Toxicity after prolonged (more than four weeks) administration of intravenous colistin

Background  

The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).     

Targeted next-generation sequencing in chronic lymphocytic leukemia: a high-throughput yet tailored approach will facilitate implementation in a clinical setting

Next-generation sequencing has revealed novel recurrent mutations in chronic lymphocytic leukemia, particularly in patients with aggressive disease. Here, we explored targeted re-sequencing as a novel strategy to assess the mutation status of genes with prognostic potential. To this end, we utilized HaloPlex targeted enrichment technology and designed a panel including nine genes: ATM, BIRC3, MYD88, NOTCH1, SF3B1 and TP53, which have been linked to the prognosis of chronic lymphocytic leukemia, and KLHL6, POT1 and XPO1, which are less characterized but were found to be recurrently mutated in various sequencing studies. A total of 188 chronic lymphocytic leukemia patients with poor prognostic features (unmutated IGHV, n=137; IGHV3-21 subset #2, n=51) were sequenced on the HiSeq 2000 and data were analyzed using well-established bioinformatics tools. Using a conservative cutoff of 10% for the mutant allele, we found that 114/180 (63%) patients carried at least one mutation, with mutations in ATM, BIRC3, NOTCH1, SF3B1 and TP53 accounting for 149/177 (84%) of all mutations. We selected 155 mutations for Sanger validation (variant allele frequency, 10–99%) and 93% (144/155) of mutations were confirmed; notably, all 11 discordant variants had a variant allele frequency between 11–27%, hence at the detection limit of conventional Sanger sequencing. Technical precision was assessed by repeating the entire HaloPlex procedure for 63 patients; concordance was found for 77/82 (94%) mutations. In summary, this study demonstrates that targeted next-generation sequencing is an accurate and reproducible technique potentially suitable for routine screening, eventually as a stand-alone test without the need for confirmation by Sanger sequencing.     

Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes

Understanding the mechanisms responsible for carbon nanotube (CNT) internalisation into live cells is considered critical both from a fundamental point of view and for further engineering of CNT-based delivery systems to intracellular targets. While several studies are focused on the development of such CNT-based delivery systems, attempts to systematically elucidate the cellular uptake mechanisms of CNTs are still rather limited. The aim of the present study is to evaluate the cellular internalisation of chemically functionalised multi-walled carbon nanotubes (f-MWCNTs) in the presence of different well-known cellular uptake inhibitors. Our data reveal how f-MWCNTs are able to translocate across cell membranes of both phagocytic and non-phagocytic cell lines. We have evidenced that at least 30-50% of f-MWCNTs are taken up by cells through an energy-independent mechanism. This characteristic makes nanotubes loaded with therapeutic or diagnostic cargos extremely interesting as the release of active molecules directly into the cytoplasm increase their biological activity and therapeutic efficacy.     

Phosphate homeotasis in healthy subjects during prolonged periodic and continuous hypokinesia

OBJECTIVE: This study aimed to show that during hypokinesia (HK), phosphate (P(i)) imbalance increases more with higher than lower physical activity and that P(i) absorption reduces more with higher than lower P(i) imbalance in subjects with higher than lower muscular activity. METHODS: Studies were conducted on 30 healthy male subjects during 364 days of HK. They were equally divided in three groups: unrestricted active control subjects (UACS), continuously hypokinetic subjects (CHKS) and periodically hypokinetic subjects (PHKS). CHKS were kept under average walking distances of 0.5+/-0.2 km day(-1) PHKS were kept under average walking distances of 0.5+/-0.1 and running average distances of 8.7+/-1.2 km day(-l) for 5 days and 2 days per week, respectively. UACS were placed under average running distances of 8.7+/-1.2 km day(-l). RESULTS: P(i) imbalance, serum, urine and fecal P(i) levels, and urine and serum calcium (Ca(2+)) levels increased significantly (p<0.05) and P(i) absorption, and serum intact parathyroid hormone (iPTH) and 1,25-dehydroxyvitamin D (1,25 (OH)(2) D(3)) levels decreased significantly (p<0.05) in CHKS and PHKS compared with their pre-HK values and their respective active control (UACS). However, the P(i) imbalance, serum, urine and fecal P(i) levels, and serum and urine Ca(2+) levels increased more significantly (p<0.05), and P(i) absorption and serum iPTH and 1,25 (OH)(2) D(3) levels decreased more significantly in PHKS than in CHKS. CONCLUSIONS: Higher P(i) imbalance with higher than lower physical activity shows that the risk of higher P(i) imbalance is inversely related to the intensity of physical activity. Lower P(i) absorption with higher than lower P(i) imbalance shows that the risk of lower P(i) absorption is inversely related to magnitude of P(i) imbalance. In conclusion P(i) imbalance increases more with higher than lower physical activity and that P(i) absorption decreases more with higher than lower P(i) imbalance indicating that during HK the use of P(i) decreases more with higher than lower physical activity.     

Does Adherence to the Mediterranean Diet Have a Protective Effect against Asthma and Allergies in Children? A Systematic Review

Dietary pattern may potentially impact on the pathogenesis of asthma and allergies. The Mediterranean Diet (MD) has significant health benefits due to its antioxidant and anti-inflammatory properties. The aim of this systematic review was to investigate the effectiveness of adherence to the MD against asthma and allergies in childhood. Hence, a systematic literature search was conducted on PubMed, ESBCO (Cinahl), Scopus, and the Cochrane Library databases up to 26 January 2022. The total number of articles obtained, after the initial search on the databases was conducted, was 301. Twelve studies were included, after the removal of duplicates and screening for eligibility. Our findings indicated a protective role of the MD against childhood asthma, but they also imply that the MD probably does not affect the development of allergies. Nevertheless, the heterogeneity and limitations of the studies highlight the need for randomized controlled trials that will focus on the pediatric population and hopefully provide more robust evidence.     

Use of the Trellis™ Peripheral Infusion System for Enhancement of rt-PA Thrombolysis in Acute Lower Limb Ischemia

The Trellis Peripheral Infusion System is an over-the-wire 0.035 guidewire compatible device, designed to isolate a region of the peripheral vasculature to allow for lytic drug infusion and dispersion. We used it successfully through a percutaneous approach in two cases of acute thrombosis of a native lower limb artery. The total amount of rt-PA used was 12 and 9 mg, respectively and was delivered through bolus injections obviating the need for a supplementary continuous infusion of the agent. The time for dissolution of thrombus was 45 and 35 minutes, respectively. No complications were observed.     

LigaSure versus clamp-and-tie thyroidectomy for benign nodular disease

BACKGROUND: LigaSure is an alternative bipolar diathermy system (BDS) combining vessel sealing with reduced thermal spread, which has been successfully used in many abdominal operations; however, there is a little experience in open thyroidectomy. This study compares the efficacy and the advantages of the LigaSure BDS when used for total thyroidectomy for benign thyroid disease with the conventional clamp-and-tie technique. METHODS: Between May 1998 and October 2002, 517 patients underwent total thyroidectomy for benign thyroid multinodular goiter. Among them, from May 1998 until May 2000, 247 patients (group I) were operated on with the conventional clamp-and-tie technique, whereas from May 2000 until October 2003, 270 patients (group II) underwent total thyroidectomy for benign multinodular goiter with LigaSure BDS through a 4-cm transverse suprasternal incision. Demographics, pathologic characteristics, gland mass, operative time, blood loss, and complications were assessed. RESULTS: There were no intraoperative complications. Thyroid mass was similar in both groups, but the operative time was shorter in group II than in group I (mean +/- standard deviation, 71 +/- 14 minutes vs 86 +/- 22 minutes; p < .01). Intraoperative total blood loss was similar between the two groups, but postoperative drain volume was less in group II than in group I (21 +/- 15 mL; p < .01). Major post-thyroidectomy complications (ie, laryngeal nerve palsy, hematoma, and hypocalcemia) occurred less frequently in the LigaSure group than in the clamp-and-tie group (0.7%, 0.4%, 1.1% vs 4%, 2%, 4.8%, respectively; p < .05). The mean +/- standard deviation postoperative hospital stay was significantly less for the patients in group II than for those in group I (2.3 +/- 1.7 days vs 2.8 +/- 1.3 days; p < .05). CONCLUSIONS: The use of the LigaSure vessel sealer for thyroid surgery is an effective and safe alternative that reduces the overall operative time and could be successfully applied through a narrow surgical incision.     

Postoperative Liver Dysfunction and Future Remnant Liver: Where Is the Limit?

Background The future remnant liver (FRL) limit for safe major hepatectomy with low risk of postoperative liver failure has not yet been well defined. Methods Between April 2000 and September 2004, every patient scheduled for major hepatectomy in our institution underwent CT-volumetry of FRL. Patients with FRL <25% underwent portal vein embolization (PVE). Exclusion criteria were PVE, associated vascular resection and liver cirrhosis. The FRL was correlated with short-term results in patients with normal liver (group A) and those with impaired liver function secondary to neoadjuvant chemotherapy or cholestasis (bilirubin >2 mg/100 ml) (group B). Liver dysfunction was defined as both PT <50% and serum bilirubin level >5 mg/100 ml for three or more consecutive days. Results A total of 119 patients were analyzed, 72 in group A and 47 in group B. The FRL value was the only significant risk factor for postoperative liver dysfunction in the univariate and multivariate analysis (p = 0.009). The FRL did not correlate with postoperative mortality and morbidity. Bilirubin and prothrombin time (PT) on days 3 and 7 were significantly correlated to FRL in both groups. In group A, patients with postoperative liver dysfunction had a FRL<30% (3 versus 0; p = 0.005). According to receiving operator characteristic (ROC) curve analysis, a FRL value of 26.5% predicted postoperative liver dysfunction with 66.7% sensitivity, 97.1% specificity, 50% positive predictive value (PPV), and 98.5% negative predictive value (NPV). In group B, patients with postoperative liver dysfunction had a FRL <35% (4 versus 0; p = 0.027). According to ROC curve analysis, a FRL value of 31.05% predicted postoperative liver dysfunction with 75% sensitivity, 79.1% specificity, 25% PPV, and 97.1% NPV. Conclusions Hepatectomy can be considered safe when FRL is >26.5% in patients with healthy liver and >31% in patients with impaired liver function.