tbuckley/cabot-search huggingface dataset:
Epidemiology and outcomes of serious influenza infections in lung cancer patients
Authors: C. D. Cooksley, E. C. Avritscher, B. N. Bekele, J. A. Jones, L. S. Elting
Journal: Journal of Clinical Oncology (2005)

7222 Background: Cancer patients (pts) respond favorably to vaccination but their healthcare may be lacking in routine prevention efforts such as annual influenza vaccinations. This population-based study describes the outcomes of potentially preventable influenza in lung cancer vs. other solid tumor pts. Methods: From the Nationwide Inpatient Sample (NIS), a sub-sample of records from 1998–2001 reporting any ICD9 diagnosis code for non-hematologic malignancy in adults and an ICD9 principal diagnosis code for influenza, bronchopneumonia or pneumonia unknown organism (485–487.x) was selected. From pneumonia cases we estimated seasonal excess influenza cases for each year and stratum by computing differences between Fall/Winter cases and Spring/Summer cases. The estimated annual number of excess influenza cases was then used to randomly extract observations from Fall/Winter discharges. Subset analyses included weighted sample means, frequencies and ANOVA. After adjusting to 2003 dollars, charges were converted to costs using 2003 Medicare cost-to-charge ratios for urban hospitals. Death and hospitalization rates were calculated using 5-year cancer prevalence estimates for the US calculated from SEER incidence and death rates. Results: Nearly one-third of the estimated annual 13,000 hospital discharges for influenza in solid tumor cancer pts occur among pts with lung cancer. Compared to other solid tumors, lung cancer pts had longer length of stay, higher mean costs, and higher inpatient (IP) case-fatality rates than others. Conclusions: Although death from influenza is a relatively rare event, in hospitalized lung cancer pts, 12% died. Diligence in adhering to recommended vaccination schedules of patients and their contacts could reduce hospitalizations and costs, as well as deaths in this high-risk population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration William Randolph Hearst Foundation
Safety and Prophylactic Efficacy Profiles of ACE910, a Humanized Bispecific Antibody Mimicking the FVIII Cofactor Function, in Japanese Hemophilia A Patients Both without and with FVIII Inhibitors: First-in-Patient Phase 1 Study
Authors: Midori Shima, Hideji Hanabusa, Masashi Taki, Tadashi Matsushita, Tetsuji Sato, Katsuyuki Fukutake, Naoki Fukazawa, Shingo Maisawa, Koichiro Yoneyama, Keiji Nogami
Journal: Blood (2014)
Reduced expression of PPAR-alpha in bronchoalveolar lavage CD4+ T cells of sarcoidosis patients
Authors: Muntasir Abo Al Hayja, Anders Eklund, Johan Grunewald, Jan Wahlström
Journal: European Respiratory Journal (2011)

Background: Sarcoidosis is a systemic inflammatory disease characterized by noncaseating granulomas affecting many organs, especially the lungs and intrathoracic lymph nodes. Activated CD4+ T cells with a type 1 cytokine profile are considered to be of central importance for the pathogenesis. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that play important regulatory roles in numerous cellular processes, including inflammation. Three PPARs have been described, namely PPAR-alpha, -beta/delta and –gamma. They are expressed in many cell types, including macrophages and T cells. The purpose of this study was to investigate on the mRNA and protein level the expression of PPARs in lung cells of sarcoidosis patients.

Methods: Seventeen sarcoidosis patients and nine healthy controls underwent bronchoscopy with broncoalveolar lavage (BAL) whereafter CD4+ T cells and alveolar macrophages (AMs) were sorted by flow cytometry and subjected to real-time PCR analysis for mRNA expression of PPARs. Immunofluorescence staining of BAL cytospin slides with anti-PPAR antibodies was also performed.

Results: PPAR-alpha relative gene expression was significantly downregulated in CD4+ T cells of sarcoidosis patients, but no differences were observed with regard to T cell expression of the other PPARs. PPAR expression in AMs did not differ between patients and controls. No differences were observed between patients with or without Lofgren's syndrome.

Conclusion: The observed downregulation of PPAR-alpha in T helper cells may contribute to ongoing inflammation in pulmonary sarcoidosis via failure to repress proinflammatory genes.
Response to: ‘CT assessment for pulmonary hypertension requires systematic assessment of cardiac, vascular and parenchymal signs’ by Marloeset al
Authors: S Rajaram, A J Swift, J M Wild, D G Kiely
Journal: Thorax (2015)

We thank Marloes et al for their comments on our recently published article and their interest in pulmonary artery (PA) size as a potential prognostic marker and also their comments regarding adjusting the measurement for body surface area (BSA).1

First, we do recognise the diagnostic value of PA size and PA to aortic (PA:Ao) ratio in selected subgroups of patients, and we have previously shown that a PA:Ao ratio ≥1 in patients with systemic sclerosis and suspected pulmonary arterial hypertension (PAH) is highly suggestive of …
Influence of body mass indexes on response to treatment in acute asthma
Authors: Ebrahim Razi, Armin Razi, Gholam Abbas Mossavi
Journal: European Respiratory Journal (2012)

Background: Increases in body mass index (BMI) are reported to influence asthma response to treatment. The aim of this study was to investigate the relationship between BMI and response to treatment in a group of patients that were referred for asthma control.

Patients and Methods: Effectiveness measurements in this analysis included percentage of changes in forced volume in 1 second (FEV1), forced volume capacity (FVC), FEV1/FVC, and FEF25-75%. A total of 293 subjects with asthma of both genders and above 18 years of age were divided into the following BMI categories: 107 (36.5%) non-overweight (BMI <25), 186 (63.5%) overweight and obese (BMI ≥25). Percentage of change was defined as change in variable between baseline and end-of-treatment.

Results: Analyses of non-overweight vs. overweight/obese asthmatics demonstrated non-significant differences in baseline FEV1 (1.62±0.56 Lit vs. 1.63±0.56 Lit L, p=0.89); FVC (2.58±0.73 Lit vs. 2.47±0.82 Lit, p=0.25); and FEF25-75% (1.04±0.55 ml/sec vs. 1.05±0.50 ml/sec, p=0.47) respectively.

Compared with non-overweight subjects, obese subjects with asthma were less responded to treatment than non obese asthmatic subjects. Percentage changes of FEV1, FVC, FEF25-75%, and FEV1/FVC in non-obese versus obese patients were: 79.57±55.14 % vs. 62.13±41.72%, p= 0.005; 47.71±33.76% vs. 39.93±28.30%, p= 0.036; 151.98±127.82% vs. 123±91.12%, p= 0.041; 20.54±15.63% vs. 15.63±11.32%, p=0.005; respectively.

Conclusion: Percentage changes of spirometric values to treatment in over weight/obese asthmatic patient were lesser in compared with non-overweight subjects.
Abstract 11456: Pressure-Driven Remodeling in Human Saphenous Veins: Evidences of Mechano-Epigenetic Effects in Intima Hyperplasia Associated to Coronary Artery By-Pass Grafting
Authors: Francesca Prandi, Marco Piola, Monica Soncini, Claudia Colussi, Eleonora Penza, Marco Agrifoglio, Gian Luca Polvani, Carlo Gaetano, Gianfranco B Fiore, Maurizio Pesce
Journal: Circulation (2013)
MRI-Essentials.com An illustrated atlas of orthopedic MRI
Authors: Bruce B Forster
Journal: British Journal of Sports Medicine (2015)

by Fischer, Guermazi, Roemer, Carrino, Crema, Grainger, Kijowski, Steinbach.

This new sports-imaging atlas provides the BJSM community with a wonderful atlas of images (there are 3283 MRI case illustrations) and clinically relevant text. This image-based learning is certainly the trend in radiology, and the authors are to be commended for compiling so many sports medicine images of generally outstanding quality in this volume (figure 1, knee MRI).



Figure 1 
Sagittal proton-density fat-suppressed images of the knee demonstrating a full-thickness ACL tear …
Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization
Authors: Jason H. Stafford, Takahisa Hirai, Lei Deng, Sophia B. Chernikova, Kimiko Urata, Brian L. West, J. Martin Brown
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell–derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy.
A phase II study examining the feasibility of long-term and low-dose oral capecitabine in newly diagnosed head and neck squamous cell carcinoma after surgery, radiation, and/or chemotherapy
Authors: A. Sukari, H. Mulrenan, K. Almhanna, Z. Kafri, H. Kim, J. Ensley, O. Kucuk, G. Yoo
Journal: Journal of Clinical Oncology (2009)

6053 Background: In advanced head and neck squamous cell carcinoma (HNSCC), the five-year survival rate is less than 40%. Although the efficacy and tolerability of continuous IV 5-Fluorouracil (5FU) therapy has been established in HNSCC, the feasibility and tolerability of long-term therapy of oral capecitabine has not been established in HNSCC. Our primary objective is to assess the feasibility of treating patients with squamous cell carcinoma of the head and neck (HNSCC) with adjuvant Capecitabine after undergone definitive treatment. The secondary objectives are to estimate time to recurrence, local-regional control and survival rates along with incidence of second primary tumors. Methods: Eligible patients with newly diagnosed locally advanced HNSCC received capecitabine 1,000 mg orally once daily for one year, after undergone definitive treatment. Patients’ compliance with oral capecitabine as will as the side effects profile was evaluated on monthly basis over the first 12 months. Feasibility, survival, progression and progression free survival were measured over 36 months. Results: Thirty five patients were enrolled in the study. 17 patients had stage IV b, 7 had stage III, and 5 had unknown primary HNSCC. All but one took at least 60% of dispensed tablets. Twenty six patients completed at least 7 months of capecitabine. Sixteen patients completed at least 10 month of capecitabine. Two years overall survival rate was 97%. Three years progression free survival was 86%. Conclusions: Adjuvant capecitabine in locally advanced HNSCC is a feasible approach with minimum side effects. A favorable 3-year progression-free survival was found as compare to historical results. We recommend a randomized phase III trail to examine the effect of one year of adjuvant capecitabine versus placebo in locally advanced HNSCC after definitive treatment. No significant financial relationships to disclose.
Phase II study of cisplatin, etoposide and concurrent radiation therapy with maintenance chemotherapy with cisplatin and gemcitabine for unresectable non-small cell lung cancer
Authors: W. Melzner, T. H. Fink, J. H. Ficker, R. Sauer, V. Strnad
Journal: Journal of Clinical Oncology (2004)

7290 Background:This phase II study has been conducted to determine the feasibility, toxicity, response rate, local control, distant metastases, and survival of concurrent chemotherapy with etoposide and cisplatin (cis) with 3D conformal radiotherapy and maintenance chemotherapy with cisplatin and gemcitabine in unresectable non-small cell lung cancer (NSCLC). Methods:From April 2001 to July 2003, 23 patients with unresectable stage III NSCLC were entered into this trial and 18 (78%) completed the treatment. Radiotherapy was given to a total dose of 66.6 Gy (1.4–1.8 Gy) plus cisplatin (20 mg/m2 d1–5, d29–34) with 2 cycles of cisplatin/etoposide chemotherapy (etoposide 90 mg/m2 d1–3, d29–31). Following concurrent chemoradiation, all patients received gemcitabine 900 mg/m2 d1 and 8 with cisplatin 70 mg/m2 d2 every 21 days for 4 cycles or carboplatin AUC 5 d1. All 23 patients received noncoplanar 3D conformal radiotherapy using 4–6 fields. Two patients (9%) had stage II, nine (39%) had stage IIIa, nine (39%) stage IIIb and three patients (13%) had stage IV disease. Results:Response rate was 64% with 2 CR and 13 PR. At present with a minimum follow up of 12 months, overall survival was 69% at 1 year. Actual local progression free survival and actual distant metastases-free survival was 65% and 74% at 1 year, respectively. Three patients (13%) showed grade 2 radiation pneumonitis and four patients (17%) esophagitis grade 3. The predominant hematologic toxicity was grade 3/4 leukopenia, reported in 55,5% of patients. Grade 3/4 thrombocytopenia occurred in 17% of patients. No patients died of treatment related toxicity. Accrual is ongoing. Conclusions:Concurrent chemotherapy with cisplatin and etoposide with 3D conformal radiotherapy and maintenance chemotherapy with cisplatin and gemcitabine is a well tolerated regimen with very good efficacy. No significant financial relationships to disclose.
TSH Receptor Cleavage Into Subunits and Shedding of the A-Subunit; A Molecular and Clinical Perspective
Authors: Basil Rapoport, Sandra M. McLachlan
Journal: Endocrine Reviews (2016)

The TSH receptor (TSHR) on the surface of thyrocytes is unique among the glycoprotein hormone receptors in comprising two subunits: an extracellular A-subunit, and a largely transmembrane and cytosolic B-subunit. Unlike its ligand TSH, whose subunits are encoded by two genes, the TSHR is expressed as a single polypeptide that subsequently undergoes intramolecular cleavage into disulfide-linked subunits. Cleavage is associated with removal of a C-peptide region, a mechanism similar in some respects to insulin cleavage into disulfide linked A- and B-subunits with loss of a C-peptide region. The potential pathophysiological importance of TSHR cleavage into A- and B-subunits is that some A-subunits are shed from the cell surface. Considerable experimental evidence supports the concept that A-subunit shedding in genetically susceptible individuals is a factor contributing to the induction and/or affinity maturation of pathogenic thyroid-stimulating autoantibodies, the direct cause of Graves' disease. The noncleaving gonadotropin receptors are not associated with autoantibodies that induce a "Graves' disease of the gonads." We also review herein current information on the location of the cleavage sites, the enzyme(s) responsible for cleavage, the mechanism by which A-subunits are shed, and the effects of cleavage on receptor signaling.
The predictive value of serum tumor markers for pathologic findings after chemotherapy for primary mediastinal nonseminomatous germ cell tumors
Authors: L. E. Kruter, K. A. Kesler, M. Yu, Z. T. Hammoud, K. M. Rieger, L. H. Einhorn
Journal: Journal of Clinical Oncology (2008)

5087 Background: While data exists on the predictive value of serum tumor markers (STM) alpha-fetoprotein and human chorionic gonadotropin for postchemotherapy pathology in testicular nonseminomatous germ cell tumors (NSGCT), similar data for primary mediastinal NSGCT (PMNSGCT) have not been reported. We undertook a study of PMNSGCT patients who received cisplatin-based chemotherapy followed by surgery to investigate the relationship between preoperative STM values and surgical pathology. Methods: From 1981–2007, 166 PMNSGCT patients who presented to our institution for surgical therapy following chemotherapy were retrospectively reviewed. Multiple variables were analyzed with respect to preoperative STM levels and the “worst” pathology identified within the residual mass {noncancer (necrosis/teratoma, 59%, n=97), persistent NSGCT with or without malignant transformation of teratoma to nongerm cell cancer (NGCCA) (31%, n=52), or pure NGCCA (10%, n=17). Results: Elevation of either STM was present in 40% (n=66) patients at the time of surgery however only 59% of these patients demonstrated pathologic evidence of malignancy with persistent NGSCT (n=34) or pure NGCCA (n=5). Thirty-seven patients had a documented rise in STM prior to surgery and demonstrated pathologic evidence of malignancy in 25 (67%) cases. All, but only 8, patients with either STM level > 1,000 uniformly demonstrated pathologic evidence of persistent NSGCT. The overall predictive value of either STM elevation for persistent NSGCT was 52% (CI 39–64%). In contrast, 100 patients presented to surgery with normal STMs and 30% (n=30) of these patients demonstrated pathologic evidence of viable malignancy. The predictive value of normal STMs for benign disease was 70% (CI 61–79%). Conclusion: STM levels following chemotherapy for PMNSGCT are imperfect predictors of residual malignant or nonmalignant pathology. These data, along with the poor response of PMNSGCT to “salvage” chemotherapy, further support our past and present policy to surgically remove residual disease after chemotherapy when deemed feasible regardless of STM status. No significant financial relationships to disclose.
Acid production in chronic hemodialysis patients.
Authors: J Uribarri, M Zia, J Mahmood, R A Marcus, M S Oh
Journal: Journal of the American Society of Nephrology (1998)

This study examines endogenous acid production in a group of stable chronic hemodialysis patients with no residual renal function who were admitted to the chronic hemodialysis unit of Mount Sinai Hospital. Net acid production was estimated by the change in body bicarbonate content, which occurs in the interdialytic period. The body bicarbonate content at any time was measured by multiplying the concentration of blood bicarbonate by the apparent bicarbonate space at that time. The apparent bicarbonate space was determined by the change in blood bicarbonate concentration induced by the intravenous administration of a known amount of sodium bicarbonate. Daily sulfuric acid production was also estimated from the reduction in body sulfate content during dialysis. The interdialytic net acid production was measured at approximately 28 mEq/d, a value much lower than that predicted from the protein catabolic rate. This reduced acid production can be explained by reduced sulfuric acid and organic acid production. The mechanism of reduced sulfuric acid production is unknown. Reduced organic acid production is explained partly by the absence of renal excretion of metabolizable organic anions, leaving only the nonmetabolizable fraction as the main source of acid in the interdialytic period.
Tunicate‐Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity
Authors: Ekavianty Prajatelistia, Sung‐Won Ju, Naresh D. Sanandiya, Sang Ho Jun, Jin‐Soo Ahn, Dong Soo Hwang
Journal: Advanced Healthcare Materials (2016)

Dentin hypersensitivity is sharp and unpleasant pains caused by exposed dentinal tubules when enamel outside of the tooth wears away. The occlusion of dentinal tubules via in situ remineralization of hydroxyapatite is the best method to alleviate the symptoms caused by dentin hypersensitivity. Commercially available dental desensitizers are generally effective only on a specific area and are relatively toxic, and their performance usually depends on the skill of the clinician. Here, a facile and efficient dentin hypersensitivity treatment with remarkable aesthetic improvement inspired by the tunicate‐self‐healing process is reported. As pyrogallol groups in tunicate proteins conjugate with metal ions to heal the torn body armor of a tunicate, the ingenious mechanism by introducing gallic acid (GA) as a cheap, abundant, and edible alternative to the pyrogallol groups of the tunicate combined with a varied daily intake of metal ion sources is mimicked. In particular, the GA/Fe 3+ complex exhibits the most promising results, to the instant ≈52% blockage in tubules within 4 min and ≈87% after 7 d of immersion in artificial saliva. Overall, the GA/metal ion complex‐mediated coating is facile, instant, and effective, and is suggested as an aesthetic solution for treating dentin hypersensitivity.
Severity and Frequency of Proximal Tubule Injury Determines Renal Prognosis
Authors: Koji Takaori, Jin Nakamura, Shinya Yamamoto, Hirosuke Nakata, Yuki Sato, Masayuki Takase, Masaaki Nameta, Tadashi Yamamoto, Aris N. Economides, Kenji Kohno, Hironori Haga, Kumar Sharma, Motoko Yanagita
Journal: Journal of the American Society of Nephrology (2015)

AKI increases the risk of developing CKD, but the mechanisms linking AKI to CKD remain unclear. Because proximal tubule injury is the mainstay of AKI, we postulated that proximal tubule injury triggers features of CKD. We generated a novel mouse model to induce proximal tubule–specific adjustable injury by inducing the expression of diphtheria toxin (DT) receptor with variable prevalence in proximal tubules. Administration of high-dose DT in mice expressing the DT receptor consistently caused severe proximal tubule–specific injury associated with interstitial fibrosis and reduction of erythropoietin production. Mild proximal tubule injury from a single injection of low-dose DT triggered reversible fibrosis, whereas repeated mild injuries caused sustained interstitial fibrosis, inflammation, glomerulosclerosis, and atubular glomeruli. DT–induced proximal tubule–specific injury also triggered distal tubule injury. Furthermore, injured tubular cells cocultured with fibroblasts stimulated induction of extracellular matrix and inflammatory genes. These results support the existence of proximal-distal tubule crosstalk and crosstalk between tubular cells and fibroblasts. Overall, our data provide evidence that proximal tubule injury triggers several features of CKD and that the severity and frequency of proximal tubule injury determines the progression to CKD.