tbuckley/cabot-search huggingface dataset:
Resveratrol and simvastatin decrease IgM secretion in Waldenström macroglobulinemia: One-year follow-up.
Authors: F. Iuliano, A. Perricelli, S. Infusino, A. Pomillo, M. Luci, P. Petitto
Journal: Journal of Clinical Oncology (2010)

e18556 Background: Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder characterized by lympho plasmacytic bone marrow infiltration along with an immunoglobulin M (IgM) monoclonal gammopathy.Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. Published data show that resveratrol and simvastatin have significant antitumor activity in WM cells line. Data is still lacking on the use of these two drugs in vivo. Methods: 6 patients (3 males and 3 females), median age 41.5 yr (range, 42–73) and asymptomatic WM (IgM-MGUS or smouldering WM(SWM), were treated with resveratrol 40 mg/die and simvastatin 20 mg/die for at least 180 days. Immunoglobulin(Ig)-M monoclonal gammopathy of undetermined significance (IgM-MGUS) was defined as a serum IgM monoclonal protein < 3 g/dL,bone marrow lymphoplasmacytic infiltration < 10%, and no evidence of constitutional symptoms, anemia, hyperviscosity, lymphadenopathy, or hepatosplenomegaly related to the lymphoplasmacytic process. Smoldering Waldenström macroglobulinemia was defined as serum IgM monoclonal protein level ≥3 g/dL and/or bone marrow lymphoplasmacytic infiltration ≥10% and no evidence of end-organ damages.At enrollment patients characteristic were: Hb level median, 12.3 g/dL, serum beta(2)-microglobulin level median 2.4 mg/L, and IgM peaks median, 2.2 g/dL.5 patients were classified as IgM-MGUS and only one patient as SWM because of bone marrow lymphoplasmacytic infiltration > 10%. All patients took regularly the drugs and there have been no adverse events.CK and LDH serum levels were kept in the normal range. Results: In all IgM-MGUS patients a reduction between 30 and 50% of the IgM peak was observed after 6 months of therapy and is still maintained at 14 months of follow-up.In SWM patient the reduction was about 25% and is maintained over time. Conclusions: Our data demonstrate clearly that the association between resveratrol with simvastatin decreases IgM secretion both in IgM-MGUS and in smouldering patients not having any adverse effects. No significant financial relationships to disclose.
Abstract 13662: Left Atrial Appendage Morphologic Pattern Determined by Computed Tomography is a Useful Predictor of High Risk Patient for Embolism With Both Paroxysmal and Persistent Atrial Fibrillation
Authors: Nobuhiko Makino, Masami Nishino, Akihiro Tanaka, Naoki Mori, Takahiro Yoshimura, Daisuke Nakamura, Masauiki Taniike, Yasuyuki Egami, Ryu Shutta, Jun Tanouchi
Journal: Circulation (2013)

Background: Left atrial appendage (LAA) is the main source of left atrial thrombus that causes systemic embolism in patients with atrial fibrillation (AF). Many reports have revealed that LAA flow velocity (LAAV) evaluated by transesophageal echocardiography (TEE) is a promising predictor for LAA thrombus. We have reported that LAA morphologic pattern determined by cardiac computed tomography (CCT) is a novel predictor for LAAV in patients with AF, but it is unclear whether the LAA morphologic pattern is a useful parameter in both paroxysmal AF (PAF) and persistent AF (PerAF).

Methods: In 124 patients with AF, TEE and CCT were performed within a week. We compared the incidence of male, hypertension, diabetes mellitus and spontaneous echo contrast (SEC) evaluated by TEE and the various CCT parameters including left atrial (LA) volume, LAA volume, number of lobes, area of LAA ostium and LAA morphologic type: chicken wing type (LAA with sharp bend) and non-chicken wing type (LAA without sharp bend) between high (LAAV≧30cm/sec) and low LAAV groups in PAF and in PerAF respectively.

Results: In PAF, less LA volume and chicken wing type were predictors for high LAAV. In PerAF, younger age, less BNP level, spontaneous echo contrast, hypertension and chicken wing type were predictors for high LAAV. Chicken wing type was an only common predictor for high LAAV in both types of AF.

Conclusions: The chicken wing type can become a stable predictor of high risk patients for embolism with both paroxysmal and persistent AF.

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Mucocutaneous Findings and Course in an Adult With Zika Virus Infection
Authors: Sarah M. Derrington, A. Paul Cellura, Laura E. McDermott, Taylor Gubitosi, Anna Marie Sonstegard, Sheng Chen, Amit Garg
Journal: JAMA Dermatology (2016)

The Zika virus epidemic has been declared a public health emergency of international concern by the World Health Organization. We describe the mucocutaneous features and histologic correlation in a patient with the acute Zika virus infection.We observed the presence of a diffuse papular descending eruption, petechiae on the palate, and hyperemic sclerae in a 44-year-old man returning from Puerto Rico with confirmatory testing for the Zika virus.A detailed awareness of mucocutaneous findings associated with Zika virus infection will support its early recognition and will facilitate elimination of Zika infection from consideration for concerned patients who present with other, more common erythematous eruptions.
281P Silibinin inhibits proliferative and invasive properties of human ovarian carcinoma cells OVCAR8 and SKOV3 through suppression of HRG/HER3 pathway
Authors: S. Javadikooshesh, M. Momeny, G. Zarrinrad, H. Yousefi, A. Poursheikhani, P. Sabouri, M. Yaghmaie, K. Alimoghaddam, A. Ghavamzadeh, J. Tavakkolibazzaz, S.H. Ghaffari
Journal: Annals of Oncology (2015)
Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States
Authors: Holly M. Biggs, Casey Barton Behravesh, Kristy K. Bradley, F. Scott Dahlgren, Naomi A. Drexler, J. Stephen Dumler, Scott M. Folk, Cecilia Y. Kato, R. Ryan Lash, Michael L. Levin, Robert F. Massung, Robert B. Nadelman, William L. Nicholson, Christopher D. Paddock, Bobbi S. Pritt, Marc S. Traeger
Journal: MMWR Recommendations and Reports (2016)

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.
Clinical Implications of Intrarenal Hemodynamic Evaluation by Doppler Ultrasonography in Heart Failure
Authors: Noriko Iida, Yoshihiro Seo, Seika Sai, Tomoko Machino-Ohtsuka, Masayoshi Yamamoto, Tomoko Ishizu, Yasushi Kawakami, Kazutaka Aonuma
Journal: JACC Heart Failure (2016)
Allogeneic Marrow Transplantation for Acute Nonlymphoblastic Leukemia&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Fefer
Journal: JNCI Journal of the National Cancer Institute (1986)

Bone marrow transplantation (BMT) from an HLA-matched sibling donor can cure 15% of end-stage patients with refractory acute leukemia. Failures are largely due to acute or chronic graft-versus-host disease, idiopathic or cytomegalovirus-associated interstitial pneumonitis, veno-occlusive disease of the liver, opportunistic infections, and leukemia relapse. The post-BMT leukemia relapse rate has been reduced from 65% to 20-40% by performing BMT in first complete remission (CR). Overall, about 50% of such patients become long-term tumor-free survivors. Younger patients do far better than older ones. A prospective comparative trial for acute nonlymphoblastic leukemia (ANL) in first CR revealed that BMT was more likely than chemotherapy to be fatal within the first 6 months after induction but that the probability of long-term tumor-free survival thereafter was significantly greater after BMT than after chemotherapy. It is recommended that patients less than 30 years old with ANL should undergo BMT while in first CR, whereas those patients over 30 years old should postpone BMT to the earliest sign of relapse.
Case 3-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Michael J. Bresnan, Gregory M. Shoukimas, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 17-year-old girl was admitted to the hospital because of a possible brain-stem lesion.She was in excellent health until one year earlier, when she slipped and fell on the lower portion of her back while performing on uneven parallel bars. On the next day she began to experience persistent numbness of the entire right leg; the leg felt "cold," and she often could not determine whether her shoe was on or off. Cervical manipulations were performed on several occasions by a chiropractor, without improvement. The leg numbness did not appear to be influenced by heat, exercise, . . .
Gastroesophageal reflux disease and Barrett’s esophagus
Authors: O. Anand, S. Wani, P. Sharma
Journal: Endoscopy (2007)

In the past year, several reports of endoscopic developments in the field of gastroesophageal reflux disease (GERD) and Barrett’s esophagus have been published that could impact the management of these diseases. For this review, we have selected five of the most relevant, original research articles published in peer-reviewed journals over the past year (September 2006 - August 2007). These publications, in our opinion, reflect some of the important developments in the diagnostic and therapeutic arena of GERD and Barrett’s esophagus.
Drug companies vow to work more closely with governments to combat antimicrobial resistance
Authors: Deborah Kirkham
Journal: BMJ (2016)

More than 80 international drug companies and key industry associations have issued a joint statement setting out how governments and industry can collaborate to overcome the growing threat of antimicrobial resistance, with a declaration launched at the World Economic Forum in Davos, Switzerland.

In the Declaration on Combating Antimicrobial Resistance commercial drug and diagnostic developers have agreed a common set of principles to support antibiotic conservation and the development of new drugs, diagnostic tests, and vaccines.1

Sally Davies, England’s chief medical officer, said, …
Optimizing Stem Cell Mobilization: Lessons Learned
Authors: Pamela S. Becker
Journal: Journal of the National Comprehensive Cancer Network (2014)

Granulocyte colony-stimulating factor is the pivotal component of mobilization regimens and the growth factor most often used for peripheral blood progenitor cell collections. When used alone or after chemotherapy, products with adequate yields of CD34(+) cells are obtained after leukapheresis, resulting in optimal blood count recovery after transplant. For patients who have had extensive prior treatment with chemotherapy and/or radiation, or treatment with specific agents, the yields may be limited. For these patients, plerixafor in combination with growth factor can be used to augment progenitor cell yield and ensure successful collection of target goals, with preservation of the integrity of the graft. Progenitor cells can similarly be collected by leukapheresis from patients for autologous use and from allogeneic donors, after a period of growth factor administration. Many chemotherapy regimens can be used before growth factor administration that serve a dual role of reducing tumor burden and enhancing the progenitor cell collection. Given modern methods, a high success rate exists for procurement of adequate stem cell products.
Development and Validation of a Clinical Trial Accrual Predictive Regression Model at a Single NCI-Designated Comprehensive Cancer Center
Authors: Wendy R. Tate, Lee D. Cranmer
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: Clinical study sites often do not achieve anticipated accrual to clinical trials, wasting critical patient, material, and human resources. The expensive and extensive process to bring a drug to approval highlights the need to streamline clinical pipeline processes. We sought to create a predictive accrual model to be used when considering clinical trial activation at the level of the individual site. Materials and Methods: This retrospective cohort study used 7 years of registry data from treatment and supportive care interventional studies at a single academic cancer center to build a negative binomial regression model with local and protocol variables known prestudy. Actual, team-predicted, and model-predicted accrual and sensitivity/specificity were calculated. Results: To build the model, 207 trials were used. Investigational drug application, disease team, number of national sites, local Institutional Review Board use, total national accrual time, accrual completed, and national enrollment goal were independently and significantly associated with accrual. Predicted accrual was 94% of actual, maintaining predictive value at multiple cutoff values. Validation included 61 trials. The model correctly predicted whether a study would accrue at least 4 subjects 75% of the time. Correlation at the category level was 44.3%, and model sensitivity and specificity are 70% and 78%, respectively. Conclusions: We identified and validated national and local key factors associated with accrual at our site. This methodology has not been previously validated broadly with the intent of trial feasibility. Model validation shows it to be an accurate and quick metric in anticipating accrual success that can be used for resource allocation.
American Society of Nephrology Renal Research Report
Journal: Journal of the American Society of Nephrology (2005)

In the spring of 2004, the Board of Advisors and the Council of the American Society of Nephrology believed it necessary to conduct a series of research retreats to steer priorities appropriately in an era of limited resources. In this regard, retreats were conducted by five working groups in areas that were identified to require distinct attention: acute renal failure, diabetic nephropathy, hypertension, transplantation, and uremic cardiovascular toxicity. The goal of each retreat was to join experts, both within and outside the renal community, to identify areas of basic science and clinical research that should receive highest priority in the next five years. The five retreat summaries with their individual listings of research priorities allow for the distillation of three overriding recommendations that strongly emanate from them:
The MM-021 Trial Of Lenalidomide Plus Low-Dose Dexamethasone In Chinese Patients With Relapsed and Refractory Multiple Myeloma: Impact Of Prior Therapies On Efficacy and Safety
Authors: Jie Jin, Xin Du, Zhen Cai, Fangping Chen, Dao-bin Zhou, Li Yu, Xiao Li, Depei Wu, Fanyi Meng, Huisheng Ai, Jianmin Wang, Jingshan Zhang, Honeylet Wortman-Vayn, Jay Mei, Jian Hou
Journal: Blood (2013)
Feasibility of combining EGFR- and VEGF(R)-targeted agents in colorectal cancer.
Authors: A. K. Larsen, V. Poindessous, D. Ouaret, K. El Ouadrani, V. F. Megalophonos, A. Batistella, A. Petitprez, A. E. Escargueil, C. Tournigand, A. De Gramont
Journal: Journal of Clinical Oncology (2011)

443 Background: The extensive cross-talk between EGFR and VEGF(R) argues for joint targeting of the two signaling pathways. Unexpectedly, large clinical trials with combinations of EGFR-targeted antibodies and bevacizumab, a VEGF-blocking antibody, showed no added benefit in colorectal cancer (CRC) patients compared to bevacizumab alone. One difference between the antibodies and the small molecule tyrosine kinase inhibitors (TKIs) is the potential of the TKIs to inhibit intracellular signaling pathways. Methods: We here characterize the activity of two TKIs, the irreversible EGFR/HER2 inhibitor BIBW2992 (B2) and the VEGFR/PDGFR/FGFR inhibitor BIBF1120 (B1) toward human CRC models in vitro and in vivo. Results: B1 and B2 together showed strong activity toward HT-29 CRC xenografts, compared to either drug alone, and was associated with increased tumor cell death. In comparison, cetuximab and bevacizumab together were no more active than either drug alone and showed exclusively cytostatic activity. Recent findings provide evidence for intracellular VEGF-signaling in epithelial tumors which synergizes with EGFR for proliferation and survival (Cell 140:268, 2010). In agreement, HT-29 tumors expressed abundant intracellular VEGFR1 as shown by immunohistochemistry. Furthermore, targeted knock-down of VEGFR1 in cellular models was accompanied by increased sensitivity to B1 and B2 combinations thereby confirming the relevance of intracellular VEGFR1 signaling for CRC survival. Conclusions: Combinations of B1 and B2 show synergistic activity in CRC models. These findings favor clinical studies with combinations of the two agents and suggest that rationally selected EGFR- and VEGF-targeted agents can be combined for clinical benefit. [Table: see text]
Correlation of pre-treatment apoptotic marker expression with response to neo-adjuvant chemotherapy in locally advanced breast cancer
Authors: V. Garimella, M. Watson, D. Manton, A. Hubbard, A. Chaturvedi, A. Maraveyas, J. Greenman, P. J. Drew, L. W. Turnbull, M. J. Lind, L. Cawkwell
Journal: Journal of Clinical Oncology (2005)

701 Background: Neoadjuvant chemotherapy is used as standard treatment for locally advanced breast cancer. The anticipated end point of cytotoxic drug therapy is the induction of cell death through apoptosis. Understanding the balance between pro- and anti-apoptotic factors within the cell may be relevant to both the prediction and monitoring of response to chemotherapy. Methods: A prospective study of 36 consecutive patients who presented with locally advanced breast cancer was performed. Serial MR scans of the breast were performed to assess the response to treatment and patients were divided into “responders” or “non-responders” using RECIST criteria. Immunohistochemical staining of formalin-fixed, paraffin-embedded pre-treatment core biopsy specimens was performed using antibodies against Bax, Bad, Bid, Bcl-2, Bcl-XL, and p53 antigens. Results: Using RECIST criteria, the group was divided in to 25 responders and 11 non-responders. The pro-apoptotic proteins Bid, Bax and Bad demonstrated loss of protein expression in 0%, 33% and 47% respectively of tumours. Anti-apoptotic proteins Bcl-XL and Bcl-2 demonstrated over expression in 8% and 83% of tumours respectively. P53 over expression was seen in 44% of tumours. Tumour grade and over-expression of Bcl-XL predicted response to chemotherapy (p=0.017 and 0.023 respectively). Multivariate hierarchical regression analysis (controlled for grade) showed that Bcl-XL and Bad were significant predictors of response to neo-adjuvant chemotherapy Conclusions: Although this is a pilot study involving a small number of patients, apoptotic markers may be useful in predicting response to chemotherapy for breast cancer patients No significant financial relationships to disclose.
Combined exposure to betalactoglobulin-derived tolerogenic peptides and synbiotics alleviates food allergy response in vivo
Authors: A. Kostadinova, B.C. Van Esch, J. Garssen, L.E.M. Willemsen, L.M.J. Knippels
Journal: Allergy (2015)

Background: At-risk infants can be prevented from developing food allergy symptoms by feeding them hypoallergenic formulas containing cow's milk protein hydrolysates. This preventive effect might be a result of oral tolerance induction by immunogenic peptide fractions in the hydrolysates. Early exposure to toleranceinducing peptides could prevent the development of allergic symptoms. It is hypothesised that synbiotics (pre- and probiotics) can further enhance tolerance induction. Method: Three-week-old female C3H/ HeOuJ mice (N = 6-8) were exposed orally to (1) PBS (positive control for allergy), to (2) whey protein (positive control for tolerance induction), or (3) a low dose mixture of beta-lactoglobulin-derived peptides (18 amino acids) with a synbiotics-enriched diet prior to sensitization. Thereafter, the mice were fed a control cow's milk protein-free diet and sensitized to whey protein using cholera toxin as an adjuvant. Mice were intradermally challenged with whey protein, and clinical symptoms, such as acute allergic skin response and anaphylactic shock, were measured. Results: The combination of the peptide intervention with a synbiotics-enriched diet resulted in a significant reduction in the acute allergic skin response compared to the allergic positive control. Furthermore, the combined peptides-synbiotics exposure prevented from developing significantly higher anaphylactic shock symptoms when compared to the sham-sensitized controls. Conclusion: Oral exposure to specific betalactoglobulin- derived peptides with synbiotics leads to protection against acute allergic responses. The beta-lactoglobulinderived peptides were administered at a dosage 100-fold lower than previously described by Meulenbroek et al. [1], therefore a combined approach like this might reduce the peptide dose needed to prevent allergy. Future research is needed for unravelling the underlying mechanisms of the preventive effect of this combined exposure.
Maternal and Neonatal Mortality After Cesarean Delivery—Reply
Authors: George Molina, Thomas G. Weiser, Alex B. Haynes
Journal: JAMA (2016)

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