Injectable ChitHCl-DDA tissue adhesive with high adhesive strength and biocompatibility for torn meniscus repair and regeneration.

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.

Intramedullary Nail vs. Plate Fixation for Pathological Humeral Shaft Fracture: An Updated Narrative Review and Meta-Analysis of Surgery-Related Factors.

(1) Background: Pathological humeral shaft fracture (PHSF) is a frequently observed clinical manifestation in the later stages of tumor metastasis. Surgical interventions are typically recommended to alleviate pain and restore functionality. Intramedullary nail fixation (INF) or plate fixation (PF) is currently recommended for the treatment of PHSF. However, there is still no standard for optimal surgical treatment. Thus, we conducted a meta-analysis comparing the clinical outcomes of INF with PF for PHSF treatment. (2) Methods: We conducted searches in databases, such as Scopus, EMBASE, and PubMed, for studies published prior to May 2023. In total, nine studies with 485 patients were reviewed. (3) Results: There were no significant differences noted in the incidence of fixation failure, local recurrence, wound complication or overall complication. However, the INF group demonstrated a significantly lower incidence of postoperative radial nerve palsy than the PF group (OR, 5.246; 95% CI, 1.548-17.774; p = 0.008). A subgroup analysis indicated that there were no statistically significant differences in fixation failure or local recurrence among subgroups categorized by the design of intramedullary nail. (4) Conclusions: Considering the short life expectancy of end-stage patients, the choice of surgical method depends on the patient's individual condition, fracture and lesion patterns, the surgeon's experience, and comprehensive discussion between the surgeon and patient.

Correlation between Subchondral Insufficiency Fracture of the Knee and Osteoarthritis Progression in Patients with Medial Meniscus Posterior Root Tear.

A medial meniscus posterior root tear (MMPRT) contributes to knee joint degeneration. Arthroscopic transtibial pullout repair (ATPR) may restore biomechanical integrity for load transmission. However, degeneration persists after ATPR in certain patients, particularly those with preoperative subchondral insufficiency fracture of the knee (SIFK). We explored the relationship between preoperative SIFK and osteoarthritis (OA) progression in retrospectively enrolled patients who were diagnosed as having an MMPRT and had received ATPR within a single institute. Based on their preoperative magnetic resonance imaging (MRI), these patients were then categorized into SIFK and non-SIFK groups. OA progression was evaluated by determining Kellgren-Lawrence (KL) grade changes and preoperative and postoperative median joint widths. SIFK characteristics were quantified using Image J (Version 1.52a). Both groups exhibited significant post-ATPR changes in medial knee joint widths. The SIFK group demonstrated significant KL grade changes (p < 0.0001). A larger SIFK size in the tibia and a greater lesion-to-tibia length ratio in the coronal view were positively correlated with more significant KL grade changes (p = 0.008 and 0.002, respectively). Thus, preoperative SIFK in patients with an MMPRT was associated with knee OA progression. Moreover, a positive correlation was observed between SIFK lesion characteristics and knee OA progression.

Plasma-Enabled Graphene Quantum Dot Hydrogel-Magnesium Composites as Bioactive Scaffolds for In Vivo Bone Defect Repair.

Bioactive and mechanically stable metal-based scaffolds are commonly used for bone defect repair. However, conventional metal-based scaffolds induce nonuniform cell growth, limiting damaged tissue restoration. Here, we develop a plasma nanotechnology-enhanced graphene quantum dot (GQD) hydrogel-magnesium (Mg) composite scaffold for functional bone defect repair by integrating a bioresource-derived nitrogen-doped GQD (NGQD) hydrogel into the Mg ZK60 alloy. Each scaffold component brings major synergistic advantages over the current alloy-based state of the art, including (1) mechanical support of the cortical bone and calcium deposition by the released Mg2+ during degradation; (2) enhanced uptake, migration, and distribution of osteoblasts by the porous hydrogel; and (3) improved osteoblast adhesion and proliferation, osteogenesis, and mineralization by the NGQDs in the hydrogel. Through an in vivo study, the hybrid scaffold with the much enhanced osteogenic ability induced by the above synergy promotes a more rapid, uniform, and directional bone growth across the hydrogel channel, compared with the control Mg-based scaffold. This work provides insights into the design of multifunctional hybrid scaffolds, which can be applied in other areas well beyond the demonstrated bone defect repair.

Platelet-Rich Fibrin-Augmented Gap-Bridging Strategy in Rabbit Anterior Cruciate Ligament Repair.

BACKGROUND: We assessed the efficacy of a novel platelet-rich fibrin (PRF)-augmented repair strategy for promoting biological healing of an anterior cruciate ligament (ACL) midsubstance tear in a rabbit model. The biological gap-bridging effect of a PRF scaffold alone or in combination with rabbit ligamentocytes on primary ACL healing was evaluated both in vitro and in vivo. HYPOTHESIS: A PRF matrix can be implanted as a provisional fibrin-platelet bridging scaffold at an ACL defect to facilitate functional healing. STUDY DESIGN: Controlled laboratory study. METHODS: The biological effects of PRF on primary rabbit ligamentocyte proliferation, tenogenic differentiation, migration, and tendon-specific matrix production were investigated for treatment of cells with PRF-conditioned medium (PRFM). Three-dimensional (3D) lyophilized PRF (LPRF)-cell composite was fabricated by culturing ligamentocytes on an LPRF patch for 14 days. Cell-scaffold interactions were investigated under a scanning electron microscope and through histological analysis. An ACL midsubstance tear model was established in 3 rabbit groups: a ruptured ACL was treated with isolated suture repair in group A, whereas the primary repair was augmented with LPRF and LPRF-cell composite to bridge the gap between ruptured ends of ligaments in groups B and C, respectively. Outcomes-gross appearance, magnetic resonance imaging, and histological analysis-were evaluated in postoperative weeks 8 and 12. RESULTS: PRFM promoted cultured ligamentocyte proliferation, migration, and expression of tenogenic genes (type I and III collagen and tenascin). PRF was noted to upregulate cell tenogenic differentiation in terms of matrix production. In the 3D culture, viable cells formed layers at high density on the LPRF scaffold surface, with notable cell ingrowth and abundant collagenous matrix depositions. Moreover, ACL repair tissue and less articular cartilage damage were observed in knee joints in groups B and C, implying the existence of a chondroprotective phenomenon associated with PRF-augmented treatment. CONCLUSION: Our PRF-augmented strategy can facilitate the formation of stable repair tissue and thus provide gap-bridging in ACL repair. CLINICAL RELEVANCE: From the translational viewpoint, effective primary repair of the ACL may enable considerable advancement in therapeutic strategy for ACL injuries, particularly allowing for proprioception retention and thus improved physiological joint kinematics.

Development of a Novel Hybrid Suture Anchor for Osteoporosis by Integrating Titanium 3D Printing and Traditional Machining.

The aim of this study is to develop a titanium three-dimensional (3D) printing novel hybrid suture anchor (HSA) with wing structure mechanism which can be opened to provide better holding power for surrounding osteoporotic bone. A screw-type anchor (5.5-mm diameter and 16-mm length) was designed with wing mechanism as well as micro dual-thread in the outer cortex bone contact area and macro single-thread in the anchor body. Both side wings can be opened by an internal screw to provide better bone holding power. The suture anchor and internal screw were manufactured using Ti6Al4V 3D printing and traditional machining, respectively. Static pullout and after dynamic 300-cyclic load (150 N) pullout tests for HSA with or without the wing open and commercial solid anchor (CSA) were performed (n = 5) in severely osteoporotic bone and osteoporotic bone to evaluate failure strengths. Comparison of histomorphometrical evaluation was performed through in vivo pig implantation of HSAs with the wing open and CSAs. The failure strengths of HSA with or without the wing open were 2.50/1.95- and 2.46/2.17-fold higher than those of CSA for static and after dynamic load pullout tests in severely osteoporotic bone, respectively. Corresponding values for static and after dynamic load pullout tests were 1.81/1.54- and 1.77/1.62-fold in osteoporotic bone, respectively. Histomorphometrical evaluation revealed that the effects of new bone ingrowth along the anchor contour for CSA and HSA were both approximately 20% with no significant difference. A novel HSA with wing mechanism was developed using 3D printing and the opened wing mechanism can be used to increase bone holding power for osteoporosis when necessary. Better failure strength of HSA than CSA under static and after dynamic load pullout tests and equivalence of bone ingrowth along the anchor contours confirmed the feasibility of the novel HSA.

Mathematical model of distal radius orientation.

Distal radius orientation is important in evaluating Colles' fracture. In most cases, the wrist was protected by a bandage, splint, or cast. Therefore, it was difficult for the radiology technician to take perfect anteroposterior and lateral view radiographs. In this study, we build a mathematical model and calculate the pronation angle needed to produce dorsal tilt, which is a volar tilt in a perfect lateral view radiograph. The formulas are all incorporated into Excel to facilitate usage.

Short-term exposure of anticoagulant rodenticides leads to the toxin accumulation from prey (Rattus losea) to predator (Elanus caeruleus).

Rodenticides are widely used around the world since the 1950s. In Taiwan, an anti-rodent operation initiated 1977 and became a regular action annually implied by the government until 2014. This anti-rodent operation caused many animals of non-target species being exposed by rodenticides and became an environmental issue. The Black-winged Kite (Elanus caeruleus) is a small-sized diurnal raptor widely distributed in the Old World continent. Since 2000, a newly colonized population of this species occurred in Taiwan. Although the Black-winged Kites may suffer from the threats of rodenticides, the population is still growing and soon became the most abundant raptor in farmlands of Taiwan. Whether the Black-winged Kite accumulates higher anticoagulant rodenticide residues than other raptors are still unclear. In this study, liver samples of Black-winged Kites were collected from 2013 to 2016, when the detected residues of anticoagulant rodenticides increased annually. The concentration of residue rodenticide was above 0.2 ppm among 30% of the detected samples, which is the toxicity threshold concentration of other raptors. In the meanwhile, the lesser ricefield rat (Rattus losea), the most common prey of Black-winged Kites, also extended the survival period after fed on rodenticide. The longer survival days after being poisoned can enhance the predation opportunity of raptors, thus affect the accumulated rodenticides in the raptors. This study demonstrates that the Black-winged Kite has higher concentration of anticoagulant rodenticide than most other raptors, which provide the case that the raptor can quickly accumulate rodenticide residues within a short period of time.

Injury mechanism affects the stability of suture-button syndesmosis fixation.

BACKGROUND: Ankle syndesmosis injury is a common condition, and the injury mechanism can be sorted into pure syndesmosis injury, Weber-B, and Weber-C type fractures. This study aims to evaluate the treatment outcomes and stability of suture-button fixation for syndesmosis injury with different injury mechanisms. We hypothesized that injury mechanisms would alter the stability of suture-button fixation. METHODS: We retrospectively reviewed 63 patients with ankle syndesmosis injury who underwent surgery with TightRope (Arthrex, Naples, FL, USA) from April 2014 to February 2019. The stability of suture-button fixation with TightRope was evaluated by comparing the preoperative, postoperative, and final follow-up measurements of tibiofibular clear space (TFCS), tibiofibular overlap (TFO), and medial clear space (MCS). A subgroup analysis for each demographic group and injury type including pure syndesmosis injury, Weber-B, and Weber-C type fractures were performed. RESULTS: Syndesmosis was effectively reduced using TightRope. After the index surgery, the tibiofibular clear space was reduced from 7.73 to 4.04 mm, the tibiofibular overlap was increased from 3.05 to 6.44 mm, and the medial clear space was reduced from 8.12 to 3.54 mm. However, syndesmosis widening was noted at the final follow-up, especially in Weber-C type fractures (TFCS 3.82 to 4.45 mm, p < 0.01 and TFO 6.86 to 6.29 mm, p = 0.04). Though widened, the final follow-up values of tibiofibular clear space and tibiofibular overlap were in the acceptable range. Postoperatively and at the final follow-up, medial clear space was found to be significantly larger in the Weber-C group than in the pure syndesmosis and Weber-B groups (p < 0.05). CONCLUSIONS: Suture-button fixation can offer anatomic reduction and dynamic fixation in syndesmosis injuries. However, when using this modality for Weber-C type fractures, more attention should be focused on the accuracy of reduction, especially of medial clear space, and rediastasis should be carefully monitored. TRIAL REGISTRATION: This trial was retrospectively approved by TMU-JIRB. Registration number N202004122, and the date of approval was May 06, 2020. LEVEL OF EVIDENCE: III.

Non-invasive and Time-dependent Blood-sugar Monitoring via Breath-derived CO2 Correlation Using Gas Chromatograph with a Milli-whistle Gas Analyzer.

A clear and positive correlation between the CO2 concentration and the blood-sugar level has been observed via a non-invasive and time-dependent monitoring of CO2 concentration from human breath, which is carried out by using a home-made gas chromatography (GC)/milli-whistle compact analyzer. The time-dependent sampling of the CO2 concentration correlated between 5.0 to 5.6% (1% = 104 ppm) in accordance with blood-sugar level variations of 80 to 110 mg/dL. The analytical method results in a rapid, continuous and non-invasive determination of blood-sugar level via measurement of the CO2 concentration exhaled from the lungs.

Analysis of DNA Damage Responses After Boric Acid-mediated Boron Neutron Capture Therapy in Hepatocellular Carcinoma.

BACKGROUND: Boron neutron capture therapy (BNCT) selectively kills tumor cells while sparing adjacent normal cells. Boric acid (BA)-mediated BNCT showed therapeutic efficacy in treating hepatocellular carcinoma (HCC) in vivo. However, DNA damage and corresponding responses induced by BA-mediated BNCT remained unclear. This study aimed to investigate whether BA-mediated BNCT induced DNA double-strand breaks (DSBs) and to explore DNA damage responses in vitro. MATERIALS AND METHODS: Huh7 Human HCC cells were treated with BA and irradiated with neutrons during BA-BNCT. Cell survival and DNA DSBs were examined by clonogenic assay and expression of phosphorylated H2A histone family member X (γH2AX), respectively. The DNA damage response was explored by determining the expression levels of DNA repair- and apoptosis-associated proteins and conducting a cell-cycle analysis. RESULTS: DNA DSBs induced by BA-mediated BNCT were primarily repaired through the homologous recombination pathway. BA-mediated BNCT induced G2/M arrest and apoptosis in HCC. CONCLUSION: Our findings may enable the identification of radiosensitizers or adjuvant drugs for potentiating the therapeutic effectiveness of BA-mediated BNCT for HCC.

Effect of Tumor Microenvironment on Selective Uptake of Boric Acid in HepG2 Human Hepatoma Cells.

BACKGROUND: Feasibility and efficacy of boric acid (BA)-mediated boron neutron capture therapy (BNCT) was first demonstrated by eliminating hepatocellular carcinoma (HCC) in a rat model. Furthermore, selective uptake of BA by liver tumor cells was shown in a rabbit model. To gain further insight, this study aimed to investigate the mechanisms of transportation and selective uptake of BA in HepG2 liver tumor cells. MATERIALS AND METHODS: Transportation of BA in HepG2 cells was analyzed by time-course assays and by analyzing the rate of diffusion versus the concentration of BA. The effect of different tumor conditions on BA uptake was studied by treating HepG2 cells with 25 µg 10B/ml BA under different concentrations of glucose, at different pH and in the presence of water-soluble cholesterol. RESULTS: HepG2 cells mainly uptake BA by simple diffusion. Cell membrane permeability may also contribute to tumor-specific uptake of BA. CONCLUSION: The selective uptake of BA was achieved primarily by diffusion, while other factors, such as low pH and increased membrane fluidity, which are hallmarks of HCC, might further enhance BA uptake.

Role of ß-naphthylalanine end-tags in the enhancement of antiendotoxin activities: Solution structure of the antimicrobial peptide S1-Nal-Nal in complex with lipopolysaccharide.

Lipopolysaccharide (LPS, endotoxin) is the major component of Gram-negative bacterial outer surface membrane. LPS released from bacteria into bloodstream during infection may cause serious unwanted stimulation of host's immune system and lead to septic shock of the patient. Recently, we have developed a strategy to increase salt resistance and LPS neutralization of short antimicrobial peptides by adding ß-naphthylalanine end-tags to their termini. Herein, correlations between membrane immersion depth, orientation, and antiendotoxin activities of the antimicrobial peptides S1 and S1-Nal-Nal have been investigated via solution structure, paramagnetic resonance enhancement, and saturation transfer difference NMR studies. Unlike the parent peptide S1, S1-Nal-Nal rotated its two terminal ß-naphthylalanine residues into the hydrophobic lipid A motif of LPS micelles. The LPS-induced inflammation may then be prohibited by the blocked lipid A motif.

Novel antimicrobial peptides with high anticancer activity and selectivity.

We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid ß-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

Treatment Results of Extracranial Malignant Germ Cell Tumor with Regimens of Cisplatin, Vinblastine, Bleomycin or Carboplatin, Etoposide, and Bleomycin with Special Emphasis on the Sites of Vagina and Testis.

BACKGROUND: The survival of children with malignant germ cell tumor (GCT) increased over the past 2 decades with platinum-based chemotherapy. This report has three objectives: (1) comparison of PVB (cisplatin, vinblastine, and bleomycin) with JEB (carboplatin, etoposide, and bleomycin) regimens; (2) treatment modality of vaginal GCT; and (3) management of stage I testicular yolk sac tumor (YST) in boys under 2 years old. METHODS: From January 1, 1987 to December 31, 2010, 81 patients with malignant extracranial GCT were treated. Two consecutive protocols, PVB followed by JEB, were used. Girls with vaginal YST received minimal surgery and chemotherapy. Boys under 2 years old with Stage I testicular YST received surgery with or without chemotherapy. RESULTS: As of June 30, 2012, the 10-year overall survival (OS) was 95 ± 3% (standard error) and the event-free survival (EFS) was 88 ± 4%. With PVB, 35 patients had 10-year OS of 91 ± 5% and EFS of 89 ± 5%. With JEB, 25 patients had 7-year OS of 96 ± 5% and EFS of 96 ± 5%. All five girls with vaginal YST were cured with vagina-preserved strategy. In 32 boys age under 2 years old with stage I YST, 16 with light chemotherapy were all in EFS, whereas two of 16 patients without chemotherapy relapsed. After PVB, six patients developed nephrotoxicity and one had pulmonary fibrosis. CONCLUSION: Girls with vaginal YST who received minimal surgery and chemotherapy had excellent prognosis and sexual organs were preservable. Light chemotherapy after surgery is a treatment option for boys under 2 years old with stage I YST to decrease relapse rate. Both JEB and PVB are effective. JEB resulted in more myelosuppression but otherwise less serious long-term toxicity than PVB.

Triple intrathecal therapy alone with omission of cranial radiation in children with acute lymphoblastic leukemia.

PURPOSE: To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed. RESULTS: Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/µL with blasts in a nontraumatic sample) nor CNS-3 (≥5 WBCs/µL with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates±SE were 84.2%±3.0% and 90.6%±2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4%±1.0%. CONCLUSION: Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT.

Minimally early morbidity in children with acute myeloid leukemia and hyperleukocytosis treated with prompt chemotherapy without leukapheresis.

BACKGROUND/PURPOSE: Patients with acute myeloid leukemia (AML) and hyperleukocytosis, defined as an initial white blood cell (WBC) count of ≥ 100 × 10(9)/L, are often treated with leukapheresis. In this study, we have reported our experience of treating AML without leukapheresis. METHODS: From November 1, 1995, to May 31, 2012, there were 74 children (≤18 years old) with de novo AML other than acute promyelocytic leukemia. Seventeen patients had an initial WBC count ≥ 100 × 10(9)/L. Prompt chemotherapy was started within hours whereas leukapheresis was not performed. RESULTS: The median age of the 17 patients with hyperleukocytosis was 7.4 years (range: 0-16 years), and the median initial WBC count was 177 × 10(9)/L (range: 117-635 × 10(9)/L). The median time between admission and initiation of chemotherapy was 4.5 hours (range: 2-72 hours) in patients with hyperleukocytosis, whereas it was 13 hours (range: 2-120 hours) in those without hyperleukocytosis. Seven patients (7/17, 41%) had one or more early complications before or during the first 2 weeks of chemotherapy. Fifteen of the 16 patients who received prompt chemotherapy achieved complete remission (93.8%), comparable with those without hyperleukocytosis (98.2%; p = 0.33). CONCLUSION: Children with AML and hyperleukocytosis, treated with prompt chemotherapy without leukapheresis, had minimal early morbidities.

Protein binding reaction enhanced by bi-directional flow driven by on-chip thermopneumatic actuator.

A microfluidic immunoassay system was developed for the study of the enhancement of protein binding reaction. The system mainly consisted of a thermopneumatic actuator and a reaction chamber. Reagent was pre-installed in the on-chip reservoir and manipulated by the actuator. Such design could eliminate the external tubing connections in order to reduce the waste of reagent and improve the portability. The on-chip actuator could manipulate the reagent bi-directionally to induce vortexes in the chamber. Enhancement of protein binding reaction was demonstrated by the protein model pair, i.e., mouse IgG and anti-mouse IgG. By such bi-directional fluid motion, more binding opportunities between suspended protein and its surface-immobilized counterpart were generated to improve the performance of immunoassay. It showed that an 83.74 % enhancement of the binding reaction was achieved, compared with the static situation. As a whole, the proposed microfluidic system is highly integrated and can enhance the protein binding efficiency using such novel design. The developed system can be easily extended to multi-reagents immunoassay protocols and provides a useful platform for point-of-care applications.

Severe infections in children with acute leukemia undergoing intensive chemotherapy can successfully be prevented by ciprofloxacin, voriconazole, or micafungin prophylaxis.

BACKGROUND: The purpose of the current study was to prevent bloodstream infection and invasive fungal infection (IFI) by administering prophylactic antibiotic and antifungal agents during intensive chemotherapy in patients being treated for acute leukemia. METHODS: Prophylaxis treatment was administered during intensive chemotherapy in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) from January 1, 2010 to December 31, 2012. Oral ciprofloxacin (at a dose of 300 mg/m(2) /12 hours) was administered after chemotherapy when a patient with AML or ALL became neutropenic and > 7 days of neutropenia was expected. Voriconazole (at a dose of 4 mg/kg/12 hours) was initiated at the onset of neutropenia in patients with AML and after 7 days of neutropenia in patients with ALL. Micafungin (at a dose of 2 mg/kg/day) was substituted for voriconazole when patients with ALL received vincristine. Prophylaxis treatment was discontinued when the absolute neutrophil count recovered to > 100/µL. All episodes of bloodstream infection, IFI, febrile neutropenia, and intensive care unit stays related to severe infection occurring between January 1, 2005 and December 31, 2012 were recorded. RESULTS: During the preprophylaxis period, 62 children with ALL and 24 children with AML experienced a total of 44 episodes of bloodstream infection and 22 episodes of IFI. Seven patients died of severe infection. In contrast, in the prophylaxis period, 10 episodes of bloodstream infection occurred and no IFIs were reported to occur in 51 patients with ALL and 14 patients with AML. Moreover, no patient died of severe infection. Episodes of febrile neutropenia and intensive care unit stay were significantly reduced during the prophylaxis period. CONCLUSIONS: Prophylaxis with ciprofloxacin and voriconazole or micafungin was found to reduce the rates of bloodstream infection and IFI in children with acute leukemia undergoing intensive chemotherapy.

Pulmonary function changes in rats with taurocholate-induced pancreatitis are attenuated by pretreatment with melatonin.

Melatonin is a free radical scavenger and broad-spectrum antioxidant with immunomodulatory effects. We studied the effects of melatonin on changes in lung function, oxidative/nitrosative stress, and inflammatory cell sequestration in an acute pancreatitis (AP)-associated lung inflammation model. Acute pancreatitis was induced by injection of 5% sodium taurocholate into the pancreatic duct of rats. Animals were randomized into control, AP, and a melatonin pretreatment (10 mg/kg)/AP group. Functional residual capacity (FRC), lung compliance (Cchord), expiratory flow rate at 50% (FEF50), airway resistance index (RI), and peak expiratory flow rate (PEF) were evaluated. White blood cell count (WBC) and hydrogen peroxide, lung lavage fluid WBC, methylguanidine, protein, lactic dehydrogenase (LDH), nitric oxide (NO), and leukotriene B4 (LTB4) levels were determined. Lung wet-to-dry weight ratio, peroxynitrite, and inducible nitric oxide synthase (NOS) mRNA and protein were measured. AP induction resulted in reductions in FRC, Cchord, FEF50, and PEF, and increase in RI and lung wet-to-dry weight ratio. Blood and lung lavage fluid WBC, lavage fluid LDH, protein, and blood hydrogen peroxide also increased. Levels of hydroxyl radicals, nitric oxide, and LTB4 in lung lavage fluid, inducible NOS mRNA, protein expression, and peroxynitrite in lung tissue also were significantly elevated. Pretreatment with melatonin attenuated obstructive and restrictive ventilatory insufficiency induced by AP. Blood and lavage WBC, lavage LDH and protein, lung edema, oxidative/nitrosative stress, and lipoxygenase pathway derivatives were also significantly attenuated by melatonin. We conclude that melatonin decreases AP-induced obstructive and restrictive lung function changes via its antioxidant and anti-inflammatory properties.