Comparison of Surgical Outcomes After Posterior Decompression by Junior or Senior Surgeons for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: Results From Retrospective Multicenter Cohort Study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate surgical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. METHODS: We included 203 patients with cervical OPLL who were followed for a minimum of 1 year after surgery. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed preoperatively and at the final follow-up using the Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) for the neck. We compared outcomes between BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and NBCS surgeons. RESULTS: BCS surgeons performed 124 out of 203 cases, while NBCS surgeons were primary in 79 cases, with 73.4% were directly supervised by a BCS surgeon. There was no statistically significant difference in surgical duration, estimated blood loss, and perioperative complication rates between the BCS and NBCS groups. Moreover, no statistically significant group differences were observed in each position of the C2-7 angle and cervical range of motion at preoperation and the final follow-up. Preoperative and final follow-up JOA scores, VAS for the neck, and JOA score recovery rate were comparable between the two groups. CONCLUSIONS: Surgical outcomes, including functional recovery, complication rates, and cervical dynamics, were comparable between the BCS and NBCS groups. Consequently, posterior decompression for cervical OPLL is considered safe and effective when conducted by junior surgeons who have undergone training and supervision by experienced spine surgeons.

5,6-dimethylxanthenone-4-acetic acid (DMXAA), a partial STING agonist, competes for human STING activation.

5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a mouse-selective stimulator of interferon gene (STING) agonist exerting STING-dependent anti-tumor activity. Although DMXAA cannot fully activate human STING, DMXAA reached phase III in lung cancer clinical trials. How DMXAA is effective against human lung cancer is completely unknown. Here, we show that DMXAA is a partial STING agonist interfering with agonistic STING activation, which may explain its partial anti-tumor effect observed in humans, as STING was reported to be pro-tumorigenic for lung cancer cells with low antigenicity. Furthermore, we developed a DMXAA derivative-3-hydroxy-5-(4-hydroxybenzyl)-4-methyl-9H-xanthen-9-one (HHMX)-that can potently antagonize STING-mediated immune responses both in humans and mice. Notably, HHMX suppressed aberrant responses induced by STING gain-of-function mutations causing STING-associated vasculopathy with onset in infancy (SAVI) in in vitro experiments. Furthermore, HHMX treatment suppressed aberrant STING pathway activity in peripheral blood mononuclear cells from SAVI patients. Lastly, HHMX showed a potent therapeutic effect in SAVI mouse model by mitigating disease progression. Thus, HHMX offers therapeutic potential for STING-associated autoinflammatory diseases.

A stress sensor, IRE1α, is required for bacterial-exotoxin-induced interleukin-1ß production in tissue-resident macrophages.

Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1ß (IL-1ß), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1ß production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1ß production, indicating that IRE1α is required for CT- or CTB-induced IL-1ß production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.

Acute malaria suppresses the B lymphocytic niche in the bone marrow through the alteration of CXCL12-abundant reticular cells.

Bone marrow is a dynamic organ composed of stem cells that constantly receive signals from stromal cells and other hematopoietic cells in the niches of the bone marrow to maintain hematopoiesis and generate immune cells. Perturbation of the bone marrow microenvironment by infection and inflammation affects hematopoiesis and may affect immune cell development. Little is known about the effect of malaria on the bone marrow stromal cells that govern the hematopoietic stem cell (HSC) niche. In this study, we demonstrate that the mesenchymal stromal CXCL12-abundant reticular (CAR) cell population is reduced during acute malaria infection. The reduction of CXCL12 and interleukin-7 signals in the bone marrow impairs the lymphopoietic niche, leading to the depletion of common lymphoid progenitors, B cell progenitors, and mature B cells, including plasma cells in the bone marrow. We found that interferon-γ (IFNγ) is responsible for the upregulation of Sca1 on CAR cells, yet the decline in CAR cell and B cell populations in the bone marrow is IFNγ-independent. In contrast to the decline in B cell populations, HSCs and multipotent progenitors increased with the expansion of myelopoiesis and erythropoiesis, indicating a bias in the differentiation of multipotent progenitors during malaria infection. These findings suggest that malaria may affect host immunity by modulating the bone marrow niche.

TLR9 plus STING Agonist Adjuvant Combination Induces Potent Neopeptide T Cell Immunity and Improves Immune Checkpoint Blockade Efficacy in a Tumor Model.

Immune checkpoint blockade (ICB) immunotherapies have emerged as promising strategies for the treatment of cancer; however, there remains a need to improve their efficacy. Determinants of ICB efficacy are the frequency of tumor mutations, the associated neoantigens, and the T cell response against them. Therefore, it is expected that neoantigen vaccinations that boost the antitumor T cell response would improve ICB therapy efficacy. The aim of this study was to develop a highly immunogenic vaccine using pattern recognition receptor agonists in combination with synthetic long peptides to induce potent neoantigen-specific T cell responses. We determined that the combination of the TLR9 agonist K-type CpG oligodeoxynucleotides (K3 CpG) with the STING agonist c-di-AMP (K3/c-di-AMP combination) significantly increased dendritic cell activation. We found that immunizing mice with 20-mer of either an OVA peptide, low-affinity OVA peptides, or neopeptides identified from mouse melanoma or lung mesothelioma, together with K3/c-di-AMP, induced potent Ag-specific T cell responses. The combined K3/c-di-AMP adjuvant formulation induced 10 times higher T cell responses against neopeptides than the TLR3 agonist polyinosinic:polycytidylic acid, a derivative of which is the leading adjuvant in clinical trials of neoantigen peptide vaccines. Moreover, we demonstrated that our K3/c-di-AMP vaccine formulation with 20-mer OVA peptide was capable of controlling tumor growth and improving survival in B16-F10-OVA tumor-bearing C57BL/6 mice and synergized with anti-PD-1 treatment. Together, our findings demonstrate that the K3/c-di-AMP vaccine formulation induces potent T cell immunity against synthetic long peptides and is a promising candidate to improve neoantigen vaccine platform.

Challenges in developing personalized neoantigen cancer vaccines.

The recent success of cancer immunotherapies has highlighted the benefit of harnessing the immune system for cancer treatment. Vaccines have a long history of promoting immunity to pathogens and, consequently, vaccines targeting cancer neoantigens have been championed as a tool to direct and amplify immune responses against tumours while sparing healthy tissue. In recent years, extensive preclinical research and more than one hundred clinical trials have tested different strategies of neoantigen discovery and vaccine formulations. However, despite the enthusiasm for neoantigen vaccines, proof of unequivocal efficacy has remained beyond reach for the majority of clinical trials. In this Review, we focus on the key obstacles pertaining to vaccine design and tumour environment that remain to be overcome in order to unleash the true potential of neoantigen vaccines in cancer therapy.

Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabe adults and children: a phase 1b randomised, controlled, double-blinded, age de-escalation trial.

Background: BK-SE36/CpG is a recombinant blood-stage malaria vaccine candidate based on the N-terminal Plasmodium falciparum serine repeat antigen5 (SE36), adsorbed to aluminium hydroxide gel and reconstituted, prior to administration, with synthetic oligodeoxynucleotides bearing CpG motifs. In healthy Japanese adult males, BK-SE36/CpG was well tolerated. This study assessed its safety and immunogenicity in healthy malaria-exposed African adults and children. Methods: A double-blind, randomised, controlled, age de-escalating clinical trial was conducted in an urban area of Ouagadougou, Burkina Faso. Healthy participants (n=135) aged 21-45 years (Cohort 1), 5-10 years (Cohort 2) and 12-24 months (Cohort 3) were randomised to receive three vaccine doses (Day 0, 28 and 112) of BK-SE36/CpG or rabies vaccine by intramuscular injection. Results: One hundred thirty-four of 135 (99.2%) subjects received all three scheduled vaccine doses. Vaccinations were well tolerated with no related Grade 3 (severe) adverse events (AEs). Pain/limitation of limb movement, headache in adults and fever in younger children (all mild to moderate in intensity) were the most frequently observed local and systemic AEs. Eighty-three of BK-SE36/CpG (91%) recipients and 37 of control subjects (84%) had Grade 1/2 events within 28 days post vaccination. Events considered by the investigator to be vaccine related were experienced by 38% and 14% of subjects in BK-SE36/CpG and control arms, respectively. Throughout the trial, six Grade 3 events (in 4 subjects), not related to vaccination, were recorded in the BK-SE36/CpG arm: 5 events (in 3 subjects) within 28 days of vaccination. All serious adverse events (SAEs) (n=5) were due to severe malaria (52-226 days post vaccination) and not related to vaccination. In all cohorts, BK-SE36/CpG arm had higher antibody titres after Dose 3 than after Dose 2. Younger cohorts had stronger immune responses (12-24-month-old > 5-10 years-old > 21-45 years-old). Sera predominantly reacted to peptides that lie in intrinsically unstructured regions of SE36. In the control arm, there were no marked fold changes in antibody titres and participants' sera reacted poorly to all peptides spanning SE36. Conclusion: BK-SE36/CpG was well-tolerated and immunogenic. These results pave the way for further proof-of-concept studies to demonstrate vaccine efficacy. Clinical trial registration: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1921, PACTR201701001921166.

Trunk orthosis with joints providing resistive force improves dynamic sagittal alignment in postoperative patients with lumbar spinal stenosis.

This study aimed to determine whether a trunk orthosis with joints providing resistive force (TORF) modifies sagittal malalignment during level walking in patients with lumbar spinal stenosis (LSS). Fifteen patients, 6 months after undergoing surgery for LSS, performed level walking at a self-selected speed while wearing a TORF. Dynamic sagittal alignment, including sagittal vertical axis, lumbar lordosis, and pelvic tilt, and spatiotemporal data as well as lower limb kinematic and kinetic data were recorded using a three-dimensional motion analysis system and six force plates. Statistical analysis was performed to compare these data with and without the TORF, respectively. Compared to the condition without the TORF, the use of the TORF significantly decreased positive sagittal vertical axis (p < 0.05) and increased the lumbar lordosis and pelvic tilt (p < 0.05). Peak hip flexion angle and extension moment during loading response (LR) significantly increased (p < 0.05), and peak hip extension angle and flexion moment during PS statistically decreased (p < 0.05). There was no difference in spatiotemporal data between the two conditions. Our findings suggest that TORF may modify the dynamic sagittal global alignment and lower limb kinematic and kinetics in postoperative LSS patients during level walking.

Akkermansia muciniphila induces slow extramedullary hematopoiesis via cooperative IL-1R/TLR signals.

Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we find that systemic single injections of Akkermansia muciniphila (A. m.), a mucin-degrading bacterium, rapidly activate BM myelopoiesis and slow but long-lasting hepato-splenomegaly, characterized by the expansion and differentiation of functional HSPCs, which we term delayed EMH. Mechanistically, delayed EMH triggered by A. m. is mediated entirely by the MYD88/TRIF innate immune signaling pathway, which persistently stimulates splenic myeloid cells to secrete interleukin (IL)-1α, and in turn, activates IL-1 receptor (IL-1R)-expressing splenic HSPCs. Genetic deletion of Toll-like receptor-2 and -4 (TLR2/4) or IL-1α partially diminishes A. m.-induced delayed EMH, while inhibition of both pathways alleviates splenomegaly and EMH. Our results demonstrate that cooperative IL-1R- and TLR-mediated signals regulate commensal bacteria-driven EMH, which might be relevant for certain autoimmune disorders.

Identification of a Self-Assembling Small-Molecule Cancer Vaccine Adjuvant with an Improved Toxicity Profile.

Protein or peptide cancer vaccines usually include immune potentiators, so-called adjuvants. However, it remains challenging to identify structurally simple, chemically accessible synthetic molecules that are effective and safe as vaccine adjuvant. Here, we present cholicamideß (6), a self-assembling small-molecule vaccine adjuvant with an improved toxicity profile and proven efficacy in vivo. We demonstrate that cholicamideß (6), which is less cytotoxic than its parent compound, forms virus-like particles to potently activate dendritic cells with the concomitant secretion of cytokines. When combined with a peptide antigen, cholicamideß (6) potentiated the antigen presentation on dendritic cells to induce antigen-specific T cells. As a therapeutic cancer vaccine adjuvant in mice, a mixture of cholicamideß (6) and a peptide antigen protected mice from the challenges of malignant cancer cells without overt toxicity. Cholicamideß (6) may offer a translational opportunity as an unprecedented class of small-molecule cancer vaccine adjuvants.

Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma.

mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA-OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy.

Navigation-Assisted Micro-Window Excision of Thoracic Ossification of Ligamentum Flavum (Mishima Surgery) in Professional Baseball Pitchers: A Case Report and Technical Note.

Background and Objectives: Thoracic ossification of the ligamentum flavum (OLF) often causes myelopathy and/or radiculopathy. The disease is frequently observed in East Asian populations. Although thoracic OLF in young athletes who have underwent decompression surgery has been reported, the removal of posterior spinal bony elements and ligamentous complex may often cause postoperative thoracolumbar instability. We established a novel surgical technique that preserves the posterior spinal elements, including the spinous processes, facet joints, and supraspinous and interspinous ligaments for thoracic OLF. This is the first case report to describe a navigation-assisted micro-window excision of thoracic OLF. Case: A 32-year-old male right-handed professional baseball pitcher with significant weakness and numbness in the left leg was referred to our hospital. The patient was diagnosed with thoracic OLF at T10-11 based on radiographic and magnetic resonance images in August 2022. After exposure of the left T10-11 laminae via a small unilateral incision, the location of T10-11 OLF was detected over the lamina by O-arm navigation. Then, the micro-window was made directly above the OLF using a navigated air drill, and the OLF was removed on the ipsilateral side. The contralateral side of OLF was also resected through the same micro-window, achieving complete spinal cord decompression. Results: The next day of the surgery, his leg weakness and numbness were significantly improved. Six weeks after the surgery, he started pitching. Three months after surgery, his symptoms had gone completely, and he pitched from the mound. Approximately 6 months after surgery, he successfully pitched in a professional baseball game. Conclusions: A navigation-assisted micro-window excision of thoracic OLF effectively preserved the spinal posterior bony elements and ligamentous complex. However, long-term clinical outcomes should be evaluated in future studies.

Maintaining early diagnosis of pancreatic adenocarcinoma in Japan: Local resilience against COVID-19.

BACKGROUND AND AIMS: This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on pancreatic adenocarcinoma (PA) practice in our region and discussed the effects of our institution's regional collaborative system, the "Early Stage Pancreatic Cancer Diagnosis Project," which was originally unrelated to this study's purpose. METHODS: We retrospectively investigated 150 patients with PA at Yokohama Rosai Hospital by defining three time periods: before (C0), during the first year (C1), and during the second year (C2) of the COVID-19 pandemic. RESULTS: Among the three periods (C0, C1, and C2), there were significantly less patients with stage I PA (14.0%, 0%, and 7.4%, p = 0.032) in C1, and significantly more patients with stage III PA (10.0%, 28.3%, and 9.3%, p = 0.014) in C1. The pandemic significantly prolonged the median durations from disease onset to patients' first visits (28, 49, and 14 days, p = 0.012). In contrast, there was no significant difference in the median durations from referral to first visit to our institution (4, 4, and 6 days, p = 0.391). CONCLUSIONS: The pandemic advanced the stage of PA in our region. Although the pancreatic referral network remained functional during the pandemic, there were delays from disease onset to patients' first visit to healthcare providers, including clinics. While the pandemic caused temporary damage to PA practice, the routine regional collaboration provided by our institution's project allowed for early resilience. A notable limitation is that the impact of the pandemic on PA prognosis was not evaluated.

Nano-particulate Toll-like Receptor 9 Agonist Potentiates the Antitumor Activity of Anti-Glypican-1 Antibody.

BACKGROUND/AIM: Monoclonal antibodies (mAbs) that target tumor antigens have recently been developed. Their antitumor activity is mainly achieved through antibody-dependent cellular cytotoxicity (ADCC) via effector cells such as tumor-infiltrated macrophages and natural killer (NK) cells. CpG oligodeoxynucleotides (ODNs) have potent antitumor activity and are considered to increase the tumor infiltration of macrophages and NK cells; however, a completely solubilized novel CpG-schizophyllan (SPG) complex, K3-SPG, displays more potent antitumor activity. We recently reported the significant antitumor activity of anti-glypican-1 (GPC1) mAb against GPC1-positive esophageal squamous cell carcinoma (ESCC) via ADCC. The aim of this study was to evaluate the potential synergistic antitumor activity of anti-GPC1 mAb and K3-SPG and elucidate the underlying mechanisms using a xenograft model of GPC1-positive human ESCC cells. MATERIALS AND METHODS: The established human esophageal cancer cell line TE14 was subcutaneously injected into SCID mice. Xenograft mice were treated with anti-GPC1 mAb, K3-SPG, or their combination. Antitumor activity was evaluated by measuring the tumor volume. For FACS analysis, agents were administrated, and tumors were resected 1 day after the final treatment. RESULTS: Anti-GPC1 mAb or K3-SPG monotherapy showed dose-dependent antitumor activity, and combination therapy with anti-GPC1 mAb and K3-SPG showed antitumor activity (p=0.0859). Flow cytometry revealed significantly increased numbers of macrophages (p=0.0133) and of the ratio of activated NK cells/total NK cells (p=0.0058) following K3-SPG or combination therapy. CONCLUSION: Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC.

Severe Shoulder Pain Caused by Lipoma Arborescens in the Subdeltoid Bursa: A Case Report.

Introduction: Lipoma arborescens is a tumor-like lesion that occurs inside joints and synovial bursae, especially in knee joints. It rarely occurs in the shoulder joints and this disease usually causes severe shoulder pain. This study aims to report a rare case of lipoma arborescens occurring in the subdeltoid bursa with severe shoulder pain. Case Report: A 59-year-old woman with severe pain and restriction of range of motion (ROM) for her right shoulder consisting for 2 months was referred to our hospital. Magnetic resonance imaging (MRI) findings revealed that a tumor-like lesion exists in the subdeltoid bursa in her right shoulder and blood examinations revealed no abnormal findings. Surgical resection of the tumor-like lesion was performed and the rotator cuff was repaired because this tumor-like lesion invaded the rotator cuff partially. Pathology examination of the resected tissues was consistent with lipoma arborescens. One year after surgery, the patient's shoulder pain was diminished and its ROM recovered. There was no significant difficulty in activities of daily living. Conclusion: Lipoma arborescens should be considered when patients present with complaints of severe shoulder pain. Even if their physical findings do not suggest rotator cuff injuries, MRI should be performed to rule out lipoma arborescens.

The Efficacy and Safety of EUS-Guided Gallbladder Drainage as a Bridge to Surgery for Patients with Acute Cholecystitis.

BACKGROUND AND AIM: This study aimed to compare the efficacy and safety of endoscopic ultrasound-guided gallbladder drainage and percutaneous transhepatic gallbladder drainage as a bridge to surgery in patients with acute cholecystitis unfit for urgent cholecystectomy. METHODS: This retrospective study included 46 patients who underwent cholecystectomy following endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) or percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis in NTT Tokyo Medical Center. We surveyed 35 patients as the EUS-GBD group and 11 patients as the PTGBD group, and compared the rate of technical success of the cholecystectomy and periprocedural adverse events. A 7-F, 10-cm double pigtail plastic stent was used for ultrasound-guided gallbladder drainage. RESULTS: The rate of technical success of cholecystectomy was 100% in both groups. Regarding postsurgical adverse events, no significant difference was noted between the two groups (EUS-GBD group, 11.4%, vs. PTGBD group, 9.0%; p = 0.472). CONCLUSIONS: EUS-GBD as a BTS seems to be an alternative for patients with AC because it can ensure lower adverse events. On the other hand, there are two major limitations in this study--the sample size is small and there is a risk of selection bias.

Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent.

The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes. However, the function of TRPM4 in immune responses in keratinocytes has not been investigated. In this study, we found that treatment with BTP2, a known TRPM4 agonist, reduced cytokine production induced by tumor necrosis factor (TNF) α in normal human epidermal keratinocytes and in immortalized human epidermal keratinocytes (HaCaT cells). This cytokine-reducing effect was not observed in TRPM4-deficient HaCaT cells, indicating that TRPM4 contributed to the control of cytokine production in keratinocytes. Furthermore, we identified aluminum potassium sulfate, as a new TRPM4 activating agent. Aluminum potassium sulfate reduced Ca2+ influx by store-operated Ca2+ entry in human TRPM4-expressing HEK293T cells. We further confirmed that aluminum potassium sulfate evoked TRPM4-mediated currents, showing direct evidence for TRPM4 activation. Moreover, treatment with aluminum potassium sulfate reduced cytokine expression induced by TNFα in HaCaT cells. Taken together, our data suggested that TRPM4 may serve as a new target for the treatment of skin inflammatory reactions by suppressing the cytokine production in keratinocytes, and aluminum potassium sulfate is a useful ingredient to prevent undesirable skin inflammation through TRPM4 activation.

Simultaneous bilateral quadriceps tendon rupture in a healthy young male: a case report.

BACKGROUND: Simultaneous bilateral quadriceps tendon rupture is rare, particularly in young individuals with no prior medical history. We present the case of a young man who presented with bilateral quadriceps tendon rupture. CASE PRESENTATION: A 27-year-old Japanese man missed a step while descending a flight of stairs, stumbled, and became aware of severe pain in both knees. He had no past medical history, but was severely obese, with a body mass index of 43.7 kg/m2 (height 177 cm, weight 137 kg). Five days after injury, he was referred to our hospital for examination and treatment. Bilateral quadriceps tendon rupture was diagnosed based on magnetic resonance imaging, and quadriceps tendon repair with suture anchor was performed on both knees 14 days after injury. The postoperative rehabilitation protocol was to immobilize both knees in extension for 2 weeks, then to gradually proceed with weight-bearing and gait training using hinged knee braces. Both knees obtained a range of motion from 0° to 130° without any extension lag by 3 months postoperatively. One year postoperatively, tenderness was evident at the suture anchor in the right knee. That suture anchor was therefore removed in a second operation, and histological evaluation of the tendon of the right knee revealed no pathological changes. As of 19 months after the primary surgery, the patient showed a range of motion from 0° to 140° in both knees, did not complain of any disability, and had fully returned to normal daily activities. CONCLUSIONS: We experienced simultaneous bilateral quadriceps tendon rupture in a 27-year-old man with no past medical history other than obesity. Suture anchor repair was performed for both quadriceps tendon ruptures and achieved a favorable postoperative outcome.

Clinical Features and Prognostic Impact of Pancreatic Ductal Adenocarcinoma without Dilatation of the Main Pancreatic Duct: A Single-Center Retrospective Analysis.

The presence of main pancreatic duct (MPD) dilatation is important for diagnosing pancreatic ductal adenocarcinomas (PDACs). However, we occasionally encounter PDAC cases without MPD dilatation. The objectives of this study were to compare the clinical findings and prognosis of pathologically diagnosed PDAC cases with and without MPD dilatation and to extract factors related to the prognosis of PDAC. The 281 patients pathologically diagnosed with PDAC were divided into two groups: the dilatation group (n = 215), consisting of patients with MPD dilatation of 3 mm or more, and the non-dilatation group (n = 66), consisting of patients with MPD dilatation less than 3 mm. We found that the non-dilatation group had more cancers in the pancreatic tail, more advanced disease stage, lower resectability, and worse prognoses than the dilatation group. Clinical stage and history of surgery or chemotherapy were identified as significant prognostic factors for PDAC, while tumor location was not. Endoscopic ultrasonography (EUS), diffusion-weighted magnetic resonance imaging (DW-MRI), and contrast-enhanced computed tomography had a high tumor detection rate for PDAC even in the non-dilatation group. Construction of a diagnostic system centered on EUS and DW-MRI is necessary for the early diagnosis of PDAC without MPD dilatation, which can improve its prognosis.