Infusion Rate Research Articles

Minimally Invasive Fusion of the First Metatarsophalangeal Joint: A Technical Report

Hallux rigidus, a common arthritic condition of the forefoot, affects a significant portion of the population, with ~8% of the population developing it at some point in their lives. Failure of first-line nonoperative treatment options may necessitate surgical treatment in symptomatic patients. Traditional surgical approaches include cheilectomy for milder cases and open arthrodesis for severe cases. The minimally invasive surgery approach to first metatarsophalangeal joint fusion is a novel technique that utilizes small incisions and arthroscopy for joint fusion. Fusion rates of 93% to 97% and low complication rates were reported by several studies on this technique. The technique involves percutaneous portal development, joint preparation and debridement, joint reduction, and fixation using k-wires and compression screws. The proper positioning of the toe is crucial to ensure optimal functional outcomes. Indications for this technique include advanced arthritis, significant scar tissue, and patient concern for cosmetic outcomes. Contraindications include poor bone quality, revision fusion, significant bone loss, active infection, or vascular compromise. Preoperative planning involves a comprehensive physical examination and imaging to assess the extent of the arthritis and any associated deformities. Complications of the procedure may include nonunion, malunion, iatrogenic thermal burns, and asymmetrical joint preparation. Postoperative management includes weight-bearing restrictions, regular follow-up visits, and gradual progression to normal activities. Preliminary results demonstrate promising outcomes for minimally invasive surgery first metatarsophalangeal fusions.

#425 Felzartamab (anti-CD38) in patients with IgA Nephropathy—interim results from the IGNAZ study

Abstract Background and Aims Most patients with IgA nephropathy (IgAN) will progress to kidney failure within 10-15 years of diagnosis. Sustained proteinuria is the best predictor of adverse long-term kidney outcomes and is a surrogate marker for efficacy. CD38+ plasma cells are likely the main source of pathogenic Gd-IgA1, and the related autoantibodies in IgAN. Felzartamab (felza; HIB202) is a recombinant purified human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to CD38 on plasma cells and is being studied across immune-mediated kidney diseases such as IgAN, Primary Membranous Nephropathy, Lupus Nephritis, and Antibody Mediated Rejection. The primary aims of the IGNAZ study were to assess: 1) efficacy of felza compared to placebo on urine protein:creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) change from baseline, and 2) the relationship between exposure, safety, and efficacy in each of 3 dose groups vs. placebo. Interim results with 15 months of follow-up from this 24-month trial are presented. Method In Part 1, 48 IgAN subjects were randomized in a 1:1:1:1 ratio across a placebo and 3 active arms in this multicenter, double-blind placebo-controlled, phase IIa trial. The M1, M2, and M3 active arms received 2 doses in 15 days, 5 doses in 2 months, and 9 doses in 5 months, respectively. In Part 2, 6 Japanese subjects received the M3 regimen, open-label, and have been followed for 9 months. Key inclusion criteria included ages 18-80 years, biopsy confirmed diagnosis of IgAN within the past 8 years, proteinuria at screening ≥1.0 g/d, eGFR ≥30 ml/min/1.73 m2 (by CKD-EPI), and background stable and maximally tolerated renin angiotensin system inhibitors. Results 48 randomized subjects were enrolled at 28 sites in the US and in 14 different countries in Europe and in Asia, of which 46 completed the treatment phase. Mean (SD) baseline characteristics (Parts 1 and 2 combined): age 41.6 (12.3) yrs, UPCR 1.67 (1.0) g/g, eGFR 74.6 (30.3) ml/min/1.73 m2. 67% of subjects were male. Intention-to-treat with felza demonstrated rapid, clinically meaningful reductions in UPCR with the maximal treatment effect being observed in the M3 9-dose regimen. In Part 1, percentage change from baseline in UPCR was −14% for placebo and −25% for M3 9-dose arm at month 3, and +9% for placebo and −35% for M3 at month 6 (Fig. A). Reductions in proteinuria observed at month 6 persisted until Month 15, 10 months after the last dose: +6% and −38% mean UPCR change from baseline for placebo and the M3 9-dose arm, respectively (Fig. B). Relatively stable eGFR values were observed for the felza arms compared to loss of eGFR in the placebo arm. Rapid, durable reductions in IgA and Gd-IgA1 levels were seen across the dosing arms, with reductions lasting 10 months after the last dose (Fig. C). IgG recovery occurred faster off-treatment than IgA. Results in the Part 2 subjects were similar to the Part 1 M3 cohort through 9 months. There were no apparent dose-dependent adverse events and no exposure-safety relationship. Treatment-emergent adverse events (TEAEs) were generally of mild or moderate intensity or toxicity grade. The most common TEAE assessed as related by study investigator was infusion related reactions (IRR), most of which occurred on the first infusion. There was one treatment-related serious AE due to an IRR. Five subjects discontinued treatment due to IRRs or drug hypersensitivity; for four of the five subjects, the infusion rate was higher than protocol-specified or had an error in pre-medication. TEAE infections were comparable between placebo and felza arms: Placebo (33.3%), M1 (33.3%), M2 (36.4%), M3 (38.5%), Part 2 (50.0%); all were Grades 1 or 2, and non-serious. Conclusion This proof-of-concept study highlights the potential for disease modification in IgAN with the anti-CD38 mAb felza and supports continued research as a potential treatment for high-risk IgAN patients. Felza treatment resulted in clinically meaningful, prolonged UPCR reductions and eGFR stabilization sustained ≥10 months after dosing was completed. Felza was generally well tolerated with rapid recovery of IgG with durable reductions in IgA and pathogenic Gd-IgA1 levels.

Reduced Subsidence With PEEK-Titanium Composite Versus 3D Titanium Cages in a Retrospective, Self-Controlled Study in Transforaminal Lumbar Interbody Fusion.

Retrospective Study. To compare subsidence and radiographic fusion rates of titanium-surface polyetheretherketone (PEEK-Ti) and 3D-Titanium (3D-Ti) cages, implanted within the same patient concurrently, during multi-level transforaminal lumbar interbody fusions (TLIF). Forty-eight patients were treated with both PEEK-Ti and 3D-Ti cages during 2- or 3-level TLIF and instrumented posterolateral fusion (108 spinal levels in all). Equivalent bone graft material was implanted within each patient. Radiographic analysis of CT and/or X-ray imaging was performed retrospectively for each spinal level throughout 12-month follow-up period. Fusion was defined as bridging trabecular bone and subsidence was incursion into one/both vertebral bodies >20% cage height. Outcomes were analyzed with Fisher's exact test. At 6-months post-operative follow-up, incidence of subsidence was significantly lower for PEEK-Ti cages, with 4.8% subsidence, compared to a 27.9% subsidence rate for 3D-Ti cages (P = .007). Fusion rates were comparable at 100% for PEEK-Ti and 95.5% for 3D-Ti. Results at 12-months showed similar but not statistically significant trends of less subsidence with PEEK-Ti than 3D-Ti cages (14.3% PEEK-Ti, 37.5% 3D-Ti), and similar fusion rates of 100% for PEEK-Ti and 91.7% for 3D-Ti. Thirty-nine out of 48 total patients were available for follow-up at 6 months and 20 patients at 12 months. CT availability at 6 and 12-months was 100% and 90%, respectively. A significantly lower subsidence rate was associated with a PEEK-Ti cage, compared to 3D-Ti, 6 months after TLIF. Results may not be generalized across technologies due to differences in cage designs; additional research studies are warranted.

Prevalence of sacroiliac joint fusion in females and males depending on parity status.

Previous research shows that sacroiliac (SI) joint fusion is age and sex dependent. Older individuals-specifically starting in the fifth or sixth decade of life-are more likely to develop SI fusion. Females have a lower frequency of SI joint fusion than males, perhaps due to pregnancy or parturition. This study examines the relationship between SI joint fusion with both sex and parity status in females. The issue is whether the prevalence of SI fusion in nulliparous females is more similar to that of males or parous females. The sample consists of 46 nulliparous females, 119 parous females, and 158 males from the William M. Bass Donated Skeletal Collection. Ages of the individuals ranged from 50 to 89 years. Sex, age, and parity status were self-reported. The frequency of SI joint fusion is significantly different among males (13.29%), nulliparous females (6.52%), and parous females (0.84%). Pairwise comparison of the three groups for SI joint fusion shows that parous females and males are significantly different, but nulliparous females are nonsignificantly different from parous females and males. Parity status does not appear to be a factor in the sexually dimorphic nature of SI joint fusion in this sample. Rather, biomechanical and hormonal factors may have a greater contribution to higher rates of SI joint fusion in males than females.

A double-blinded randomised controlled study of fluid restriction versus liberal fluid during induction of labour: A pilot study.

Excess intravenous fluid for women requiring an induction of labour may adversely affect the duration of labour and maternal/neonatal outcomes. This study aimed to determine the difference in duration of labour and outcomes with a low background infusion rate, compared to liberal background intravenous fluid management. A double blind randomised controlled pilot study was performed on 200 women who underwent induction of labour at a single institution. Women were randomised to an intravenous rate of 40 mL/h versus 250 mL/h of Hartmann's solution. Fluid boluses were strictly controlled to limit bias. This trial was registered with the Australian clinical trial registry: ACTRN12621001298808. Analysis of the total amount of fluid received showed good separation with Group 1 (40 mL/h) receiving 1,736 mL less than Group 2 (250 mL/h), median (interquartile range) 841 mL (458, 1691) versus 2,577 mL (1620, 4326) (P < 0.001). Median duration of labour was shorter in Group 1 by 24 min (P = ns). Subset analysis of nulliparous women showed that duration of labour was shorter in Group 1 by 83.5 min (P = ns). As this was a pilot study, a significant difference in duration of labour or secondary outcomes was not seen. Given the increasing numbers of nulliparous women having an induction of labour, potential for adverse maternal and neonatal outcomes and the associated higher rate of operative birth, this study guides power calculations and supports proof of concept for future research into optimum fluid management during induction of labour for these women.

How Much Do You Fuse? A Comparison of Cell Fusion Assays in a Breast Cancer Model

Cell fusion is a biological process that is crucial for the development and homeostasis of different tissues, but it is also pathophysiologically associated with tumor progression and malignancy. The investigation of cell fusion processes is difficult because there is no standardized marker. Many studies therefore use different systems to observe and quantify cell fusion in vitro and in vivo. The comparability of the results must be critically questioned, because both the experimental procedure and the assays differ between studies. The comparability of the fluorescence-based fluorescence double reporter (FDR) and dual split protein (DSP) assay was investigated as part of this study, in which general conditions were kept largely constant. In order to be able to induce both a high and a low cell fusion rate, M13SV1 breast epithelial cells were modified with regard to the expression level of the fusogenic protein Syncytin-1 and its receptor ASCT2 and were co-cultivated for 72 h with different breast cancer cell lines. A high number of fused cells was found in co-cultures with Syncytin-1-overexpressing M13SV1 cells, but differences between the assays were also observed. This shows that the quantification of cell fusion events in particular is highly dependent on the assay selected, but the influence of fusogenic proteins can be visualized very well.

Clinical and Radiographic Outcomes of Anterior Lumbar Interbody Fusions Using a Titanium Cage with a Biomimetic Surface.

We analyzed clinical and radiographic outcomes in patients undergoing anterior lumbar interbody fusions (ALIFs) using a new biomimetic titanium fusion cage (Titan nanoLOCK interbody, Medtronic, Minneapolis, Minnesota, United States). This specialized cage employs precise nanotechnology to stimulate inherent biochemical and cellular osteogenic reactions to the implant, aiming to amplify the rate of fusion. To our knowledge, this is the only study to assess early clinical and radiographic results in ALIFs. We conducted a retrospective review of data for patients who underwent single or multilevel ALIF using this implant between October 2016 and April 2021. Indications for treatment were spondylolisthesis, postlaminectomy syndrome, or spinal deformity. Clinical and radiographic outcome data for these patients were collected and assessed. A total of 84 patients were included. The mean clinical follow-up was 36.6 ± 14 months. At 6 months, solid fusion was seen in 97.6% of patients. At 12 months, solid fusion was seen in 98.8% of patients. Significant improvements were seen in patient-reported outcome measures (PROMs; visual analog scale and Oswestry Disability Index) at 6 and 12 months compared with the preoperative scores (p < 0.001). One patient required reoperation for broken pedicle screws 2 days after the ALIF. None of the patients required readmission within 90 days of surgery. No patients experienced an infection. ALIF using a new titanium interbody fusion implant with a biomimetic surface technology demonstrated high fusion rates (97.6%) as early as 6 months. There was significant improvement in PROMs at 6 and 12 months.

A Nationwide Comparison of Outcomes and Resource Use in Staged vs Simultaneous Cervical and Lumbar Fusions: A Retrospective Database Study

Background: Although the coexistence of cervical and lumbar spinal conditions is fairly common, surgical treatments are usually staged, even though simultaneous fusion of the cervical and lumbar spine may be a viable option for appropriate candidates. Purpose: We sought to investigate the outcomes of staged vs simultaneous cervical and lumbar fusions in terms of differences in postoperative complications and resource use. Methods: We performed a retrospective cohort study using claims data from the 2006 to 2020 all-payer Premier Health Database. Data were extracted for patients who underwent both a cervical and a lumbar fusion procedure either simultaneously (same hospitalization) or staged (within 1 year). Multivariable regression models measured the association between simultaneous or staged procedures and combined complications (including venous thromboembolism, infection, acute renal failure, or vascular/pulmonary/gastrointestinal complications), intensive care unit (ICU) admission, and prolonged length of stay. We report odds ratios (ORs) and 95% confidence intervals (CI). Results: Overall, 560 (5.2%) and 10 187 (94.8%) of total 10 747 cervical and lumbar fusion procedures were performed simultaneously and staged, respectively. When comparing outcomes after simultaneous procedures to those after staged procedures (for which outcomes from the cervical and lumbar procedures were pooled), simultaneous procedures were associated with higher rates of ICU admission and longer hospital stays, but there were no differences in rates of combined complications. Conclusion: Our retrospective, nationwide database study found that simultaneous cervical and lumbar fusion is relatively rare and its rates of complications do not differ meaningfully from those of staged procedures. However, we found an association between simultaneous cervical and lumbar fusion and higher rates of ICU admission and prolonged length of stay. Further study is warranted.

Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study.

Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24hours) in the pediatric intensive care unit (PICU). We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24hours in mechanically ventilated children. We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p=0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n=4), hypersecretion (n=14), tachycardia (n=6), and nystagmus (n=2). There were no significant changes in hemodynamic variables 24h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p<0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.

Comparison of transforaminal and posterior lumbar interbody fusion outcomes in patients receiving a novel allograft versus rhBMP-2: a radiographic and patient-reported outcomes analysis.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been demonstrated to achieve the highest rates of arthrodesis in multilevel lumbar fusion but is also associated with possible perioperative morbidity. A novel allograft (OSTEOAMP) is a differentiated allograft that retains growth factors supporting bone healing. The authors sought to compare the clinical and radiographic outcomes of rhBMP-2 and the novel allograft in lumbar interbody arthrodesis to determine if the latter may be a safer and equally effective alternative to rhBMP-2 for single- and multilevel posterior or transforaminal lumbar interbody fusion (PLIF or TLIF). Patients who underwent single- or multilevel TLIF or PLIF using either OSTEOAMP or rhBMP-2 at the authors' institution over a 2-year period were prospectively followed for 12 months. Healthcare utilization, safety measures, patient satisfaction, physical disability (measured on the Oswestry Disability Index [ODI]), back and leg pain (on the numeric rating scale [NRS]), quality of life (on the EQ-5D scale), and return to work (RTW) were prospectively recorded. For purposes of this study, this consecutive series was retrospectively analyzed and pseudarthrosis rates were assessed at 2 years of follow-up. All patients (100%) had both 12-month patient-reported outcome follow-up and 24-month clinical and radiographic follow-up. One thousand one hundred fifty-four patients (654 treated with OSTEOAMP, 500 with rhBMP-2) were prospectively enrolled in the institutional registry. After propensity score matching, there were no significant baseline differences between 330 novel allograft and 330 rhBMP-2 cases. Perioperative morbidity and 90-day hospital readmission (3.3% vs 2.4%, p = 0.485) did not significantly differ between the novel allograft and the rhBMP-2 cases. At the 2-year follow-up, symptomatic pseudarthrosis requiring revision surgery occurred in 8 patients (2.4%) with OSTEOAMP and 6 patients (1.8%) with rhBMP-2 (p = 0.589). The overall fusion rate at 2 years was similar between groups (p = 0.213). Both groups showed significant and equivalent improvement in patient-reported outcome measures (PROMs) from baseline to 12-month follow-up, with no significant difference in 1-year mean NRS leg pain score (2.5 vs 2.7), ODI (25 vs 26), quality-adjusted life years (0.73 vs 0.73), satisfaction (83% vs 80%), or RTW (6.6 vs 7 weeks). In the authors' institutional experience, OSTEOAMP is a clinically viable substitute for rhBMP-2 for single- and multilevel lumbar fusion. This novel allograft provides clinically effective arthrodesis and improvements in PROMs comparable to rhBMP-2 with a similar safety profile. Additional indications and outcome assessment in longitudinal studies are needed to further characterize this allogeneic graft.

Performance of subcutaneous continuous glucose monitoring in adult critically ill patients receiving vasopressor therapy.

Background Subcutaneous continuous glucose monitoring (CGM) may facilitate glucose control in the ICU. We aimed to assess the accuracy of CGM (Dexcom G6) against arterial blood glucose (ABG) in adult critically ill patients receiving intravenous insulin infusion and vasopressor therapy. We also aimed to assess feasibility and tolerability of CGM in this setting. Methods We included ICU patients receiving mechanical ventilation, insulin, and vasopressor therapy. Numerical accuracy was assessed by the mean absolute relative difference (MARD), overall, across arterial glucose strata, over different noradrenaline equivalent infusion rates, and over time since CGM start. MARD below 14% was considered acceptable. Clinical accuracy was assessed using Clarke Error Grid (CEG) analysis. Feasibility outcome included number and duration of interrupted sensor readings due to signal loss. Tolerability outcome included skin reactions related to sensor insertion or sensor adhesives. Results We obtained 2946 paired samples from 40 patients (18 with type 2 diabetes) receiving a median (IQR) maximum noradrenaline equivalent infusion rate of 0.18 (0.08-0.33) µg/kg/min during CGM. Overall, MARD was 12.7 (95% CI 10.7-15.3) % and 99.8% of CGM readings were within CEG zones A and B. MARD values ≥14% were observed when ABG was outside target range (6-10 mmol/l [108-180 mg/dl]) and with noradrenaline equivalent infusion rates above 0.10 µg/kg/min. Accuracy improved with time after CGM start, reaching MARD values below 14% after 36 hours. We observed four episodes of interrupted sensor readings due to signal loss ranging from 5 to 20 minutes. We observed no skin reactions related to sensor insertion or sensor adhesives. Conclusions In our ICU cohort of patients receiving vasopressor infusion, subcutaneous CGM demonstrated acceptable overall numerical and clinical accuracy. However, suboptimal accuracy may occur outside glucose ranges of 6-10 mmol/l (108-180 mg/dl), during higher dose vasopressor infusion, and during the first 36 hours after CGM start.

CONTINUOUS LEFT STELLATE GANGLION BLOCK DURING VT ABLATION TO SLOW VT AND IMPROVE ABLATION OUTCOME

Abstract Introduction Perioperative management of advanced patients with indication to ventricular tachycardia (VT) ablation is complex. A PAINESD score ≥ 15 was proposed to identify those who might benefit from pre–emptive mechanical cardiopulmonary support (MCS). We present a case successfully managed with continuous percutaneous left stellate ganglion block (C–PLSGB). Case A 71–year–old diabetic man with severe post–ischemic cardiomyopathy (LVEF 24%, NYHA Class III) and chronic pulmonary disease was admitted for electrical storm with multiple ICD shocks due to poorly tolerated monomorphic VT (MMVT) at 176 bpm resistant to anti–tachycardia pacing (ATP), despite ongoing chronic oral therapy with amiodarone and carvedilol. Poorly tolerated and ATP–resistant MMVTs at 170–180 bpm recurred despite intravenous (iv) amiodarone and lidocaine (20 mcg/kg/min) and oral propranolol. Ultrasound guided C–PLSGB was therefore started; lidocaine was chosen for the continuous infusion due to the short half–life, at the initial dose of 10 mg/h; 6 hours later, his poorly tolerated MMVT recurred at 167 bpm. Therefore, at first we increased iv lidocaine to 30 mcg/kg/min, without benefit, then we increased C–PLSGB at 37.5 mg/h and decreased iv lidocaine to 20 mcg/kg/min due to neurological symptoms. With this regimen, the patient stayed VT free for 2 hours, then the clinical VT recurred at 130 bpm, with good hemodynamic tolerability and ATP–response. C–PLSGB infusion was than increased to 75 mg/h, with no more VT. Endocardial VT ablation was planned. Despite a very high PAINESD score (31) we decided to avoid pre–emptive MCS. We stopped lidocaine (both iv and as C–PLSGB) 2 hours before ablation. As soon as the patient came in the EP room (before instrumentation), the clinical MMVT recurred at 133 bpm. C–PLSGB was then resumed (initially at 100 mg/h for 30 minutes, then at 37.5 mg/h). The MMVT then spontaneously recurred at 133 bpm: it was mapped and ablated in the medio–apical anterior wall, with acute VT interruption. A second VT morphology then appeared, that was mapped and ablated at a more basal site, despite a partial epicardial component of the circuit was identified. C–PLSGB was then stopped and no more VT occurred nor were induced 1 hour later. At 8 months the patient is still alive with no more VT. Conclusion C–PLSGB with individually tailored infusion rates could be used during VT ablation as a mean to reduce VT cycle length and allow for mapping without MCS.

CHARCOT NEUROARTHROPATHY: SURGICAL OUTCOMES FOLLOWING HIND- AND MIDFOOT RECONSTRUCTION. A MINIMUM 12-MONTH FOLLOW-UP FROM A TERTIARY HOSPITAL

BackgroundCorrective fusion of a deformed / unstable Charcot neuroarthropathy (CN)of the midfoot and hindfoot is performed with the aim to prevent ulcers and maintain patient mobility.MethodsBetween October 2007 and July 2018, 103 CN mid and hind foot corrections in 95 patients were performed. There were 34 hind-foot, 38 mid-foot and 31 combined hind and mid-foot surgeries. 83 feet had single stage corrections, whereas 20 required a staged operation.ResultsNinety-five patients were prospectively followed up. The mean patient age in our study was 57 years (21 – 85). Twenty-seven patients had type1 diabetes, 64 patients had type 2 and 4 patients had a neuropathy secondary to other conditions. Forty patients (42%) were offered a below knee amputation prior to attending our foot clinic. At a mean follow up of 56 months (12 – 140) we achieved 100% limb salvage with a 75% full bone fusion rate. There were 17 mortalities within our cohort at a mean period of 3 years. Ninety-seven percent (n=92) patients were mobilizing post-operatively in orthotic footwear. Fifty-two feet had pre-operative ulcers. Post-operatively 17 feet (16 patients) had persistent ulceration. Eight patients had ulcer resolution following further surgery and alteration of footwear, one patient has been listed for a below knee amputation for unstable non-union, whilst the remaining 7 patients have stable ulcers which are managed with dressings. Of the 26 feet (25 patients) with non-unions, 6 patients had revision fixation procedures whilst 8 patients required minor surgical procedures. The remaining 11 patients are stable non-unions who are asymptomatic and weight bearing. Other complications included a deep infection rate of 8% (n=7).ConclusionWe demonstrated a 100% limb salvage rate and an 83% success rate in ulcer resolution. We recommend this be done with the support of the multi-disciplinary team.

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 &lt; 0.001) and intraoperative bleeding (p &lt; 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 &lt; 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 &gt; 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.

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.