Κυριακή 19 Νοεμβρίου 2017

Course and predictors of post-traumatic stress disorder in a cohort of psychologically distressed patients with cancer: A 4-year follow-up study

BACKGROUND

Scant evidence exists on the long-term course of cancer-related post-traumatic stress disorder (PTSD). This is among the few studies worldwide, and the first in the South-East Asian region, to prospectively evaluate PTSD in patients with cancer using gold-standard clinical interviews. The objective of the study was to assess the course and predictors of PTSD in adult patients with cancer in a South-East Asian population.

METHODS

A prospective, longitudinal study was conducted in a cohort of 469 consecutively recruited patients (aged ≥18 years) with various cancer types within 1 month of diagnosis at a single oncology referral center. Only patients who had significant psychological distress (Hospital Anxiety and Depression Scale total cutoff score ≥16) underwent the PTSD module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID) at at 6-months follow-up. All patients completed the SCID at the 4-year follow-up assessment regardless of their initial Hospital Anxiety and Depression Scale score.

RESULTS

In an analysis combining patients who had both full and subsyndromal PTSD, there was a 21.7% incidence of PTSD at the 6-month follow-up assessment (n = 44 of 203 SCID-interviewed patients), with rates dropping to 6.1% at the 4-year follow-up assessment (n = 15 of 245 SCID-interviewed patients). Patients with breast cancer (compared with those who had other types of cancer) were 3.68 times less likely to develop PTSD at 6-months, but not at 4-years follow-up.

CONCLUSIONS

The overall rates of PTSD decreased with time, but one-third of patients (34.1%) who were initially diagnosed had persistent or worsening PTSD 4 years later. There is a need for early identification of this subset of patients who have cancer with PTSD to design risk-targeted interventions. Cancer 2017. © 2017 American Cancer Society.



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Course and predictors of post-traumatic stress disorder in a cohort of psychologically distressed patients with cancer: A 4-year follow-up study

BACKGROUND

Scant evidence exists on the long-term course of cancer-related post-traumatic stress disorder (PTSD). This is among the few studies worldwide, and the first in the South-East Asian region, to prospectively evaluate PTSD in patients with cancer using gold-standard clinical interviews. The objective of the study was to assess the course and predictors of PTSD in adult patients with cancer in a South-East Asian population.

METHODS

A prospective, longitudinal study was conducted in a cohort of 469 consecutively recruited patients (aged ≥18 years) with various cancer types within 1 month of diagnosis at a single oncology referral center. Only patients who had significant psychological distress (Hospital Anxiety and Depression Scale total cutoff score ≥16) underwent the PTSD module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID) at at 6-months follow-up. All patients completed the SCID at the 4-year follow-up assessment regardless of their initial Hospital Anxiety and Depression Scale score.

RESULTS

In an analysis combining patients who had both full and subsyndromal PTSD, there was a 21.7% incidence of PTSD at the 6-month follow-up assessment (n = 44 of 203 SCID-interviewed patients), with rates dropping to 6.1% at the 4-year follow-up assessment (n = 15 of 245 SCID-interviewed patients). Patients with breast cancer (compared with those who had other types of cancer) were 3.68 times less likely to develop PTSD at 6-months, but not at 4-years follow-up.

CONCLUSIONS

The overall rates of PTSD decreased with time, but one-third of patients (34.1%) who were initially diagnosed had persistent or worsening PTSD 4 years later. There is a need for early identification of this subset of patients who have cancer with PTSD to design risk-targeted interventions. Cancer 2017. © 2017 American Cancer Society.



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Magnesium sulfate and ophthalmic artery Doppler velocimetry in patients with severe preeclampsia: a case series

In the present study, we used Doppler velocimetry in the ophthalmic artery to evaluate the hemodynamic status of the intracranial vasculature. This is the first time in the literature that indices of ophthalmi...

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Standardised noxious stimulation-guided individual adjustment of remifentanil target-controlled infusion to prevent haemodynamic responses to laryngoscopy and surgical incision: A randomised controlled trial

BACKGROUND The surgical plethysmographic index (SPI) is one of the available indexes of the nociception–antinociception (NAN) balance. Individually adjusting the NAN balance to prevent somatic responses to noxious stimulation remains a challenge. OBJECTIVES To assess whether guiding remifentanil administration according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt the haemodynamic response to tracheal intubation and surgical incision. DESIGN Prospective randomised multicentre controlled study. SETTING Two Belgian university hospitals from January 2014 to April 2015. PATIENTS After ethic review board approval and informed consent, 48 American Society of Anesthesiologists I or II adult patients scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS Patients were randomly assigned to a SPI group, where remifentanil effect-site concentration was adjusted according to NANCAL, or a control group, where it was fixed at 4 ng ml−1. Propofol concentration was always adjusted to maintain the bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical tetanic stimulation during 30 s at the wrist before tracheal intubation and before surgical incision. MAIN OUTCOME MEASURES The primary endpoint was the efficacy of the NANCAL-guided remifentanil administration to prevent the haemodynamic response to tracheal intubation and surgical incision. The secondary aim was to compare the ability of SPI, analgesia nociception index, pupil diameter and mean arterial pressure response to NANCAL to predict the haemodynamic response to tracheal intubation and surgical incision. RESULTS Our SPI response to NANCAL-based correcting scheme for remifentanil administration was not superior to a fixed remifentanil concentration at blunting the haemodynamic response to tracheal intubation or surgical incision. Among all tested NAN balance indices, only mean arterial pressure had significant predictive ability with regard to the haemodynamic response to surgical incision. CONCLUSION Further research is needed to define the best NANCAL stimulus and the best remifentanil correcting scheme to help individualised tailoring of antinociception for each specific subpopulation of surgical patients. TRIAL REGISTRATION Clinicaltrials.gov NCT: 02884310; http://ift.tt/2B2PCiQ. Correspondence to Aline Defresne, MD, Department of Anaesthesia and Intensive Care Medicine, CHR Citadelle, Bd du 12eme de Ligne, 1, 4000 Liege, Belgium E-mail: adefresne@chu.ulg.ac.be © 2017 European Society of Anaesthesiology

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Lung Isolation in the Patient With a Difficult Airway

One-lung ventilation is routinely used to facilitate exposure for thoracic surgical procedures and can be achieved via several lung isolation techniques. The optimal method for lung isolation depends on a number of factors that include (1) the indication for lung isolation, (2) anatomic features of the upper and lower airway, (3) availability of equipment and devices, and (4) the anesthesiologist's proficiency and preferences. Though double-lumen endobronchial tubes (DLTs) are most commonly utilized to achieve lung isolation, the use of endobronchial blockers offer advantages in patients with challenging airway anatomy. Anesthesiologists should be familiar with existing alternatives to the DLT for lung isolation and alternative techniques for DLT placement in the patient with a difficult airway. Newer technologies such as videolaryngoscopy with or without adjunctive fiberoptic bronchoscopy may facilitate intubation and lung isolation in difficult airway management. Accepted for publication October 3, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Randal S. Blank, MD, PhD, Department of Anesthesiology, Thoracic Anesthesia, University of Virginia Health System, PO Box 800710-0710, Charlottesville, VA 22908. Address e-mail to rsb8p@virginia.edu. © 2017 International Anesthesia Research Society

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Ultrasound-Assisted Versus Fluoroscopic-Guided Lumbar Sympathetic Ganglion Block: A Prospective and Randomized Study

BACKGROUND: Fluoroscopy (FL)-guided lumbar sympathetic ganglion block (LSGB) is widely performed to diagnose and manage various diseases associated with sympathetically maintained pain. Recently, numerous ultrasound (US)-assisted procedures in pain medicine have been attempted, showing an advantage of low radiation exposure. This randomized, prospective trial compared the procedural outcomes and complications between FL-guided and US-assisted LSGBs. METHODS: Fifty LSGBs were randomly divided into 2 groups: FL-guided (FL group) or US-assisted (US group) LSGB group. Both groups received FL-guided or US-assisted LSGB with 10 mL of 0.25% levobupivacaine. The primary end point was the total procedure time. Secondary outcomes were success rate, imaging time, onset time (based on temperature rise), dosage of radiation exposure, other procedure-related outcomes, and complications. RESULTS: Total procedure time and success rate were not statistically different between the 2 groups, whereas imaging time of the US group was longer than that of the FL group (P = .012). The onset time was faster in the US group (P = .019), and bone touching during the procedure was less frequent in the US group (P = .001). Moreover, radiation exposure was significantly lower in the US group than in the FL group (P

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Perioperative Noninvasive Blood Pressure Monitoring

The most commonly monitored variable for perioperative hemodynamic management is blood pressure. Several indirect noninvasive blood pressure monitoring techniques have been developed over the last century, including intermittent techniques such as auscultation (Riva-Rocci and Korotkoff) and oscillometry (Marey) and continuous techniques. With the introduction of automated noninvasive blood pressure devices in the 1970s, the oscillometric technique quickly became and remains the standard for automated, intermittent blood pressure measurement. It tends to estimate more extreme high and low blood pressures closer to normal than what invasive measurements indicate. The accuracy of the oscillometric maximum amplitude algorithm for estimating mean arterial pressure is affected by multiple factors, including the cuff size and shape, the shape of the arterial compliance curve and arterial pressure pulse, and pulse pressure itself. Additionally, the technique typically assumes a consistent arterial compliance and arterial pressure pulse, thus changes in arterial compliance and arrhythmias that lead to variation in the pressure pulse can affect accuracy. Volume clamping, based on the Penaz principle, and arterial tonometry provide continuous tracking of the arterial pressure pulse. The ubiquitous use of blood pressure monitoring is in contrast with the lack of evidence for optimal perioperative blood pressure targets. Accepted for publication September 27, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Kai Kuck, PhD, Department of Anesthesiology, University of Utah Medical School, 30 N 1900 E Room 3c444, Salt Lake City, UT 84132. Address e-mail to kai.kuck@hsc.utah.edu. © 2017 International Anesthesia Research Society

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How to Survive in Anaesthesia, 5th ed

No abstract available

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Two-Year Follow-Up Survey: Views of US Anesthesiologists About Health Care Costs and Future Practice Roles

Anesthesiologists' perspectives on US health care finance reform are increasingly germane to recent policy reforms. The aim of this follow-up survey was to examine how anesthesiologists' views of health care costs and future practice roles have changed since 2014. Six thousand randomly chosen active members of the American Society of Anesthesiologists were again surveyed and were also asked several new questions regarding specialties and perioperative management. Results showed an increase in self-reported understanding of the perioperative surgical home. Government, insurance companies, and pharmaceutical companies saw an increase in perceived "major responsibility" for cost reduction. Respondents vastly preferred that patient care under the perioperative surgical home be multidisciplinary. Accepted for publication September 1, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Joseph B. Rinehart, MD, Department of Anesthesiology & Perioperative Care, University of California, Irvine, 101 The City Dr S, Orange, CA 92868. Address e-mail to jrinehar@uci.edu. © 2017 International Anesthesia Research Society

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Reducing Maternal Mortality in Papua New Guinea: Contextualizing Access to Safe Surgery and Anesthesia

Papua New Guinea has one of the world's highest maternal mortality rates with approximately 215 women dying per 100,000 live births. The sustainable development goals outline key priority areas for achieving a reduction in maternal mortality including a focus on universal health coverage with safe surgery and anesthesia for all pregnant women. This narrative review addresses the issue of reducing maternal mortality in Papua New Guinea by contextualizing the need for safe obstetric surgery and anesthesia within a structure of enabling environments at key times in a woman's life. The 3 pillars of enabling environments are as follows: a stable humanitarian government; a safe, secure, and clean environment; and a strong health system. Key times, and their associated specific issues, in a woman's life include prepregnancy, antenatal, birth and the postpartum period, childhood, adolescence and young womanhood, and the postchildbearing years. Accepted for publication September 8, 2017. Funding: None. The author declares no conflicts of interest. This review was undertaken as part of work completed by Associate Professor Dennis at the University of Sydney as part of the completion of her Master of International Public Health. Reprints will not be available from the author. Address correspondence to Alicia T. Dennis, MBBS, PhD, MIPH, PGDipEcho, FANZCA, Department of Anaesthesia, The Royal Women's Hospital, The University of Melbourne, Locked Bag 300, Corner Grattan St & Flemington Rd, Parkville, Victoria 3052, Australia. Address e-mail to alicia.dennis@thewomens.org.au. © 2017 International Anesthesia Research Society

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Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough After Brief Surgery: A Prospective Randomized Trial

BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the incidence of cough and throat pain on emergence after surgery lasting more than 2 hours. However, alkalinized lidocaine needs 60–120 minutes to cross the ETT cuff membrane; therefore, its usefulness in shorter duration surgery is unknown. This prospective double-blind randomized controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of emergence cough after surgeries lasting 90 minutes before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S) was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane, rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values. Opioids administered in prophylaxis of extubation cough were proscribed. A standardized "no touch" emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was instructed to open his eyes and extubation occurred once a directed response was noted. RESULTS: A total of 213 patients were randomized and 100 patients in each group completed the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in group AL was 0.55 (0–0.94, P = .045). Total amount of opioids administered (P = .194), ETT cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ± 29 minutes in group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia emergence cough after surgeries with an average duration of slightly

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The Science of Local Anesthesia: Basic Research, Clinical Application, and Future Directions

Local anesthetics have been used clinically for more than a century, but new insights into their mechanisms of action and their interaction with biological systems continue to surprise researchers and clinicians alike. Next to their classic action on voltage-gated sodium channels, local anesthetics interact with calcium, potassium, and hyperpolarization-gated ion channels, ligand-gated channels, and G protein–coupled receptors. They activate numerous downstream pathways in neurons, and affect the structure and function of many types of membranes. Local anesthetics must traverse several tissue barriers to reach their site of action on neuronal membranes. In particular, the perineurium is a major rate-limiting step. Allergy to local anesthetics is rare, while the variation in individual patient's response to local anesthetics is probably larger than previously assumed. Several adjuncts are available to prolong sensory block, but these typically also prolong motor block. The 2 main research avenues being followed to improve action of local anesthetics are to prolong duration of block, by slow-release formulations and on-demand release, and to develop compounds and combinations that elicit a nociception-selective blockade. Accepted for publication October 16, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Markus W. Hollmann, MD, PhD, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Address e-mail to m.w.hollmann@amc.uva.nl. © 2017 International Anesthesia Research Society

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Improvement of the Elevated Tryptase Criterion to Discriminate IgE- From Non–IgE-Mediated Allergic Reactions

BACKGROUND: Differentiating between immunoglobulin E (IgE)-dependent and IgE-independent hypersensitivity reactions may improve the etiologic orientation and clinical management of patients with allergic reactions in the anesthesia setting. Serum tryptase levels may be useful to discriminate the immune mechanism of allergic reactions, but the diagnostic accuracy and optimal cutpoint remain unclear. We aimed to compare the diagnostic accuracy of tryptase during reaction (TDR) alone and the TDR/basal tryptase (TDR/BT) ratio for discriminating IgE- from non–IgE-mediated allergic reactions, and to estimate the best cut point for these indicators. METHODS: We included 111 patients (45% men; aged 3–99 years) who had experienced an allergic reaction, even though the allergic reaction could be nonanaphylactic. Allergy tests were performed to classify the reaction as an IgE- or non–IgE-mediated one. The area under the curve (AUC) of the receiver operating characteristic analysis was performed to estimate the discriminative ability of TDR and TDR/BT ratio. RESULTS: An IgE-mediated reaction was diagnosed in 49.5% of patients, of whom 56% met anaphylaxis criteria. The median (quartiles) TDR for the IgE-mediated reactions was 8.0 (4.9–19.6) and 5.1 (3.5–8.1) for the non–IgE-mediated (P = .022). The median (quartiles) TDR/BT ratio was 2.7 (1.7–4.5) in IgE-mediated and 1.1 (1.0–1.6) in non–IgE-mediated reactions (P

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Anesthesia Medication Handling Needs a New Vision

No abstract available

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Effects of Increasing Airway Pressures on the Pressure of the Endotracheal Tube Cuff During Pelvic Laparoscopic Surgery

BACKGROUND: Tracheal tube cuff pressures exceeding the perfusion pressures of the tracheal mucosa have been associated with complications such as sore throat, tracheal mucosa ulcers, tracheal rupture, and subglottic stenosis. Despite appropriate inflation, many factors can increase the tracheal cuff pressure during mechanical ventilation. This prospective observational cohort study was designed to test the hypothesis that during a clinical model of decreasing respiratory compliance, the pressure within the endotracheal tube cuff will rise in direct relationship to increases in the airway pressures. METHODS: Twenty-eight adult obese patients (BMI ≥30 kg/m2) scheduled for elective laparoscopic gynecologic procedures were enrolled. All patients received general anesthesia utilizing endotracheal tubes with low-pressure high-volume cuffs. After baseline adjustment of the cuff pressure to 25 cm H2O, the airway pressures and endotracheal cuff pressures were continuously measured using pressure transducers connected to the anesthesia circuit and cuff pilot, respectively. Data on cuff and airway pressures, mechanical ventilation parameters, intraabdominal pressures, and degree of surgical table inclination were collected throughout the anesthetic procedure. General linear regression models with fixed and random effects were fit to assess the effect of increases in airway pressures on cuff pressure, after adjusting for covariates and the clustered structure of the data. RESULTS: The mean (standard deviation) age and body mass index were 42.2 (8.8) years and 37.7 (5.1) kg/m2, respectively. After tracheal intubation, the cuffs were overinflated (ie, intracuff pressures >30 cm H2O) in 89% of patients. The cuff pressures significantly changed after concomitant variations in the airway pressures from a mean (standard error) value of 29.6 (1.30) cm H2O before peritoneal insufflations, to 35.6 (0.68) cm H2O after peritoneal insufflation, and to 27.8 (0.79) cm H2O after peritoneal deflation (P

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Epidural Space Identification With Loss of Resistance Technique for Epidural Analgesia During Labor: A Randomized Controlled Study Using Air or Saline—New Arguments for an Old Controversy

BACKGROUND: The best technique to identify the epidural space for labor analgesia is still unclear despite the publication of various randomized controlled studies and meta-analyses. Our aim was to assess the superiority of the saline loss of resistance (SLOR) technique over the air loss of resistance (ALOR) technique with respect to the quality of the block. METHODS: Consenting parturients admitted to our obstetric suite for spontaneous or induced labor were randomized to receive epidural analgesia using either the ALOR or SLOR technique. Our primary outcome was to compare the impact of the SLOR and ALOR technique on pain score improvement measured 30 minutes after administration of epidural block. Our secondary outcomes included the density of motor blockade and analgesic efficacy measured at 30 minutes. Primary and secondary outcomes were compared using the Student t test and Mann-Whitney U test. Statistical significance was set at P

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Case 14431: A Case of Dyspnea and Weakness

ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR CASE 14431 A CASE OF DYSPNEA AND WEAKNESS Medical Department First admission. A German-American salesman sixty years old entered January 24…

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Case 14432: How Long is an Apparently Cured Streptococcus Sepsis Still Dangerous?

CASE 14432 HOW LONG IS AN APPARENTLY CURED STREPTOCOCCUS SEPSIS STILL DANGEROUS? Surgical Department A married New England woman thirty-three years old entered through the Emergency Ward July 28 complaining of pain in the right upper quadrant with chills and fever. Two months before admission she…

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Case 14421: General Glandular Enlargement Lasting Thirty Years or More

ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES CASE 14421 GENERAL GLANDULAR ENLARGEMENT LASTING THIRTY YEARS OR MORE Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR Medical Department An American stationary fireman forty-three years old entered…

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Case 14422: Possibilities in the Treatment of a Case of Advanced Pulmonary Tuberculosis

Dr. Cabot : I don't know. I don't think that can be due to this disease. A Student : How do you account for glands decreasing in size? Dr. Cabot : X-ray treatment accounts for it. Perhaps also he had some terminal infection. Any terminal infection that we can name tends to make the glands and…

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Case 14281: Jaundice and Ascites in a Boy of Eighteen



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Case 14282: Fever, Weakness and Pain in the Right Axilla



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Case 14272: Cause of Diarrhea?

fed the patient passed through the ulcer of the ileum into this abscess cavity in the abdominal wall, and from there out through the umbilicus. Except for this abscess cavity it was a typical dry type of tuberculous peritonitis with widespread adhesions and the surfaces studded with tubercles. The…

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Case 14271: Ascites at Seventeen Months

ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR CASE 14271 ASCITES AT SEVENTEEN MONTHS Medical Department A girl baby seventeen months old entered March 20. The complaints were abdominal distention…

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Case 14192: A Persistent Bullous Eruption

ing is said about emaciation. She does not seem to have had cough any length of time. There is no reason to suspect tuberculosis except for the râles. They are perfectly proper to hear over a pneumonia. Miss Painter : She is recorded as well nourished. Dr. Cabot : Should we consider a pulmonary…

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Case 14191: Coma

ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES CASE 14191 COMA Medical Department An unmarried Irish-American woman sixtyseven years old entered the hospital March 17 in coma. The history is limited to a few facts obtained from a brother who did not live with…

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Case 14162: Epigastric Pain, Conflicting Symptoms, Subsequently Elucidated

that without a hypertrophied heart he could have died from his kidneys, without more definite evidence of an acute nephritis. CASE 14162 EPIGASTRIC PAIN, CONFLICTING SYMPTOMS, SUBSEQUENTLY ELUCIDATED Medical Department A married Canadian woman fifty-eight years old came to the Out-Patient…

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Case 14161: Dyspnea without Obvious Cause

ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR CASE 14161 DYSPNEA WITHOUT OBVIOUS CAUSE Medical Department A Canadian teamster fifty-two years old entered February 2 complaining of difficulty in…

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Case 14152: Early Symptoms of Neuritis; Subsequent Involvement of Spinal Cord. Anacidity. Blood Not Consistent with Primary Anemia. Improvement Both before and after Taking Liver

· tive blood culture means something, negative means nothing. A Physician : Does not a fixation of gravity mean chronic nephritis, or can it occur from kidney infarcts? Dr. Cabot : I think I can remember here cases where we have been shown at post-mortem extensive infarctions or emboli Avithout…

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Case 14151: Hematuria, Dyspnea and Acute Arthritis

ANTE-MORTEM ANDPOST-MORTEMRECORDS AS USEDIN WEEKLY CLINICO-PATHOLOGICALEXERCISES Edited by R. C. Cabot, M.D. F.M.PAINTER,A.B.ASSISTANTEDITOR CASE 14151 HEMATURIA, DYSPNEA AND ACUTE ARTHRITIS Medical Department A married colored Avoman twenty-four years old was sent from the Out-Patient Department…

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Case 14092: An Obscure Abdominal Situation

' ' Pneumocooci predominant. ' ' That means nothing. That temperature is very low. One Avonders if he closed his mouth. I should not take it too seriously. "Pressure signs developed in the left back." That is the lingo of 1910. It means that in the left back there was a patch of dullness and…

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Case 14091: Recurrent Multiple Arthritis

ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR CASE 14091 RECURRENT MULTIPLE ARTHRITIS Medical Department First admission. An American schoolboy fourteen years old entered May 16 complaining of…

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Case 14011: Fever and Cheyne-Stokes Breathing at Seventy-Eight

ANTE-MORTEM AND POST-MORTEM RECORDSAS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR CASE 14011 FEVER AND CHEYNE-STOKES BREATHING AT SEVENTY-EIGHT Medical Department A Nova Scotian seventy-eight years old, formerly a teamster, was…

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Case 14012: Operation with Confusing Findings

Arteriosclerosis. Post-operative enucleation of the left eye for glaucoma. Bronchopneumonia. DR. RICHARD C. CABOT's DIAGNOSIS Pneumococcus meningitis. Hypertrophy of heart. Pneumonia. ANATOMIC DIAGNOSES 1. Primary fatal lesion. Pneumococcus meningitis. 2. Secondary or terminal lesions. Enucleation…

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Case 13542: Was the Patient Misinformed?

Dentón's is by far the most detailed and careful work that has been done, I think, on the pathology of pellagra. He Avorked on very fresh material. The changes in the cord have been described by various people, but there is nothing very characteristic about them. Dr. Cabot : Are esophageal lesions…

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Case 13541: A Case with Anasarca, Cyanosis, Symmetrical Dermatitis, Diarrhea, Mass in the Abdomen and Psychosis

CaseRecords of the MassachusettsGeneralHospital ANTE-MORTEM AND POST-MORTEM RECORDS AS USED IN WEEKLY CLINICO-PATHOLOGICAL EXERCISES Edited by R. C. Cabot, M.D. F. M. PAINTER, A.B. ASSISTANT EDITOR CASE 13541 A CASE WITH ANASARCA, CYANOSIS, SYMMETRICAL DERMATITIS, DIARRHEA, MASS IN THE ABDOMEN AND…

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ASCT2 defined by enzyme-mediated activation of radical sources enhances malignancy of GD2-plus small cell lung cancer

Abstract

Ganglioside GD2 is specifically expressed in small cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we performed enzyme-mediated activation of radical sources combined with mass spectrometry in GD2 positive (+) SCLC cells. Consequently, we identified ASC amino-acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2. We showed that ASCT2 was highly expressed in glycolipid-enriched microdomain/rafts in GD2(+) SCLC cells, and co-localized with GD2 in proximity ligation assay and immunocytostaining, and bound with GD2 in immuneoprecipitation/TLC-immunostaining. Malignant phenotypes of GD2(+) SCLC cells were enhanced via glutamine uptake, and were suppressed by L-γ-glutamyl-p-nitroanilide, a specific inhibitor of ASCT2, via reduced phosphorylation of p70 S6K1 and S6. These results suggested that ASCT2 enhances glutamine uptake in GEM/rafts in GD2(+) SCLC cells, leading to the enhancement of cell proliferation and migration through increased phosphorylation of mTORC1 signaling axis.

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Detection of CTCs in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells

Abstract

Circulating tumor cells (CTCs) are newly discovered biomarkers of cancers. Although many systems detect CTCs, a gold standard has not yet been established. We analyzed CTCs in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (−) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTCs were detected in 6 of 23 patients with cervical cancers (26.0%). The expression of CTCs did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTCs originated from HPV-infected cancer cells. These CTCs were all negative for cytokeratins. The CTCs detected by our system were genetically confirmed. CTCs derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.

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Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma

Abstract

Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in PCNSL. On the other hand, mutational analyses using cell-free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell-free DNA from PCNSL patients, we performed droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in consecutive 14 PCNSL patients from whom paired tumor-derived DNA and cell-free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor-derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell-free DNAs evaluated by ddPCR (14/14) and TDS (13/14), MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell-free DNAs was traced in five patients; unexpectedly, the mutations disappeared after the chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell-free DNA and could be used as non-invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL.

This article is protected by copyright. All rights reserved.



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via IFTTT

ASCT2 defined by enzyme-mediated activation of radical sources enhances malignancy of GD2-plus small cell lung cancer

Abstract

Ganglioside GD2 is specifically expressed in small cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we performed enzyme-mediated activation of radical sources combined with mass spectrometry in GD2 positive (+) SCLC cells. Consequently, we identified ASC amino-acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2. We showed that ASCT2 was highly expressed in glycolipid-enriched microdomain/rafts in GD2(+) SCLC cells, and co-localized with GD2 in proximity ligation assay and immunocytostaining, and bound with GD2 in immuneoprecipitation/TLC-immunostaining. Malignant phenotypes of GD2(+) SCLC cells were enhanced via glutamine uptake, and were suppressed by L-γ-glutamyl-p-nitroanilide, a specific inhibitor of ASCT2, via reduced phosphorylation of p70 S6K1 and S6. These results suggested that ASCT2 enhances glutamine uptake in GEM/rafts in GD2(+) SCLC cells, leading to the enhancement of cell proliferation and migration through increased phosphorylation of mTORC1 signaling axis.

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Detection of CTCs in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells

Abstract

Circulating tumor cells (CTCs) are newly discovered biomarkers of cancers. Although many systems detect CTCs, a gold standard has not yet been established. We analyzed CTCs in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (−) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTCs were detected in 6 of 23 patients with cervical cancers (26.0%). The expression of CTCs did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTCs originated from HPV-infected cancer cells. These CTCs were all negative for cytokeratins. The CTCs detected by our system were genetically confirmed. CTCs derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.

This article is protected by copyright. All rights reserved.



http://ift.tt/2zhuNCQ

Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma

Abstract

Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in PCNSL. On the other hand, mutational analyses using cell-free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell-free DNA from PCNSL patients, we performed droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in consecutive 14 PCNSL patients from whom paired tumor-derived DNA and cell-free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor-derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell-free DNAs evaluated by ddPCR (14/14) and TDS (13/14), MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell-free DNAs was traced in five patients; unexpectedly, the mutations disappeared after the chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell-free DNA and could be used as non-invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL.

This article is protected by copyright. All rights reserved.



http://ift.tt/2mKxTK2