Pulmonary arterial hypertension: guidelines and unmet clinical needs.

The term pulmonary arterial hypertension (PAH) identifies a heterogeneous group of diseases characterized by a progressive increase in pulmonary arterial resistance (PVR), which causes a significant burden in terms of quality of life, right heart failure and premature death. The pathogenesis of PAH is not completely clear: the remodeling of the small pulmonary vessels is crucial, causing an increase in the resistance of the pulmonary circle. Its diagnosis is based on cardiac catheterization of the right heart. According to the present hemodynamic definition of pulmonary hypertension (PH) proposed by the Guidelines of the European Society of Cardiology/European Respiratory Society (ESC-ERS), the mean pulmonary arterial pressure (mPAP) values are ≥25 mmHg. In case of PAH, apart from an mPAP value ≥25 mmHg, patients must have a >3 Wood units increase in PVR and normal pressure values of the left heart. PH is a pathophysiological condition observed in more than 40 different diseases, while PAH is a primary disease of the pulmonary bloodstream potentially treatable with specific drugs. PAH is a severe complication of systemic sclerosis (SSc) affecting about 10% of the patients. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. In fact, despite awareness of the negative impact of SSc-PAH on quality of life and survival, as well as on the severity of lung function, at the moment standardized and shared guidelines and/or screening programs for the diagnosis and the subsequent early treatment of PAH in SSc are not available. The aim of the present paper is to highlight the lights and shadows of SSc-PAH, unraveling the unmet clinical needs on this topic with a proposal of clinical-diagnostic and therapeutic guidelines.

Effect of intravenous supplementation of a new essential amino acid formulation in hemodialysis patients.

Protein energy undernutrition (PEU) and abnormalities of amino acid (AA) metabolism are common in maintenance hemodialysis patients (MHP). A new EAA formulation (BS695), enriched with valine and threonine, containing some histidine, and low in phenylalanine and methionine was recently developed. We randomly supplemented 11 MHP with this solution (treated group, TG) and 10 MHP with a standard AA solution containing both essential and non-essential AA (control group, CG). Both groups received 3.65 g of nitrogen, i.v. three times per week during hemodialysis for six months. During treatment, dietary intake remained stable in both groups. Before treatment, after three and six months of treatment, and six months after the end of treatment, we determined routine blood chemistries, anthropometry, serum protein levels (albumin, transferrin), delayed cutaneous sensitivity (Multi-test), protein catabolic rate (PCR), plasma AA content and motor nerve conduction velocity (MNCV). Before treatment PEU, predominantly of marasmic type, was common. After treatment anthropometry and immune response were unchanged in both groups; PCR increased more in CG than in TG; serum albumin levels decreased significantly only in CG; MNCV improved in TG and worsened in CG. These preliminary results suggest that this new EAA formulation may have beneficial effects on some nutrition related abnormalities of MHP. Better results might occur with long-term AA supplementation, particularly if it is associated with a higher energy intake.

Muscle biopsy studies in chronically uremic patients: evidence for malnutrition.

Evidence for muscle protein wasting and abnormal muscle metabolism is common in uremia. Muscle DNA content is considered a reliable reference standard in normal and undernourished adults. Muscle RNA content rapidly changes during starvation and refeeding. The ratio of noncollagen alkali-soluble proteins (ASP) to DNA is considered to be an estimate of the cytoplasmic volume of a single cell, and the RNA: DNA ratio is an index of the ribosomal capacity for protein synthesis. Muscle DNA, RNA, ASP, water, and fat content were determined in muscle biopsy specimens from chronically uremic patients receiving conservative treatment (CT), maintenance hemodialysis (two centers), or CAPD. Nutrient intake was low and the anthropometric indices were decreased in all groups of patients, except in the hemodialysis patients from one center. Serum proteins and muscle ASP: DNA and RNA: DNA ratios were decreased. The nutritional status was reassessed in some malnourished CAPD patients after about one year of careful nutritional advice and was unchanged. These results suggest that chronically uremic patients on CT are often malnourished, primarily because of an inadequate protein and/or energy intake. Muscle nucleic acid and protein content are useful tools for nutritional assessment at a cellular level in humans with chronic renal failure and can be used to monitor the response to nutritional therapy.

[Prevention of viral hepatitis B with specific gamma globulin. Results of 2 years' experience in a hemodialysis center]. / Profilassi dell'epatite virale B con gamma globuline specifiche. Risultati di due aunni di esperienza in un Centro di Emodialisi.

Prophylaxis with gamma globulins specific for virus hepatitis B was carried out at the Trieste Haemodialysis Centre from December 1979 to December 1981. Since no clear distinction could be drawn between HBsAg-positive dialysed subjects, all staff and patients at the Centre were regarded as constantly at risk for contagion, and hence in the post-exposure state. Those who refused prophylaxis were excluded, together with surface antigen carriers and subjects with antibodies. Specific gamma globulins (Uman-Big) were given at a dose of 0.06 cc/kg at intervals of 90-105 days, together with 0.02 cc/kg standard gamma globulins for conjectured protection against non-A and non-B hepatitis. No allergic reactions worthy of not were observed. Only one patient positivised of all those who underwent continuous prophylaxis. New carriers of HBsAg gradually decreased in number from 1976 to 1981, initially due to the adoption of disposable filters, subsequently owing to partial separation of Au-positives, and finally, in a significant manner, with the introduction of prophylaxis with specific gamma globulins.

Simple methods for nutritional assessment in hemodialyzed patients.

Uremic patients undergoing hemodialysis are often catabolic and malnourished. To treat malnutrition effectively, a preliminary nutritional assessment is needed. Available techniques should enable the clinician to readily detect the presence of malnutrition and to follow the response to nutritional therapy. In a group of chronic uremic patients undergoing maintenance hemodialysis, the authors evaluated the nutritional status with the following indices: 1) assessment of the somatic fat and protein compartments by means of anthropometric measurements (weight/height ratio, triceps and subscapular skinfold thickness, and arm muscle circumference); 2) assessment of the visceral protein compartment (serum total protein, albumin, transferrin, pseudocholinesterase, C3, and immunoglobulin content); 3) assessment of cell-mediated immunity by means of skin tests ("skin window," PPD and phytohemagglutinin) and blood lymphocyte content; and 4) assessment of the dietary intake of nutrients with dietary diaries. Anthropometric indices, serum protein content (except immunoglobulins), and the immune response was generally lower than in normal subjects, suggesting a mixed marasmus-like and kwashiorkor-like pattern of protein-calorie malnutrition. The protein intake was normal, whereas the energy intake tended to be low. Protein intake was significantly correlated with the predialysis serum urea nitrogen. Due to the difficulties in improving oral energy intake and the negative nitrogen balance reported during the days of dialysis therapy, patients were given intravenous supplements of essential or essential and nonessential amino acids for 2 months. The effects of this short-term supplementation were limited.