tbuckley/cabot-search huggingface dataset:
GMC starts consultation on SHO training Improvements agreed in GP retainer scheme New moves on mental health BMA council supports Scottish action on PFI hospital BMA council election 1998-2000
Authors: Linda Beecham
Journal: BMJ (1998)

The General Medical Council is to consult widely on recommendations from a working group on senior house officer (SHO) training.

SHOs form the largest group of trainees, but the working group's chairman, Professor Andrew Elkington, told the council last week that a lot still remained to be done about their training. The new booklet, The Early Years , would, he said, complement the booklet for preregistration house officers, The New Doctor .

The draft calls for good education and training that is flexible enough to meet SHOs' personal needs and professional aspirations. They should receive suitable careers advice, and relevant clinical and educational supervision, and appropriate provision should be made for their welfare. The booklet includes sections on the purpose, aims, and content of training. It emphasises the importance of supervision and support. SHOs must always have access to a senior colleague who can advise them in any clinical situation.

NHS trusts should ensure that SHOs have suitable on site living facilities; …
Seizure Recurrence after a First Unprovoked Seizure
Authors: W. Allen Hauser, V. Elving Anderson, Ruth B. Loewenson, Stella M. McRoberts
Journal: New England Journal of Medicine (1982)

We studied 244 patients (of all ages) who presented with a first unprovoked seizure and were followed for a median of 22 months in order to ascertain the risk of subsequent seizures. The cumulative risks of recurrence were 16 per cent at 12 months, 21 per cent at 24 months, and 27 per cent at 36 months after the initial seizure. The risk of recurrence in patients with a history of prior neurologic insult was 34 per cent; all recurrences in this group were observed within the first 20 months. Only 17 per cent of patients without such a history (classified as idiopathic) had a recurrence by 20 months; recurrence in this group was 26 per cent by 36 months. Patients with no recurrence for 36 months did not have a recurrence after that time. Among idiopathic cases the risk of recurrence was increased in patients with generalized spike-wave electroen-cephalograms (50 per cent at 18 months) and in those who had a sibling with seizures (35 per cent at four months). Age at first seizure, sex, seizure type, onset with status epilepticus, or abnormality on neurologic examination did not affect the risk of recurrence. (N Engl J Med. 1982; 307:522–8.)
The Role of Changing Clinical Practices in the Rising Costs of Hospital Care
Authors: Jonathan A. Showstack, Mary Hughes Stone, Steven A. Schroeder
Journal: New England Journal of Medicine (1985)

To assess whether changes in clinical practice have contributed to rising hospital costs, we studied 2011 patients who were hospitalized at the University of California, San Francisco, in 1972, 1977, or 1982. For most of the 10 diagnoses studied, there was little change in total use of services by patients. In-hospital survival did not differ during the decade, and length of stay, numbers of special-care days, and use of laboratory services generally remained the same or declined. Only for patients with acute myocardial infarction did the use of imaging procedures increase substantially (e.g., cardiac catheterization was provided to 2 per cent of patients in 1977 and 40 per cent in 1982). Contrary to conventional wisdom, "little-ticket" procedures, such as laboratory tests, did not contribute to rising costs, and new imaging techniques were commonly substituted for older, more invasive procedures. The primary causes of rising costs were the provision of surgery to patients admitted for acute myocardial infarction, delivery, or respiratory distress syndrome of the newborn and the provision of other intensive treatments for the critically ill. (N Engl J Med 1985; 313:1201–7.)
A novel xenograft model to test the ovarian toxicity of chemotherapy agents in women
Authors: K. H. Oktay, O. Oktem
Journal: Journal of Clinical Oncology (2007)

19504 Background: Many chemotherapeutic agents, especially of alkylating family, alter fertility in premenopausal females (1). While the impact of well-established agents such as cyclophosphamide (Cy) on fertility is well known (2), data are not available for newer agents. Moreover it is not practically possible to determine the individual ovarian-toxicity of each drug and the cellular mechanism of this damage from clinical trials.Thus our specific aim was to develop a xenograft model to characterize the impact of chemotherapy agents on human ovary. Methods: Ovarian pieces of 2x2 mm from 24 wk old abortuses were xenografted subcutaneously to immunodeficient mice (SCID) (n=52). At this gestational age ovarian histology is simiar to young females. Half of the animals received a single dose of 200 mg/kg of Cy intraperitoneally 14 days after the xenografting, while the other half received saline. Grafts were recovered from the control and treated mice 12, 24, 48, and 72h after the Cy injection (n=6–7 per time point), and serially sectioned for primordial follicle counts. Apoptosis was assessed with TUNEL assay. PECAM-1 staining, as well as intra-vital fluorescein conjugated lectin and Evans blue labeling were performed to assess microvasculature by confocal microscopy. All experiments were performed in triplicate. Results: While there was only 12 % loss 12h following the treatment compared to controls (p&gt;0.05), the follicle loss significantly increased at 24h (53%, p&lt;0.01) and peaked at 48h (93 %, p&lt;0.0001), and reduced at 72h (70 %, p&lt;0.001). TUNEL staining peaked at 12h, earlier than the follicle loss; then decreased at 24h and 48h, and faded at 72h. Less than 1% of follicles were TUNEL positive in controls. Xenograft vasculature was similar to non-xenografted tissue indicating that the ex vivo tissue drug delivery was similar to the in vivo delivery. Conclusions: A single injection of a typical dose of Cy can result in the loss of up to 93 % of ovarian reserve in a human ovarian xenograft model, consistent with the data from clinical trials. Fetal ovarian xenografting is a promising model to characterize the gonadotoxic effects of current and emerging cancer drugs without a need for lengthy clinical studies. 1. J Clin Oncol. 2006;24:2917–31 2. Hum Reprod Update. 2004;10:251–66. No significant financial relationships to disclose.
PTH-120 Albi score predicts survival independently of hepatic venous pressure gradient (HVPG) and indocyanine green (ICG) clearance in HCC patients undergoing resection
Authors: S Onali, A Marshall, D Sharma, P O’Donoghue, E Dannhorn, P Johnson, J O’Beirne
Journal: Gut (2015)

<h3>Introduction</h3> A new evidence based model, the Albumin-Bilirubin (ALBI) grade,<sup>1</sup>has been recently proposed for assessing liver function in patients with hepatocellular carcinoma (HCC). We aimed to evaluate the impact of ALBI in predicting decompensation and survival after liver resection (LR) for HCC. <h3>Method</h3> Consecutive patients undergoing resection for HCC between 2011–2014 at the Royal Free Hospital were evaluated. Demographic, clinical data and histopathological features of resected tumour were collected. Patients underwent HVPG and ICG clearance measurement to evaluate potential resectability. ALBI score was calculated pre and post-operatively. Patients were divided into 3 categories (ALBI 1,2,3) according to published ALBI score cut-offs. Cox regression was used to identify predictors of decompensation and survival post LR. <h3>Results</h3> 48 patients were included with a median post LR follow up 17 months (1–54): male 42(87.5%), mean age 63 years (28–83). Median HVPG 6 mmHg (2–15), median ICG PDR 18.2 (6.1–29.4), median ICG R15 6.5 (1.2–19.2). All patients had a Child Pugh score A5. 46 (96%) had a pre-LR ALBI grade 1 and 2 (4%) had an ALBI grade 2. Clinically significant portal hypertension (HVPG ≥10 mmHg) was found in 11 (23%) patients. Eight (19%) patients had an ICG PDR &lt;15, while three (6%) had ICG R15 &gt;15. Thirty (62.5%) patients underwent an anatomical resection, while 18 (37.5%) had a wedge resection. Post-LR decompensation was observed in 5(10%) patients: ascites n = 4, encephalopathy n = 1 at a median of 10 days post-LR. 12(25%) patients had HCC recurrence after a mean time of 11 months (5–28). 7(15%) died after a mean follow up of 15 months (1–40), 3 of them due to tumour recurrence. Patients with 1 HCC &lt;30 mm had 100% survival (mean follow up 20 months, range 9–32). 2 patients with pre-LR ALBI grade 2 died after 7 and 11 months due to HCC recurrence and decompensated cirrhosis, respectively. Cox regression analysis of pre LR variables (HVPG, ICG, CPS, ALBI, HCC size) showed that the only factor associated with survival was pre-LR ALBI score (p = 0.019). <h3>Conclusion</h3> ALBI, an evidence based prognostic score specific to HCC, provides significant information regarding LR outcome in patients with HCC, independently of HVPG, ICG clearance and Child Pugh Score. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Johnson PJ, <i>et al</i>. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. <i>J Clin Oncol</i>. 2015;33(6):550–8
SEMA4A Contributes Eosinopillic Phenotypes in Asthma and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
Authors: Yohei Maeda, Masaki Hayama, Kazuya Takeda, Atsushi Kumanogoh, Hidenori Inohara
Journal: Journal of Allergy and Clinical Immunology (2016)
S43 Mortality following surgical lung biopsy for the diagnosis of interstitial lung disease in the United States: 2000–2011
Authors: JP Hutchinson, TM McKeever, AW Fogarty, RB Hubbard
Journal: Thorax (2015)

<h3>Introduction</h3> Surgical lung biopsy can help to achieve a specific diagnosis in interstitial lung disease, but has associated risks. Most currently available mortality data come from case series. <h3>Objective</h3> We aimed to assess in-hospital mortality following surgical lung biopsy for interstitial lung disease in a national secondary care dataset. <h3>Methods</h3> Data were obtained from the Nationwide Inpatient Sample, an anonymised yearly sample of US community hospitals developed for the Healthcare Cost and Utilisation Project (HCUP). We identified cases from 2000–2011 using International Classification of Diseases (ICD-9-CM) codes for interstitial lung disease, and procedure codes for surgical lung biopsies. Lung resections and cases of lung cancer were excluded. We estimated numbers of biopsies nationwide and in-hospital mortality, and used multivariate logistic regression to assess risk factors for mortality, adjusting for sex, age, geographic region, co-morbidity, type of operation, and provisional diagnosis. <h3>Results</h3> We estimated there to be around 12,000 surgical lung biopsies performed annually for interstitial lung disease in the United States, two-thirds of which were performed electively. In-hospital mortality was 1.7% for elective procedures, but significantly higher for non-elective procedures (16.0%). Male sex, increasing age, increasing co-morbidity, open surgery and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease related interstitial lung disease were risk factors for increased mortality. <h3>Conclusions</h3> In-hospital mortality following elective surgical lung biopsy for interstitial lung disease is just under 2%, but significantly higher for unplanned procedures. The mortality risk and risk factors for death should be taken into account when counselling patients on whether to pursue a histological diagnosis.
Boerhaave's Syndrome
Authors: R Gopalan, C G Cooke
Journal: New England Journal of Medicine (2000)

Figure 1. A 71-year-old man began to have burning substernal pain while he was eating a sandwich. The pain became excruciating, worsened with breathing, and was accompanied by dyspnea. On admission to the hospital, he had hypoxemia, an elevated blood pressure, coarse rales in both lung bases, epigastric and flank tenderness, and diminished bowel sounds. A nasogastric tube was inserted, and a small amount of bloody fluid was removed. Computed tomography of the chest through the superior mediastinum with the use of intravenous and oral contrast medium showed air (A) in the mediastinum adjacent to the esophagus (E) and the . . .
Inability of Antiserum Active in Antibody-Dependent Cellular Cytotoxicity and Arming Tests To Protect Against Simian Virus 40 Tumor Cell Challenge.&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: S O Prather, R W Geller, R N Lausch
Journal: JNCI Journal of the National Cancer Institute (1979)

Previous studies have shown that simian virus 40 (SV40) hamster tumor cells that were pretreated with antiserum from syngeneic hosts sensitized to SV40 were killed following exposure to nonsensitized spleen cells. In this study preincubation of nonadherent spleen or lymph node cells with SV40 antiserum rendered the cells specifically cytotoxic for the SV40-transformed fibroblasts. The capacity of a particular antiserum to “arm” (i.e., to be made specifically cytotoxic) was comparable with Its ability to mediate antibody-dependent cellular cytotoxicity (ADCC). Experiments were performed to determine if the SV40 antiserum had prophylactic activity. Two hours after passive transfer of serum, cytotoxic effector cells could be demonstrated in the blood, spleen, and mesenteric lymph node, and the recipients’ sera were active in ADCC tests. Nevertheless, such hosts were not resistant to challenge with small numbers of SV40 tumor cells that were given intradermally or intracardiacly, nor was tumor growth suppressed by addition of normal lymph node cells to the antiserum-pretreated tumor cell inoculum. Thus SV40 antiserum, active at high titer in ADCC and arming assays, did not prevent or delay growth of SV40 tumor isografts.
MER-101–03, a multicenter, phase II study to compare MER-101 20mg tablets to intravenous zoledronic acid 4mg in prostate cancer patients
Authors: C. McHugh, K. Madigan, A. Walsh, J. Fox, T. W. Leonard, J. B. Quint
Journal: Journal of Clinical Oncology (2009)

5161 Background: The primary objective of this study is to examine the pharmacodynamic effects of two different regimens of zoledronic acid, Orazol 20 mg tablets versus Zometa 4mg IV infusion once-monthly therapy on biomarkers in male bisphosphonate-naïve hormone-refractory prostate cancer patients. Methods: The study is an open-label, multi-center phase II clinical trial to compare oral Orazol 20 mg tablets weekly, to infusions of intravenous Zometa 4mg monthly, in males with hormone-refractory prostate cancer, bone metastases, and no prior bisphosphonate treatment. Patients were assigned into one of three cohorts. The three treatments administered were IV Zometa, 4 mg, 15 minute infusion, Day 0 and Day 28; Orazol po, 20 mg, Days 0, 7, 14, 21, 28, 35, 42, and 49; and Orazol po, 20 mg, Days 0, 1, 2, 3, 28, 35, 42, and 49. The study population consisted of men with hormone refractory prostate cancer as evidenced by history of rising PSA levels (last 2 of 3 PSA levels must be above nadir), who are bisphosphonate-naive, and have radiographically-confirmed bone metastases. Efficacy assessments: The primary endpoints are the assessment of response of four biomarkers, urinary NTX, serum CTX, serum bone specific alkaline phosphatase, and serum calcium on days -7, 0, 7, 14, 21, 28, 35, 42, 49, and 56. Secondary endpoints are assessments of performance and pain scores based on ECOG performance status, BPI, and analgesic use. Safety assessments include physical examinations, vital signs and body weight, hematology panel, urinalysis, and blood chemistry panel. Results: The results demonstrated a rapid decrease for all four biomarkers. This decrease was seen at seven days, and was sustained throughout the study. There were no statistically significant differences between any of the treatments in the primary and secondary endpoints. Conclusions: From the results of MER-101–03, Orazol weekly therapy appears to be as effective as Zometa, based on the biomarkers analyzed. Orazol offers a substantial improvement in therapy over IV infusion for patients, with efficacy that is at least comparable based on the results obtained here. No significant financial relationships to disclose.
Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia
Authors: Yanan Gao, Juan Gao, Minghao Li, Yawei Zheng, Yajie Wang, Hongyan Zhang, Weili Wang, Yajing Chu, Xiaomin Wang, Mingjiang Xu, Tao Cheng, Zhenyu Ju, Weiping Yuan
Journal: Journal of Hematology & Oncology (2016)

The constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link between PI3K/Akt and mTOR kinase, the role of Rheb1 in AML remains unexplored. Our study aims to explore the role of Rheb1 in AML and estimate whether Rheb1 could be a potential target of AML treatment.The expressions of Rheb1 and other indicated genes were analyzed using real-time PCR. AML mouse model was established by retrovirus transduction. Leukemia cell properties and related signaling pathways were dissected by in vitro and in vivo studies. The transcriptional changes were analyzed via gene chip analysis. Molecular reagents including mTOR inhibitor and mTOR activator were used to evaluate the function of related signaling pathway in the mouse model.We observed that Rheb1 is overexpressed in AML patients and the change of Rheb1 level in AML patients is associated with their median survival. Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function. In addition, Rheb1 deletion arrested cell cycle progression and enhanced apoptosis of AML cells. Furthermore, while Rheb1 deletion reduced mTORC1 activity in AML cells, additional rapamycin treatment further decreased mTORC1 activity and increased the apoptosis of Rheb1 (Δ/Δ) AML cells. The mTOR activator 3BDO partially rescued mTORC1 signaling and inhibited apoptosis in Rheb1 (Δ/Δ) AML cells.Our data suggest that Rheb1 promotes AML progression through mTORC1 signaling pathway and combinational drug treatments targeting Rheb1 and mTOR might have a better therapeutic effect on leukemia.
PWE-060 Is a false positive faecal calprotectin as false as you think?
Authors: D Alzoubaidi, L Asser, T Price, K Lithgo, D Housley, MW Johnson
Journal: Gut (2015)

<h3>Introduction</h3> There is a clear need for a simple unambiguous test to differentiate between functional and true organic disease. This would have the effect of reducing the number of unnecessary investigations such as colonoscopies, whist reducing health service costs. Faecal calprotectin is a well validated non-invasive faecal inflammatory marker capable of differentiating functional (e.g. Irritable Bowel Syndrome) from organic (e.g. Inflammatory Bowel Disease). A recent BMJ meta-analysis suggested that it had 93% sensitivity and 96% specificity, with a false positive rate of 9%. The false positives were labelled as patients with a high faecal calprotectin who had subsequently undergone normal gastroscopy and colonoscopy. We decided to investigate this further. <h3>Method</h3> All the patients who had undergone a small bowel capsular endoscopy in our unit from 2011 to 2014 were indentified. Patients with an unexplained positive faecal calprotectin were selected (regardless of their referral indication). A retrospective analysis of the capsule findings was then made in those patients who had undergone normal endoscopic investigation. We excluded those with a positive endoscopy. This left us with 21 patients with a positive faecal calprotectin who had negative endoscopies. <h3>Results</h3> A total of 206 patients underwent capsule endoscopy between 2011 and 2014. Of these 46 had raised faecal calprotectin levels. 160 were excluded because of positive endoscopic findings. This lead to a total of 21 patients with raised faecal calprotectin and normal endoscopic investigations, labelled as false positives. Within this group 71.4% were found to have small bowel pathology including 12 (57.14%) patients with enteropathy, 2 (9.52%) patients had angiodysplasia and 1 (4.76%) with small bowel malignancy. <h3>Conclusion</h3> The documented false positive rate of 9% may not be as accurate as we previously thought. In our unit capsule endoscopy highlighted a pathological explanation in 71.4% and possible small bowel Crohn’s Disease in 57.14% of patients. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;<b>341</b>:c3369
Hospital and Health-Center Facilities in Massachusetts
Authors: Vlado A. Getting, A. Daniel Rubenstein, Claire F. Ryder
Journal: New England Journal of Medicine (1948)

The acute shortage of hospital beds experienced everywhere in the country during the past few years resulted in 1946 in the enactment of Public Law 725 by the Seventy-Ninth Congress. This act, the Hospital Survey and Construction Act, previously known as Senate Bill 191, or the Hill-Burton Bill, was the first and only bill to be endorsed in Congressional hearings by the American Public Health Association, the American Hospital Association and the American Medical Association. The purpose of the Act is to enable communities throughout the nation to construct hospitals and health-center facilities under a federal grants-in-aid program for a . . .
Case 4-2001
Authors: Peter W. Bates, Eugene J. Mark
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 26-year-old man was admitted to the hospital because of pain, erythema, and swelling of the legs.The patient had been well until two weeks earlier, when he had had occasional cramps in his thighs while walking. Four days before admission, his left ankle became swollen and painful, even at rest, and there was limitation of motion. Two days before admission, the pain increased and interfered with his ability to walk, and the ankle appeared red. The administration of cephalexin and indomethacin was ineffective. On the day of admission, the right ankle also became painful, erythematous, and . . .
<i>Mycobacterium chelonae</i>Wound Infections after Plastic Surgery Employing Contaminated Gentian Violet Skin-Marking Solution
Authors: Thomas J. Safranek, William R. Jarvis, Loretta A. Carson, Lucy B. Cusick, Lee A. Bland, Jana M. Swenson, Vella A. Silcox
Journal: New England Journal of Medicine (1987)

From April 1 to October 31, 1985, postoperative surgical-wound infections due to rapidly growing mycobacteria developed in eight patients undergoing cosmetic plastic surgery performed by one surgeon. All infections followed either face-lift or augmentation-mammoplasty procedures performed in the surgeon's office; no infections occurred after surgical procedures performed at the hospital or after other surgical procedures performed at the office. An epidemiologic investigation implicated a gentian violet skin-marking solution as the source of the infections (P less than 0.001). Among patients exposed to the gentian violet, infection was significantly more likely to develop in those undergoing a face lift or augmentation mammoplasty than in those undergoing blepharoplasty (P less than 0.001). Additional risk factors for infection included the postoperative use of antibiotics and glucocorticoids. Mycobacterium chelonae, subspecies abscessus, was isolated from the gentian violet stock used by the surgeon and from five of the eight patients. Additional studies showed that the same organism was present in the gentian violet stock at the pharmacy that supplied the agent to the surgeon. After a sterile skin-marking agent was substituted for the contaminated agent, no further cases occurred.