Elucidating the Impact of Surfactants on the Performance of Dissolving Microneedle Array Patches.

The need for biocompatible polymers capable of dissolving in the skin while exhibiting reasonable mechanical features and delivery efficiency limits the range of materials that could be utilized in fabricating dissolving microneedle array patches (MAPs). The incorporation of additives, such as surfactants, during microneedle fabrication might be an alternative solution to overcome the limited range of materials used in fabricating dissolving MAPs. However, there is a lacuna in the knowledge on the effect of surfactants on the manufacture and performance of dissolving MAPs. The current study explores the role of surfactants in the manufacture and performance of dissolving MAPs fabricated from poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) loaded with the model drugs, ibuprofen sodium and itraconazole. Three nonionic surfactants, Lutrol F108, Pluronic F88, and Tween 80, in solutions at varying concentrations (0.5, 1.0, and 2.0% w/w) were loaded into these dissolving MAPs. It was discovered that all of the dissolving MAPs that incorporated surfactant displayed a lower reduction in the microneedle height (≈10%) relative to the control formulation (≈20%) when subjected to a compressive force of 32 N. In addition, the incorporation of surfactants in some instances enhanced the insertion profile of these polymeric MAPs when evaluated using ex vivo neonatal porcine skin. The incorporation of surfactant into ibuprofen sodium-loaded dissolving MAPs improved the insertion depth of MAPs from 400 µm down to 600 µm. However, such enhancement was not apparent when the MAPs were loaded with the model hydrophobic drug, itraconazole. Skin deposition studies highlighted that the incorporation of surfactant enhanced the delivery efficiency of both model drugs, ibuprofen sodium and itraconazole. The incorporation of surfactant enhanced the amount of ibuprofen sodium delivered from 60.61% up to ≈75% with a majority of the drug being delivered across the skin and into the receptor compartment. On the other hand, when surfactants were added into MAPs loaded with the model hydrophobic drug itraconazole, we observed enhancement in intradermal delivery efficiency from 20% up to 30%, although this did not improve the delivery of the drug across the skin. This work highlights that the addition of nonionic surfactant is an alternative formulation strategy worth exploring to improve the performance and delivery efficiency of dissolving MAPs.

Preliminary results of two novel devices for epiphysiodesis in the reduction of excessive predicted final height in tall stature.

BACKGROUND: In the treatment of tall stature, the reduction of excessive predicted final height can either be achieved by hormonal treatment or surgically by temporary (tED) or permanent (pED) epiphysiodesis. The present study evaluates the preliminary results of two novel devices for tED and pED around the knee to reduce the predicted final height. MATERIALS AND METHODS: A retrospective analysis was performed to evaluate the clinical and radiographic outcome after bilateral epiphysiodesis for the treatment of tall stature. A cohort of 34 patients (16 girls, 18 boys) who underwent either tED or pED between 2015 and 2020 were eligible for analysis based on the electronic patient records and picture archiving and communication system of our orthopaedic teaching hospital. tED was conducted in 11 patients (32%) through bilateral implantation of four RigidTacks™ (Merete, Berlin, Germany) around the knee. Twenty-three patients (68%) received pED, performed with an EpiStop™ trephine (Eberle, Wurmberg, Germany). The mean overall follow-up time was 2.9 years. RESULTS: The mean age at surgery was 12.3 years in girls and 13.2 years in boys. Patients had a mean body height of 175.2 cm in girls and 184.7 cm in boys at surgery. The mean predicted final height was 191.4 cm in girls and 210.4 cm in boys. At the last follow-up, 26 patients (76.5%) had achieved skeletal maturity. The mean height of skeletally mature patients was 187.2 cm in girls and 198.5 cm in boys. A mean reduction of the predicted final height of 5.9 cm in girls and 8.7 cm in boys was achieved, corresponding to a reduction in remaining growth of 46% in girls and 38% in boys. Secondary frontal plane deformities of the knee were detected in 5/11 patients (45.5%) in the tED group and 1/23 treatments (4.3%) in the pED group. CONCLUSIONS: tED and pED have both proven to be efficient at achieving growth inhibition to reduce excessive predicted height. However, tED has been associated with an increased risk of secondary angular deformities of the knee. Furthermore, the risk of implant-related complications and the necessity of a subsequent surgical intervention for implant removal have led our study group to abandon tED when treating tall stature. Long-term results of both procedures are pending.

[Release of moveable segments after dorsal stabilization : Impact on affected discs]. / Freigabe von Bewegungssegmenten nach dorsaler Stabilisierung : Auswirkung auf die betroffenen Bandscheiben.

BACKGROUND: Bisegmental dorsal stabilization is a common treatment option for instable compression fractures of the thoracolumbar spine; however, it remains unknown to what extent bridging compromises intervertebral discs. OBJECTIVES: The purpose of this study was to determine the disc height and functional features in comparison to healthy intervertebral discs after removal of the dorsal fixator and particularly under consideration of the time span between dorsal stabilization and implant removal (IR). MATERIAL AND METHODS: The IR was performed in 19 patients after an average of 13 months (range 8-24 months) after dorsal stabilization of instable vertebral compression fractures of the thoracolumbar junction and lumbar spine. An additional ventral monosegmental spondylodesis was performed in 10 patients with incomplete burst fractures. Thus, a total of 28 intervertebral discs were temporarily bridged (bridged discs), with an adjacent endplate fracture in 10 (injured discs) and no adjacent bony lesion in 18 discs (healthy discs). The intervertebral discs superior and inferior to the instrumentation were selected as controls (control discs). Standardized conventional lateral radiographs were taken prior to and after IR as well as after 6 months. Additionally, standardized lateral radiographs in flexion and extension were taken. The intervertebral disc height (disc height) was determined by two independent board approved orthopedic observers by measuring the anterior, central and dorsal intervertebral disc spaces on all lateral radiographs as well as the intervertebral disc angles (disc angle) defined by the intervertebral upper and lower endplates in the flexion and extension views. Intradisc function (disc function) was defined as the difference between the disc angle in extension and flexion. The measurements were repeated after 12 months. Univariate analysis was performed using ANOVA and significance was set at p < 0.05. Interobserver and intraobserver comparisons of the disc heights and the disc angles were determined with intraclass correlation coefficients. RESULTS: No significant differences were seen in disc function and disc height between the controls and the bridged discs at all times of measurement; however, injured discs showed a significantly reduced disc height and disc angle in extension compared to healthy discs (p = 0.028 and p = 0.027, respectively). Additionally, patients with IR during the first 12 months had significantly reduced disc heights compared to those patients with delayed IR within the second postoperative year (p = 0.018). Interobserver and intraobserver agreement for disc function was 0.80 (95 % confidence interval CI: 0.68-0.88) and 0.85 (95 % CI 0.76-0.90), respectively. The interobserver and intraobserver correlations for disc height were 0.85 (95 % CI: 0.76-0.90) and 0.93 (95 % CI 0.88-0.95), respectively. CONCLUSION: Bridging of an intervertebral disc with IR within 24 months does not cause immediate loss of disc function or reduction of disc height; however, temporary bridging in combination with an adjacent endplate fracture causes significant reduction of disc height and loss of extension. Additionally, no beneficial effects could be seen by reducing the time span between stabilization and IR to below 12 months.

Study on the water retention curve of shredded municipal solid waste considering the compressibility of specimens based on the centrifuge method.

The water retention curve (WRC) of municipal solid waste (MSW) is the important hydraulic parameter for the study of unsaturated seepage analysis in landfills. Due to the compressibility and degradability of the waste, the search for a method to quickly and accurately test its water retention curve (WRC) is a current problem that needs to be solved. In this paper, considering the volume change of the waste specimens in test, the test principle of centrifuge testing of WRC is corrected to make it applicable to the testing of waste WRC. In addition, the WRCs of 20 MSW specimens with typical landfill compositions and porosities are measured using the corrected centrifuge test. The effects of compositions and porosities of waste specimens on WRC parameters were analyzed. The results are summarized as follows. Disregarding the height reduction of specimens resulted in overestimated matric suction values and underestimating volume water content values. By comparing uncorrected and corrected values, the maximum difference of the matric suction and volumetric water content reach 233 kPa and 11%, respectively. This study can provide a reference for accurately measuring the WRC of MSW using a centrifuge. For the waste specimen without kitchen and yard waste, composition had less of an effect on the WRC of waste compared to porosity. The effect of the content of the non-absorbable fraction on the residual volumetric water content θr and the parameter nv in the van Genuchten model was significant. The initial porosity n had a great effect on the parameter α.

Midterm Results of Mitral Valve Repair Using Loop Technique With Simple Height Reduction of the Large Posterior Leaflet.

OBJECTIVE: Systolic anterior motion (SAM) is one of the most serious problems in mitral valve repair. Height reduction is a key procedure to solve SAM, and there are limited data on the surgical results of height reduction procedure. This study is to assess the effectiveness and midterm results of simple height reduction procedure for SAM in patients with severe mitral regurgitation (MR). METHODS: From 2008 to 2022, 50 patients underwent loop technique with an additional simple height reduction procedure for prevention of SAM. We examined the midterm results of patients with simple height reduction regarding recurrent MR and reoperation. The follow-up period ranged from 171 to 3,816 days (median, 883 days). RESULTS: There were 338 patients (87%) who underwent loop technique without height reduction and 50 patients (13%) who underwent loop technique with height reduction. After the height reduction procedure, SAM was prevented in 44 patients, and 6 patients needed volume loading to suppress SAM. Freedom from recurrence of moderate to severe or severe MR at 1, 3, and 5 years was 98%, 88%, and 88% in the height reduction group versus 98%, 96%, and 94% in the group with loop technique alone (P = 0.074). Receiver operating characteristic curves showed that a systolic dimension of 26 mm had a sensitivity of 75% and a specificity of 83% for predicting SAM after height reduction. CONCLUSIONS: Loop technique with simple height reduction was a simple, secure, and effective procedure to prevent SAM and recurrent significant MR in the midterm periods.

Does re-ossification after palliative radiotherapy for spinal bone metastases help maintain vertebral body height?

BACKGROUND CONTEXT: After palliative radiotherapy of spinal bone metastases, re-ossification is sometimes observed in bone with osteolytic changes. However, it remains unknown whether the re-ossification that is observed after radiotherapy is associated with preservation of vertebral body height. PURPOSE: To investigate whether re-ossification observed after palliative radiotherapy can contribute to the preservation of vertebral body height. STUDY DESIGN: This is a retrospective observational study. PATIENTS SAMPLE: We investigated 111 vertebral bodies in 54 patients that underwent palliative radiotherapy at a single center for painful osteolytic/mixed metastatic spinal tumors in solid tumors between 2016 and 2020. OUTCOME MEASURES: The outcome measures were the presence of re-ossification and vertebral body height reduction on the CT image. METHODS: Re-ossification was evaluated according to the MD Anderson response classification criteria, and sagittal CT images were used to evaluate vertebral body height. A vertebral body ID was assigned to the irradiated vertebral body, and continuous CT images obtained for each vertebral body ID were evaluated. The median number of evaluation periods for each vertebral body was 4, and the total number of periods was 463. Logistic regression analysis was performed to investigate factors related to the occurrence of vertebral body height reduction before the subsequent CT. As a subanalysis, factors related to re-ossification were investigated. RESULTS: The following primary cancer types were observed: lung cancer, 41 vertebral bodies; breast cancer, 19; renal cell cancer, 15; other, 36. A total of 62.2% showed re-ossification. The median time to confirmation of re-ossification by CT was 2 months. Factors significantly associated with vertebral body height reduction were presence of vertebral body height reduction before radiotherapy (odds ratio [OR] 6.8, 95% confidence interval [CI] 2.0-63, p=.01) and no re-ossification (OR 137, 95% CI 22-3469, p<.01). Factors associated with re-ossification were the type of cancer and total radiation dose. Those with lung cancer and those with a total radiation dose of 20 Gy or less were more prone to re-ossification. CONCLUSIONS: Re-ossification was observed in 62.2% of vertebral bodies after palliative radiotherapy for painful osteolytic/mixed metastatic spinal tumors. The re-ossification group demonstrated significantly less vertebral body height reduction when compared with the non-re-ossification group. The presence of re-ossification may potentially serve an important role in maintaining vertebral body height.

Hard and soft tissue changes and long-term stability after vertical height reduction genioplasty using biodegradable fixation.

The aim of this work was to analyse the stability of vertical height reduction genioplasty using biodegradable material, as well as to determine vertical changes of hard and soft tissues during this procedure. Forty patients underwent vertical height reduction genioplasty using two types of biodegradable fixation (Biosorb FX® or OSTEOTRANS-MX®), combined with mandibular setback surgery. We assessed lateral cephalographs over time (pre-operation; immediately post-operation; 3 months, 6 months and 12 months post-operation). We found a mean vertical difference of 0.22mm (standard deviation (SD)=0.49mm) at the menton point immediately post-operation, compared with 12 months post-operation. And there was no statistical significance(P>0.05). The chin hard tissue remained stable from the immediate post-operation period to 1 year post-operation, and the chin soft tissue remained stable from 3 months to 1 year post-operation. The regression equation describing the replacement of hard tissue with soft tissue change, between pre-operation and 12 months post-operation is y=0.590x+0.885 (R2=0.300, P<0.001). We confirm that the use of biodegradable fixation is a stable method, in terms of skeletal tissues, and a relatively stable method, in terms of soft tissues. In vertical height reduction genioplasty, soft tissue does not reflect 100% of the vertical tissue reduction in hard tissues. This data may influence establishment of surgical treatment objectives.

Adjacent disc height reduction and clinical outcome after intradiscal cement leakage.

OBJECTIVE: The purpose of this study is to evaluate the effect of intradiscal cement leakage on the height of adjacent cement-containing discs and the resulting clinical efficacy after kyphoplasty. METHODS: A total of 124 patients were included and classified into two groups: group A included 20 patients with intradiscal leakage, and group B contained 104 patients without intradiscal leakage. The mean follow-up time was 20.56±3.51 months. The height of the corresponding discs in both groups was measured using Farfan's method. Clinical efficacy was assessed using the Visual Analog Scale and Oswestry Disability Index scores at each follow-up time. RESULTS: The anterior disc height, posterior disc height and Farfan Index significantly decreased in both groups at last follow-up. The disc height reduction was 9.19±2.89% in group A and 3.88±2.70% in group B, which was significantly different between the groups (P<0.01). The disc height reduction rate was 29.39±7.90% in group A and 12.75±8.18% in group B, which was also a statistically significant difference (P<0.01). The VAS and ODI scores improved significantly after surgery and maintained at last follow-up, and there was no statistically significant difference between Groups A and B. CONCLUSION: Intradiscal cement leakage was associated with the degeneration of cement-containing disc but did not reduce the clinical efficacy at early stages.

Root restriction: A tool for improving volume utilization efficiency in bioregenerative life-support systems.

The objective of this study was to evaluate root restriction as a tool to increase volume utilization efficiency in spaceflight crop production systems. Bell pepper plants (Capsicum annuum cv. California Wonder) were grown under restricted rooting volume conditions in controlled environment chambers. The rooting volume was restricted to 500ml and 60ml in a preliminary trial, and 1500ml (large), 500ml (medium), and 250ml (small) for a full fruiting trial. To reduce the possible confounding effects of water and nutrient restrictions, care was taken to ensure an even and consistent soil moisture throughout the study, with plants being watered/fertilized several times daily with a low concentration soluble fertilizer solution. Root restriction resulted in a general reduction in biomass production, height, leaf area, and transpiration rate; however, the fruit production was not significantly reduced in the root restricted plants under the employed environmental and horticultural conditions. There was a 21% reduction in total height and a 23% reduction in overall crown diameter between the large and small pot size in the fruiting study. Data from the fruiting trial were used to estimate potential volume utilization efficiency improvements for edible biomass in a fixed production volume. For fixed lighting and rooting hardware situations, the majority of improvement from root restriction was in the reduction of canopy area per plant, while height reductions could also improve volume utilization efficiency in high stacked or vertical agricultural systems.