tbuckley/cabot-search huggingface dataset:
Extramedullary Involvement at Relapse in Acute Promyelocytic Leukemia Patients Treated or Not With All-<i>Trans</i> Retinoic Acid: A Report by the Gruppo Italiano Malattie Ematologiche dell’Adulto
Authors: Giorgina Specchia, Francesco Lo Coco, Marco Vignetti, Giuseppe Avvisati, Paola Fazi, Francesco Albano, Francesco Di Raimondo, Bruno Martino, Felicetto Ferrara, Carmine Selleri, Vincenzo Liso, Franco Mandelli
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Recent reports of extramedullary disease (EMD) at recurrence in acute promyelocytic leukemia (APL) have raised increasing concern about a possible role of retinoic acid (RA) therapy. PATIENTS AND METHODS: We analyzed the risk of developing EMD localization at relapse in APL patients enrolled onto two consecutive studies of the Gruppo Italiano Malattie Ematologiche dell’Adulto. The studies investigated chemotherapy alone (LAP0389) versus RA plus chemotherapy (AIDA). RESULTS: When all relapse types were taken into account, 94 (51%) of 184 patients and 131 (18%) of 740 patients who attained hematologic remission underwent relapse in the LAP0389 and AIDA studies, respectively (P &lt; .0001). EMD localization was documented in five (5%) of 94 and 16 (12%) of 131 patients (P = .08). Hematologic and/or molecular relapse was diagnosed concomitantly in all but two patients with EMD in the AIDA study. For patients in the LAP0389 and AIDA series, the probability of EMD localization of any type at relapse was 3% and 4.5%, respectively (P = .79), while the probability of CNS involvement was 0.6% and 2% (P = .28). No significant differences were found with regard to mean WBC count and promyelocytic leukemia/retinoic acid receptor-alpha junction type in comparisons of patients with EMD and hematologic relapse. CONCLUSION: APL patients receiving all-trans retinoic acid in addition to chemotherapy have no increased risk of developing EMD at relapse as compared with those treated with chemotherapy alone.
Prevention of peristomal skin excoriation
Authors: M. V. Phadke
Journal: Journal of Clinical Oncology (2009)

e20746 Background: Purpose of this paper is to prevent the peristomal skin excoriations. So far there has not been any permanent solution for this complication. Approximately 45% of patients with stoma suffer from this problem and are told to learn to live with it. It is important to understand the pathogenesis of any complication before a solution can be found. The excoriation results from digestion of the epithelium by enzymes in the mucus flowing out of the stoma. The liquid contents of the feces, because of their physical property, run along the mesenteric border of the intestine which is shorter than the anti-mesenteric border. This is complicated by bacterial contamination present in feces. It is essential to have intact mucosa all around the stoma. Skin is less resistant to bacterial invasion when compared with mucosa. When peristalsis starts, it tends to pull the mesenteric corner of the stoma inside the peritoneal cavity. This will continue till the mesenteric corner comes to the skin level. At this point there is no mucosa to protect and the liquid intestinal contents, instead of dropping in the bag leak over the skin and start digesting the epithelium. To change the mechanics of peristalsis, it is necessary to separate the mucosal (inner) tube from the serous (outer) tube. Once this is achieved, the peristalsis affects only the serous tube and has no effect on the mucus tube which forms the lumen of the stoma. This results in a 360 degree mucosal protection of the stoma. Methods: Delayed-Primary Self-Maturation a technique of constructing stoma described by Phadke was utilized in constructing all ileostomies and colostomies. Primary maturation of stoma is avoided. The stoma is left obstructed with staples. It is opened with electro-cautery only after good peristalsis has returned. The opening is at the anti-mesenteric corner. Mucosal cuff protrudes and is pushed by peristalsis. It everts and debrides the eschar of serositis, exposing the granulation tissue. The cuff rolls out and auto-grafts over the granulation tissue. The margins of the cuff come in contact with dermis of the opening in skin and complete the maturation process. Results: 63 Colostomies and 17 Ileostomies were constructed using this technique. All complications were prevented. Conclusions: DPSM technique will prevent peristomal skin excoriations and all other complications. No significant financial relationships to disclose.
Non–Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases
Authors: Hideko Isozaki, Eiki Ichihara, Nagio Takigawa, Kadoaki Ohashi, Nobuaki Ochi, Masayuki Yasugi, Takashi Ninomiya, Hiromichi Yamane, Katsuyuki Hotta, Katsuya Sakai, Kunio Matsumoto, Shinobu Hosokawa, Akihiro Bessho, Toshiaki Sendo, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Cancer Research (2016)

Crizotinib is the standard of care for advanced non-small cell lung cancer (NSCLC) patients harboring the anaplastic lymphoma kinase (ALK) fusion gene, but resistance invariably develops. Unlike crizotinib, alectinib is a selective ALK tyrosine kinase inhibitor (TKI) with more potent antitumor effects and a favorable toxicity profile, even in crizotinib-resistant cases. However, acquired resistance to alectinib, as for other TKIs, remains a limitation of its efficacy. Therefore, we investigated the mechanisms by which human NSCLC cells acquire resistance to alectinib. We established two alectinib-resistant cell lines that did not harbor the secondary ALK mutations frequently occurring in crizotinib-resistant cells. One cell line lost the EML4-ALK fusion gene, but exhibited increased activation of insulin-like growth factor-1 receptor (IGF1R) and human epidermal growth factor receptor 3 (HER3), and overexpressed the HER3 ligand neuregulin 1. Accordingly, pharmacologic inhibition of IGF1R and HER3 signaling overcame resistance to alectinib in this cell line. The second alectinib-resistant cell line displayed stimulated HGF autocrine signaling that promoted MET activation and remained sensitive to crizotinib treatment. Taken together, our findings reveal two novel mechanisms underlying alectinib resistance that are caused by the activation of alternative tyrosine kinase receptors rather than by secondary ALK mutations. These studies may guide the development of comprehensive treatment strategies that take into consideration the various approaches ALK-positive lung tumors use to withstand therapeutic insult.
Synthesis and characterization of a new vertebroplasty cement based on gold-containing PMMA microspheres
Authors: Eva Jacobs, Ketie Saralidze, Alex K. Roth, Joost J.A. de Jong, Joop P.W. van den Bergh, Arno Lataster, Boudewijn T. Brans, Menno L.W. Knetsch, Ivan Djordjevic, Paul C. Willems, Leo H. Koole
Journal: Biomaterials (2015)
A novel mutation in the POLE2 gene causing combined immunodeficiency
Authors: Francesco Frugoni, Kerry Dobbs, Kerstin Felgentreff, Hasan Aldhekri, Bandar K. Al Saud, Rand Arnaout, Afshan Ashraf Ali, Avinash Abhyankar, Fayhan Alroqi, Silvia Giliani, Mayra Martinez Ojeda, Erdyni Tsitsikov, Sung-Yun Pai, Jean Laurent Casanova, Luigi D. Notarangelo, John P. Manis
Journal: Journal of Allergy and Clinical Immunology (2015)
Epidemiological survey of asthma in children aged 1-14 years in the Vinnitsa Region, Ukraine between 2011 and 2012
Authors: Oleksandr Katilov
Journal: European Respiratory Journal (2013)

OBJECTIVE: To investigate the prevalence rate and risk factors for asthma in children from the Vinnitsa Region, who were aged from 1-14 years between 2011 and 2012, and to provide scientific evidence for the prevention and treatment of childhood asthma. A case-control study (1:1) and logistic regression analysis were used to investigate the risk factors for childhood asthma.

RESULTS: Of the 7168 children surveyed, 169 were diagnosed with asthma, with a total prevalence rate of 2.36%. The prevalence rate was higher in males than in females (3.06% vs 1.55%, P<0.01). Of the 169 cases, 115 (68.1%) had their first asthma attack before the age of 3 years, 95 (56.2%) had moderate attacks, 159 (94.1%) had sudden attacks, 86 (50.9%) suffered from asthma during periods of seasonal change, 97 (57.4%) had attacks before going to bed, 157 (92.9%) suffered from asthma caused by respiratory infection, and 159 (94.1%) had sneezing as the sign of oncoming attack. The case-control study (including the 169 asthma cases and 169 healthy children) and logistic regression analysis both showed that the independent risk factors for asthma in children were a personal history of drug allergy (OR=3.431, 95%CI: 1.240-9.496, P=0.018), a history of food allergy (OR=4.043, 95%CI: 1.669-9.795, P= 0.002), allergic rhinitis (OR=9.686, 95%CI: 5.137-18.263, P<0.001), and a family history of allergy (OR=4.059, 95%CI: 2.054-8.018, P<0.001).

CONCLUSIONS: The prevalence rate of asthma was 2.36% in children aged 1-14 years in the Vinnitsa Region, Ukraine between 2011 and 2012. The prevalence rate had not increased when compared with the rate in this region 10 years earlier (2.39%).
Nephrosis in Nigerian Children
Authors: H. M. Gilles, R. G. Hendrickse
Journal: BMJ (1963)

Watson (1905), reviewing the clinical features of Plasmodium malariae infections, remarked on the presence of oedema and albuminuria in several of his patients.In 1912 Clarke wrote: "I believe that the occurrence of oedema in the tropics, of such a nature as to make one think of parenchymatous nephritis, is a reason for making a search for quartan malaria parasites imperative."McFie and Ingram (1917) reported nine cases of the nephrotic syndrome from the Gold Coast; all the patients were under 10 years of age and all had P. malariae in the peripheral blood.Giglioli (1930) made a survey of kidney disease and its relation to malaria in British Guiana during 1923-9, and noted the close relationship between P. malariae and the nephrotic syndrome.Subsequent reports from Sumatra, Kenya, New Guinea, and India all supported Giglioli's hypothesis (Surbek, 1931 ; Lambers, 1932; Maegraith (1948), after critically reviewing the literature, Carrothers, 1934; Indian Medical Gazette, 1942).accepted the association between P. malariae and the nephrotic syndrome.Despite all the above reports, in recent years the whole question seems to have been reopened and a notable tone of incredulity is manifested in some of the modern textbooks dealing with medicine in the tropics.Luder (1958) concluded that the association is still unproved, and Trowell (1960) suggested that the time was ripe for the reassessment of the whole problem.The " nephrotic syndrome " is common in Ibadan, and P. malariae infection is prevalent.We have reinvestigated the epidemiological relationship between these two condi- tions.This paper reports the results of this investigation and includes only such clinical and pathological findings as are necessary to establish the diagnosis of the nephrotic syndrome.We have in addition tried to assess the short- term effect of antimalarial therapy in our patients.For the purpose of this study the criteria for diagnosing the nephrotic syndrome were: oedema, massive albumin- uria, severe hypoproteinaemia, no azotaemia, and normal blood-pressure.We did not demand hypercholesterolaemia as a criterion, although in fact it was present in almost all the patients.
A randomized, double-blind, placebo-controlled, phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC)
Authors: V. A. Miller, A. Das, M. Rossi
Journal: Journal of Clinical Oncology (2009)

LBA8002 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
CD44 expression in oral rinses: a potential early detection strategy for head and neck cancer
Authors: Elizabeth Franzmann, Erika Reategui, Kara Hamilton, Rakesh Singal, W. Jarrard Goodwin
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3506 

Introduction: Currently only 50% of head and neck squamous cell carcinoma patients (HNSCC) are cured. Cure rates could improve if the disease is detected at an earlier stage. In this study we investigate whether the purported HNSCC tumor marker, soluble CD44 (solCD44), reliably distinguishes between HNSCC and benign disease. Since promoter hypermethylation suppresses gene expression, we also examine whether promoter hypermethylation is present in HNSCC patients with false negative solCD44 results.

Methods: We performed the solCD44 ELISA on oral rinses from 102 patients with HNSCC and 69 control patients with benign diseases of the upper aerodigestive tract (UADT) and history of tobacco or alcohol use to determine the sensitivity and specificity of the test for differentiating HNSCC from benign disease. We also performed the test on oral rinses form 6 patients with various grades of UADT squamous cell dysplasia. Furthermore, we evaluated CD44 promoter hypermethylation using methylation specific PCR on oral rinses from 11 HNSCC subjects with low solCD44 levels and 11 control patients matched for risk factor behavior, demographics and solCD44 level.

Results: Mean salivary solCD44 levels were 24.4± 32.0 ng/ml for HNSCC patients (range 0.99-201ng/ml) and 9.9 ±16.1 ng/ml (range 0.73-124 ng/ml) for the patients with benign disease (p<0.0001). After controlling for potential confounders, we found that solCD44 levels were elevated in HNSCC patients regardless of risk behavior or demographic factors. Depending on cut-off point and HNSCC site, sensitivity ranged from 62-70 % and specificity ranged from 75-88%. Fifty percent of patients without invasive disease had elevated solCD44 levels that were either associated with presence of dysplasia or imminent malignant progression. In our pilot study, 9/11 HNSCC patients with low solCD44 levels and 0/11 controls showed CD44 promoter hypermethylation.

Conclusions: The solCD44 test can distinguish cancer from benign disease with sensitivity and specificity comparable to other widely used screening tests such as the PSA test for prostate cancer. Our pilot work suggests that in HNSCC patients, when solCD44 levels are low, CD44 hypermethylation is usually present. Since controls did not show CD44 hypermethylation, this marker in combination with the solCD44 test may significantly increase sensitivity without adversely affecting specificity. Further confirmation of our preliminary results regarding CD44 hypermethylation in HNSCC is ongoing. In conclusion, the solCD44 may be a useful test for early detection of HNSCC when used in combination with CD44 hypermethylation.
Amelioration of junctional epidermolysis bullosa due to exon skipping
Authors: C. Kowalewski, J. Bremer, A. Gostynski, K. Wertheim‐Tysarowska, K. Wozniak, J. Bal, M.F. Jonkman, A.M.G. Pasmooij
Journal: British Journal of Dermatology (2015)

Mutations in the COL17A1 gene lead to the genetic blistering disorder junctional epidermolysis bullosa generalized intermediate type (JEB-gen-intermed). Antisense oligonucleotide-mediated exon skipping is a strategy that aims to skip the mutation-containing exon and thereby produce a smaller but functional protein. COL17A1 is an interesting candidate, as 53 of the 55 exons (96%) can be skipped without disturbing the reading frame. Information on the functionality of the shortened protein product is important in order to obtain support for this therapeutic strategy. Here we report a patient with JEB-gen-intermed with amelioration of the phenotype due to exon 49 skipping by two distinct mechanisms - premature termination codon-induced exon skipping and revertant mosaicism - both of which induced skipping of the same exon. The patient was compound heterozygous for two inherited COL17A1 mutations, a frameshift mutation in exon 18 (c.1490_1491delinsT, p.Ala497Valfs*23) and a nonsense mutation in exon 49 (c.3487G>T, p.Glu1163Ter). Upon clinical examination, skin patches were found that were resistant to blister formation. In these patches, naturally corrected cells were present that harboured an additional splice-site mutation, c.3419-1G>T, resulting in skipping of the mutation-containing exon 49. This natural gene therapy phenomenon shows that type XVII collagen with residues 1140-1169 deleted is largely functional. In addition, in affected skin cells a low level of exon 49 skipping was observed. Our results support the notion that skipping of a mutated in-frame exon in COL17A1 ameliorates the phenotype.
Preoperative chemoradiation (CRT) with concurrent capecitabine (Cap), oxaliplatin (Ox), and bevacizumab (Bev) in patients with locally advanced rectal cancer (RC): Effects on pathological complete response (pCR) and surgical complications.
Authors: T. Hoehler, K. Dellas, D. Riesenbeck, T. Reese, F. Wuerschmidt, C. Roedel, W. Wagner, H. Zuehlke, M. Richter, J. Dunst
Journal: Journal of Clinical Oncology (2011)

3630 Background: Preoperative CRT is the standard of care for patients with locally advanced RC (stage II and III). Pathological complete response (pCR) after CRT predicts a favourable prognosis. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab to capecitabine/oxaliplatin and radiation (CapOx-RT) on pCR rate and surgical complications. Methods: 70 patients with rectal cancer (uT3-4; N0/1, M0), ECOG <2, were enrolled in 6 centers. The patients received RT (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with Bev 5 mg/kg (d1, d15, d29), Cap 825 mg/m2 bid (d1-14, d22-35) and Ox 50 mg/ m2 (d1, d8, d22, d29). Primary study objective was the pCR rate. Results: 69 patients received the complete CRT treatment. CRT was well tolerated. One GI perforation and 2 thromboses were reported. pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT<cT and ypN<cN) was achieved in 32 (46.4%) and 34 (49.3%) patients, respectively. 69 patients had surgery, 66 (96%) patients had a R0 resection. The average duration of the surgical procedure was 239 min (+10). Frequency of multivisceral resections (14%), intraoperative (8%) and postoperative complications (43%), re-laparotomies (8%), rebleeding (3%) and anastomotic leakages (5/40 anastomoses) requiring surgical interventions were in the expected range. There was no surgical mortality (0%). Conclusions: The addition of Bev to CapOx-RT was well tolerated and did not lead to increased perioperative morbidity or mortality. However, pCR rate was not improved in comparison to other trials that used Cap or Cap/Ox in preoperative CRT.
Review: Corticosteroids reduce mechanical ventilation and ARDS in inpatients with community-acquired pneumonia
Authors: Arjun B. Chatterjee
Journal: Annals of Internal Medicine (2015)

Source Citation Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163:519-28. 26258555
Siddharta Mukherjee’s three laws of medicine
Authors: Richard Lehman
Journal: BMJ (2015)

How medicine always defies lawgivers

The Laws of Medicine is an arresting title for a very small book.1 It follows the author Siddharta Mukherjee’s The Emperor of All Maladies, 2 an equally arresting title for a very large book. Both are a delight to read and adopt a similar style. Real clinical stories are turned into parables and aphorisms that illustrate various aspects of real clinical medicine. In that way they not only resonate with clinicians but, more importantly, offer a wide readership the opportunity to understand and share in the deep issues of how medicine advances and how medical decisions are made.

Anyone who tries to lay down laws for medicine is bound to be accused of hubris. But there is a gentle irony in Mukherjee’s title, which he immediately subverts with the subtitle “Field Notes from an Uncertain Science.” At the end of the book he explicitly throws off the cloak of the lawgiver to reveal the real oncology teacher offering three challenging assertions for his new residents to chew over. He happily concedes that lots of similar “laws” could be devised. The essays on the three laws included in the book follow the great tradition begun by Montaigne and Bacon and exemplified in post-war British medicine by Richard Asher3 and Peter Medawar.4 The laws all address the central paradox that “medicine asks you to make perfect …
hKChIP2 is a functional modifier of hKv4.3 potassium channels Cloning and expression of a short hKChIP2 splice variant
Authors: N Decher
Journal: Cardiovascular Research (2001)

Objective: The Ca2+ independent transient outward K+ current (Ito1) in the heart is responsible for the initial phase of repolarization. The hKv4.3 K+ channel α-subunit contributes to the Ito1 current in many regions of the human heart. Consistently, downregulation of hKv4.3 transcripts in heart failure and atrial fibrillation is linked to reduction in Ito1 conductance. The recently cloned KChIP family of calcium sensors has been shown to modulate A-type potassium channels of the Kv4 K+ channel subfamily. Methods and results: We describe the cloning and tissue distribution of hKChIP2, as well as its functional interaction with hKv4.3 after expression in Xenopus oocytes. Furthermore, we isolated a short splice variant of the hKChIP2 gene (hKCNIP2), which represents the major hKChIP2 transcript. Northern blot analyses revealed that hKChIP2 is expressed in the human heart and occurs in the adult atria and ventricles but not in the fetal heart. Upon coexpression with hKv4.3 both hKChIP2 isoforms increased the current amplitude, slowed the inactivation and increased the recovery from inactivation of hKv4.3 currents. For the first time we analyzed the influence of a KChIP protein on the voltage of half-maximal inactivation of Kv4 channels. We demonstrate that the hKChIP2 isoforms shifted the half-maximal inactivation to more positive potentials, but to a different extent. By elucidating the genomic structure, we provide important information for future analysis of the hKCNIP2 gene in candidate disorders. In the course of this work we mapped the hKCNIP2 gene to chromosome 10q24. Conclusions: Heteromeric hKv4.3/hKChIP2 currents more closely resemble native epicardial Ito1, suggesting that hKChIP2 is a true β-subunit of human cardiac Ito1. As a result hKChIP2 might play a role in cardiac diseases, where a contribution of Ito1 has been shown.
P-221 Acquired 5-FU resistance in CRC models is accompanied by upregulation of VEGF-VEGFR1 signaling, increased migration and invasion that can be attenuated by aflibercept
Authors: A. Bouygues, P. Mesange, M. Ayadi, M. Chiron, E. Dochy, T. Andre, A. de Gramont, A. Larsen
Journal: Annals of Oncology (2015)
Bortezomib sensitizes human glioblastoma stem cells to adoptive natural killer cell cytotoxicity
Authors: Steven Grossenbacher, Erik Ames, Stephanie Mac, Yuyou Duan, Syed Azeem, Robert Canter, William Murphy
Journal: Journal for ImmunoTherapy of Cancer (2015)

Few criteria exist for identifying which babies merit special nursing care, and many asymptomatic babies are offered such care unnecessarily. Birth weight is usually used to identify babies in need of special care at birth, but gestational age is a better discriminator. Babies of more than 35 weeks9 gestation do not normally require admission to a special care nursery. Those preterm babies who are admitted can usually be discharged at 37 weeks9 gestation even if they still weigh less than 2000 g.