tbuckley/cabot-search huggingface dataset:
A phase II trial of biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, interferon, and digoxin in melanoma matients
Authors: M. I. Khan, B. Taft, M. A. Rasku, D. Laber, J. Chesney, D. M. Miller
Journal: Journal of Clinical Oncology (2007)

8573 Background: Patients with stage IV metastatic melanoma have limited treatment options. Epidemiological studies have demonstrated that there is a lower death rate from breast cancer in patients who are on digoxin therapy (6%) when compared with patients who are not on digoxin therapy (34%). Recent in vitro studies have shown that digoxin inhibits growth and causes apoptosis in multiple cell lines including breast cancer cells (MCF-7), non-small cell lung cancer cells, HeLa cells, renal adenocarcinoma cells (TK-10), neuroblastoma cells, and prostate cancer cells. In addition digoxin enhances the efficacy of chemotherapy against melanoma cells in vitro. Consequently, the addition of digoxin may augment the cytotoxic effects of bio-chemotherapy against stage IV melanoma. Methods: Twenty-seven patients with stage IV melanoma without CNS metastasis with a median age of 51 years (25–69), were enrolled in this open label phase II clinical trial. ECOG performance status was 0 to 1. Patients had normal cardiac, pulmonary, renal and liver function tests. Patients received digoxin 0.25 mg daily throughout all cycles. Patients were hospitalized in ICU for 5 days to receive the therapy and supportive care. Treatment schedule: dacarbazine, IV, 800 mg/m 2 on day 1; cisplatin, IV, 20 mg/m 2 on days 1–4; vinblastine, IV, 1.2 mg/m 2 on days 1–4; IL-2, IV over 24 hours, 9 M IU/m 2 on days 1–4; interferon, SC, 5 MU/m 2 on days 1–5. After completing 2 cycles (28 days per cycle) patients were evaluated for response by CT and/or FDG-PET imaging studies. Patients who experienced a SD, PR, or CR then completed 2 more cycles of this therapy. There was no treatment related mortality. Results: Seven patients achieved CR (25.9%), five patients had a PR (18.5%), and six patients had a SD (22.2%). The overall clinical benefit was 66.6%. Nine patients (33.3%) experienced progressive disease and were taken off the protocol. Eleven patients (40%) are alive and sixteen patients (60%) have died. Conclusions: Our preliminary data demonstrate that the addition of digoxin to bio-chemotherapy may have a synergistic effect on patients with melanoma. Accrual to this trial is on-going and final overall survival and progression free survival will be evaluated in the future. No significant financial relationships to disclose.
Safety profile, efficacy and patient comfort with propofol sedation in outpatient fibreoptic bronchoscopy
Authors: Puneet Khanna, Vikas Maurya, Vipin Kauts, Rajesh Pande
Journal: European Respiratory Journal (2012)

Introduction:   Procedural sedation is suggested in outpatient bronchoscopy to improve tolerance & patient satisfaction. Propofol, a short acting intravenous hypnotic, offers advantages over benzodiazepines/opiates.    Objectives:   We analyzed the feasibility, efficacy & safety profile of propofol administered by a trained nurse for outpatient bronchoscopy.    Methods:   A total of 276 flexible bronchoscopies performed between 2009 & 2011 using propofol sedation only without premedication were retrospectively reviewed. Patient demographics, indications, type of procedure, procedure time, medication doses, comfort level on 10cm verbal analogue scale (VAS, 0-10, 0=excellent, 10=unbearable) & adverse events were analyzed from procedure records.    Results:   Of the 276, two-thirds (182, 66%) patients were male with an average age of 56 years (range 18−82) & an average weight of 73 kg. Indications included diagnostic BAL (127, 46%), TBLB (68,25%), TBNA (41,15%) & EBB (22,8%). Average procedure time was 36 minutes (range 12−145). Average propofol dose was 1.86 mg.kg -1  (range 0.12−20 mg.kg -1 ). Minor adverse events (21, 7.6%) included hypotension (19, 7%), transient hypoxia (8, 3%) & tachycardia (5, 2%). Major adverse events (death,intubation, ICU stay, or hospitalization) occured in 7 (2.5%), of which 3 (1%) were attributed to sedation, 2 (0.7%) to hemoptysis, & 1 each to hypoxia & bronchospasm. There were no procedure-related deaths. A majority (196, 71%) reported VAS of 4-6 with good amnesia, while 56 (20%) had VAS > 6 & 24 (8.6%) had VAS     Conclusions:   Propofol is an easy to administer, safe, & effective procedural sedative for outpatient bronchoscopies providing acceptable comfort.
Mediation of opioid analgesia by a truncated 6-transmembrane GPCR
Authors: Zhigang Lu, Jin Xu, Grace C. Rossi, Susruta Majumdar, Gavril W. Pasternak, Ying-Xian Pan
Journal: Journal of Clinical Investigation (2015)

The generation of potent opioid analgesics that lack the side effects of traditional opioids may be possible by targeting truncated splice variants of the μ-opioid receptor. μ-Opioids act through GPCRs that are generated from the Oprm1 gene, which undergoes extensive alternative splicing. The most abundant set of Oprm1 variants encode classical full-length 7 transmembrane domain (7TM) μ-opioid receptors that mediate the actions of the traditional μ-opioid drugs morphine and methadone. In contrast, 3-iodobenzoyl-6β-naltrexamide (IBNtxA) is a potent analgesic against thermal, inflammatory, and neuropathic pain that acts independently of 7TM μ-opioid receptors but has no activity in mice lacking a set of 6TM truncated μ-opioid receptor splice variants. Unlike traditional opioids, IBNtxA does not depress respiration or result in physical dependence or reward behavior, suggesting it acts through an alternative μ-opioid receptor target. Here we demonstrated that a truncated 6TM splice variant, mMOR-1G, can rescue IBNtxA analgesia in a μ-opioid receptor-deficient mouse that lacks all Oprm1 splice variants, ablating μ-opioid activity in these animals. Intrathecal administration of lentivirus containing the 6TM variant mMOR-1G restored IBNtxA, but not morphine, analgesia in Oprm1-deficient animals. Together, these results confirm that a truncated 6TM GPCR is both necessary and sufficient for IBNtxA analgesia.
South Korea scrambles to contain MERS virus
Authors: O. Dyer
Journal: BMJ (2015)

South Korea’s president, Park Geun-hye, has called on her government to do everything possible to stop the spread of Middle East respiratory syndrome coronavirus in the country, as schools close and citizens rush to buy face masks and sanitisers. “South Koreans are getting anxious,” said Park at a meeting with health officials to plan a quarantine strategy.

More than 1600 people were quarantined or under observation on Thursday 4 June, and over 1100 schools had closed their doors. The number of verified cases rose overnight by six to 36, making South Korea’s MERS outbreak the biggest to date outside Saudi Arabia, where the virus has killed …
Contralateral breast cancer: clinical characteristics and impact on prognosis.
Authors: E A Healey, E F Cook, E J Orav, S J Schnitt, J L Connolly, J R Harris
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the characteristics of patients with unilateral breast cancer who subsequently develop contralateral breast cancer (CBC), to assess their prognosis relative to patients who do not develop a CBC, and to assess the feasibility of using conservative surgery (CS) and radiotherapy (RT) to treat CBC. MATERIALS AND METHODS Of 1,624 women treated with CS and RT for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, 77 developed an invasive CBC. Sixty-two CBCs were treated with CS and RT. The median follow-up duration was 95 months from the time of initial breast cancer diagnosis, and 63 months from CBC diagnosis. RESULTS The cumulative actuarial rate of CBC was 7.0% at 10 years, and the annual incidence rate for CBC was relatively constant. Young age predicted for CBC. When age was analyzed by decade the relative risk (RR) for older patients compared with younger patients was 0.79 (95% confidence interval [CI], 0.62 to 1.01). The presence of lobular carcinoma in situ (LCIS), higher tumor stage, and lack of adjuvant systemic therapy also predicted for CBC with borderline significance. Multivariate analyses showed that CBC was associated with a statistically significant greater likelihood of local recurrence (LR) or distant recurrence (RR, 1.68; 95% CI, 1.03 to 2.71), and distant-only recurrence (RR, 2.17; 95% CI, 1.28 to 3.69). Among assessable patients treated with bilateral RT, 28 of 31 ipsilateral and 11 of 11 contralateral breasts had an excellent or good overall cosmetic outcome at 5 years, and treatment-related complications were minimal. CONCLUSION We conclude that (1) young age is associated with a greater likelihood of CBC, (2) patients who develop a CBC have a greater subsequent risk of distant relapse as compared with patients without CBC, and (3) it is feasible to deliver sequential nonoverlapping bilateral RT without compromising the cosmetic outcome or increasing complications.
Translation and validation of the King's brief interstitial lung disease (K-BILD) questionnaire in French, Italian and Dutch
Authors: M. Wapenaar, A.S. Patel, S.S. Birring, V. Cottin, C. Vancheri, R.T. Van Domburg, E.W.P. Bakker, M.S. Wijsenbeek
Journal: European Respiratory Journal (2014)

Introduction and Aim 

The K-BILD is a validated questionnaire assessing health status in patients with Interstitial Lung Disease (ILD). The aim of this study was to translate and validate the K-BILD in France, Italy, and the Netherlands.

Methods 

The K-BILD questionnaire was translated following a forward-backward multi-step procedure by translators fluent in both English and the native language. This version was reviewed by ILD physicians. The forward translations were reviewed by the original authors to confirm face validity remained unchanged. Through face-to-face structured interviews the translations were tested for relevance, applicability and comprehensiveness in patients with different stages of severity of ILD.

Results 

Twenty-two patients with ILD were interviewed; 7 females (32%), mean (range) age 66 years (39-86), mean (range) FVC % predicted 73 (39-94), mean (range) TLCOc % predicted 48 (26-98). ILD diagnoses were Idiopathic Pulmonary Fibrosis (n= 17), Non-Specific Interstitial Pneumonia (n= 3), collagen-vascular disease associated ILD (n=1), other (n=1).

The Dutch translation was adapted after 5 patient interviews and review by authors for semantic equivalence. After re-test in 6 patients no further alterations were needed. The French translation needed small adaptations after review by physicians and authors, the Italian translation none.

Conclusion 

The translated K-BILD is a well-received tool that is both a relevant and comprehensive measure of health status for patients with ILD in France, Italy and the Netherlands.

Future research 

Studies examining the concurrent validity, internal consistency, repeatability and responsiveness are ongoing.
Unusual metastases in lung cancer
Authors: Othmen Neffati, Ines Akrout, Hanene Smadhi, Leila ElFekih, Tawaddod Khmis, Dorra Greb, Hela Hassen, Hajer BenAbdelghaffar, Souraya Fenniche, Mohamed Lamine Megdiche
Journal: European Respiratory Journal (2013)

Introduction :   Common sites of lung cancer metastases are liver, bone, brain and adrenal. However, few other locations have been described in the literature such as cutaneous, muscular, renal, pancreatic and cardiac.   Purpose:  Illustrate the unusual locations of lung cancer metastases.   Methods :   A retrospective study conducted during a period of five years including the patients with lung cancer and unusual metastatic sites.   Results:  Eleven patients (9men and 2women) with a mean age of 52 years [32-70]. The mean duration of symptoms was 2.5 months. Histological types were: adenocarcinoma (7 cases), a small cell carcinoma (2 cases), squamous cell carcinoma(1 case) and a large cell cancer(1case). Two patients had more than one metastasis (two different sites). There were cutaneous metastases (4cases), renal (4cases), pancreatic (2cases), ovarian (1case), cardiac (1case) and musclular (1case). Metastasis had revealed lung cancer in one case. The histological diagnosis of lung cancer was confirmed by bronchial biopsy (6cases) percutaneous CT guided biopsy (1case) mediastinoscopy (1case) and the biopsy of ovarian site (1case). Chemotherapy was given in nine cases and palliative treatment in two cases. The evolution was rapidly progressive in all patients. The median survival was 4 months.   Conclusion:  Unusual metastases in lung cancer have a poor prognosis because of a late diagnosis. These are often asymptomatic and discovered in radiology. Therefore, their screening should be systematic.
Fulvestrant in metastatic breast cancer: Safety, efficacy, and role as mainteinance therapy for heavily pretreated patients
Authors: G. Carillio, G. Scandurra, R. Aiello, E. Taibi, A. Mazzola, M. Alì, S. Bagnato, G. Fallica, M. Chiarenza, M. Caruso
Journal: Journal of Clinical Oncology (2008)

1133 Background: Chemotherapy is the most aggressive medical option for metastatic breast cancer patients. However, treatment is frequently associated to severe hematological toxicity that compels a chemotherapy-rest. Hormone-sensitive metastatic breast cancer patients could benefit in these cases from a monthly intramuscular injection of fulvestrant, a pure estrogen receptors antagonist. Methods: Since November 2005 to December 2007 we tested objective responses, clinical benefit, and safety of once-a-month fulvestrant 250 mg as therapy after disease progression or for maintenance of heavily pretreated hormone-sensitive breast cancer patients. Results: Among 121 enrolled patients, 101 of them were evaluable: 98 females and 3 males, ECOG performance status (PS) 0–3, median age 59 years (range 27–87), HER-2/neu overexpression in 16%, bone plus visceral disease in 73% of cases. All the patients were pretreated with at least 2 endocrine therapy lines and a median of 3 chemotherapy regimens (range 1–8). Fulvestrant was administered for a median duration of 6 months (range 3–26). We observed 14 partial responses and 50 disease stabilizations lasting at least 6 months, with a clinical benefit rate of 64%. Despite the disease progression several patients could slowly remove the chemotherapy toxicity, improve their quality of life, and receive further antiblastic drugs. A PS improvement was often observed in elderly patients (more than 70 years), compared with the younger women (less than 50 years), probably due to either major chemotherapy toxicities with following recovery in the elderly or more frequent HER2/neu overexpression with aggressive disease in the younger patients. Tumor markers reduction didn't always correlate with therapy activity, that probably reflects the progressive drug steady state reachable after 3 to 6 months of treatment. Safety of fulvestrant was excellent. We recorded only a systemic intolerance reaction leading to treatment interruption and very unusual symptoms of muscle pain in the injecton site. Conclusions: Fulvestrant is an effective and optimally tolerated therapy for metastatic breast cancer and heavily pretreated patients who need a chemotherapy-rest for toxicity recovery. No significant financial relationships to disclose.
Plant constituents of cotton dust and lung effects after inhalation
Authors: R Rylander
Journal: European Respiratory Journal (1988)

Experiments were performed to assess pulmonary reactions after inhalation of cotton dusts with different levels of tannins, terpenoid aldehydes and bacterial endotoxins. Guinea-pigs were exposed to cotton dust. Free lung cells were obtained by lavage 24 h later. A dose-response relationship was found between the number of neutrophils and the amount of endotoxin in the dust. No influence of terpenoid aldehyde or tannin levels could be detected. Cotton mill workers were exposed to dust from glanded and glandless cottons in an experimental cardroom. The average decreases in forced expiratory volume in one second (FEV1) over the workday after carding the two cottons were the same, although levels of dust, tannin or terpenoid aldehydes were different. The level of airborne endotoxin was, however, equal. The results support observations from other studies on the importance of endotoxin for the development of the acute reactions observed after cotton dust exposure.
Cleaning Hospital Room Surfaces to Prevent Health Care–Associated Infections
Authors: Jennifer H. Han, Nancy Sullivan, Brian F. Leas, David A. Pegues, Janice L. Kaczmarek, Craig A. Umscheid
Journal: Annals of Internal Medicine (2015)

The cleaning of hard surfaces in hospital rooms is critical for reducing health care–associated infections. This review describes the evidence examining current methods of cleaning, disinfecting, and monitoring cleanliness of patient rooms, as well as contextual factors that may affect implementation and effectiveness. Key informants were interviewed, and a systematic search for publications since 1990 was done with the use of several bibliographic and gray literature resources. Studies examining surface contamination, colonization, or infection with Clostridium difficile, methicillin-resistant Staphylococcus aureus, or vancomycin-resistant enterococci were included. Eighty studies were identified—76 primary studies and 4 systematic reviews. Forty-nine studies examined cleaning methods, 14 evaluated monitoring strategies, and 17 addressed challenges or facilitators to implementation. Only 5 studies were randomized, controlled trials, and surface contamination was the most commonly assessed outcome. Comparative effectiveness studies of disinfecting methods and monitoring strategies were uncommon. Future research should evaluate and compare newly emerging strategies, such as self-disinfecting coatings for disinfecting and adenosine triphosphate and ultraviolet/fluorescent surface markers for monitoring. Studies should also assess patient-centered outcomes, such as infection, when possible. Other challenges include identifying high-touch surfaces that confer the greatest risk for pathogen transmission; developing standard thresholds for defining cleanliness; and using methods to adjust for confounders, such as hand hygiene, when examining the effect of disinfecting methods.
The absence of representations causes inconsistencies in visual perception
Authors: Jeroen B. J. Smeets, Eli Brenner
Journal: Behavioral and Brain Sciences (2001)

In their target article, O'Regan &amp; Noë (O&amp;N) give convincing arguments for there being no elaborate internal representation of the outside world. We show two more categories of empirical results that can easily be understood within the view that the world serves as an outside memory that is probed only when specific information is needed.
College sexual assault defense program for women halved rape risk
Authors: M. McCarthy
Journal: BMJ (2015)

A sexual assault training program for women in their first year of college successfully halved their risk of being raped, Canadian researchers have reported in a new study in the New England Journal of Medicine .1 The training, which included instruction in verbal and physical self defense, also reduced the risk of attempted rape, attempted sexual coercion, and non-consensual sexual contact.

In a statement the study’s lead author, Charlene Senn, professor of psychology and women’s studies at the University of Windsor in Windsor, Ontario, said, “What this shows us is that, while we wait for effective programs for men or for cultural shifts in attitudes to happen, there is something practical we can do to give young women the tools they need to better protect themselves from sexual assault.”

It is estimated that as many as 25% of women are sexually …
Monosomal karyotype is an independent predictor of survival in patients with higher‐risk myelodysplastic syndrome
Authors: Ruixian Xing, Chengwen Li, Robert Peter Gale, Yue Zhang, Zefeng Xu, Tiejun Qin, Bing Li, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Shiqiang Qu, Zhijian Xiao
Journal: American Journal of Hematology (2014)

A monosomal karyotype (MK) correlates with poor survival in patients with acute myeloid leukemia, although whether this is also the case in patients with myelodysplastic syndrome (MDS) remains controversial. Some studies report a correlation between a MK and a worse survival, whereas others claim that this correlation arises because of a confounding effect between a MK and a complex karyotype (CK). To address this question, we analyzed the clinical data and karyotypes of 610 adults with MDS. A MK was identified in 60 patients, of whom 55 (92%) also fulfilled the criteria for a CK. Conversely, a CK was found in 85 patients, of whom 55 (65%) also had a MK. To determine the impact of a MK on survival, 464 patients who received nonintensive therapies for MDS were analyzed separately. Patients with a MK demonstrated worse survival than those without a MK in univariate analyses (median, 8 months [95% CI, 3-12 months] versus 83 months [63-103 months]; P < 0.001). This effect was observed predominately in the cohorts of higher-risk patients according to the Revised International Prognostic Scoring System and the World Health Organization Prognostic Scoring System (HR [hazard ratio] 3.94 [1.97-7.89]; P < 0.001 and 4.937 [2.45-9.94]; P < 0.001, respectively) and surpassed the impact of a CK in the final survival models. Our data suggest that the addition of MK as a binary variable could improve the predictive accuracy of current models to estimate the survival of patients with MDS.