Heterogeneous osteoimmune profiles via single-cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment.

Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell-cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.

Psychiatric adverse events following COVID-19 vaccination: a population-based cohort study in Seoul, South Korea.

Evidence has suggested an increased risk of psychiatric manifestations following viral infections including coronavirus disease-2019 (COVID-19). However, psychiatric adverse events (AEs) after COVID-19 vaccination, which were documented in case reports and case series, remain unclear. This study is aimed to investigate the psychiatric AEs after COVID-19 vaccination from a large population-based cohort in Seoul, South Korea. We recruited 50% of the Seoul-resident population randomly selected from the Korean National Health Insurance Service (KNHIS) claims database on 1, January, 2021. The included participants (n = 2,027,353) from the Korean National Health Insurance Service claims database were divided into two groups according to COVID-19 vaccination. The cumulative incidences per 10,000 of psychiatric AEs were assessed on one week, two weeks, one month, and three months after COVID-19 vaccination. Hazard ratios (HRs) and 95% Confidence interval (CIs) of psychiatric AEs were measured for the vaccinated population. The cumulative incidence of depression, anxiety, dissociative, stress-related, and somatoform disorders, sleep disorders, and sexual disorders at three months following COVID-19 vaccination were higher in the vaccination group than no vaccination group. However, schizophrenia and bipolar disorders showed lower cumulative incidence in the vaccination group than in the non-vaccinated group. Depression (HR [95% CI] = 1.683 [1.520-1.863]), anxiety, dissociative, stress-related, and somatoform disorders (HR [95% CI] = 1.439 [1.322-1.568]), and sleep disorders (HR [95% CI] = 1.934 [1.738-2.152]) showed increased risks after COVID-19 vaccination, whereas the risks of schizophrenia (HR [95% CI] = 0.231 [0.164-0.326]) and bipolar disorder (HR [95% CI] = 0.672 [0.470-0.962]). COVID-19 vaccination increased the risks of depression, anxiety, dissociative, stress-related, and somatoform disorders, and sleep disorders while reducing the risk of schizophrenia and bipolar disorder. Therefore, special cautions are necessary for administering additional COVID-19 vaccinations to populations vulnerable to psychiatric AEs.

Autoimmune adverse event following COVID-19 vaccination in Seoul, South Korea.

BACKGROUND: There is growing evidence that the coronavirus disease 2019 (COVID-19) vaccination can affect the regulation of the immune system, leading to the development of autoimmune diseases. However, the autoimmune adverse events (AEs) after COVID-19 vaccination remain largely unclear. OBJECTIVE: We sought to investigate the autoimmune AEs after COVID-19 vaccination from a population-based cohort in South Korea. METHODS: A total of 4,203,887 participants, representing 50% of the population residing in Seoul, were recruited from the National Health Insurance Service database and then divided into 2 groups on the basis of COVID-19 vaccination. The cumulative incidence, hazard ratios (HRs), and 95% CIs of autoimmune AEs were assessed following COVID-19 vaccination. RESULTS: The incidence of vitiligo has been observed to be significantly higher in the vaccination group compared with the no vaccination group. The cumulative incidence of vitiligo began to show a significant difference starting 2 weeks after vaccination, and it reached 2.2% in the vaccination group and 0.6% in the no vaccination group by 3 months after COVID-19 vaccination. Vitiligo (HR, 2.714; 95% CI, 1.777-4.146) was an increased risk among autoimmune AEs. Furthermore, the risk of vitiligo was the highest for heterologous vaccination (HR, 3.890; 95% CI, 2.303-6.573) compared with using cDNA vaccine (HR, 2.861; 95% CI, 1.838-4.453) or mRNA vaccine (HR, 2.475; 95% CI, 1.607-3.813). CONCLUSIONS: Vitiligo as an autoimmune AE was noted to be substantially higher in the COVID-19-vaccinated group compared with the controls. Therefore, the occurrence of vitiligo could be considered as one of the significant AEs post-COVID-19 vaccination.

Tumor-intrinsic and Cancer-associated Fibroblast Subtypes Independently Predict Outcomes in Pancreatic Cancer.

OBJECTIVE: To assess the utility of tumor-intrinsic and cancer-associated fibroblast (CAF) subtypes of pancreatic ductal adenocarcinoma (PDAC) in predicting response to neoadjuvant therapy (NAT) and overall survival. BACKGROUND: PDAC remains a deadly disease with limited treatment options, and both the tumor as well as the microenvironment play an important role in pathogenesis. Gene expression-based tumor-intrinsic subtypes (classical and basal-like) have been shown to predict outcomes, but tumor microenvironment subtypes are still evolving. METHODS: RNA-sequencing was performed on 114 deidentified resected PDAC tumors. Clinical data were collected by retrospective chart review. Single sample classifiers (SSCs) were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using log-rank test. RESULTS: Patients who received NAT had an increase in overall survival (OS), with median survival of 27.9 months compared to 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (HR 0.64, P=0.076). Either tumor-intrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtype had the best outcomes. When evaluated together, patients with classical-restCAF subtype had the best OS and basal-permCAF the worst OS (P<0.0001). NAT patients with classical-restCAF subtype demonstrated the longest OS compared to the other groups (P=0.00041). CONCLUSIONS: CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting survival with or without neoadjuvant FOLFIRINOX in PDAC. Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy.

Myofibroblastic cancer-associated fibroblast subtype heterogeneity in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a fibrotic stroma that has both tumor-promoting and tumor-restraining properties. Different types of cancer-associated fibroblasts (CAFs) have been described. Here, we investigated whether CAFs within the same subtype exhibit heterogeneous functions. METHODS: We evaluated the gene and protein expression differences in two myofibroblastic CAF (myCAF) lines using single-cell and bulk RNA-sequencing. We utilized proliferation and migration assays to determine the effect of different CAF lines on a tumor cell line. RESULTS: We found that myCAF lines express an activated stroma subtype gene signature, which is associated with a shorter survival in patients. Although both myCAF lines expressed α-smooth muscle actin (α-SMA), platelet-derived growth factor-α (PDGFR-α), fibroblast-activated protein (FAP), and vimentin, we observed heterogeneity between the two lines. Similarly, despite being consistent with myCAF gene expression overall, heterogeneity within specific genes was observed. We found that these differences extended to the functional level where the two myCAF lines had different effects on the same tumor cell line. The myCAF216 line, which had slightly increased inflammatory CAF-like gene expression and higher protein expression of α-SMA, PDGFR-α, and FAP was found to restrain migration of tumor cells. CONCLUSIONS: We found that two myCAF lines with globally similar expression characteristics had different effects on the same tumor cell line, one promoting and the other restraining migration. Our study highlights that there may be unappreciated heterogeneity within CAF subtypes. Further investigation and attention to specific genes or proteins that may drive this heterogeneity will be important.

The efficacy of anterior vertebral body tethering in lenke type 6 curves for adolescent idiopathic scoliosis.

PURPOSE: Spinal fusion is the standard treatment for severe forms of adolescent idiopathic scoliosis (AIS). However, with the lowest instrumented vertebra that is usually located at L3 or L4, patients are prone to develop adjacent segment degeneration in the long term. Vertebral body tethering (VBT) as motion preserving technique has become an alternative for select patients with AIS. Several studies have presented the outcome after thoracic VBT but no study has analyzed the outcome after VBT for Lenke type 6 curves. METHODS: This is a retrospective single center data analysis of patients who have had bilateral VBT for Lenke type 6 curves and a minimum follow up of 24 months. Radiographic analysis was performed on several time points. Suspected tether breakages were additionally analyzed with respect to location and time at occurrence. RESULTS: 25 patients were included. Immediate thoracic curve correction was 55.4% and 71.7% for TL/L curves. Loss of correction was higher for TL/L curves and resulted in a correction rate of 48.3% for thoracic curves and 48.9% for TL/L curves at 24 months post-operatively. 22 patients were suspected to have at least one segment with a tether breakage. Three patients required a re-VBT but no patient received posterior spinal fusion. CONCLUSION: Bilateral VBT for Lenke type 6 curves is feasible and shows a significant curve correction for thoracic and TL/L curves at a minimum of 24 months post-operatively. Tether breakage rate and loss of correction remain an unfavorable observation that needs to be improved in the future.

Radiological Outcomes of Re-tethering for Adolescent Idiopathic Scoliosis: A 2-to-5-year Follow-Up Case Series After Index Vertebral Body Tethering Failure.

PURPOSE: Vertebral Body Tethering (VBT) has been shown to have a less predictable outcome compared to spinal fusion in patients with adolescent idiopathic scoliosis (AIS). Tether breakage is a common mechanical event that sometimes leads to loss of correction. No data has been published that evaluates the outcome of re-tethering in patients who underwent revision surgery for failed VBT, which was the purpose of this study. METHODS: This is an analysis of a prospectively collected single center database of 290 patients who have had VBT. Patients for this study were included if they have had re-tethering after failed VBT and a minimum follow up of 24 months after index surgery as well as a minimum follow up of 12 months after revision surgery. Revision surgeries included tether exchange, tether reinforcement and/or mono- and bisegmental lateral fusion. Main outcome of interest was curve magnitude at latest follow up. RESULTS: 11 patients were identified who received VBT for 16 curves of which 13 curves have had failed index surgery. Mean follow up from index surgery was 40 months, time between index and revision surgery was 22 months and latest follow up after revision surgery 19 months. Re-tethering resulted in an additional correction of 42% for thoracic and 63% for thoracolumbar curves. These results remained clinically stable with only minor loss of correction at final follow up. No patient underwent or was indicated for spinal fusion. CONCLUSION: Re-tethering is feasible and able to achieve additional correction and a sustainable result.

Early-term outcome of apical fusion with vertebral body tethering for thoracolumbar curves in adolescent idiopathic scoliosis: a preliminary study.

INTRODUCTION: Vertebral body tethering (VBT) has become an alternative option for select patients with idiopathic scoliosis. However, studies have shown a high number of tether breakages, specifically after thoracolumbar (TL) VBT, that can have a negative impact on the outcome, when the breakage occurs within the first year after surgery. In order to overcome this problem, we have started to apply an apical fusion (AF) in combination with TL VBT for select patients. This study aims to analyze the outcome after AF plus VBT. METHODS: This is a retrospective single surgeon's data analysis. All patients were included who have had TL VBT after January 2022 and a follow-up of 12 months. Patients were grouped based on whether they only had VBT or VBT + AF. RESULTS: Twenty-five patients were analyzed (15 VBT, 10 VBT + AF). Both groups showed a significant curve correction for thoracic and TL curves. Minor loss of correction was observed in both groups. A significant difference was seen regarding early tether breakages, which were found in 60% of VBT patients and 10% of VBT + AF patients. CONCLUSION: The preliminary data shows a significant reduction of early tether breakages when TL VBT is applied in combination with AF.

Assessing the Reproducibility of the Structured Abstracts Generated by ChatGPT and Bard Compared to Human-Written Abstracts in the Field of Spine Surgery: Comparative Analysis.

BACKGROUND: Due to recent advances in artificial intelligence (AI), language model applications can generate logical text output that is difficult to distinguish from human writing. ChatGPT (OpenAI) and Bard (subsequently rebranded as "Gemini"; Google AI) were developed using distinct approaches, but little has been studied about the difference in their capability to generate the abstract. The use of AI to write scientific abstracts in the field of spine surgery is the center of much debate and controversy. OBJECTIVE: The objective of this study is to assess the reproducibility of the structured abstracts generated by ChatGPT and Bard compared to human-written abstracts in the field of spine surgery. METHODS: In total, 60 abstracts dealing with spine sections were randomly selected from 7 reputable journals and used as ChatGPT and Bard input statements to generate abstracts based on supplied paper titles. A total of 174 abstracts, divided into human-written abstracts, ChatGPT-generated abstracts, and Bard-generated abstracts, were evaluated for compliance with the structured format of journal guidelines and consistency of content. The likelihood of plagiarism and AI output was assessed using the iThenticate and ZeroGPT programs, respectively. A total of 8 reviewers in the spinal field evaluated 30 randomly extracted abstracts to determine whether they were produced by AI or human authors. RESULTS: The proportion of abstracts that met journal formatting guidelines was greater among ChatGPT abstracts (34/60, 56.6%) compared with those generated by Bard (6/54, 11.1%; P<.001). However, a higher proportion of Bard abstracts (49/54, 90.7%) had word counts that met journal guidelines compared with ChatGPT abstracts (30/60, 50%; P<.001). The similarity index was significantly lower among ChatGPT-generated abstracts (20.7%) compared with Bard-generated abstracts (32.1%; P<.001). The AI-detection program predicted that 21.7% (13/60) of the human group, 63.3% (38/60) of the ChatGPT group, and 87% (47/54) of the Bard group were possibly generated by AI, with an area under the curve value of 0.863 (P<.001). The mean detection rate by human reviewers was 53.8% (SD 11.2%), achieving a sensitivity of 56.3% and a specificity of 48.4%. A total of 56.3% (63/112) of the actual human-written abstracts and 55.9% (62/128) of AI-generated abstracts were recognized as human-written and AI-generated by human reviewers, respectively. CONCLUSIONS: Both ChatGPT and Bard can be used to help write abstracts, but most AI-generated abstracts are currently considered unethical due to high plagiarism and AI-detection rates. ChatGPT-generated abstracts appear to be superior to Bard-generated abstracts in meeting journal formatting guidelines. Because humans are unable to accurately distinguish abstracts written by humans from those produced by AI programs, it is crucial to exercise special caution and examine the ethical boundaries of using AI programs, including ChatGPT and Bard.

Analysis of the association between vestibular schwannoma and hearing status using a newly developed radiomics technique.

PURPOSE: Vestibular schwannoma is a benign tumor originating from Schwann cells surrounding the eighth cranial nerve and can cause hearing loss, tinnitus, balance problems, and facial nerve disorders. Because of the slow growth of the tumor, predicting the hearing function of patients with vestibular schwannoma's is important to obtain information that would be useful for deciding the treatment modality. This study aimed to analyze the association between magnetic resonance imaging features and hearing status using a new radiomics technique. METHODS: We retrospectively analyzed 115 magnetic resonance images and hearing results from 73 patients with vestibular schwannoma. A total of 70 radiomics features from each tumor volume were calculated using T1-weighted magnetic resonance imaging. Radiomics features were classified as histogram-based, shape-based, texture-based, and filter-based. The least absolute shrinkage and selection operator method was used to select the radiomics features among the 70 features that best predicted the hearing test. To ensure the stability of the selected features, the least absolute shrinkage and selection operator method was repeated 10 times. Finally, features set five or more times were selected as radiomics signatures. RESULTS: The radiomics signatures selected using the least absolute shrinkage and selection operator method were: minimum, variance, maximum 3D diameter, size zone variance, log skewness, skewness slope, and kurtosis slope. In random forest, the mean performance was 0.66 (0.63-0.77), and the most important feature was Log skewness. CONCLUSIONS: Newly developed radiomics features are associated with hearing status in patients with vestibular schwannoma and could provide information when deciding the treatment modality.

Accuracy of models to prognosticate survival after surgery for pancreatic cancer in the era of neoadjuvant therapy.

BACKGROUND: Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). METHODS: We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. RESULTS: A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. CONCLUSIONS: Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

The neuro-protective role of telomerase via TERT/TERF-2 in the acute phase of spinal cord injury.

PURPOSE: To investigate the interaction of telomerase activity and telomere length on neuro-protection or neuro-degeneration effects after spinal cord injury (SCI). METHODS: A contusive SCI model was developed using 56 Sprague-Dawley rats. Seven rats were allocated into acute injury phase groups (1, 3, 8, 24, and 48 h), and sub-acute and chronic injury phase groups (1, 2, and 4 weeks). Telomerase activity was assessed by telomerase reverse transcriptase (TERT) and telomeric repeat binding factor-2 (TERF-2). Differentiation of activated neural stem cells was investigated by co-expression of neuronal/glial cell markers. Apoptosis expression was also investigated by caspase-3, 8, and 9 using terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Immunofluorescence staining and western blotting were performed for quantitative analyses. RESULTS: Expression of TERT increased gradually until 24 h post-injury, and was decreased following SCI (P < 0.05). TERF-2 also was increased following SCI until 24 h post-injury and then decreased with time (P < 0.05). Co-localization of TERT and TERF-2 was higher at 24 h post-injury. High expression of TERT was seen in neurons (Neu N Ab), however, expression of TERT was relatively lower in astrocytes and oligodendrocytes. Apoptosis analysis showed persistent high expression of caspases-3, -9, and -8 during the observation period. CONCLUSIONS: Increased TERT and TERF-2 activity were noted 24 h post-injury in the acute phase of SCI with TERF-2 maintaining telomeric-repeat length. Our results suggest that increased activity of telomere maintenance may be related to neuro-protective mechanisms against subsequent apoptosis resulting from DNA damage after acute SCI.

Significance of paraspinal muscle quality in risk between single and multiple osteoporotic vertebral fractures.

PURPOSE: To compare paraspinal muscle quality between patients with single and multiple osteoporotic vertebral fractures (OVFs) and evaluate the role of the paraspinal muscles in OVFs. METHODS: A total of 262 consecutive patients with OVFs were retrospectively analyzed in two groups: those with single OVF (n = 173) and those with multiple OVFs (n = 89). The cross-sectional area (CSA) and fatty degeneration of the paraspinal muscles were calculated from axial T2-weighted magnetic resonance imaging at the level of the L4 upper endplate by manual tracing in ImageJ software. Pearson's correlation analysis was performed to analyze correlations of paraspinal muscle quality to multiple OVFs. RESULTS: FD in all the paraspinal muscles was significantly higher in the multiple OVF group than the single OVF group (all p < 0.005). The functional CSA (fCSA) of the paraspinal muscles was significantly lower in the multiple OVF group than the single OVF group (all Ps < 0.001), except for the erector spine (p = 0.304). The Pearson's correlation analysis showed significant positive inter-correlations for the fCSAs of all the paraspinal muscles and the occurrence of multiple OVFs. CONCLUSIONS: The pure muscle volumes of the multifidus, psoas major, and quadratus lumborum were lower in patients with multiple OVFs than in those with a single OVF. Furthermore, the inter-correlation among all the paraspinal muscles indicate that the muscle-bone crosstalk profoundly existed in vertebral fracture cascade. Therefore, special attention to paraspinal muscle quality is needed to prevent progression to multiple OVFs.

Fusion rates based on type of bone graft substitute using minimally invasive scoliosis surgery for adolescent idiopathic scoliosis.

BACKGROUND: Minimally invasive scoliosis surgery (MISS) is currently introduced on novel technique for surgical treatment of adolescent idiopathic scoliosis (AIS). This study is aimed to evaluate the efficacy of facet fusion in MISS compared to posterior fusion in conventional open scoliosis surgery (COSS) and compare facet fusion rates based on three bone graft substitutes in MISS for adolescent idiopathic scoliosis (AIS). METHODS: Eighty six AIS patients who underwent scoliosis surgery were divided into two groups: the COSS group and the MISS group. COSS was performed through posterior fusion with allograft. MISS was applied via facet fusion with three bone graft substitutes. The MISS group was further divided into three subgroups based on graft substitute: Group A (allograft), Group B (demineralized bone matrix [DBM]), and group C (demineralized cancellous bone chips). Fusion rate was measured using conventional radiographs to visualize loss of correction > 10°, presence of lysis around implants, breaks in fusion mass, and abnormal mobility of the fused segment. RESULTS: The fusion rates showed no significant difference in COSS and MISS groups (p = 0.070). In the MISS group, the fusion rates were 85, 100, and 100% in groups A, B, and C, respectively, with no significant difference (p = 0.221). There were no statistical differences between groups A, B, and C in terms of correction rate, fusion rate, and SRS-22 scores (p > 0.05). CONCLUSIONS: The facet fusion in MISS showed comparable to posterior fusion in COSS with regard to radiological and clinical outcomes. Furthermore, the type of graft substitute among allograft, DBM, and demineralized cancellous bone chips did not affect facet fusion rate or clinical outcomes in MISS. Therefore, MISS showed comparable fusion rate (with no influences on the type of graft substitute) and clinical outcomes to those of COSS in the surgical treatment of AIS.

Audiologic results of total ossicular replacement prosthesis bypassing the stapes suprastructure in canal wall down mastoidectomy.

OBJECTIVES: Sometimes performing PORP adequately is challenging when the stapes is tilted or the suprastructure is partially damaged owing to inflammation or infection. In such cases, the implementation of a TORP bypassing the stapes can be a useful alternative. This study aimed to investigate whether bypassing the stapes suprastructure during total ossicular replacement prosthesis (TORP) affects postoperative complications or audiological outcomes. MATERIAL AND METHODS: Among 104 patients who underwent open cavity mastoidectomy and ossiculoplasty using a titanium prosthesis at Korea University Ansan Hospital between January 2012 and December 2019, we compared the preoperative and postoperative audiological results and surgical complications of 52, 21, and 31 patients who underwent partial ossicular replacement prosthesis (PORP), TORP bypassing the remaining stapes suprastructure, and TORP on the stapes footplate or oval window, respectively. RESULTS: The air-bone gap before surgery was significantly different in the TORP on the stapes footplate group (34.2 ± 12.0 dB) than that in the PORP (22.9 ± 13.8 dB) and TORP bypassing the stapes groups (20.7 ± 11.5 dB, p < 0.001). After surgery, there were no significant differences among the groups (p = 0.818). The air-bone gap difference before surgery was associated with the presence of stapes before surgery (p < 0.001). There was no difference in the proportion of postoperative tympanic perforation, whether it was a revision surgery, malleus status, or the size of perforation of the tympanic membrane among the three groups. CONCLUSION: When performing ossiculoplasty using TORP, bypassing the stapes did not affect surgical and audiologic outcomes.

Analysis of hearing prognosis risk factors in pediatric unilateral sudden sensorineural hearing loss.

OBJECTIVES: Pediatric idiopathic sudden hearing loss (PISSNHL) is a rare disease with no established factor affecting its prognosis. In this study, we investigate the risk factors affecting the prognosis of PISSNHL. MATERIAL AND METHODS: Among the patients who visited our hospital from January 2010 to December 2021, the characteristics associated prognosis of 54 patients with unilateral PISSNHL were retrospectively confirmed. RESULTS: Patients' recovery was determined by applying Siegel's criteria (SC) and AAO-HNS criteria (AC). Twenty-seven (50 %) and 29 patients (54.3 %) recovered for SC and AC, respectively. Age, sex, side, duration between onset and treatment, administration of intra-tympanic steroid injection, accompanying symptoms (tinnitus and dizziness), BMI, serum creatinine level, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte count (PLR), lymphocyte count, and platelet count were not significantly different between the recovery group and the poor recovery group (P > 0.05). The patients were divided into five groups according to the initial hearing of the affected ear and again according to their audiogram type. The initial hearing levels, hearing level severity, and the audiogram type were significantly different between the deaf group (>100 dB HL) and the non-deaf group (P < 0.05). CONCLUSION: The prognosis of PISSNHL is closely related to the initial hearing at the onset. If the initial hearing level is <100 dB, the recovery rate is approximately 50 %, therefore requiring active treatment and emotional support. It may also be related to the type of audiometric curve.

Osteobiologies for Spinal Fusion from Biological Mechanisms to Clinical Applications: A Narrative Review.

Degenerative lumbar spinal disease (DLSD), including spondylolisthesis and spinal stenosis, is increasing due to the aging population. Along with the disease severity, lumbar interbody fusion (LIF) is a mainstay of surgical treatment through decompression, the restoration of intervertebral heights, and the stabilization of motion segments. Currently, pseudoarthrosis after LIF is an important and unsolved issue, which is closely related to osteobiologies. Of the many signaling pathways, the bone morphogenetic protein (BMP) signaling pathway contributes to osteoblast differentiation, which is generally regulated by SMAD proteins as common in the TGF-ß superfamily. BMP-2 and -4 are also inter-connected with Wnt/ß-catenin, Notch, and FGF signaling pathways. With the potent potential for osteoinduction in BMP-2 and -4, the combination of allogenous bone and recombinant human BMPs (rhBMPs) is currently an ideal fusion material, which has equalized or improved fusion rates compared to traditional materials. However, safety issues in the dosage of BMP remain, so overcoming current limitations will provide significant advancement in spine surgery. In the future, translational research and the application of clinical study will be important to overcome the current limitations of spinal surgery.

Relationship between degree of separation of endplate cartilage and severity of intervertebral disc herniation.

Degeneration of intervertebral disc and fissures in the anulus was caused by compression and distraction, which lead to nucleus pulposus herniation. However, controversy remains regarding the exact mechanism behind disc herniation. The aim of this study is to analyze histologically the differences between the three types of disc herniations in an attempt to infer the underlying mechanism. Disc samples extracted from 49 patients who underwent discectomy of the lumbar region were studied by histological analysis. The severity of disc herniation was classified as bulging, protrusion, extrusion, or sequestration based on preoperative magnetic resonance imaging measurements. For comparative analysis of sequestration characteristics, 49 patients were classified into either the sequestration or the non-sequestration group (i.e., protrusion and extrusion) according to disc herniation type. Forty of the 49 patients had cartilage present in their disc samples upon histological analysis. The endplate cartilage-containing samples included two of four (50%) protruded disc patients, 22 of 29 (75.9%) extruded disc patients, and 16 of 16 (100%) sequestrated disc patients and had statistical significance (p = 0.019). There were no significant differences in age, sex, body mass index, length of hospital stays, injection history, surgical methods, and Visual Analog Scale between the sequestration and non-sequestration group (all p > 0.05). Separation of endplate cartilage increased with the severity of disc herniation. Therefore, the mechanism of disc herniation should consider the connection with endplate cartilage as an initiating link in the mechanical failure of intervertebral discs.

Direct Comparison of In-Person Versus Virtual Interviews for Complex General Surgical Oncology Fellowship in the COVID-19 Era.

BACKGROUND: In the era of coronavirus disease 2019 (COVID-19), many Complex General Surgical Oncology (CGSO) fellowship programs implemented virtual interviews (VI) during the 2020 interview season. At our institution, we had the unique opportunity to conduct an in-person interview (IPI) prior to the pandemic-related travel restrictions, and a VI after the restrictions were in place. OBJECTIVE: The goal of this study was to understand how the VI model compares with the traditional IPI approach. METHODS: Online surveys were distributed to both groups, collecting feedback on their interview experience. Responses were evaluated using a two-sample t test assuming equal variances. RESULTS: Twenty-three of 26 (88%) applicants completed the survey. Most applicants reported that the interview gave them a satisfactory understanding of the CGSO fellowship (100% IPI, 92% VI) and the majority in both groups felt that the interview experience allowed them to accurately represent themselves (92% and 82%, respectively). All participants in the IPI group felt they were able to get an adequate understanding of the culture of the program, while only 64% in the VI group agreed with that statement (p = 0.02). IPI applicants were more likely to agree that the interview experience was sufficient to allow them to make a ranking decision (92% vs. 54%; p = 0.04). CONCLUSIONS: While the VI modality offers several advantages over the IPI, it still falls short in conveying some of the more subjective aspects of the programs, including program culture. Strategies to provide applicants with better insight into these areas during the VI will be important moving forward.

Pathologic nodal staging for clinically node negative soft tissue sarcoma of the extremities.

BACKGROUND AND OBJECTIVES: Synovial, clear cell, angiosarcoma, rhabdomyosarcoma, and epithelioid (SCARE) soft tissue sarcoma are at risk for nodal involvement, although the nodal positivity rates and impact on prognostication in clinically node negative patients are not well described. METHODS: Patients with extremity SCARE sarcoma without clinical nodal involvement undergoing surgical resection in the National Cancer Database (2004-2017) were included. Logistic regression was used to evaluate the likelihood of nodal surgery and nodal positivity. Kaplan-Meier method and Cox regression were used to assess associations of nodal status to overall survival. RESULTS: We included 4158 patients, and 669 patients (16%) underwent regional lymph node surgery (RLNS). On multivariable logistic analysis, patients with epithelioid (odds ratio [OR]: 3.77; p < .001) and clear cell (OR: 6.38; p < .001) were most likely to undergo RLNS. Forty-five patients (7%) had positive nodes. Clear cell sarcoma (14%) and angiosarcoma (13%) had the highest rates of nodal positivity. Patients with positive nodes had reduced 5-year overall survival, and the stratification was largest in clear cell and angiosarcoma. CONCLUSION: Discordance exists between selection for pathologic nodal evaluation and factors associated with nodal positivity. Clinically node negative patients with clear cell and angiosarcoma should be considered for pathologic nodal evaluation.