Corrigendum: Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in vivo.

[This corrects the article DOI: 10.3389/fmicb.2018.00696.].

Effect of urea cream on sorafenib-associated hand-foot skin reaction in patients with hepatocellular carcinoma: A multicenter, randomised, double-blind controlled study.

BACKGROUND: Hand-foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment in patients with hepatocellular carcinoma (HCC). In the present study, we aimed to investigate the role of urea cream in the prevention of HFSR or amelioration of HFSR severity. PATIENTS AND METHODS: Patients with HCC were treated with either placebo cream or urea cream for 12 weeks concomitantly with sorafenib treatment. HFSR development, the Hand-Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire score, and adverse events were assessed at 2, 4, 8 and 12 weeks. RESULTS: Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analysed. The urea cream group showed a trend towards a lower cumulative incidence of any-grade HFSR (log-rank, P = 0.247) and severe HFSR of grade II or higher (log-rank, P = 0.394) without statistical significance. In the incidence by time point, the incidence of severe HFSR of grade II or higher was significantly lower in the urea cream group than in the placebo control group at 2 weeks (13.8% versus 23.9%, P = 0.042). The urea cream group showed a significantly better HF-QoL questionnaire score than the placebo control group (11.8 versus 19.7, P = 0.014) at 12 weeks. CONCLUSIONS: Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream may be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03212625).

Clinician preferences for complete-arch fixed implant-supported prostheses: A survey of the membership of the Pacific Coast Society for Prosthodontics.

STATEMENT OF PROBLEM: Current in vivo and in vitro research has difficulty keeping pace with the rapid evolution of materials, protocols, and designs of the complete-arch fixed implant-supported prosthesis. PURPOSE: The purpose of this survey was to determine the current prevalence of usage of various treatment modalities and materials for complete-arch fixed implant-supported prostheses. MATERIAL AND METHODS: From November to December of 2018, a survey invitation was sent out to members of the Pacific Coast Society for Prosthodontics (PCSP). The survey was hosted online, and asked a series of 18 questions related to the materials, protocols, and design preferences for complete-arch fixed implant-supported prostheses. The prompt included the suggestion that answers should be based on preferences for ideal treatment of a hypothetical completely edentulous patient seeking fixed, implant-supported prostheses, assuming sufficient native bone and an opposing complete-arch fixed implant-supported prosthesis. RESULTS: Of 133 invitations sent via email, 45 (34%) surveys were started and 48 (36%) were completed. Pertinent results are summarized in histograms with color coding in each answer group to indicate the total number of arches the person had treated (a proxy for experience). Most respondents were in private practice (73%) and had completed more than 21 arches of fixed implant-supported prostheses (62%). Nearly half (49%) of the respondents preferred 6 implants in the maxilla, while the preferred number in the mandible was highly varied between 4 (33%), 5 (27%), and 6 (29%) implants. Three-fourths (75%) preferred bone-level implant designs, and the plurality was ambivalent on the use of a platform-switched design (48%). Two-thirds (67%) preferred to deliver a complete-arch fixed provisional prosthesis at the time of surgery. Two-thirds (67%) preferred to make the definitive impression by using rigidly splinted, open-tray copings. While most (67%) preferred to fabricate the definitive maxillary and mandibular prostheses with identical occlusal materials, the specifics of material selection between arches varied greatly. In the maxilla, a plurality preferred anatomic contour zirconia with titanium bases (33%). In the mandible, a plurality preferred laboratory-processed resin with denture teeth over a milled metal bar (32%). CONCLUSIONS: While a wide range of protocols, designs, and materials exist in the use of the complete-arch fixed implant-supported prosthesis, these results provide a snapshot of current clinical preferences in the Western United States.

Characterization of Two Novel Bacteriophages Infecting Multidrug-Resistant (MDR) Acinetobacter baumannii and Evaluation of Their Therapeutic Efficacy in Vivo.

Acinetobacter baumannii is emerging as a challenging nosocomial pathogen due to its rapid evolution of antibiotic resistance. We report characterization of two novel bacteriophages, PBAB08 and PBAB25, infecting clinically isolated, multidrug-resistant (MDR) A. baumannii strains. Both phages belonged to Myoviridae of Caudovirales as their morphology observed under an electron microscope. Their genomes were double stranded linear DNAs of 42,312 base pairs and 40,260 base pairs, respectively. The two phages were distinct from known Acinetobacter phages when whole genome sequences were compared. PBAB08 showed a 99% similarity with 57% sequence coverage to phage AB1 and PBAB25 showed a 97% similarity with 78% sequence coverage to phage IME_AB3. BLASTN significant alignment coverage of all other known phages were <30%. Seventy six and seventy genes encoding putative phage proteins were found in the genomes of PBAB08 and PBAB25, respectively. Their genomic organizations and sequence similarities were consistent with the modular theory of phage evolution. Therapeutic efficacy of a phage cocktail containing the two and other phages were evaluated in a mice model with nasal infection of MDR A. baumannii. Mice treated with the phage cocktail showed a 2.3-fold higher survival rate than those untreated in 7 days post infection. In addition, 1/100 reduction of the number of A. baumannii in the lung of the mice treated with the phage cocktail was observed. Also, inflammatory responses of mice which were injected with the phage cocktail by intraperitoneal, intranasal, or oral route was investigated. Increase in serum cytokine was minimal regardless of the injection route. A 20% increase in IgE production was seen in intraperitoneal injection route, but not in other routes. Thus, the cocktail containing the two newly isolated phages could serve as a potential candidate for therapeutic interventions to treat A. baummannii infections.

A Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy of Carvedilol vs. Propranolol to Reduce Portal Pressure in Patients With Liver Cirrhosis.

OBJECTIVES: Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis. More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient (HVPG) than propranolol. The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol. METHODS: A total of 110 patients with a baseline HVPG value >12 mm Hg were allocated randomly to receive either carvedilol or propranolol. The HVPG measurement was repeated after 6 weeks of daily medication. The primary end point was a ≥20% fall in HVPG compared with baseline or <12 mm Hg. RESULTS: The difference in the proportion of responders in the carvedilol (49.1%) vs. propranolol (30.9%) groups did not reach statistical significance in the intention-to-treat analysis (P=0.08). However, among patients with a model for end-stage liver disease (MELD) score ≥15, carvedilol resulted in a significantly greater response than that of propranolol (7/12, 58.3% vs. 0/10, 0%; P=0.005). Similarly, carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 (46.2 vs. 0%; P=0.046). The presence of ascites also had a significant influence on the response rate (51.5 vs. 24.2%; P=0.042). A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons (P=0.005). Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different. CONCLUSIONS: Overall, carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient. However, this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to understand the relative risk benefit.