any of the parameters studied. However, when patients were grouped according to the degree of oxalate excretion, hyperoxaluric SF had a higher arachidonic acid content and arachidonic/linoleic acid ratio than SF with normal oxalate excretion. CONCLUSIONS: Our results do not confirm the finding of an increased arachidonic acid content of red blood cell membrane in SF. On the contrary, reduced arachidonic acid levels were found in our patients. However, hyperoxaluric SF had a relatively higher arachidonic acid content than SF with normal urinary oxalate excretion.

Inadequate diagnosis and therapy of arterial hypertension as causes of left ventricular hypertrophy in uremic dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in the dialyzed population, possibly because of inadequate diagnosis and therapy of arterial hypertension. The purpose of this study was to ascertain the adequacy of our approach in correctly identifying and treating arterial hypertension in our dialysis center. METHODS: Fifty-five dialyzed uremics were studied by continuous ambulatory blood pressure (BP) monitoring, which started before a single hemodialysis (HD) session, continued for 24 hours after HD ended, and was repeated for 15 minutes before the beginning of the next HD. Clinical pre-HD and post-HD routine BP measurements taken the month preceding BP monitoring were retrieved, and echocardiography was performed. RESULTS: LVH was present in 46 out of 55 patients, and clinical pre-HD arterial hypertension was present in 36 out of 55. There were discrepancies between clinical and monitored BPs, mostly concerning diastolic pre-HD BP since BP readings were lower than monitored BP records (P < 0.0002). Although both clinical and monitored BPs bore strong direct correlations with the left ventricular mass (LVM), the closest correlations were those for monitored BP. Four groups of patients were identified by BP monitoring: group A (N = 14), with persistently normal BP, and group D (N = 13), with persistently supranormal BP levels. There were also two other groups (group B, N = 19; and group C, N = 9), whose BP values were high before HD, normalized after HD, and then increased again either soon after HD (group C) or later on following HD (group B). Monthly averaged clinical pre-HD mean BP values differed significantly among the four groups [91 +/- 10 (SD) mm Hg in group A, 101 +/- 7 in group B, 106 +/- 6 in group C, and 106 +/- 7 in group D; P < 0.0001, analysis of variance], as did their corresponding LVMs [132 +/- 27 g/m2 body surface area (BSA), 156 +/- 26, 201 +/- 51, and 200 +/- 36; P < 0.0001]. There were also differences in dialytic age, which was significantly longer in group A patients (109 +/- 54 months), who also tended to have higher, although not significantly higher, Kt/V(urea) values. No differences, however, were detected among the groups as far as type, dosages, and number of antihypertensive drugs given to each individual patient. CONCLUSIONS: The high prevalence of LVH in the dialysis population might be the result of inadequate diagnosis and therapy of arterial hypertension. Arterial hypertension, in fact, was insufficiently treated in our dialysis center, since patients with varying degrees of severity of both arterial hypertension and LVH were kept on antihypertensive therapy of similar strength. Undertreatment may have resulted from not having recognized and/or from having underestimated the severity of arterial hypertension since some clinical BPs were measured incorrectly. Reluctance to use more aggressive antihypertensive therapy might also result from the deceptive feeling of "normalized" BP that one has following volume unloading with dialysis. This causes both the BP to run out of control between dialyses and LVH to worsen.

Detection of anti-erythropoietin antibodies in haemodialysis patients treated with recombinant human-erythropoietin.

An enzyme-immunoassay was developed to evaluate the presence of anti-erythropoietin antibodies in plasma samples obtained from renal failure patients treated with recombinant human erythropoietin (rh-EPO). The assay was specific and reproducible. Normal donors had no antibodies to EPO, while 67% of treated patients were positive to the assay. While the specificity of anti-EPO IgG antibodies was high, their affinity for the antigen was low. This finding can be explained by the very small differences in the structure of rh-EPO compared to that of natural EPO. The assay described could be useful in evaluating the long-term effects of rh-EPO treatment on the control of anaemia in renal failure patients.

Persistent secondary hyperparathyroidism after renal transplantation.

BACKGROUND: The persistence of secondary hyperparathyroidism after renal transplantation is frequent and often complicated by overt hypercalcemia. Recent investigations have shown an effect of the different vitamin D receptor (VDR) genotypes on parathyroid hormone (PTH) secretion in both primary and secondary hyperparathyroidism. The aims of this study were (i) to assess whether persistent secondary hyperparathyroidism after renal transplantation is characterized by any change in calcium-controlled PTH secretion, and (ii) whether different VDR allelic distributions might play any role on this setting. METHODS: Eighty-one cadaveric renal transplantation recipients, followed-up for at least 12 months, were checked for PTH, other primary metabolic and clinical variables, and VDR B/b alleles (BsmI). In 22 of these the following parameters were evaluated: (a) kinetics parameters of the Ca-PTH relation curve; (b) vertebral mineral density; (c) calcitriol serum levels; (d) PTH-related peptide serum levels; and (e) urinary hydroxyproline. RESULTS: According to the stabilised PTH levels (reached by the third month), the patients were divided in two groups: group A (N = 40, PTH < 80 pg/ml) and group B (N = 41, PTH > 80 pg/ml). Group B differed from group A in that patients had higher PTH levels at the time of transplantation, were older in age, and spent more time on dialysis. Group B had increased maximal and minimal PTH levels, and higher set-point levels than Group A. The patients with the BB pattern of VDR genotype were characterized by the lowest PTH levels both at time of transplantation and after stabilization, and lower set point values than patients with Bb and bb patterns. CONCLUSIONS: Our study suggests that (i) the severity of pre-existing secondary hyperparathyroidism is the main factor determining its persistence after renal transplantation, (ii) persistent secondary hyperparathyroidism is characterized by an autonomous pattern of PTH secretion, (iii) the VDR BB genotype seems to be related to lower PTH levels.

Angiotensin-converting enzyme gene polymorphism and reversibility of uremic left ventricular hypertrophy following long-term antihypertensive therapy.

BACKGROUND: Prolonged antihypertensive therapy might be less effective in reversing the left ventricular hypertrophy (LVH) in uremics bearing the deleted (DD) allele of the angiotensin converting enzyme (ACE) gene than in patients with the inserted (II) allele or in those heterozygous (ID) for the gene. METHODS: Thirteen DD and 17 II + ID hemodialyzed uremics were followed-up with yearly echocardiography and 24-hour blood pressure (BP) monitoring over five years while on an antihypertensive therapy that included ACE inhibitors as first line drugs. RESULTS: In the II + ID group there were significant decreases of the left ventricular mass index (LVMi) and of both systolic and diastolic BPs. These changes were less pronounced in the DD group, but the difference was not statistically significant given the wide overlap between the two groups. Further analysis of the data revealed that the only factor associated to a decreased LVMi was the decrease of the systolic BP irrespective of the ACE gene genotype of each individual patient. CONCLUSIONS: The ACE-gene genotype does not necessarily predict the extent to which LVMi will be lowered by ACE-inhibitors therapy. The LVH of hypertensive uremics is amenable by long-term antihypertensive therapy provided that it results in significantly decreased systolic blood pressure.

Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects.

Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.