Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 192
1.
Clin Case Rep ; 12(6): e9049, 2024 Jun.
Article En | MEDLINE | ID: mdl-38910834

Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between palliative measures and surgery. This case indicates that total talar replacement is an effective intervention for localized talar metastases and highlights the importance of early intervention. A 48-year-old man was diagnosed with a pathologic talar fracture due to talar metastases was observed after 8 years of chemotherapy following a diagnosis of lung adenocarcinoma. Despite radiotherapy, the patient's activities of daily living (ADLs) deteriorated due to pain on walking, prompting a request for surgical intervention. Total talar replacement was performed, allowing the patient to begin full weight-bearing ambulation 2 weeks post-operatively. Total talar replacement appears to be an effective treatment for localized talar metastases and should be performed as early as possible.

2.
Thorac Cancer ; 15(17): 1390-1394, 2024 Jun.
Article En | MEDLINE | ID: mdl-38698706

The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.


Acrylamides , Aniline Compounds , Antitubercular Agents , ErbB Receptors , Lung Neoplasms , Mutation , Tuberculosis, Pulmonary , Humans , Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Aniline Compounds/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Female , ErbB Receptors/genetics , Tuberculosis, Pulmonary/drug therapy , Aged, 80 and over , Antitubercular Agents/therapeutic use , Indoles , Pyrimidines
3.
Arerugi ; 73(2): 171-179, 2024.
Article Ja | MEDLINE | ID: mdl-38522931

BACKGROUND: Itch is the most troublesome symptom of atopic dermatitis, and it is important to assess it appropriately for optimal treatment. We discussed issues regarding itch and the most appropriate methods of assessment at the Atopic Itch Consensus Meeting (AICOM), attended by physicians and researchers with expertise in itch treatment and research. METHODS: The AICOM participants prepared a draft consensus statement that addressed the most appropriate itch assessment methods for age groups <2 years, 2-6 years, 7-14 years, and ≥15 years. Consensus was defined as agreement by ≥80% of the participants. RESULTS: Votes were cast by 20 participants (8 dermatologists, 7 pediatricians, and 5 researchers), and a consensus on the best current methods of itch assessment was reached with 95% agreement. For infants and preschool children, because subjective evaluation is difficult, a checklist for itch assessment was developed for caregivers. CONCLUSION: For itch assessment, we recommend subjective evaluation by the patient using a rating scale. For infants and preschoolers, evaluation should be done by the caregiver using a checklist, combined with objective evaluation (of skin lesions, for example) by a physician. We anticipate that more objective itch assessment indices will be established in the future.


Dermatitis, Atopic , Pruritus , Infant , Child, Preschool , Humans , Severity of Illness Index , Pruritus/diagnosis , Pruritus/etiology , Dermatitis, Atopic/complications , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/therapy
4.
Cureus ; 16(2): e53803, 2024 Feb.
Article En | MEDLINE | ID: mdl-38465079

BACKGROUND: The biomechanical effect of distal tibial oblique osteotomy (DTOO) on osteoarthritic ankles has not been investigated. Using finite element (FE) models, we aimed to elucidate the effect of DTOO on the ankle contact pressure (CP) distribution. METHODS: This study included two patients with ankle osteoarthritis who underwent DTOO and one asymptomatic control. Patient-specific FE models were reconstructed by matching standing radiographs with supine computed tomography scans. The joint contact area (CA) and maximum CP on the articular surface of the talus were calculated before and after DTOO and compared with those of the control. RESULTS: In the control, the CA was 584 mm2 and the maximum CP was 2.6 MPa. In case 1, the CA increased by 125% from 166 mm2 preoperatively to 375 mm2 postoperatively, accompanied by a 36% decrease in the maximum CP from 9.8 MPa to 6.3 MPa. Similarly, in case 2, the CA increased by 46% from 301 mm2 to 439 mm2, accompanied by a 27% decrease in the maximum CP from 6.7 MPa to 4.9 MPa. CONCLUSIONS: This study suggests DTOO improves the biomechanics of the ankle, but not sufficiently compared to the control. This analytical approach may enhance understanding of ankle pathophysiology and assist in the design of the ideal corrective osteotomy.

5.
Intern Med ; 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38403772

Nuclear protein of the testis carcinoma (NUTC) is a rare and aggressive malignancy. We herein report a case of NUTC in the lung characterized by a bronchial lesion and elevated alpha-fetoprotein levels. A 35-year-old Japanese man presented to our institution with suspected advanced lung cancer based on a histological examination. Subsequently, next-generation sequencing (NGS) yielded a positive BRD4-NUTM1 fusion. In addition, positive NUT immunostaining of the lung biopsy specimen confirmed NUTC in the lungs. Systemic chemotherapy and radiotherapy showed a temporary response, with decreased serum alpha-fetoprotein levels. We highlight this case of a prompt diagnosis by NGS of NUTC in a young individual with a rapidly progressing tumor.

6.
Transl Lung Cancer Res ; 12(10): 2098-2112, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-38025818

Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.

7.
Cancer Sci ; 114(11): 4343-4354, 2023 Nov.
Article En | MEDLINE | ID: mdl-37715310

Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Humans , Mice , Anaplastic Lymphoma Kinase/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Interleukin-15 , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Receptor Protein-Tyrosine Kinases/genetics
8.
Sci Rep ; 13(1): 15851, 2023 09 22.
Article En | MEDLINE | ID: mdl-37740003

This study aimed to clarify the clinical utility of the sourcil roundness index (SRI), a novel index for quantifying the asphericity of the acetabular concavity, by determining (1) the difference in the SRI between dysplastic and normal hips and (2) the correlation between the SRI and radiographic parameters of hip dysplasia. We reviewed standing anteroposterior pelvic radiographs of 109 dysplastic and 40 normal hips. The SRI was determined as the ratio of the distance from the medial edge of the sourcil to the most concave point of the acetabular sourcil (A) to the distance from the medial to the lateral edge of the sourcil (B). The formula for SRI is (A/B) × 100-50 (%), with an SRI of 0% indicating a perfectly spherical acetabulum, and higher SRI values indicating a more aspherical shape. The median SRI was greater in patients with hip dysplasia than in normal hips (5.9% vs. - 1.4%; p < 0.001). Furthermore, the median SRI was greater in the severe dysplasia subgroup (18.9%) than in the moderate (3.5%) and borderline-to-mild (- 1.3%) dysplasia subgroups (p < 0.05). Quantification of acetabular concavity asphericity by the SRI showed that dysplastic hips had a more lateral acetabular concave point than normal hips, and that the severity of hip dysplasia had an effect on the acetabular concavity asphericity.


Ascomycota , Hip Dislocation, Congenital , Hip Dislocation , Humans , Acetabulum/diagnostic imaging , Hip Dislocation/diagnostic imaging , Hyperplasia
9.
Intern Med ; 2023 Sep 15.
Article En | MEDLINE | ID: mdl-37722894

A 55-year-old man with stage IV lung adenocarcinoma was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab. Approximately 100 days after treatment initiation, he became disoriented and presented to the emergency department with a high fever. Blood tests revealed liver and kidney dysfunctions. Subsequently, the patient developed generalized convulsions that required intensive care. He was clinically diagnosed with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Organ damage was gradually controlled with immunosuppressive drugs, including steroids, and the patient was discharged. Successful treatment is rare in patients with CRS, including ICANS, during immune checkpoint inhibitor treatment for solid tumors.

10.
Bone Joint J ; 105-B(7): 743-750, 2023 Jul 01.
Article En | MEDLINE | ID: mdl-37399069

Aims: To clarify the mid-term results of transposition osteotomy of the acetabulum (TOA), a type of spherical periacetabular osteotomy, combined with structural allograft bone grafting for severe hip dysplasia. Methods: We reviewed patients with severe hip dysplasia, defined as Severin IVb or V (lateral centre-edge angle (LCEA) < 0°), who underwent TOA with a structural bone allograft between 1998 and 2019. A medical chart review was conducted to extract demographic data, complications related to the osteotomy, and modified Harris Hip Score (mHHS). Radiological parameters of hip dysplasia were measured on pre- and postoperative radiographs. The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan-Meier product-limited method, and a multivariate Cox proportional hazard model was used to identify predictors for failure. Results: A total of 64 patients (76 hips) were included in this study. The median follow-up period was ten years (interquartile range (IQR) five to 14). The median mHHS improved from 67 (IQR 56 to 80) preoperatively to 96 (IQR 85 to 97) at the latest follow-up (p < 0.001). The radiological parameters improved postoperatively (p < 0.001), with the resulting parameters falling within the normal range in 42% to 95% of hips. The survival rate was 95% at ten years and 80% at 15 years. Preoperative Tönnis grade 2 was an independent risk factor for TOA failure. Conclusion: Our findings suggest that TOA with structural bone allografting is a viable surgical option for correcting severely dysplastic acetabulum in adolescents and young adults without advanced osteoarthritis, with favourable mid-term outcomes.


Hip Dislocation, Congenital , Hip Dislocation , Young Adult , Adolescent , Humans , Hip Dislocation/surgery , Treatment Outcome , Bone Transplantation , Retrospective Studies , Acetabulum/diagnostic imaging , Acetabulum/surgery , Hip Dislocation, Congenital/diagnostic imaging , Hip Dislocation, Congenital/surgery , Hip Dislocation, Congenital/complications , Osteotomy/methods , Allografts
11.
Bone Joint J ; 105-B(7): 760-767, 2023 Jul 01.
Article En | MEDLINE | ID: mdl-37399111

Aims: The aims of this study were to validate the Forgotten Joint Score-12 (FJS-12) in the postoperative evaluation of periacetabular osteotomy (PAO), identify factors associated with joint awareness after PAO, and determine the FJS-12 threshold for patient-acceptable symptom state (PASS). Methods: Data from 686 patients (882 hips) with hip dysplasia who underwent transposition osteotomy of the acetabulum, a type of PAO, between 1998 and 2019 were reviewed. After screening the study included 442 patients (582 hips; response rate, 78%). Patients who completed a study questionnaire consisting of the visual analogue scale (VAS) for pain and satisfaction, FJS-12, and Hip disability and Osteoarthritis Outcome Score (HOOS) were included. The ceiling effects, internal consistency, convergent validity, and PASS thresholds of FJS-12 were investigated. Results: The median follow-up was 12 years (interquartile range 7 to 16). The ceiling effect of FJS-12 was 7.2%, the lowest of all the measures examined. FJS-12 correlated with all HOOS subscales (ρ = 0.72 to 0.77, p < 0.001) and pain and satisfaction-VAS (ρ = -0.63 and 0.56, p < 0.001), suggesting good convergent validity. Cronbach's α was 0.95 for the FJS-12, which indicated excellent internal consistency. The median FJS-12 score for preoperative Tönnis grade 0 hips (60 points) was higher than that for grade 1 (51 points) or 2 (46 points). When PASS was defined as pain-VAS < 21 and satisfaction-VAS ≥ 77, the FJS-12 threshold that maximized the sensitivity and specificity for detecting PASS was 50 points (area under the curve (AUC) = 0.85). Conclusion: Our results suggest that FJS-12 is a valid and reliable assessment tool for patients undergoing PAO, and the threshold of 50 points may be useful to determine patient satisfaction following PAO in clinical settings. Further investigation of the factors influencing postoperative joint awareness may enable improved prediction of treatment efficacy and informed decision-making regarding the indication of PAO.


Hip Dislocation, Congenital , Hip Dislocation , Humans , Hip Dislocation/surgery , Hip Dislocation, Congenital/surgery , Hip Dislocation, Congenital/complications , Acetabulum/surgery , Treatment Outcome , Osteotomy/methods , Pain , Hip Joint/surgery , Retrospective Studies
12.
J Gen Fam Med ; 24(4): 264-265, 2023 Jul.
Article En | MEDLINE | ID: mdl-37484124

Here we report a case of sarcoidosis which demonstrated with bilateral ankle arthritis. We usually do not consider sarcoidosis routinely for the differential diagnosis of acute arthritis, however, up to 15 to 25% of sarcoidosis complicate arthritis, typically in ankle joints. Sarcoid arthritis is reported to occur mainly in young northern Europe women, whereas this case intimate that we should take sarcoidosis into account as the differential diagnosis of ankle arthralgia also among Asian men especially when combining upper respiratory symptoms.

13.
Am J Case Rep ; 24: e939719, 2023 Jun 26.
Article En | MEDLINE | ID: mdl-37363883

BACKGROUND The incidence of septic arthritis of a native joint caused by group B streptococcus (GBS, Streptococcus agalactiae) has been on the rise in non-pregnant women. GBS commonly colonizes the female genital tract. However, only a few reports have discussed serious cases of GBS infection, endocarditis, and joint infection associated with the Papanicolaou (Pap) smear test, which is routinely conducted to detect cervical cancer. Specifically, to the best of our knowledge, there have been few reports about arthroscopic treatment for septic arthritis of the ankle caused by GBS. CASE REPORT A 60-year-old woman, who had previously completed the treatment of total laparoscopic hysterectomy with bilateral adnexectomy and postoperative chemotherapy for ovarian cancer, underwent a routine Pap smear test. Four weeks later, she suddenly presented with high fever and abdominal pain. The pain and swelling in her left ankle gradually worsened. Finally, septic arthritis of the ankle was diagnosed, and thus the patient underwent emergent arthroscopic irrigation and debridement. GBS was isolated from both the ankle fluid and blood culture. After surgical intervention and intravenous antibiotic administration, the patient's symptoms gradually improved. Four months later, the patient had no ankle pain or restriction of ankle motion. CONCLUSIONS Although cervical cytology tests are essential in screening for cervical cancer, transient bacteremia can be induced by the tests. Thus, physicians must watch out for the development of septic arthritis caused by GBS when patients present with fever or swollen joints after a recent Pap smear test. Emergent diagnosis and appropriate surgical intervention is also important.


Arthritis, Infectious , Uterine Cervical Neoplasms , Humans , Female , Middle Aged , Streptococcus agalactiae , Debridement , Pain , Arthritis, Infectious/diagnosis , Arthritis, Infectious/surgery , Arthritis, Infectious/drug therapy
14.
Sci Rep ; 13(1): 8288, 2023 05 22.
Article En | MEDLINE | ID: mdl-37217756

This study aimed to (1) set a reference value for anterior center edge angle (ACEA) for preoperative planning of periacetabular osteotomy (PAO), (2) investigate the effects of pelvic rotation and inclination from false profile (FP) radiographs on the measured ACEA, and (3) determine the "appropriate range of positioning" for FP radiograph. This single-centered, retrospective study analyzed 61 patients (61 hips) who underwent PAO from April 2018 and May 2021. ACEA was measured in each digitally reconstructed radiography (DRR) image of the FP radiograph reconstructed in different degrees of pelvic rotation. Detailed simulations were performed to determine the "appropriate range of positioning" (0.67 < ratio of the distance between the femoral heads to the diameter of the femoral head < 1.0). The vertical-center-anterior (VCA) angle was measured on the CT sagittal plane considering the patient-specific standing positions, and its correlation with the ACEA was investigated. The reference value of ACEA was determined by receiver operating characteristic (ROC) curve analysis. The ACEA measurement increased by 0.35° for every 1° pelvic rotation approaching the true lateral view. The pelvic rotation with the "appropriate range of positioning" was found at 5.0° (63.3-68.3°). The ACEA on the FP radiographs showed a good correlation with the VCA angle. The ROC curve revealed that an ACEA < 13.6° was associated with inadequate anterior coverage (VCA < 32°). Our findings suggest that during preoperative PAO planning, an ACEA < 13.6° on FP radiographs indicates insufficient anterior acetabular coverage. Images with the "appropriate positioning" can also have a measurement error of 1.7° due to the pelvic rotation.


Acetabulum , Hip Dislocation , Humans , Retrospective Studies , Acetabulum/diagnostic imaging , Acetabulum/surgery , Radiography , Hip Joint/surgery , Hip Dislocation/diagnostic imaging
15.
Sci Rep ; 13(1): 8688, 2023 05 29.
Article En | MEDLINE | ID: mdl-37248313

There are no reports on hip kinetics including contact forces and muscle activities during the golf swing after total hip arthroplasty (THA). The aim of this study was to identify the characteristics of three-dimensional dynamics during the golf swing. Ten unilateral primary THA patients participated in motion capture test of their driver golf swing. The driver swing produced approximately 20-30° of rotation in both lead and trail replaced hips. The mean hip contact forces (HCFs) of lead and trail replaced hips were 5.1 and 6.6 × body weight, respectively. Left and right THAs showed similar HCFs of lead and trail hips. More than 60% of the Percent maximum voluntary isometric contraction was found in bilateral iliopsoas muscles in all unilateral THA. Three factors [female sex, lower modified Harris Hip Score, and higher HCF of surgical side] were associated with the golf-related replacement hip pain. Golf is an admissible sport after THA because driver swings do not contribute excessive rotation or contact forces to hip prostheses. HCF could be reduced through swing adjustments, which may allow patients with golf-related replacement hip pain to develop a comfortable golf game free from pain.


Arthroplasty, Replacement, Hip , Golf , Humans , Female , Arthroplasty, Replacement, Hip/adverse effects , Golf/physiology , Movement/physiology , Muscle, Skeletal/physiology , Arthralgia , Biomechanical Phenomena
16.
Cancer Sci ; 114(6): 2400-2413, 2023 Jun.
Article En | MEDLINE | ID: mdl-36916958

Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Mice , Carcinogenesis/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Transformation, Neoplastic/genetics , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Lung Neoplasms/genetics , Humans
17.
Lung Cancer ; 178: 1-10, 2023 04.
Article En | MEDLINE | ID: mdl-36753780

OBJECTIVES: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored. MATERIALS AND METHODS: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined. RESULTS: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity. CONCLUSION: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.


Lung Neoplasms , Animals , Mice , Humans , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Lung Neoplasms/pathology , CD8-Positive T-Lymphocytes/pathology , Adaptor Proteins, Signal Transducing , Mice, Inbred C57BL , ErbB Receptors/genetics , Cell Line, Tumor , Tumor Microenvironment
18.
Mol Clin Oncol ; 18(2): 7, 2023 Feb.
Article En | MEDLINE | ID: mdl-36761388

Intravesical immunotherapy using bacillus Calmette-Guérin (BCG) is recommended for patients with intermediate- to high-risk non-muscle invasive bladder cancer. Bladder tuberculosis (TB) is a rare complication of BCG therapy. The present study describes the case of a 73-year-old man who underwent intravesical BCG therapy for urothelial carcinoma in situ of the bladder. Red patches around the resection scar were first detected 1 year and 5 months after BCG treatment; these findings gradually spread to encompass more of the bladder wall. Transurethral biopsy revealed a benign lesion, but the patient developed bilateral hydronephrosis and mild voiding dysfunction. The patient was eventually diagnosed with bladder TB by mycobacterial urine culture and TB-specific polymerase chain reaction (PCR). The patient was given multidrug therapy (isoniazid, rifampicin and ethambutol) and their bladder TB was completely cured; however, their voiding dysfunction and bilateral hydronephrosis did not fully improve. Bladder TB can occur long after intravesical BCG administration and cystoscopy findings consistent with inflammation can be the key to suspecting this condition. Acid-fast examination and PCR testing of a urine sample are necessary for early diagnosis.

19.
J Orthop Sci ; 28(3): 677-682, 2023 May.
Article En | MEDLINE | ID: mdl-35153123

BACKGROUND: This study aims to evaluate the accuracy of the axis connecting both anterior superior iliac spines (ASIS axis) as the absolute pelvic axis. No study has ever verified the accuracy of ASIS axis particularly on the AP pelvic radiograph, which cannot be specified on it. METHODS: Sixty patients who underwent total knee arthroplasty and fifty patients with femoral neck fracture were recruited as subjects without hip deformities and their CT scan data were collected. We defined the line through both center of femoral heads as absolute reference axis of pelvis three-dimensionally. On the coronal plane, the errors between the femoral head axis and the axes through six pelvic landmarks in total, including ASIS were analyzed. On the axial plane, the errors of the lines through four landmarks were analyzed in the same way. Finally, on the coronal images, the mediolateral diameter of the obturator foramen and the mediolateral distance between the midline of the sacrum and the pelvic cavity were measured to evaluate bilateral symmetry of the pelvis. RESULTS: The errors tended to be smaller as the axes were closer to the femoral head axis (axes connecting bilateral superior aspects of the acetabulum and the teardrops) and the ASIS axis errors were moderate. The obturator foramen based on the ASIS axis was more asymmetrical than the femoral head axis. CONCLUSION: Adjusting the pelvic tilt and rotation, surgeons should not always rely on the ASIS and refer to appropriate, close to the hip joint references in each case.


Ilium , Pelvis , Humans , Acetabulum , Hip Joint , Ilium/diagnostic imaging , Sacrum
20.
Arthroplast Today ; 19: 101067, 2023 Feb.
Article En | MEDLINE | ID: mdl-36471771

Background: Prosthetic joint infection, which is caused by implant treatment, is a severe complication. Consequently, silver-containing hydroxyapatite (Ag-HA)-coated implants have been developed to prevent prosthetic joint infection by combining Ag with HA. The Ag-HA-coated total hip prosthesis, which combines the antibacterial activity of Ag and the osteoconductivity of HA, is the first antibacterial cementless total hip prosthesis worldwide. This study aimed to evaluate the short-term outcomes of total hip arthroplasty (THA) with Ag-HA-coated implants. Methods: Overall, 50 hips with various disabling hip diseases and postoperative infection risks that underwent a primary THA using an Ag-HA total hip prosthesis were enrolled. The patients included 37 women (41 hips) and 8 men (9 hips), and the mean age at the time of surgery was 77 years. The clinical outcomes and hip function before and at 5 years postoperatively were measured using the Japanese Orthopaedic Association hip score. Implant stability was assessed, and postoperative complications were also examined. Results: The Japanese Orthopaedic Association score increased in all cases and improved from 41 to 86 points after the THA (P < .001). Radiography revealed no implant failure. Dislocation and deep vein thrombosis also occurred in 1 case each. However, there were no adverse reactions associated with Ag, and argyria was not observed in any case. Additionally, none of the patients experienced infection following the surgery. Conclusions: Silver-containing hydroxyapatite-coated implants significantly enhanced patients' daily activities without any adverse effects on the human body attributed to Ag, and they are expected to reduce postoperative infections.

...