Outcomes of Revascularisation for Treating Lifestyle-Limiting Intermittent Claudication in Aboriginal and Torres Strait Islander People and Non-Indigenous Patients from North Queensland: A Retrospective Cohort Study.

Background: This retrospective analysis of an ongoing prospective cohort study aimed to assess the outcome of revascularisation for treating lifestyle-limiting intermittent claudication caused by peripheral artery disease (PAD) in Aboriginal and Torres Strait Islander Peoples and non-Indigenous North Queenslanders. Methods: Consenting patients with PAD who underwent endovascular or open revascularisation procedures for treating lifestyle-limiting intermittent claudication were included. The primary outcome measure was major adverse limb events (MALEs), defined as major amputation or the requirement for repeat open or endovascular revascularisation. Results: Of the 378 included patients, 18 (4.8%) identified as Aboriginal and/or Torres Strait Islander Peoples. During a mean follow-up (standard deviation) of 6.0 (3.9) years, the incidence of MALE was similar in the Aboriginal and Torres Strait Islander People and non-Indigenous Australians (absolute percentage: 50.0% vs. 40.6%, log rank p = 0.59). In both unadjusted and adjusted analyses, Aboriginal and Torres Strait Islander Peoples and non-Indigenous Australians had similar risks of MALE (unadjusted hazard ratio, HR, 1.20, 95% confidence interval, CI, 0.61, 2.36; adjusted HR 1.02, 95%CI 0.50, 2.06). Conclusions: This study suggests that Aboriginal and Torres Strait Islander People are under-represented in the population of patients undergoing revascularisation to treat intermittent claudication. Due to small numbers it cannot be reliably concluded that Aboriginal and Torres Strait Islander People and non-Indigenous Australians have similar rates of MALE.

It Takes Two to Tangle: Microneedle Patches Co-delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms.

Wound biofilms pose a great clinical challenge. Herein, this work reports a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti-PBP2a and engineers antimicrobial peptides W379. In vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng mL-1 W379 and 250 ng mL-1 anti-BPB2a decreases the bacterial count from ≈3.31 × 107 CFU mL-1 to 1.28 × 102 CFU mL-1 within 2 h without eliciting evident cytotoxicity. Ex vivo testing indicates W379 and anti-PBP2a co-loaded microneedle patch displayed a remarkable reduction of bacterial load by ≈7.18 log CFU after administered only once within 48 h. The bacterial count is significantly diminished compared to the treatment by either W379 or anti-PBP2a-loaded alone microneedle patches. When administered twice within 48 h, no bacteria are identified. Further in vivo study also reveals that after two treatments of W379 and anti-PBP2a co-loaded PVP microneedle patches within 48 h, the bacterial colonies are undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti-PBP2a co-loaded PVP microneedle patches hold great promise in treating wound biofilms.

Outcomes of Negative Pressure Wound Therapy on Immediate Breast Reconstruction after Mastectomy.

Immediate expander/implant-based breast reconstruction after mastectomy has become more sought after by patients. Although many patients choose this technique due to good aesthetic outcomes, lack of donor site morbidity, and shorter procedure times, it is not without complications. The most reported complications include seroma, infection, hematoma, mastectomy flap necrosis, wound dehiscence, and implant exposure, with an overall complication rate as high as 45%. Closed incision negative pressure therapy (ciNPT) has shown value in wound healing and reducing complications; however, the current literature is inconclusive. We aimed to examine if ciNPT improves outcomes for patients receiving this implant-based reconstruction. Methods: This is a retrospective single-institution study evaluating the ciNPT device, 3M Prevena Restor BellaForm, on breast reconstruction patients. The study was performed between July 1, 2019 and October 30, 2020, with 125 patients (232 breasts). Seventy-seven patients (142 breasts) did not receive the ciNPT dressing, and 48 patients (90 breasts) received the ciNPT dressing. Primary outcomes were categorized by major or minor complications. Age, BMI, and final drain removal were summarized using medians and quartiles, and were compared with nonparametric Mann-Whitney test. Categorical variables were compared using chi-square or Fisher exact test. Results: There was a statistically significant reduction in major complications in the ciNPT group versus the standard dressing group (P = 0.0247). Drain removal time was higher in the ciNPT group. Conclusion: Our study shows that ciNPT may help reduce major complication rates in implant-based breast reconstruction patients.

Effect of Dietary Supplements Which Upregulate Nitric Oxide on Walking and Quality of Life in Patients with Peripheral Artery Disease: A Meta-Analysis.

This systematic review pooled evidence from randomised controlled trials (RCTs) on the effectiveness of dietary upregulators of nitric oxide (NO) in improving the walking and quality of life of patients with peripheral artery disease (PAD). RCTs examining the effect of dietary upregulators of NO in patients with PAD were included. The primary outcome was the maximum walking distance. Secondary outcomes were the initial claudication distance, the six-minute walking distance, quality of life, the ankle-brachial pressure index (ABI), adverse events and risk of mortality, revascularisation or amputation. Meta-analyses were performed using random effects models. The risk of bias was assessed using Cochrane's ROB-2 tool. Leave-one-out and subgroup analyses were conducted to assess the effect of individual studies, the risk of bias and intervention type on pooled estimates. Thirty-four RCTs involving 3472 participants were included. Seven trials tested NO donors, nineteen tested antioxidants, three tested NO synthase inducers and five tested enhancers of NO availability. Overall, the dietary supplements significantly improved the initial claudication (SMD 0.34; 95%CI 0.04, 0.64; p = 0.03) but not maximum walking (SMD 0.13; 95%CI -0.17, 0.43; p = 0.39) distances. Antioxidant supplements significantly increased both the maximum walking (SMD 0.36; 95%CI 0.14, 0.59; p = 0.001) and initial claudication (SMD 0.58; 95%CI 0.26, 0.90; p < 0.001) distances. The dietary interventions did not improve the physical function domain of the Short Form-36 (SMD -0.16; 95%CI -0.32, 0.00; p = 0.38), ABI or risk of adverse events, mortality, revascularisation or amputation. Dietary NO upregulators, especially antioxidants, appear to improve the initial claudication distance in patients with PAD. Larger high-quality RCTs are needed to fully examine the benefits and risks of these treatments. PROSPERO Registration: CRD42022256653.

Triggered release of antimicrobial peptide from microneedle patches for treatment of wound biofilms.

Biofilms pose a great challenge for wound management. Herein, this study describes a near-infrared (NIR) light-responsive microneedle patch for on-demand release of antimicrobial peptide for treatment of wound biofilms. IR780 iodide as a photothermal conversion agent and molecularly engineered peptide W379 as an antimicrobial agent are loaded in dissolvable poly(vinylpyrrolidone) (PVP) microneedle patches followed by coating with a phase change material 1-tetradecanol (TD). After placing in an aqueous solution or biofilm containing wounds ex vivo and in vivo, upon exposure to NIR light, the incorporated IR780 induces light-to-heat conversion, causing the melting of TD. This leads to the dissolution of PVP microneedles, enabling the release of loaded W379 peptide from the microneedles into surrounding regions (e.g., solution, biofilm, wound bed). Compared with traditional microneedle patches, NIR light responsive microneedle patches can program the release of antimicrobial peptide and show high antibacterial efficacy in vitro. Meanwhile, this work indicates that NIR light responsive TD-coated, W379-loaded PVP microneedle patches show excellent antibiofilm activities ex vivo and in vivo. Additionally, this microneedle system could be a promising platform for delivering other antimicrobial agents.

Evaluation and outcomes of a 5-year assisted peritoneal dialysis program.

BACKGROUND: In 2016, Peritoneal Dialysis Assist (PDA) was implemented in British Columbia, Canada, as a pilot program to allow patients with physical, cognitive and social impairments to access an independent dialysis modality. This is a presentation of the usage and 5-year clinical outcomes of our provincial assisted peritoneal dialysis (PD) program. METHODS: Patients who utilised long-term or respite PDA services in British Columbia, Canada, from 2016 to 2021 were included in this program evaluation. Incident and prevalent patient numbers were characterised annually as well as indications for PDA and patient demographics both annually and over time. Outcomes of interest included death, transfer to haemodialysis, transplantation and cessation of the PDA program but retention on PD. RESULTS: Three hundred twenty-two total patients received services through the PDA program. The percentage of PD patients supported by long-term PDA service has grown to 11.2% in the most recent year. Patients spend a median of 13.6 (95% CI: 11.0, 16.1) months on long-term PDA, prolonging overall patient duration on PD by a little over a year. Of the patients who exited the long-term PDA program, 73 (37.4%) were able to utilise the service until they died. CONCLUSION: PDA is an accessible, patient-centric service with clear and standardised referral criteria. Through the implementation of a local PDA program, patients have accessed PD and may have extended their PD life span, through avoidance of in-centre haemodialysis, by over 13 months during this 5-year study period. A significant proportion of patients on long-term PDA were able to use their preferred kidney replacement modality at home until they reached end of life.

Remotely Delivered Monitoring and Management of Diabetes-Related Foot Disease: An Overview of Systematic Reviews.

BACKGROUND: Diabetes-related foot disease (DFD) management requires input from multiple healthcare professionals, and has worse outcomes for people living in remote localities by comparison to urban areas. Remotely delivered healthcare may reduce this disparity. This overview summarizes current evidence on the effectiveness, stakeholder perceptions, and cost-effectiveness of remotely delivered healthcare for DFD. METHODS: A search of 5 databases was conducted to identify systematic reviews published between January 2000 and June 2020. Eligible reviews were those evaluating remotely delivered monitoring or management of patients at risk of or with active DFD, or clinicians managing these patients. Risk of bias was assessed using the AMSTAR-2 tool. RESULTS: Eight reviews were eligible for inclusion, including 88 primary studies and 8509 participants, of which 36 studies involving 4357 participants evaluated remotely delivered monitoring or management of DFD. Only one review had a low risk of bias, with most reviews demonstrating limited search strategies and poor reporting of participants. Evidence on effectiveness was mixed, with meta-analyses demonstrating long-term ulcer healing and mortality were not significantly different between telehealth and standard care groups, although the lower-limb amputation rate was significantly decreased in one meta-analysis. Perceptions of telehealth by patients and clinicians were generally positive, whilst acknowledging limitations relating to access and use. Cost-effectiveness data were limited, with poor reporting preventing clear conclusions. CONCLUSIONS: Remotely delivered healthcare of DFD is well received by patients and clinicians, but its effectiveness is unclear. High quality trials are needed to evaluate the risks and benefits of remotely delivered DFD management.

Cross-Suturing is Effective for Teaching Suturing Skills: A Randomized, Controlled Trial.

INTRODUCTION: Basic suturing is a skill expected from graduating medical students. A proposed concept to increase suturing competency is to integrate art by mixing cross-stitching with suturing. We hypothesize that students trained with "cross-suturing" would improve suturing performance. METHODS: We performed a randomized controlled trial of preclinical medical students using an art-based cross-stitching method intervention compared with conventional suturing. Both groups were provided with an introductory suturing video. Assessment of simple interrupted suturing were conducted preintervention and postintervention, and at 2-wk follow-up with a video review by blinded expert raters using the American College of Surgeons basic suturing and knot tying performance rating tool. Students completed a self-assessment of proficiency, confidence, and anxiety. Statistical analysis was performed using unpaired t-tests. RESULTS: A total of 16 preclinical medical students participated. Self-assessment and objective suturing performance were comparable in the preintervention measurements. The intervention group showed significant improvement compared to the control group with median (interquartile range) self-assessment scores 9 (8.5-9) compared with 6.5 (6-7.5) (P < 0.01) and objective performance scores of 25.25 (22.75-27) compared with 16.5 (14.5-18.5) (P < 0.01). The intervention group showed retained skills at the 2-wk follow up with no differences in self-assessment or objective suturing scores immediately postintervention compared with two-wk follow-up with self-assessment scores of 9 (8.5-9) versus 9 (8-9) at 2 wk (P = 0.16) and objective performance score of 25.25 (22.75-27) versus 24.75 (23.5-26.5) at 2 wk (P = 0.29). CONCLUSIONS: The cross-suturing intervention improved suturing skills in this cohort. This low-cost approach to medical student surgical education should be explored on a larger scale.

A qualitative study of medical students' perceptions of resident feedback.

CONTEXT: Residents play a pivotal role in medical students' clinical education. From a feedback lens, the near-peer relationship between student and resident holds the potential to foster an educational alliance that could influence learning. We undertook the current qualitative study to explore medical students' perceptions of feedback experiences with residents, addressing when, how and why (and conversely when not and why not) resident feedback plays a role in their clinical education. METHODS: Our methodology was qualitative interpretive description, informed by phenomenology. We conducted 24 semi-structured interviews with third and fourth year medical students at one institution. The interviews aimed to foster rich discussion about students' feedback experiences with residents during clinical rotations. Data collection and analysis proceeded iteratively. Initial interviews were independently open-coded by three investigators and then collaboratively refined. Codes were applied to subsequent interviews, and new codes were developed. During the final stages of analysis, we organised our themes by drawing on a sociocultural perspective to examine students' perceptions of relationship-building with residents and when and how this influenced feedback and learning. RESULTS: From the students' perspectives, when residents contributed to building interpersonal relationships with students, this in turn influenced students' receptivity to both encouraging and constructive feedback conversations. In the context of resident-student relationships that were perceived as supportive, resident feedback influenced how students approached learning and working in the clinical environment, as well as students' visions of their future selves. In unsupportive relationships, students were less inclined to engage in feedback with residents and students noted resident behaviours that they wanted to avoid in themselves. CONCLUSION: Residents are uniquely positioned to create a strong educational alliance with students in which feedback conversations can flourish. Focusing educational efforts on resident feedback conversations has the potential to significantly impact the feedback culture of our clinical environments.

Codelivery of 1α,25-Dihydroxyvitamin D3 and CYP24A1 Inhibitor VID400 by Nanofiber Dressings Promotes Endogenous Antimicrobial Peptide LL-37 Induction.

Surgical site infections represent a significant clinical problem. Herein, we report a nanofiber dressing for topical codelivery of immunomodulating compounds including 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and VID400, a CYP24A1 inhibitor in a sustained manner, for inducing the expression of the endogenous cathelicidin antimicrobial peptide (CAMP) gene encoding the hCAP18 protein, which is processed into the LL-37 peptide. Nanofiber wound dressings with coencapsulation of 1,25(OH)2D3 and VID400 were generated by electrospinning. Both 1,25(OH)2D3 and VID400 were coencapsulated into nanofibers with loading efficiencies higher than 90% and exhibited a prolonged release from nanofiber membranes longer than 28 days. Incubation with 1,25(OH)2D3/VID400-coencapsulated poly(ϵ-caprolactone) nanofiber membranes greatly induced the hCAP18/LL-37 gene expression in monocytes, neutrophils, and keratinocytes in vitro. Moreover, the administration of 1,25(OH)2D3/VID400-coencapsulated nanofiber membranes dramatically promoted the hCAP18/LL-37 expression in dermal wounds created in both human CAMP transgenic mice and human skin tissues. The 1,25(OH)2D3- and VID400-coencapsulated nanofiber dressings enhanced innate immunity via the more effective induction of antimicrobial peptide than the free drug alone or 1,25(OH)2D3-loaded nanofibers. Together, 1,25(OH)2D3/VID400-embedded nanofiber dressings presented in this study show potential in preventing surgical site infections.

Bias estimation in study design: a meta-epidemiological analysis of transcatheter versus surgical aortic valve replacement.

BACKGROUND: Paucity of RCTs of non-drug technologies lead to widespread dependence on non-randomized studies. Relationship between nonrandomized study design attributes and biased estimates of treatment effects are poorly understood. Our purpose was to estimate the bias associated with specific nonrandomized study attributes among studies comparing transcatheter aortic valve implantation with surgical aortic valve replacement for the treatment of severe aortic stenosis. RESULTS: We included 6 RCTs and 87 nonrandomized studies. Surgical risk scores were similar for comparison groups in RCTs, but were higher for patients having transcatheter aortic valve implantation in nonrandomized studies. Nonrandomized studies underestimated the benefit of transcatheter aortic valve implantation compared with RCTs. For example, nonrandomized studies without adjustment estimated a higher risk of postoperative mortality for transcatheter aortic valve implantation compared with surgical aortic valve replacement (OR 1.43 [95% CI 1.26 to 1.62]) than high quality RCTs (OR 0.78 [95% CI 0.54 to 1.11). Nonrandomized studies using propensity score matching (OR 1.13 [95% CI 0.85 to 1.52]) and regression modelling (OR 0.68 [95% CI 0.57 to 0.81]) to adjust results estimated treatment effects closer to high quality RCTs. Nonrandomized studies describing losses to follow-up estimated treatment effects that were significantly closer to high quality RCT than nonrandomized studies that did not. CONCLUSION: Studies with different attributes produce different estimates of treatment effects. Study design attributes related to the completeness of follow-up may explain biased treatment estimates in nonrandomized studies, as in the case of aortic valve replacement where high-risk patients were preferentially selected for the newer (transcatheter) procedure.

Network Meta-Analysis Comparing the Outcomes of Treatments for Intermittent Claudication Tested in Randomized Controlled Trials.

Background No network meta-analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short- (<1 year), moderate- (1 to <2 years), and long-term (≥2 years) follow-up in people with intermittent claudication. Methods and Results A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health-related quality of life. Network meta-analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty-six trials involving 4256 patients were included. At short-term follow-up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9-157.7), SET (MD, 186.8 m; 95% CrI, 136.4-237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6-430.6), but not ER (MD, 82.5 m; 95% CrI, -2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, -24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate-term follow-up, SET (MD, 201.1; 95% CrI, 89.8-318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3-546.9), but not home exercise therapy (MD, 99.4; 95% CrI, -174.0 to 374.9) or ER (MD, 84.2; 95% CrI, -35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long-term follow-up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta-analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively. Conclusions This network meta-analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.

Simultaneous Delivery of Multiple Antimicrobial Agents by Biphasic Scaffolds for Effective Treatment of Wound Biofilms.

Biofilms pose a major challenge to control wound-associated infections. Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, a biphasic scaffold is reported as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO3 , Ga(NO3 )3 , and vancomycin, are incorporated into nanofiber mats by coaxial electrospinning, which enables sustained delivery of these drugs. The antimicrobial agents-incorporated dissolvable microneedle arrays allow direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds are able to eradicate both methicillin-resistant Staphylococcus aureus (MRSA) and MRSA/Pseudomonas aeruginosa blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprises of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds.

Association of gout with major adverse cardiovascular events and all-cause mortality in patients with peripheral artery disease.

BACKGROUND AND AIMS: Prior epidemiological studies have suggested that individuals with gout are at greater risk of cardiovascular events, but there have been no studies in people with peripheral artery disease (PAD). The aim of this study was to investigate the relationship between gout and major adverse cardiovascular events (MACE) and all-cause mortality in people with PAD. METHODS: Participants with a range of PAD presentations, including carotid artery disease, aortic or peripheral aneurysm and lower limb PAD, were prospectively recruited from outpatient vascular departments within Australia. MACE (myocardial infarction, stroke or cardiovascular death) and all-cause mortality were identified through out-patient follow-up and linked medical records. Propensity-score matching was undertaken to generate a matched cohort of patients with and without a history of gout. Kaplan-Meier survival analysis and Cox-proportional hazard analysis were used to examine the association of gout with MACE and all-cause mortality. RESULTS: A total of 4308 people with PAD, of whom 334 had a history of gout, were included and followed for a median (inter-quartile range) of 2.1 (0.1-5.9) years. In the unadjusted analyses, participants with gout were at increased risk of MACE (hazard ratio, HR 1.37, 95% confidence intervals, CI 1.09-1.71, p = 0.006) and all-cause mortality (HR 1.38, 95% 1.13-1.68, p = 0.002), however, the associations were lost in the adjusted analyses. In the propensity-score matched cohort, gout was not significantly associated with an increased risk for MACE or all-cause mortality. CONCLUSIONS: Gout was not independently associated with increased cardiovascular events in PAD patients.

Dissolvable Microneedles Coupled with Nanofiber Dressings Eradicate Biofilms via Effectively Delivering a Database-Designed Antimicrobial Peptide.

Biofilms in chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Herein, we report a Janus-type antimicrobial dressing for eradication of biofilms in chronic wounds. The dressing consists of electrospun nanofiber membranes coupled with dissolvable microneedle arrays to enable effective delivery of a database-designed antimicrobial peptide to both inside and outside biofilms. This antimicrobial dressing exhibited high efficacy against a broad spectrum of resistant pathogens in vitro. Importantly, such a dressing was able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms in both an ex vivo human skin wound infection model and a type II diabetic mouse wound infection model after daily treatment without applying surgical debridement. Most importantly, the dressing can also completely remove the Pseudomonas aeruginosa and MRSA, dual-species biofilm in an ex vivo human skin infection model. In addition, our computational simulations also suggested that microneedles were more effective in the delivery of peptides to the biofilms than free drugs. Our results indicate that the Janus-type antimicrobial dressings may provide an effective treatment and management of chronic wound polymicrobial infections.

Mesenchymal stem cell-laden, personalized 3D scaffolds with controlled structure and fiber alignment promote diabetic wound healing.

The management of diabetic wounds remains a major therapeutic challenge in clinics. Herein, we report a personalized treatment using 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with bone marrow mesenchymal stem cells (BMSCs). The 3D scaffolds have customizable sizes, depths, and shapes, enabling them to fit a variety of type 2 diabetic wounds. In addition, the 3D scaffolds are shape-recoverable in atmosphere and water following compression. The BMSCs-laden 3D scaffolds are capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition. Further, such scaffolds inhibit the formation of M1-type macrophages and the expression of pro-inflammatory cytokines IL-6 and TNF-α and promote the formation of M2-type macrophages and the expression of anti-inflammatory cytokines IL-4 and IL-10. Taken together, BMSCs-laden, 3D nanofiber scaffolds with controlled structure and alignment hold great promise for the treatment of diabetic wounds. STATEMENT OF SIGNIFICANCE: In this study, we developed 3D radially and vertically aligned nanofiber scaffolds to transplant bone marrow mesenchymal stem cells (BMSCs). We personalized 3D scaffolds that could completely match the size, depth, and shape of diabetic wounds. Moreover, both the radially and vertically aligned nanofiber scaffolds could completely recover their shape and maintain structural integrity after repeated loads with compressive stresses. Furthermore, the BMSCs-laden 3D scaffolds are able to promote granulation tissue formation, angiogenesis, and collagen deposition, and switch the immune responses to the pro-regenerative direction. These 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with BMSCs offer a robust, customizable platform potentially for a significant improvement of managing diabetic wounds.

Duraplasty Using Autologous Fascia Lata and Latissimus Dorsi Free Flap for Chronic Cerebrospinal Fluid Leak.

Cerebrospinal fluid (CSF) leak is a common complication after cranial surgery. Therefore, after neurosurgical procedures it is crucial to obtain a dural repair that is complete and watertight. There are many techniques that have been described attempting to achieve this goal. However, there are complicating factors (eg, poor tissue viability, need for future radiation, comorbidities, infection, size of the dural defect, multiple operations) that may require a more comprehensive approach to achieve an optimal healing environment. The authors present a technique that uses a muscle free flap to vascularize an autologous fascia lata graft, preserving the viability of the graft and reinforcing its healing ability.The authors applied this technique to a single patient with chronic CSF leak from poor tissue healing after treatments for recurrent medulloblastoma. After harvesting a fascia lata graft with appropriate size, the graft was sutured into the dural defect in a watertight fashion. A latissimus dorsi muscle free flap was harvested and anastomosed to a saphenous vein Corlett loop/AV fistula to the facial artery. The flap was than sutured to the graft. A drain was left in place and a skin graft was applied to the muscle flap.At 8 months follow-up the patient was able to continue with her treatment and has had a stable repair without leak or breakdown. The authors present an algorithm to facilitate dural repair selection.Duraplasty using autologous fascia lata reinforced with a free muscle flap is an effective technique to control chronic CSF leaks, especially when the dura is poorly vascularized and less viable.

Systematic review and meta-analysis of the association between intraluminal thrombus volume and abdominal aortic aneurysm rupture.

BACKGROUND: Intraluminal thrombus (ILT) is present in most abdominal aortic aneurysms (AAAs), although its role in AAA progression is controversial. METHODS: A literature search was performed to identify studies that investigated the association between ILT volume and AAA rupture. A study assessment tool was developed to assess the methodologic quality of included studies. A meta-analysis was conducted using an inverse variance-weighted random-effects model to compare the ILT volume in ruptured and asymptomatic intact AAAs. Leave-one-out sensitivity analyses were conducted to assess the robustness of the findings. A subanalysis was performed including studies in which patients with asymptomatic intact and ruptured AAAs were matched for aortic diameter. Interstudy heterogeneity was assessed using the I2 statistic. RESULTS: Eight studies involving 672 patients were included in this systematic review. Meta-analysis of all studies found a greater ILT volume in patients with ruptured AAAs than in patients with asymptomatic intact AAAs (standardized mean difference, 0.56; 95% confidence interval, 0.17-0.96; P = .005; I2 = 79.8%). Sensitivity analyses suggested that the findings were robust; however, aortic diameter was significantly larger in ruptured than in asymptomatic intact AAAs (mean ± standard deviation, 78 ± 18 and 64 ± 15 mm, respectively; P < .001). In the subanalysis of studies that matched for diameter, no significant difference in ILT volume between groups was found (standardized mean difference, 0.03; 95% confidence interval, -0.27 to 0.33; P = .824; I2 = 0%). CONCLUSIONS: This meta-analysis suggests that ILT volume is greater in patients with ruptured AAAs than in patients with asymptomatic intact AAAs, although this is most likely due to the larger diameter of ruptured AAAs.

Outcome of patients with relapsed or refractory anaplastic large cell lymphoma who have failed brentuximab vedotin.

Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate that is highly effective in patients with relapsed/refractory anaplastic large cell lymphoma (ALCL). However, survival outcomes following suboptimal response or subsequent relapse are not well known. We conducted a multicenter study analyzing outcomes of patients with relapsed/refractory ALCL who have received BV with a secondary focus on survival after progression following BV. A total of 56 patients were treated with BV for relapsed or refractory ALCL. The overall response rate to BV was 73% with complete response (CR) rate of 46%. The median failure-free survival and overall survival (OS) after BV were 15.5 month and not reached, respectively. The median duration of response was 27.6 months in patients who achieved CR by BV, while the median OS of those who did not achieve CR by BV was 9.5 months. There was no significant difference in OS between those who underwent stem cell transplant (SCT) and those who did not in patients who achieved CR after BV. However, if patients were in PR after BV, SCT was associated with significantly longer OS. Thirty patients experienced progressive disease on BV or required a subsequent treatment. The median OS after BV failure was 2.9 months with 2-year OS of 27.1%. There were seven long-term survivors (≥12 months) following failure. After an adequate response to subsequent salvage therapy, five patients underwent subsequent SCT (three allogeneic and two autologous), four of which were long-term survivors (17+, 25+, 32+, and 50+ months). In conclusion, BV failure is associated with a poor outcome in patients with ALCL, which defines a small but important group with unmet need. SCT may have benefit in patients with relapsed/refractory ALCL who failed BV.

Iron overload in lower international prognostic scoring system risk patients with myelodysplastic syndrome receiving red blood cell transfusions: Relation to infections and possible benefit of iron chelation therapy.

BACKGROUND: An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. METHODS: We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). RESULTS: 138 transfused MDS patients were lower IPSS risk. 59 received ICT; median duration was 13 months. There was no significant difference between groups in neutrophil count at first RBC transfusion or first infection. Infections included: bacterial, n = 88; viral; fungal; and mycobacterial; n = 2 each. In ICT and non-ICT patients, respectively, infections were (number [%]): patients, 23 (40.0%) and 22 (27.8%); episodes (median [range]), 2 (1-6) and 2 (1-5); hospitalizations, 16 (27.1%) and 8 (10.1%); and deaths, 0 (0%) and 1 (1.3%), p = NS for all. Median overall survival (OS) from first RBC transfusion was superior in ICT patients, p = 0.01, and remained significant in a multivariate analysis (MVA), p = 0.003. Median time to first infection (TTI) was 27 and 7.8 months, respectively, p < 0.0001, and ICT remained significant for TTI in an MVA, p = 0.02, hazard ratio 0.3. For ICT patients with blast count <5%, TTI was significantly superior (p = 0.004). CONCLUSIONS: In this retrospective analysis, for lower IPSS risk MDS patients receiving RBC transfusions, though number and type of infections were similar between groups and despite similar neutrophil counts, time to first infection was significantly longer in ICT patients (p < 0.0001). These results should be confirmed in larger, prospective analyses.