CD74 is expressed in a subset of pediatric acute myeloid leukemia patients and is a promising target for therapy: a report from the Children's Oncology Group.

As curative therapies for pediatric AML remain elusive, identifying potential new treatment targets is vital. We assessed the cell surface expression of CD74, also known as the MHC-II invariant chain, by multidimensional flow cytometry in 973 patients enrolled in the Children's Oncology Group AAML1031 clinical trial. 38% of pediatric AML patients expressed CD74 at any level and a comparison to normal hematopoietic cells revealed a subset with increased expression relative to normal myeloid progenitor cells. Pediatric AML patients expressing high intensity CD74 typically had an immature immunophenotype and an increased frequency of lymphoid antigen expression. Increased CD74 expression was associated with older patients with lower WBC and peripheral blood blast counts, and was enriched for t(8;21), trisomy 8, and CEBPA mutations. Overall, high CD74 expression was associated with low-risk status, however 26% of patients were allocated to high-risk protocol status and 5-year event free survival was 53%, indicating that a significant number of high expressing patients had poor outcomes. In vitro pre-clinical studies indicate that anti-CD74 therapy demonstrates efficacy against AML cells but has little impact on normal CD34+ cells. Together, we demonstrate that CD74 is expressed on a subset of pediatric AMLs at increased levels compared to normal hematopoietic cells and is a promising target for therapy in expressing patients. Given that nearly half of patients expressing CD74 at high levels experience an adverse event within 5 years, and the availability of CD74 targeting drugs, this represents a promising line of therapy worthy of additional investigation.

Verification of surface-guided radiation therapy (SGRT) alignment for proton breast and chest wall patients by comparison to CT-on-rails and kV-2D alignment.

BACKGROUND: Surface-guided radiation therapy (SGRT) systems have been widely installed and utilized on linear accelerators. However, the use of SGRT with proton therapy is still a newly developing field, and published reports are currently very limited. PURPOSE: To assess the clinical application and alignment agreement of SGRT with CT-on-rails (CTOR) and kV-2D image-guided radiation therapy (IGRT) for breast treatment using proton therapy. METHODS: Four patients receiving breast or chest wall treatment with proton therapy were the subjects of this study. Patient #1's IGRT modalities were a combination of kV-2D and CTOR. CTOR was the only imaging modality for patients #2 and #3, and kV-2D was the only imaging modality for patient #4. The patients' respiratory motions were assessed using a 2-min surface position recorded by the SGRT system during treatment. SGRT offsets reported after IGRT shifts were recorded for each fraction of treatment. The agreement between SGRT and either kV-2D or CTOR was evaluated. RESULTS: The respiratory motion amplitude was <4 mm in translation and <2.0° in rotation for all patients. The mean and maximum amplitude of SGRT offsets after application of IGRT shifts were ≤(2.6 mm, 1.6° ) and (6.8 mm, 4.5° ) relative to kV-2D-based IGRT; ≤(3.0 mm, 2.6° ) and (5.0 mm, 4.7° ) relative to CTOR-based IGRT without breast tissue inflammation. For patient #3, breast inflammation was observed for the last three fractions of treatment, and the maximum SGRT offsets post CTOR shifts were up to (14.0 mm, 5.2° ). CONCLUSIONS: Due to the overall agreement between SGRT and IGRT within reasonable tolerance, SGRT has the potential to serve as a valuable auxiliary IGRT tool for proton breast treatment and may improve the efficiency of proton breast treatment.

Targeted therapy in glomerular diseases.

Targeted therapy has emerged as a more precise approach to treat glomerular diseases, focusing on specific molecular or cellular processes that contribute to disease development or progression. This approach complements or replaces traditional immunosuppressive therapy, optimizes supportive care, and provides a more personalized treatment strategy. In this review, we summarize the evolving understanding of pathogenic mechanisms in immune-mediated glomerular diseases and the developing targeted therapies based on these mechanisms. We begin by discussing pan-B-cell depletion, anti-CD20 rituximab, and targeting B-cell survival signaling through the BAFF/APRIL pathway. We also exam specific plasma cell depletion with anti-CD38 antibody. We then shift our focus to complement activation in glomerular diseases, which is involved in antibody-mediated glomerular diseases, such as IgA nephropathy, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis. Non-antibody-mediated complement activation occurs in glomerular diseases, including C3 glomerulopathy, complement-mediated atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. We discuss specific inhibition of terminal, lectin, and alternative pathways in different glomerular diseases. Finally, we summarize current clinical trials targeting the final pathways of various glomerular diseases, including kidney fibrosis. We conclude that targeted therapy based on individualized pathogenesis should be the future of treating glomerular diseases.

A Fc-VEGF chimeric fusion enhances PD-L1 immunotherapy via inducing immune reprogramming and infiltration in the immunosuppressive tumor microenvironment.

BACKGROUND: Immunotherapy is an emerging cancer therapy with potential great success; however, immune checkpoint inhibitor (e.g., anti-PD-1) has response rates of only 10-30% in solid tumor because of the immunosuppressive tumor microenvironment (TME). This affliction can be solved by vascular normalization and TME reprogramming. METHODS: By using the single-cell RNA sequencing (scRNAseq) approach, we tried to find out the reprogramming mechanism that the Fc-VEGF chimeric antibody drug (Fc-VFD) enhances immune cell infiltration in the TME. RESULTS: In this work, we showed that Fc-VEGF121-VEGF165 (Fc-VEGF chimeric antibody drug, Fc-VFD) arrests excess angiogenesis and tumor growth through vascular normalization using in vitro and in vivo studies. The results confirmed that the treatment of Fc-VFD increases immune cell infiltration including cytotoxic T, NK, and M1-macrophages cells. Indeed, Fc-VFD inhibits Lon-induced M2 macrophages polarization that induces angiogenesis. Furthermore, Fc-VFD inhibits the secretion of VEGF-A, IL-6, TGF-ß, or IL-10 from endothelial, cancer cells, and M2 macrophage, which reprograms immunosuppressive TME. Importantly, Fc-VFD enhances the synergistic effect on the combination immunotherapy with anti-PD-L1 in vivo. CONCLUSIONS: In short, Fc-VFD fusion normalizes intratumor vasculature to reprogram the immunosuppressive TME and enhance cancer immunotherapy.

Aldh inhibitor restores auditory function in a mouse model of human deafness.

Genetic hearing loss is a common health problem with no effective therapy currently available. DFNA15, caused by mutations of the transcription factor POU4F3, is one of the most common forms of autosomal dominant non-syndromic deafness. In this study, we established a novel mouse model of the human DFNA15 deafness, with a Pou4f3 gene mutation (Pou4f3Δ) identical to that found in a familial case of DFNA15. The Pou4f3(Δ/+) mice suffered progressive deafness in a similar manner to the DFNA15 patients. Hair cells in the Pou4f3(Δ/+) cochlea displayed significant stereociliary and mitochondrial pathologies, with apparent loss of outer hair cells. Progression of hearing and outer hair cell loss of the Pou4f3(Δ/+) mice was significantly modified by other genetic and environmental factors. Using Pou4f3(-/+) heterozygous knockout mice, we also showed that DFNA15 is likely caused by haploinsufficiency of the Pou4f3 gene. Importantly, inhibition of retinoic acid signaling by the aldehyde dehydrogenase (Aldh) and retinoic acid receptor inhibitors promoted Pou4f3 expression in the cochlear tissue and suppressed the progression of hearing loss in the mutant mice. These data demonstrate Pou4f3 haploinsufficiency as the main underlying cause of human DFNA15 deafness and highlight the therapeutic potential of Aldh inhibitors for treatment of progressive hearing loss.

Measurements of fetal dose with Mevion S250i proton therapy system with HYPERSCAN.

PURPOSE: To characterize potential dose to the fetus for all modes of delivery (dynamic adaptive aperture, static adaptive aperture, and no adaptive aperture) for the Mevion S250i Proton Therapy System with HYPERSCAN and compare the findings with those of other available proton systems. MATERIALS AND METHODS: Fetal dose measurements were performed for all three modes of dose delivery on the Mevion S250i Proton therapy system with HYPERSCAN (static aperture, dynamic aperture and uncollimated). Standard treatment plans were created in RayStation for a left-sided brain lesion treated with a vertex field, a left lateral field, and a posterior field. Measurements were performed using WENDI and the RANDO with the detector placed at representative locations to mimic the growth and movement of the fetus at different gestational stages. RESULTS: The fetal dose measurements varied with fetus position and the largest measured dose was 64.7 µSv per 2 Gy (RBE) fraction using the dynamic aperture. The smallest estimated fetal dose was 45.0 µSv per 2 Gy (RBE) at the base of the RANDO abdomen (47 cm from isocenter to the outer width of WENDI and 58.5 cm from the center of the WENDI detector) for the static aperture delivery. The vertex fields at all depths had larger contributions to the total dose than the other two and the dynamic aperture plans resulted in the highest dose measured for all depths. CONCLUSION: The reported doses are lower than reported doses using a double-scattering system. This work suggests that avoiding vertex fields and using the static aperture will help minimize dose to the fetus.

[Enhancing Understanding Among Intensive Care Unit Nurses of Lower Back Musculoskeletal Disorders and Associated Risks].

BACKGROUND & PROBLEMS: Work-related musculoskeletal disorders (WMSDs) have received the most attention worldwide of the various diseases addressed by the field of occupational medicine. In intensive care units (ICUs), patients with critical illness typically rely heavily on assistance provided by nurses to engage in daily life and rehabilitation activities. This dependence increases the risk of nurses experiencing WMSDs. An injury screening revealed that 56.4% of the nurses working in the ICU of the case hospital faced a mild risk of lower back musculoskeletal disorders and that the main contributor to this risk was lack of understanding among these nurses of lower-back-related WMSDs. PURPOSE: This project was designed to enhance understanding of lower back WMSDs among the ICU nurses and to reduce the percentage of nurses facing a mild risk of contracting WMSDs. RESOLUTIONS: 1. Organize integrated courses to introduce human-induced hazards and enhance nurses' understanding and prevention of WMSDs. 2. Design slogans, posters, and teaching videos to promote awareness of patient turning tips and procedures to prevent nurses from experiencing WMSDs due to incorrect force application. 3. Design illustrations highlighting risky postures commonly performed by nurses in ICUs that may cause lower back WMSDs to prevent the occurrence of human-induced injuries. RESULTS: The rate of correct understanding of lower back WMSDs in the target nurse population improved from 73.8% to 96.2%. In addition, the percentage of those assessed with a mild risk of contracting lower back musculoskeletal injuries decreased from 56.4% to 25.5%. CONCLUSIONS: This project promoted multifaceted improvement measures based on the WMSD screening and risk classification and management processes stipulated by Taiwan's Ministry of Labor to increase understanding of lower back WMSDs among ICU nurses and reduce the percentage of those facing a mild risk of contracting WMSDs.

Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells.

Plasma levels of angiopoietin-2 are increased in patients with chronic kidney disease (CKD). Moreover, mouse models of progressive kidney disease also demonstrate increased angiopoietin-2 in both plasmas and kidneys. The role of dysregulated angiopoietins in the progression of kidney disease has not been thoroughly investigated. Here, we found in a cohort of 319 patients with CKD that plasma angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratios were positively associated with the development of kidney failure. In mice with progressive kidney disease induced by either ureteral obstruction or ischemia-reperfusion injury, overexpression of human angiopoietin-1 in the kidney tubules not only reduced macrophage infiltration in the initial stage post-injury but also attenuated endothelial cell apoptosis, microvascular rarefaction, and fibrosis in the advanced disease stage. Notably, angiopoietin-1 attenuated chemokine C-C motif ligand 2 (CCL2) expression in the endothelial cells of the fibrosing kidneys, and these protective effects led to attenuation of functional impairment. Mechanistically, angiopoietin-1 reduced CCL2-activated macrophage migration and protected endothelial cells against cell apoptosis induced by angiopoietin-2 and Wnt ligands. Based on this, we applied L1-10, an angiopoietin-2 inhibitor, to the mouse models of progressive kidney disease and found inhibitory effects on macrophage infiltration, microvascular rarefaction, and fibrosis. Thus, we defined the detrimental impact of increased angiopoietin-2 on kidney survival of patients with CKD which appears highlighted by angiopoietin-2 induced endothelial CCL2-activated macrophage infiltration and endothelial cell apoptosis in their kidneys undergoing fibrosis.

Differences in Practitioner Experience, Practice Type, and Profession in Attitudes Toward Growing Contact Lens Practice.

OBJECTIVE: To investigate eye care practitioners' attitudes and perceptions toward potential interventions that can enhance contact lens (CL) practice across the world, and how this is influenced by their practice setting. METHODS: A self-administered, anonymized survey was constructed in English and then forward and backward translated into six more languages. The survey was distributed online via social media platforms and mailing lists involving reputed international professional bodies. RESULTS: In total, 2,222 responses from 27 countries with sufficient responses were analyzed (53% females, median age- 37 years). Most of the respondents were optometrists (81.9%) and 47.6% were from stand-alone/independent practices. Median working experience in CL prescribing was 11.0 years (IQR: 18.0, 4-22 years). Over two-third of them declared themselves to be very hopeful (22.9%) or hopeful (45.1%) about the future of their CL practice. Among the potential interventions proposed, continuous update of knowledge and skills and competently managing CL-related complications were rated the most important (median score: 9/10 for each). Practitioners working in national/regional retail chains expressed higher proactivity in recommending CLs (9/10) than those in local chains, hospitals, and universities (for all 8/10, P <0.05). National differences were also identified in eye care practitioner attitudes and perceptions ( P <0.05). CONCLUSIONS: The study provided important information to delineate a variety of elements characterizing CL practice across the world. These insights can serve as a basis to design strategies at national and international levels.

Spectrum of cancer patients receiving renal biopsy.

BACKGROUND: The frontier of onco-nephrology, particularly renal complications of cancer and treatment, remains unexplored. We revisit the fundamental tool of diagnosing kidney disease, renal biopsy, in cancer patients with renal manifestation. METHODS: Patients who received renal biopsy from July 2015 to July 2019 were analyzed. Primary outcomes included end-stage renal disease (ESRD), mortality, and catastrophic outcome defined as either ESRD or mortality. A Cox proportional hazards model and Kaplan-Meier technique were used to assess the association with outcome measurements and survival analyses. Immunosuppression after renal biopsy and response to the treatment were evaluated. RESULTS: Among the 77 patients, the median age was 66 years (interquartile range [IQR] 59-73 years) and 46 (59.7%) were male. At the time of renal biopsy, 57 patients (74%) had various degrees of renal insufficiency. Tubulointerstitial damage score, quantified by renal pathology, were associated with higher hazards of ESRD (hazard ratio [HR], 1.77; 95% confidence interval [95% CI], 1.20 to 2.61; P = 0.004) and catastrophic outcome (HR, 1.30; 95% CI, 0.99 to 1.70; P = 0.058). The response rate to immunosuppression was lower in those diagnosed with tubulointerstitial nephritis (1 of 4 patients, 25%) than those with glomerulopathy (10 of 20 patients, 50%). CONCLUSION: Renal biopsy may improve diagnostic accuracy and assist in treatment guidance of cancer patients with renal manifestation. Renal biopsy should be encouraged with clinical indication. Collaboration between oncologists and nephrologists is of paramount importance to provide more comprehensive care for caner patients.

[Applying Multiple Strategies to Enhance the Completion Rate of Critical Care in COVID-19 Patients].

BACKGROUND & PROBLEMS: Taiwan entered the community transmission stage of COVID-19 in May 2021, with numbers of locally confirmed cases and critical cases increasing sharply. Medical institutions deployed special units to treat patients. In our hospital, a special COVID-19 intensive care units staffed with nursing personnel across various specialties was established. The rate of COVID-19 critical care completion among nurses in this unit was 79.1%. The reasons for non-completion were found to include limited intensive care standards for COVID-19; inadequate training, teaching aids, and practice manuals; and the overwhelming amount of new COVID-19-related information and updates. PURPOSE: The aim of this project was to increase the team's COVID-19 critical care completion rate from 79.1% to 93.5%. RESOLUTIONS: Multiple strategies were implemented, including: (1) providing online education and training, (2) establishing a platform for sharing COVID-19-related updates, (3) creating a QR-code accessible COVID-19 reference database, (4) creating a COVID-19 practice manual, and (5) providing simulation training sessions on wearing personal protective equipment during critical care. RESULTS: The critical-care completion rate for patients with COVID-19 infection increased significantly in this unit from 79.1% to 98.2%, which exceeded the project goal. CONCLUSIONS: Implementing a multi-strategy intervention that includes both online and simulation training may be effective in improving the critical care completion rate for patients with COVID-19 infection.

Kidney pericyte hypoxia-inducible factor regulates erythropoiesis but not kidney fibrosis.

Prolyl hydroxylase domain enzyme (PHD) inhibitors are effective in the treatment of chronic kidney disease (CKD)-associated anemia by stabilizing hypoxia inducible factor (HIF), thereby increasing erythropoietin and consequently erythropoiesis. However, concern for CKD progression needs to be addressed in clinical trials. Although pre-clinical studies showed an anti-inflammatory effect in kidney disease models, the effect of PHD inhibitors on kidney fibrosis was inconsistent probably because the effects of HIF are cell type and context dependent. The major kidney erythropoietin-producing cells are pericytes that produce erythropoietin through HIF-2α-dependent gene transcription. The concern for the impact of HIF in pericytes on kidney fibrosis arises from the fact that pericytes are the major precursor cells of myofibroblasts in CKD. Since cells expressing Gli1 fulfill the morphologic and anatomic criteria for pericytes, we induced Gli1+ cell-specific HIF stabilization or knockout to study the impact of HIF in pericytes on kidney pathology of mice with or without fibrotic injury induced by unilateral ureteral obstruction. Compared with the littermate controls, mice with pericyte-specific HIF stabilization due to von Hippel-Lindau protein or PHD2 knockout showed increased serum erythropoietin and polycythemia rather than a discernible difference in kidney fibrosis. Compared with Gli1+ pericytes sorted from littermate controls, Gli1+ pericytes sorted from PHD2 knockout mice showed increased erythropoietin gene expression rather than discernible changes in Col1a1 or Acta2 expression. Furthermore, pericyte-specific knockout of HIF-1α or HIF-2α did not affect kidney fibrosis. Thus, our study supports the absence of negative effects of PHD inhibitors on kidney fibrosis of mice despite HIF stabilization in pericytes.

Transforming growth factor-ß1 decreases erythropoietin production through repressing hypoxia-inducible factor 2α in erythropoietin-producing cells.

BACKGROUND: Renal erythropoietin (EPO)-producing (REP) cells produce EPO through hypoxia-inducible factor (HIF) 2α-activated gene transcription. Insufficient EPO production leads to anemia in patients with chronic kidney disease. Although recombinant EPO is effective to improve anemia, no reliable REP cell lines limit further progress of research and development of novel treatment. METHODS: We screened Epo mRNA expression in mouse fibroblast cell lines. Small interfering RNA specific for HIF1α or HIF2α was transfected to study Epo expression in C3H10T1/2 cells. The effect of transforming growth factor-ß1 (TGF-ß1) on HIF-EPO axis was studied in C3H10T1/2 cells and mice. RESULTS: Similar to mouse REP pericytes, C3H10T1/2 cells differentiated to α-smooth muscle actin+ myofibroblasts after exposure to TGF-ß1. Specific HIF knockdown demonstrated the role of HIF2α in hypoxia-induced Epo expression. Sustained TGF-ß1 exposure increased neither DNA methyltransferase nor methylation of Epas1 and Epo genes. However, TGF-ß1 repressed HIF2α-encoding Epas1 promptly through activating activin receptor-like kinase-5 (ALK5), thereby decreasing Epo induction by hypoxia and prolyl hydroxylase domain inhibitor roxadustat. In mice with pro-fibrotic injury induced by ureteral obstruction, upregulation of Tgfb1 was accompanied with downregulation of Epas1 and Epo in injured kidneys and myofibroblasts, which were reversed by ALK5 inhibitor SB431542. CONCLUSION: C3H10T1/2 cells possessed the property of HIF2α-dependent Epo expression in REP pericytes. TGF-ß1 induced not only the transition to myofibroblasts but also a repressive effect on Epas1-Epo axis in C3H10T1/2 cells. The repressive effect of TGF-ß1 on Epas1-Epo axis was confirmed in REP pericytes in vivo. Inhibition of TGF-ß1-ALK5 signaling might provide a novel treatment to rescue EPO expression in REP pericytes of injured kidney.

Angiopoietin-2 is associated with metabolic syndrome in chronic kidney disease.

BACKGROUNDS: Metabolic syndrome is a subclinical status in promoting atherosclerotic cardiovascular disease and type 2 diabetes mellitus. The significance of metabolic syndrome and pathophysiology in chronic kidney disease is not investigated. METHODS: We enrolled adult patients with CKD stages 3 to 5 from December 2006 to December 2007. Metabolic syndrome was defined by the US National Cholesterol Education Programme Adult Treatment Panel III guidelines. Plasma levels of angiogenic growth factors were measured. Univariate and multivariate logistic regression analyses were used. RESULTS: Total 451 patients were analyzed with median estimated glomerular filtration rate of 27.0 ml/min per 1.73m2 (interquartile range 14.3-41.3). Patients with metabolic syndrome were older (P = 0.002), had higher percentage using diuretics (P = 0.002) but lower percentage using pentoxifylline (P = 0.017). Patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein (P < 0.0001), uric acid (P = 0.009) and angiopoietin-2 (P = 0.001). Multivariate logistic regression analyses revealed significant association between plasma levels of angiopoietin-2 and metabolic syndrome (P = 0.042). CONCLUSION: The prevalence of metabolic syndrome in advanced CKD was higher than general population. CKD patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein, uric acid and angiopoietin-2. Plasma levels of angiopoietin-2 were significantly associated with metabolic syndrome in patients with CKD. Metabolic syndrome in CKD may be not only a prognostic factor but also an interventional target, possibly through ameliorating inflammation. Prospective and interventional studies are necessary to establish the pathophysiology.

Long-Term Outcome on the Mal-Seating of Ceramic-on-Ceramic Articulation in Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty with ceramic-on-ceramic articulation aims to decrease wear, osteolysis, and aseptic loosening. A metal-backed ceramic liner was developed to reduce the risk of liner fracture. However, a significant number of cases of mal-seating of the metal-backed ceramic liner were observed in the 2000s, and there were concerns about their outcome. This review aims to investigate the long-term performance of the mal-seated ceramic liner. METHODS: From July 2003 to March 2007, 35 ceramic-on-ceramic total hip arthroplasties were performed with the Trident acetabular system. Clinical assessment, radiological analysis, and outcome assessment were performed. The prevalence of liner mal-seating and its long-term outcomes were investigated. RESULTS: There was liner mal-seating in 8 hips (22.9%). One liner was exchanged in the early postoperative period. No revision surgery was required for the remaining 7 hips at a mean follow-up of 14 years. All patients were free of hip pain with a mean Harris Hip Score of 94.7 at the most recent follow-up. No adverse event was observed. CONCLUSION: The long-term outcomes of the mal-seated liner were favorable. However, surgeons should exercise meticulous surgical technique to achieve a properly aligned liner within the acetabular shell to minimize this potentially correctable error.

Chronotype and depressive symptoms: A moderated mediation model of sleep quality and resilience in the 1st-year college students.

OBJECTIVE: Depression is highly prevalent among 1st-year college students, and evening chronotype is an important risk factor associated with depression. This study investigates the mediating role of sleep quality and the moderating role of resilience between chronotype and depressive symptoms. METHODS: A total of 4531 students were included in this cross-sectional study. Mediation and moderated mediation models were applied. RESULTS: The association between chronotype and depressive symptoms was partially mediated by sleep quality, and the direct and indirect effects were moderated by resilience. The negative correlation between chronotype and depressive symptoms was significant in students with low levels of resilience compared with moderate/high levels. The positive correlation between sleep quality and depressive symptoms was strongest in low-level resilience students. CONCLUSION: This study reveals that greater eveningness is associated with poorer sleep quality among 1st-year college students, which may lead to severer depression, and highlights the importance of resilience training in reducing depressive symptoms.

A time-saving-modified Giemsa stain is a better diagnostic method of Helicobacter pylori infection compared with the rapid urease test.

BACKGROUND: Despite having chronic gastritis, most people infected by Helicobacter pylori (H. pylori) are asymptomatic and have no specific clinical signs and symptoms. H. pylori infection can be diagnosed by several detection methods. Giemsa stain and rapid urease test (CLO test) are the most performed tests of H. pylori infection at first-line clinical examination because of their simplicity and reliability. However, the sensitivity of CLO test is significantly reduced in patients with atrophic gastritis and intestinal metaplasia, and the weaknesses of Giemsa stain are higher cost and time-consuming. METHODS: The Giemsa stain was modified in several staining solutions and procedures based on the simplified Giemsa technique described by Gray, Wyatt, & Rathbone (1986). The modified Giemsa stain is examined its efficacy and compared with the CLO test using 233 H. pylori-infected patients with gastric disease. RESULTS: The modified Giemsa stain is comparable to the traditional one. Statistical analysis indicated that the modified Giemsa stain obtains greater accuracy in H. pylori-infected patients with gastritis and ulcer than the CLO test (48.1% vs. 43.7%). Moreover, considering the prognosis of different symptoms of gastric diseases, the modified Giemsa stain has a more accurate prognosis than combination symptoms (P = 1.8E-05 vs. P = 5.49E-05). The modified Giemsa stain is confirmed to be better than CLO test using 233 H. pylori-infected patients with gastric disease. CONCLUSIONS: The modified Giemsa stain is more simplified and time-saving than traditional Giemsa stain, which is comparable to the traditional one and is confirmed to be better than CLO test using 233 H. pylori-infected patients with gastric disease. In clinical examination, this modified Giemsa stain can be applied to routine examination and provides quick and accurate diagnosis and prognosis to H. pylori-infected patients with gastric diseases.

Using failure mode and effects analysis (FMEA) to generate an initial plan check checklist for improved safety in radiation treatment.

PURPOSE: To apply failure mode and effect analysis (FMEA) to generate an effective and efficient initial physics plan checklist. METHODS: A team of physicists, dosimetrists, and therapists was setup to reconstruct the workflow processes involved in the generation of a treatment plan beginning from simulation. The team then identified possible failure modes in each of the processes. For each failure mode, the severity (S), frequency of occurrence (O), and the probability of detection (D) was assigned a value and the risk priority number (RPN) was calculated. The values assigned were based on TG 100. Prior to assigning a value, the team discussed the values in the scoring system to minimize randomness in scoring. A local database of errors was used to help guide the scoring of frequency. RESULTS: Twenty-seven process steps and 50 possible failure modes were identified starting from simulation to the final approved plan ready for treatment at the machine. Any failure mode that scored an average RPN value of 20 or greater was deemed "eligible" to be placed on the second checklist. In addition, any failure mode with a severity score value of 4 or greater was also considered for inclusion in the checklist. As a by-product of this procedure, safety improvement methods such as automation and standardization of certain processes (e.g., dose constraint checking, check tools), removal of manual transcription of treatment-related information as well as staff education were implemented, although this was not the team's original objective. Prior to the implementation of the new FMEA-based checklist, an in-service for all the second checkers was organized to ensure further standardization of the process. CONCLUSION: The FMEA proved to be a valuable tool for identifying vulnerabilities in our workflow and processes in generating a treatment plan and subsequently a new, more effective initial plan checklist was created.

Changes in albuminuria during the spontaneous breathing trial: A prospective observational study.

BACKGROUND: We hypothesized urine albumin concentration may detect the early increasing cardiac load during the spontaneous breathing trial (SBT). The purpose of our study is to determine whether the changes in urine albumin concentration before and after the SBT correlate with SBT outcome. METHODS: This prospective observational study was conducted from January 2013 to September 2013. Patients receiving endotracheal tube intubation due to acute respiratory failure were included. Urine albumin concentration was measured upon admission to the intensive care unit, before and after the SBT. RESULTS: A total of 211 patients with respiratory failure were screened. Finally, 69 patients were included for analysis. Among the 69 patients received the SBT, 61 patients passed the SBT while 8 patients didn't. Urine albumin concentration upon admission was 251.00 ± 108.21 mg/g in the SBT success group and 260.87 ± 77.95 mg/g in the SBT failure group (p = 0.97). The mean percent change in urine albumin concentration during the SBT was significantly higher in the SBT failure group (+58.44%) than in the SBT success group (+13.11%) (p = 0.02). Univariable and multivariable logistic regression model showed that the difference of urine albumin concentration before and after the SBT correlated significantly with SBT failure (adjusted OR:1.04, p = 0.01). CONCLUSION: This open label pilot study demonstrates the significant association of the changes in urine albumin concentration with SBT outcome. Further study is warranted to investigate the predictive value of urine albumin concentration.

Angiopoietin 1 influences ischemic reperfusion renal injury via modulating endothelium survival and regeneration.

BACKGROUND: Damage to the endothelium due to ischemia reperfusion injury (IRI) leads to a disruption of the microvasculature, which could be influenced by angiopoietin 1 via its effects on endothelium. We investigated the physiological and therapeutic roles of angiopoietin 1 in renal IRI using angiopoietin 1 knockout and over-expression mice. METHODS: Renal IRI was induced by clamping the right renal artery seven days after left uninephrectomy for 25 min followed by reperfusion. A whole body angiopoietin 1 knockout was achieved by induction with tamoxifen. The renal tubule over-expression of angiopoietin 1 was induced by doxycycline. RESULTS: In the normal mice, the renal expression of angiopoietin 1 increased 7 days to 14 days after IRI. The angiopoietin 1 knockout caused a delay in the recovery of renal function, less tubular regeneration and more residual tubular necrosis. The endothelial density was lower and the VE-cadherin protein loss was greater in the knockout mice. The over-expression of angiopoietin 1 attenuated the tubular necrosis and renal function impairment 1 and 3 days after IRI. The loss of the endothelium was ameliorated in the over-expression mice. This protective effect was associated with the up-regulation of the gene expression of epidermal growth factor, hepatocyte growth factor, and insulin like growth factor-1 and less tubular apoptosis. The over-expression of angiopoietin 1 stimulated tumor necrosis factor-α, C-C chemokine receptor type 2 and CX3C chemokine receptor 1 inflammatory gene expression, but did not influence macrophage infiltration. CONCLUSIONS: Altogether, the augmentation and downregulation of angiopoietin 1 attenuated renal damage and impaired renal recovery, respectively, by influencing the survival/regeneration of the endothelium. The manipulation of angiopoietin 1 represents a novel therapeutic approach for the treatment of ischemic kidney injury.