HOW WE DO IT: the Keystone flap for large skin defects: our experience with 30 consecutive cases.

BACKGROUND: The keystone perforator-based fasciocutaneous island flap is a method of locoregional skin defect reconstruction, consisting of two conjoined V to Y advancement flaps. In this article, we report a series of 30 consecutive cases in various body parts with the aim to demonstrate the versatility of the keystone flap in the reconstruction of various skin defects after removal of a suspected malignant skin lesion and evaluate our clinical experience while maintaining oncological safety and good aesthetic results. METHODS: Patients who underwent keystone flap reconstruction between January 2016 and January 2021 were retrospectively reviewed. Their demographics, operative details, oncological data and postoperative details were obtained from the institution's internal electronic patient records system. RESULTS: The majority of the skin defects were the result of an oncologic resection (97%, n = 29) and were located in the pretibial region (47%, n = 14). In five cases (17%) there was a need for a double keystone flap to cover the skin defect. One or more risk factors (hypertension, smoking, anticoagulation, …) were identified in 22 patients (73%). Minor complications (partial wound dehiscence, effusion or surgical site infection) occurred in ten cases (33%) which were resolved with conservative wound management or systemic antibiotics. There were no major postoperative flap-related complications such as flap failure or need for re-surgery. CONCLUSION: In our experience, the keystone island flap is an effective and reliable technique to attain a single stage tension-free closure of large skin defects. Due to its low technical complexity and high success rate, we consider it a feasible alternative to other reconstructive flaps and grafts for direct closure of secondary defects.

Quality improvement strategies to prevent falls in older adults: a systematic review and network meta-analysis.

BACKGROUND: Falls are a common occurrence and the most effective quality improvement (QI) strategies remain unclear. METHODS: We conducted a systematic review and network meta-analysis (NMA) to elucidate effective quality improvement (QI) strategies for falls prevention. Multiple databases were searched (inception-April 2017). We included randomised controlled trials (RCTs) of falls prevention QI strategies for participants aged ≥65 years. Two investigators screened titles and abstracts, full-text articles, conducted data abstraction and appraised risk of bias independently. RESULTS: A total of 126 RCTs including 84,307 participants were included after screening 10,650 titles and abstracts and 1210 full-text articles. NMA including 29 RCTs and 26,326 patients found that team changes was statistically superior in reducing the risk of injurious falls relative to usual care (odds ratio [OR] 0.57 [0.33 to 0.99]; absolute risk difference [ARD] -0.11 [95% CI, -0.18 to -0.002]). NMA for the outcome of number of fallers including 61 RCTs and 40 128 patients found that combined case management, patient reminders and staff education (OR 0.18 [0.07 to 0.47]; ARD -0.27 [95% CI, -0.33 to -0.15]) and combined case management and patient reminders (OR, 0.36 [0.13 to 0.97]; ARD -0.19 [95% CI, -0.30 to -0.01]) were both statistically superior compared to usual care. CONCLUSIONS: Team changes may reduce risk of injurious falls and a combination of case management, patient reminders, and staff education, as well as case management and patient reminders may reduce risk of falls. Our results can be tailored to decision-maker preferences and availability of resources. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42013004151).

Comparisons of Interventions for Preventing Falls in Older Adults: A Systematic Review and Meta-analysis.

Importance: Falls result in substantial burden for patients and health care systems, and given the aging of the population worldwide, the incidence of falls continues to rise. Objective: To assess the potential effectiveness of interventions for preventing falls. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Ageline databases from inception until April 2017. Reference lists of included studies were scanned. Study Selection: Randomized clinical trials (RCTs) of fall-prevention interventions for participants aged 65 years and older. Data Extraction and Synthesis: Pairs of reviewers independently screened the studies, abstracted data, and appraised risk of bias. Pairwise meta-analysis and network meta-analysis were conducted. Main Outcomes and Measures: Injurious falls and fall-related hospitalizations. Results: A total of 283 RCTs (159 910 participants; mean age, 78.1 years; 74% women) were included after screening of 10 650 titles and abstracts and 1210 full-text articles. Network meta-analysis (including 54 RCTs, 41 596 participants, 39 interventions plus usual care) suggested that the following interventions, when compared with usual care, were associated with reductions in injurious falls: exercise (odds ratio [OR], 0.51 [95% CI, 0.33 to 0.79]; absolute risk difference [ARD], -0.67 [95% CI, -1.10 to -0.24]); combined exercise and vision assessment and treatment (OR, 0.17 [95% CI, 0.07 to 0.38]; ARD, -1.79 [95% CI, -2.63 to -0.96]); combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30 [95% CI, 0.13 to 0.70]; ARD, -1.19 [95% CI, -2.04 to -0.35]); and combined clinic-level quality improvement strategies (eg, case management), multifactorial assessment and treatment (eg, comprehensive geriatric assessment), calcium supplementation, and vitamin D supplementation (OR, 0.12 [95% CI, 0.03 to 0.55]; ARD, -2.08 [95% CI, -3.56 to -0.60]). Pairwise meta-analyses for fall-related hospitalizations (2 RCTs; 516 participants) showed no significant association between combined clinic- and patient-level quality improvement strategies and multifactorial assessment and treatment relative to usual care (OR, 0.78 [95% CI, 0.33 to 1.81]). Conclusions and Relevance: Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of fall-prevention intervention may depend on patient and caregiver values and preferences.

Seeking effective interventions to treat complex wounds: an overview of systematic reviews.

BACKGROUND: Numerous, often multi-faceted regimens are available for treating complex wounds, yet the evidence of these interventions is recondite across the literature. We aimed to identify effective interventions to treat complex wounds through an overview of systematic reviews. METHODS: MEDLINE (OVID interface, 1946 until October 26, 2012), EMBASE (OVID interface, 1947 until October 26, 2012), and the Cochrane Database of Systematic Reviews (Issue 10 of 12, 2012) were searched on October 26, 2012. Systematic reviews that examined adults receiving care for their complex wounds were included. Two reviewers independently screened the literature, abstracted data, and assessed study quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. RESULTS: Overall, 99 systematic reviews were included after screening 6,200 titles and abstracts and 422 full-texts; 54 were systematic reviews with a meta-analysis (including data on over 54,000 patients) and 45 were systematic reviews without a meta-analysis. Overall, 44% of included reviews were rated as being of high quality (AMSTAR score ≥ 8). Based on data from systematic reviews including a meta-analysis with an AMSTAR score ≥ 8, promising interventions for complex wounds were identified. These included bandages or stockings (multi-layer, high compression) and wound cleansing for venous leg ulcers; four-layer bandages for mixed arterial/venous leg ulcers; biologics, ultrasound, and hydrogel dressings for diabetic leg/foot ulcers; hydrocolloid dressings, electrotherapy, air-fluidized beds, and alternate foam mattresses for pressure ulcers; and silver dressings and ultrasound for unspecified mixed complex wounds. For surgical wound infections, topical negative pressure and vacuum-assisted closure were promising interventions, but this was based on evidence from moderate to low quality systematic reviews. CONCLUSIONS: Numerous interventions can be utilized for patients with varying types of complex wounds, yet few treatments were consistently effective across all outcomes throughout the literature. Clinicians and patients can use our results to tailor effective treatment according to type of complex wound. Network meta-analysis will be of benefit to decision-makers, as it will permit multiple treatment comparisons and ranking of the effectiveness of all interventions. Please see related article: http://dx.doi.org/10.1186/s12916-015-0326-3.

Relationship between road traffic noisescape and urban form in Hong Kong.

This paper reports on a study which explored the possible relationship between road traffic noisescape and urban form in Hong Kong. A total of 212 residential complexes from 11 contrasting urban forms were sampled, and their noise levels assessed both at dwelling and neighbourhood scales by noise mapping. Its findings indicate that residential complexes with different urban forms have significantly different noisescape attributes. There is a strong correlation between the noise characteristics and morphological indicators at the dwelling scale. A less obstreperous noisescape is associated with urban forms with lower road and building densities, and with building arrangements which provide self-noise screening. These findings suggest that urban form is an influential determinant of the noisescape in the urban environment, and they point to the need to rethink the conventional approach to managing the urban acoustic environment.

True Prevalence of Unforeseen N2 Disease in NSCLC: A Systematic Review + Meta-Analysis.

Patients with unforeseen N2 (uN2) disease are traditionally considered to have an unfavorable prognosis. As preoperative and intraoperative mediastinal staging improved over time, the prevalence of uN2 changed. In this review, the current evidence on uN2 disease and its prevalence will be evaluated. A systematic literature search was performed to identify all studies or completed, published trials that included uN2 disease until 6 April 2023, without language restrictions. The Newcastle-Ottawa Scale (NOS) was used to score the included papers. A total of 512 articles were initially identified, of which a total of 22 studies met the predefined inclusion criteria. Despite adequate mediastinal staging, the pooled prevalence of true unforeseen pN2 (9387 patients) was 7.97% (95% CI 6.67-9.27%), with a pooled OS after five years (892 patients) of 44% (95% CI 31-58%). Substantial heterogeneity regarding the characteristics of uN2 disease limited our meta-analysis considerably. However, it seems patients with uN2 disease represent a subcategory with a similar prognosis to stage IIb if complete surgical resection can be achieved, and the contribution of adjuvant therapy is to be further explored.

Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation by inhibiting Th17-associated pro-inflammatory gene expression.

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity. We investigated the therapeutic effects of green tea extract (GTE) and its major component, epigallocatechin-3-gallate (EGCG), on a murine model of experimental autoimmune uveoretinitis (EAU). Oral administration of GTE, EGCG, dexamethasone, or water, which started 5 days before the induction, was fed every two days to each group. On day 21 post induction, the eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT), fundus fluorescein angiography (FFA) and electroretinography (ERG) prior to sacrificing the animals for histological assessments and gene expression studies. Retinal-choroidal thicknesses (RCT) and major retinal vessel diameter were measured on OCT sections and FFA images, respectively. Comparing to water-treated EAU animals, GTE attenuated uveitis clinical manifestations, RCT increase (1.100 ± 0.013 times vs 1.005 ± 0.012 times, P < 0.001), retinal vessel dilation (308.9 ± 6.189 units vs 240.8 units, P < 0.001), ERG amplitudes attenuation, histopathological ocular damages, and splenomegaly in EAU mice. The therapeutic effects of GTE were dose dependent and were comparable to dexamethasone. EGCG, a major active constituent of GTE, partially alleviated uveitic phenotypes including recovering visual function. Th-17 associated pro-inflammatory gene [interleukin 1 beta (IL-1ß), IL-6, IL-17A, and tumor necrosis factor alpha (TNF-α)] expressions were down regulated by GTE and EGCG treatments, which showed no detectable morphological defects in liver and kidney in non-induced and EAU mice. Our findings suggest that GTE consumption can serve as a potent therapeutic agent as well as a food supplement for developing alternative treatments against autoimmune uveitis.

Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells.

Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.

Knowledge synthesis methods for generating or refining theory: a scoping review reveals that little guidance is available.

OBJECTIVES: To describe and compare, through a scoping review, emerging knowledge synthesis methods for generating and refining theory, in terms of expertise required, similarities, differences, strengths, limitations, and steps involved in using the methods. STUDY DESIGN AND SETTING: Electronic databases (e.g., MEDLINE) were searched, and two reviewers independently selected studies and abstracted data for qualitative analysis. RESULTS: In total, 287 articles reporting nine knowledge synthesis methods (concept synthesis, critical interpretive synthesis, integrative review, meta-ethnography, meta-interpretation, meta-study, meta-synthesis, narrative synthesis, and realist review) were included after screening of 17,962 citations and 1,010 full-text articles. Strengths of the methods included comprehensive synthesis providing rich contextual data and suitability for identifying gaps in the literature, informing policy, aiding in clinical decisions, addressing complex research questions, and synthesizing patient preferences, beliefs, and values. However, many of the methods were highly subjective and not reproducible. For integrative review, meta-ethnography, and realist review, guidance was provided on all steps of the review process, whereas meta-synthesis had guidance on the fewest number of steps. CONCLUSION: Guidance for conducting the steps was often vague and sometimes absent. Further work is needed to provide direction on operationalizing these methods.

A scoping review identifies multiple emerging knowledge synthesis methods, but few studies operationalize the method.

OBJECTIVES: To systematically identify, define, and classify emerging knowledge synthesis methods through a scoping review. STUDY DESIGN AND SETTING: MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Methodology Register, the Cochrane Database of Systematic Reviews, Social Sciences Abstracts, Library and Information Science Abstracts, Philosopher's Index, and Education Resources Information Center were searched to identify articles reporting emerging knowledge synthesis methods across the disciplines of health, education, sociology, and philosophy. Two reviewers independently selected studies and abstracted data for each article. RESULTS: In total, 409 articles reporting on 25 knowledge synthesis methods were included after screening of 17,962 titles and abstracts and 1,010 potentially relevant full-text articles. Most of the included articles were an application of the method (83.9%); only 3.7% were seminal articles that fully described the method (i.e., operationalized the steps). Most of the included articles were published after 2005. The methods were most commonly used across the fields of nursing, health care science and services, and health policy. CONCLUSION: We found a lack of guidance on how to select a knowledge synthesis method. We propose convening an international group of leaders in the knowledge synthesis field to help clarify emerging approaches to knowledge synthesis.

Interventions to decrease the risk of adverse cardiac events for patients receiving chemotherapy and serotonin (5-HT3) receptor antagonists: a systematic review.

BACKGROUND: Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists are effective antiemetics, yet may cause adverse cardiac events, such as arrhythmia. We aimed to identify interventions that mitigate the cardiac risk of 5-HT3 receptor antagonists. METHODS: Electronic databases, trial registries, and references were searched. Studies on patients undergoing chemotherapy or surgery examining interventions to monitor cardiac risk of 5-HT3 receptor antagonists were included. Search results were screened and data from relevant studies were abstracted in duplicate. Risk of bias of included studies was assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) group's risk-of-bias tool. Due to a dearth of included studies, meta-analysis was not conducted. RESULTS: Two randomized clinical trials (RCT) and 1 non-randomized clinical trial (NRCT) were included after screening 7,637 titles and abstracts and 1,554 full-text articles. Intravenous administration of different dolasetron doses was examined in the NRCT, while dolasetron versus ondansetron and palonosetron versus ondansetron were examined in the RCT. Electrocardiogram (ECG) was the only intervention examined to mitigate cardiac harm. No differences in ECG evaluations were observed between dolasetron or palonosetron versus ondansetron after 15 minutes, 24 hours, and 1 week post-administration in the 2 RCTs. Four deaths were observed in one RCT, which were deemed unrelated to palonosetron or ondansetron administration. Minor increases in PR and QT intervals were observed in the NRCT for dolasetron dosages greater than 1.2 mg/kg 1-2 hours post-administration, but were deemed not clinically relevant. CONCLUSIONS: ECG monitoring of chemotherapy patients administered with 5-HT3 receptor antagonists did not reveal clinically significant differences in arrhythmia between the medications at the examined time periods. The usefulness of ECG to monitor chemotherapy patients administered with 5-HT3 receptor antagonists remains unclear, as all patients received ECG monitoring. TRIAL REGISTRATION: PROSPERO registry number: CRD42013003565.

A splice-site mutation leads to haploinsufficiency of EXT2 mRNA for a dominant trait in a large family with multiple osteochondromas.

Multiple osteochondromas (MO) is an autosomal-dominant disorder and mutations in EXT1 and EXT2 account up to 78% of the cases studied, including missense, nonsense, frameshift, and splice-site mutations. EXT1 and EXT2 encode glycosyltransferases required for the synthesis of heparan sulfate (HS) chains. The molecular pathogenesis underlying these mutations is still largely unknown. A heterozygous c.1173 + 1G > T (EXT2) mutation was identified in a three-generation 34-member MO family and is present in all 19 affected members. The consequence of this mutation is exon 7 being spliced out, and the result is a shift in the codon-reading frame from position 360 (R360) of the amino acid sequence leading to a premature termination codon, and the mutant mRNA is degraded to an undetectable level. Interestingly, HS glycosaminoglycans were also undetectable in the cartilage cap of the tumors by immunostaining. Full penetrance of this mutation in all affected members ranging from 5 to 70 years of age suggests this primary defect in EXT2 mRNA level, in conjunction with other cellular changes such as enhanced heparanase expression, can produce profound effect on the synthesis of HS chains in cartilage, the consequence of which impacts on the regulation of chondrocyte proliferation and differentiation.

Environmental quality of urban parks and open spaces in Hong Kong.

It is widely purported that urban parks and open spaces can improve the urban environment by cleansing the air and reducing the noise. However, such environmental functions can be constrained by the size and the location of urban parks in very dense cities. This study examines the air and acoustic environment and heavy metal contamination in Hong Kong urban parks and open spaces. Using a hybrid field measurement and computer simulation approach, the study has found that while the air quality in urban parks is better than that of the roadside, it is not significantly different from that of the ambient conditions. Noise levels in the urban parks are not significantly lower than those at the typical home environment in Hong Kong. Heavy metals in urban park dust are slightly lower than that found at the roadside and are broadly comparable to those found at typical homes and nursery schools. These findings lend support to the postulation that the capability of urban parks and open spaces in dense cities to improve the urban environment is rather limited and call for a re-examination of the role of urban parks in enhancing urban livability. The findings also have implications on how urban parks in dense cities should be designed and managed.