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The purpose of this systematic review and meta-analysis is to perform a systematic review and meta-analysis of previous studies on minimally invasive scoliosis surgery (MISS) in adolescents with idiopathic scoliosis (AIS). Some data on MISS in AIS compared with conventional open scoliosis surgery (COSS) are conflicting. A systematic literature search was conducted in Medline, Embase, and Cochrane Library, including studies reporting outcomes for MISS in AIS. The meta-analysis compared the operative, radiological, and clinical outcomes and complications between MISS and COSS in patients with AIS. Of the 208 records identified, 15 nonrandomized studies with 1,369 patients (reviews and case reports are excluded) were included in this systematic review and meta-analysis. The mean scale was 6.1, and eight of the 15 included studies showed satisfactory quality using the Newcastle-Ottawa scale. For operative outcomes, MISS had significant benefits in terms of estimated blood loss (standard mean difference [SMD], −1.87; 95% confidence interval [CI], −2.94 to −0.91) and hospitalization days (SMD, −2.99; 95% CI, −4.45 to −1.53) compared with COSS. However, COSS showed significantly favorable outcomes for operative times (SMD, 1.71; 95% CI, 0.92–2.51). No significant differences were observed in radiological outcomes, including Cobb’s angle of the main curve and thoracic kyphosis. For clinical outcomes, MISS showed significant benefits on the visual analog scale score (SMD, −0.91; 95% CI, −1.36 to −0.47). The overall complication rates of MISS were similar to those of COSS (SMD, 0.96; 95% CI, 0.61–1.52). MISS using the posterior approach provides equivalent radiological and clinical outcomes and complication rates compared with COSS. Considering the lower estimated blood loss, shorter hospitalization days, and longer operative times in MISS, COSS is still the mainstay of surgical treatment in AIS; however, MISS using the posterior approach is also one of the surgical options of choice in the case of moderate AIS.

BackgroundDue 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. ObjectiveThe 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. MethodsIn 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. ResultsThe 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

Poststroke seizure is a potential complication of stroke, which is the most frequent acute symptomatic seizure in adults. Patients with stroke may present with an abnormal or aggressive behavior accompanied by altered mental status and symptoms, such as hemiparesis, dysarthria, and sensory deficits. Although stroke manifestations that mimic seizures are rare, diagnosing poststroke seizures can be challenging when accompanied with negative postictal symptoms. Differential diagnoses of poststroke seizures include movement disorders, syncope, and functional (nonepileptic) seizures, which may present with symptoms similar to seizures. Furthermore, it is important to determine whether poststroke seizures occur early or late. Seizures occurring within and after 7 d of stroke onset were classified as early and late seizures, respectively. Early seizures have the same clinical course as acute symptomatic seizures; they rarely recur or require long-term antiseizure medication. Conversely, late seizures are associated with a risk of recurrence similar to that of unprovoked seizures in a patient with a focal lesion, thereby requiring long-term administration of antiseizure medication. After diagnosis, concerns regarding treatment strategies, treatment duration, and administration of primary and secondary prophylaxis often arise. Antiseizure medication decisions for the initiation of short-term primary and long-term secondary seizure prophylaxis should be considered for patients with stroke. Antiseizure drugs such as lamotrigine, carbamazepine, lacosamide, levetiracetam, phenytoin, and valproate may be administered. Poststroke seizures should be diagnosed systematically through history with differential diagnosis; in addition, classifying them as early or late seizures can help to determine treatment strategies.

(1) Background and objectives: Running-related injuries (RRIs) are commonly attributed to improper running posture and overuse. This study aims to analyze the running motions of individuals with and without RRIs using a sensor-free method, which offers a user-friendly and straightforward approach. (2) Materials and Methods: A total of 155 runners were divided into two groups: the normal runner group (runners who had never been injured, n = 50) and the RRI group (runners who had experience at least one injury while running, n = 105). The forward head posture (FHP), trunk lean, hip rotation, horizontal movement of the center of gravity (COG), vertical movement of the COG, pelvic rotation, hip hike, and type of strike were measured for posture analysis. (3) Results: We found that the left–right balance of the pelvis and the spinal posture during running were associated with RRIs. The difference in hip hike and FHP emerged as key predictors of running-related musculoskeletal injury occurrence from our logistic regression analysis. (4) Conclusions: Identifying pathological movements in runners through running motion analysis without the use of sensors can be instrumental in the prevention and treatment of RRIs.

Abstract Pelvic fixation is performed to obtain proper coronal and sagittal alignment when the pelvic obliquity is more than 15º in patients with neuromuscular scoliosis (NMS). Since many NMS patients were wheelchair or bed-ridden status, there has been controversy on the effect of pelvic fixation. Therefore, the purpose of this study is to analyze the effects of pelvic fixation on correction of spinal deformity and quality of life (QoL) in NMS patients. A total of 77 NMS patients who underwent deformity correction were divided into three groups and retrospectively analyzed preoperatively, postoperatively, and at 2-year follow-up: pelvic fixation group (Group A, n = 16), fixed to S1 (Group B, n = 33), and fixed to L5 (Group C, n = 28). The correction rate of scoliosis was 60.0%, 58.0%, and 56.7% in groups A, B, and C, respectively, with no statistical difference (P > 0.05). The correction rate of pelvic obliquity was 61.3%, 42.8%, and 57.5% in respective groups A, B, and C, with no significance (P > 0.05). The correction loss of scoliosis and pelvic obliquity showed no statistical significance between three groups for 2-year follow-up (all Ps > 0.05). There were no significant differences regarding clinical outcomes and postoperative complications among the three groups (all Ps > 0.05). Therefore, pelvic fixation using iliac screws is not substantially influencing radiological and clinical outcomes in the patients with NMS.

Abstract Background Para-aortic lymph node (PALN) metastases from primary pelvic malignancies are often treated with resection, but recurrence is common. We report toxicity and oncologic outcomes for patients with PALN metastases from gastrointestinal and gynecologic malignancies treated with resection and intraoperative electron radiotherapy (IORT). Methods We retrospectively identified patients with recurrent PALN metastases who underwent resection with IORT. All patients were included in the local recurrence (LR) and toxicity analyses. Only patients with primary colorectal tumors were included in the survival analysis. Results There were 26 patients with a median follow up of 10.4 months. The rate of para-aortic local control (LC) was 77% (20/26 patients) and the rate of any cancer recurrence was 58% (15/26 patients). Median time from surgery and IORT to any recurrence was 7 months. The LR rate for those with positive/close margins was 58% (7/12 patients) versus 7% (1/14 patients) for those with negative margins (p = 0.009). 15% (4/26 patients) developed surgical wound and/or infectious complications, 8% (2/26 patients) developed lower extremity edema, 8% (2/26 patients) experienced diarrhea, and 19% (5/26 patients) developed an acute kidney injury. There were no reported nerve injuries, bowel perforations, or bowel obstructions. For patients with primary colorectal tumors (n = 19), the median survival (OS) was 23 months. Conclusions We report favorable LC and acceptable toxicity for patients receiving surgical resection and IORT for a population that has historically poor outcomes. Our data show disease control rates similar to literature comparisons for patients with strong risk factors for LR, such as positive/close margins.

Key Clinical Message When massive bleeding is anticipated during endoscopic sinonasal tumor removal, a vessel sealing device is useful for successful tumor removal.

Objective The safety and clinical usefulness of minimally invasive scoliosis surgery (MISS) has been reported in various studies. However, freehand pedicle screwing in MISS remains technically challenging. The purpose of this study is to evaluate the accuracy and safety of pedicle screw placement using the freehand technique in adolescent idiopathic scoliosis (AIS) patients treated with MISS compared to conventional open scoliosis surgery (COSS). Methods We included 76 patients who underwent deformity correction for AIS. Computed tomography scans were used to assess screw violations divided into 2 groups according to the surgical technique: MISS or COSS. Anterior violations were classified into grade 0, 1 (no contact with internal organs), and 2 (contact with internal organs). Medial and lateral violations were classified into grade 0, 1 ( < 2 mm), and 3 ( ≥ 2 mm). grade 2 were considered critical violations. Results A total of 630 and 1,174 pedicle screws were inserted in the MISS and COSS groups, respectively. The overall critical violation rates of the MISS and COSS groups were 16.8% (106 screws) and 14.0% (165 screws) (p = 0.116). Medial critical violations on the left side in the middle thoracic region frequently occurred in the MISS group compared to the COSS group (p = 0.003). There were no statistical differences in the complications. Conclusion Pedicle screw placement using the freehand technique in MISS for AIS patients provided similar accuracy and safety compared to COSS. Pedicle screws inserted on the left side of the middle thoracic region, exhibited more medial critical violations in the MISS group.

Abstract 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.

Owing to rapidly changing global demographics, adult spinal deformity (ASD) now accounts for a significant proportion of the Global Burden of Disease. Sagittal imbalance caused by age-related degenerative changes leads to back pain, neurological deficits, and deformity, which negatively affect the health-related quality of life (HRQoL) of patients. Along with the recognized regional, global, and sagittal spinopelvic parameters, poor paraspinal muscle quality has recently been acknowledged as a key determinant of the clinical outcomes of ASD. Although the Scoliosis Research Society-Schwab ASD classification system incorporates the radiological factors related to HRQoL, it cannot accurately predict the mechanical complications. With the rapid advances in surgical techniques, many surgical options for ASD have been developed, ranging from minimally invasive surgery to osteotomies. Therefore, structured patient-specific management is important in surgical decision-making, selecting the proper surgical technique, and to prevent serious complications in patients with ASD. Moreover, utilizing the latest technologies such as robotic-assisted surgery and machine learning, should help in minimizing the surgical risks and complications in the future.

Proximal junctional problems are among the potential complications of surgery for adult spinal deformity (ASD) and are associated with higher morbidity and increased rates of revision surgery. The diverse manifestations of proximal junctional problems range from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). Although there is no universally accepted definition for PJK, the most common is a proximal junctional angle greater than 10° that is at least 10° greater than the preoperative measurement. PJF represents a progression from PJK and is characterized by pain, gait disturbances, and neurological deficits. The risk factors for PJK can be classified according to patient-related, radiological, and surgical factors. Based on an understanding of the modifiable factors that contribute to reducing the risk of PJK, prevention strategies are critical for patients with ASD.

Abstract Background Interspinous devices have been introduced as alternatives to decompression or fusion in surgery for degenerative lumbar diseases. This study aimed to investigate 15-year survivorship and risk factors for reoperation of a Device for Intervertebral Assisted Motion (DIAM) in surgery for 1-level lumbar disc herniation (LDH). Methods A total of 94 patients (54 men and 40 women) underwent discectomy and DIAM implantation for 1-level LDH, with a mean follow-up of 12.9 years (range, 6.3–15.3 years). The mean age was 46.2 years (range, 21–65 years). Sixty-two patients underwent DIAM implantation for L4–5, 27 for L5–6, and 5 for L3–4. Reoperations due to any reason associated with DIAM implantation level or adjacent levels were defined as failure and used as the end point of determining survivorship. Results During the 15-year follow-up, 8 patients (4 men and 4 women) underwent reoperation due to recurrence of LDH at the DIAM implantation level, a reoperation rate of 8.5%. The mean time to reoperation was 6.5 years (range, 0.8–13.9 years). Kaplan-Meier analysis showed a cumulative survival rate of the DIAM implantation of 97% at 5 years, 93% at 10 years, and 92% at 15 years after surgery; the cumulative reoperation rate of the DIAM implantation was 3% at 5 years, 7% at 10 years, and 8% at 15 years after surgery. Mean survival time was predicted to be 14.5 years (95% CI, 13.97–15.07). The log-rank test and Cox proportional hazard model showed that age, sex, and location did not significantly affect the reoperation rate of DIAM implantation. Conclusions Our results showed that DIAM implantation significantly decreased reoperation rate for LDH in the 15-year survivorship analysis. We suggest that DIAM implantation could be considered a useful intermediate step procedure for LDH surgery. To the best of our knowledge, this is the longest follow-up study in which surgical outcomes of interspinous device surgery were reported.

Abstract Background Gas forming infection of the spine is a consequence of vertebral osteomyelitis, necrotizing fasciitis, or a gas-forming epidural abscess, which is very rare and fatal conditions. This is the rare case of necrotizing fasciitis that rapidly progressed from the lumbar area to upper thoracic area. Case presentation A 58-year-old male complained of lower back pain with fever and chills. The patient had a history of uncontrolled diabetes mellitus without diabetic medication over the previous 3 months, and he had received several local injections around the lumbar area. Laboratory data revealed white blood cell count of 19,710 /mm3, erythrocyte sedimentation of 40 mm/h, and C-reactive protein of 30.7 mg/L. Radiological findings revealed a small amount of air bubbles in the paraspinal area and lumbar epidural spaces. The patient refused emergency surgery and was discharged from the hospital. The patient re-visited the emergency department two days after discharge complaining of more severe back pain with persistent fever, and his vital signs had deteriorated, with low blood pressure and tachycardia. K. pneumoniae was isolated in cultures from ultrasound-guided aspirates and peripheral blood. The follow-up radiographs revealed aggressive dissemination of innumerable air bubbles from the lumbar area to the T5 level. The patient underwent emergent decompressive laminectomy and debridement of infected paravertebral fascia and musculature. Despite intensive care for deteriorated vital signs and his back wound, the patient died on postoperative day 3 due to multi-organ failure. Conclusions Necrotizing fasciitis involving the spine is a very rare disease with life-threatening conditions, rapid progression, and a high mortality rate. Therefore, prompt surgical treatment with a high index of suspicion is imperative to prevent potentially fatal conditions in similar extremely rare cases.

Abstract Background Among the several complications associated with anterior cervical discectomy and fusion (ACDF), airway compromise is considered one of the serious life-threatening conditions and usually requires emergent treatment, including airway establishment and hematoma evacuation surgery. Postoperative retropharyngeal hematoma commonly occurred during the on immediate phase with airway compromise, but have a rarity on late onset of this complication. Enlightened by this existing fact, we report the first case of delayed onset postoperative retropharyngeal hematoma after anterior cervical surgery with a sequela of tracheal stricture. Case presentation A 55-year-old male underwent ACDF for disc herniation at C5–6 that had not responded to conservative treatment over 3 months. The symptoms significantly improved after surgery, and he was discharged on postoperative day 3. On the 7 days after ACDF, the patient complained of sudden-onset left-deviated neck swelling. The follow-up plain radiographs and neck-enhanced computed tomography (CT) scans showed anterior and right lateral displacement of the airway including the trachea by a large retropharyngeal hematoma. We performed an emergent forceful endotracheal intubation that was maintained for 2 days until the patient underwent hematoma evacuation surgery. On the second day after hematoma evacuation surgery, the patient complained of hoarseness with a foul breath odor. Laryngoscopy showed tracheal ischemic mucosal damage that had been induced by forceful endotracheal intubation. Antibiotics and systemic corticosteroids were administered, and the symptoms improved. One month after hematoma evacuation surgery, he complained of dyspnea on exertion, and laryngoscopy showed tracheal stricture. The patient underwent bronchoscopic dilatation and is doing well without recurrence of symptoms. Conclusions Early surgery to remove the delayed onset retropharyngeal hematoma, rather than forceful endotracheal intubation followed by delayed surgery, might yield better results and avoid unexpected complications of tracheal stricture.

Abstract With the progression of acute cholecystitis, antimicrobial therapy becomes important for infection control. Current antibiotic recommendations were mostly based on reports of patients with acute cholangitis whose bile specimens were sampled from the biliary tract. However, as most infections of acute cholecystitis are limited to the gallbladder, direct sampling from the site increases the probability of identifying the causative pathogen. We investigated 321 positive bile cultures from 931 patients with acute cholecystitis who underwent laparoscopic cholecystectomy between January 2003 and December 2017. The frequency of enterococci declined (P = 0.041), whereas that of Enterobacteriales (P = 0.005), particularly Escherichia (P = 0.008), increased over time. The incidence of ciprofloxacin-resistant Enterobacteriales showed a significant increasing trend (P = 0.031). Vancomycin-resistant E.faecium, carbapenem-resistant Enterobacteriales, and extended-spectrum beta-lactamase-producing Enterobacteriales were recently observed. In grade I and II acute cholecystitis, there were no significant differences in perioperative outcomes in patients with and without early appropriate antimicrobial therapy. In conclusion, the changing incidence of frequently isolated microorganisms and their antibiotic resistance over time would be considered before selecting antibiotics for the treatment of acute cholecystitis. Surgery might be a crucial component of infection control in grade I and II acute cholecystitis.

Adult spinal deformity (ASD) is characterized by three-dimensional abnormalities of the thoracic or thoracolumbar spine that exerts significant impacts on the health-related quality of life (HRQoL). With the important effects that deformity of the sagittal plane exerts on the HRQoL, there have been paradigm shifts in ASD evaluation and management. Loss of lumbar lordosis is recognized as a key driver of ASD followed by reducing kyphosis, pelvic retroversion, and knee flexion. The Scoliosis Research Society (SRS)– Schwab classification reflects the sagittal spinopelvic parameters that correlate pain and disability in ASD patients. Although the SRS–Schwab classification provides a realignment target framework for surgeons, a structured patient-specific systemic approach is crucial for the process of decision-making. ASD management should be focused on restoring age-specific harmonious alignment and should consider the comorbidities and risk factors of each patient to prevent catastrophic complications and enhance the HRQoL.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer cases, with more than 850,000 new diagnoses per year globally. Recent trends in the United States have shown that liver cancer mortality has continued to increase in both men and women, while 5-year survival remains below 20%. Understanding key mechanisms that drive chronic liver disease progression to HCC can reveal new therapeutic targets and biomarkers for early detection of HCC. In that regard, many studies have underscored the importance of alternative splicing as a source of novel HCC prognostic markers and disease targets. Alternative splicing of pre-mRNA provides functional diversity to the genome, and endows cells with the ability to rapidly remodel the proteome. Genes that control fundamental processes, such as metabolism, cell proliferation, and apoptosis, are altered globally in HCC by alternative splicing. This review highlights the major splicing factors, RNA binding proteins, transcriptional targets, and signaling pathways that are of key relevance to HCC. We highlight primary research from the past 3–5 years involving functional interrogation of alternative splicing in rodent and human liver, using both large-scale transcriptomic and focused mechanistic approaches. Because this is a rapidly advancing field, we anticipate that it will be transformative for the future of basic liver biology, as well as HCC diagnosis and management.

CD73, a cell‐surface N‐linked glycoprotein that produces extracellular adenosine, is a novel target for cancer immunotherapy. Although anti‐CD73 antibodies have entered clinical development, CD73 has both protumor and antitumor functions, depending on the target cell and tumor type. The aim of this study was to characterize CD73 regulation in human hepatocellular carcinoma (HCC). We examined CD73 expression, localization, and activity using molecular, biochemical, and cellular analyses on primary HCC surgical specimens, coupled with mechanistic studies in HCC cells. We analyzed CD73 glycan signatures and global alterations in transcripts encoding other N‐linked glycoproteins by using mass spectrometry glycomics and RNA sequencing (RNAseq), respectively. CD73 was expressed on tumor hepatocytes where it exhibited abnormal N‐linked glycosylation, independent of HCC etiology, tumor stage, or fibrosis presence. Aberrant glycosylation of tumor‐associated CD73 resulted in a 3‐fold decrease in 5′‐nucleotidase activity (P

The contingent valuation method is applied to determine how much consumers would be willing to pay to reduce copper in their drinking water and what factors influence their willingness to pay (WTP). The annual mean WTP per household was estimated using survey data from nine counties in southwestern Minnesota where copper contamination is high. The annual mean WTP per household varied from a low range of $30.41 to $43.61 for Chippewa County to a high range of $39.79 to $57.06 for Nobles County. The aggregate WTP for all nine counties was estimated to range from $1.66 to $2.38 million. However, the estimated WTP may not be sufficient to pay the cost of providing improved water through public water systems for small communities in southwestern Minnesota.

This study estimates the benefits to agricultural and human health of reducing ozone in the San Joaquin Valley of California, and the costs of ozone control. The San Joaquin Valley's highly valued crops suffer from high ozone levels. Federal and state primary ozone standards are based on health effects, not effects on other sectors, and do not consider costs of attaining the standards. The methods here allow comparison of both total and marginal benefits and costs. The results suggest that net gains can be achieved for the entire valley by reducing ozone below 1990 levels, although results vary by region.

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a characteristic pattern of early metastasis, which is driving a search for biomarkers that can be used to detect the cancer at an early stage. Recently, the actin-associated protein palladin was identified as a candidate biomarker when it was shown that palladin is mutated in a rare inherited form of PDA, and overexpressed in many sporadic pancreas tumors and premalignant precursors. In this study, we analyzed the expression of palladin isoforms in murine and human PDA and explored palladin's potential use in diagnosing PDA. We performed immunohistochemistry and immunoblot analyses on patient samples and tumor-derived cells using an isoform-selective monoclonal antibody and a pan-palladin polyclonal antibody. Immunoblot and real-time quantitative reverse transcription-PCR were used to quantify palladin mRNA levels in human samples. We show that there are two major palladin isoforms expressed in pancreas: 65 and 85-90 kDa. The 65 kDa isoform is expressed in both normal and neoplastic ductal epithelial cells. The 85-90 kDa palladin isoform is highly overexpressed in tumor-associated fibroblasts (TAFs) in both primary and metastatic tumors compared to normal pancreas, in samples obtained from either human patients or genetically engineered mice. In tumor-derived cultured cells, expression of palladin isoforms follows cell-type specific patterns, with the 85-90 kDa isoform in TAFs, and the 65 kDa isoform predominating in normal and neoplastic epithelial cells. These results suggest that upregulation of 85-90 kDa palladin isoform may play a role in the establishment of the TAF phenotype, and thus in the formation of a desmoplastic tumor microenvironment. Thus, palladin may have a potential use in the early diagnosis of PDA and may have much broader significance in understanding metastatic behavior.

The ability of the transcription factor NF-kappaB to upregulate anti-apoptotic proteins has been linked to the chemoresistance of solid tumors to standard chemotherapy. In contrast, recent studies have proposed that, in response to doxorubicin, NF-kappaB can be pro-apoptotic through repression of anti-apoptotic target genes. However, there is little evidence analyzing the outcome of NF-kappaB inhibition on the cytotoxicity of doxorubicin in studies describing pro-apoptotic NF-kappaB activity. In this study, we further characterize the activation of NF-kappaB in response to doxorubicin and evaluate its role in chemotherapy-induced cell death in sarcoma cells where NF-kappaB is reported to be pro-apoptotic. Doxorubicin treatment in U2OS cells induced canonical NF-kappaB activity as evidenced by increased nuclear accumulation of phosphorylated p65 at serine 536 and increased DNA-binding activity. Co-treatment with a small molecule IKKbeta inhibitor, Compound A, abrogated this response. RT-PCR evaluation of anti-apoptotic gene expression revealed that doxorubicin-induced transcription of cIAP2 was inhibited by Compound A, while doxorubicin-induced repression of other anti-apoptotic genes was unaffected by Compound A or siRNA to p65. Furthermore, the combination of doxorubicin and canonical NF-kappaB inhibition with Compound A or siRNA to p65 resulted in decreased cell viability measured by trypan blue staining and MTS assay and increased apoptosis measured by cleaved poly (ADP-ribose) polymerase and cleaved caspase 3 when compared to doxorubicin alone. Our results demonstrate that doxorubicin-induced canonical NF-kappaB activity associated with phosphorylated p65 is anti-apoptotic in its function and that doxorubicin-induced repression of anti-apoptotic genes occurs independent of p65. Therefore, combination therapies incorporating NF-kappaB inhibitors together with standard chemotherapies remains a viable method to improve the clinical outcomes in patients with advanced stage malignancies.

Study Design: A retrospective cohort study. Objective: To evaluate the mid-term effect of intervertebral disc degeneration (DD) in patients with adolescent idiopathic scoliosis (AIS) who underwent pedicle screw instrumentation (PSI) and rod derotation (RD) with direct vertebral rotation (DVR). Summary of Background Data: Posterior spinal fusion is a mainstay of surgical treatment in AIS, and DVR is considered a main corrective maneuver for vertebral rotation. However, the mid-term effect of intervertebral DD after DVR is still unknown in AIS. Methods: A total of 336 vertebrae for 48 patients with AIS who underwent PSI and RD with DVR were retrospectively assessed for intervertebral DD. They were divided into two groups based upon intervertebral DD, defined as Pfirmann grade more than IV. The Pfirrmann grade and modic change were evaluated at the disc above the uppermost instrumented vertebra (UIV), the disc below the lowest instrumented vertebra (LIV), and the lumbar disc levels. Results: With the 11.6 years of mean follow-up, 41.7% (20/48) of patients exhibited DD, while modic changes were observed in 4.2% (2/48) of the included patients. The discs below the LIV, L4-5, and L5-S1 were significantly shown to have an increasing trend of Pfirmann grade. The preoperative thoracic kyphosis was significantly lower in the DD group (22.0°) than in the non-DD group (31.4°) (P = 0.025) and negatively correlated with DD (r = -0.482, P = 0.018). The Pfirrmann grade of L5-S1 showed a high level of correlation with DD (r = 0.604, P < 0.001). Conclusions: The degenerative change at the disc below the LIV, L4-5, and L5-S1 levels was observed following PSI and RD with DVR. Thoracic hypokyphosis may negatively influence intervertebral discs in patients with AIS required for deformity correction. Therefore, the restoration of thoracic kyphosis is important to prevent long-term DD in AIS. [ABSTRACT FROM AUTHOR]

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 (OS). 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 tumorintrinsic 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 were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using the log-rank test. Results: Patients who received NAT had an increase in OS, with a median survival of 27.9 months compared with 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (hazard ratio: 0.64, P=0.076). Either tumorintrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtypes had the best outcomes. When evaluated together, patients with the classical-restCAF subtype had the best OS and basalpermCAF the worst OS (P< 0.0001). Patients undergoing NAT with the classical-restCAF subtype demonstrated the longest OS compared with the other groups (P=0.00041). Conclusions: CAF subtypes have an additive effect over tumorintrinsic 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. [ABSTRACT FROM AUTHOR]

Study Design. A retrospective cohort study. Objective. To evaluate long-term rotational changes in the vertebrae of patients with adolescent idiopathic scoliosis (AIS) who underwent direct vertebral rotation (DVR). Summary of Background Data. DVR using thoracic pedicle screws, a rotational corrective maneuver used in the surgical treatment of AIS, was introduced in 2004. Although DVR is considered to be the main axial corrective maneuver, the long-term rotational changes of vertebrae following this treatment are not well understood. Materials and Methods. A total of 135 vertebrae that underwent DVR using thoracic pedicle screws with a minimum five-year follow-up were retrospectively assessed for the vertebral rotation angle. The vertebral rotation of the apical vertebra (AV) and distal end vertebra (EV) was evaluated using the Nash-Moe scale, the rotational angle to the sacrum (RAsac), and the Aaro and Dahlborn method. The Student t test (paired means) was used for continuous variables, and the χ2 test was used for categorical variables, as appropriate. A comparison of two and three groups used a one-way repeated measures analysis of variance, and the post hoc analysis used the Bonferroni test. Results. The mean Nash-Moe scale of distal EV showed statistically significant differences between preoperative and postoperative values (P= 0.034) and no statistically significant difference between postoperative and last follow-up values (P=1.000). The last follow-up RAsac of AV did not differ significantly from the preoperative RAsac of AV (P= 0.515). The last follow-up RAsac of distal EV was significantly lower than the preoperative RAsac of distal EV (P= 0.001). The Pearson correlation analysis showed that the last follow-up RAsac of distal EV was correlated with the Cobb angle of the main curve (r= 0.459, P=0.004), loss of correction (r= 0.541, P=0.001), and lowest instrumented vertebra tilt angle (r= 0.504, P=0.001) Conclusions. The rotation regression phenomenon in AV and rotation maintenance in distal EV were observed after DVR over an average 10-year follow-up. These findings suggest that the DVR in the surgical treatment of AIS has a positive long-term effect on the stabilization of distal EV from the point of view of axial rotation. [ABSTRACT FROM AUTHOR]

This article is an editorial that honors the significant achievements and contributions of Professor Se-Il Suk to pedicle screw instrumentation and related surgical techniques in spinal deformity. The article highlights Professor Suk's impact on modern spine surgery through pedicle screw instrumentation and discusses his pioneering work in using pedicle screw fixation in the thoracic spine, posterior vertebral column resection, and direct vertebral rotation. These techniques have allowed for safer and more efficient treatment options for spinal deformities. The article acknowledges Professor Suk's recognition and awards for his contributions to the field of spine surgery. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]