Neutrophil to Lymphocyte Ratio as a Predictor of Poor Prognosis in Metastatic Pancreatic Cancer Patients Treated with Nab-Paclitaxel plus Gemcitabine: A Propensity Score Analysis.

BACKGROUND: High neutrophil to lymphocyte ratio (NLR) has shown to be a predictor of poor outcomes in various malignancies, including pancreatic cancer. METHODS: We assessed 70 consecutive pts with histologically confirmed mPC who received chemotherapy with nab-paclitaxel/gemcitabine at two different European oncologic centers between January 2012 and November 2015. Variables assessed for prognostic correlations included age ≥ 66, sex, Karnofsky PS score, primary tumor site, baseline CA19.9 level ≥ 59xULN, 12-week decrease of the CA19.9 level ≥ 50% from baseline, basal bilirubin level, baseline NLR, biliary stent implantation, and liver metastasis. Survival analyses were generated according to the Kaplan-Meier method. Univariate and multivariate analyses were performed by a Cox proportional hazard model. RESULTS: According to NLR values, the patients were divided into two groups: high and low. Low group patients showed a better median PFS (7 months versus 5 months) and median OS (13 months versus 7 months) in respect to high group patients. At multivariate analysis, Karnofsky PS < 80% (HR = 0.4; CI 0.2-1.2), liver metastases (HR = 0.4; CI 0.18-0.82), and NLR ≥ 5 (HR = 2.7; 95% CI 1.4-5.2) were predictors of poorer OS. Based on the presence of one or more independent prognostic factors, three risk categories were identified: good-risk, intermediate-risk and poor-risk. The median OS was 22, 10, and 7 months, respectively. CONCLUSIONS: Baseline NLR is an independent predictor of survival of patients with mPC receiving palliative chemotherapy and could be useful to develop a simple clinical score to identify a subgroup of patients with a low chance to benefit from chemotherapy.

Mesangial hypercellularity predicts antiproteinuric response to dual blockade of RAS in primary glomerulonephritis.

The greater antiproteinuric efficacy of converting enzyme inhibitor and angiotensin II receptor blocker combination (CEI+ARB), versus monotherapy with either drug, is not a consistent finding. We evaluated the clinicopathologic predictors of response to CEI+ARB in 43 patients with primary glomerulonephritis (GN), never treated with immunosuppressive drugs, and with persistent proteinuria after CEI alone. Main histological lesions were analyzed by obtaining on 557 glomeruli and 165 arteries formal score of mesangial cellularity, glomerulosclerosis, tubulointerstitial damage, mononuclear cell infiltration, arteriosclerosis, and arteriolar hyalinosis. Duration of CEI and CEI+ARB therapy was similar (4.7+/-2.4 and 5.0+/-1.5 months). Proteinuria (g/day) decreased from 3.5+/-2.9 to 2.4+/-2.3 after CEI, and to 1.5+/-1.3 after CEI+ARB (P<0.0001). Reduction of proteinuria after CEI+ARB was greater in proliferative versus non-proliferative GN (-63.3+/-23.4 versus 42.4+/-23.7%, respectively; P=0.006). When patients were categorized in responders and non-responders to CEI+ARB, no difference between the two groups was detected in any demographic or clinical variable, whereas histology showed in responders a greater prevalence of proliferative GN (71.4 versus 31.8%, P=0.009) and higher score of mesangial cellularity (1.76+/-0.53 versus 1.20+/-0.22, P<0.0001). At multiple regression analysis (r(2)=0.476, P=0.001), response to CEI+ARB resulted independently related only to mesangial cellularity (P<0.0001). In conclusion, the best independent predictor of antiproteinuric efficacy of CEI+ARB in patients with primary GN is the degree of mesangial cellularity. This finding supports the experimental evidence that high angiotensin II contributes to proliferation of mesangial cells.

[Hypertension in patients on hemodialysis: the role of salt intake]. / L'ipertensione arteriosa nell'uremico in emodialisi: importanza dell'intake di sale.

In the 1960s, about 10% of hemodialysis (HD) patients had hypertension; the current percentage of hypertensive patients has risen to 70-75%. The scarce implementation of low-salt diets and the increment of dialysate sodium concentration aimed at ameliorating treatment tolerability are the main causes of the currently poor hypertension control. Considerable sodium intake activates a vicious circle: an increase in serum osmolarity, greater thirst and greater water intake, high inter-dialytic weight gains, need for large ultrafiltration rates, more frequent episodes of intradialytic hypotension, failure to achieve dry weight, progressive extra-cellular volume (ECV) expansion, and finally, blood pressure (BP) increase. Therefore, many studies have pointed out the importance of a low-salt diet in HD; it has been proven that the normalization of BP and ECV overload with a low-salt diet is associated with left ventricular hypertrophy regression and diastolic dysfunction improvement. Preparing meals with fresh foods, using spices, avoiding salt when cooking, and drastically limiting salty foods reduce dietary sodium down to about 6 g/day. Sodium intake during inter-dialytic periods can easily be assessed by measuring the changes in serum sodium concentration and in body weight.

[Clinical management of the patient affected with acute renal failure (ARF) secondary to volume depletion]. / Gestione clinica del paziente con insufficienza renale acuta (IRA)da ipovolemia.

Most cases of ARF are secondary to volume depletion. In the literature, very few scientific publications address the problem of what to do when confronted with such a patient. As regarding the diagnosis of hypovolemia, an accurate history and physical examination can help to determine both the presence and etiology of volume depletion; postural hypotension (decrement in systolic blood pressure of more than 20 mmHg after standing from the supine position), associated with a pulse increment of 30 beats/min or more and dizziness are specific symptoms of hypovolemia. Laboratory indices are useful to diagnose volume depletion, but their interpretation is not simple, and they may not be available in the non-nephrologic environment. Fluid replacement therapy in hypovolemia is largely dependent upon the type of fluid that has been lost and concurrent electrolytic and acid-base disorders. Patients with hypernatremia and volume depletion should receive mild hypotonic solutions, whereas those with hyponatremia and hypovolemia should receive mild hypertonic solutions. The entity of reinfusion depends on daily losses. Conversely, monitoring of body weight can be considered an adequate index of fluid balance. Concerning the treatment of ARF, the use of loop diuretics in the early phases of pre-renal ARF decrease oxygen consumption in the tubular cells by inhibiting transcellular sodium transport, therefore preventing or limiting ischemic cell injury. The use of loop diuretics should also be evaluated in intermediate syndrome and ischemic NTA where diuretics can, respectively, reduce renal ischemia and convert oliguric ARF into the non-oliguric form.