Occult clear cell carcinoma arising from oxidative stress­exposed cystic adenomyosis: A case report.

Although adenomyosis is a benign uterine disease, it can turn malignant in rare instances. Cystic adenomyosis is a rare variation of adenomyosis, arising from which 8 cases of clear cell carcinoma have been reported. However, to the best of our knowledge, there have been no previous reports describing the mechanism by which clear cell carcinoma develops from cystic adenomyosis. The present report documents a case of a 73-year-old woman who was referred to Kanazawa University Hospital (Kanazawa, Japan) because of cystic adenomyosis, with a solid part inside the cyst. The patient was diagnosed with cystic adenomyosis at Shonan Obstetrics and Gynecology Hospital (Hakusan, Japan) 17 years prior; however, the size of the cyst increased after menopause. Therefore, malignant transformation was suspected, which warranted simple abdominal hysterectomy and bilateral salpingo-oophorectomy. The final diagnosis of the present case was uterine corpus cancer, clear cell carcinoma, stage IA. Immunohistochemical staining revealed that the normal and transitional atypical epithelial cells lining the cyst wall, in addition to the clear cell carcinoma cells (which were inside mural nodules located on the cyst wall), were positive for 8-hydroxy-20-deoxyguanosine. This observation suggested the presence of chronic oxidative stress around the cystic adenomyosis. Therefore, the present case suggests the possible involvement of chronic oxidative stress in the malignant transformation of cystic adenomyosis to clear cell carcinoma. This mechanism of malignant transformation of cystic adenomyosis appears to be similar to that of the malignant transformation of endometriotic cysts. Therefore, if the size of the cystic adenomyosis increases after menopause or if the solid part appears in the cyst in future cases, then the possibility of malignant transformation should be considered.

Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.

Epithelial ovarian cancer (EOC) is often diagnosed in advanced stage with peritoneal dissemination. Recent studies indicate that aberrant accumulation of collagen fibers in tumor stroma has a variety of effects on tumor progression. We refer to remodeled fibrous stroma with altered expression of collagen molecules, increased stiffness, and highly oriented collagen fibers as tumor-associated fibrosis (TAF). TAF contributes to EOC cell invasion and metastasis in the intraperitoneal cavity. However, an understanding of molecular events involved is only just beginning to emerge. Further development in this field will lead to new strategies to treat EOC. In this review, we focus on the recent findings on how the TAF contributes to EOC malignancy. Furthermore, we will review the recent initiatives and future therapeutic strategies for targeting TAF in EOC.

The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype.

Although a wide variety of mechanisms take part in the secondary injury phase of spinal cord injury (SCI), inflammation is the most important factor implicated in the sequelae after SCI. Being central to the inflammation reaction, macrophages and their polarization are a topic that has garnered wide interest in the studies of SCI secondary injury. The glucagon-like peptide 1 (GLP-1) receptor agonist exenatide has been shown to enhance the endoplasmic reticulum stress response and improve motor function recovery after spinal cord injury (SCI). Since exenatide has also been reported to induce the production of M2 cells in models of cerebral infarction and neurodegenerative diseases, this study was conducted to examine the effects of exenatide administration on the inflammation process that ensues after spinal cord injury. In a rat contusion model of spinal cord injury, the exenatide group received a subcutaneous injection of 10 µg exenatide immediately after injury while those in the control group received 1 mL of phosphate-buffered saline. Quantitative RT-PCR and immunohistochemical staining were used to evaluate the effects of exenatide administration on the macrophages infiltrating the injured spinal cord, especially with regard to macrophage M1 and M2 profiles. The changes in hind limb motor function were assessed based on Basso, Beattie, Bresnahan locomotor rating scale (BBB scale) scores. The improvement in BBB scale scores was significantly higher in the exenatide group from day 7 after injury and onwards. Quantitative RT-PCR revealed an increase in the expression of M2 markers and anti-inflammatory interleukins in the exenatide group that was accompanied by a decrease in the expression of M1 markers and inflammatory cytokines. Immunohistochemical staining showed no significant difference in M1 macrophage numbers between the two groups, but a significantly higher number of M2 macrophages was observed in the exenatide group on day 3 after injury. Our findings suggest that exenatide administration promoted the number of M2-phenotype macrophages after SCI, which may have led to the observed improvement in hind limb motor function in a rat model of SCI.

Elucidating the structural changes of cellulose molecules and dynamics of Na ions during the crystal transition from cellulose I to II in low temperature and low concentration NaOH solution.

Low-concentration alkali treatments at low temperatures facilitate the crystal transition of cellulose I to II. However, the transition mechanism remains unclear. Hence, in this study, we traced the transition using in situ solid-state 13C CP/MAS NMR, WAXS, and 23Na NMR relaxation measurements. In situ solid-state 13C CP/MAS NMR and WAXS measurements revealed that soaking cellulose in NaOH at low temperatures disrupts the intramolecular hydrogen bonds and lowers the crystallinity of cellulose. The dynamics of Na ions (NaOH) play a crucial role in causing these phenomena. 23Na NMR relaxation measurements indicated that the Na-ion correlation time becomes longer during the crystal transition. This transition requires the penetration of Na ions (NaOH) into the cellulose crystal and a reduction in Na-ion mobility, which occurs at low temperatures or high NaOH concentrations. The interactions between cellulose and NaOH disrupt intramolecular hydrogen bonds, inducing a conformational change in the cellulose molecules into a more stable arrangement. This weakens the hydrophobic interactions of cellulose, and facilitates the penetration of NaOH and water into the crystal, leading to the formation of alkali cellulose. Our findings suggest that a strategy to control NaOH dynamics could lead to the discovery of a novel preparation method for cellulose II.

Impact of COVID-19 and Closed Transmission of SARS-CoV-2 during the First Wave in Toyama Prefecture, Japan, March 30 to May 18, 2020.

We studied 226 patients in Toyama Prefecture who were notified of COVID-19 during the first wave between March 30 and May 18, 2020. Of the 226 patients, 22 (9.7%) died, most (95%) of whom were aged ≥65 years. A large cluster comprising 59 patients (41 residents and 18 staff members) was identified in a nursing home on April 17. No deaths occurred among staff members; however, 12 of the 41 residents (29%) died. Although the threshold cycle (Ct) values were significantly lower in the 20-64 and ≥65 years age groups than in the <20 years age group, no correlation was found between the Ct values and severity, fatal outcome, or secondary infection. The haplotype network of 145 SARS-CoV-2 isolates (64%) from 226 patients was analyzed. The viral genomes of the case groups differed by less than five nucleotide bases. These data suggest that the SARS-CoV-2 strains, which were initially introduced into Toyama Prefecture in late March and early April 2020, and their closely related strains, identified as lineage B.1.1, circulated during the first wave. The reduced inter-prefectural mobility of local residents may support the lack of strain diversity in SARS-CoV-2 during the first wave of the state of emergency.

Assessing Procedural Accuracy in Lateral Spine Surgery: A Retrospective Analysis of Percutaneous Pedicle Screw Placement with Intraoperative CT Navigation.

Percutaneous pedicle screws (PPSs) are commonly used in posterior spinal fusion to treat spine conditions such as trauma, tumors, and degenerative diseases. Precise PPS placement is essential in preventing neurological complications and improving patient outcomes. Recent studies have suggested that intraoperative computed tomography (CT) navigation can reduce the dependence on extensive surgical expertise for achieving accurate PPS placement. However, more comprehensive documentation is needed regarding the procedural accuracy of lateral spine surgery (LSS). In this retrospective study, we investigated patients who underwent posterior instrumentation with PPSs in the thoracic to lumbar spine, utilizing an intraoperative CT navigation system, between April 2019 and September 2023. The system's methodology involved real-time CT-based guidance during PPS placement, ensuring precision. Our study included 170 patients (151 undergoing LLIF procedures and 19 trauma patients), resulting in 836 PPS placements. The overall PPS deviation rate, assessed using the Ravi scale, was 2.5%, with a notably higher incidence of deviations observed in the thoracic spine (7.4%) compared to the lumbar spine (1.9%). Interestingly, we found no statistically significant difference in screw deviation rates between upside and downside PPS placements. Regarding perioperative complications, three patients experienced issues related to intraoperative CT navigation. The observed higher rate of inaccuracies in the thoracic spine suggests that various factors may contribute to these differences in accuracy, including screw size and anatomical variations. Further research is required to refine PPS insertion techniques, particularly in the context of LSS. In conclusion, this retrospective study sheds light on the challenges associated with achieving precise PPS placement in the lateral decubitus position, with a significantly higher deviation rate observed in the thoracic spine compared to the lumbar spine. This study emphasizes the need for ongoing research to improve PPS insertion techniques, leading to enhanced patient outcomes in spine surgery.

Administration of the GLP-1 receptor agonist exenatide in rats improves functional recovery after spinal cord injury by reducing endoplasmic reticulum stress.

After spinal cord injury (SCI), endoplasmic reticulum (ER) stress has been reported to be an integral part of the secondary injury process that causes apoptosis of glial cells, leading to remyelination failure. This report focuses on exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely used to treat diabetes, as a potential agent to improve functional outcome after SCI by improving the ER stress response. Exenatide administered subcutaneously immediately after injury and 7 days later in a rat model of moderate contusive SCI revealed significant improvement in hindlimb function without any hypoglycemia. Changes in the expression of glucose regulatory protein 78 (GRP78), an endoplasmic reticulum chaperone that protects against ER stress, and C/EBP homologous transcription factor protein (CHOP), a pro-apoptotic transcription factor in the apoptosis pathway were examined as indices of ER stress. We found that administration of exenatide after SCI suppressed CHOP while increasing GRP78 in the injured spinal cord, leading to a significant decrease in tissue damage and a significant increase in oligodendrocyte progenitor cell survival. This study suggests that administration of exenatide after SCI decreases ER stress and improves functional recovery without any apparent side-effects.

Ovarian cancer: Novel mechanisms and therapeutic targets regarding the microenvironment in the abdominal cavity.

Ovarian cancer is an intractable disease that is mostly diagnosed at an advanced stage and has a high recurrence rate. The early development of characteristic peritoneal dissemination via ascites contributes to a poor prognosis. Based on the "seed and soil" theory, ovarian cancer is considered to form a disseminated tumor that interacts with the peritoneum; superficial mesothelial cells are structurally important. Thus far, we have reported that peritoneal mesothelial cells, which originally are ecological defenses, transform into ovarian cancer-associated mesothelial cells, which are allies of cancer. They are found to be actively involved in the formation of a friendly "soil" that promotes the survival of "seeds" of ovarian cancer cells. We also demonstrated that the progression of ovarian cancer and the induction of its refractory nature are partially mediated through competition and cooperation between ovarian cancer and mesothelial cells. We believe that it is necessary to shift the aim of treatment strategies from solely targeting cancer cells to focusing on the crosstalk between the surrounding environment and ovarian cancer, an approach that ultimately aims to achieve "coexistence" with cancer through disease control.

Desynchronization between Food Intake and Light Stimulations Induces Uterine Clock Quiescence in Female Mice.

BACKGROUND: Dysmenorrhea is associated with breakfast skipping in young women, suggesting that fasting in the early active phase disrupts uterine functions. OBJECTIVES: To investigate the possible involvement of the uterine clock system in fasting-induced uterine dysfunction, we examined core clock gene expressions in the uterus using a 28-h interval-fed mouse model. METHODS: Young female mice (8 wk of age) were divided into 3 groups: group I (ad libitum feeding), group II (time-restricted feeding, initial 4 h of the active period every day), and group III (time-restricted feeding for 8 h with a 28-h cycle). Groups II and III have the same fasting interval of 20 h. After analyzing feeding and wheel running behaviors during 2 wk of dietary restriction, mice were sacrificed at 4-h intervals, and the expression profiles of clock genes in the uterus and liver were examined by qPCR. RESULTS: The mice in group I took food mainly during the dark phase and those in group II during the initial 4 h of the dark phase, whereas those in group III delayed feeding time by 4 h per cycle. In all groups, spontaneous wheel running was observed during the dark phase. There was no difference in the quantity of feeding and the amount of running exercise among the 3 groups during the second week. The mRNA expressions of peripheral clock genes, Bmal1, Clock, Per1, Per2, Cry1, Nr1d1, and Dbp and a clock-controlled gene, Fabp1, in the uterus showed rhythmic oscillations with normal sequential expression cascade in groups I and II, whereas their expressions decreased and circadian cycles disappeared in group III. In contrast, liver core clock genes in group III showed clear circadian cycles. CONCLUSIONS: Fluctuations in the timing of the first food intake impair the uterine clock oscillator system to reduce clock gene expressions and abolish their circadian rhythms.

The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship.

The circadian rhythm, which is necessary for reproduction, is controlled by clock genes. In the mouse uterus, the oscillation of the circadian clock gene has been observed. The transcription of the core clock gene period (Per) and cryptochrome (Cry) is activated by the heterodimer of the transcription factor circadian locomotor output cycles kaput (Clock) and brain and muscle Arnt-like protein-1 (Bmal1). By binding to E-box sequences in the promoters of Per1/2 and Cry1/2 genes, the CLOCK-BMAL1 heterodimer promotes the transcription of these genes. Per1/2 and Cry1/2 form a complex with the Clock/Bmal1 heterodimer and inactivate its transcriptional activities. Endometrial BMAL1 expression levels are lower in human recurrent-miscarriage sufferers. Additionally, it was shown that the presence of BMAL1-depleted decidual cells prevents trophoblast invasion, highlighting the importance of the endometrial clock throughout pregnancy. It is widely known that hormone synthesis is disturbed and sterility develops in Bmal1-deficient mice. Recently, we discovered that animals with uterus-specific Bmal1 loss also had poor placental development, and these mice also had intrauterine fetal death. Furthermore, it was shown that time-restricted feeding controlled the uterine clock's circadian rhythm. The uterine clock system may be a possibility for pregnancy complications, according to these results. We summarize the most recent research on the close connection between the circadian clock and reproduction in this review.

A multicenter case-control study of self-expanding metallic stent versus trans-anal colorectal tube for stage II/III non-right-sided obstructive colon cancer.

BACKGROUND: Self-expanding metallic stent (SEMS) and trans-anal colorectal tube (TCT) are alternative treatments to conventional emergency surgery for non-right-sided obstructive colon cancer (NROCC). However, the one with better short- and long-term outcomes remains controversial. Thus, this multicenter case-control study aimed to analyze and compare SEMS and TCT for NROCC. METHODS: Patients with stage II/III NROCC who underwent surgery between January 2010 and December 2019 at either of the eight selected Japanese affiliate hospitals were, retrospectively, reviewed. Baseline characteristics between the SEMS and TCT groups were adjusted by propensity score (PS) matching. RESULTS: Among 239 reviewed patients (SEMS: 76, TCT: 163), 180 were finally included in two well-balanced cohorts through PS: SEMS group (65 patients) and TCT group (115 patients). Technical success, clinical success, morbidity, and short-term mortality were not significantly different between the two groups. SEMS placement achieved significantly higher rates for primary resection/anastomosis without stoma (SEMS: 90.8% vs. TCT: 77.4%, p < 0.001) and laparoscopic surgery (SEMS: 64.6% vs. TCT: 43.5%, p < 0.001) than TCT placement. However, 5-year overall survival (SEMS: 83.7% vs. TCT: 86.4%; p = 0.822) and 5-year relapse-free survival (SEMS: 64.7% vs. TCT: 66.4%; p = 0.854) showed no significant differences between these groups. CONCLUSIONS: Both SEMS and TCT revealed similar long-term outcomes, but SEMS placement was better in achieving primary resection/anastomosis and laparoscopic surgery in patients with stage II/III NROCC.

Somnolence and Dizziness During Mirogabalin Treatment in Patients With Neuropathic Pain Related to Lumbar Disease Who Switched From Pregabalin: A Retrospective Study.

STUDY DESIGN: Multicenter retrospective study. OBJECTIVES: To investigate adverse events (AEs) in patients with neuropathic pain related to lumbar disease who switched to mirogabalin from pregabalin. METHODS: This study surveyed the records of 82 patients with peripheral neuropathic leg pain related to lumbar disease who switched to mirogabalin from pregabalin. We evaluated AEs associated with pregabalin and mirogabalin, the continuation rate of mirogabalin, and the pain-relieving effect at 4 weeks after switching from pregabalin to mirogabalin. We compared patients who switched due to lack of efficacy (LoE group) and patients who switched due to AEs (AE group). RESULTS: The incidence rates of somnolence and dizziness with pregabalin were 12.2% and 14.6%, respectively, while the incidence rates with mirogabalin were reduced to 7.3% for somnolence and 4.9% for dizziness. The incidence of AEs with pregabalin was significantly higher in the AE group (LoE group: 11.1%, AE group 100%), especially for somnolence (LoE group: 3.2%, AE group: 47.1%) and dizziness (LoE group: 4.8%, AE: 52.9%). After switching, the incidences of AEs with mirogabalin were not significantly different between the 2 groups (LoE group: 15.9%, AE group: 23.5%), including for somnolence (LoE group: 7.9%, AE group: 5.9%) and dizziness (LoE group: 4.8%, AE group: 5.9%). There were no significant differences in continuation rate of mirogabalin or the pain-relieving effect between groups. CONCLUSIONS: The patients who experience somnolence and dizziness with pregabalin might be able to continue safely receiving treatment for their pain by switching to mirogabalin.

Efficacy of minocycline hydrochloride aspiration sclerotherapy with additional monoethanolamine oleate aspiration sclerotherapy for symptomatic hepatic cysts.

AIM: Minocycline hydrochloride (MINO) aspiration sclerotherapy (AS) has been widely used for treating hepatic cysts (HC). However, cyst recurrence remains problematic. Information on monoethanolamine oleate (EO) AS, another effective HC treatment, is currently limited. We investigated the efficacy of EO on ineffective MINO treatments, and the relationship between MINO AS and cyst fluid pH. METHODS: A total of 22 cases with symptomatic HC underwent AS with 500 mg of MINO from January 2016 to June 2021. Cyst fluid pH was measured before and after MINO injection. Cyst volume ratio (CVR, %) after 2 weeks was calculated as follows:cyst volume 2 weeks after MINO injection / pre-treatment cyst volume × 100. Treatment was completed if CVR after 2 weeks was ≤35% (MINO-group). For patients with CVR >35%, 2 g of EO was added (MINO/EO-group). Cyst volume ratio was measured every 12 months thereafter. RESULTS: There were no recurrence symptoms in any of the patients during follow-up. Of the 22 cases, 21 had CVR ≤20% after 12 months. The MINO/EO-group (n = 8) tended to have smaller CVRs after 12 months than the MINO-group (n = 14). Cyst volume ratio after 2 weeks was correlated to pH change (p = 0.012) and was larger in patients whose pH decreased by <1.5 (p = 0.015). All adverse events were mild, including in elderly patients. CONCLUSION: Adding EO is an effective and safe treatment for symptomatic HC when MINO AS alone is insufficient. Patients with pH decreases of <1.5 should be considered for additional EO treatment.

An Analysis of Whether a New Formula Can Predict Proximal Junctional Failure in Adult Spinal Deformity Patients with Global Kyphosis.

OBJECTIVE: A new formula containing terms for age and sagittal curvature reported by the International Spine Study Group is ideal lumbar lordosis (iLL) = pelvic incidence - 0.3 thoracic kyphosis - 0.5Age + 10. However, there are no reports of whether proximal junctional failure (PJF) can be predicted using this formula. We assessed the utility of this formula in PJF in patients with adult spinal deformity with global kyphosis using the Roussouly classification. METHODS: Forty-four patients with adult spinal deformity global kyphosis (mean age 70.0 years) who underwent multiple levels of lateral lumbar interbody fusion combined with posterior instrumentation were included. Patients were divided into 2 groups: PJF and non-PJF. Demographic, surgical, and radiological parameters were compared. The iLL was calculated according to the new formula, and spinal parameters were compared preoperatively, immediately after, and at the final follow-up. RESULTS: PJF occurred in 11 of 44 (25.0%) patients. Patients with PJF had a large preoperative and postoperative TK, but there was no statistically significant difference in iLL between PJF and non-PJF patients (33.4° vs. 30.2°, P = 0.357). In addition, there was no statistically significant difference in LL and iLL changes (ΔiLL) immediately after surgery (19.0° vs. 23.4°, P = 0.379). Furthermore, there was no correlation between ΔiLL immediately after surgery and at the final follow-up and the proximal junctional angle at the final follow-up. CONCLUSIONS: The results of ΔiLL suggest that overcorrection needs to be addressed but that this new formula, including age adjustment, may not predict PJF.

[Measurement of Airborne Radioactivity in the Inpatient Room after Administering [177Lu]Lu-PSMA-617 to Humans].

OBJECTIVE: [177Lu]Lu-PSMA-617 is a radioisotope used in nuclear medicine. It is necessary to take appropriate measures to limit its exposure and ensures its airborne concentrations do not exceed legally permitted levels. Therefore, the purpose of this study was to measure the airborne radioactivity concentration in the inpatient room after administering [177Lu]Lu-PSMA-617 to humans. METHODS: Three males with advanced prostate-specific membrane antigen (PSMA)-positive metastatic castration resistant prostate cancer were intravenously administered [177Lu]Lu-PSMA-617 (7.4 GBq ± 10%) in an inpatient room, and the airborne radioactivity concentrations were measured at two locations in the room (in the center of the room and at the bedside) using a filter collection method. RESULTS: After administration of [177Lu]Lu-PSMA-617, the airborne radioactivity concentrations measured were below the limit of detection (1.1 × 10-6 Bq/cm3 or 9.5 × 10-7 Bq/cm3) in all three humans, and all concentrations were consistently below the standard value of 1/10,000 of 2 × 10-2 Bq/cm3, the legal airborne concentration limit of 177Lu. CONCLUSION: The results of this study confirmed that the airborne concentration of [177Lu]Lu-PSMA-617 after administration to humans was below the legally permitted level.

Treatment of Lumbar Degenerative Disease by Lateral Lumbar Interbody Fusion in Patients Under and Over 80 Years of Age.

OBJECTIVES: The purpose of this study was to compare clinical and radiological results of lateral lumbar interbody fusion (LLIF) for lumbar degenerative disease in patients under the age of 80 years with those over the age of 80 years. METHODS: One hundred two patients who underwent LLIF without direct decompression were enrolled, including 92 patients who were less than 80 years (group A) and 10 over 80 years (group B). All patients were evaluated using numerical evaluation scale scores for low back pain, leg pain, and leg numbness, as well as demographic data, surgical data, and imaging data before and after LLIF surgery. RESULTS: Patients over the age of 80 years were found to have longer hospital stays (P = 0.006) and more postoperative muscle weakness (P = 0.011) and endplate injuries (P = 0.038). In addition, each numerical evaluation scale score improved significantly from preoperative to postoperative (P < 0.001). However, the changes in scores between preoperative and postoperative for each numerical evaluation scale were not significantly different between the 2 groups. Statistically significant increases in lumbar lordosis preoperatively compared with postoperatively were observed in patients under 80 years but did not change in those over 80 years. CONCLUSIONS: These data suggest a need for awareness of intraoperative endplate injury and postoperative motor weakness. Critically, indirect decompression with LLIF in lumbar degenerative disease in patients over age 80 as well as those under age 80 has shown satisfactory clinical and radiological results. This study shows that age alone should not prevent older people from undergoing LLIF.

Analysis of cell-free circulating DNA fragment size and level in patients with lumbar canal stenosis.

Cell-free circulating DNA (cfDNA), extracted by liquid biopsy, has been studied as a noninvasive biomarker for various diseases. The potential of cfDNA fragment size and level as a marker in lumbar canal stenosis (LCS) patients has never been studied. We investigated whether cfDNA is a biomarker of low back pain, leg pain, leg numbness severity in patients with an LCS. Blood samples were obtained from patients with LCS (n = 22) before and immediately after spinal surgery. Plasma DNA was isolated and examined for cfDNA fragment size and concentration. A cohort of healthy volunteers (n = 5) constituted the control group. The cfDNA fragment size tended to be shorter in patients than in healthy controls, but this difference was not significant (P = .186). cfDNA level was significantly higher in LCS patients (mean 0.614 ± 0.198 ng/µL, range 0.302-1.150 ng/µL) than in healthy controls (mean 0.429 ± 0.064 ng/µL, range 0.366-0.506 ng/µL) (P = .008). cfDNA level correlated positively with average pain (r = .435, P = .026) and leg numbness (r = .451, P = .018). cfDNA fragment size did not differ from before to after surgery, but cfDNA level increased postoperatively in patients with LCS. This was the first study investigating whether cfDNA fragment size and level are associated with pain in patients with LCS. Our findings suggest that cfDNA level may be an objective indicator of pain and surgical invasiveness in patients with LCS.

[A case of gastric cancer showing a durable response after the discontinuation of nivolumab due to the early onset of immune-related adverse events].

The Japanese guidelines for the treatment of gastric cancer recommend nivolumab as third-line chemotherapy for metastatic gastric cancer. We report a case of gastric cancer exhibiting a durable response after the discontinuation of nivolumab due to the early onset of immune-related adverse event (irAE). A 64-year-old man with advanced HER2-positive gastric cancer and distant lymph node metastasis received nivolumab as fourth-line therapy. After two courses of nivolumab, the lymph nodes showed progression. However, the treatment was discontinued because of interstitial pneumonia as an irAE. Disease regression was sustained for approximately 11 months without the readministration of nivolumab.

Anti-inflammatory effects of differential molecular weight Hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation.

BACKGROUND: The biological functions of Hyaluronic acid are related to its molecular weight and binding to its receptor, Toll-like receptor4 (TLR4) or CD44. Recent studies have shown that low-molecular-weight Hyaluronic acid (LMW-HA) exhibits proinflammatory effects, while high-molecular-weight Hyaluronic acid (HMW-HA) functions as an anti-inflammatory factor. UVB-induced epidermal inflammation is mainly mediated by endogenous molecules, such as damage-associated molecular patterns (DAMPs), that cause severe skin damage by activating TLR signaling pathways. OBJECTIVE: Since both LMW- and HMW-HA have inhibitory functions on TLR-mediated macrophage inflammation, HA is assumed to suppress UVB-induced DAMP-mediated inflammation in the skin. In this study, both Ultra- low-molecular-weight Hyaluronic acid (uLMW-HA) and HMW-HA were found to inhibit UVB-induced keratinocyte inflammation. METHODS: HaCaT cells were treated with medium containing Hyaluronic acid at the appropriate concentration after 15 mJ/cm2 irradiation. Secreted protein levels were determined with ELISA kits. Expression levels of proteins downstream of TLR4 were detected by Simple Western system. RESULTS: By competitively binding to TLR4, uLMW-HA downregulated Calprotectin-induced TRAF6 expression, which might be the direct process by which uLMW-HA decreased UVB-induced IL-6 secretion. Reduced　CD44 variant (CD44v) expression in keratinocytes attenuated the inhibitory effect of both uLMW-HA and HMW-HA on UVB-induced inflammation, which indicated the involvement of CD44v in HA-regulated anti-inflammatory activity. CONCLUSION: Overall, this research indicates that Hyaluronic acid is more than a moisturizer; it is also a biologically effective material that can prevent the excessive skin inflammation caused in daily life, especially in the late stages after sunburn.

The Effect of Preoperative Neuropathic Pain and Nociceptive Pain on Postoperative Pain Intensity in Patients with the Lumbar Degenerative Disease Following Lateral Lumbar Interbody Fusion.

OBJECTIVE: The purpose of this study was to analyze whether the type of preoperative pain affects the improvement in postoperative pain intensity in patients with a lumbar degenerative disease (LDD). METHODS: We retrospectively reviewed 93 patients who underwent lateral lumbar interbody fusion (LLIF) without direct decompression. All patients were evaluated using Numeric Rating Scale (NRS) scores for low back pain (NRSLBP), leg pain (NRSLP), and leg numbness (NRSLN) and imaging data before and after LLIF surgery. Based on the Japanese version of the painDETECT scores, patients were classified into 3 groups: a neuropathic pain (NeP) group, a nociceptive pain (NocP) group, and an intermediate mixed pain group. RESULTS: The Japanese version of the painDETECT identified NeP in 20.4% of patients with LDD prior to LLIF. Preoperative NRSLBP, NRSLP, and NRSLN scores were higher in the NeP group than those in the NocP group. All types of pain improved after LLIF surgery. The NRSLBP score 12 months after surgery was higher in the NeP group (3.8 ± 2.8) than that in the NocP group (1.9 ± 2.2) (P = 0.008). Similar results were obtained with NRSLP (NeP group = 3.1 ± 2.8, NocP group = 1.5 ± 2.0, P = 0.010). CONCLUSIONS: Although LLIF was useful for relieving all types of preoperative pain in LDD patients, the NRS scores for preoperative pain were higher in the NeP group than those in the NocP group, and the postoperative NRSLBP and NRSLP score was significantly higher in the NeP group. Thus, controlling preoperative NeP may improve therapeutic efficacy.