Predictors of Treatment Resistance Across Different Clinical Subtypes of Depression: Comparison of Unipolar vs. Bipolar Cases.

OBJECTIVE: Treatment-resistant depression (TRD) and treatment-resistant bipolar depression (TRBD) poses a significant clinical and societal burden, relying on different operational definitions and treatment approaches. The detection of clinical predictors of resistance is elusive, soliciting clinical subtyping of the depressive episodes, which represents the goal of the present study. METHODS: A hundred and thirty-one depressed outpatients underwent psychopathological evaluation using major rating tools, including the Hamilton Rating Scale for Depression, which served for subsequent principal component analysis, followed-up by cluster analysis, with the ultimate goal to fetch different clinical subtypes of depression. RESULTS: The cluster analysis identified two clinically interpretable, yet distinctive, groups among 53 bipolar (resistant cases = 15, or 28.3%) and 78 unipolar (resistant cases = 20, or 25.6%) patients. Among the MDD patients, cluster "1" included the following components: "Psychic symptoms, depressed mood, suicide, guilty, insomnia" and "genitourinary, gastrointestinal, weight loss, insight". Altogether, with broadly defined "mixed features," this latter cluster correctly predicted treatment outcome in 80.8% cases of MDD. The same "broadly-defined" mixed features of depression (namely, the standard Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition-DSM-5-specifier plus increased energy, psychomotor activity, irritability) correctly classified 71.7% of BD cases, either as TRBD or not. LIMITATIONS: Small sample size and high rate of comorbidity. CONCLUSIONS: Although relying on different operational criteria and treatment history, TRD and TRBD seem to be consistently predicted by broadly defined mixed features among different clinical subtypes of depression, either unipolar or bipolar cases. If replicated by upcoming studies to encompass also biological and neuropsychological measures, the present study may aid in precision medicine and informed pharmacotherapy.

[Sudden cardiac death in patient with CKD].

Despite significant improvements in technology of dialysis delivery, cardiovascular disease remains the mayor cause of death in dialysis patients. Individuals with End Stage Renal Disease (ESRD( present an high incidence of coronary artery disease, arrhythmia and sudden cardiac death (SCD). This review summarizes the current available literature regarding the physiopathology, the risk factors and potential interventions to reduce the risk of SCD in dialysis patients, including medical therapy or defibrillators.

Muscle stimulation in elderly patients with CKD and sarcopenia.

OBJECTIVES: Aim of our study was to assess the potential effects of high-tone external muscle stimulation (HTEMS) on improvement of endothelial dysfunction (ED) and kidney damage in elderly patients with chronic kidney disease (CKD), sarcopenia and/or serious physical disability with a high Multidisciplinary Prognostic Index (MPI). METHODS: We enrolled 12 consecutive CKD patients with MPI > 0,66 from January 1st, 2008 to December 31st, 2014. Six patients underwent a 2-hours HTEMS during the first day (group A) and the other six patients (group B) underwent a sham experiment with HTEMS without power supply. After 24 hours, patients of group A were shifted to group B and vice-versa. Nitrite/nitrate (NOx), endotheline-1 (ET-1) and urine creatinine concentration were measured in all patients. RESULTS: During HTEMS urine amount increased by 22% (p=0.049), so did urine creatinine that increased by 40%, (p=0.034) and creatinine clearance that increased by 26% (p=0.041). There was no statistical difference in urine nitrogen (that raised by 11%, p=0.526), urine sodium (that reduced by 42%, p=0.121) and urine potassium levels (p=0,491). At the same time, NOx changed from 44.15.1 to 38.45.3 M/L after 1 hour, to 36.44.8 M/L after 2 hours, to 41.15.7 M/L after 3 hours and to 46,95.0 M/L after 4 hours (p=0.008) during HTEMS, while it did not vary during the sham section of the experiment, respectively 43.66.1 M/L , 436.4 M/L, 42.85.5 M/L, 434.7 M/L, and 42.85.8 M/L (p=0.992). CONCLUSION: Our study showed that HTEMS may improve microcirculation and, through this mechanism, may reduce kidney damage in elderly patients with CKD and severe muscle atrophy.

[A short report: Blood pressure variability and outcomes in chronic kidney disease long survivors patients]. / Short report: la variabilità della pressione arteriosa influenza la mortalità cardiovascolare e la morte renale in pazienti con Chronic Kidney Disease (CKD) and long survivors.

In the last decade blood pressure variability (BPV) measured during a follow-up of hypertensive chronic kidney disease (CKD) patients or hemodialysis patients has received a even major attention. The aim of our study is to study the relationship between BPV and mortality and/or dialysis initiation in long survivors CKD patients. We conducted a historical prospective observational multicentric study in 131 subjects still alive at 31st December 2010, when ended a our previous study published on Nephrology Dialysis Transplantation. Long Survivors patients were younger (p<0.01) and had a lower BPV compared to the original population. Moreover, they had creatinine levels significantly lower (p<0.019), so as lower phosphate levels (p<0.05) and higher hemoglobin (p<0.05). During a mean follow-up of 80.713.4 months, 63 patients (48.1%) died and 49 of them (37.4%) started dialysis treatment. In this group, 28 patients died after dialysis initiation. Kaplan-Meier curves showed a significant association between BPV and cardiovascular mortality risk (Hazard Ratio [HR]: 1.061; 95% Confidence Interval [CI]: 1.0351.093; p = 0.001) and between BPV and renal death (HR 1.049; 95% CI: 10121.74; P = 0.001). In conclusions, our data in long survivors patients showed that BPV can be used for mortality cardiovascular and renal death risk stratification in CKD patients.

High-tone external muscle stimulation in patients with acute kidney injury (AKI): beneficial effects on NO metabolism, asymmetric dimethylarginine, and endothelin-1.

OBJECTIVES: The aim of this study was to assess potential effects of high-tone external muscle stimulation (HTEMS) on parameters of endothelial dysfunction (ED) in patients with acute kidney injury (AKI). BACKGROUND: The bad outcome of AKI patients is markedly influenced by ED, microinflammation, oxidative stress and protein hypercatabolism. Recently, we have shown that intradialytic application of HTMS was associated with a faster resolution of AKI. Here, we investigated in the same cohort of patients whether parameters of ED such as nitric oxide (NO), asymmetric-dimethylarginine (ADMA), and endothelin 1 (ET-1) are modulated by HTEMS as compared to non-HTEMS-treated AKI patients. METHODS: In a post-hoc study we analyzed plasma samples of the 34 AKI patients stage 5, of whom 17 underwent intradialytic HTEMS treatment while the other 17 served as AKI dialysis controls. Measurements included plasma nitrate and nitrite (NOx), ADMA, ET-1 and were performed before and on days 3, 7, 14, 21, and 28 after start of daily dialysis. Additional 16 healthy volunteers served as controls. RESULTS: Initially, in both AKI groups NOx levels were markedly lower and ADMA and ET-1 levels were higher compared to the healthy controls. After initiation of daily hemodialysis the HTEMS group showed a faster improvement of NOx and ET-1 (after 1 week) and ADMA levels (after 2 weeks) compared to the No- HTEMS group. After 2 weeks, all parameters of the HTEMS group were not different from healthy controls, while the No-HTEMSAKI group needed 3 - 4 weeks. CONCLUSION: Our findings suggest for the first time that in AKI patients, application of HTEMS is associated with a faster normalization of lowered NOx and elevated ADMA and ET-1 plasma levels. We hypothesize that the more rapid amelioration of these parameters in the HTEMS group contributed to the accelerated recovery of AKI. With regard to the small study groups with different causes of AKI, investigations in a greater number of AKI patients is required.

[The devil teaches us his tricks... and also how to hide them]. / Quando il diavolo fa le pentole ma anche i coperchi.

Spontaneous ureteric ruptures is a rare condition [1]and bilateral ureteric rupture is even more uncommon. Few cases are described in the literature in which bilateral ureteric rupture is associated to dermatomyositis [2]or to intra-arterial contrast medium application for infrarenal aortic stent placement [3]. We discuss here a case of bilateral ureteric rupture in a 74-year-old man with bladder cancer, presenting oliguric acute kidney failure and a light abdominal pain.

[An unusual case of acute kidney insufficiency]. / Un caso insolito di Insufficienza renale acuta.

Acute aortic dissection (AAD) is a life-threatening condition with high morbidity and mortality, that involves renal arteries in at least 5-10% so leading to renal ischemia and insufficiency. AAD presenting with anuria and the necessity of renal replacement therapy occurs rarely. Here we describe a case of a hypertensive and obese patient presenting with anuria and acute kidney injury, who underwent to hemodialysis and later was diagnosed with aortic dissection. Through this case, we underline the importance of considering AAD as an important differential in patients with a long history of uncontrolled hypertension presenting with anuria.

Vascular calcification and subendocardial ischemia in hemodialysis patients: a new morpho-functional score to assess cardiovascular risk: the Solofra score.

BACKGROUND: ESRD (end-stage renal disease) patients have a high cardiovascular mortality risk. A morphofunctional approach of vascular calcifications and myocardial perfusion is needed for the management of ESRD patients. We used SEVR (sub-endocardial viability ratio) and Kauppila score from the dialysis population of the Independent study to create a new morpho-functional score to assess cardiovascular risk in this population (the Solofra score). MATERIALS AND METHODS: 184 patients were followed-up for 36 months. A side lumbar X-ray was performed to assess vascular calcifications of lumbar aorta using the Kauppila score. Central aortic pressure and pulse velocity wave (PWV) were assessed at the carotid artery site. Myocardial perfusion was estimated with SEVR. Independent risk mortality factors were identified with univariate regression analysis (p<0.01); significance was defined as p<0.05. RESULTS: Kauppila score was 13±10(range 0-24); PWV was 9.5±4 m/sec; basal SEVR was 1.3±0.9. We observed an improvement of ROC curves for SEVR and Kauppila score together compared to the ones for SEVR or Kauppila score alone. CONCLUSION: A quantitative analysis of vascular calcifications should be associated to a qualitative evaluation of arterial damage to better estimate cardiovascular mortality risk of ESRD patients. Further studies are needed to verify our hypothesis.

[Hemodialysis improves the subendocardial viability ratio]. / Il trattamento emodialitico migliora Sub-Endocardial Viability Ratio.

The subendocardial viability ratio (SEVR), a parameter introduced by Buckberg, represents a non-invasive measure of myocardial perfusion related to left ventricular work. AIM. The aim of this study was to verify if dialysis may determine modifications of SEVR and how these modifications are modulated in the 2-day interdialytic period. METHODS.We studied 54 subjects of mean age 6314 years and receiving dialysis for 3215 months. Exclusion criteria were diabetes, resistant hypertension and peripheral vascular diseases and intradialytic hypotension evidenced during the study dialysis session. Pulse wave velocity and SEVR assessments were performed during the third dialysis session of the week, before (pre-HD) and after (post-HD) dialysis, in 2-day interdialytic period after and at the beginning of the following dialysis session. RESULTS.Dialysis reduces PWV, in particular the tertile with the lowest PWV presents the highest percentage reduction (-26%) compared with the second and the third tertiles. In the same way, dialysis leads to an increase of SEVR and patients in the tertile with the highest SEVR values maintain high SEVR values during dialysis and in the interdialytic period. Patients with severe vascular calcifications present higher PWV value and lower SEVR value. CONCLUSIONS.The results of present study demonstrate that ultrafiltration improves PWV (with a mean reduction of 16%) and SEVR (increase of 13%) and that the severity of vascular calcifications influences the effect of ultrafiltration on these two parameters. More studies are certainly necessary to verify our findings. Considered the higher mortality of patients with higher SEVR, it would be important to understand if new dialytic strategies are needed in patients with higher PVW and lower SEVR values.

Treatment of hypertension in Italian nephrology out-patient clinics: the THIN Study.

Optimal pressure control is crucial to prevent cardiovascular events in hypertensive patients. However, well-controlled blood pressure is encountered only in a small percentage of hypertensive patients managed by general practitioners, cardiologists, diabetologists, and hypertension specialists. This study aimed to evaluate the target of blood pressure obtained in Italian nephrology out-patient clinics. Data were collected by questionnaire sent to nephrology out-clinics. Questions were pertinent to patient's clinical characteristics, lifestyle, biochemistry, blood pressure at the first and last visit, and antihypertensive medications. Data pertinent to 1,632 patients were collected. More frequent causes of hypertension were essential hypertension (26%), hypertension secondary to renal insufficiency (16%), and diabetes (10%). At admission the systolic blood pressure was more than 140 mm Hg in 98% and diastolic blood pressure was more than 90 mm Hg in 95% of patients; at the last visit a normalized systolic and diastolic blood pressure was found in 38% and in 75% of patients. A higher normalization rate was achieved in essential hypertensive patients compared with patients with hypertension secondary to chronic renal insufficiency and diabetes. These data indicate that improvement is obtained by nephrologists in controlling essential hypertension although more effective strategies in the management of hypertension in patients with reduced renal function and in diabetic patients still are required.