Intraosseous Administration Research Articles

Models of Patient Derived Hematopoietic Stem Cell Xenografts for Assessing Individual Human Radiosensitivity

There are different approaches to assessing the human individual radiosensitivity. In this study, individual radiosensitivity was assessed in terms of survival and recovery of human hematopoietic stem cells (HSC) after acute gamma irradiation of humanized mice. Immunodeficient NOD SCID mice were transplanted with cord blood HSC intravenously, peripheral or umbilical cord blood HSC intraosseously. The estimated D0 value for human HSCs was 1.19 Gy (95٪ CI 0.90 to 1.74), 0.99 Gy (95٪ CI 0.87 to 1.15), and 0.93 Gy (95٪ CI 0.61 to 1.91) for the three methods of obtaining humanized mice, respectively. For all three methods of mouse humanization, statistically similar models that describe the dependence of HSC survival on the acute gamma irradiation dose in the range of 0.5—1.5 Gy were obtained. Thus, intraosseous administration of peripheral blood HSCs to immunodeficient mice can be effectively used to assess the response of human HSCs to radiation exposure. Comparison of the HSC number (CD34+ cells) and their descendants (CD45+ cells) in non-irradiated and irradiated mice humanized with cells from the same donor on days 3 and 14 after irradiation makes it possible to evaluate the processes of radiation-induced death and recovery of HSCs. A coefficient calculated as the ratio of the proportion of HSCs among all human cells in the bone marrow of humanized mice on the 14th day to the proportion of HSCs on the 3rd day after irradiation was proposed to assess the response to radiation exposure. This coefficient had an inverse linear dependence on the radiation dose, differed in mice with increased and normal radiosensitivity, and increased with the use of the radioprotector cysteamine in humanized mice. We propose to use this coefficient for a comparative assessment of human radiosensitivity.

Pharmacokinetic and pharmacodynamic evaluation of various vasopressin doses and routes of administration in a neonatal piglet model

Epinephrine is the only recommended vasopressor during neonatal cardiopulmonary resuscitation. However, there are concerns about the potential adverse effects of epinephrine, which might hamper efficacy during cardiopulmonary resuscitation. An alternative might be vasopressin, which has a preferable adverse effect profile, however, its optimal dose and route of administration is unknown. We aimed to compare the pharmacodynamics and pharmacokinetics of various vasopressin doses administered via intravenous (IV), intraosseous (IO), endotracheal (ETT), and intranasal (IN) routes in healthy neonatal piglets. Forty-four post-transitional piglets (1–3 days of age) were anesthetized, intubated via a tracheostomy, and randomized to receive vasopressin via intravenous (control), IO, ETT, or IN route. Heart rate (HR), arterial blood pressure, carotid blood flow, and cardiac function (e.g., stroke volume, ejection fraction) were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the observation period for pharmacodynamics and pharmacokinetic analysis. Significant changes in hemodynamic parameters were observed following IO administration of vasopressin while pharmacokinetic parameters were not different between IV and IO vasopressin. Administration of vasopressin via ETT or IN did not change hemodynamic parameters and had significantly lower maximum plasma concentrations and systemic absorption compared to piglets administered IV vasopressin (p < 0.05). The IV and IO routes appear the most effective for vasopressin administration in neonatal piglets, while the ETT and IN routes appear unsuitable for vasopressin administration.

Mechanisms of Chimeric Cell Therapy in Duchenne Muscular Dystrophy.

Despite scientific efforts, there is no cure for Duchenne muscular dystrophy (DMD), a lethal, progressive, X-linked genetic disorder caused by mutations in the dystrophin gene. DMD leads to cardiac and skeletal muscle weakness, resulting in premature death due to cardio-pulmonary complications. We have developed Dystrophin Expressing Chimeric (DEC) cell therapy, DT-DEC01, by fusing human myoblasts from healthy donors and from DMD patients. Preclinical studies on human DEC cells showed increased dystrophin expression and improved cardiac, pulmonary, and skeletal muscle function after intraosseous administration. Our clinical study confirmed the safety and efficacy of DT-DEC01 therapy up to 24 months post-administration. In this study, we conducted in vitro assays to test the composition and potency of DT-DEC01, assessing chimerism level and the presence of dystrophin, desmin, and myosin heavy chain. Myoblast fusion resulted in the transfer of healthy donor mitochondria and the creation of chimeric mitochondria within DT-DEC01. The Pappenheim assay confirmed myotube formation in the final product. This study highlights the unique properties of DT-DEC01 therapy and their relevance to DMD treatment mechanisms.

Complicaciones de la administración intraósea de vancomicina en artroplastia total de cadera

IntroductionThe incidence of periprosthetic joint infection (PJI) in hip surgeries has significantly decreased thanks to intravenous (IV) antibiotic prophylaxis. However, in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or those at risk of colonization, it is necessary to include vancomycin in the prophylaxis. Intraosseous administration of vancomycin could enhance its effectiveness in total hip arthroplasty (THA). Materials and methodsA retrospective study was conducted between March and December 2023 involving 53 patients scheduled for primary THA with colonization risk factors. The median age of the patients was 67 years (range 61 to 75), and all received treatment with intraosseous vancomycin (500mg). Detailed records and documentation of complications during hospitalization and the first three months post-surgery were maintained. As a secondary outcome measure, the incidence of PJI was explored. ResultsWe administered 500mg of intraosseous vancomycin, injected into the greater trochanter, along with standard IV prophylaxis. The incidence of complications was 1.64%. The PJI rate at 90 days was 0%. ConclusionsIntraosseous administration of low-dose vancomycin in THA for patients at risk of MRSA colonization, combined with standard IV prophylaxis, was shown to be safe and did not present significant adverse effects. Furthermore, this strategy eliminates the logistical challenges associated with timely vancomycin administration.Level of evidence IV: Case Series.

“Intraosseous administration of tenecteplase for thrombolysis of an acute ischemic stroke”

IntroCurrent guidelines for acute ischemic stroke recommend timely administration of intravascular thrombolytic therapy to promote functional and neurologic outcomes. Tenecteplase is an emerging off-label therapy for this indication and being utilized by various institutions due to its simpler administration strategy. In emergent situations in which intravenous access cannot be obtained, intraosseous access is a viable option for medication administration. However, there has been minimal published cases to support the efficacy and safety of intraosseous administration of tenecteplase for acute ischemic stroke. CaseWe describe the case of a 51-year-old woman who developed acute ischemic stroke within our institution. Due to difficulty achieving intravenous access and time-dependent efficacy of thrombolytic therapy, the decision was made to administer tenecteplase by the intraosseous route. Stroke symptoms improved within 48 hours following administration without complication. ConclusionIntraosseous administration of tenecteplase may be considered for treatment of acute ischemic stroke if intravenous access is unattainable.

Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect

Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects, substantial tumor recurrence, and long-lasting bone reconstruction post tumor resection. Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices. Here, by deposition of calcium-based bilayer coating on the surface, a Mg-based composite implant platform is developed with tailored degradation characteristics, simultaneously integrated with chemotherapeutic (Taxol) loading capacity. The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles, not only in eliciting desirable osteoinductivity, but allows for modification of tumor microenvironment (TME) owing to the continuous release of degradation products. Specifically, the sustainable H2 evolution and Ca2+ from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction, which in turn leads to significant tumor-growth inhibition in vivo. In addition, the local chemotherapeutic delivery of the implant minimizes toxicity and side effects, but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model. Taken together, a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model.

Cell-based therapies hold promise for novel therapeutic strategies in regenerative medicine. We previously characterized in vitro human umbilical di-chimeric cells (HUDCs) created via the ex vivo fusion of human umbilical cord blood (UCB) cells derived from two unrelated donors. In this in vivo study, we assessed HUDC safety and biodistribution in the NOD SCID mouse model at 90 days following the systemic intraosseous administration of HUDCs. Twelve NOD SCID mice (n = 6/group) received intraosseous injection of donor UCB cells (3.0 × 106) in Group 1, or HUDCs (3.0 × 106) in Group 2, without immunosuppression. Flow cytometry assessed hematopoietic cell surface markers in peripheral blood and the presence of HLA-ABC class I antigens in lymphoid and non-lymphoid organs. HUDC safety was assessed by weekly evaluations, magnetic resonance imaging (MRI), and at autopsy for tumorigenicity. At 90 days after intraosseous cell administration, the comparable expression of HLA-ABC class I antigens in selected organs was found in UCB control and HUDC therapy groups. MRI and autopsy confirmed safety by no signs of tumor growth. This study confirmed HUDC biodistribution to selected lymphoid organs following intraosseous administration, without immunosuppression. These data introduce HUDCs as a novel promising approach for immunomodulation in transplantation.

SAFETY AND EFFICACY OF INTRAOSSEOUS ROPIVACAINE IN LOWER EXTREMITY (SORE) STUDY

IntroductionDay stay surgery for anterior cruciate ligament (ACL) reconstructions is an increasingly common practice and has driven clinicians to come up with postoperative pain regimes that allow same day mobilisation and a safe and timely discharge. There is a paucity of literature surrounding the use of intraosseous (IO) ropivacaine used as a Bier's block to provide both intraoperative and postoperative analgesia in lower limb surgery.MethodsThis patient blinded, pilot study randomised 15 patients undergoing ACL reconstruction to receive either IO ropivacaine 1.5 or 2.0 mg/kg; or 300 mg of ropivacaine as local infiltration (standard of care). Toxic plasma levels of ropivacaine have been defined in the literature and therefore the primary outcome for this study was arterial plasma concentration of ropivacaine as a means to determine its safety profile. Samples were taken via an arterial line at prespecified times after tourniquet deflation. Secondary outcomes that we were interested in included immediate postoperative pain scores using the visual analogue scale (VAS) and perioperative opioid equivalent consumption.ResultsParticipants had a mean age of 27.8 (SD 9.2) years and 87% (13/15) were male. All patients in the intervention group receiving IO ropivacaine had plasma concentrations well below the threshold for central nervous system (CNS) toxicity (0.60 µg/ml). The highest plasma concentration was achieved in the intervention group receiving 1.5 mg/kg dose of ropivacaine reaching 3.59 mg/ml. This would equate to 0.22 µg/ml of free plasma ropivacaine. There were no differences across the three groups regarding pain scores or perioperative opioid consumption.ConclusionsThis study demonstrates that IO administration of 0.2% ropivacaine is both safe and effective in reducing perioperative pain in patients undergoing ACL reconstruction. There may be scope to increase the IO dose further or utilise other analgesics via the IO regional route to improve perioperative pain relief.

Лечение гонартроза с применением аутологической обогащенной тромбоцитами плазмы

Injections of platelet-rich plasma are considered to be a promising treatment. Medicines acting on the subchondral bone can improve tissue's structure and slow down destruction of the articular cartilage. This study aimed to analyze the results of intraarticular and intraosseous administration of platelet-rich plasma (PRP) in gonarthrosis cases. One hundred and eighty-seven participants (gonarthrosis stages 1 through 3) were divided into three groups. Group 1 (treatment group) received intraarticular PRP injections, group 2 (comparison group) — intraosseous PRP injections. For assessment purposes, we used the SF-36 survey and visual analog scale. Three months after the treatment, initial pain level decreased in both groups 1 and 2. In group 1, the prevalence of synovitis went down after 3 months, in group 2 — after 6 months (21.9 and 31.3%, respectively; p &lt; 0.05). Six months after the treatment, soft tissue swelling around the joint was registered less often in groups 1 and 2 (8.2 and 8.3%, respectively). As for the physical component of the quality of life, it improved in group 1 after 3 months (70.40%), in group 2 — after 6 months (69.80%); as for the mental component, the dynamics was acknowledged positive 3 months after the treatment in groups 1 and 2 (64.30 and 65.10%, respectively), and 6 months after the treatment (65.10 and 66.40%, respectively). Thus, administration of PRP in gonarthrosis cases attenuate pain and improves the quality of life. In terms of alleviation of the clinical symptoms and improvement of the physical component of patients' lives, intraosseous PRP injections performed significantly better.

Intraosseous Administration of Medications in Total Knee Arthroplasty: An Opportunity for Improved Outcomes and Superior Compliance.

Intraosseous Administration of Medications in Total Knee Arthroplasty: An Opportunity for Improved Outcomes and Superior Compliance.

Amelioration of Morphological Pathology in Cardiac, Respiratory, and Skeletal Muscles Following Intraosseous Administration of Human Dystrophin Expressing Chimeric (DEC) Cells in Duchenne Muscular Dystrophy Model.

Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutation in the dystrophin gene. Currently there is no cure for DMD. We introduced a novel human Dystrophin Expressing Chimeric (DEC) cell therapy of myoblast origin and confirmed the safety and efficacy of DEC in the mdx mouse models of DMD. In this study, we assessed histological and morphological changes in the cardiac, diaphragm, and gastrocnemius muscles of the mdx/scid mice after the transplantation of human DEC therapy via the systemic-intraosseous route. The efficacy of different DEC doses was evaluated at 90 days (0.5 × 106 and 1 × 106 DEC cells) and 180 days (1 × 106 and 5 × 106 DEC cells) after administration. The evaluation of Hematoxylin & Eosin (H&E)-stained sectional slices of cardiac, diaphragm, and gastrocnemius muscles included assessment of muscle fiber size by minimal Feret's diameter method using ImageJ software. The overall improvement in muscle morphology was observed in DMD-affected target muscles in both studies, as evidenced by a shift in fiber size distribution toward the wild type (WT) phenotype and by an increase in the mean Feret's diameter compared to the vehicle-injected controls. These findings confirm the long-term efficacy of human DEC therapy in the improvement of overall morphological pathology in the muscles affected by DMD and introduce DEC as a novel therapeutic approach for DMD patients.

The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis

Background: Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. Purpose/Hypothesis: The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. Study Design: Controlled laboratory study. Methods: A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. Results: Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. Conclusion: IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. Clinical Relevance: Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.

Intraosseous vancomycin in total knee arthroplasty

intravenous antibiotic prophylaxis has significantly reduced the incidence of periprosthetic joint infection (PJI) in knee surgeries. However, for patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or those at risk of colonization, prophylaxis should include vancomycin. Intraosseous (IO) administration of vancomycin could enhance its effectiveness in total knee arthroplasty (TKA). a retrospective review was conducted, including 143 patients at risk of PJI scheduled for TKA who received IO vancomycin along with intravenous (IV) cefazolin, referred to as group I (GI), between May 2021 and December 2022. The occurrence of complications in the first three postoperative months was evaluated. Results were compared with 140 patients without risk factors who received standard IV prophylaxis, designated as group II (GII). in GI, 500 mg of IO vancomycin was administered, injected into the proximal tibia, in addition to standard IV prophylaxis. In GII, patients received only IV cefazolin. The incidence of complications was 1.64% in GI and 1.4% in GII. The PJI rate at 90 postoperative days was 0.69% in GI and 0.71% in GII. IO vancomycin administration, along with standard IV prophylaxis, provides a safe and effective alternative for patients at risk of MRSA colonization. This approach minimizes complications associated with IV vancomycin use and addresses logistical challenges of timely administration.

INNOVATIVE THERAPIES IN REGENERATIVE MEDICINE AND TRANSPLANTATION

Introduction: In the past decade we have observed fast development of a new medical fields including regenerative medicine and reconstructive transplantation of the vascularized composite allografts (VCA). The VCA procedures include the new generation of face transplants, hand transplants and many other organs which opened a new reconstructive option for severely damaged patients. The lecture summarizes the risks and benefits of the VCA transplants specifically in the context of the need for life-long immunosuppression to extend VCA survival. Aim: Novel therapeutic strategies of different cell- based therapies are discussed with special emphasizes on the new generation of the donor-recipient chimeric cells used as a supportive tolerogenic therapy for VCA transplants. Material and Methods: Development of the preclinical studies carried in the experimental animal models for creation of the chimeric cells is outlined. This is followed by the creation of the human hematopoietic chimeric cells of the bone marrow and the Umbilical Cord Blood cells origin, confirming tolerogenic and immunomodulatory properties of these new cell-based therapies for application in theVCA and solod organ transplantation. Further development of chimeric cells in the field of regenerative medicine include creation of the Dystrophin Expressing Chimeric (DEC) cells as a novel therapeutic approach for patients with Duchenne muscular dystrophy (DMD). Results: In preparation to clinical applications DEC cells safety and efficacy was tested in the mdx mouse models of DMD. The safety of DEC biodistribution to the DMD- affected target organs of heart, diaphragm and gastrocnemius muscle was confirmed and correlated with improvement in functional tests assessed by echocardiography, plethysmography and standard tests of muscle strengths. These encouraging results observed in preclinical studies lead to the development of the clinical protocol for DMD patients. Currently the DT-DEC01 therapy was applied to seven DMD patients. Both, safety and efficacy of DT-DEC01 cells was confirmed up to 24 months after systemic intraosseous administration to the DMD patients. Conclusions: This pilot clinical study introduces DEC cells as a novel universal therapeutic approach for treatment of DMD and other muscular dystrophies regardless of gene mutation and ambulatory status of the patients.

Transplantation of Donor-Recipient Chimeric Cells Restores Peripheral Blood Cell Populations and Increases Survival after Total Body Irradiation-Induced Injury in a Rat Experimental Model.

Current therapies for acute radiation syndrome (ARS) involve bone marrow transplantation (BMT), leading to graft-versus-host disease (GvHD). To address this challenge, we have developed a novel donor-recipient chimeric cell (DRCC) therapy to increase survival and prevent GvHD following total body irradiation (TBI)-induced hematopoietic injury without the need for immunosuppression. In this study, 20 Lewis rats were exposed to 7 Gy TBI to induce ARS, and we assessed the efficacy of various cellular therapies following systemic intraosseous administration. Twenty Lewis rats were randomly divided into four experimental groups (n = 5/group): saline control, allogeneic bone marrow transplantation (alloBMT), DRCC, and alloBMT + DRCC. DRCC were created by polyethylene glycol-mediated fusion of bone marrow cells from 24 ACI (RT1a) and 24 Lewis (RT11) rat donors. Fusion feasibility was confirmed by flow cytometry and confocal microscopy. The impact of different therapies on post-irradiation peripheral blood cell recovery was evaluated through complete blood count, while GvHD signs were monitored clinically and histopathologically. The chimeric state of DRCC was confirmed. Post-alloBMT mortality was 60%, whereas DRCC and alloBMT + DRCC therapies achieved 100% survival. DRCC therapy also led to the highest white blood cell counts and minimal GvHD changes in kidney and skin samples, in contrast to alloBMT treatment. In this study, transplantation of DRCC promoted the recovery of peripheral blood cell populations after TBI without the development of GVHD. This study introduces a novel and promising DRCC-based bridging therapy for treating ARS and extending survival without GvHD.

Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic–Intraosseous Administration

Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by mutations in the dystrophin gene, leading to muscle degeneration and wasting. Electromyography (EMG) is an objective electrophysiological biomarker of muscle fiber function in muscular dystrophies. A novel, DT-DEC01 therapy, consisting of Dystrophin Expressing Chimeric (DEC) cells created by fusing allogeneic myoblasts from normal donors with autologous myoblasts from DMD-affected patients, was assessed for safety and preliminary efficacy in boys of age 6–15 years old (n = 3). Assessments included EMG testing of selected muscles of upper (deltoideus, biceps brachii) and lower (rectus femoris and gastrocnemius) extremities at the screening visit and at 3, 6, and 12 months following systemic–intraosseous administration of a single low dose of DT-DEC01 therapy (Bioethics Committee approval no. 46/2019). No immunosuppression was administered. Safety of DT-DEC01 was confirmed by the lack of therapy-related Adverse Events or Serious Adverse Events up to 22 months following DT-DEC01 administration. EMG of selected muscles of both, ambulatory and non-ambulatory patients confirmed preliminary efficacy of DT-DEC01 therapy by an increase in motor unit potentials (MUP) duration, amplitudes, and polyphasic MUPs at 12 months. This study confirmed EMG as a reliable and objective biomarker of functional assessment in DMD patients after intraosseous administration of the novel DT-DEC01 therapy.

Intraosseous regional prophylaxis in total knee arthroplasty.

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date.

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration

Duchenne Muscular Dystrophy (DMD) is a progressive and fatal muscle-wasting disease with no known cure. We previously reported the preliminary safety and efficacy up to six months after the administration of DT-DEC01, a novel Dystrophin Expressing Chimeric (DEC) cell therapy created by fusion of myoblasts of DMD patient and the normal donor. In this 12-month follow-up study, we report on the safety and functional outcomes of three DMD patients after the systemic intraosseous administration of DT-DEC01. The safety of DT-DEC01 was confirmed by the absence of Adverse Events (AE) and Severe Adverse Events (SAE) up to 21 months after intraosseous DT-DEC01 administration. The lack of presence of anti-HLA antibodies and Donors Specific Antibodies (DSA) further confirmed DT-DEC01 therapy safety. Functional assessments in ambulatory patients revealed improvements in 6-Minute Walk Test (6MWT) and timed functions of North Star Ambulatory Assessment (NSAA). Additionally, improvements in PUL2.0 test and grip strength correlated with increased Motor Unit Potentials (MUP) duration recorded by Electromyography (EMG) in both ambulatory and non-ambulatory patients. DT-DEC01 systemic effect was confirmed by improved cardiac and pulmonary parameters and daily activity recordings. This follow-up study confirmed the safety and preliminary efficacy of DT-DEC01 therapy in DMD-affected patients up to 12 months after intraosseous administration. DT-DEC01 introduces a novel concept of personalized myoblast-based cellular therapy that is irrespective of the mutation type, does not require immunosuppression or the use of viral vectors, and carries no risk of off target mutations. This establishes DT-DEC01 as a promising and universally effective treatment option for all DMD patients.Graphical

A multimodal intraosseous infusion of morphine and ketorolac decreases early postoperative pain and opioid consumption following total knee arthroplasty

BackgroundMultimodal pain management regimens and intraosseous infusion of morphine are two novel techniques that show promise in decreasing postoperative pain and opioid consumption following total knee arthroplasty. However, no study has analyzed the intraosseous infusion of a multimodal pain management regimen in this patient population. The purpose of our investigation was to examine the intraosseous administration of a multimodal pain regimen comprised of morphine and ketorolac during total knee arthroplasty with regard to immediate and 2-week postoperative pain, opioid pain medication intake, and nausea levels. MethodsIn this prospective cohort study with comparisons to a historical control group, 24 patients were prospectively enrolled to receive an intraosseous infusion of morphine and ketorolac dosed according to age-based protocols while undergoing total knee arthroplasty. Immediate and 2-week postoperative Visual Analog Score (VAS) pain scores, opioid pain medication intake, and nausea levels were recorded and compared against a historical control group that received an intraosseous infusion of morphine alone. ResultsDuring the first four postoperative hours, patients who received the multimodal intraosseous infusion experienced lower VAS pain scores and required less breakthrough intravenous pain medication than those patients in our historical control group. Following this immediate postoperative period, there were no additional differences between groups in terms of pain levels or opioid consumption, and there were no differences in nausea levels between groups at any time. ConclusionsOur multimodal intraosseous infusion of morphine and ketorolac dosed according to age-based protocols improved immediate postoperative pain levels and reduced opioid consumption in the immediate postoperative period for patients undergoing total knee arthroplasty.

Impact of the route of adrenaline administration in patients suffering from out-of-hospital cardiac arrest on 30-day survival with good neurological outcome (ETIVIO study)

BackgroundOver the past decades, international guidelines for cardiopulmonary resuscitation (CPR) have changed the recommendation for alternative routes for drug administration. Until now, evidence for the substantial superiority of one route with respect to treatment outcome after CPR has been lacking. The present study compares the effects of intravenous (IV), intraosseous (IO) and endotracheal (ET) adrenaline application during CPR in out-of-hospital cardiac arrest (OHCA) on clinical outcomes within the database of the German Resuscitation Registry (GRR).MethodsThis registry analysis was based on the GRR cohort of 212,228 OHCA patients between 1989 and 2020. Inclusion criteria were: OHCA, application of adrenaline, and out-of-hospital CPR. Excluded from the study were patients younger than 18 years, those who had trauma or bleeding as suspected causes of cardiac arrest, and incomplete data sets. The clinical endpoint was hospital discharge with good neurological outcome [cerebral performance category (CPC) 1/2]. Four routes of adrenaline administration were compared: IV, IO, IO + IV, ET + IV. Group comparisons were done using matched-pair analysis and binary logistic regression.ResultsIn matched-pair group comparisons of the primary clinical outcome hospital discharge with CPC 1/2, the IV group (n = 2416) showed better results compared to IO (n = 1208), [odds ratio (OR): 2.43, 95% confidence interval (CI): 1.54–3.84, p < 0.01] and when comparing IV (n = 8706) to IO + IV (n = 4353), [OR: 1.33, 95% CI: 1.12–1.59, p < 0.01]. In contrast, no significant difference was found between IV (n = 532) and ET + IV (n = 266), [OR: 1.26, 95% CI: 0.55–2.90, p = 0.59]. Concurrently, binary logistic regression yielded a highly significant effect of vascular access type (χ² = 67.744(3), p < 0.001) on hospital discharge with CPC1/2, with negative effects for IO (regression coefficient (r.c.) = − 0.766, p = 0.001) and IO + IV (r.c. = − 0.201, p = 0,028) and no significant effect for ET + IV (r.c. = 0.117, p = 0.770) compared to IV.ConclusionsThe GRR data, collected over a period of 31 years, seem to emphasize the relevance of an IV access during out-of-hospital CPR, in the event that adrenaline had to be administered. IO administration of adrenaline might be less effective. ET application, though removed in 2010 from international guidelines, could gain importance as an alternative route again.