tbuckley/cabot-search huggingface dataset:
Transbronchial Lung Cryobiopsy in Diffuse Interstitial Lung Diseases . . . Bent but Not Broken
Authors: Ritesh Agarwal, Sahajal Dhooria, Inderpaul S. Sehgal, Ravindra Mehta, Vallandaraman Pattabhiraman, Ashutosh N. Aggarwal, Amanjit Bal, Arjun Srinivasan, Karan Madan, Anant Mohan, Prashant Chhajed, Rajiv Goyal, Jayachandra Akkaraju, Dharmesh Patel
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

in TBLC has been reported not only with respect to complications but also with respect to the quality and size of the biopsies.In a previous study, Almeida and colleagues assessed 100 TBLCs performed in patients with suspected diffuse lung disease (2).When they compared the first 50 TBLCs with the next 50 TBLCs, they found that the length and area of the biopsies were smaller and the diagnostic yield was lower in the first group, and all parameters improved when the bronchoscopists gained more experience.In their study, Almeida and colleagues reported a median length of 5.0 mm in the first 50 biopsies and 6.0 mm in the next 50 biopsies.Romagnoli and colleagues reported a level of agreement between external blinded versus local pathology reports as fair to moderate, with k values of 0.22-0.51.The k values for individual pathologists are not presented, and as noted above for bronchoscopy, there may be a learning curve for pathologic evaluations of cryobiopsies.In support of this, previous studies (which included the same external pathologist as in the present study) reported k values between 0.59 and 0.61 (5,6).With regard to the agreement between the pathologic diagnosis based on the two types of specimens and the final diagnosis at the second multidisciplinary assessment or the final treatment (Table 2 andTable E3 in the online supplement of Reference 1), there is no statistically significant difference by conventional standards between the two types of specimens in terms of performance when evaluated by a chi-square test or Fisher's exact test on simple 2 3 2 tables, even though there is trend in favor of SLB.This emphasizes the need for further research into this important subject before any conclusions can be made.The TBLCs were compared with SLBs as the gold standard.However, the accuracy of SLB has never been proven, and previous studies (7) have clearly shown that SLBs can also provide discordant results when performed in different lobes; thus, the perception of SLB as the gold standard requires careful consideration.The study by Romagnoli and colleagues certainly indicates that more research into the accuracy of TBLC is warranted, but their results cannot stand alone and should not discourage the continued use of TBLC in interstitial lung disease.
Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT
Authors: Noga Shem-Tov, Christophe Peczynski, Myriam Labopin, Maija Itälä-Remes, Didier Blaise, Hélène Labussière-Wallet, Gerard Socié, Nicolaus Kröger, Stephan Mielke, Boris Afanasyev, Patrice Chevallier, Johanna Tischer, Grzegorz Helbig, Pavel Jindra, Zinaida Peric, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
Journal: Leukemia (2019)
Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial
Authors: Gholamreza Roshandel, Masoud Khoshnia, Hossein Poustchi, Karla Hemming, Farin Kamangar, Abdolsamad Gharavi, Mohammad Reza Ostovaneh, Alireza Nateghi, Masoud Majed, Behrooz Navabakhsh, Shahin Merat, Akram Pourshams, Mahdi Nalini, Fatemeh Malekzadeh, Masoumeh Sadeghi, Noushin Mohammadifard, Nizal Sarrafzadegan, Mohammad Naemi-Tabiei, Abdolreza Fazel, Paul Brennan, Arash Etemadi, Paolo Boffetta, Neil Thomas, Tom Marshall, Kar Keung Cheng, Reza Malekzadeh
Journal: The Lancet (2019)
Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia
Authors: Sujit K. Mohanty, Inna Lobeck, Bryan Donnelly, Phylicia Dupree, Ashley Walther, Sarah Mowery, Abigail Coots, Alexander Bondoc, Rachel M. Sheridan, Holly M. Poling, Haley Temple, Monica McNeal, Karol Sestak, Ruchi Bansal, Greg Tiao
Journal: Hepatology (2019)

Background and Aims Biliary atresia (BA) is a devastating neonatal cholangiopathy that progresses to fibrosis and end‐stage liver disease by 2 years of age. Portoenterostomy may reestablish biliary drainage, but, despite drainage, virtually all afflicted patients develop fibrosis and progress to end‐stage liver disease requiring liver transplantation for survival. Approach and Results In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling human BA and has been used to study mechanistic aspects of the disease. Unfortunately, nearly all RRV‐infected pups succumb by day of life 14. Thus, in this study we generated an RRV‐TUCH rotavirus reassortant (designated as T R(VP2,VP4) ) that when injected into newborn mice causes an obstructive jaundice phenotype with lower mortality rates. Of the mice that survived, 63% developed Ishak stage 3‐5 fibrosis with histopathological signs of inflammation/fibrosis and bile duct obstruction. Conclusions This model of rotavirus‐induced neonatal fibrosis will provide an opportunity to study disease pathogenesis and has potential to be used in preclinical studies with an objective to identify therapeutic targets that may alter the course of BA.
Surveillance after primary breast cancer treatment: What motivates ASCO experts?
Authors: Harveshp D. Mogal, Emad S. Allam, Julie A. Margenthaler, Ling Chen, Katherine S. Virgo, Frank E. Johnson
Journal: Journal of Clinical Oncology (2012)

e19593 Background: Breast carcinoma is the most common cancer among American women except for skin cancer. Over 200,000 patients are diagnosed with breast cancer annually in the U.S. Most receive curative-intent treatment. About 2.5 million women with a history of breast cancer are now alive and eligible for surveillance. ASCO has published evidence-based guidelines for surveillance after primary breast cancer treatment but dramatic variation in the actual practice patterns of ASCO clinicians has been shown. We sought to evaluate potential factors that motivate expert clinicians as they design their own surveillance strategies. Methods: A custom-designed survey instrument with 11 questions about putative motivating factors was e-mailed to the 3,245 ASCO members who had indicated that breast cancer was a major focus of their clinical practice. Responses were submitted on a 10-level Likert-type scale. The percentage of responses for each point on the scale for each of the potential motivating factors was tabulated. We ranked the factors in accordance with the percentage responses on the scale. Results: 1,013 responses (31%) were submitted; 734 (73%) were evaluable. “Potential detection of a second primary breast cancer” was the strongest motivating factor (53% with a score of "strongly agree"). Conclusions: We believe this is the first empirical evidence about factors that may motivate expert clinicians in selecting surveillance strategies. Understanding these factors may be useful in devising methods to decrease the present variation in these strategies. [Table: see text]
Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases
Authors: Ji Young Chang, Soo Jung Park, Eun Suk Jung, Sung-Ae Jung, Chang Mo Moon, Jaeyoung Chun, Jae Jun Park, Eun Sun Kim, Yehyun Park, Tae-Il Kim, Won Ho Kim, Jae Hee Cheon
Journal: Clinical Gastroenterology and Hepatology (2019)
Use of Prediction Intervals in Network Meta-analysis
Authors: Lifeng Lin
Journal: JAMA Network Open (2019)

Network meta-analysis (NMA) is an increasingly popular tool to synthesize direct and indirect evidence for simultaneously comparing multiple treatments. Although guidelines have been developed to improve NMAs,1 the quality of methodology and reporting of many NMAs is inconsistent with the rapid growth of their publication rates.2 Within the context of conventional pairwise meta-analyses, it has been advocated to routinely report 95% prediction (or predictive) intervals (PIs) alongside 95% CIs.3,4 Prediction intervals give the range within which the results of a future study might lie. They can also be used to effectively appraise heterogeneity and avoid the problems of the popular I2 statistic.5 However, the practice of using PIs is uncommon in NMAs.

As in conventional meta-analyses, heterogeneity frequently exists in NMAs owing to differences in study setting, participants, treatment definitions, and so on. This may affect the validity and interpretation of the NMA. To account for heterogeneity, random-effects models are usually applied, and evidence users often focus on the summarized overall results with 95% CIs.

Confidence intervals and PIs are used for different purposes. Suppose an NMA compares multiple treatments for obesity, with its primary outcome as weight loss. Confidence intervals describe uncertainty in overall weight loss for various treatment comparisons among the populations in the NMA. As such, their widths typically shrink toward 0 as the number of studies increases. In addition to uncertainty in overall results, PIs’ widths incorporate the variation caused by heterogeneity between different studies. When a new patient comes to the clinic, PIs (rather than CIs) should be used to predict the new patient’s weight loss and thus recommend the optimal treatment.
GP who worked shifts for out-of-hours service while on sick leave is struck off
Authors: Clare Dyer
Journal: BMJ (2019)

A salaried GP who worked shifts at an out-of-hours service while claiming sick pay from his practice has been struck off the UK medical register after being found guilty of “serious and persistent dishonesty.”

Isaac Baidoo’s work at Corby Urgent Care Centre came to the notice of the practice partners when the centre sent the surgery a letter about a patient they had in common. The letter revealed that he had worked there on 28 May 2017 despite having submitted a sick note to the general practice covering the last two weeks of May. In fact, Baidoo had worked at …
Antimicrobial use trends, Israel, 2012 to 2017
Authors: Yaakov Dickstein, Elizabeth Temkin, Debby Ben-David, Yehuda Carmeli, Mitchell J Schwaber
Journal: Eurosurveillance (2019)

Background In 2012, Israel’s National Center for Infection Control initiated a national stewardship programme that included mandatory annual reporting of antimicrobial use. Here we present nationwide Israeli data for the period 2012 to 2017. Aim The goal of this study was to detect trends in antimicrobial use in Israel following the introduction of the stewardship programme, as part of an assessment of the programme’s impact. Methods In this retrospective observational study, data were collected from Israel’s health maintenance organisations (HMOs), acute care hospitals and post-acute care hospitals (PACHs). Acute care hospital data were collected for general medical and surgical wards, and medical/surgical intensive care units (ICUs). Data were converted into defined daily doses (DDD), with use rates presented as DDD per 1,000 insured/day in the community and DDD per 100 patient-days in hospitals and PACHs. Trends were analysed using linear regression. Results Antimicrobial use decreased across sectors between 2012 and 2017. In the community, the decrease was modest, from 22.8 to 21.8 DDD per 1,000 insured per day (4.4%, p = 0.004). In acute care hospitals, antibiotic DDDs per 100 patient-days decreased from 100.0 to 84.0 (16.0%, p = 0.002) in medical wards, from 112.8 to 94.2 (16.5%, p = 0.004) in surgical wards and from 154.4 to 137.2 (11.1%, p = 0.04) in ICUs. Antimicrobial use decreased most markedly in PACHs, from 29.1 to 18.1 DDD per 100 patient-days (37.8%, p = 0.005). Conclusion Between 2012 and 2017, antimicrobial use decreased significantly in all types of healthcare institutions in Israel, following the introduction of the nationwide antimicrobial stewardship programme.
Highly effective elimination of low Her2 (1+) expressing tumor cells by trifunctional antibody ertumaxomab
Authors: Michael Jaeger, Peter Ruf, Juergen Hess, Alexandra Schoberth, Horst Lindhofer
Journal: Cancer Research (2008)

2405  Her2 has become an important therapeutic target for antibody-directed treatment of breast cancer with overexpressed Her2 (3+ or 2+/FISH pos.). Currently, no approved antibody-based therapy is available for breast cancer patients with low Her2 expression (1+ or 2+/FISH neg.). Ertumaxomab is a trifunctional bispecific antibody targeting Her2 and CD3 with selective binding to activating Fcγ type I/III-receptors, resulting in the formation of a tri-cell complex between tumor cells, T-cells and accessory cells. Ertumaxomab therapy resulted in radiographically confirmed clinical responses in a phase I trial involving metastasized breast cancer patients with low and high Her2 expressing tumors. Furthermore, in vitro data demonstrated ertumaxomab cytotoxicity at about 100-fold lower concentrations than trastuzumab using the Her2 high expressing cell line SK-BR-3 (Kiewe et al., CCR, 12:3085, 2006).  In this study, we compared the ability to mediate tumor cell killing of ertumaxomabto trastuzumab usinglow Her2 expressing tumor cell lines of different origins. Unstimulated PBMCs of healthy donors and the different cell lines were incubated with the respective antibodies at varying concentrations. After 4 days immune effector cells were removed and dose response was measured by evaluating the tumor cell killing using a cell viability assay (XTT). In addition, cytokine pattern in the supernatants were analyzed.  Under conditions found to be optimal for trastuzumab to kill Her2 overexpressing cells, only ertumaxomab was able to eliminate the tumor cell lines that express Her2 at low level (1+). Cytotoxicity induced by ertumaxomab was observed already at concentrations as low as 1ng/ml and controls demonstrated that tumor cell lysis was dependent on the binding to Her2. In contrast to trastuzumab, ertumaxomab activity was accompanied by a Th1 type cytokine release including IL-2, IL-6, TNF-α and IFN-γ underlining the unique mode of action of trifunctional antibodies. In conclusion, ertumaxomab was able to induce immune effector cell stimulation and cellular cytotoxicity against various tumor cell lines including Her2 low expressing cells. Thus, ertumaxomab may provide a new antibody-based therapeutic option for breast cancer patients with low level expression of the Her2 target antigen who are not eligible for trastuzumab treatment.
Complete remission of patients with heavily pretreated uterine sarcomas by weekly bevacizumab and temozolomide.
Authors: Kazuki Takasaki, Sayaka Ikeda, Hiroko Matsuura, Kazuya Kudoh, Tomoyuki Yoshikawa, Hiroko Kouta, Masashi Takano, Ryoko Kikuchi, Miyuki Horikoshi, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2019)

11051 Background: Uterine sarcomas are associated with poor prognosis snce the complete remission is extreme rare. Therefore, treatment with chemotherapy including eribulin or trabectedin, hormone therapy or molecular-targeted therapy including pazopanib or olaratumab was expectd, but the effect is not satisfactory. Thus, we evaluated the effects of temozoromide (T), derivateives of dacarbazine, and bevacizumab (B) (TB) containing or not cabozantinib (C), a multikinase inhibitor of MET, AXL, RET and VEGFR2 (TBC) in heavily pretreated cases of uterine sarcomas. Methods: From 2009 to 2018, 29 patients (pts) with heavily pretreated uterine sarcomas were enrolled. Fifteen of 29 patients were treated with T (80mg/body/day) and B (2mg/kg; days1, 8 and 15, q 4 weeks) (TB). Since 2013, C (140mg/body/week) was added to TB (TBC, n = 14). Treatment was continued until disease progression and/or unmanageable toxicities. Response was evaluated with the response evaluation criteria in solid tumors (RECIST) v1.1, and adverse events were assessed by common terminology criteria for adverse events (CTCAE) v4.0. Results: Seven pts (24 %) had carcinosarcoma, fifteen (52 %) had leiomyosarcoma, five (17 %) had undifferentiated uterine sarcoma, one (3 %) had adenosarcoma, and one (3 %) had uterine sarcoma-not other specified. Twenty-three of 29 pts were subjected to response evaluation. Five pts (22 %) had complete response (CR), three (13 %) had partial response, six (26 %) had stable disease (SD). The response rate (RR: CR+PR) and disease-control rate (DCR: CR+PR+SD) were 35 % and 70 %, respectively. The median progression-free survival was 6.5 (2-89) months. When adding C to T and B, DCR was improved from 64 % (TB) to 75% (TBC). Median administration of cycles is 7 (TB) and 5 (TBC). There were 2 dead cases from perforation, but toxicity was almost mild and manageable. Conclusions: We have experienced 5 cases of CR by TB or TBC. Moreover, addition of C to T and B resulted in better disease-control rate. Compared to other reported treatment, TB combined with C could be substantially effective in cases with heavily pretreated uterine sarcomas. These results warrant further prospective and randomized studies.
Efficacy of a Clinical Prediction Rule to Identify Febrile Young Infants at Low Risk for Serious Bacterial Infections
Authors: Brett Burstein, Jesse Papenburg
Journal: JAMA Pediatrics (2019)

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Prevalence of Deep Surgical Site Infection After Repair of Periarticular Knee Fractures
Authors: Grayson R. Norris, Jake X. Checketts, Jared T. Scott, Matt Vassar, Brent L. Norris, Peter V. Giannoudis
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Surgical management of periarticular knee fractures can be challenging, and adverse outcomes may be severe. Recent literature indicates that the rate of periarticular knee surgical site infection (SSI) may range from 2% to 88% depending on the fracture site. <h3>Objective</h3> To examine the prevalence of deep SSI and the rate of septic arthritis after surgical repair of fractures around the knee. <h3>Data Sources</h3> The electronic databases MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to July 1, 2018. <h3>Study Selection</h3> Eligible studies had to specifically report deep SSI rates and include fractures in the distal femur, patella, tibial plateau, or proximal tibia. Risk factors that were associated with increased the risk of deep SSI were also examined. <h3>Data Extraction and Synthesis</h3> This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were extracted by multiple investigators. Comprehensive Meta-Analysis software was used for the pooling of data, using either random-effects or fixed-effects models, with respect to the degree of statistical heterogeneity present. Data analyses were conducted in October 2018. <h3>Main Outcomes and Measures</h3> The primary outcome was overall prevalence of deep SSI after periarticular knee fracture repair. The secondary outcomes were the overall prevalence of septic arthritis, risk factors associated with deep SSI, and the most commonly cultured bacteria specimens found periarticular knee infections. <h3>Results</h3> Of 6928 articles screened, 117 articles met inclusion criteria and were included in analysis. Among 11 432 patients included in analysis, 653 patients (5.7%) experienced deep SSIs, most commonly among patients with proximal tibia fractures (56 of 872 patients [6.4%]). Among studies that included information on septic arthritis, 38 of 1567 patients (2.4%) experienced septic arthritis. The 2 most commonly reported bacteria were methicillin-resistant<i>Staphylococcus aureus</i>, found in 67 SSIs, and methicillin-susceptible<i>S aureus</i>, found in 53 SSIs. Sixty-two studies (53.0%) in the sample received a Coleman Methodological Score of poor (&lt;50 points). <h3>Conclusions and Relevance</h3> Deep SSIs occurred in nearly 6% of periarticular knee fracture repairs, and 2.4% of SSIs were associated with septic arthritis. Surgeons managing these injuries should be vigilant when wounds are not pristine. Efforts should be made to elevate the quality of research conducted not only in this subject but also in orthopedic surgery as a whole.