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The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas are reported to underlie lymphomagenesis. However, our understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here we constructed a single-cell transcriptome atlas of more than 100,000 NHCs collected from 27 human samples, including LNs and various nodal lymphomas, and it revealed 30 distinct subclusters, including some that were previously unrecognized. Notably, this atlas was useful for comparative analyses with lymphoma NHCs, which revealed an unanticipated landscape of subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs. This facilitates our understanding of stromal remodelling in lymphoma and highlights potential clinical biomarkers. Our study largely updates NHC taxonomy in human LNs and analysis of disease status, and provides a rich resource and deeper insights into LN and lymphoma biology to advance lymphoma management and therapy. Abe et al. profile, characterize and compare non-haematopoietic cells in normal human lymph nodes versus nodal lymphomas from patients, providing insights into stromal modelling in health and disease.

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.

Giant cell tumors of soft tissue (GCT-ST) arising in the breast are extremely rare. Herein, we report a case of a 45-year-old woman with a 5-cm mass in her left breast. Ultrasonography revealed a mainly well-circumscribed mass that contained a cystic lesion. Magnetic resonance imaging showed a fibrous capsule-covered mass that contained a high-intensity area, suggesting hemorrhaging. Ultrasound-guided core needle biopsy (CNB) revealed mononuclear histiocytic cells with a round shape or spindled appearance that was mixed with multinucleated giant cells. Immunohistochemical analysis revealed CD68-positive staining in the mononuclear and giant cells but negative staining for pancytokeratin. Preoperatively, the tumor was highly suspected of being GCT-ST. Histopathological results after a left mastectomy showed similar findings to CNB. The final diagnosis was GCT-ST in the breast. To the best of our knowledge, this is the first case report of a GCT-ST arising in the breast diagnosed by ultrasound-guided CNB.

Intramammary metastasis of renal cell carcinoma (RCC) is extremely rare, accounting for only 1.5% of all intramammary metastases. Distinguishing intramammary metastases from benign tumors and breast cancer is clinically problematic. Some patients undergo excessive surgery after a misdiagnosis of breast cancer instead of a mammary tumor. We performed a core needle biopsy (CNB) of a breast mass that developed in a 71-year-old woman after surgeries for bilateral RCC and breast cancer, leading to a diagnosis of intramammary metastasis of RCC. In this case, the CNB and immunohistochemical examination were critical for reaching a definitive diagnosis. We conclude that, when examining patients with mammary tumors, establishing their history of malignant tumors may help diagnose intramammary metastasis and select the best treatment strategy.

Nab-paclitaxel (nab-PTX) is a nanoparticle albumin-bound paclitaxel and, as such, is free of solvents like ethanol and polyoxyethylene castor oil. The absence of solvents from this formulation has several practical advantages: it has a shorter infusion time, it negates the need for premedications for hypersensitivity reactions, and it can be administered to patients with alcoholic hypersensitivity. It is thought that nab-paclitaxel will be in widespread use in the near future because of its convenience and efficacy. Here, we report the case of a breast cancer patient who developed hemorrhagic cystitis potentially due to treatment with nab-paclitaxel. The patient was 69-year old lady with stage IIB left breast cancer. She was due to undergo neoadjuvant chemotherapy and started weekly treatment with nab-paclitaxel. On the second day of the first cycle of treatment, she experienced symptoms of cystitis, but was not hemorrhagic and the symptoms were managed with antibiotics. After the third cycle, the symptoms of cystitis became severe, and she was diagnosed with hemorrhagic cystitis and discontinued chemotherapy with nab-paclitaxel. This is the first case report of hemorrhagic cystitis associated with nab-paclitaxel.

T follicular helper (T FH ) cell lymphomas (TFHLs) are characterized by T FH -like properties and accompanied by substantial immune-cell infiltration into tumor tissues. Nevertheless, the comprehensive understanding of tumor-cell heterogeneity and immune profiles of TFHL remains elusive. To address this, we conducted single-cell transcriptomic analysis on 9 lymph node (LN) and 16 peripheral blood (PB) samples from TFHL patients. Tumor cells were divided into 5 distinct subclusters, with significant heterogeneity observed in the expression levels of T FH markers. Copy number variation (CNV) and trajectory analyses indicated that the accumulation of CNVs, together with gene mutations, may drive the clonal evolution of tumor cells towards T FH -like and cell proliferation phenotypes. Additionally, we identified a novel tumor-cell-specific marker, PLS3. Notably, we found a significant increase in exhausted CD8 + T cells with oligoclonal expansion in TFHL LNs and PB, along with distinctive immune evasion characteristics exhibited by infiltrating regulatory T, myeloid, B, and natural killer cells. Finally, in-silico and spatial cell-cell interaction analyses revealed complex networking between tumor and immune cells, driving the formation of an immunosuppressive microenvironment. These findings highlight the remarkable tumor-cell heterogeneity and immunoevasion in TFHL beyond previous expectations, suggesting potential roles in treatment resistance.

Metformin is widely prescribed for patients with type 2 diabetes mellitus (DM). Its use for patients with type 1 has been considered a contraindication because of possible adverse effects such as lactic acidosis. However, metformin has been recently used with insulin therapy to reduce insulin‐dose requirements in Type 1 DM.An 81‐year‐old Japanese woman with type 1 DM was treated with insulin and metformin. She was admitted to our hospital due to altered mental state and hypotensive shock via a referral from her primary care physician. The patient had severe lactic acidosis and acute kidney injury with hyperkalemia with the suspected cause being the use of metformin. She was treated successfully with hemodialysis (HD).Although the independent predictive factor of mortality due to metformin‐associated lactic acidosis is a prothrombin time (PT) activity of less than 50% in 24 hours, we recommend that HD should be performed for a patient with severe lactic acidosis even if the initial PT activity is normal.

Background The objective of this study was to evaluate the efficacy of hydroxyapatite nanoparticles (HANPs) in comparison to zinc oxide nanoparticles (ZnO NPs) in occluding dentinal tubules (DTs). Managing dentin hypersensitivity (DH) and assessing the resilience of anti-hypersensitivity treatments present significant clinical challenges. Hence, it is imperative to explore the impact of NPs on DH treatment. Methods In this study, twenty- seven orthodontically extracted teeth with no caries or restorations were employed to produce 27 dentin discs. These discs were created by slicing the teeth coronally and subsequently subjecting them to a 20-second etching using 37% orthophosphoric acid to simulate DH conditions and eliminate the smear layer. The dentin discs were then randomly assigned to three groups: Group I (etched control), Group II (HANPs), where dentin discs were treated with carboxymethyl cellulose ( CMC) dental hydrogel loaded with HANPs, and Group III (ZnO NPs), where dentin discs received treatment with CMC dental hydrogel loaded with ZnO NPs. Finally, the dentin discs underwent various analyses, including profilometric assessment to measure surface roughness (SRa) of dentin discs, qualitative assessment using scanning electron microscopy (SEM) to evaluate DT occlusion and quantitative assessment SEM images using Image J software platform. Results Analysis of the dentin discs revealed that Group I had the highest SRa measuring 1.52 ± 0.08 μm, followed by Group II, measuring 1.21 ± 0.06 μm, while Group III exhibited the lowest SRa measuring 1.20 ± 0.05 μm. SEM examination indicated that Group III displayed the most extensive DT occlusion, followed by Group II, while Group I exhibited the lowest level of occlusion. The results from the SEM analysis were quantitatively validated through additional analysis using Image J software. Statistical analysis (ANOVA and post hoc Tukey’s test, p  ≤ 0.05) revealed significant differences between groups, thereby rejecting the null hypothesis. Conclusions The application of ZnO NPs demonstrates a positive impact on both the qualitative and quantitative aspects of DH. Highlights • The inclusion of ZnO NPs is anticipated to enhance clinical outcome in reducing dentin hypersensitivity by occluding dentinal tubules • All authors agree with the submission • The work has not been published or submitted for publication elsewhere, either completely or in part, or in another form or language • No conflict of interest with the authors in this work

Background Dentin hypersensitivity (DH) is a prevalent dental issue characterized by sharp pain of short duration. Although the exact cause of DH remains debated, the hydrodynamic theory explains its mechanism. Furthermore, various methods, such as potassium-containing toothpaste, mouthwash, and chewing gum, have been attempted to address DH. However, recent research has explored the potential of nanoparticles (NPs) for DH treatment due to their biocompatibility and bioactive properties. Methods Twenty-seven sound premolars extracted for orthodontic purposes were utilized in the present study to obtain 27 mid-coronal dentin discs. These discs were then etched with 37% orthophosphoric acid for 20 s to expose dentinal tubules (DTs) and simulate DH. Subsequently, dentin discs were rinsed with distilled water for 1 min. These dentin discs were randomly allocated into 3 groups: Group I (etched control), Group II (the etched dentin discs were treated with a carboxymethyl cellulose (CMC) dental hydrogel scaffold loaded with 20% HANPs), and Group III (the etched dentin discs were treated with a CMC dental hydrogel scaffold loaded with 20% ZnO NPs). After 7 days, Group II and III underwent erosive challenge to evaluate the protective effect of the nanoparticle treatments. Finally, the dentin discs were analyzed using profilometric analysis to measure surface roughness (SRa), scanning electron microscopy (SEM) to evaluate DT occlusion, computer-assisted SEM image analysis using Image J. Results Among the groups, Group I exhibited the highest SRa following the DH simulation. Group II showed lower SRa compared to group III. SEM analysis indicated that Group III displayed more occluded DTs compared to Group II. Group I showed the most unoccluded DTs. The SEM analysis results were further quantitatively confirmed using Image J. Conclusions The results indicated that both HANPs and ZnO NPs exhibited promising outcomes; however, ZnO NPs demonstrated superior effectiveness in resisting erosive wear compared to HANPs. Highlights The inclusion of ZnO NPs is anticipated to enhance clinical outcome in reducing dentine hypersensitivity by occluding dentinal tubules and resist erosive challenges. All authors agree with the submission. The work has not been published or submitted for publication elsewhere, either completely or in part, or in another form or language. No conflict of interest with the authors in this work.

Both thin basement membrane nephropathy (TBMN) and autosomal dominant Alport syndrome (ADAS) are types of hereditary nephritis resulting from heterozygous mutations in COL4A3 or COL4A4 genes. Although TBMN is characterized by hematuria and thinning of the glomerular basement membrane (GBM) with excellent renal prognosis, some patients develop end-stage renal disease (ESRD) later in life. In contrast, although AS is characterized by progressive nephropathy with lamellation of the GBM, there are some patients diagnosed with ADAS from a family history of ESRD but who only suffer from hematuria with GBM thinning. These findings indicate a limitation in distinction between TBMN and ADAS. Diagnosis of AS is significant because it facilitates careful follow-up and early treatment, whereas diagnosis of TBMN can underestimate the risk of ESRD. However, some experts are against using the term ADAS as the phenotypes of heterozygous variants vary from no urinary abnormality to ESRD, even between family members with the same mutations, indicating that unknown secondary factors may play a large role in the disease severity. These diagnostic difficulties result in significant confusion in clinical settings. Moreover, recent studies revealed that the number of patients with chronic kidney disease caused by these gene mutations is far higher than previously thought. The aim of this article is to review differing opinions regarding the diagnosis of heterozygous COL4A3 or COL4A4 variants, and to highlight the importance for nephrologists to recognize this disease, and the importance of the need to reclassify this disease to minimize the current confusion.