Feasibility of the analytical dose calculation method for Au-198 brachytherapy.

PURPOSE: A dose calculation algorithm Computed Tomography (CT)-based analytical dose calculation method (CTanly), which can correct for subject inhomogeneity and size-dependent scatter doses, was applied to the 198Au seed. In this study, we evaluated the effectiveness of the CTanly method by comparing the gold standard Monte Carlo (MC) method and the conventional TG43 method on two virtual phantoms and patient CT images simulating oral cancer. METHODS: As virtual phantoms, a water phantom and a heterogeneous phantom with soft tissue inserted cubic fat, lung, and bone were used. A 2-mm-thick lead plate was also inserted into the heterogeneous phantom as a dose attenuator. Virtual 198Au seeds and a 2-mm-thick lead plate were placed on the patient CT images. Dose distributions obtained via the TG43 and CTanly methods were compared with those of the MC by gamma analysis with 2%/2-mm thresholds. The computation durations were also compared. RESULTS: In the water phantom, dose distributions comparable to those obtained via the MC method were obtained regardless of the algorithm. For the inhomogeneity phantom and patient case, the CTanly method showed an improvement in the gamma passing rate and dose distributions similar to those of the MC method were obtained. The computation time, which was days with the MC method, was reduced to minutes with the CTanly method. CONCLUSIONS: The CTanly method is effective for 198Au seed dose calculations and takes a shorter time to obtain the dose distributions than the MC method.

Malignant Hip Flexion Failure Syndrome: An Oncologic Disease Compared to Malignant Psoas Syndrome.

Malignant psoas syndrome (MPS) causes painful hip immobilization when a malignant tumor reaches the psoas muscle. However, there exists a different condition in which a malignant tumor invades the psoas muscle, leading to hip flexion failure without painful hip immobilization. This study aimed to define malignant hip flexion failure syndrome (MHFFS) as tumors located in the upper lumbar region or at the lesser trochanter of the femur, near the origin or termination of the psoas muscle, and to compare its prevalence, characteristics, and outcomes with those of classical MPS. We analyzed 291 patients who received palliative radiotherapy (RT) in the lumbar, pelvic, and lower leg regions from 2013 to 2023. The prevalence of MPS and MHFFS, pathological features, distinctive clinical presentations, treatment modalities, and treatment outcomes have been summarized. We also defined the 'Clinical sign reported by Ishikawa and Teramura (IT sign)' to describe the characteristic action of lifting the affected lower leg with both hands in MHFFS cases and assessed its clinical significance. Among the 291 patients, 6 (2.1%) had MHFFS and 11 (3.8%) had MPS. MHFFS resulted from metastatic tumors in the 11th and 12th thoracic vertebrae, as well as the 1st and 2nd lumbar vertebrae or the lesser trochanter of the femur, and it was characterized by hip and groin pain along with hip flexion dysfunction. All cases showed a positive IT sign. The response to RT varied, with symptomatic improvement observed in 50% of the patients. MPS is characterized by tumor invasion of the psoas muscle, causing severe lumbosacral nerve pain. Strong opioids were used for pain management in all patients, and epidural anesthesia was required in some patients. The median survival time of patients with MPS and MHFFS was 13.2 months. MPS required opioids more potently than MHFFS, but MHFFS responded relatively well to early RT.

Subclinical rejection and allograft survival in kidney transplantation: protocol for a systematic review and meta-analysis.

INTRODUCTION: Subclinical rejection (SCR) refers to the presence of acute rejection without accompanying kidney allograft dysfunction. The impact of SCR on long-term graft survival remains a subject of ongoing debate. METHODS AND ANALYSIS: We will perform a systematic search of databases including MEDLINE, Embase and Cochrane Central, from January 1995 to November 2023. We will include English-language studies involving adult kidney transplant patients who investigated SCR. We will exclude studies focused on 'for-cause' biopsies. Both title, abstract screening and full-text screening will be performed by two or more reviewers. The primary outcome of this study will be death-censored allograft loss. The secondary outcome will include development of subsequent rejection. For time-dependent outcomes, we will prioritise HRs and the 95% CIs. In cases where HRs are unavailable, we will calculate risk ratios based on the recorded events. The risk of bias will be assessed using the Cochrane Collaboration's revised tool for assessing the risk of bias in randomised trials and the Newcastle-Ottawa scale for cohort studies. We will employ a random effects model. We will evaluate heterogeneity using the I2 variable. We will assess publication bias by funnel plots, Begg and Mazumdar test, and Egger's test. ETHICS AND DISSEMINATION: Ethics approval does not apply as no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023463536.

The Completion of Postoperative Radiotherapy After Breast-Conserving Surgery in a Patient With Recurrent Erythema Multiforme: A Case Report.

Radiotherapy (RT) can induce dermatitis and exacerbate a patient's preexisting skin conditions. We present a case of RT in a 61-year-old Japanese woman with a history of erythema multiforme (EM). She was diagnosed with a nodule on her right breast during therapy for EM. EM was noticed on the anterior chest and upper and lower extremities. RT was initially postponed due to exacerbation of EM before postoperative RT for right breast cancer. However, considering that EM tends to recur every one to two months, RT was commenced during a period of less active dermatitis, and a total dose of 50 Gy of conventional irradiation was successfully administered. One year after RT, there was no EM recurrence, dermatitis development, obvious late effects, or radiation pneumonitis. Our experience suggests that RT can be administered relatively safely to patients with recurrent EM but should be administered with caution.

Leptomeningeal carcinomatosis from breast cancer initially mimicking cerebral infarction on MRI.

A female patient in her early 50s with breast cancer underwent breast-conserving surgery, followed by radiation therapy. She developed multiple lung and bone metastases and was started on chemotherapy with bevacizumab and paclitaxel 3 years later. After 6 months of chemotherapy, she developed a decline in conversation and memory. Magnetic resonance imaging (MRI) was conducted and showed multiple cortical and subcortical lesions and nodules with restricted diffusion but with no contrast enhancement on gadolinium (Gd) enhanced T1-weighted image, raising a suspicion of Trousseau's syndrome. A follow-up MRI revealed unchanged signal intensity of the lesions but with minimal enlargement. The cerebrospinal fluid cytology was negative for malignancy. Consequently, an open biopsy of the cortical lesion was conducted. Histopathology showed that the tumor cells were morphologically similar to the primary breast cancer extending from the brain surface along the Virchow-Robin spaces, which yielded a diagnosis of leptomeningeal carcinomatosis from breast cancer. Contrast enhancement on Gd-MRI may be impaired in case of tumor spread along the perivascular space or in patients treated with bevacizumab.

Prognostic Factors and Impact of Therapeutic Intervention in Patients With Brain Metastases at the Initial Presentation.

Background Studies investigating the normative characteristics and prognosis of patients diagnosed with brain metastases (BMs) at the onset of cancer are scarce. Therefore, we analyzed real-world treatment options. Methodology This retrospective study enrolled 112 patients newly diagnosed with BM between May 2006 and October 2021. The variables examined included patients' age, sex, recurrence split analysis, Glasgow prognostic score (GPS), number of lesions, tumor size, peripheral brain tumor edema, targeted therapy, supportive care, chemotherapy, and date of onset. Prognostic factors were assessed using recursive partitioning analysis (RPA), graded prognostic assessment (GPA) scores, and GPS scoring, with magnetic resonance imaging (MRI) and computed tomography (CT) studies. Primary treatment comprised whole-brain radiotherapy (WBRT), with regular follow-up. Results Data from 112 survivors were analyzed, revealing a median overall survival time (MST) of 7.7 months, with some patients surviving beyond 24 months post-WBRT. Univariate analysis revealed associations between MST and RPA class, GPS, and treatment modalities (including targeted therapy and chemotherapy). RPA class 2, GPS of 0, and targeted therapy were identified as predictors of better prognosis in the multivariate analysis. In the subgroup not receiving chemotherapy, no significant difference in prognosis was seen between groups with or without WBRT. Conclusions Alongside RPA, scores indicating chronic inflammatory changes, including GPS, were confirmed as crucial prognostic factors. Moreover, treatment with molecularly targeted drugs correlated with favorable prognoses. The treatment-naïve group exhibited poorer prognoses, and WBRT was not deemed a significant prognostic factor in the chemotherapy group.

A Case of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer in a Patient With Fabry Disease.

Fabry disease is a metabolic disorder caused by a deficiency in lysosomal enzymes and is inherited as an X-chromosomal disorder. Patients with Fabry disease have a low incidence of cancer, and reports of malignant tumors, especially in the thoracic region, are rare. In this case report, we describe our experience with radiation therapy following breast-conserving surgery in a patient with left breast cancer and Fabry disease, and we review the existing literature. The patient, a woman in her 40s, required postoperative irradiation for left breast cancer (pT1N0M0). There were several patients with Fabry disease in her family, and the diagnosis of Fabry disease was made five years ago. Cardiac function evaluation revealed no significant abnormalities, but a myocardial biopsy had suggested the presence of Fabry disease. Due to the relatively preserved distance between the heart and the chest wall, the patient received heart-shielded three-dimensional conformal radiation therapy at a dose of 53.2 Gy in 20 fractions, without the use of deep-inspiration breath-hold or intensity-modulated radiotherapy. After treatment was completed, only mild radiation dermatitis was observed. Six months have passed since treatment, and there have been no serious adverse events.

Thoracic Spinal Metastasis With Hip Flexion Failure and Psoas Muscle Atrophy Successfully Improved With Radiotherapy: A Case Report.

When a malignant tumor infiltrates the psoas muscle, it is termed malignant psoas syndrome (MPS). We are reporting this case because the malignancy led to atrophy of the psoas muscle, and the clinical course differed from the typical presentation of MPS. A 72-year-old Japanese female with advanced sigmoid colon cancer and multiple metastases had been undergoing systemic chemotherapy for four years. She complained of severe back pain on a numeric rating scale (NRS) of 4-5, left groin pain, and hip flexion weakness. Although she could stand up, she started experiencing difficulties while walking and became reliant on a wheelchair. At the time of referral to our department, her performance status was 2. On examination, she was capable of hip adduction and abduction, and flexion was impossible on the left side and possible on the right side. Imaging revealed metastases to the 11th and 12th thoracic vertebrae, extending to the upper portion of the first lumbar vertebra, leading to atrophy of the left psoas major muscle and impairment of hip flexion. She received palliative radiation therapy (RT) of 30 Gy in 10 fractions over a period of 2 weeks. Following RT, she had grade 1 skin inflammation but no severe complications. Two weeks after RT, her pain improved (NRS 0-1) and she regained hip flexion. When hip flexion failure occurs in patients with malignant tumors, it is important to recognize that it may be caused by a tumor located near the lower thoracic or upper lumbar spine, even if the psoas muscle itself is not directly infiltrated by the tumor.

Glasgow prognostic score for assessing the efficacy of whole-brain radiation therapy in cases of recursive partitioning analysis class 2 and class 3 multiple brain metastases: a retrospective study.

PURPOSE: Whole-brain radiotherapy (WBRT) may not be beneficial for patients with brain metastases (BMs). The Glasgow Prognostic Score (GPS) is a suggested prognostic factor for malignancies. However, GPS has never been assessed in patients with BMs who have undergone WBRT. The purpose of this study was to determine whether GPS can be used to identify subgroups of patients with BMs who have a poor prognosis, such as recursive partitioning analysis (RPA) Class 2 and Class 3, and who will not receive clinical prognostic benefits from WBRT. MATERIALS AND METHODS: A total of 180 Japanese patients with BMs were treated with WBRT between May 2008 and October 2015. We examined GPS, age, Karnofsky Performance Status (KPS), RPA, graded prognostic assessment (GPA), number of lesions, tumor size, history of brain surgery, presence of clinical symptoms, and radiation doses. RESULTS: The overall median survival time (MST) was 6.1 months. seventeen patients (9.4%) were alive more than 2 years after WBRT. In univariate analysis, KPS ≤ 70 (p = 0.0066), GPA class 0-2 (p = 0.0008), > 3 BMs (p = 0.012), > 4 BMs (p = 0.02), patients who received ≥ 3 Gy per fraction (p = 0.0068), GPS ≥ 1 (p = 0.0003), and GPS ≥ 2 (p = 0.0009) were found to significantly decrease the MST. Patients who had brain surgery before WBRT (p = 0.036) had a longer survival. On multivariate analysis, GPS ≥ 1 (p = 0.008) was found to significantly decrease MST. CONCLUSION: Our results suggest that GPS ≥ 1 indicates a poor prognosis in patients undergoing WBRT for intermediate and poor prognosis BMs.

Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus.

AIM: To compare the therapeutic effects of glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 receptor agonists (GLP-1RAs) or GLP-1RAs in Japanese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library up to July 2023. Randomized controlled trials (RCTs) that compared GLP-1RAs or GIP/GLP-1RAs in Japanese patients with T2D were selected. A network meta-analysis was conducted to indirectly compare the treatments, focusing on efficacy in reducing glycated haemoglobin (HbA1c) levels and body weight (BW). RESULTS: A total of 18 RCTs were included in this analysis. Tirzepatide 15 mg showed the most significant reduction in HbA1c levels and BW compared with subcutaneous semaglutide 1.0 mg and oral semaglutide 14 mg (HbA1c: mean difference [95% confidence interval] -0.52 [-0.96; -0.08] and - 1.23 [-1.64; -0.81]; BW: -5.07 [-8.28; -1.86] and -6.84 [-8.97; -4.71], respectively). Subcutaneous semaglutide showed a superior reduction in HbA1c compared with oral semaglutide. Both subcutaneous and oral semaglutide were more effective than conventional GLP-1RAs, such as dulaglutide, liraglutide and lixisenatide. CONCLUSIONS: Among Japanese patients with T2D, tirzepatide showed the greatest effectiveness in reducing HbA1c levels and inducing weight loss. The study provides evidence to guide GLP-1RA treatment strategies in Japanese patients with T2D.

An Unusual Case of Hip Flexion Failure Caused by Bone Metastasis From Hepatocellular Carcinoma Infiltrating the Psoas Muscle.

When malignant tumors infiltrate the psoas muscle, they can result in what is referred to as malignant psoas syndrome (MPS). We are reporting this case as the malignant tumor had invaded the psoas muscle, and the clinical course of the patient differed from that of typical MPS. A 75-year-old male patient with liver cancer presented with pain around the right hip joint and difficulty in flexing the right hip joint, resulting in gait disturbance. There was no painful immobilization of the right hip, and the patient was able to extend the lower extremity. A CT scan revealed multiple liver tumors, multiple bone metastases, and swelling of the psoas muscle contiguous with the tumor at the lesser trochanter of the right femur. There were no apparent intracranial or spinal cord lesions, and no obvious abnormalities were detected around the psoas muscle in the abdominal cavity. Palliative radiation therapy was administered at a dose of 20 Gy in five fractions for pain relief. One month later, a follow-up CT scan presented no change in the shape of the tumor; however, the swelling of the right psoas muscle had improved. Unfortunately, the patient passed away 1 month after irradiation because of progressive liver and renal failure. When a patient with a malignant tumor presents with periprosthetic hip pain and hip flexion failure, one should consider the possibility of a malignant tumor in the lesser trochanter.

Combination of sacubitril/valsartan and blockade of the PI3K pathway enhanced kidney protection in a mouse model of cardiorenal syndrome.

Aims: Angiotensin receptor-neprilysin inhibitor (ARNI) is an established treatment for heart failure. However, whether ARNI has renoprotective effects beyond renin-angiotensin system inhibitors alone in cardiorenal syndrome (CRS) has not been fully elucidated. Here, we examined the effects of ARNI on the heart and kidneys of CRS model mice with overt albuminuria and identified the mechanisms underlying ARNI-induced kidney protection. Methods and results: C57BL6 mice were subjected to chronic angiotensin II infusion, nephrectomy, and salt loading (ANS); they developed CRS phenotypes and were divided into the vehicle treatment (ANS-vehicle), sacubitril/valsartan treatment (ANS-ARNI), and two different doses of valsartan treatment (ANS-VAL M, ANS-VAL H) groups. Four weeks after treatment, the hearts and kidneys of each group were evaluated. The ANS-vehicle group showed cardiac fibrosis, cardiac dysfunction, overt albuminuria, and kidney fibrosis. The ANS-ARNI group showed a reduction in cardiac fibrosis and cardiac dysfunction compared with the valsartan treatment groups. However, regarding the renoprotective effects characterized by albuminuria and fibrosis, ARNI was less effective than valsartan. Kidney transcriptomic analysis showed that the ANS-ARNI group exhibited a significant enhancement in the phosphoinositide 3-kinase (PI3K)-AKT signalling pathway compared with the ANS-VAL M group. Adding PI3K inhibitor treatment to ARNI ameliorated kidney injury to levels comparable with those of ANS-VAL M while preserving the superior cardioprotective effect of ARNI. Conclusion: PI3K pathway activation has been identified as a key mechanism affecting remnant kidney injury under ARNI treatment in CRS pathology, and blockading the PI3K pathway with simultaneous ARNI treatment is a potential therapeutic strategy for treating CRS with overt albuminuria.

Optimal Bladder Condition in Volumetric Modulated Arc Therapy for Prostate Cancer: The Role of Superior-Inferior Lengths of the Bladder and Dose Constraints.

Background Optimal bladder conditions based on dose constraints in prostate cancer radiation therapy (RT) are important. In this study, the superior-inferior (SI) lengths of the bladder were assessed to define the ideal bladder state for RT. Materials and methods In this study, 50 prostate cancer cases treated with three-dimensional conformal radiation therapy between January and December 2021 were retrospectively analyzed. Using their CT data, a volumetric modulated arc therapy (VMAT) plan was simulated. Bladder dose constraints and dimensions, including SI, right-left (RL), and anterior-posterior (AP) lengths, were assessed. In total, 28 cases met the dose constraints and 22 cases did not meet the dose constraints.  Results Median bladder volumes (BVs) for compliant and non-compliant cases were 163.6 ml and 88.5 ml, respectively (p<0.0001). For compliant plans, median bladder dimensions were RL: 78 mm, AP: 89 mm, and SI: 51 mm. Non-compliant plans showed RL: 72 mm, AP: 84 mm, and SI: 42 mm, with significant differences (SI: p=0.0004, RL: p=0.0065, AP: p=0.037). Established thresholds were SI: 46 mm, RL: 92 mm, AP: 75 mm, and BV: 142.8 ml. SI showed the strongest correlation with BV (coefficient: 0.78). Conclusions This study analyzed the SI lengths of the bladder concerning dose constraints in VMAT for prostate cancer. It was concluded that smooth treatment planning could be achieved with proper consideration of the bladder's SI distance. Further case collection and prospective studies are warranted.

Primary mucinous carcinoma of the skin.

Key Clinical Message: Mucinous carcinoma of the skin is clinically characterized by good mobility, slow growth, a macroscopically smooth surface, no easy contact bleeding, and no internal flow on color Doppler; it is thus difficult to distinguish from benign tumors. Abstract: A 58-year-old man presented to our clinic complaining of a right cheek induration, growing over the previous 6 months. The tumor surface was smooth, pink, did not bleed easily, and approximately 10 mm in size with good mobility. Ultrasonography revealed a well-circumscribed hypoechoic homogenous tumor with posterior acoustic enhancement; color Doppler displayed no internal flow. Preoperative diagnosis was intradermal type nevus or dermatofibroma. An excisional biopsy was performed under local anesthesia. The biopsy specimen unexpectedly showed tumor cells with an epithelial alveolar configuration floating in a mucin lake. The tumor cells contained enlarged nuclei and formed atypical columnar epithelium, arranged in fused, honeycomb-like glandular ducts, indicating mucinous carcinoma.

Nacα protects the larval fat body from cell death by maintaining cellular proteostasis in Drosophila.

Protein homeostasis (proteostasis) is crucial for the maintenance of cellular homeostasis. Impairment of proteostasis activates proteotoxic and unfolded protein response pathways to resolve cellular stress or induce apoptosis in damaged cells. However, the responses of individual tissues to proteotoxic stress and evoking cell death program have not been extensively explored in vivo. Here, we show that a reduction in Nascent polypeptide-associated complex protein alpha subunit (Nacα) specifically and progressively induces cell death in Drosophila fat body cells. Nacα mutants disrupt both ER integrity and the proteasomal degradation system, resulting in caspase activation through JNK and p53. Although forced activation of the JNK and p53 pathways was insufficient to induce cell death in the fat body, the reduction of Nacα sensitized fat body cells to intrinsic and environmental stresses. Reducing overall protein synthesis by mTor inhibition or Minute mutants alleviated the cell death phenotype in Nacα mutant fat body cells. Our work revealed that Nacα is crucial for protecting the fat body from cell death by maintaining cellular proteostasis, thus demonstrating the coexistence of a unique vulnerability and cell death resistance in the fat body.

Acute myocarditis after the third dose of COVID-19 mRNA-1273 vaccine.

Myocarditis caused by the mRNA-1273 coronavirus disease 2019 vaccine must be considered for patients complaining of acute constant general fatigue postvaccination.

Effects of a High-Protein Diet on Kidney Injury under Conditions of Non-CKD or CKD in Mice.

Considering the prevalence of obesity and global aging, the consumption of a high-protein diet (HPD) may be advantageous. However, an HPD aggravates kidney dysfunction in patients with chronic kidney disease (CKD). Moreover, the effects of an HPD on kidney function in healthy individuals are controversial. In this study, we employed a remnant kidney mouse model as a CKD model and aimed to evaluate the effects of an HPD on kidney injury under conditions of non-CKD and CKD. Mice were divided into four groups: a sham surgery (sham) + normal diet (ND) group, a sham + HPD group, a 5/6 nephrectomy (Nx) + ND group and a 5/6 Nx + HPD group. Blood pressure, kidney function and kidney tissue injury were compared after 12 weeks of diet loading among the four groups. The 5/6 Nx groups displayed blood pressure elevation, kidney function decline, glomerular injury and tubular injury compared with the sham groups. Furthermore, an HPD exacerbated glomerular injury only in the 5/6 Nx group; however, an HPD did not cause kidney injury in the sham group. Clinical application of these results suggests that patients with CKD should follow a protein-restricted diet to prevent the exacerbation of kidney injury, while healthy individuals can maintain an HPD without worrying about the adverse effects.