Pola-R-CHP for frontline therapy in DLBCL: Are we saving money by spending more?

The study by Kambhampati et al. offers the first European perspective on cost-effectiveness of pola-R-CHP in the frontline line treatment of DLBCL patients. Nevertheless, the applicability of these results in other European settings remain questionable: Germany is indeed a wealthy country with wide access to cellular therapies in earlier lines, while this might not be the case for other European countries. The presented data must be re-assessed when long term data on PFS and OS from the POLARIX trial are available, ideally considering also real-life data. Similar CEAs in other European health care systems as well as in specific subgroups of patients are welcome to offer a broader perspective on the potential role of pola-R-CHP in Europe. Commentary on: Kambhampati et al. Cost effectiveness of polatuzumab vedotin in combination with chemoimmunotherapy (pola-R-CHP) in previously untreated diffuse large B-cell lymphoma in Germany. Br J Haematol 2023;202:771-775.

Effect of malolactic fermentation by Pediococcus damnosus on the composition and sensory profile of Albariño and Caiño white wines.

AIM: This study was aimed to investigate the influence of malolactic fermentation (MLF) on sensory profile and organoleptic characteristics of Albariño and Caiño white wines. METHODS AND RESULTS: Autochthonous bacteria were isolated from wines after alcoholic fermentation (AF) and further identified as Pediococcus damnosus by 16S rRNA gene sequence analysis. When a commercial Oenococcus oeni starter was inoculated into Albariño and Caiño white wines to perform MLF, which was checked by HPLC quantification of malic and lactic acids, it was shown that autochthonous Ped. damnosus strains were able to predominate over the commercial O. oeni starter and perform MLF in Caiño wine. By contrast, neither commercial strain nor indigenous Pediococcus carried out MLF in Albariño wine. However, MLF was achieved when autochthonous strains that predominated in Caiño were inoculated into Albariño. Sensory analysis showed that after the MLF Albariño increased its body and softness, while Caiño result a more mature wine. CONCLUSIONS: MLF can positively affect Albariño and Caiño wines giving them new attributes. Pediococci isolated and characterized in this work can successfully perform MLF without negative effects on the wine, because no production of biogenic amines or exopolysaccharides by the selected pediococcus strains was detected. SIGNIFICANCE AND IMPACT OF THE STUDY: The effect of MLF in the sensory profile of Albariño and Caiño wines has never been studied before. Results obtained in this work showed that Ped. damnosus strains can be considered as a new topic of investigation on malolactic starter.

Role of fosfomycin tromethamine in modulating non-specific defence mechanisms in chronic uremic patients towards ESBL-producing Escherichia coli.

Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to interact in such a way that improve the therapy for infectious diseases. In immunocompromised patients highly susceptible to microbial infections with high morbidity and mortality, several metabolic and functional alterations in PMNs, mostly related to microbicidal activity, are observed. Therefore, the antibiotic of choice should have a good antimicrobial effect without impairing host defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from healthy subjects and immunocompromised patients (haemodialysed and renal transplant recipients), against an ESBL-producing Escherichia coli, the most common aetiological agent in urinary tract infections (UTIs). FT is considered a first line drug in the eradication of UTIs due to its appropriate antimicrobial spectrum, oral bioavailability and minimal risk of microbial resistance. Our results provide evidence that FT is able to induce enhancement of the depressed phagocytic response of PMNs from patients on chronic haemodialysis and from renal transplant recipients, restoring their primary functions in vitro against ESBL-producing E. coli. All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT.

[Epstein Barr viral load monitoring in mononuclear lymphocytes and serum of renal transplant recipients using a quantitative PCR protocol]. / Monitoraggio della carica virale dell'EBV nei linfomonociti e nel siero di trapiantati renali mediante un protocollo di PCR quantitativa.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD), ranging from lymphoid hyperplasia to clonal malignancy, are severe complications arising in solid organ transplant patients; their reported incidence ranges from 1 to 20%, according to factors such as type of transplanted organ and age of recipients. A strong correlation between Epstein-Barrvirus (EBV) infection, the grade and type of immunosuppression and the development of PTLD has been recognized. The detection and quantification of EBV-DNA load in peripheral blood have been utilized as prognostic markers for the development of PTLD, showing a correlation between high levels of EBV-DNA in the blood and the development of PTLD. In this study, we monthly monitored EBV viral load in 15 renal transplant recipients for six months. The number of EBV-DNA copies was measured in peripheral blood mononuclear cells (PBMC) and serum samples by a quantitative PCR protocol developed in our laboratory. METHODS: Our EBV-DNA quantification protocol employs a previous screening of samples containing a significant number of viral DNA copies (>=1000 copies/105 PBMC or 100 mL serum) by semi-quantitative PCR followed by a precise quantification of the only significant samples by quantitative-competitive (QC)-PCR. RESULTS: Our 15 renal transplant patients neither developed PTLD nor had recurrent acute illnesses or acute graft rejections during the study. The results obtained in the monthly follow up of EB viral load in PBMC samples confirmed its fluctuation in asymptomatic patients reported in the literature. In particular, 5/14 (35.7%) of EBV seropositive patients had an EBV-DNA load equal to 1000 EBV copies /105 PBMC, and 1/14 (7.1%) reached 5000 EBV copies /105 PBMC at least once in our study. In the EBV seronegative patient, EBV-DNA in PBMC samples was always undetectable (less than 100 DNA copies/105 PBMC). EBV-DNA load in all serum samples was less than threshold value of our quantification protocol (<100 DNA copies/100 mL serum). With regard to the immunosuppressive treatment, it should be noted that 66.7% of the six patients in whom EBV load reached values equal to or higher than 1000 DNA copies/105 PBMC, were on FK506 whereas only 33.3% of them were on CyA. CONCLUSIONS: Since the high positive predictive value of EB viral load in peripheral blood for diagnosis of PTLD reported by several Authors, and the described absence of correlation between the serological evidence of EBV reactivation and EB viral load, EBV viral load measurement in PBMC and serum samples using quantitative PCR techniques is a powerful diagnostic tool to monitor transplanted patients at risk of developing PTLD.

Leucemia monocítica em cão. Relato de caso

O artigo não apresenta resumo.

Improved phagocyte response by co-amoxiclav in renal transplant recipients.

BACKGROUND: Infectious diseases are a major source of morbidity and mortality for immunosuppressed transplant recipients and the antimicrobial chemotherapy can be often less effective in these individuals, because the contribution of underlying host defenses is absent. METHODS: The influence of co-amoxiclav on the functions of polymorphonuclear granulocytes (PMNs) from renal transplant recipients were investigated. RESULTS: PMNs from renal transplant recipients showed a diminished phagocytic activity with reduced phagocytosis and bactericidal activity against intracellular Klebsiella pneumoniae, compared to that seen with PMNs from healthy subjects. Co-amoxiclav significantly elicited the functions of PMNs from uremic patients, resulting in an increased percentage of ingested klebsiellae and in a higher bactericidal effect (98-99%), compared with the drug-free control system. When PMNs were collected from renal transplant recipients treated with co-amoxiclav a significant high increase in both phagocytosis and killing activity were detected, showing the co-amoxiclav capability of "restoring" even in vivo the depressed primary functions of PMNs. CONCLUSIONS: The interesting beneficial properties of co-amoxiclav, which result in restoring the phagocyte-dependent response in renal transplant patients both in vitro and in vivo, may make this drug more suitable for the treatment of infections in patients with defects of phagocyte functions.

Outcome of dialysis patients submitted to coronary revascularization.

Cardiovascular disease accounts for almost half of the total mortality in patients with end stage renal disease (ESRD). It has recently been debated whether coronary revascularization has the same rate of risks and successes in this cohort of patients compared to patients without renal disease. Since 1991, 17 dialysis patients were submitted to coronary revascularization in our center. Seven patients were following peritoneal, 10 hemodialytic treatment. Four patients were submitted to percutaneous transluminal coronary angioplasty (PTCA) and 13 to surgical revascularization (CABG). In 2 patients the coronary lesion was unique, in the others stenosis of multiple vessels were found. Six patients were diabetic. The mean age at the onset of the coronary artery disease (CAD) was 57.17 +/- 11.6 years. The mean time elapsed from the onset of the CAD and the performance of the PTCA or CABG was 30.1 +/- 35.4 months. The mean time from beginning of dialysis treatment to revascularization was 48.2 +/- 39.6 months. Mean hemoglobin values were 9.7 +/- 1 g/dL, mean phosphorus values were 5.2 +/- 8.7 mg/dL, mean cholesterol values were 211 +/- 49.5 mg/dL. The procedure was technically successful in all patients. Mean survival was 25.09 +/- 28.12 months. Twelve patients died, 5 of whom within one month. Survival at one month was 70.5%, at 6 months 58.8%, at one year 52.9%, at 2 years 47%. There was neither significant difference patients submitted to PTCA and those submitted to CABG, nor between diabetic and non-diabetic patients. In conclusion, coronary revascularization in our experience is a high risk procedure in dialysis patients. The reasons for this could be the severe general conditions of these patients affected with diffuse vasculopathy and the long time elapsed since the onset of the ischemic cardiopathy. Thus, our results could suggest the opportunity of performing earlier screening of coronary situation and revascularization treatment in CAD dialysis patients.

GIT (Glucose Infusion Test): polycentric evaluation of a new test for vascular access recirculation.

Introduction. Vascular access recirculation (AR), which is often unacknowledged, remains an important cause of inadequate dialytic dose. The glucose infusion test (GIT) is a new method for detecting and quantifying AR. This paper reports on a polycentric evaluation of the new test and a comparison with the classical Urea-test (UT). Methods. GIT protocol comprises withdrawal from the arterial port (sample A), injection into the venous drip chamber of 1 g glucose in 4 seconds, withdrawal from the arterial port (sample B) continuously from 13 to 17 seconds. Glucose is determined on A and B by a reflectance photometer. If B = A then there is no recirculation. If B exceeds A by at least 20 mg/dl there is recirculation. AR quantification: AR% = (B-A) / 20. GIT was performed on 623 patients from eleven dialysis centers to screen the patients for AR. Subsequently, GIT and Urea-test (UT) were compared in 189 paired tests. The reproducibility of GIT and UT was studied in 28 paired tests performed in sequence. Results. The screening test by GIT was positive in 68 cases (11 %). The majority of positivities was found in central venous catheters (CVC, 27/50 cases, 54 %), whereas only 7 % of artero-venous fistulas (AVF) were positive. In the CVC group, Tesio catheters were more frequently positive compared to Dual Lumen Catheters (64 % vs. 29 %). The comparison GIT - UT showed that results matched in 162 tests (79 negative and 83 positive both by GIT and UT), showing that on the grounds of UT, GIT has high sensitivity and specificity. In 27 tests GIT was positive, but UT negative. This disagreement is due to the different minimal limit of detection, 1 % for GIT and 5% for UT. The reproducibility was greater with GIT than with UT with a lower D% (respectively -0.6 +/- 2.5 and -0.4 +/- 6.1 %, p<0.001) and a lower coefficient of variation (17 vs 33 %). Conclusions. The screening of 623 patients by GIT confirmed that AR in AVF is normally absent, whereas an un-expectedly high frequency of moderate AR in CVC was found. The GIT-UT comparison showed that the new test is simple and immediate, and gives results with higher accuracy, sensitivity and reproducibility than UT.

Two years of experience with a new device system: a multicenter study.

Peritonitis is a crucial complication of peritoneal dialysis. Over the last few years, new device systems have been developed to reduce episodes of peritonitis caused by exogenous contamination. Remarkable improvement has been obtained by modifying the original connection between the catheter and the bag with the introduction of the Y-set. The aims of this study were to test the reliability and simple use of a double-bag system without disinfectant in-line (Gemini, Gambro) and to evaluate the incidence of peritonitis in a 2-year period of follow-up. In a group of 167 patients, enrolled in 14 dialysis units in Italy, with a follow-up of 2433 patient-months, we observed 82 episodes of peritonitis in 52 patients, with a cumulative incidence of 1 episode every 29.7 patient-months. At 12 months the percentage of patients peritonitis-free was 69.7%, and at 24 months it was 62.8%. The training to complete the bag exchange, assessed by patient and nursing staff, was defined as "easy" in 61% of the cases and "difficult" in only 12% of the cases. The percentage of patients requiring a partner was 23%. For patients this device system presents easy handling in terms of the bag exchange, and it may prevent peritonitis.

["Prophylactic" video-laparoscopic cholecystectomy]. / La colecistectomia videolaparoscopica "profilattica".

The authors examine the prophylaxis of infections caused by cholelithiasis in kidney and heart transplant candidates as a new indication for videolaparoscopic cholecystectomy (VLC). The study included 6 patients in dialysis for chronic renal insufficiency and one patient suffering from cyanogenic congenital cardiopathy with asymptomatic gallbladder calculosis. The results obtained show that there are no substantial differences compared to patients without associated pathologies and justifies the inclusion of "prophylactic" VLC in preparatory treatment protocols for kidney and heart transplant in patients suffering from cholelithiasis. The authors emphasise the necessary technical measures to prevent hemorrhage, intraoperative loss of CO2 and postoperative laparoceles.

[Surgical interventions in dialysis patients in Piedmont: data from the Regional Registry. Working Group of the Piedmont Registry of Dialysis and Transplantation]. / Interventi chirurgici nei pazienti in dialisi in Piemonte: dati dal Registro Regionale (RPDT). Gruppo di lavoro dell'RPDT.

In this work surgical events in a large population of chronic dialysis patients are analysed. Data are obtained from the Regional (Piedmont) Registry of Dialysis and Transplantation (RPDT), that has collected information since 1981 about all chronic dialysis patients in the Region. Since 1984, causes of admission to-hospital are registered. Surgical causes of hospitalization, for purposes not related to uremia, were 538 (20% of all surgical admissions). In patients younger than 65 years, these hospitalizations account for about 6% of the cases, whereas in patients older than 65 they are less than 5%. As expected, a higher number of surgical operations is observed in diabetics, while on the contrary the lowest is performed in nephroangiosclerosis patients. Cardiovascular and bowel diseases represent almost 50% of all surgical needs. Postoperative mortality was 5.8% within 45 days from admission. Cardiac and infectious diseases and cachexia represent the more frequent causes of death. In 27 out of 28 cases at least one high risk condition was present.

[Choice of dialysis methods as initial substitutive treatment: trends in the last 10 years]. / Scelta di metodiche dialitiche quale primo trattamento sostitutivo: evoluzione negli ultimi dieci anni.

The authors report data from the Regional Piedmontese Registry about the evolution of choices concerning dialytic therapy in the 20 regional dialysis Units during the years 1981-1990. They confirm a scale-down of acetate dialysis that is replaced with bicarbonate dialysis; besides a limited use of convective dialysis whereas peritoneal dialysis is steady. At the same time they remark an increase in admittance to dialysis and older patients.

[The value of albumin and cholesterol blood levels as indicators of the risk of death in dialysis. Working Group of the Piedmont Registry of Dialysis and Transplantation]. / Il valore dei livelli di albuminemia e colesterolemia come indicatori del rischio di morte in dialisi. Gruppo di lavoro dell'RPDT.

In recent years, the availability of large epidemiological series allowed identification of biochemical outcome markers in the dialysis population. Interest towards albumin and cholesterol levels is motivated by their easy availability and by the presence of a strong short-term effect on mortality and morbidity. The aim of the study was an analysis of the relationship between albumin and cholesterol levels at start of dialysis and mortality (gross mortality and Kaplan Meier survival curves). Data were obtained from the Piedmont Regional Registry of Dialysis and Transplantation (Northern Italy Region, about 4,400,000 inhab, 20 Dialysis Centers, open acceptance since mid '70, yearly information on 100% of patients) in the period 1981-1990 (4734 patients on file). Only non diabetic patients with follow-up > = 1 month, who started treatment in the Region, were selected. Patients with renal function recovery were excluded. Albumin levels were dichotomized at 3.5 g/dl. Cholesterol was stratified into 3 levels (< 150, 150-250, > or = 300 mg/dl). The choice of dividing the study into 2 periods (1980-1985 vs 1986-1990) is due to the fact that 1984 has been the year of switch from acetate to bicarbonate dialysis. Prevalence of albumin and cholesterol under the normal range (22% and 15%) is low and rises with age and presence of high risk conditions. A a good correlation with the risk of death of these biochemical markers (stronger for albumin at least in the short term) was observed. No correlations are found with risk of death and elevated cholesterol levels (low number of cases).(ABSTRACT TRUNCATED AT 250 WORDS)

[Automated peritoneal dialysis (APD). Experience in 42 patients]. / La dialisi peritoneale automatizzata (APD). Esperienza in 42 pazienti.

Automated peritoneal dialysis (APD) is currently considered as one of the most attractive home treatments for uremic patients. However, relevant costs and the presence of a dialysis machine prevent a wider diffusion of this technique. In this work we discuss the results obtained in 42 patients (12 females, 30 males) treated by two dialysis units of the Piedmont Region. Patients' characteristics. Eighty-three percent of the females and 66.5% of the males are under 65 years of age; glomerulo-nephritis and nephroangiosclerosis account for the most frequent renal diseases (28.5 each); a high risk condition is recorded in 52.5% of cases. Twenty-two patients were transferred to APD from CAPD (patient's request in 59% of cases, clinical problems in the remaining). RESULTS. Forty-five percent of cases are working full or part-time, 12% are not caring for self. Peritonitis rate accounts for 1 episode every 42 patient-months. Biochemical control is satisfactorily achieved (mean values: urea 137.8 mg/dl, creatinine 11 mg/dl, calcium 10.2 mg/dl, phosphate 5.7 mg/dl, albumin 4.3 g/dl, cholesterol 234 mg/dl, triglycerides 195 mg/dl). Technical assistance was requested on average once every 16 months of treatment. CONCLUSION. Negative drawbacks of APD, mainly related to elevated costs and technical complexity, are fully counterbalanced by satisfactory social and clinical rehabilitation, wider indications to peritoneal dialysis with respect to CAPD, lower rates of peritonitis and limited technical needs.

Beta-thalassemia syndromes and pregnancy.

The literature relating to homozygous beta-thalassemia and the problems these patients have during their pregnancy is reviewed and another case report of a twin pregnancy in a homozygous beta-thalassemia individual is included. The majority of cases described refer to the intermedia clinical form of the hematological problem because patients with thalassemia major generally have poor sexual development. Although the reported cases had a greater frequency of delayed development, only one woman suffered from infertility and required ovulation induction agents. The thalassemia pregnant mother faces deleterious consequences resulting from chronic anemia and in nonsplenectomized patients there remains the risk of the onset of a hypersplenic crisis. The problems of splenectomized patients during pregnancy is also discussed. The chronic anemia of thalassemic patients predisposes to a poor fetal outcome with greater fetal loss, preterm labor, and intrauterine growth retardation.

Death in conditions of cachexia: the price for the dialysis treatment of the elderly?

Death in conditions of cachexia is increasing in potential dialysis patients, as treated cohorts are aging, the mean age of new patients increased and access to treatment is unlimited. The present study analyzes the clinical features of 417 deaths in conditions of cachexia recorded in 1981 to 1990 in the Dialysis and Transplantation Registry of a northern Italian region, Piedmont (about 4,400,000 inhabitants, 20 dialysis centers; 4,734 patients on file at December 31, 1990; yearly information on 100% of the cases). Death in conditions of cachexia increased from 105 cases in the first four years taken into account (1981 to 1984), to 107 in the last two years (1989 to 1990). Prevalence is higher in the elderly (85% of the death over age 60). Most patients (90.5%) were at high clinical risk. To assess whether the frequency of this diagnosis reflected the wide acceptance of elderly patients for dialysis and was a marked of vascular disease, a specific inquiry was conducted about 107 cachectic deaths recorded from 1989 to 1990: 82.5% of the patients had diffused vascular disease, 11.5% were already cachectic when dialysis was initiated, and 66% were in cachexia at least six months before death. Since mean age of patients dying in condition of cachexia increased from 68.8 in the period of 1981 to 1984 to 70.3 years in 1989 to 1990, and mean time on dialysis from 2.8 years in 1981 to 1984 to 70.3 years in 1989 to 1990, the higher prevalence is not likely to be due to lack of care of elderly patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic patients on dialysis: a changing picture.

Prevalence of diabetic patients on dialysis is often considered a marker of overall acceptance rate for dialysis; however, even when acceptance policy is open, incidence of diabetic patients varies widely. Epidemiological differences of diabetes incidence all over the world partly explain the discrepancies. Incidence of diabetic patients accepted for dialysis (1981 to 82: 6 p.m.p.; 1989 to 90: 11.5 p.m.p.) differs according to age and sex in the setting analyzed (Piedmont, Northern Italian region, about 4,400,000 inhabitants, 20 dialysis centers, open acceptance since the mid-70s, yearly information on 100% of patients, gathered by a Dialysis and Transplantation Registry). Patterns changed remarkably during the 10 years considered (1981 to 90). Incidence was higher in males (10.4 p.m.p. in the period 1981 to 90), with a peak at ages 60 to 69. Incidence remained relatively stable in the younger patients, but increased in the elderly, mainly in males, rising from 6.23 in 1981 to 82 to 12.88 p.m.p. in 1989 to 90 (males, all ages). In conclusion, the demographic characteristics of diabetic patients with ESRD accepted for dialysis is changing. The stability of incidence of younger patients reassures about the open acceptance policy, at least in these ages. The increase in the elderly probably reflects the longer lifespan of diabetic patients in the overall population. The possibility of a hidden preselection must be further assessed. Future provisions of dialysis needs must take into account the trend towards an increase of this high risk, elderly population.

In vitro and in vivo efficacy of a new connector device for continuous ambulatory peritoneal dialysis.

The purpose of this study was to evaluate the in vitro and in vivo efficacy of a new connection system for continuous ambulatory peritoneal dialysis (CAPD), called the T-set. With this system the patient wears a 27-cm extension line filled with Amuchina during the dwell time; the bag is made of a fill container linked to a drainage tube with a Y-shaped set. For bag exchange, only one connection is needed and this is subsequently flushed with the entire drainage volume. The in vitro efficacy of the system was tested with 20 sets filled with 10 mL of Amuchina and inoculated in the distal lumen with 2.1 x 10(3) colony-forming units (cfu) of S. aureus. After an incubation of 4-6 hours at 35-37 degrees C, three dialysate samples per set were collected, respectively, at the beginning of drainage and filling. All 120 samples were negative, whereas two control sets, filled with a phosphate-buffered saline, had positive drainage samples, and at least one positive infusion sample, indicating the efficacy of Amuchina in sterilizing the system under conditions simulating touch contamination. To evaluate the in vivo efficacy, safety, and acceptability of the T-system, a prospective randomized controlled trial was performed in seven centers: a control group (CG) of 56 patients (follow-up: 952.3 months, mean +/- SD: 17.0 +/- 7.8) was treated with a long branch (21 patients) or short branch (35 patients) Y-set and a test group (TG) of 66 patients (follow-up:898.1 months, mean +/- SD: 13.6 +/- 7.8) with the T-set.(ABSTRACT TRUNCATED AT 250 WORDS)