Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose–Response Curves in Worsening Refractory Congestive Heart Failure

Introduction: Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Methods: Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0–24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24–48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. Results: After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose–response curves in these patients. Conclusion: These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF

Clofarabine and Treosulfan as Conditioning for Matched Related and Unrelated Hematopoietic Stem Cell Transplantation: Results from the Clo3o Phase II Trial

ABSTRACT Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for patients with hematologic malignancies. The ideal conditioning regimen before allo-HSCT has not been established. We conducted a Phase II study to evaluate the tolerability and efficacy of clofarabine and treosulfan as conditioning regimen before allo-HSCT. The primary objective was to evaluate the cumulative incidence of nonrelapse mortality (NRM) on day +100. Forty-four patients (36 with acute myelogenous leukemia, 5 with acute lymphoblastic leukemia, 3 with myelodysplastic syndromes) were enrolled. The median patient age was 47 years, and the median duration of follow-up was 27 months. The conditioning regimen was based on clofarabine 40 mg/m2 (days -6 to -2) and treosulfan 14 g/m2 (days -6 to -4). Allogeneic hematopoietic stem cells were derived from a sibling (n = 22) or a well-matched unrelated donor (n = 22). Graft-versus-host disease (GVHD) prophylaxis consisted of antithymocyte globulin, rituximab, cyclosporine, and a short-course of methotrexate. The regimen allowed for rapid engraftment and a 100-day NRM of 18%, due mainly to bacterial infections. The incidences of grade II-IV acute GVHD and chronic GVHD were 16% and 19%, respectively. The rates of overall survival (OS), progression-free survival, and relapse at 2 years were 51%, 31%, and 50%, respectively. Significantly different outcomes were observed between patients with low-intermediate and patients with high-very high Disease Risk Index (DRI) scores (1-year OS, 78% and 24%, respectively). Our findings show that the use of treosulfan and clofarabine as a conditioning regimen for allo-HSCT is feasible, with a 78% 1-year OS in patients with a low-intermediate DRI score. However, 1-year NRM was 18%, and despite the intensified conditioning regimen, relapse incidence remains a major issue in patients with poor prognostic risk factors

"Diagnosis on the Dock" project: A proactive screening program for diagnosing pulmonary tuberculosis in disembarking refugees and new SEI model.

Abstract Objective From 2011 to 2017, the total number of refugees arriving in Europe, particularly in Italy, climbed dramatically. Our aim was to diagnose pulmonary TB in migrants coming from the African coast using a clinical-based port of arrival (PoA) screening program. Methods From 2016 to 2018, migrants coming via the Mediterranean Route were screened for body temperature and the presence of cough directly on the dock: if they were feverish with productive cough, their sputum was examined with NAAT; with a dry cough, they underwent Chest-X-ray (CXR). Those migrants with positive NAAT or CXR suggestive for TB were admitted to our ward. In addition, we plotted an SEI simulation of our project to evaluate the epidemiological impact of our screening. Results Out of 33.676 disembarking migrants, 314 (0.9%) had fever and cough: 80 (25.47%) with productive cough underwent NAAT in sputum, and 16 were positive for TB; 234 (74.52%) with dry cough had a CXR examination, and 39 were suggestive of TB, later confirmed by mycobacterial culture. The SEI-new model analysis demonstrated that our screening program significantly reduced TB spreading all over the country. Conclusions For possible future high migrant flows, PoA screening for TB has to be considered feasible and effective in decreasing TB spreading

Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity

Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study

Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration.info:eu-repo/semantics/publishedVersio

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

26 páginas, 4 figuras, 3 tablasOur clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D+I Plan co-funded with European Regional Development Funds (ERDF) [Grants PI18/00147 and PI21/00103 to CE]; the Fundació La Marató TV3 [Grants 20143130 and 20143131 to BPD and CE]; and by the Generalitat Valenciana [Grant PROMETEO/2018/135 to CE]. Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014–2020). PS had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. IH has a PFIS-PhD fellowship [FI19/00072]. ASM has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA)Peer reviewe

Dry-farming yield of herbaceous crops for energy grown in Mediterranean environment. First results.

Results of a two-year trial carried out in southern Italy to compare the biomass production of different herbaceous crops for energy under rainfed conditions are reported. The compared species were: Cynara cardunculus, Crambe abyssinica, Brassica napus var. oleifera, Brassica carinata, Carthamus tinctorius, Helianthus annuus, Helianthus tuberosus, Arundo donax, Sorghum bicolor var. saccharatum, Sorghum bicolor x S. dochna. Very different rain courses were recorded in the two years. In the first year, B. carinata, B. napus, C. tinctorius, C. abyssinica produced 1.3, 1.0, 1.1 and 1.3 t ha-1 of seed respectively, while in the second year such values raised to 2.4, 2.1, 1.8 and 1.9 t ha-1. C. cardunculus showed the higher yield of 20.6 t ha-1 d.m. in the second year. Also H. annuus, H tuberosus, S. bicolor saccharatum and S. bicolor x S. dochna showed higher productions in the second year, with values of 1.4, 4.2, 16.4 and 19.5 t ha-1 respectively for seed, dry tubers and dry biomass. A. donax reached 9.2 t ha-1 d.m. at the first harvesting, in the second year

Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome

ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease

Role of nephron sparing surgery in the treatment of centrally located renal tumors.

OBJECTIVES: In recent years many long-term data have suggested that nephron sparing surgery can be considered as an effective method of treatment also in patients with small, solitary, unilateral renal cell carcinoma and a normal contralateral kidney. Generally, partial nephrectomy is performed for peripheral tumors and usually is limited to imperative indication for central tumors to avoid hemodialysis. We retrospectively evaluate the value of tumor location on technical and oncological results, particularly in patients with elective indication. PATIENTS AND METHODS: Between 1993 and 2002, 112 patients underwent nephron sparing surgery at our institution. The tumor was centrally and peripherally located in 22 and in 90 cases, respectively. The tumor was discovered in 13 (56%) central and in 57 (63%) peripheral tumors incidentally. The indication was imperative in 12 and elective in 10 patients for central group, while it was imperative in 34 and elective in 56 patients for peripheral group. RESULTS: The mean renal ischemia time was longer in central group compared to peripheral group (20.81 versus 18.8 minutes p&lt;0.05) and the collecting system was violated more frequently in central group (53% versus 28% p&lt;0.05). Postoperative complications were higher for central tumors compared to peripheral tumors (18% versus 4% p&lt;0.05) but the ultimate mean serum creatinine level was similar for central and peripheral tumors (1.36 versus 1.22 mg/dl). The mean tumor size was 39.69 mm in central group and 32.77 mm in peripheral group (p&lt;0.05). The mean diameter of central tumors in imperative indication was 42 mm while in elective indication was 32 mm (p&lt;0.05). Pathological tumor stage was T1 to T3 in 18 (82%), 1 (4%) and 3 (14%) cases in central group and in 81 (88%), 6 (7%) and 5 (5%) cases in peripheral group. Grades was 1 to 3 in 4 (18%), 15 (68%) and 3 (14%) cases in central group and in 21 (23%), 61 (66%) and 10 (11%) cases in peripheral group. There was no difference in 5-year cancer specific survival (91% versus 98%) or postoperative local tumor recurrences (9% versus 6%) in central tumors compared to peripheral tumors and there was no local recurrence in elective partial nephrectomy performed in central tumors. CONCLUSIONS: Nephron sparing surgery is technically more demanding in patients with central tumors. However there were no significant differences in cancer specific survival and local recurrence between centrally versus peripherally located tumors. Elective partial nephrectomy can be performed also in patients with central tumors as long as really less than 4 cm

Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome

<div><p>ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.</p></div