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.

Popeye's sign: A diagnostic clue.

Key Clinical Message: Sudden onset bulging of the upper arm may indicate biceps tendon rupture. Abstract: We describe a 72-year-old man with Popeye's sign. The patient experienced a sudden shock in his right humerus while mowing grass with his right arm using wide sweeps of a scythe. His right upper arm had an obvious bulging appearance after 3 days, indicating a rupture of the biceps tendon.

Falciform ligament hernia: combination of key CT findings.

A male patient in his early 90s with no history of abdominal surgery was referred to us for abdominal pain and vomiting. An abdominal computed tomography (CT) demonstrated dilated small bowel with a double beak sign and poorly enhanced wall, which indicated a closed-loop obstruction that leads to strangulation. A closed-loop bowel was located in front of the anterior and medial segments of the liver and to the right of the round ligament of the liver on axial images. Sagittal images revealed that the round ligament has deviated downward and 2 adjacent narrowed intestines were located at its cranial side. These CT findings suggested the hernia orifice was in the falciform ligament. Emergency surgery for highly suspected bowel ischemia revealed the falciform ligament hernia. A combination of the CT findings played a key role, including the double beak sign, the location of the closed-loop small bowel, and the downward deviation of the round ligament, although preoperative CT diagnosis of falciform ligament hernia is a diagnostic challenge.

Development of a collapsed cone convolution/superposition dose calculation algorithm with a mass density-specific water kernel for magnetic resonance-guided radiotherapy.

This study aimed to develop and validate a collapsed cone convolution for magnetic resonance-guided radiotherapy (CCCMR). The 3D energy deposition kernels (EDKs) were generated in water in a 1.5-T transverse magnetic field. The CCCMR corrects the inhomogeneity in simulation geometry by referring to the EDKs according to the mass density between the interaction and energy deposition points in addition to density scaling. Dose distributions in a water phantom and in slab phantoms with inserted inhomogeneities were calculated using the Monte Carlo (MC) and CCCMR. The percentage depth dose (PDD) and off-axis ratio (OAR) were compared, and the gamma passing rate (3%/2 mm) was evaluated. The CCCMR simulated asymmetric dose distributions in the simulation phantoms, especially the water phantom, and all PDD and OAR profiles were in good agreement with the findings of the MC. The gamma passing rates were >99% for each field size and for the entire region. In the inhomogeneity phantoms, although the CCCMR underestimated dose in the low mass density regions, it could reconstruct dose changes at mass density boundaries. The gamma passing rate for the entire region was >95% for the field size of 2 × 2 cm2, but it was 68.9-86.7% for the field sizes of ≥5 × 5 cm2. Conclusively, in water, the CCCMR can obtain dose distributions comparable to those with the MC. Although the dose differences between them were mainly in inhomogeneity regions, the possibility of the effective use of the CCCMR in small field sizes was demonstrated.

Effects of sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, and their combination on albuminuria in diabetic patients.

AIMS: Diabetes mellitus (DM) is the leading cause of chronic kidney disease. Albuminuria is associated with an increased risk of cardiovascular mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) and mineralocorticoid receptor antagonists (MRAs) protect against albuminuria; however, their combined effects on albuminuria are unclear. We performed a network meta-analysis to investigate the effects of SGLT2-Is, MRAs and their combination on albuminuria in type 2 DM. METHODS: We systematically searched PubMed, Medline, EMBASE and the Cochrane Library from inception up to 20 November 2022. We selected randomized control and crossover trials that compared MRAs, SGLT2-Is, MRAs + SGLT2-Is, or a placebo in patients with type 2 DM with a urinary albumin-creatinine ratio (UACR) ≥30 mg/g creatinine. The primary outcome was the change in the UACR. RESULTS: This meta-analysis analysed 17 studies with 34 412 patients. The use of combination treatment with SGLT2-Is and MRAs was associated with lower albuminuria compared with the use of SGLT2-Is, MRAs, or the placebo alone [mean difference (95% CI): -34.19 (-27.30; -41.08), -32.25 (-24.53; -39.97) and -65.22 (-57.97; -72.47), respectively]. Treatment with SGLT2-Is or MRAs alone caused a significant reduction in UACR compared with the placebo [mean difference (95% CI): -31.03 (-28.35; -33.72) and -32.97 (-29.68; -36.27), respectively]. The effects of MRAs on the UACR are comparable with those of SGLT2-Is. Sensitivity analyses showed similar results. CONCLUSION: Combination therapy with SGLT2-Is and MRAs was associated with lower albuminuria in patients with type 2 DM compared with monotherapy with SGLT2-Is or MRAs alone.