Infusion Rate Research Articles

Comparison of mMO-TLIF via Midline Incision Versus MIS-TLIF via Wiltse Approach in Lumbar Degenerative Disease

Abstract Background To compare the clinical and radiological outcomes of modified mini-open transforaminal lumbar interbody fusion (mMO-TLIF) via posterior midline incision for "targeted limited dissection" versus minimal invasive transforaminal lumbar interbody fusion (MIS-TLIF) via Wiltse approach in lumbar degenerative diseases. Methods A total of 60 consecutive patients in our center from January 2019 to March 2020 were enrolled, including 30 patients who were treated with mMO-TLIF via posterior midline incision and 30 treated with MIS-TLIF through the Wiltse approach. Perioperative parameters were recorded. The questionnaires of Oswestry Disability Index (ODI) and Visual Analogue Score (VAS) were conducted before the operation and after the operation (3 days, 1 week, and 2 years). CT and MRI radiological outcomes were evaluated before the operation and at a 2-year follow-up. Results There were no significant differences in the general data, gender, age, and BMI between the two groups. All patients were successfully operated without intraoperative complications. There were significant differences between the two groups in the operation time (p < 0.001) and intraoperative bleeding (p < 0.05). There was no difference in ODI and VAS scores between groups pre- and post-operatively, but they were both significantly improved compared to those before the operation (p < 0.01). At a 2-year follow-up, the paraspinal muscle atrophy and fat infiltration were increased comparing to pre-operation, but the difference was also not statistically significant (p > 0.05). In addition, both the two groups’ fusion rates were more than 90% at a 2-year follow-up, however, no difference was detected between the two groups. Conclusion mMO-TLIF via midline incision for “targeted limited dissection” could achieve similar clinical and radiological outcomes as MIS-TLIF for lumbar degenerative disease.

Treatment of cervical ossification of posterior longitudinal ligament with titanium alloy trabecular bone three-dimensional printed artificial vertebral body

To evaluate the effectiveness of using titanium alloy trabecular bone three-dimensional (3D) printed artificial vertebral body in treating cervical ossification of the posterior longitudinal ligament (OPLL). A retrospective analysis was conducted on clinical data from 45 patients with cervical OPLL admitted between September 2019 and August 2021 and meeting the selection criteria. All patients underwent anterior cervical corpectomy and decompression, interbody bone graft fusion, and titanium plate internal fixation. During operation, 21 patients in the study group received titanium alloy trabecular bone 3D printed artificial vertebral bodies, while 24 patients in the control group received titanium cages. There was no significant difference in baseline data such as gender, age, disease duration, affected segments, or preoperative pain visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), vertebral height, and C 2-7Cobb angle ( P>0.05). Operation time, intraoperative blood loss, and occurrence of complications were recorded for both groups. Preoperatively and at 3 and 12 months postoperatively, the functionality and symptom relief were assessed using JOA scores, VAS scores, and NDI evaluations. The vertebral height and C 2-7 Cobb angle were detected by imaging examinations and the implant subsidence and intervertebral fusion were observed. The operation time and incidence of complications were significantly lower in the study group than in the control group ( P<0.05), while the difference in intraoperative blood loss between the two groups was not significant ( P>0.05). All patients were followed up 12-18 months, with the follow-up time of (14.28±4.34) months in the study group and (15.23±3.54) months in the control group, showing no significant difference ( t=0.809, P=0.423). The JOA score, VAS score, and NDI of the two groups improved after operation, and further improved at 12 months compared to 3 months, with significant differences ( P<0.05). At each time point, the study group exhibited significantly higher JOA scores and improvement rate compared to the control group ( P<0.05); but there was no significantly difference in VAS score and NDI between the two groups ( P>0.05). Imaging re-examination showed that the vertebral height and C 2-7Cobb angle of the two groups significantly increased at 3 and 12 months after operation ( P<0.05), and there was no significant difference between 3 and 12 months after operation ( P>0.05). At each time point, the vertebral height and C 2-7Cobb angle of the study group were significantly higher than those of the control group ( P<0.05), and the implant subsidence rate was significantly lower than that of the control group ( P<0.05). However, there was no significant difference in intervertebral fusion rate between the two groups ( P>0.05). Compared to traditional titanium cages, the use of titanium alloy trabecular bone 3D-printed artificial vertebral bodies for treating cervical OPLL results in shorter operative time, fewer postoperative complications, and lower implant subsidence rates, making it superior in vertebral reconstruction.

Prospective comparative study of unilateral biportal endoscopic transforaminal lumbar interbody fusion and endoscopic transforaminal lumbar interbody fusion for treatment of single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis

To compare the effectiveness of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) and endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis. Between November 2019 and May 2023, a total of 81 patients with single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis who met the selection criteria were enrolled. They were randomly divided into UBE-TLIF group (39 cases) and Endo-TLIF group (42 cases). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, body mass index, surgical segment, and preoperative visual analogue scale (VAS) scores for low back and leg pain, Oswestry Disability Index (ODI), and serum markers including creatine kinase (CK) and C reactive protein (CRP). Total blood loss (TBL), intraoperative blood loss, hidden blood loss (HBL), postoperative drainage volume, and operation time were recorded and compared between the two groups. Serum markers (CK, CRP) levels were compared between the two groups at 1 day before operation and 1, 3, and 5 days after operation. Furthermore, the VAS scores for low back and leg pain, and ODI at 1 day before operation and 1 day, 3 months, 6 months, and 12 months after operation, and intervertebral fusion rate at 12 months after operation were compared between the two groups. All surgeries were completed successfully without occurrence of incision infection, vascular or nerve injury, epidural hematoma, dural tear, or postoperative paraplegia. The operation time in UBE-TLIF group was significantly shorter than that in Endo-TLIF group, but the intraoperative blood loss, TBL, and HBL in UBE-TLIF group were significantly more than those in Endo-TLIF group ( P<0.05). There was no significant difference in postoperative drainage volume between the two groups ( P>0.05). The levels of CK at 1 day and 3 days after operation and CRP at 1, 3, and 5 days after operation in UBE-TLIF group were slightly higher than those in the Endo-TLIF group ( P<0.05), while there was no significant difference in the levels of CK and CPR between the two groups at other time points ( P>0.05). All patients were followed up 12 months. VAS score of low back and leg pain and ODI at each time point after operation significantly improved when compared with those before operation in the two groups ( P<0.05); there was no significant difference in VAS score of low back and leg pain and ODI between the two groups at each time point after operation ( P>0.05). There was no significant difference in the intervertebral fusion rate between the two groups at 12 months after operation ( P>0.05). UBE-TLIF and Endo-TLIF are both effective methods for treating degenerative lumbar spinal stenosis with lumbar spondylolisthesis. However, compared to Endo-TLIF, UBE-TLIF requires further improvement in minimally invasive techniques to reduce tissue trauma and blood loss.

Impact of Postoperative Bracing Following Spinal Fusion for Degenerative Lumbar Conditions: An Updated Meta-Analysis of Randomized Controlled Trials.

There is a lack of consensus on the use of postoperative bracing for lumbar degenerative conditions. Spine surgeons typically determine whether to apply postoperative braces based primarily on clinical experience rather than robust, evidence-based medical data. Thus, the present study sought to assess the impact of postoperative bracing on clinical outcomes, complications, and fusion rates following lumbar fusion surgery in patients with degenerative spinal conditions. Only randomized controlled studies published between January 1990 and 20 October 2023 were included in this meta-analysis. The primary outcome measures consisted of pre- and postoperative assessments of the Oswestry Disability Index (ODI) and visual analog scale (VAS) scores. Improvements in VAS and ODI scores were analyzed in the early postoperative period (1 month after operation) and at final follow-up, respectively. The analysis also encompassed fusion rates and complications. Five studies with 362 patients were included in the present meta-analysis. In the early postoperative period, the brace group showed a relatively better improvement in ODI scores compared with the no-brace group (19.47 vs 18.18), although this difference was not statistically significant (P = 0.34). Similarly, during the late postoperative period, the brace group demonstrated a slightly greater improvement in VAS scores in comparison to the no-brace group (4.05 vs 3.84), but this difference did not reach statistical significance (P = 0.30). The complication rate was relatively lower in the brace group compared with the no-brace group (14.9% vs 17.4%), although there was no statistical difference between the 2 groups (P = 0.83). Importantly, there were no substantial differences in fusion rates between patients with or without braces. The present meta-analysis revealed that the implementation of a brace following lumbar fusion surgery did not yield substantial differences in terms of postoperative pain relief, functional recovery, complication rates, or fusion rates when compared with cases where no brace was employed. This meta-analysis provides valuable insights into the clinical impact of postoperative bracing following lumbar fusion surgery for degenerative spinal conditions.

Serotonin Promotes Vesicular Association and Fusion by Modifying Lipid Bilayers.

The primary event in chemical neurotransmission involves the fusion of a membrane-limited vesicle at the plasma membrane and the subsequent release of its chemical neurotransmitter cargo. The cargo itself is not known to have any effect on the fusion event. However, amphiphilic monoamine neurotransmitters (e.g., serotonin and dopamine) are known to strongly interact with lipid bilayers and to affect their mechanical properties, which can in principle impact membrane-mediated processes. Here, we probe whether serotonin can enhance the association and fusion of artificial lipid vesicles in vitro. We employ fluorescence correlation spectroscopy and total internal reflection fluorescence microscopy to measure the attachment and fusion of vesicles whose lipid compositions mimic the major lipid components of synaptic vesicles. We find that the association between vesicles and supported lipid bilayers is strongly enhanced in a serotonin dose-dependent manner, and this drives an increase in the rate of spontaneous fusion. Molecular dynamics simulations and fluorescence spectroscopy data show that serotonin insertion increases the water content of the hydrophobic part of the bilayer. This suggests that the enhanced membrane association is likely driven by an energetically favorable drying transition. Other monoamines, such as dopamine and norepinephrine, but not other related species, such as tryptophan, show similar effects on membrane association. Our results reveal a lipid bilayer-mediated mechanism by which monoamines can themselves modulate vesicle fusion, potentially adding to the control toolbox for the tightly regulated process of neurotransmission in vivo.

External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. The maximum TG concentration (TGmax) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE.

Effects of flow rate accuracy in two-day anticancer drug infusion with disposable pumps on plasma drug concentrations.

Elastomeric pumps have a curved infusion rate profile over infusion time. Chemically driven pumps can overcome such limitations of elastomeric pumps and infuse constantly. However, studies on the pharmacokinetic benefit of chemically-driven pumps are insufficient. This study aimed to determine effects of constant infusion with a chemically-driven pump on plasma drug concentrations compared to elastomeric pumps. Infusion rate profiles of a chemically driven pump and two elastomeric pumps were measured in vitro tests under three height conditions of drug reservoir. Plasma drug concentrations were estimated using a pharmacokinetic model of 5-fluorouracil (5FU). The chemically-driven pump was more accurate than elastomeric pumps during the total infusion time (Root-mean-square-error (RMSE): 3% vs. 13%) which thus reduced its deviation of plasma 5FU concentration over time to one-fifth of that with an elastomeric pump. The chemically-driven pump had less than 5% of RMSE despite the influence of height difference. Although chemically-driven pumps maintained plasma 5FU concentration successfully and elastomeric pumps did not, both pumps were proper for 5FU infusion because the time-dependent changes in infusion rate did not affect the area under the curve. Chemically driven pumps would be more advantageous for drugs that are sensitive to their plasma concentrations.

Frequency of Common and Uncommon BRAF Alterations among Colorectal and Non-Colorectal Gastrointestinal Malignancies.

The predictive and prognostic role of BRAF alterations has been evaluated in colorectal cancer (CRC); however, BRAF alterations have not been fully characterized in non-CRC gastrointestinal (GI) malignancies. In the present study, we report the frequency and spectrum of BRAF alterations among patients with non-CRC GI malignancies. Patients with CRC and non-CRC GI malignancies who underwent somatic tumor profiling via a tissue-based or liquid-based assay were included in this study. Gain-of-function BRAF alterations were defined as pathogenic/likely pathogenic somatic short variants (SVs), copy number amplifications ≥8, or fusions (RNA or DNA). Among 51,560 patients with somatic profiling, 40% had CRC and 60% had non-CRC GI malignancies. BRAF GOF alterations were seen more frequently in CRC (8.9%) compared to non-CRC GI malignancies (2.2%) (p < 0.001). Non-CRC GI malignancies with the highest prevalence of BRAF GOF alterations were bile duct cancers (4.1%) and small intestine cancers (4.0%). Among BRAF GOF alterations, class II (28% vs. 6.8%, p < 0.001) and class III (23% vs. 14%, p < 0.001) were more common in non-CRC GI malignancies. Among class II alterations, rates of BRAF amplifications (3.1% vs. 0.3%, p < 0.001) and BRAF fusions (12% vs. 2.2%, p < 0.001) were higher in non-CRC GI malignancies compared to CRC. Non-CRC GI malignancies demonstrate a distinct BRAF alteration profile compared to CRC, with a higher frequency of class II and III mutations, and more specifically, a higher incidence of BRAF fusions. Future studies should evaluate clinical implications for the management of non-CRC GI patients with BRAF alterations, especially BRAF fusions.

A comparison of anterior reconstruction of spinal defect using nano-hydroxyapatite/polyamide 66 cage and autologous iliac bone for thoracolumbar tuberculosis: a stepwise propensity score matching analysis.

Previous studies have confirmed the advantages and disadvantages of autogenous iliac bone and nano-hydroxyapatite/polyamide 66 (n-HA/PA66) cage. However, there is no conclusive comparison between the efficacy of the two implant materials in spinal tuberculosis bone graft fusion. The aim of this study was to analyze the mid-to long-term clinical and radiologic outcomes between n-HA/PA66 cage and autogenous iliac bone for anterior reconstruction application of spinal defect for thoracolumbar tuberculosis. We retrospectively reviewed all patients who underwent anterior debridement and strut graft with n-HA/PA66 cage or iliac bone combined with anterior instrumentations between June 2009 and June 2014. One-to-one nearest-neighbor propensity score matching (PSM) was used to match patients who underwent n-HA/PA66 cage to those who underwent iliac bone. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) and visual analogue score (VAS). Radiographic evaluations included cage subsidence and segmental angle. At the end of the PSM analysis, 16 patients from n-HA/PA66 cage group were matched to 16 patients in Iliac bone group. The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values in the n-HA/PA66 group decreased significantly from 33.19 ± 10.89 and 46.63 ± 15.65 preoperatively, to 6.56 ± 2.48 and 9.31 ± 3.34at the final follow-up, respectively (p < 0.001). There were no significant differences in the CRP and ESR values between the two groups at the final follow-up. The VAS and JOA scores in the iliac bone and n-HA/PA66 group were significantly improved at the 3-month follow-up postoperatively (both p < 0.001). Then, improvements of VAS and JOA scores continue long at final follow-up. However, there were no significant differences in the VAS and JOA scores at any time point between the two groups (p > 0.05). Although the segmental angle (SA) significantly increased after surgery in both groups, there was no significant difference at any time point after surgery (p > 0.05). There were no significant differences in the cage subsidence and fusion time between the two groups. Overall, our data suggest that the n-HA/PA66 cage outcomes are comparable to those in the autogenous iliac bone, with a similar high fusion rate as autogenous iliac bone.

Benefits of dexmedetomidine during noninvasive mechanical ventilation in major abdominal surgery patients with postoperative respiratory failure.

The efficacy of non-invasive mechanical ventilation (NIMV) on the postoperative ARF is conflicting and the failure rate of NIMV in this patient population is high. In our study, we hypothesized that the use of dexmedetomidine during NIMV in major abdominal surgical patients can reduce NIMV failure without significant side affect. Medical records of patients who underwent major abdominal surgery, admitted to our general surgery intensive care unit (ICU), developed postoperative ARF, received NIMV (with oro-nasal mask) and dexmedetomidine infusion were enrolled in this study. The infusion rate was adjusted to maintain a target sedation level of a Richmond Agitation-Sedation Scale (RASS) (-2)-(-3). The sedation was stopped when NIMV was discontinued. A total of 60 patients, 42 (70.0%) male, and 18 (30.0%) female, with a mean age of 68 ± 11 years were included in the study. The mean APACHE II score was 20 ± 6. Dexmedetomidine was infused for a median of 25 h (loading dose of 0.2 mcg/kg for 10 min, maintained at 0.2-0.7 mcg/kg/h, titrated every 30 min). RASS score of all study group significantly improved at the 2 h of dexmedetomidine initiation (+3 vs. -2, p = 0.01). A targeted sedation level was achieved in 92.5% of patients. Six (10.0%) patients developed bradycardia and 5 (8.3%) patients had hypotension. The mean NIMV application time was 23.4 ± 6.1 h. Seven (11.6%) patients experienced NIMV failure, all due to worsening pulmonary conditions, and required intubation and invasive ventilation. Fifty-three (88.3%) patients were successfully weaned from NIMV with dexmedetomidine sedation and discharged from ICU. The duration of NIMV application and ICU stay was shorter in NIMV succeded group (21.4 ± 3.2 vs. 29.9 ± 6.4; p = 0.012). Our study suggests that dexmedetomidine demonstrates effective sedation in patients with postoperative ARF during NIMV application after abdominal surgery. Dexmedetomidine can be considered safe and capable of improving NIMV success.

Comparison of minimally invasive transforaminal lumbar interbody fusion and midline lumbar interbody fusion in patients with spondylolisthesis

BackgroundThis study aimed to compare surgical outcomes, clinical outcomes, and complications between minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and midline lumbar interbody fusion (MIDLIF) in patients with spondylolisthesis.MethodsThis study retrospectively compared the patients who underwent MIS TLIF (n = 37) or MIDLIF (n = 50) for spinal spondylolisthesis. Data of surgical outcomes (postoperative one-year fusion rate and time to bony fusion), clinical outcomes (visual analog scale [VAS] for pain and Oswestry Disability Index [ODI] for spine function), and complications were collected and analyzed.ResultsThere was more 2-level fusion in MIDLIF (46% vs. 24.3%, p = 0.038). The MIS TLIF and MIDLIF groups had similar one-year fusion rate and time to fusion. The MIDLIF group had significantly lower VAS at postoperative 3-months (2.2 vs. 3.1, p = 0.002) and postoperative 1-year (1.1 vs. 2.1, p = < 0.001). ODI was not significantly different. The operation time was shorter in MIDLIF (166.1 min vs. 196.2 min, p = 0.014). The facet joint violation is higher in MIS TLIF (21.6% vs. 2%, p = 0.009). The other complications were not significantly different including rate of implant removal, revision, and adjacent segment disease.ConclusionIn this study, postoperative VAS, operation time, and the rate of facet joint violation were significantly higher in the MIS TLIF group. Comparable outcomes were observed between MIDLIF and MIS TLIF in terms of fusion rate, time to fusion, and postoperative ODI score.

Targeting of C-ROS-1 Activity Using a Controlled Release Carrier to Treat Craniosynostosis in a Preclinical Model of Saethre-Chotzen Syndrome

Saethre-Chotzen syndrome (SCS) is one of the most prevalent craniosynostosis, caused by a loss-of-function mutation in the TWIST-1 gene, with current treatment options relying on major invasive transcranial surgery. TWIST-1 haploinsufficient osteogenic progenitor cells exhibit increased osteogenic differentiation potential due to an upregulation of the transmembrane tyrosine kinase receptor, C-ROS-1, a TWIST-1 target gene known to promote bone formation. The present study assessed the efficacy of suppressing C-ROS-1 activity using a known chemical inhibitor to C-ROS-1, crizotinib, to halt premature coronal suture fusion in a preclinical mouse model of SCS. Crizotinib (1 μM, 2 μM, or 4 μM) was administered locally over the calvaria of Twist‐1del/+ heterozygous mice prior to coronal suture fusion using either a nonresorbable collagen sponge (quick drug release) or a resorbable sodium carboxymethylcellulose microdisk (slow sustained release). Coronal suture fusion rates and bone parameters were determined by μCT imaging and histomorphometric analysis of calvaria postcoronal suture fusion. Results demonstrated a dose-dependent increase in the efficacy of crizotinib to maintain coronal suture patency, with no adverse effects to brain, kidney, liver, and spleen tissue, or blood cell parameters. Moreover, crizotinib delivered on microdisks resulted in a greater efficacy at a lower concentration to reduce bone formation at the coronal suture sites compared to sponges. However, the bone inhibitory effects were found to be diminished by over time following cessation of treatment. Our findings lay the foundation for the development of a pharmacological nonsurgical, targeted approach to temporarily maintain open coronal sutures in SCS patients. This study could potentially be used to develop similar therapeutic strategies to treat different syndromic craniosynostosis conditions caused by known genetic mutations.

The influence of spheroid maturity on fusion dynamics and micro-tissue assembly in 3D tumor models

Three-dimensional (3D) cell culture has been used in many fields of biology because of its unique advantages. As a representative of the 3D systems, 3D spheroids are used as building blocks for tissue construction. Larger tumor aggregates can be assembled by manipulating or stacking the tumor spheroids. The motivation of this study is to investigate the behavior of the cells distributed at different locations of the spheroids in the fusion process and the mechanism behind it. To this aim, spheroids with varying grades of maturity or age were generated for fusion to assemble micro-tumor tissues. The dynamics of the fusion process, the motility of the cells distributed in different heterogeneous architecture sites, and their reactive oxygen species profiles were studied. We found that the larger the spheroid necrotic core, the slower the fusion rate of the spheroid. The cells that move were mainly distributed on the spheroid’s surface during fusion. In addition to dense microfilament distribution and low microtubule content, the reactive oxygen content was high in the fusion site, while the non-fusion site was the opposite. Last, multi-spheroids with different maturities were fused to complex micro-tissues to mimic solid tumors and evaluate Doxorubicin’s anti-tumor efficacy.

MULTICENTRE RANDOMIZED CONTROLLED STUDY OF SUBTALAR ARTHRODESIS USING ALLOSTEM VERSUS AUTOLOGOUS BONE GRAFT

IntroductionAlloStem/Cellular Bone Allograft and autologous bone graft are accepted methods for managing hindfoot degenerative arthritis. The purpose was to evaluate outcomes of AlloStem and autograft in subtalar arthrodesis and compare overall fusion rates.MethodsThis study was conducted in IRB compliance. Patients between 18–80 years who qualified for a subtalar fusion were randomized 1:1 to AlloStem or autologous graft. The AOFAS hindfoot ankle scale, FFI-R and SF-12 were collected pre-operatively, 6 weeks, 3 &amp; 6 months, 1 and 2 year. Weight-bearing 3-view ankle X-rays were done at the same intervals. A CT scan was obtained at 6 months.Results140 patients were enrolled; 124 patients had surgery(60-AlloStem and 64-Control). Withdrawals included 14 voluntarily before surgery and 2 intra-operative failures. 19 were lost to follow-up. Mean age for AlloStem was 56.69(20.3–79.6) and Autograft was 54.60(20.74–80.07). 59 AlloStem patients completed their 6 month visit and 45 completed 2 years. AOFAS score improved: 40.02 at pre-op to 72.16(6 mo) to 79.51 at 1 year and 80.38 at 2 year. SF-12 improved 58.29 at pre-op to 65.67 at 6 month and 71.59 at 2 year. FFI-R improved 236.88 at pre-op to 203.53 at 6 month 149.93 at 2 year.60 Autograft patients completed their 6 month visit and 51 patients completed their 2 year. AOFAS score improved 42.89 at pre-op to 75.67 (6 mo) to 79.75 at 1 year and 78.62 at 2 year. Autograft SF-12 improved 60.55 at pre-op to 70.40 at 6 month and 75.26 at 2 year. Autograft FFI-R improved 217.16 at pre-op to 166.77 at 6 month and 145.43 at 2 year. AlloStem patients had a mean posterior fusion rate of 28.9% at 6 months whereas the Autograft had 46.3%(p=.049). Non-union rates were AlloStem(9/57)(15.7%) whereas Autograft was 3/60(5%).ConclusionAlloStem trended to be inferior to Autologous graft.

Drift drives the evolution of chromosome number II: The impact of range size on genome evolution in Carnivora.

Chromosome number is a fundamental genomic trait that is often the first recorded characteristic of a genome. Across large clades, a common pattern emerges: many or even most lineages exhibit relative stasis, while a handful of lineages or species exhibit striking variation. Despite recent developments in comparative methods, most of this heterogeneity is still poorly understood. It is essential to understand why some lineages have rapid rates of chromosome number evolution, as it can impact a variety of other traits. Previous research suggests that biased female meiotic drive may shape rates of karyotype evolution in some mammals. However, Carnivora exhibits variation that this female meiotic drive model cannot explain. We hypothesize that variation in effective population size may underlie rate variation in Carnivora. To test this hypothesis, we estimated rates of fusions and fissions while accounting for range size, which we use as a proxy for effective population size. We reason fusions and fissions are deleterious or underdominant and that only in lineages with small range sizes will these changes be able to fix due to genetic drift. In this study, we find that the rates of fusions and fissions are elevated in taxa with small range sizes relative to those with large range sizes. Based on these findings, we conclude that 1) naturally occurring structural mutations that change chromosome number are underdominant or mildly deleterious, and 2) when population sizes are small, structural rearrangements may play an important role in speciation and reduction in gene flow among populations.

ENHANCING NOSE- TO- BRAIN DELIVERY OF PIRIBEDIL: DEVELOPMENT OF A NANOSUSPENSION DISPERSED IN NASAL IN-SITU GELLING SYSTEM

Objective: This study focuses on improving the delivery of Piribedil, a poorly soluble drug, to the brain through the nasal route using a nanosuspension in a nasal in-situ gel. Methods: The nanosuspension was prepared using the sonoprecipitation method. Quality-by-Design (QbD) principles were used to optimize both the formulation and process parameters. The optimal process parameters were determined as sonication time (7.09 min), sonication amplitude (83.44%), and infusion rate (2.41 mL/min) with a desirability value of 0.970. Results: The nanosuspension exhibited an average particle size ranging from 46.7 nm to 50.1 nm, and polydispersity index values between 0.393 and 0.425. Zeta potential values ranged from -33.78 ± 1.86 mV to -35.06 ± 2.12 mV, indicating favorable stability. FTIR studies revealed molecular interactions between Piribedil and stabilizers. XRPD and DSC analyses showed the transition from a crystalline to an amorphous state in the nanosuspension. Dissolution studies demonstrated significantly accelerated dissolution for the Piribedil nanosuspension, attributed to its nanosize and improved wettability. Stability assessments confirmed the robustness of the nanosuspension. Conclusion: This innovative approach offers potential solutions for drug solubility challenges and blood-brain barrier penetration, holding promise for effective brain-targeted treatments.

Effect of lidocaine on intraoperative blood pressure variability in patients undergoing major vascular surgery

BackgroundDynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures.MethodsWe performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups.ResultsAll calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products.ConclusionIn high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability.Trial registrationClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.

A Novel and Low-Cost Cloud-Enabled IoT Integration for Sustainable Remote Intravenous Therapy Management

Intravenous therapy is the standard medical procedure that is used for administering medications directly into the vein. The automated drug infusion devices are designed in such a way that they provide exact medication doses with safety measures included. On the other hand, this is why they must be regularly watched by healthcare providers. This paper introduces a cloud-based IoT drug infusion system that was developed to address remote patient care needs. This system enables remote, accurate, and secure management of medication delivery. Its key contributions include allowing healthcare providers to control and monitor IV infusions remotely while maintaining safety features. The system consists of a microcontroller that is responsible for data processing, a control system that oversees infusion rate regulation, and an IoT-based framework that allows for remote monitoring and alerts via a user-friendly web interface. This new approach to care will therefore improve patient care by providing remote management of medications.

Impact of surgical risk factors for non-union on lumbar spinal fusion outcomes using cellular bone allograft at 24-months follow-up

BackgroundThe current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union.MethodsA prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT 02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up.ResultsA total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p < 0.05) in both low and high-risk groups. The low-risk group showed enhanced improvement at multiple timepoints in EQ-5D, ODI, VAS-Back pain and VAS-Leg pain scores compared to the high-risk group (p < 0.05). The number of AEs were similar among risk groups.ConclusionsThis study demonstrates high fusion rates following lumbar spinal surgery using CBA, regardless of associated risk factors. Patient reported outcomes and fusion rates were not adversely affected by risk factor profiles.Trial registrationNCT 02969616 (21/11/2016).

A comparison of two versus five epineural sutures to achieve successful polyethylene glycol (PEG) nerve fusion in a rat sciatic nerve repair model.

We compared rates of successful polyethylene glycol (PEG) nerve fusion between two epineural suture repairs (2SR) and five epineural suture repairs (5SR) in a rat sciatic nerve transection neurorrhaphy model. We hypothesise that the two and five epineural neural suture repair groups will achieve a similar rate of PEG fusion. Twenty-five Lewis rats underwent bilateral sciatic nerve transection. Primary neurorrhaphy (PN) consisting of 2SR in one hind limb and 5SR in the contralateral hind limb was performed utilizing PEG fusion. Successful PEG fusion was confirmed by a distal muscle twitch after nerve stimulation proximal to the nerve fusion site. Sciatic nerve conduction velocity (SNCV) across the repair site and the force generated by tibialis anterior muscle (TAM) contraction were also compared between the 2SR and 5SR groups. Success rates were 100% for the 2SR and the 5SR groups. No statistically significant differences in SNCV (P = 0.444) or isometric tetanic TAM contractile force (P = 0.820) were observed between 2SR and 5SR in the setting of PEG fusion. These findings demonstrate no significant difference in successful PEG fusion between the 2SR and 5SR groups. In addition, the findings demonstrate no statistically significant differences in SNCV or isometric tetanic TAM contractile force following sciatic nerve transection when performing a 2SR or 5SR PN in the setting of PEG fusion. Successful PEG fusion can be achieved acutely with either a two or five-epineural suture repair in a rat model.