Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.

The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.

The Effect of Age-adjusted Sagittal Alignment on the Result of Posterior Decompression Surgery for Lumbar Spinal Canal Stenosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to compare the outcomes of posterior decompression surgery for lumbar spinal canal stenosis (LSS) in patients with preoperative sagittal malalignment to those without, after adjusting for age and sex. SUMMARY OF BACKGROUND DATA: Sagittal balance is an important factor in spine surgery and is thought to affect postoperative outcomes following LSS. However, the relationship between sagittal malalignment and postoperative outcomes has not been thoroughly examined. METHODS: We included 533 patients who underwent surgical treatment for LSS and also achieved two-year follow-up. Patients were categorized into either a malalignment (MA+) group (69 patients) or a matched-alignment (MA-) group (348 patients) based on age-adjusted preoperative sagittal alignment. We compared the baseline and two-year postoperative health-related quality of life (HRQOL) using the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores. We also calculated clinical efficacy using the minimal clinically important difference (MCID) based on JOABPEQ scores, and age- and sex-adjusted JOABPEQ scores two years after surgery. Differences between groups were examined using the Mann‒Whitney U test and χ 2 analysis, where applicable. RESULTS: Both groups showed an improved HRQOL after decompression surgery. Similar proportions of patients showed substantial improvement, as estimated by the MCID, in four out of five subdomains of the JOABPEQ. A significantly smaller proportion of patients in the MA+ group showed substantial improvement in lumbar function. The age- and sex-adjusted HRQOL scores two years after surgery were lower in the MA+ group, particularly in the lumbar function and social life function subdomains of the JOABPEQ. CONCLUSION: The effects of posterior decompression surgery alone can still be observed at least two years postoperatively for patients with LSS and concomitant sagittal malalignment. Patients with sagittal malalignment may experience lower HRQOL than those without this type of malalignment.

Microenvironmental modulation in tandem with human stem cell transplantation enhances functional recovery after chronic complete spinal cord injury.

While rapid advancements in regenerative medicine strategies for spinal cord injury (SCI) have been made, most research in this field has focused on the early stages of incomplete injury. However, the majority of patients experience chronic severe injury; therefore, treatments for these situations are fundamentally important. Here, we hypothesized that environmental modulation via a clinically relevant hepatocyte growth factor (HGF)-releasing scaffold and human iPS cell-derived neural stem/progenitor cells (hNS/PCs) transplantation contributes to functional recovery after chronic complete transection SCI. Effective release of HGF from a collagen scaffold induced progressive axonal elongation and increased grafted cell viability by activating microglia/macrophages and meningeal cells, inhibiting inflammation, reducing scar formation, and enhancing vascularization. Furthermore, hNS/PCs transplantation enhanced endogenous neuronal regrowth, the extension of graft axons, and the formation of circuits around the lesion and lumbar enlargement between host and graft neurons, resulting in the restoration of locomotor and urinary function. This study presents an effective therapeutic strategy for severe chronic SCI and provides evidence for the feasibility of regenerative medicine strategies using clinically relevant materials.

Rehabilitative Training Enhances Therapeutic Effect of Human-iPSC-Derived Neural Stem/Progenitor Cells Transplantation in Chronic Spinal Cord Injury.

Cell transplantation therapy using human-induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a new therapeutic strategy for spinal cord injury (SCI). Preclinical studies have demonstrated the efficacy of hiPSC-NS/PCs transplantation in the subacute phase of SCI. However, locomotor recovery secondary to hiPSC-NS/PCs transplantation is limited in the chronic phase, suggesting that additional treatment, including rehabilitative training, is required to ensure recovery. The therapeutic potential of hiPSC-NS/PCs that qualify for clinical application is yet to be fully delineated. Therefore, in this study, we investigated the therapeutic effect of the combined therapy of clinical-grade hiPSC-NS/PCs transplantation and rehabilitative training that could produce synergistic effects in a rodent model of chronic SCI. Our findings indicated that rehabilitative training promoted the survival rate and neuronal differentiation of transplanted hiPSC-NS/PCs. The combination therapy was able to enhance the expressions of the BDNF and NT-3 proteins in the spinal cord tissue. Moreover, rehabilitation promoted neuronal activity and increased 5-HT-positive fibers at the lumbar enlargement. Consequently, the combination therapy significantly improved motor functions. The findings of this study suggest that the combined therapy of hiPSC-NS/PCs transplantation and rehabilitative training has the potential to promote functional recovery even when initiated during chronic SCI.

A review of regenerative therapy for spinal cord injury using human iPS cells.

Spinal cord injury (SCI) has been considered to cause sudden, irreversible loss of function in patients. However, developments in stem cell biology and regenerative medicine are changing this conventional notion. Here we reviewed the overview of regenerative medicine of SCI. As a consequence of the establishment of human induced pluripotent stem cells (hiPSCs), hiPSC-based therapies for SCI, such as neural stem/progenitor cell (NS/PC) transplantation, have emerged as promising therapeutic modalities. Using several animal models, hiPSC-NS/PC transplantation into subacute injured spinal cords has been repeatedly demonstrated to improve locomotor function. Some biological mechanisms underlying this improvement have been proposed. In particular, combined with advanced neuroscience techniques such as designer receptors exclusively activated by designer drugs (DREADDs), neuronal relay theory, in which the transplanted cell-derived neurons reconstruct disrupted neuronal circuits, was proven to be involved histologically, pharmaceutically, electrophysiologically, and via in vivo bioimaging. Based on these findings, hiPSC-NS/PC transplantation for subacute SCI was moved ahead to a clinical study on human patients. At the same time, the search for effective treatments for chronic SCI is proceeding gradually, combining hiPSC-NS/PC transplantation with other treatment modalities such as rehabilitation, pharmaceutical interventions, or optimal scaffolds. In addition to NS/PCs, oligodendrocyte precursor cells (OPCs) are also a promising cell source for transplantation, as demyelinated axons affected by SCI can be repaired by OPCs. Therapies with OPCs derived from hiPSCs are still in preclinical studies but have shown favorable outcomes in animal models. In the future, several therapeutic options may be available according to the pathological conditions and the time period of SCI. Moreover, the application of regenerative therapy for the spinal cord could be broadened to degenerative disorders, such as spinal canal stenosis. Summary sentence: A historical review of human induced pluripotent stem cell (hiPSC) based cell transplantation therapy for spinal cord injury (SCI), in particular about footsteps of hiPSC-derived neural stem/progenitor cell transplantation, recent clinical study, and its future perspective.

A non-invasive system to monitor in vivo neural graft activity after spinal cord injury.

Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI.

Modulation by DREADD reveals the therapeutic effect of human iPSC-derived neuronal activity on functional recovery after spinal cord injury.

Transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) is considered to be a promising therapy for spinal cord injury (SCI) and will soon be translated to the clinical phase. However, how grafted neuronal activity influences functional recovery has not been fully elucidated. Here, we show the locomotor functional changes caused by inhibiting the neuronal activity of grafted cells using a designer receptor exclusively activated by designer drugs (DREADD). In vitro analyses of inhibitory DREADD (hM4Di)-expressing cells demonstrated the precise inhibition of neuronal activity via administration of clozapine N-oxide. This inhibition led to a significant decrease in locomotor function in SCI mice with cell transplantation, which was exclusively observed following the maturation of grafted neurons. Furthermore, trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results highlight the significance of engrafting functionally competent neurons by hiPSC-NS/PC transplantation for sufficient recovery from SCI.

Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function.

In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.

Acute regrowth and dissemination of a mature spinal cord teratoma after partial resection.

A 23-year-old man presented with difficulty walking and leg pain and numbness. MRI revealed a cystic mass at Th11-12 and a pineal-region tumour. The patient underwent surgery to resect the thoracic-level mass. The tumour adhered strongly to the neural tissue and could only be partially resected. On pathological examination, the resected tumour was diagnosed as a mature teratoma. The tumour regrew and disseminated within 3 months after resection. Both the spinal cord tumour and the tumour in the pineal region shrank significantly after chemotherapy and radiotherapy. Although the tumour was pathologically diagnosed as a mature teratoma, we suspect that the residual tumour contained an immature or malignant component. Thus, careful follow-up observation is mandatory after partial resection of a mature teratoma. In addition, because teratomas can disseminate in the central nervous system, the presence of teratoma should prompt an examination of both the spinal cord and brain.

Association between time to surgery and 90-day mortality after hip fracture: A retrospective cohort study of 1734 cases.

BACKGROUND: It remains unclear whether early surgical intervention can reduce mortality after surgery in hip fracture patients. The aim of this study was to investigate the association between time from injury to surgery and mortality rate within 90 days after hip fracture surgery. METHODS: We retrospectively identified 1827 patients who underwent hip fracture surgery in a tertiary care center in Japan between April 2007 and March 2017. After applying exclusion criteria (patients with spontaneous fracture, multiple fractures, revision surgery, total hip arthroplasty, or a refusal to participate), 1734 patients were included. We extracted data concerning patients' age, race, sex, operative procedure, American Society of Anesthesiologists (ASA) score, days from injury to surgery (injury-surgery days), and days from admission to surgery (admission-surgery days), which could affect 90-day mortality after surgery. Variables associated with 90-day mortality were determined using multivariate logistic regression analysis. RESULTS: The 90-day postoperative mortality rate was 3.5% (60 of 1734). Multivariable analysis showed that injury-surgery days were not associated with 90-day mortality (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.80 to 1.05; P = 0.19), and that older age (OR, 1.06; 95% CI, 1.02 to 1.10; P = 0.005), male sex (OR, 3.62; 95% CI, 1.86 to 7.03; P < 0.001) and high ASA score (OR, 2.10; 95% CI, 1.06 to 4.18; P = 0.034) significantly increased 90-day mortality. In addition, admission-surgery days were not associated with 90-day mortality (OR, 0.95; 95% CI, 0.83 to 1.09; P = 0.45). CONCLUSION: Our results demonstrated that time from injury to surgery was not associated with mortality within 90 days after surgery after adjusting for age, sex, operative procedure, and ASA score.

Pacemaker Lead Dislodgement Due to Left Shoulder Dislocation: A Case Report.

CASE: A 63-year-old man with a cardiac pacemaker presented with a left shoulder dislocation. His heart rate was 46 beats per minute, and pacemaker testing demonstrated an elevated pacing threshold, a decreased sensing threshold, and stable pacemaker lead impedance. Lead dislodgement due to the shoulder dislocation was suspected, and the patient underwent repositioning of the lead. CONCLUSION: When a patient with a pacemaker dislocates a shoulder, it should be confirmed that the heart rate is above the programmed lower rate of the pacemaker; electrocardiography should be performed, and the pacing parameters should be checked to ensure that pacing failure is not overlooked.