Classifying early infant feeding status from clinical notes using natural language processing and machine learning.

The objective of this study is to develop and evaluate natural language processing (NLP) and machine learning models to predict infant feeding status from clinical notes in the Epic electronic health records system. The primary outcome was the classification of infant feeding status from clinical notes using Medical Subject Headings (MeSH) terms. Annotation of notes was completed using TeamTat to uniquely classify clinical notes according to infant feeding status. We trained 6 machine learning models to classify infant feeding status: logistic regression, random forest, XGBoost gradient descent, k-nearest neighbors, and support-vector classifier. Model comparison was evaluated based on overall accuracy, precision, recall, and F1 score. Our modeling corpus included an even number of clinical notes that was a balanced sample across each class. We manually reviewed 999 notes that represented 746 mother-infant dyads with a mean gestational age of 38.9 weeks and a mean maternal age of 26.6 years. The most frequent feeding status classification present for this study was exclusive breastfeeding [n = 183 (18.3%)], followed by exclusive formula bottle feeding [n = 146 (14.6%)], and exclusive feeding of expressed mother's milk [n = 102 (10.2%)], with mixed feeding being the least frequent [n = 23 (2.3%)]. Our final analysis evaluated the classification of clinical notes as breast, formula/bottle, and missing. The machine learning models were trained on these three classes after performing balancing and down sampling. The XGBoost model outperformed all others by achieving an accuracy of 90.1%, a macro-averaged precision of 90.3%, a macro-averaged recall of 90.1%, and a macro-averaged F1 score of 90.1%. Our results demonstrate that natural language processing can be applied to clinical notes stored in the electronic health records to classify infant feeding status. Early identification of breastfeeding status using NLP on unstructured electronic health records data can be used to inform precision public health interventions focused on improving lactation support for postpartum patients.

Analytical techniques for the characterization of nanoparticles for mRNA delivery.

Nanotechnology-assisted RNA delivery has gotten a tremendous boost over the last decade and made a significant impact in the development of life-changing vaccines and therapeutics. With increasing numbers of emerging lipid- and polymer-based RNA nanoparticles progressing towards the clinic, it has become apparent that the safety and efficacy of these medications depend on the comprehensive understanding of their critical quality attributes (CQAs). However, despite the rapid advancements in the field, the identification and reliable quantification of CQAs remain a significant challenge. To support these efforts, this review aims to summarize the present knowledge on CQAs based on the regulatory guidelines and to provide insights into the available analytical characterization techniques for RNA-loaded nanoparticles. In this context, routine and emerging analytical techniques are categorized and discussed, focusing on the operation principle, strengths, and potential limitations. Furthermore, the importance of complementary and orthogonal techniques for the measurement of CQAs is discussed in order to ensure the quality and consistency of analytical methods used, and address potential technique-based differences.

Aqueous remote loading of model cationic peptides in uncapped poly(lactide-co-glycolide) microspheres for long-term controlled release.

Remote loading microencapsulation of peptides into polymer microspheres without organic solvent represents a promising alternative to develop long-acting release depots relative to conventional encapsulation methods. Here, we formulated drug-free microspheres from two kinds of uncapped poly(lactide-co-glycolides) (PLGAs), i.e., ring-opening polymerized Expansorb® DLG 50-2A (50/50, 11.2 kDa) and Expansorb® DLG 75-2A (75/25, 9.0 kDa), and evaluated their potential capacity to remote-load and control the release of two model peptides, leuprolide and octreotide. Degradation and erosion kinetics, release mechanism, and storage stability was also assessed. As control formulations, peptide was loaded in the same PLGA 75/25 polymer by the conventional double emulsion-solvent evaporation method (W/O/W) and remote loaded in polycondensation poly(lactic-co-glycolic acid) 75/25 (Wako 7515, 14.3 kDa). Loading content of 6.7%-8.9% w/w (~ 67%-89% encapsulation efficiency (EE)) was attained for octreotide, and that of 9.5% w/w loading (~ 95% EE) was observed for leuprolide, by the remote loading paradigm. Octreotide and leuprolide were both slowly and continuously released in vitro from the remote-loaded Expansorb® DLG 75-2A MPs for over 56 days, which was highly similar to that observed from traditionally-loaded formulations by W/O/W (8.8% loading, 52.8% EE). The faster release kinetics was observed for the faster degrading PLGA 50/50 remote-loaded Expansorb® DLG 50-2A MPs relative to microspheres from the PLGA 75/25 Expansorb® DLG 75-2A. Despite slight differences in degradation kinetics, the release mechanism of octreotide from the Expansorb® microspheres, whether remote loaded or by W/O/W, was identical as determined by release vs. mass loss curves. Octreotide acylation was also minimal (< ~ 10%) for this polymer. Finally, drug-free Expansorb® DLG 75-2A MPs displayed excellent storage stability over 3 months. Overall, this work offers support for the use of ring-opening Expansorb® PLGA-based microspheres to remote load peptides to create simple and effective long-acting release depots.

Assessing the Quality of Reporting on Quality Improvement Initiatives in Breast Reconstruction: A Systematic Review.

BACKGROUND: There has been a recent increase in the number and complexity of quality improvement (QI) studies in breast reconstruction. To assist with the development of thorough QI reporting practices, with the goal of improving the transferability of these initiatives, the authors conducted a systematic review of studies describing the implementation of QI initiatives in breast reconstruction. The authors used the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guideline to appraise the quality of reporting of these initiatives. METHODS: English language articles published in Embase, MEDLINE, CINAHL, and the Cochrane databases were searched. Quantitative studies evaluating the implementation of QI initiatives in breast reconstruction were included. The primary endpoint of interest in this review was the distribution of studies according to SQUIRE 2.0 criteria scores in proportions. Abstracts and full-text screening, and data extraction were completed independently and in duplicate by the review team. RESULTS: The authors screened 1107 studies, of which 53 full texts were assessed and 35 met inclusion criteria. In our assessment, only three studies (9%) met all 18 SQUIRE 2.0 criteria. SQUIRE 2.0 criteria that were met most frequently were abstract, problem description, rationale, and analysis. The lowest SQUIRE 2.0 scores appeared in the interpretation criteria. CONCLUSIONS: Significant opportunity exists to improve QI reporting in breast reconstruction, especially in the realm of costs, strategic tradeoffs, ethical considerations, project sustainability, and potential for spread to other contexts. Improvements in these areas will help to further advance the transferability of QI initiatives in breast reconstruction.

Family planning (KB) practices and the impact on Papuan women reproductive health.

OBJECTIVE: This study aims to describe and analyze KB or family planning practices and their impact on Papuan women. A case study was conducted in Waena Village, one of the Kampung KB in Jayapura City, Papua. METHODS: The research method used is descriptive qualitative using an ethnographic approach. The determination of the informants was done purposively by assigning one of the key informants. Data collection includes in-depth interviews and observation. Data analysis includes data reduction, data description, and interpretation. RESULTS: The results showed that women of childbearing age carried out the practice of KB by using various forms of birth control. Some use birth control pills and spiral birth control (intrauterine contraception). In addition, the family planning program has provided education to increase knowledge about reproductive health, types of diseases so that women feel more valued and cared for by men with the existence of KB program. Moreover, the existence of the Kampung KB program also has an impact on community social activities, such as educate adolescents and children to have a clean and healthy lifestyle oriented toward family welfare. CONCLUSION: The Kampung KB program in Waena Village has educated the public about reproductive health, which significantly affects community order.

A comparison of patient-reported outcomes between Alloderm and Dermacell in immediate alloplastic breast reconstruction: A randomized control trial.

BACKGROUND: Alloderm and Dermacell are the two leading human acellular dermal matrices (ADM) in immediate breast reconstruction (IBR). Despite differences in sterility, consistency, thickness and cost, there are no comparative trials to date to compare patient-reported outcome measures (PROM) between the two products. The purpose of this study was to determine if there was a difference in patient-reported outcomes (as measured by the BREAST-Q) between patients reconstructed with Alloderm and Dermacell. METHODS: A single center, open-label, randomized control trial of patients undergoing IBR with an implant for breast cancer or breast cancer prophylaxis was performed. Patients were randomized to either Alloderm or Dermacell. Baseline demographic data were compared, and linear mixed models were used to identify associations with BREAST-Q over time. RESULTS: Between June 2016 and October 2018, 62 patients were randomized into two groups, 31(50%) Alloderm and 31(50%) Dermacell. Of these, 23(74%) patients in the Alloderm group and 27(87%) patients of the Dermacell group filled out BREAST-Q questionnaires. Baseline BREAST-Q scores with respect to satisfaction with breasts, psychosocial well-being, sexual well-being, and physical well-being were similar between groups (p>0.05). At 3 months postoperatively, the Alloderm group had a statistically significant improvement with respect to satisfaction with breasts (67 vs 53, p = 0.03), satisfaction with overall results (85 vs 61, p = 0.003), satisfaction with the surgeon (89 vs 67, p = 0.01), and satisfaction with information provided (74 vs 59, p = 0.02). At 12 months postoperatively, there were no statistically significant differences in PROM between groups (p>0.05). CONCLUSION: We report the first randomized controlled trial to date comparing patient-reported outcomes of the two most commonly used ADMs in IBR in Canada. Although a short-term analysis favors the use of Alloderm, there does not appear to be any difference in outcomes between the two products in the longer term.

Field Tracer Tests to Evaluate Transport Properties of Tryptophan and Humic Acid in Karst.

The monitoring of water quality, especially of karst springs, requires methods for rapidly estimating and quantifying parameters that indicate contamination. In the last few years, fluorescence-based measurements of tryptophan and humic acid have become a promising tool to assess water quality in near real-time. In this study, we conducted comparative tracer tests in a karst experimental site to investigate the transport properties and behavior of tryptophan and humic acid in a natural karst aquifer. These two tracers were compared with the conservative tracer uranine. Fluorescence measurements were conducted with an online field fluorometer and in the laboratory. The obtained breakthrough curves (BTCs) and the modeling results demonstrate that (1) the online field fluorometer is suitable for real-time fluorescence measurements of all three tracers; (2) the transport parameters obtained for uranine, tryptophan, and humic acid are comparable in the fast flow areas of the karst system; (3) the transport velocities of humic acid are slower and the resulting residence times are accordingly higher, compared to uranine and tryptophan, in the slower and longer flow paths; (4) the obtained BTCs reveal additional information about the investigated karst system. As a conclusion, the experiments show that the transport properties of tryptophan are similar to those of uranine while humic acid is partly transported slower and with retardation. These findings allow a better and quantitative interpretation of the results when these substances are used as natural fecal and contamination indicators.

Family planning (KB) practices and the impact on Papuan women reproductive health

Objective: This study aims to describe and analyze KB or family planning practices and their impact on Papuan women. A case study was conducted in Waena Village, one of the Kampung KB in Jayapura City, Papua. Methods: The research method used is descriptive qualitative using an ethnographic approach. The determination of the informants was done purposively by assigning one of the key informants. Data collection includes in-depth interviews and observation. Data analysis includes data reduction, data description, and interpretation. Results: The results showed that women of childbearing age carried out the practice of KB by using various forms of birth control. Some use birth control pills and spiral birth control (intrauterine contraception). In addition, the family planning program has provided education to increase knowledge about reproductive health, types of diseases so that women feel more valued and cared for by men with the existence of KB program. Moreover, the existence of the Kampung KB program also has an impact on community social activities, such as educate adolescents and children to have a clean and healthy lifestyle oriented toward family welfare. Conclusion: The Kampung KB program in Waena Village has educated the public about reproductive health, which significantly affects community order. (AU)

The Impact of Delaying Breast Reconstruction on Patient Expectations and Health-Related Quality of Life: An Analysis Using the BREAST-Q.

PURPOSE: An understanding of patient expectations predicts better health outcomes following breast reconstruction. No study to date has examined how patient expectations for breast reconstruction and preoperative health-related quality of life vary with time since breast cancer diagnosis. METHODS: Women consulting for breast reconstruction to a single surgeon's practice over a 13-month period were enrolled in this cross-sectional study. Patients were asked to prospectively complete the BREAST-Q expectations and preoperative reconstruction modules. A retrospective chart review was then performed on eligible patients, and patient demographics, cancer-related factors, and comorbidities were collected. BREAST-Q scores were transformed using the equivalent Rasch method. Multivariate linear regression models were constructed to assess the association between BREAST-Q scores and time since cancer diagnosis. RESULTS: Sixty-five patients met inclusion criteria for analysis and are characterized by a mean age of 53 ± 11 (34-79) years and a mean body mass index of 28 ± 6 (19-49). Most patients were treated by mastectomy (58%) or lumpectomy (23%). At the time of retrospective chart review, 29 (43%) patients had undergone reconstruction, most of which were delayed (59%). The mean latency from cancer diagnosis to reconstruction was 685 ± 867 days (range: 28-3322 days). Latency from cancer diagnosis to reconstruction was associated with a greater expectation of pain (ß = 0.5; standard error [SE] = 0.005; 95% confidence interval [CI]: 0.003-0.027; P < .05), and a slower expectation for recovery (ß = -0.5; SE = 0.004; 95% CI: -0.021 to -0.001; P < .05) after breast reconstruction. Latency from cancer diagnosis to reconstruction was associated with an increase in preoperative psychosocial well-being (ß = 0.578; SE 0.009; 95% CI: 0.002-0.046; P < .05). CONCLUSION: Delaying breast reconstruction may negatively impact patient expectations of postoperative pain and recovery. Educational interventions aimed at understanding and managing patient expectations in the preoperative period may improve health-related quality of life and patient-related outcomes following initial breast cancer surgery.

OBJECTIF: La compréhension des attentes des patientes est prédictive de meilleurs résultats cliniques après une reconstruction mammaire. Jusqu'à présent, aucune étude n'a porté sur la manière dont les attentes des patientes à l'égard de la reconstruction mammaire et de la qualité de vie liée à la santé avant l'opération varient dans le temps à compter du diagnostic de cancer du sein. MÉTHODOLOGIE: Les femmes qui ont consulté le cabinet d'un seul chirurgien en vue d'une reconstruction mammaire sur une période de 13 mois ont participé à la présente étude transversale. Les patientes ont été invitées à remplir de manière prospective les modules BREAST-Q sur les attentes préopératoires et la reconstruction. Les chercheurs ont ensuite procédé à un examen rétrospectif des dossiers des patients admissibles, puis ont colligé des données sur la démographie des patients, les facteurs liés au cancer et les morbidités associées. Ils ont transformé les scores BREAST-Q à l'aide du modèle de Rasch équivalent. Ils ont construit des modèles de régression linéaire multivariés pour évaluer l'association entre les scores BREAST-Q et la période écoulée depuis le diagnostic de cancer. RÉSULTATS: Soixante-cinq patientes respectaient les critères d'inclusion. Elles se caractérisaient par un âge moyen de 53 ± 11 ans (34 à 79 ans) et un indice de masse corporelle moyen de 28 ± 6 (19 à 49). La plupart des patientes ont été traitées par mastectomie (58 %) ou lumpectomie (23 %). Au moment de l'analyse rétrospective des dossiers, 29 (43 %) avaient subi une reconstruction, dont la plupart avaient été retardées (59 %). La latence moyenne entre le diagnostic de cancer et la reconstruction était de 685 ± 867 jours (plage de 28 à 3 322 jours). La latence entre le diagnostic de cancer et la reconstruction s'associait à une plus grande anticipation de la douleur (ß=0,5; ÉT=0,005; intervalle de confiance [IC] à 95 % de 0,003 à 0,027; P<0,05) et à des anticipations plus basses envers la convalescence (ß = -0,5; ÉT = 0,004; IC à 95 % de -0,021 à -0,001; P<0,05) après la reconstruction mammaire. La latence entre le diagnostic de cancer et la reconstruction était liée à une augmentation du bien-être psychosocial préopératoire (ß = 0,578; ÉT = 0,009; IC à 95 % de 0,002 à 0,046; P<0,05). CONCLUSION: Le report de la reconstruction mammaire peut avoir un effet négatif sur l'anticipation des patientes à l'égard de la douleur préopératoire et de la convalescence. Des interventions pédagogiques pour comprendre et gérer les attentes des patientes pendant la période préopératoire peuvent améliorer la qualité de vie liée à la santé et les résultats cliniques des patientes après la chirurgie initiale d'un cancer du sein.

A Randomized Controlled Trial Comparing Alloderm-RTU with DermACELL in Immediate Subpectoral Implant-Based Breast Reconstruction.

BACKGROUND: The effectiveness of different acellular dermal matrices (ADM) used for implant-based reconstruction immediately following mastectomy is an important clinical question. A prospective randomized clinical trial was performed to evaluate the superiority of DermACELL over Alloderm-RTU in reducing drain duration. METHODS: Patients undergoing mastectomy with subpectoral immediate and permanent implant-based breast reconstruction were randomized to Alloderm-RTU or DermACELL. The primary outcome was seroma formation, measured by the duration of postoperative drain placement. Secondary outcomes included: post drain removal seroma aspiration, infection, redbreast syndrome, wound dehiscence, loss of the implant, and unplanned return to the operating room. RESULTS: 62 patients were randomized for 81 mastectomies (41 Alloderm-RTU, 40 DermACELL). Baseline characteristics were similar. There was no statistically significant difference in mean drain duration (p = 0.16), with a trend towards longer duration in the Alloderm-RTU group (1.6 days; 95%CI, 0.7 to 3.9). The overall rate of minor and major complications were statistically similar between the two groups; although patients with Alloderm-RTU had 3 times as many infections requiring antibiotics (7.9% vs. 2.5%) with a risk difference of 5.4 (95%CI -4.5 to 15.2), and twice as many unplanned returns to the operating room (15.8% vs. 7.5%) with a risk difference of 8.3 (95% CI -5.9 to 22.5) as DermACELL. CONCLUSION: This is the first prospective randomized clinical trial comparing the two most commonly used human-derived ADMs. There was no statistically significant difference in drain duration, minor, or major complications between DermACELL over Alloderm-RTU in immediate subpectoral permanent implant-based breast reconstruction post-mastectomy.

Ambulatory latissimus dorsi flap breast reconstruction: A prospective cohort study of an enhanced recovery after surgery (ERAS) protocol.

PURPOSE: Enhanced recovery after surgery (ERAS) protocols improve quality of recovery and decrease length of stay for patients undergoing both alloplastic and autologous breast reconstruction. Their use in latissimus dorsi (LD) flap reconstruction has not been well established. The purpose of this study was to compare postoperative outcomes, length of stay, and total costs in a prospectively enrolled group of patients who underwent LD flap breast reconstruction using an ERAS protocol to those of a retrospective cohort of patients who were treated with a traditional recovery after surgery (TRAS) protocol. METHODS: In a prospective cohort study conducted from 2016 to 2019, an ERAS protocol was implemented for patients undergoing LD flap breast reconstruction. The primary outcome was 24-h discharge, and secondary outcomes were readmission rate, complications, and quality of recovery. Outcomes of patients who underwent LD flap reconstruction with the ERAS protocol were compared with those of a retrospective cohort of patients who underwent LD flap reconstruction with TRAS protocols. RESULTS: Twenty patients enrolled in the ERAS group were compared with 58 patients in the TRAS group. Postoperatively, 100% of ERAS patients were discharged within 24 h (60% on the same day) as compared to 21% (9% on the same day) in the TRAS group (p<0.0001). Minor and major complication rates were similar (30% ERAS vs. 33% TRAS and 20% ERAS vs. 10% TRAS, respectively, p > 0.05). There was significant reduction in length of stay and total cost between the two groups (6.4 h vs. 58.5 h (p = 0.003) and $5,666.80 vs. $8890.25 (p = 0.0003), respectively). CONCLUSIONS: Breast reconstruction with the LD flap can be performed safely and effectively in the ambulatory setting. The implementation of an ERAS protocol was successful in discharging all patients home within 24 h, and the expedited discharge was associated with an acceptable complication rate, reduced length of stay, and excellent quality of recovery. Conversion from TRAS to ERAS protocols was associated with $3,223.45 cost savings per patient.

Fluorescence-based multi-parameter approach to characterize dynamics of organic carbon, faecal bacteria and particles at alpine karst springs.

Karst springs, especially in alpine regions, are important for drinking water supply but also vulnerable to contamination, especially after rainfall events. This high variability of water quality requires rapid quantification of contamination parameters. Here, we used a fluorescence-based multi-parameter approach to characterize the dynamics of organic carbon, faecal bacteria, and particles at three alpine karst springs. We used excitation emission matrices (EEMs) to identify fluorescent dissolved organic material (FDOM). At the first system, peak A fluorescence and total organic carbon (TOC) were strongly correlated (Spearman's rs of 0.949), indicating that a large part of the organic matter is related to humic-like substances. Protein-like fluorescence and cultivation-based determination of coliform bacteria also had a significant correlation with rs=0.734, indicating that protein-like fluorescence is directly related to faecal pollution. At the second system, which has two spring outlets, the absolute values of all measured water-quality parameters were lower; there was a significant correlation between TOC and humic-like fluorescence (rs=0.588-0.689) but coliform bacteria and protein-like fluorescence at these two springs were not correlated. Additionally, there was a strong correlation (rs=0.571-0.647) between small particle fractions (1.0 and 2.0µm), a secondary turbidity peak and bacteria. At one of these springs, discharge was constant despite the reaction of all other parameters to the rainfall event. Our results demonstrated that i) all three springs showed fast and marked responses of all investigated water-quality parameters after rain events; ii) a constant discharge does not necessarily mean constant water quality; iii) at high contamination levels, protein-like fluorescence is a good indicator of bacterial contamination, while at low contamination levels no correlation between protein-like fluorescence and bacterial values was detected; and iv) a combination of fluorescence measurements and particle-size analysis is a promising approach for a rapid assessment of organic contamination, especially relative to time-consuming conventional bacterial determination methods.

Comparing the thoracodorsal and internal mammary vessels as recipients for microsurgical autologous breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: Our aim was to determine whether the thoracodorsal (Td) vessels have comparable clinical outcomes to the internal mammary (IM) vessels as recipients for autologous free tissue transfer for breast reconstruction. METHODS: Systematic searches of MEDLINE, EMBASE, CENTRAL, and World of Science from inception to June 2016 were performed by two independent reviewers. Studies that included adult females undergoing autologous free tissue transfer for breast reconstruction were selected. The two comparison groups were the use of IM or Td as recipient vessels. Our primary outcome was rate of flap survival. We assessed the methodologic quality of included studies using the JADAD and MINOR scales. RESULTS: A total of 1897 patients underwent 2644 free abdominal flap tissue transfer in the 10 articles that were included in our analysis. There was one randomized controlled study (Jadad score 2/5) and 9 nonrandomized controlled studies (MINORS scores 11-19/24). There was no difference between the uses of either vessel in terms of flap loss (1.18; 95% CI 0.71-1.95). Complication rate among the IM vessels ranged from 5 to 12%, compared with 3.4-12% among Td vessels. Hematoma and seroma rates were variable. Fat necrosis was higher with Td vessels in two studies. Performing Td vessels anastomosis was associated with shorter operative time and higher risk of encountering unusable vessel. CONCLUSION: Both recipient vessels are safe, reliable and demonstrate equivocal results in the absence of contraindications. Utilizing either as a first-line vessel is reasonable, depending on surgeons' preference or certain clinical scenarios. QUESTION: Therapeutic, Level of evidence: III.

Breast reconstruction following conservative mastectomies: predictors of complications and outcomes.

Breast reconstruction can be performed using a variety of techniques, most commonly categorized into an alloplastic approach or an autologous tissue method. Both strategies have certain risk factors that influence reconstructive outcomes and complication rates. In alloplastic breast reconstruction, surgical outcomes and complication rates are negatively impacted by radiation, smoking, increased body mass index (BMI), hypertension, and prior breast conserving therapy. Surgical factors such as the type of implant material, undergoing immediate breast reconstruction, and the use of fat grafting can improve patient satisfaction and aesthetic outcomes. In autologous breast reconstruction, radiation, increased BMI, certain previous abdominal surgery, smoking, and delayed reconstruction are associated with higher complication rates. Though a pedicled transverse rectus abdominis myocutaneous (TRAM) flap is the most common type of flap used for autologous breast reconstruction, pedicled TRAMs are more likely to be associated with fat necrosis than a free TRAM or deep inferior epigastric perforator (DIEP) flap. Fat grafting can also be used to improve aesthetic outcomes in autologous reconstruction. This article focuses on factors, both patient and surgical, that are predictors of complications and outcomes in breast reconstruction.

Synthesis of hetero-polymer functionalized nanocarriers by combining surface-initiated ATRP and RAFT polymerization.

Smart nanocarriers are created based on a bi-functional hetero-initiator for RAFT and ATRP technique, bi-functionalizing mesoporous silica nanoparticles with two polymer types. The pH-dependent behavior of PDEAEMA as the gatekeeper polymer is verified by electrokinetic measurements and a controlled release behavior is demonstrated using doxorubicin as the drug.

How acidic is the lidocaine we are injecting, and how much bicarbonate should we add?

BACKGROUND: The infiltration of local anesthetics can be painful, which is likely due, in part, to their acidity. In spite of a Cochrane study that recommended neutralizing lidocaine with bicarbonate to decrease the pain of injection, not many surgeons have adopted the practice, and there are many 'recipes' for how much bicarbonate one should add. OBJECTIVE: To determine the acidity of lidocaine and the correct ratio of bicarbonate that should be added to neutralize lidocaine to achieve body pH. METHODS: Fifty samples each of commonly used anesthetics (lidocaine 1% and 2%, with and without epinephrine 1:100,000) were obtained and tested for pH. Data were also analyzed according to whether the vials had been previously opened. Ten additional samples of lidocaine 1% with 1:100,000 epinephrine were titrated against sodium bicarbonate 8.4% and tested for pH and the presence of precipitate. RESULTS: A solution of 1% lidocaine with 1:100,000 epinephrine had a mean (± SD) pH of 4.24±0.42, and 2% lidocaine with 1:100,000 epinephrine had a mean pH of 3.93±0.43. Plain 1% lidocaine had a pH of 6.09±0.16, and plain 2% lidocaine had a pH of 6.00±0.27. Epinephrine-containing solutions were more acidic when they had been previously opened. One per cent lidocaine with epinephrine required 8.4% sodium bicarbonate at a ratio of 1.1 mL:10 mL to 1.8 mL:10 mL to achieve the target tissue pH of 7.38 to 7.62. CONCLUSION: Lidocaine with epinephrine was approximately 1000 times more acidic than subcutaneous tissue. The addition of bicarbonate to the local anesthetic solution is simple to perform and is inexpensive. The proper volume ratio of 8.4% sodium bicarbonate to 1% lidocaine with 1:100,000 epinephrine is approximately 1 mL:10 mL. Surgeons should be more aware of the simplicity and value of buffering with bicarbonate to decrease the pain of injection.

HISTORIQUE: L'infiltration d'anesthésiques locaux peut être douloureuse, ce qui est probablement causé, en partie, par leur acidité. Même si une étude antérieure a recommandé de neutraliser la lidocaïne avec du bicarbonate pour atténuer la douleur de l'injection, peu de chirurgiens ont adopté cette pratique, et il existe de nombreuses « recettes ¼ de la quantité de bicarbonate à ajouter. OBJECTIF: Déterminer l'acidité de la lidocaïne et le bon ratio de bicarbonate à y ajouter pour la neutraliser et parvenir au pH corporel. MÉTHODOLOGIE: Les chercheurs ont obtenu 50 échantillons de chacun des anesthésiques couramment utilisés (lidocaïne 1% et 2%, avec et sans dilution d'adrénaline 1:100 000) et en ont vérifié le pH. Ils ont également analysé les données pour vérifier si les fioles avaient été ouvertes au préalable. Ils ont titré dix échantillons supplémentaires de lidocaïne1% contenant de l'adrénaline 1:100 000 à l'aide de bicarbonate de sodium 8,4 %, puis ont vérifié le pH et la présence de précipité. RÉSULTATS: Une dilution 1:100 000 de lidocaïne 1 % contenant de l'adrénaline avait un pH moyen (±ÉT) de 4,24±0,42, et la lidocaïne 2 % contenant de l'adrénaline, un pH de 3,93±0,43. La lidocaïne 1 % seule avait un pH de 6,09±0,16, et la lidocaïne 2 % seule, un pH de 6,00±0,27. Les solutions contenant de l'adrénaline étaient plus acides lorsqu'elles avaient été ouvertes au préalable. De la lidocaïne 1 % contenant de l'adrénaline devait contenir 8,4 % de bicarbonate de sodium à une dilution de 1,1:10 à 1,8:10 pour parvenir au pH tissulaire ciblé de 7,38 à 7,62. CONCLUSION: La lidocaïne contenant de l'adrénaline était environ 1 000 fois plus acide que les tissus sous-cutanés. Il est simple et peu coûteux d'ajouter du bicarbonate à une solution anesthésique locale. La bonne proportion entre le volume de bicarbonate de sodium 8,4 % et la lidocaïne 1 % accompagnée d'adrénaline 1:100 000 est d'environ 1:10. Les chirurgiens devraient connaître la simplicité et la valeur d'utiliser une solution tampon de bicarbonate pour atténuer la douleur de l'injection.

SNAP-23 and syntaxin-3 are required for chemokine release by mature human mast cells.

Mast cells play a key role in allergic and non-allergic disease by releasing a broad array of mediators. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs) are necessary for membrane fusion events during mast cell exocytosis. We have shown recently that the SNAREs SNAP-23, syntaxin (STX)-4, vesicle associated membrane protein (VAMP)-7, and VAMP-8 are required for release of pre-stored histamine by mast cells. Here we analyze the involvement of different SNARE isoforms in exocytosis of de novo synthesized chemokines in mast cells isolated from human intestine. Following IgE receptor cross-linking, mast cells released substantial amounts of the chemokines CXCL8, CCL2, CCL3, and CCL4. Measurement of SNARE mRNA expression revealed only a moderate up-regulation of mRNA for STX-4 after stimulation for 1.5h. Inhibition of SNAP-23 or STX-3 abolished IgE mediated release of the chemokines CXCL8, CCL2, CCL3, and CCL4. In contrast, blocking of STX-2, or VAMP-3 did not affect the chemokine release. Inhibition of STX-4 or VAMP-8 resulted in a reduced release of CXCL8, but not of CCL2, CCL3, or CCL4. Inhibition of STX-6 attenuated the release of CXCL8 and CCL2, inhibition of VAMP-7 that of CCL3. In summary, STX-3 and SNAP-23 are crucial for the release of all chemokines in mature human mast cells whereas other SNAREs affect only release of selected chemokines.

Determination of correct implant size in radial head arthroplasty to avoid overlengthening: surgical technique.

BACKGROUND: Insertion of a radial head implant that results in radial overlengthening has been associated with altered elbow kinematics, increased radiocapitellar joint forces, capitellar erosions, early-onset arthritis, and loss of elbow flexion. The purpose of this study was to identify clinical and radiographic features that may be used to diagnose overlengthening of the radius intraoperatively and on postoperative radiographs. METHODS: Radial head implants of varying thicknesses were inserted into seven cadaver specimens, which were then assessed clinically and radiographically. Eight stages were examined: the intact specimen (stage 1); repair of the lateral collateral ligament (stage 2); radial head resection with repair of the lateral collateral ligament (stage 3); insertion of an implant of the correct thickness (stage 4); and insertion of an implant that resulted in radial overlengthening of 2 mm (stage 5), 4 mm (stage 6), 6 mm (stage 7), or 8 mm (stage 8). The specimens were tested with and without muscle loading to simulate resting muscle tone and surgical paralysis, respectively. At each stage, radiographs were made to measure the ulnohumeral joint space and the lateral ulnohumeral joint was visually assessed. RESULTS: We identified no difference, with regard to medial ulnohumeral joint incongruity as seen radiographically, among stages 1 through 6 during the tests with muscle loading. A significant difference in medial ulnohumeral joint incongruity was found in stages 7 (p = 0.003) and 8 (p < 0.001). The clinical (visually assessed) lateral ulnohumeral joint space gap was negligible in stages 1 through 4 but increased significantly at all stages involving overlengthening (gross gap, 0.9 mm with 2 mm of erlengthening [p = 0.005], 2.3 mm with 4 mm of overlengthening [p < 0.001], 3.4 mm with 6 mm [p < 0.001], and 4.7 mm with 8 mm [p < 0.001]). CONCLUSIONS: Incongruity of the medial ulnohumeral joint becomes apparent radiographically only after overlengthening of the radius by ≥6 mm. Intraoperative visualization of a gap in the lateral ulnohumeral joint is a reliable indicator of overlengthening following the insertion of a radial head prosthesis.

Determination of correct implant size in radial head arthroplasty to avoid overlengthening.

BACKGROUND: Insertion of a radial head implant that results in radial overlengthening has been associated with altered elbow kinematics, increased radiocapitellar joint forces, capitellar erosions, early-onset arthritis, and loss of elbow flexion. The purpose of this study was to identify clinical and radiographic features that may be used to diagnose overlengthening of the radius intraoperatively and on postoperative radiographs. METHODS: Radial head implants of varying thicknesses were inserted into seven cadaver specimens, which were then assessed clinically and radiographically. Eight stages were examined: the intact specimen (stage 1); repair of the lateral collateral ligament (stage 2); radial head resection with repair of the lateral collateral ligament (stage 3); insertion of an implant of the correct thickness (stage 4); and insertion of an implant that resulted in radial overlengthening of 2 mm (stage 5), 4 mm (stage 6), 6 mm (stage 7), or 8 mm (stage 8). The specimens were tested with and without muscle loading to simulate resting muscle tone and surgical paralysis, respectively. At each stage, radiographs were made to measure the ulnohumeral joint space and the lateral ulnohumeral joint was visually assessed. RESULTS: We identified no difference, with regard to medial ulnohumeral joint incongruity as seen radiographically, among stages 1 through 6 during the tests with muscle loading. A significant difference in medial ulnohumeral joint incongruity was found in stages 7 (p = 0.003) and 8 (p < 0.001). The clinical (visually assessed) lateral ulnohumeral joint space gap was negligible in stages 1 through 4 but increased significantly at all stages involving overlengthening (gross gap, 0.9 mm with 2 mm of overlengthening [p = 0.005], 2.3 mm with 4 mm of overlengthening [p < 0.001], 3.4 mm with 6 mm [p < 0.001], and 4.7 mm with 8 mm [p < 0.001]). CONCLUSIONS: Incongruity of the medial ulnohumeral joint becomes apparent radiographically only after overlengthening of the radius by >or=6 mm. Intraoperative visualization of a gap in the lateral ulnohumeral joint is a reliable indicator of overlengthening following the insertion of a radial head prosthesis.

Vesicle associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells.

Mediator release from mast cells (MC) is a crucial step in allergic and non-allergic inflammatory disorders. However, the final events in response to activation leading to membrane fusion and thereby facilitating degranulation have hitherto not been analyzed in human MC. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNARE) represent a highly conserved family of proteins that have been shown to mediate intracellular membrane fusion events. Here, we show that mature MC isolated from human intestinal tissue express soluble N-ethylmaleide sensitive factor attachment protein (SNAP)-23, Syntaxin (STX)-1B, STX-2, STX-3, STX-4, and STX-6 but not SNAP-25. Furthermore, we found that primary human MC express substantial amounts of vesicle associated membrane protein (VAMP)-3, VAMP-7 and VAMP-8 and, in contrast to previous reports about rodent MC, only low levels of VAMP-2. Furthermore, VAMP-7 and VAMP-8 were found to translocate to the plasma membrane and interact with SNAP-23 and STX-4 upon activation. Inhibition of SNAP-23, STX-4, VAMP-7 or VAMP-8, but not VAMP-2 or VAMP-3, resulted in a markedly reduced high-affinity IgE receptor-mediated histamine release. In summary, our data show that mature human MC express a specific pattern of SNARE and that VAMP-7 and VAMP-8, but not VAMP-2, are required for rapid degranulation.