Single-Fraction Palliative High-Dose-Rate Brachytherapy for Symptom Management in a 97-Year-Old Patient With Dementia.

Background: Delivering cancer treatment to elderly patients with dementia is often challenging. We describe performing palliative surface mold brachytherapy (SMBT) in an elderly patient with advanced dementia for pain control using music therapy to assist with agitation. Case Description: The patient was a 97-year-old Japanese woman with advanced dementia. Exudate was observed from her tumor, and she complained of Grade 2 severity pain using Support team assessment schedule (STAS), especially when undergoing would dressings. Given her advanced dementia, she was not considered a candidate for radical surgery or external beam radiotherapy. We instead treated her with high-dose-rate (HDR) SMBT. Due to her advanced dementia associated with agitation, she could not maintain her position. She was able to remain calm while listening to traditional Japanese enka music, which enables our team to complete her radiation without using anesthetics or sedating analgesics. Her localized pain severity decreased ≤21 days and the exudate fluid disappeared ≤63 days after HDR-SMBT. Her tumor was locally controlled until her death from intercurrent disease 1 year after HDR-SMBT. Discussion: Single fraction palliative HDR-SMBT was useful for successful treatment of skin cancer in an elderly patient. Traditional Japanese music helped reduce her agitation to complete HDR-SMBT. For elderly patients with agitation associated with dementia, we should consider using music and music therapy to facilitate radiation therapy.

Combined external radiotherapy and single-fraction palliative high-dose-rate interstitial brachytherapy for a patient with a base of tongue cancer who had a previous radiation history.

Only a few studies have explored whether high-dose-rate interstitial brachytherapy (HDR-ISBT) can be indicated as a palliative/symptomatic treatment. We present the good results of palliative treatment using HDR-ISBT combined with external beam radiotherapy (ERT) in a patient of base of tongue cancer (cT4aN1M0). The patient was an 81-year-old male who complained of local pain. He had a previous irradiation history for head and neck cancer receiving ERT with systemic chemotherapy and radical surgery 15 years ago. Since it might be difficult for him to receive radical radiation doses using ERT alone, palliative ERT of relatively lower doses of 37.5 Gy in 15 fractions was selected. One month after ERT, HDR-ISBT was implemented as a booster. Considering the burden on physical condition, single-fraction HDR-ISBT was selected. We employed a new technique in which we did not penetrate the ventral surface of the tongue to reduce the risk of infection and bleeding. The planning-aim dose was 9.5 Gy. The dose that covered 90% of the clinical target volume was 9.6 Gy. The treatment ended without any problems. Acute complications were not observed. The tumor size decreased, and local pain disappeared at post-treatment day 84. No late complications were observed. Two years and 8 months after the treatment, the patient is alive without any obvious recurrence. Additional single-fraction HDR-ISBT boost may be a useful modality as a palliative/symptomatic intent. The implantation technique and dose-fraction schedule may be important for the safe treatment of older patients or those with poor performance status.

Artificial intelligence-aided lytic spinal bone metastasis classification on CT scans.

PURPOSE: Spinal bone metastases directly affect quality of life, and patients with lytic-dominant lesions are at high risk for neurological symptoms and fractures. To detect and classify lytic spinal bone metastasis using routine computed tomography (CT) scans, we developed a deep learning (DL)-based computer-aided detection (CAD) system. METHODS: We retrospectively analyzed 2125 diagnostic and radiotherapeutic CT images of 79 patients. Images annotated as tumor (positive) or not (negative) were randomized into training (1782 images) and test (343 images) datasets. YOLOv5m architecture was used to detect vertebra on whole CT scans. InceptionV3 architecture with the transfer-learning technique was used to classify the presence/absence of lytic lesions on CT images showing the presence of vertebra. The DL models were evaluated via fivefold cross-validation. For vertebra detection, bounding box accuracy was estimated using intersection over union (IoU). We evaluated the area under the curve (AUC) of a receiver operating characteristic curve to classify lesions. Moreover, we determined the accuracy, precision, recall, and F1 score. We used the gradient-weighted class activation mapping (Grad-CAM) technique for visual interpretation. RESULTS: The computation time was 0.44 s per image. The average IoU value of the predicted vertebra was 0.923 ± 0.052 (0.684-1.000) for test datasets. In the binary classification task, the accuracy, precision, recall, F1-score, and AUC value for test datasets were 0.872, 0.948, 0.741, 0.832, and 0.941, respectively. Heat maps constructed using the Grad-CAM technique were consistent with the location of lytic lesions. CONCLUSION: Our artificial intelligence-aided CAD system using two DL models could rapidly identify vertebra bone from whole CT images and detect lytic spinal bone metastasis, although further evaluation of diagnostic accuracy is required with a larger sample size.

Venous Rupture Following Transcatheter Arterial Embolization for Inferior Mesenteric Type II Arteriovenous Malformation.

We treated a 64-year-old man who had an inferior mesenteric arteriovenous malformation with multiple shunts. As multiple varicosities in the draining vein became enlarged, two dilated shunts on the superior rectal and sigmoid colon arteries were coil embolized. Two days after embolization, a varicosity near the shunt (65 mm diameter) ruptured, causing intra-abdominal hemorrhage and surgical hemostasis. There were thrombi in the ruptured varicosity and its draining vein. The likely cause was a pressure increase in the incompletely thrombosed varicosity due to shunt blood flow from the remaining shunts after embolization.

Eggshell membrane modulates gut microbiota to prevent murine pre-cachexia through suppression of T helper cell differentiation.

BACKGROUND: Cachexia is a life-threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 (Il10) gene transfer is known to improve cachexia by downregulating Il6. Here, we used an IL10-knockout mouse model to simulate cachexia and investigate the effects of eggshell membrane (ESM), a resistant protein, on general pre-cachexia symptoms, which is particularly important for the development of cachexia therapeutics. METHODS: Five-week-old male C57BL6/J mice were fed an AIN-93G powdered diet (WT), and 5-week-old male B6.129P2-Il10 < tm1Cgn>/J (IL10-/- ) mice were fed either the AIN-93G diet (KO) or an 8% ESM-containing diet (KOE) for 28 weeks. The tissue weight and levels of anaemia-, blood glucose-, lipid metabolism-, and muscular and colonic inflammation-related biochemical markers were measured. Transcriptomic analysis on liver and colon mucus and proteomic analysis on skeletal muscle were performed. Ingenuity Pathway Analysis was used to identify molecular pathways and networks. Caecal short-chain fatty acids (SCFAs) were identified using HPLC, and caecal bacteria DNA were subjected to metagenomic analysis. Flow cytometry analysis was performed to measure the CD4+ IL17+ T cells in mesenteric lymph nodes. RESULTS: The body weight, weight of gastrocnemius muscle and fat tissues, colon weight/length ratio, plasma HDL and NEFA, muscular PECAM-1 levels (P < 0.01), plasma glucose and colonic mucosal myeloperoxidase activity (P < 0.05) and T helper (Th) 17 cell abundance (P = 0.071) were improved in KOE mice over KO mice. Proteomic analysis indicated the protective role of ESM in muscle weakness and maintenance of muscle formation (>1.5-fold). Transcriptomic analysis revealed that ESM supplementation suppressed the LPS/IL1-mediated inhibition of RXR function pathway in the liver and downregulated the colonic mucosal expression of chemokines and Th cell differentiation-related markers (P < 0.01) by suppressing the upstream BATF pathway. Analysis of the intestinal microenvironment revealed that ESM supplementation ameliorated the microbial alpha diversity and the abundance of microbiota associated with the degree of inflammation (P < 0.05) and increased the level of total organic acids, particularly of SCFAs such as butyrate (2.3-fold), which could inhibit Th1 and Th17 production. CONCLUSIONS: ESM supplementation ameliorated the chief symptoms of cachexia, including anorexia, lean fat tissue mass, skeletal muscle wasting and reduced physical function. ESM also improved colon and skeletal muscle inflammation, lipid metabolism and microbial dysbiosis. These results along with the suppressed differentiation of Th cells could be associated with the beneficial intestinal microenvironment and, subsequently, attenuation of pre-cachexia. Our findings provide insights into the potential of ESM in complementary interventions for pre-cachexia prevention.

Gene Recruitments and Dismissals in the Argonaut Genome Provide Insights into Pelagic Lifestyle Adaptation and Shell-like Eggcase Reacquisition.

The paper nautilus or greater argonaut, Argonauta argo, is a species of octopods which is characterized by its pelagic lifestyle and by the presence of a protective spiral-shaped shell-like eggcase in females. To reveal the genomic background of how the species adapted to the pelagic lifestyle and acquired its shell-like eggcase, we sequenced the draft genome of the species. The genome size was 1.1 Gb, which is the smallest among the cephalopods known to date, with the top 215 scaffolds (average length 5,064,479 bp) covering 81% (1.09 Gb) of the total assembly. A total of 26,433 protein-coding genes were predicted from 16,802 assembled scaffolds. From these, we identified nearly intact HOX, Parahox, Wnt clusters, and some gene clusters that could probably be related to the pelagic lifestyle, such as reflectin, tyrosinase, and opsin. The gene models also revealed several homologous genes related to calcified shell formation in Conchiferan mollusks, such as Pif-like, SOD, and TRX. Interestingly, comparative genomics analysis revealed that the homologous genes for such genes were also found in the genome of the shell-less octopus, as well as Nautilus, which has a true outer shell. Therefore, the draft genome sequence of Arg. argo presented here has helped us to gain further insights into the genetic background of the dynamic recruitment and dismissal of genes to form an important, converging extended phenotypic structure such as the shell and the shell-like eggcase. Additionally, it allows us to explore the evolution of from benthic to pelagic lifestyles in cephalopods and octopods.

The full mitochondrial genome sequence of the greater argonaut Argonauta argo (Cephalopoda, Argonautoidea) and its phylogenetic position in Octopodiformes.

The greater argonaut Argonauta argo is a species of the paper nautilus (Argonautidae), which is a family in Octopoda. In this paper, we report its full mitogenome sequence, which was obtained from a specimen collected in the Japan Seas near Oki Island, Shimane Prefecture, in Japan. The sequence was determined using the NGS Illumina HiSeq platform. With its 37 genes, the mitogenome shows a typical metazoan and Octopoda genomic structure, and similar to the mitogenome of the previously reported congener, A. hians. To confirm A. argo phylogenetic position in Octopoda, we conducted maximum likelihood phylogenetic analysis, using a data set including publicly available 17 Octopodiformes, five Decapodiformes, three Nautiloids and two outgroup Conchiferans. The result confirmed the affinity of Argonautidae to Tremoctopus, and the sister group position of this clade against the rest of incirrate Octopods. The mitogenome and phylogeny of A. argo reported here will be useful for future studies involving this enigmatic species, including on the reacquisition of external calcified shell structures in mollusks.

Complete mitochondrial genome of the Pacific limpet Cellana nigrolineata (Gastropoda: Patellogastropoda) determined by shotgun sequencing using the Illumina NGS platform.

The Pacific limpet Cellana nigrolineata is one of the most commonly found limpets in the intertidal shores of Japan. Here, we report the full mitogenome sequence of an individual specimen of the species, which was collected from the intertidal rocky beach in the Nada beach of Gobo City, Wakayama, Japan (33.8316 N, 135.1751 E), in 2018. The sequence was determined by the shotgun sequencing method using the NGS Illumina MiSeq platform. The genomic structure of C. nigrolineata is the same as the previously reported congener, C. radiata, which shows a representative Nacellidae and metazoan mitogenomic structures. The mitogenome has all of its 37 genes included in its 16,153 bp, with one control region located between the tRNA-Cys and tRNA-Gly genes. In order to clarify the phylogenetic position of C. nigrolineata in Gastropoda, a data set including the mitogenomes of 10 patellogastropods, 10 non-patellogastropod gastropods, and four outgroups were used in maximum likelihood inferences. Although with some exceptions, the resulting phylogeny supported the monophylies of traditionally accepted gastropod subclasses, and thus confirms the position of C. nigrolineata in Patellogastropoda.

Hydrophilic Shell Matrix Proteins of Nautilus pompilius and the Identification of a Core Set of Conchiferan Domains.

Despite being a member of the shelled mollusks (Conchiferans), most members of extant cephalopods have lost their external biomineralized shells, except for the basally diverging Nautilids. Here, we report the result of our study to identify major Shell Matrix Proteins and their domains in the Nautilid Nautilus pompilius, in order to gain a general insight into the evolution of Conchiferan Shell Matrix Proteins. In order to do so, we performed a multiomics study on the shell of N. pompilius, by conducting transcriptomics of its mantle tissue and proteomics of its shell matrix. Analyses of obtained data identified 61 distinct shell-specific sequences. Of the successfully annotated 27 sequences, protein domains were predicted in 19. Comparative analysis of Nautilus sequences with four Conchiferans for which Shell Matrix Protein data were available (the pacific oyster, the pearl oyster, the limpet and the Euhadra snail) revealed that three proteins and six protein domains were conserved in all Conchiferans. Interestingly, when the terrestrial Euhadra snail was excluded, another five proteins and six protein domains were found to be shared among the four marine Conchiferans. Phylogenetic analyses indicated that most of these proteins and domains were probably present in the ancestral Conchiferan, but employed in shell formation later and independently in most clades. Even though further studies utilizing deeper sequencing techniques to obtain genome and full-length sequences, and functional analyses, must be carried out in the future, our results here provide important pieces of information for the elucidation of the evolution of Conchiferan shells at the molecular level.