Febrile neutropenia and its associated hospitalization in breast cancer patients on docetaxel-containing regimen: A retrospective cohort study on duration of prophylactic GCSF administration.

PURPOSE: To compare febrile neutropenia (FN) incidence and hospitalization among breast cancer patients on docetaxel with no granulocyte colony-stimulating factors (GCSF) primary prophylaxis (PP), 4/5-day PP, or 7-day PP. METHODS: We identified 3916 breast cancer patients using docetaxel-cyclophosphamide (TC), doxorubicin-cyclophosphamide then docetaxel (AC-T), fluorouracil-epirubicin-cyclophosphamide then docetaxel (FEC-T), docetaxel-carboplatin-trastuzumab (TJH), or docetaxel-doxorubicin-cyclophosphamide (TAC) from a hospital pharmacy dispensing database in Hong Kong between 2014 and 2016. Patients were offered GCSF within 5 days since administering docetaxel. Outcomes included FN incidence, time to first hospitalization, hospitalization rate, and duration. RESULTS: In TC regimen, FN incidence (with odds ratio, OR) of patients with no PP, 4/5-day PP, and 7-day PP was 21.69%, 7.95% (OR 0.31, p < 0.001), and 5.33% (OR 0.20, p < 0.001), respectively. In TJH regimen, FN incidence of patients with no PP, 4/5-day PP, and 7-day PP was 38.26%, 8.33% (OR 0.15, p < 0.001), and 8.57% (OR 0.15, p < 0.001), respectively. FN incidence of patients on AC-T regimen with no PP and 4/5-day PP was 20.93% and 6.84%, respectively (OR 0.28, p = 0.005); with FEC-T regimen, the incidence was 9.91% and 4.77%, respectively (OR 0.46, p = 0.035). Only 3.27% FN cases were not hospitalized. Mean (±standard deviation, SD) time to first hospitalization was 8.21 ± 2.44 days. Mean (±SD) duration of hospitalization for patients with no PP, 4/5-day PP, and 7-day PP was 4.66 ± 2.60, 4.37 ± 2.85, and 5.12 ± 2.97 days, respectively. CONCLUSION: GCSF prophylaxis in breast cancer patients on docetaxel could reduce FN incidence and hospitalization. 4/5-day PP demonstrated similar efficacy to 7-day PP with superior saving benefits on healthcare expenditure.

Sagittal alignment and mobility of the thoracolumbar spine are associated with radiographic progression of secondary hip osteoarthritis.

OBJECTIVE: To identify predictors of radiographic progression of hip osteoarthritis (OA) over 12 months among functional hip impairments and spinal alignment and mobility. DESIGN: Fifty female patients with secondary hip OA, excluding those with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA over 12 months (>0.5 mm in JSW) as dependent variable, logistic regression analyses were performed to identify predictors for hip OA progression among functional impairments of the hip and spine with and without adjustment for age, body mass index (BMI), and minimum JSW at baseline. The independent variables were hip pain, Harris hip score (HHS), hip morphological parameters, hip passive range of motion (ROM) and muscle strength, and alignment and mobility of the thoracolumbar spine at baseline. RESULTS: Twenty-one (42.0%) patients demonstrated radiographic progression of hip OA. Multivariable logistic regression analysis showed that larger anterior inclination of the spine in standing position (adjusted OR [95% CI], 1.37 [1.04-1.80]; P = 0.028) and less thoracolumbar spine mobility (adjusted OR [95% CI], 0.96 [0.92-0.99]; P = 0.037) at baseline were statistically significantly associated with radiographic progression of hip OA, even after adjustment for age, BMI, and minimum JSW. CONCLUSIONS: The findings suggest that spinal alignment and mobility should be considered when assessing risk and designing preventive intervention for radiographic progression of secondary hip OA.

Mortality and morbidity of extremely low birth weight infants in Hong Kong, 2010-2017: a single-centre review.

BACKGROUND: Extremely low birth weight (ELBW) infants exhibit high rates of mortality and morbidity. We retrospectively assessed factors associated with mortality and morbidity among ELBW infants. METHODS: Perinatal demographic data were reviewed for all ELBW infants born between 2010 and 2017 at a tertiary neonatal unit. RESULTS: For non-survivors (21% of ELBW infants) and survivors, the median gestational ages were 24.1 and 26.2 weeks, respectively, and median birth weights were 650 g and 780 g, respectively (all P<0.001). Regression analyses showed that non-survival was positively associated with lower gestational age (adjusted odds ratio [aOR]=6.71 for every 1-week decrease; 95% confidence interval [CI]=1.73-26.00; P=0.006) and grade 3 or 4 intraventricular haemorrhage (aOR=29.23; 95% CI=1.39-613.84; P=0.030); non-survival was negatively associated with the presence of bronchopulmonary dysplasia (aOR=0.01; 95% CI= <0.001-0.23; P=0.005); length of neonatal intensive care unit stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=89.60; 95% CI=43.86-135.34; P<0.001); and length of hospital stay for survivors was positively associated with the presence of necrotising enterocolitis (B-coefficient=2.08; 95% CI=0.43-3.73; P=0.015) and a low Apgar score at 1 minute (B-coefficient=-0.63; 95% CI=-1.04 to -0.22; P=0.003). CONCLUSION: Extremely low birth weight infants exhibited significant mortality and morbidity; there was no survival prior to 23.6 weeks' gestation or below 550 g birth weight. The presence of grade 3 or 4 intraventricular haemorrhage was independently associated with non-survival. Survivors were significantly more likely to exhibit bronchopulmonary dysplasia; survivors with necrotising enterocolitis were more likely to require longer stays in the neonatal intensive care unit and in hospital.

Effects of Swaddled and Sponge Bathing Methods on Signs of Stress and Pain in Premature Newborns: Implications for Evidence-Based Practice.

AIMS: To determine the effects of sponge baths and swaddled bathing on premature infants' vital signs, oxygen saturation levels, crying times, pain, and stress levels. METHODS: This study was a clinical trial with a crossover design. Data were conducted in the neonatal intensive care unit of a public hospital in Denizli, Turkey. A total of 35 premature infants, who were born at 33-37 weeks gestation with a birth weight <1,500 g, were enrolled in the study. Two bathing methods were applied at 3-day intervals. Vital signs and oxygen saturation levels were measured before and at minutes 1, 5, 15, 30 after bathing. Infants' bathing was video recorded to assess pain and stress behaviors. The pain and stress behaviors of infants were evaluated by independent observers. A significance level of .05 was used for all statistical analyses. RESULTS: There were statistically significant differences between bathing methods on vital signs, oxygen saturation levels, and crying times. Levels of stress and pain according to bathing type were significantly higher in the sponge bath condition (p < .05). LINKING EVIDENCE TO ACTION: Swaddled bathing has a positive effect on the infant's vital signs, oxygen saturation levels, crying time, and level of stress and pain compared to the sponge bath condition. Swaddled bathing is a harmless and safe nursing practice.

Daily cumulative hip moment is associated with radiographic progression of secondary hip osteoarthritis.

OBJECTIVE: To investigate whether higher daily cumulative hip moment at baseline is associated with subsequent radiographic progression of hip osteoarthritis (OA) over 12 months. DESIGN: Fifty patients with secondary hip OA, excluding patients with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA (>0.5 mm/year in JSW) as dependent variable (yes/no), univariable and multivariable logistic regression analyses were performed to assess the association between load-related parameters during gait (i.e., peak hip moment, hip moment impulse, and daily cumulative hip moment [product of hip moment impulse and mean steps/day]) and hip OA progression with and without adjustment for age, body weight, and minimum JSW. RESULTS: Of the 50 patients (47.4 ± 10.7 years old), 21 (42.0%) were classified into the progression group. The higher daily cumulative hip moment in the frontal plane at baseline was statistically significantly associated with radiographic progression of hip OA (adjusted odds ratio (OR) [95% confidence interval (CI)], 1.34 [1.06-1.70]; P = 0.013). The higher daily cumulative hip moment in the sagittal plane was also approaching significance in its association with hip OA progression (adjusted OR, 1.80 [0.99-3.26]; P = 0.052). CONCLUSIONS: In the female patients with secondary hip OA, higher daily cumulative hip moment, particularly in the frontal plane, was a predictor of radiographic progression of hip OA over 12 months. Reduction in daily cumulative hip moment by modification in gait and physical activity may potentially slow hip OA progression.

Lowering levels of bed occupancy is associated with decreased inhospital mortality and improved performance on the 4-hour target in a UK District General Hospital.

OBJECTIVE: To evaluate whether there is an association between an intervention to reduce medical bed occupancy and performance on the 4-hour target and hospital mortality. METHODS: This before-and-after study was undertaken in a large UK District General Hospital over a 32 month period. A range of interventions were undertaken to reduce medical bed occupancy within the Trust. Performance on the 4-hour target and hospital mortality (hospital standardised mortality ratio (HSMR), summary hospital-level mortality indicator (SHMI) and crude mortality) were compared before, and after, intervention. Daily data on medical bed occupancy and percentage of patients meeting the 4-hour target was collected from hospital records. Segmented regression analysis of interrupted time-series method was used to estimate the changes in levels and trends in average medical bed occupancy, monthly performance on the target and monthly mortality measures (HSMR, SHMI and crude mortality) that followed the intervention. RESULTS: Mean medical bed occupancy decreased significantly from 93.7% to 90.2% (p=0.02). The trend change in target performance, when comparing preintervention and postintervention, revealed a significant improvement (p=0.019). The intervention was associated with a mean reduction in all markers of mortality (range 4.5-4.8%). SHMI (p=0.02) and crude mortality (p=0.018) showed significant trend changes after intervention. CONCLUSIONS: Lowering medical bed occupancy is associated with reduced patient mortality and improved ability of the acute Trust to achieve the 95% 4-hour target. Whole system transformation is required to create lower average medical bed occupancy.

Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients.

Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.

Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial.

STUDY DESIGN: Lithium has attracted much attention as a neuroregenerative agent for spinal cord injury in animal models. We hypothesized that the lithium can be beneficial to patients with spinal cord injury. The safety and pharmacokinetics of lithium has been studied in our earlier phase I clinical trial, indicating its safety. This is a phase II clinical trial to evaluate its efficacy on chronic spinal cord injury patients. OBJECTIVES: The aim of this study was to investigate the efficacy of lithium on chronic spinal cord injury patients. SETTING: A major spinal cord injury rehabilitation center in Beijing, China. METHODS: Randomized, double-blind, placebo-controlled 6-week parallel treatment arms with lithium carbonate and with placebo. A total of 40 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was titrated or placebo was simulated to maintain the serum lithium level of 0.6-1.2 mmol l(-1) for 6 weeks, followed by a 6-month follow-up. The functional outcomes and the neurological classifications, as well as the safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. RESULTS: No significant changes in the functional outcomes and the neurological classifications were found. The only significant differences were in the pain assessments using visual analog scale comparing the lithium and the placebo group. No severe adverse event was documented in the study. CONCLUSION: The lithium treatment did not change the neurological outcomes of patients with chronic spinal cord injury. It is worth to investigate whether lithium is effective in the treatment of neuropathic pain in chronic spinal cord injury. SPONSORSHIP: China Spinal Cord Injury Network Company Limited.

Neuroprotective effects of minocycline on double-stranded RNA-induced neurotoxicity in cultured cortical neurons.

1. Minocycline, memantine,and glycoconjugate were assessed for their ability to protect cultured primary cortical neurons against double-stranded RNA-induced neurotoxicity. 2. Minocycline but not memantine or glycoconjugate protected cultured cells and warrants further investigation.

The Regulation of Chemerin and CMKLR1 Genes Expression by TNF-α, Adiponectin, and Chemerin Analog in Bovine Differentiated Adipocytes.

Adipokines, adipocyte-derived protein, have important roles in various kinds of physiology including energy homeostasis. Chemerin, one of adipocyte-derived adipokines, is highly expressed in differentiated adipocytes and is known to induce macrophage chemotaxis and glucose intolerance. The objective of the present study was to investigate the changes of chemerin and the chemokine-like-receptor 1 (CMKLR1) gene expression levels during differentiation of the bovine adipocyte and in differentiated adipocytes treated with tumor necrosis factor-α (TNF-α), adiponectin, leptin, and chemerin (peptide analog). The expression levels of the chemerin gene increased at d 6 and 12 of the differentiation period accompanied by increased cytoplasm lipid droplets. From d 6 onward, peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) gene expression levels were significantly higher than that of d 0 and 3. In contrast, CMKLR1 expression levels decreased at the end of the differentiation period. In fully differentiated adipocytes (i.e. at d 12), the treatment of TNF-α and adiponectin upregulated both chemerin and CMKLR1 gene expression levels, although leptin did not show such effects. Moreover, chemerin analog treatment was shown to upregulate chemerin gene expression levels regardless of doses. These results suggest that the expression of chemerin in bovine adipocyte might be regulated by chemerin itself and other adipokines, which indicates its possible role in modulating the adipokine secretions in adipose tissues.

A three-month, open-label, single-arm trial evaluating the safety and pharmacokinetics of oral lithium in patients with chronic spinal cord injury.

OBJECTIVES: Lithium has recently been found to enhance neuronal regeneration and differentiation. This arouses its potential use to treat spinal cord injury patients. The safety and pharmacokinetics of lithium are not verified for this group of patients as their internal organ functions may change. This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of lithium in spinal cord injury patients. METHODS: A total of 20 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was given in divided dose to maintain the serum lithium level 0.6-1.2 mmol l(-1) for 6 weeks. Safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. RESULTS: No severe adverse event was documented. All blood parameters remained stable. Nausea and vomiting were the most common complaints but tolerance was improved in 2 weeks for most subjects. A wide range of oral doses was required to maintain serum lithium level at the targeted range. However, the dose for individual subject was relatively constant. CONCLUSION: This phase 1 clinical trial is the first report indicating the safety of lithium in chronic spinal cord injury patients. It is well tolerated after the first 2 weeks. Individual titration of lithium is essential to maintain an optimal serum lithium level but once the desirable level is achieved, the oral dose remains relatively unchanged for maintenance.

Infantile cortical hyperostosis (Caffey disease): a possible misdiagnosis as physical abuse.

Infantile cortical hyperostosis (Caffey disease) is a rare self-limiting inflammatory bony disease of early infancy. We report a 1-month-old Chinese boy with Caffey disease who presented with painful swelling over his shins bilaterally. Physical abuse was initially suspected, but the radiological findings of periosteal thickening over multiple bones (particularly the mandible), symmetrical involvement, diaphyseal involvement with sparing of the epiphysis, made Caffey disease a likely diagnosis. This report highlights that infantile cortical hyperostosis is an important differential diagnosis for children suspected of being abused, and clinicians should have a high index of suspicion to avoid misdiagnosis.

Enzyme-mediated one-pot synthesis of hydrogel with the polyphenol cross-linker for skin regeneration.

Polyphenols can trigger immunity that activates intracellular anti-inflammatory signaling and prevents external infections. In this study, we report the fabrication of chitosan-based hydrogels with epigallocatechin gallate (EGCG) using enzyme-mediated one-pot synthesis. The tyrosinase-mediated oxidative reaction of the phenolic rings of EGCG with the primary amines on chitosan results in stable EGCG-chitosan hydrogels. The EGCG concentrations contributed to the cross-linking density and physical properties of EGCG-chitosan hydrogels. Furthermore, EGCG-chitosan hydrogels maintained intrinsic properties such as antibacterial and antioxidant effects. When endotoxin-activated RAW 264.7 macrophage cells were cultured with EGCG-chitosan hydrogels, the hydrogels reduced the inflammatory response of the RAW 264.7 cells. Furthermore, subcutaneous implantation of EGCG-chitosan hydrogels reduced endogenous macrophage and monocyte activation. When the EGCG-chitosan hydrogels were applied to a full-skin defect wound, they facilitated skin regeneration. Our study demonstrates that the one-pot synthesized EGCG-chitosan hydrogels can be applied in broad tissue regeneration applications that require immune modulation.

Malignant fibrous histiocytoma complicating nephrogenic systemic fibrosis post liver transplantation.

A 46-year-old man with cirrhosis secondary to hepatitis C virus infection and alcohol underwent orthotopic liver transplantation, which required urgent re-grafting because of biliary sepsis from necrosis of the left liver lobe. Recovery was complicated by renal failure and nephrogenic systemic fibrosis (probably related to intravenous gadolinium exposure). He subsequently developed a malignant fibrous histiocytoma. We present this case highlighting the occurrence of two rare conditions in the same patient following liver transplantation. We believe this is the first case of its kind to be reported.

Effect of ultrasonic treatment on swine wastewater solubilization.

In order to accelerate hydrolysis known to be the rate-limiting step of the overall digestion process for swine wastewater, an ultrasonic treatment process was tested for the solubilization of the swine wastewater. The effectiveness of ultrasonic solubilization of the swine wastewater under various operational conditions was compared by means of an increment of soluble organics in the treated swine wastewater and the hydrolysis rate constant. Ultrasonic treatment resulted in the high degree of solubilization of particulate organics in the swine wastewater and the degree of solubilization increased with increasing supplied energy. The highest extent of an increment of SCOD concentration and SCOD/TCOD ratio at the end of the operation time of 60 min was 109.7 and 117.5%, respectively, under 120 W power output and 20(o)C operating temperature conditions. The observed highest hydrolysis rate constant described by pseudo-first order rate constant was 2.94 h(-1) under the same conditions. Based on the estimated activation energy from modeling using the Arrhenius equation, ultrasonic solubilization of the swine wastewater under higher supplied energy conditions was more dependent on the operating temperature, which was consistent with the experimentally obtained results. Based on the investigation into the effect of gas type and gas delivery methods for ultrasonic solubilization of the swine wastewater, oxygen gas bubbling through the liquid showed the highest degree of an increment of soluble organics possibly attributed to the influent of oxygen in an increase of radicals during the sonolysis.

The olfactory conditioning in the early postnatal period stimulated neural stem/progenitor cells in the subventricular zone and increased neurogenesis in the olfactory bulb of rats.

The olfactory memory acquired during the early postnatal period is known to be maintained for a long period, however, its neural mechanism remains to be clarified. In the present study, we examined the effect of olfactory conditioning during the early postnatal period on neurogenesis in the olfactory bulb of rats. Using the bromodeoxyuridine-pulse chase method, we found that the olfactory conditioning, which was a paired presentation of citral odor (conditioned stimulus) and foot shock (unconditioned stimulus) in rat pups on postnatal day 11, stimulated the proliferation of neural stem/progenitor cells in the anterior subventricular zone (aSVZ), but not in the olfactory bulb, at 24 h after the conditioning. However, the number of newborn cells in the olfactory bulb was increased at 2 weeks, but not 8 weeks, after such conditioning. Neither the exposure of a citral odor alone nor foot shock alone affected the proliferation of neural stem/progenitor cells in the aSVZ at 24 h after and the number of newborn cells in the olfactory bulb at 2 weeks after. The majority of newborn cells in the olfactory bulb of either the conditioned rats or the unconditioned rats expressed the neural marker NeuN, thus indicating that the olfactory conditioning stimulated neurogenesis in the olfactory bulb. These results suggest that olfactory conditioning during the early postnatal period temporally stimulates neurogenesis in the olfactory bulb of rats.