Hyperbaric oxygen treatment for mastectomy flap ischaemia: A case series of 50 breasts.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) has been suggested as an effective intervention to limit necrosis of ischaemic skin flaps after mastectomy. The purpose of this study was to evaluate outcomes of HBOT in the largest series of patients to date with mastectomy flap ischaemia. METHODS: A retrospective analysis was performed of 50 breasts requiring HBOT for mastectomy flap ischaemia. The severity of the ischaemia or necrosis was evaluated by four independent observers using the skin ischaemia necrosis (SKIN) score. Multivariate logistic regression analyses were used to assess associations between risk factors and re-operation. RESULTS: HBOT was started a median of 3 days (range 1-23) after surgery and continued for a median of 12 sessions (range 6-22). The breast SKIN surface area scores (n = 175 observations by the independent observers) improved in 34% (of observations) and the depth scores deteriorated in 42% (both P < 0.01). Both the surface area and depth scores were associated with the need for re-operation: higher scores, reflecting more severe necrosis of the mastectomy flap, were associated with increased need for re-operation. Twenty-nine breasts (58%) recovered without additional operation. Pre-operative radiotherapy (OR 7.2, 95% CI 1.4-37.3) and postoperative infection (OR 15.4, 95% CI 2.6-89.7) were risk factors for re-operation in multivariate analyses. CONCLUSIONS: In this case series, the surface area of the breast affected by ischaemia decreased during HBOT, and most breasts (58%) did not undergo an additional operation. A randomised control trial is needed to confirm or refute the possibility that HBOT improves outcome in patients with mastectomy flap ischaemia.

The effect of hyperbaric oxygen treatment on late radiation tissue injury after breast cancer: A case-series of 67 patients.

INTRODUCTION: Late radiation tissue injury (LRTI) after breast cancer may benefit from hyperbaric oxygen treatment (HBOT). This study aimed to report the LRTI symptom scores up to 12 months after HBOT and identify risk factors for poor scores. METHODS: A case-series of 67 patients who underwent a mean of 44 sessions of HBOT was analysed. LRTI symptoms were scored at four time points using the LENT-SOMA scale (Late Effects in Normal Tissues - Subjective, Objective, Management, and Analytic), a visual analog scale for pain, and the range of shoulder motion. RESULTS: Between starting HBOT and 12 months after HBOT 57 patients (85%) reported at least one point improvement in their LENT-SOMA score. Median pain and fibrosis scores improved significantly between the start and end of HBOT (P < 0.001), and remained stable three and 12 months after HBOT. The median breast oedema score improved significantly 12 months after HBOT (P = 0.003). Median shoulder abduction increased significantly from 90 to 165 degrees (P = 0.001) and median shoulder anteflexion increased significantly from 115 to 150 degrees (P = 0.004). Various risk factors were identified for poor scores despite HBOT; the most common risk factor was a poor score at start of HBOT. CONCLUSIONS: In this case-series, patients who underwent HBOT for LRTI after breast cancer reported significant improvement in pain, fibrosis, oedema, and shoulder movement. The improvement persisted up to 12 months after HBOT. A poor score at the start of HBOT was predictive for a poor score 12 months after HBOT.

Stratification of chronic and complex wounds according to healing characteristics: a retrospective study.

OBJECTIVE: Wound risk-stratified analyses are clinically relevant as they can assist in identifying hard-to-heal wounds. The aim of the study is to develop risk categories for wound healing based on a limited number of reliably recordable clinical data. METHOD: This retrospective study used observational data. The primary outcome measure was wound healing at the end of treatment and the secondary outcome measure was the time to wound healing. A stratification model using regression analyses was developed to assign the patients to risk categories for wound healing and the time-to-heal. RESULTS: The study cohort comprised of 540 patients. The most common wound diagnoses were diabetic ulcers, wounds in irradiated areas and wound dehiscence after surgery. Average wound duration before starting treatment at the wound centre was 11.7 months. Healing was achieved in 382 (71%) wounds, after an average treatment time of 4.4 months. A total of four risk categories for wound healing were developed by combining wound diagnosis (favourable versus unfavourable) and duration (<3 months versus >3 months). These risk categories demonstrated healing percentages ranging from 69-97% (p=0.0004) and mean time-to-healing varying from 2.7-5.9 months (p=0.01). CONCLUSION: Using two clinical wound variables, diagnosis and duration, stratification categories were identified with significant associations with wound healing outcomes. Longer wound duration and unfavourable diagnoses, when combined into unfavourable risk categories, were associated with a lower percentage of wound healing and a longer treatment time until healing.

Reliability of the Dutch Cleft Speech Evaluation Test and Conversion to the Proposed Universal Scale.

The Dutch cleft speech evaluation test (DCSET) has been implemented by the speech-language pathologists nationwide in the Netherlands since 2003, but the inter- and intrarater reliability was unknown. Two speech-language pathologists experienced in evaluating cleft speech assessed audio recordings of 20 children with cleft speech using the DCSET, and reassessed the recordings 2 weeks later. Intra- and interrater reliability was calculated, but found to be unacceptable after the first phase of this study using audio recordings. Following consensus training and some modifications in the scoring scales, the study was repeated using video recordings of 20 different children with cleft speech. Results from the second phase of this study using standardized video recordings showed fair, moderate, and good reliability on different subsets of the DCSET. Intrarater reliability (Kappa 0.59-1.00) was greater than interrater reliability (Kappa 0.33-0.79). Interrater reliability agreement was good (Kappa 0.63-0.79) for consonant production errors and speech understandability and acceptability, moderate (Kappa 0.59) for the resonance of the nasal passage, and fair (Kappa 0.33-0.37) for the resonance of the mixed and denasal passages. Subsequently, an algorithm was made to convert the DCSET scales to universal scales for international comparison of cleft speech as suggested by Henningsson et al in 2008.

Use of epidermal skin grafts in chronic wounds: a case series.

In stalled, chronic wounds, more aggressive and proactive wound closure efforts are needed. We describe adjunctive use of epidermal grafting in patients with chronic wounds. Wound bed preparation consisted of surgical necrotectomy or sharp debridement, hyperbaric oxygen therapy, negative pressure wound therapy, compression therapy, platelet-rich plasma therapy and/or heparan sulphate agents. Epidermal grafts were harvested from the patient's thigh and applied to the wound. Wound and donor site healing was monitored. A total of 78 patients (average age = 64·1 ± 15·6 years) were included in the study. Common comorbidities included hypertension (47·4%), venous insufficiency (37·2%) and obesity (28·2%). Average wound duration was 13·2 months (range: 0·3-180 months). The most common wound types were dehiscence (29·5%), radiation ulcer (24·4%) and venous ulcer (17·9%). Total time from epidermal grafting to wound closure was 10·0 ± 7·3 weeks. Of the 78 wounds, 66 (84·6%) reached full wound closure (49 < 3 months, 16 > 3 months, 1 without time data). Of 78 wounds, 10 (12·8%) underwent partial wound healing, while 2 wounds (2/78; 2·6%) remained unhealed. These results suggest that wound surface reduction can be achieved by proactive early application of biological therapies and epidermal skin grafts, which may help decrease time to wound healing.

Self-reported speech problems in adolescents and young adults with 22q11.2 deletion syndrome: a cross-sectional cohort study.

BACKGROUND: Speech problems are a common clinical feature of the 22q11.2 deletion syndrome. The objectives of this study were to inventory the speech history and current self-reported speech rating of adolescents and young adults, and examine the possible variables influencing the current speech ratings, including cleft palate, surgery, speech and language therapy, intelligence quotient, and age at assessment. METHODS: In this cross-sectional cohort study, 50 adolescents and young adults with the 22q11.2 deletion syndrome (ages, 12-26 years, 67% female) filled out questionnaires. A neuropsychologist administered an age-appropriate intelligence quotient test. The demographics, histories, and intelligence of patients with normal speech (speech rating=1) were compared to those of patients with different speech (speech rating>1). RESULTS: Of the 50 patients, a minority (26%) had a cleft palate, nearly half (46%) underwent a pharyngoplasty, and all (100%) had speech and language therapy. Poorer speech ratings were correlated with more years of speech and language therapy (Spearman's correlation= 0.418, P=0.004; 95% confidence interval, 0.145-0.632). Only 34% had normal speech ratings. The groups with normal and different speech were not significantly different with respect to the demographic variables; a history of cleft palate, surgery, or speech and language therapy; and the intelligence quotient. CONCLUSIONS: All adolescents and young adults with the 22q11.2 deletion syndrome had undergone speech and language therapy, and nearly half of them underwent pharyngoplasty. Only 34% attained normal speech ratings. Those with poorer speech ratings had speech and language therapy for more years.

Platybasia in 22q11.2 deletion syndrome is not correlated with speech resonance.

BACKGROUND: An abnormally obtuse cranial base angle, also known as platybasia, is a common finding in patients with 22q11.2 deletion syndrome (22q11DS). Platybasia increases the depth of the velopharynx and is therefore postulated to contribute to velopharyngeal dysfunction. Our objective was to determine the clinical significance of platybasia in 22q11DS by exploring the relationship between cranial base angles and speech resonance. METHODS: In this retrospective chart review at a tertiary hospital, 24 children (age, 4.0-13.1 years) with 22q11.2DS underwent speech assessments and lateral cephalograms, which allowed for the measurement of the cranial base angles. RESULTS: One patient (4%) had hyponasal resonance, 8 (33%) had normal resonance, 10 (42%) had hypernasal resonance on vowels only, and 5 (21%) had hypernasal resonance on both vowels and consonants. The mean cranial base angle was 136.5° (standard deviation, 5.3°; range, 122.3-144.8°). The Kruskal-Wallis test showed no significant relationship between the resonance ratings and cranial base angles (P=0.242). Cranial base angles and speech ratings were not correlated (Spearman correlation=0.321, P=0.126). The group with hypernasal resonance had a significantly more obtuse mean cranial base angle (138° vs. 134°, P=0.049) but did not have a greater prevalence of platybasia (73% vs. 56%, P=0.412). CONCLUSIONS: In this retrospective chart review of patients with 22q11DS, cranial base angles were not correlated with speech resonance. The clinical significance of platybasia remains unknown.

Exploring a neurogenic basis of velopharyngeal dysfunction in Tbx1 mutant mice: no difference in volumes of the nucleus ambiguus.

OBJECTIVE: Velopharyngeal hypotonia seems to be an important factor in velopharyngeal dysfunction in 22q11.2 deletion syndrome, but the etiology is not understood. Because TBX1 maps within the typical 22q11.2 deletion and Tbx1-deficient mice phenocopy many findings in patients with the 22q11.2 deletion syndrome, TBX1 is considered the major candidate gene in the etiology of these defects. Tbx1 heterozygosity in mice results in abnormal vocalization 7 days postnatally, suggestive of velopharyngeal dysfunction. Previous case-control studies on muscle specimens from patients and mice revealed no evidence for a myogenic cause of velopharyngeal dysfunction. Velopharyngeal muscles are innervated by cranial nerves that receive signals from the nucleus ambiguus in the brainstem. In this study, a possible neurogenic cause underlying velopharyngeal dysfunction in Tbx1 heterozygous mice was explored by determining the size of the nucleus ambiguus in Tbx1 heterozygous and wild type mice. METHODS: The cranial motor nuclei in the brainstems of postnatal day 7 wild type (n=4) and Tbx1 heterozygous (n=4) mice were visualized by in situ hybridization on transverse sections to detect Islet-1 mRNA, a transcription factor known to be expressed in motor neurons. The volumes of the nucleus ambiguus were calculated. RESULTS: No substantial histological differences were noted between the nucleus ambiguus of the two groups. Tbx1 mutant mice had mean nucleus ambiguus volumes of 4.6 million µm(3) (standard error of the mean 0.9 million µm(3)) and wild type mice had mean volumes of 3.4 million µm(3) (standard error of the mean 0.6 million µm(3)). Neither the difference nor the variance between the means were statistically significant (t-test p=0.30, Levene's test p=0.47, respectively). CONCLUSIONS: Based on the histology, there is no difference or variability between the volumes of the nucleus ambiguus of Tbx1 heterozygous and wild type mice. The etiology of velopharyngeal hypotonia and variable speech in children with 22q11.2 deletion syndrome warrants further investigation.

In search of the optimal surgical treatment for velopharyngeal dysfunction in 22q11.2 deletion syndrome: a systematic review.

BACKGROUND: Patients with the 22q11.2 deletion syndrome (22qDS) and velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery. This systematic review seeks to determine whether a particular surgical procedure results in superior speech outcome or less morbidity. METHODOLOGY/ PRINCIPAL FINDINGS: A combined computerized and hand-search yielded 70 studies, of which 27 were deemed relevant for this review, reporting on a total of 525 patients with 22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4 evidence. The methodological quality of these studies was assessed using criteria based on the Cochrane Collaboration's tool for assessing risk of bias. Heterogeneous groups of patients were reported on in the studies. The surgical procedure was often tailored to findings on preoperative imaging. Overall, 50% of patients attained normal resonance, 48% attained normal nasal emissions scores, and 83% had understandable speech postoperatively. However, 5% became hyponasal, 1% had obstructive sleep apnea (OSA), and 17% required further surgery. There were no significant differences in speech outcome between patients who underwent a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty, Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was a trend that a lower percentage of patients attained normal resonance after a fat injection or palatoplasty than after the more obstructive pharyngoplasties (11-18% versus 44-62%, p = 0.08). Only patients who underwent pharyngeal flaps or sphincter pharyngoplasties incurred OSA, yet this was not statistically significantly more often than after other procedures (p = 0.25). More patients who underwent a palatoplasty needed further surgery than those who underwent a pharyngoplasty (50% versus 7-13%, p = 0.03). CONCLUSIONS/ SIGNIFICANCE: In the heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can be made to minimize the morbidity of further surgery by choosing to perform a pharyngoplasty directly instead of only a palatoplasty.

Histology of the pharyngeal constrictor muscle in 22q11.2 deletion syndrome and non-syndromic children with velopharyngeal insufficiency.

Plastic surgeons aim to correct velopharyngeal insufficiency manifest by hypernasal speech with a velopharyngoplasty. The functional outcome has been reported to be worse in patients with 22q11.2 deletion syndrome than in patients without the syndrome. A possible explanation is the hypotonia that is often present as part of the syndrome. To confirm a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome, specimens of the pharyngeal constrictor muscle were taken from children with and without the syndrome. Histologic properties were compared between the groups. Specimens from the two groups did not differ regarding the presence of increased perimysial or endomysial space, fiber grouping by size or type, internalized nuclei, the percentage type I fibers, or the diameters of type I and type II fibers. In conclusion, a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome could not be confirmed.

A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients.

INTRODUCTION: Following trauma, patients may suffer an overwhelming pro-inflammatory response and immune paralysis resulting in infection and multiple organ failure (MOF). Various potentially immunomodulative interventions have been tested. The objective of this study is to systematically review the randomized controlled trials (RCTs) that investigate the effect of potentially immunomodulative interventions in comparison to a placebo or standard therapy on infection, MOF, and mortality in trauma patients. METHODS: A computerized search of MEDLINE, the Cochrane CENTRAL Register of Controlled Trials, and EMBASE yielded 502 studies, of which 18 unique RCTs were deemed relevant for this study. The methodological quality of these RCTs was assessed using a critical appraisal checklist for therapy articles from the Centre for Evidence Based Medicine. The effects of the test interventions on infection, MOF, and mortality rates and inflammatory parameters relative to the controls were recorded. RESULTS: In most studies, the inflammatory parameters differed significantly between the test and control groups. However, significant changes in infection, MOF, and mortality rates were only measured in studies testing immunoglobulin, IFN-γ, and glucan. CONCLUSIONS: Based on level 1b and 2b studies, administration of immunoglobulin, IFN-γ, or glucan have shown the most promising results to improve the outcome of trauma patients.