The preparation of porcine (Tyr-A14-2H) insulin and its characterization by mass spectrometry

The title compound was prepared by catalytic deiodination of (Tyr-A14-3-I) insulin with deuterium gas. Under special conditions (large excess of PdO in CH3OD/D2O at pH 9.2) developed to minimize problems due to poisoning of the catalyst, deuterated insulin was produced in yields of about 35% after purification by reversed phase HPLC. For analysis, the deuterated insulin was digested with V8 protease and was shown by mass spectrometry to have incorporated deuterium to an extent of 96.6 atom %, exclusively in a pentapeptide containing Tyr A14. The title compound should prove useful to those workers studying insulin by mass spectrometry, and use of the method with tritium gas in place of deuterium should permit the preparation of a specifically labelled radioactive insulin analogue which behaves identically to the natural hormon

Effect of Vancomycin Therapy for Osteomyelitis on Colonization by Methicillin-Resistant Staphylococcus aureus: Lack of Emergence of Glycopeptide Resistance

Abstract Background: In treating orthopedic infections, the long-term impact of vancomycin therapy on colonization by methicillin-resistant Staphylococcus aureus (MRSA) and the emergence of vancomycin-intermediate S. aureus is unknown. Design: Prospective surveillance of the effect of long-term vancomycin therapy on colonization by MRSA and the emergence of vancomycin-intermediate S. aureus. Methods: Thirty-four patients with MRSA osteomyelitis that was microbiologically documented were longitudinally observed for the emergence of vancomycin-intermediate S. aureus at 3 body sites (wound, anterior nares, and groin) during the initial period of vancomycin therapy and at the 2-month follow-up. Twenty patients received the standard dose (20 mg/kg/d) for 34 ± 6 days and 14 patients received a high dose (40 mg/kg/d) of vancomycin for 37 ± 9 days. Results: During vancomycin treatment, global MRSA carriage (all body sites) fell from 100% to 25% in the group of patients receiving the standard dose of vancomycin, and from 100% to 40% in the group receiving the high dose. During the 2-month follow-up period after vancomycin therapy, global MRSA carriage increased from 25% to 55% in the group receiving the standard dose and decreased from 43% to 36% in the group receiving the high dose. Conclusion: Therapy with a high dose of vancomycin contributes to the sustained eradication of MRSA carriage without promoting the emergence of glycopeptide resistanc

Reaction mechanism of trypsin-catalysed semisynthesis of human insulin studied by fast atom bombardment mass spectrometry

The production of semisynthetic human insulin for therapeutic purposes is of considerable importance. During trypsin-catalysed transformation of pig insulin into an ester of insulin of human sequence, the alanyl residue at position B30 is removed and replaced with an esterified residue of threonine. We have carried out this transformation in a medium enriched in 18OH2 and studied the product by MS. In contrast to a previous report, we find that incorporation of label into the B29−B30 peptide bond occurs during the transformation with threonine methyl ester in aqueous N, N-dimethylacetamide. Quantitative data are presented and the implications of these findings are discusse

The Value of Suction Drainage Fluid Culture during Aseptic and Septic Orthopedic Surgery: A Prospective Study of 901 Patients

There are no guidelines on the value of suction drainage fluid culture (SDC), and it is difficult to determine whether the organisms cultured from suction drainage fluid samples are pathogenic or simply contaminants. We performed 2989 cultures of suction drainage fluid samples obtained, during a 1-year period, from 901 patients who underwent aseptic or septic orthopedic surgery (946 operations). The culture results were analyzed to evaluate their ability to detect postoperative infection after aseptic operations or to detect either a persistent or new episode of sepsis in patients known to have infection. For aseptic operations, the sensitivity of SDC was 25%, the specificity was 99%, the positive predictive value was 25%, and the negative predictive value was 99%. For septic operations, the sensitivity of SDC was 81%, the specificity was 96%, the positive predictive value was 87%, and the negative predictive value was 94%. We conclude that, for aseptic orthopedic surgery, SDC is not useful in detecting postoperative infection. However, for septic orthopedic surgery, it is of clinical importanc

Noninfectious Wound Complications in Clean Surgery: Epidemiology, Risk Factors, and Association with Antibiotic Use

Background: Noninfectious wound complications are frequent and often are confused with and treated as infection. Methods: We assessed the epidemiology, impact, risk factors, and associations with antibiotic use of noninfectious wound complications in clean orthopedic and trauma surgery. We report a single-center, prospective, observational study in an orthopedic department. Results: Among 1,073 adult patients, 630 (59%) revealed clinically relevant postoperative noninfectious wound complications, leading to a significant prolongation of hospital stay (14 vs. 12days; Wilcoxon rank-sum test; p<0.02) compared with patients without complications. The most frequent and severe complications were discharge with dehiscence (n=437; 41%) and hematoma (n=379; 35%). Forty-seven patients (47/630; 7%) underwent reoperation for dehiscence (n=39) or hematoma (n=8). These patients made up 4.3% of the entire study population (47/1,073). In multivariate analysis, an ASA score ≥2 points, age≥60years, surgery duration for ≥90min, implant-related surgery, and poor compliance toward nurses' recommendations were pronounced risk factors for these complications, whereas antibiotic-related parameters had no influence. Staple use was significantly associated with wound discharge but not with hematoma. Conclusions: Wound complications, such as dehiscence with discharge or hematoma after clean orthopedic and trauma surgery, are frequent with an overall incidence of 60%. Although they lead to few surgical reinterventions, they prolong hospital stay by 2days. Few clinical parameters show association with wound complications. Among them, improvements of patient compliance and avoidance of staples use for skin closure are the most promising actions to decrease complication ris

The B-MaP-C study: Breast cancer management pathways during the COVID-19 pandemic. Study protocol.

Introduction: Approximately 55,000 women in the United Kingdom are diagnosed with new breast cancer annually. Since emerging in December 2019, SARS-CoV-2 (coronavirus disease 2019, COVID-19) has become a global pandemic, affecting healthcare delivery worldwide. In response to the pandemic, multiple guidelines were issued to assist with rationalising breast cancer care. The primary aim of the B-MaP-C study is to audit and describe breast cancer management of patients newly diagnosed with breast cancer during the COVID-19 pandemic against pre-COVID-19 management practice in the UK. The implications of changes to management will be determined and the impact of a COVID-19 diagnosis on the patient's breast cancer management will be determined. Methods and analysis: This is a multi-centre collaborative audit of consecutive breast cancer patients undergoing treatment decisions during the acute and recovery phases of the COVID-19 pandemic. All patients with newly diagnosed primary breast cancer, whose treatment was decided in a multidisciplinary meeting from the 16th March 2020, are eligible for inclusion. Ethics and dissemination: As this is an audit ethical approval is not required. Each participating centre is required to register the study locally and obtain local governance approvals prior to commencement of data collection. Local audit data will be available to individual participating units for governance purposes. The results of the data analysis will be submitted for publication, as well as disseminated via the ABS newsletter and a webinar. All data will be presented at national and international conferences, circumstances permitting. Registration details: Each participating centre received local governance audit registration

Evidence of pseudoprogression in patients treated with PD1/ PDL1 antibodies across tumor types

Background: PD(L)1 antibodies (anti-PD(L)-1) have been a major breakthrough in several types of cancer. Novel patterns of response and progression have been described with anti-PD(L)-1. We aimed at characterizing pseudoprogression (PSPD) among patients with various solid tumor types treated by anti-PD(L)-1. Methods: All consecutive patients (pts) enrolled in phase 1 trials with advanced solid tumors and lymphomas treated in phase I clinical trials evaluating monotherapy by anti-PD(L)-1 at Gustave Roussy were analyzed. We aimed to assess prevalence and outcome of PSPD across tumor types. We also intended to describe potential clinical and pathological factors associated with PSPD. Results: A total of 169 patients treated with anti-PD(L)-1 were included in the study. Most frequent tumor types included melanoma (n = 57) and non-small cell lung cancer (n = 19). At first tumor evaluation 77 patients (46%) presented with immune unconfirmed progressive disease. Six patients (8%) experienced PSPD: 2 patients with partial response; 4 patients with stable disease. Increase in target lesions in the first CT-scan was more frequently associated to PSPD (67% vs 33%; P = .04). Patients with a PSPD had a superior survival when compared to patients progressing (median OS: 10.7 months vs 8.7 months; P = .07). Conclusions: A small subset of PSPD patients may experience response after an initial progression. Assessment of the current strategy for immune-related response evaluations may require further attention

Standardizing the classification of skin tears: validity and reliability testing of the International Skin Tear Advisory Panel Classification System in 44 countries

Background: Skin tears are acute wounds that are frequently misdiagnosed and under‐reported. A standardized and globally adopted skin tear classification system with supporting evidence for diagnostic validity and reliability is required to allow assessment and reporting in a consistent way. Objectives:To measure the validity and reliability of the International Skin Tear Advisory Panel (ISTAP) Classification System internationally. Methods: A multicountry study was set up to validate the content of the ISTAP Classification System through expert consultation in a two‐round Delphi procedure involving 17 experts from 11 countries. An online survey including 24 skin tear photographs was conducted in a convenience sample of 1601 healthcare professionals from 44 countries to measure diagnostic accuracy, agreement, inter‐rater reliability and intrarater reliability of the instrument. Results:A definition for the concept of a ‘skin flap’ in the area of skin tears was developed and added to the initial ISTAP Classification System consisting of three skin tear types. The overall agreement with the reference standard was 0·79 [95% confidence interval (CI) 0·79–0·80] and sensitivity ranged from 0·74 (95% CI 0·73–0·75) to 0·88 (95% CI 0·87–0·88). The inter‐rater reliability was 0·57 (95% CI 0·57–0·57). The Cohen's Kappa measuring intrarater reliability was 0·74 (95% CI 0·73–0·75). Conclusions: The ISTAP Classification System is supported by evidence for validity and reliability. The ISTAP Classification System should be used for systematic assessment and reporting of skin tears in clinical practice and research globally.info:eu-repo/semantics/publishedVersio

Assessment of glenohumeral subluxation in poststroke hemiplegia: Comparison between ultrasound and fingerbreadth palpation methods

© 2014 American Physical Therapy Association. Background. Glenohumeral subluxation (GHS) is a common poststroke complication. Treatment of GHS is hampered by the lack of objective, real-time clinical measurements.Objective. The aims of this study were: (1) to compare an ultrasound method of GHS measurement with the fingerbreadth palpation method using a receiver operating characteristic curve (ROC) and (2) to report the sensitivity and specificity of this method.Design. A prospective study was conducted.Setting. The study was conducted in local hospitals and day centers in the southwest of England.Patients. One hundred five patients who had one-sided weakness following a first-time stroke (51 men, 54 women; mean age_71 years, SD_11) and who gave informed consent were enrolled in the study.Measurements. Ultrasound measurements of acromion–greater tuberosity (AGT) distance were used for the assessment of GHS. Measurements were undertaken on both shoulders by a research physical therapist trained in shoulder ultrasound with the patient seated in a standardized position. Fingerbreadth palpation assessment of GHS was undertaken by a clinical physical therapist based at the hospital, who also visited the day centers.Results. The area under the ROC curve was 0.73 (95% confidence interval [95% CI]_0.63, 0.83), suggesting that the ultrasound method has good agreement compared with the fingerbreadth palpation method. A cutoff point of _0.2 cm AGT measurement difference between affected and unaffected shoulders generated a sensitivity of 68% (95% CI_51%, 75%), a specificity of 62% (95% CI_47%, 80%), a positive likelihood ratio of 1.79 (95% CI_1.1, 2.9), and a negative likelihood ratio of 0.55 (95% CI_0.4, 0.8).Limitations. Clinical therapists involved in the routine care of patients conducted the fingerbreadth palpation method. It is likely that they were aware of the patients’ subluxation status.Conclusion. The ultrasound method can detect minor asymmetry (_0.5 cm) and has the potential advantage over the fingerbreadth palpation method of identifying patients with minor subluxation