Clinical characteristics and prognosis of patients with incidentally discovered chest wall sarcoma compared with those of symptomatic patients.

OBJECTIVE: Sarcomas of the bone and soft tissues are detected after the onset of pain, detectable mass and related symptoms in the absence of a standardized screening examination. However, primary chest wall sarcomas can be incidentally detected upon chest X-ray or computed tomography. Previous studies of incidental primary chest wall sarcomas lack prognosis and disease-specific clinical data. This study aimed to investigate the prognoses of patients with incidental chest wall sarcomas and compare them with those of symptomatic patients. METHODS: This study included 18 patients diagnosed with primary chest wall sarcoma between 2010 and 2023. Patient information such as age, sex, tumour diameter, tumour location, symptoms, treatment, time to treatment initiation, pathological diagnosis and outcome were retrospectively analysed. RESULTS: Among the 18 patients, the sarcomas were incidentally detected in five by chest X-ray and computed tomography in three and two patients, respectively. The pathological diagnoses of the patients were Ewing sarcoma, Chondrosarcoma grade 1, grade 2, periosteal osteosarcoma and malignant peripheral nerve sheath tumour. The patients had no symptoms at the first visit to our hospital, and no lesions in other organs were detected at the time of the initial examination. At the final follow-up, the patients remained disease-free after radical treatment. The tumour sizes of the five patients were significantly smaller than those of patients with symptoms (P = 0.003). CONCLUSIONS: The incidental detection of chest wall sarcomas and consequent early detection and treatment of tumours improves patient prognosis relative to that of symptomatically diagnosed patients.

The inter-laboratory validation study of EpiSensA for predicting skin sensitization potential.

The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)-based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre-/pro-haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within- (WLR) and between-laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non-sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals.

Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

BACKGROUNDS: There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). METHODS: We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of < .6 cm2 /m2 and a mean AV pressure gradient (AVPG) of < 40 mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. RESULTS: Of 100 patients (mean age 79.5 ± 7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1% ± 15.9%; resting stroke volume index 35.8 ± 7.7 mL/m2 ; Qrest 171.8 ± 34.9 mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest < 200 mL/s and Qstress ≥200 mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p = .030), as well as Qrest and Qstress < 200 mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p = .001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200 mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. CONCLUSIONS: Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study.

OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-µm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

Hair follicle stem cell progeny heal blisters while pausing skin development.

Injury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that HF development can be sacrificed for the sake of epidermal wound regeneration. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.

Evaluation of cholesterol crystals in carotid plaque by dual energy computed tomography.

Cholesterol crystals (CCs) in carotid plaques might be an indicator of vulnerability, although they have not been fully investigated and non-invasive methods of assessment have not been established. This study examines the validity of assessing CCs using dual-energy computed tomography (DECT) that uses X-rays with different tube voltages for imaging, allowing material discrimination. We retrospectively evaluated patients who had undergone preoperative cervical computed tomography angiography and carotid endarterectomy between December 2019 and July 2020. We developed CC-based material decomposition images (MDIs) by scanning CCs crystallized in the laboratory using DECT. We compared the percentage of CCs in stained slides defined by cholesterol clefts with the percentage of CCs displayed by CC-based MDIs. Thirty-seven pathological sections were obtained from 12 patients. Thirty-two sections had CCs; of these, 30 had CCs on CC-based MDIs. CC-based MDIs and pathological specimens showed a strong correlation. Thus, DECT allows the evaluation of CCs in carotid artery plaques.

Principal component analysis of texture features for grading of meningioma: not effective from the peritumoral area but effective from the tumor area.

PURPOSE: To investigate whether texture features from tumor and peritumoral areas based on sequence combinations can differentiate between low- and non-low-grade meningiomas. METHODS: Consecutive patients diagnosed with meningioma by surgery (77 low-grade and 28 non-low-grade meningiomas) underwent preoperative magnetic resonance imaging including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1WI (CE-T1WI). Manual segmentation of the tumor area was performed to extract texture features. Segmentation of the peritumoral area was performed for peritumoral high-signal intensity (PHSI) on T2WI. Principal component analysis was performed to fuse the texture features to principal components (PCs), and PCs of each sequence of the tumor and peritumoral areas were compared between low- and non-low-grade meningiomas. Only PCs with statistical significance were used for the model construction using a support vector machine algorithm. k-fold cross-validation with receiver operating characteristic curve analysis was used to evaluate diagnostic performance. RESULTS: Two, one, and three PCs of T1WI, apparent diffusion coefficient (ADC), and CE-T1WI, respectively, for the tumor area, were significantly different between low- and non-low-grade meningiomas, while PCs of T2WI for the tumor area and PCs for the peritumoral area were not. No significant differences were observed in PHSI. Among models of sequence combination, the model with PCs of ADC and CE-T1WI for the tumor area showed the highest area under the curve (0.84). CONCLUSION: The model with PCs of ADC and CE-T1WI for the tumor area showed the highest diagnostic performance for differentiating between low- and non-low-grade meningiomas. Neither PHSI nor PCs in the peritumoral area showed added value.

Associations between infant and young child feeding (IYCF) practice and attitudes toward intimate partner violence (IPV) in Timor-Leste.

BACKGROUND: Both the proportions of malnutrition among children and women's justifying partner's intimate partner violence (IPV) are high in Timor-Leste. However, no study has looked at the associations between acceptable infant and young child feeding (IYCF) and women's attitudes toward IPV, as a women's empowerment index. In light of the lack of evidence described above, the study objective was to examine associations between IYCF practice and attitudes toward IPV in Timor-Leste and other women's characteristics. METHODS: A secondary analysis of children's records from the Demographic and Health Survey Timor-Leste 2016 was conducted using a cross-sectional design. Univariable and multivariable analyses were performed to investigate associations between acceptable IYCF and women's agreement that men are justified in beating their wives for five specific reasons and socio-economic factors. RESULTS: The day before the survey, 33.4% of mothers gave their child at least the minimum dietary diversity and 46.4% at least the minimum meal frequency; and 15.0% practiced acceptable IYCF. Among all respondents, 17.5% did not agree that all five specific reasons for beating are justified. The adjusted odds ratio (aOR) of acceptable IYCF for mothers who did not agree was 1.51 (95% confidence interval [CI] 1.09-2.09) compared to those who agreed. The aOR of acceptable IYCF for mothers who worked outside the home was 1.48 (95% CI 1.16-1.96) compared to those who did not. Compared to mothers in the poorest quintile, the aORs of acceptable IYCF among those in the poorer, middle, richer, and richest quintiles were 1.33 (95% CI 0.83-2.21), 1.90 (95% CI 1.15-3.14), 2.01 (95% CI 1.17-3,45), and 2.99 (95% CI 1.63-5.50) respectively. Compared to children aged 6-11 months, the aORs of acceptable IYCF for children aged 12-17 months and 18-23 months were 2.14 (95% CI 1.54-2.97) and 1.63 (95% CI 1.14-2.34), respectively. CONCLUSIONS: Acceptable IYCF was associated with mothers' attitudes toward wife-beating, wealth quintile, and mother's work. Factors that we found associated with IYCF were all related to women's empowerment. It implies that women's empowerment is a key to improving mothers' childcare. Merely promoting a specific childcare practice may not be enough for better child health.

Primary Malignant Lymphoma of the Cauda Equina Diagnosed after Decompression for Lumbar Spinal Stenosis: A Case Report.

Primary malignant lymphoma confinement to the cauda equina is rare. Only 14 cases of primary malignant lymphoma in the cauda equina have been reported. In these cases, the clinical features were similar to those of lumbar spinal canal stenosis (LSCS). This report describes a case of diffuse large B-cell lymphoma of the cauda equina that was diagnosed after decompression surgery for LSCS. An 80-year-old man presented with gait disturbance due to progressive muscle weakness in the lower extremities over the previous two months. He was diagnosed with LSCS, and decompression surgery was performed. However, the muscle weakness worsened after surgery; therefore, he was referred to our department. Plain magnetic resonance imaging (MRI) revealed swelling of the cauda equina. It demonstrated marked homogenous enhancement by gadolinium-diethylenetriamine pentaacetic acid. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed diffuse accumulation of 18F-FDG in the cauda equina. These imaging findings were consistent with those of cauda equina lymphomas. To confirm the diagnosis, we performed an open biopsy of the cauda equina. Histological examination indicated diffuse large B-cell lymphoma. Considering the patient's age and activities of daily living, further treatment was not performed. The patient died four months after the first surgery. Rapid progression of muscle weakness, which cannot be prevented by decompression surgery, and swollen cauda equina on MRI may be signs of this disorder. Gadolinium-enhanced MRI, 18F-FDG PET, and histological investigation of the cauda equina should be performed for diagnosing primary malignant lymphoma of the cauda equina.

Spontaneous Shrinkage of isocitrate dehydrogenase (IDH)-mutant astrocytoma caused by intra-tumoural cyst rupture: a case report.

BACKGROUND: T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign is a specific imaging finding of isocitrate dehydrogenase (IDH)-mutant astrocytomas. Histologically, a hypointense area on FLAIR images indicates the presence of microcysts. Here we report a case of IDH-mutant astrocytoma that shrunk spontaneously. CASE DESCRIPTION: A 26-year-old woman presented with a complaint of headache. Her magnetic resonance (MR) images revealed a lesion mass with a T2-FLAIR mismatch sign in the left frontal lobe. Subsequently, after 1 month, she was referred to our department, and we found that the lesion had unexpectedly shrunk; however, no further shrinkage was observed in the next 3 months. Furthermore, a biopsy was performed, and the results indicated a diagnosis of astrocytoma, IDH-mutant CNS WHO grade 3. Thus, she underwent subtotal resection. We found no neurological deficits in the patient, and she received 60 Gy of radiotherapy at the local site and chemotherapy with nimustine hydrochloride (ACNU), followed by the administration of ACNU every 8 weeks for 2 years. Overall, after 36 months of tumour resection, she was in good health and exhibited no recurrence. Notably, her histological and MR image findings suggested that the macroscopic cyst was formed by the fusion of microcysts, which is a characteristic feature of IDH-mutant astrocytoma with a T2-FLAIR mismatch sign, and that the tumour shrunk because of the rupture of the cyst in the Sylvian cistern. CONCLUSION: The present case report suggests that IDH-mutant astrocytoma cannot be ruled out even when the lesion shrinks spontaneously.

Collagen XVII deficiency alters epidermal patterning.

Vertebrates exhibit patterned epidermis, exemplified by scales/interscales in mice tails and grooves/ridges on the human skin surface (microtopography). Although the role of spatiotemporal regulation of stem cells (SCs) has been implicated in this process, the mechanism underlying the development of such epidermal patterns is poorly understood. Here, we show that collagen XVII (COL17), a niche for epidermal SCs, helps stabilize epidermal patterns. Gene knockout and rescue experiments revealed that COL17 maintains the width of the murine tail scale epidermis independently of epidermal cell polarity. Skin regeneration after wounding was associated with slender scale epidermis, which was alleviated by overexpression of human COL17. COL17-negative skin in human junctional epidermolysis bullosa showed a distinct epidermal pattern from COL17-positive skin that resulted from revertant mosaicism. These results demonstrate that COL17 contributes to defining mouse tail scale shapes and human skin microtopography. Our study sheds light on the role of the SC niche in tissue pattern formation.

The "Organic" Descriptor and Its Association With Commercial Cigarette Health Risk Expectancies, Subjective Effects, and Smoking Topography: A Pilot Human Laboratory Study.

INTRODUCTION: The purpose of this mixed-method pilot study was to: (1) examine whether the "organic" descriptor affects smokers' health risk expectancies, subjective ratings of smoking, and topography, and (2) describe how smokers interpret the "organic" descriptor and relate it to their subjective smoking experience. METHODS: Twenty-two daily smokers (45.5% men, 81.8% non-Hispanic White, M (SD) age = 47.3 [12.7], M (SD) cigarettes/day = 14.5 [5.1]) completed a within-person laboratory study. Following a baseline session, smokers attended 2 experimental sessions where they smoked a study-provided cigarette (identical across conditions) paired with either an "organic" or conventional (e.g., no "organic") descriptor condition and completed subjective and behavioral measures. Participants completed a semi-structured interview at the last visit. RESULTS: Relative to the conventional cigarette, more participants rated the "organic" cigarette as healthier, having fewer chemicals, and having a more favorable burn rate (P's < 0.05). There were no differences in total puff volume by condition (P = 0.42). Stratifying by gender, men inhaled 225 ml (SE = 82.7) more in the conventional condition (P = 0.02); women inhaled 408 ml (SE = 233.3) more in the organic condition (P = 0.11). A common understanding of "organic" was that the product was "…less processed... like less chemicals and it's more natural." Some believed that "organic" cigarettes contained fewer chemicals, which in turn produced a "much cleaner and healthier smoking cigarette" and that they could "taste the difference." CONCLUSIONS: Findings support that smokers associate the "organic" descriptor with health and reduced harm. This descriptor may differentially impact puffing behavior by gender. IMPLICATIONS: This study provides qualitative and quantitative data regarding how the "organic" descriptor influences adult daily smokers' perceptions and use of cigarettes. After smoking two identical cigarettes described as "organic" and conventional (e.g., no "organic"), smokers expressed more problematic health expectancies about the "organic" cigarette condition, providing further empirical support that the "organic" descriptor is associated with expectancies of reduced harm. The source of reduced harm was understood to be fewer chemicals in the organic cigarette. Though preliminary, findings suggest that "organic" may differentially affect puffing behavior by gender.

Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders.

Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. Cases comprised six females and two males, with a median age of 56.5 years (range, 46-71 years) and a median disease duration of 62.5 months (range, 0.6-252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for GFAP: (i) astrocyte lysis: extensive loss of astrocytes with fragmented and/or dust-like particles; (ii) progenitor recruitment: loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (iii) protoplasmic gliosis: presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (iv) fibrous gliosis: lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.

Hospital-Wide Surveillance of Fracture Risk Assessment by Both FRAX and Medication Patterns in Acute Care Hospital.

To identify patients at a high risk for primary and secondary osteoporotic fractures using fracture risk assessments performed using the current method and the proposed method, in an acute care hospital and to identify departments where high-risk patients are admitted. This retrospective study included patients aged 40-90 years who were hospitalized at Fujita Health University Hospital. We collated the clinical data and prescriptions of all study participants. We also gathered data pertaining to risk factors according to Fracture Risk Assessment Tool (FRAX). Of the 1595 patients, the mean number of major osteoporotic fracture risk predicted using FRAX was 11.73%. The department of rheumatology showed the highest fracture risk (18.55 ± 16.81) and had the highest number of patients on medications that resulted in reduced bone mineral density (1.07 ± 0.98 medication). Based on the FRAX, the proportion of patients in the high-risk group in this department was significantly higher compared with those in the remaining departments with respect to glucocorticoid administration, rheumatoid arthritis, and secondary osteoporosis. However, the departments included in the high-risk group were not necessarily the same as the departments included in the top group, based on the administered medications. FRAX score is calculated based on various risk factors; however, only glucocorticoid corresponds to medications. We should focus on medication prescription patterns in addition to FRAX to improve fracture risk assessment in hospital-wide surveillance. Therefore, we recommend the use of FRAX along with the prescribed medications to identify departments that admit high-risk patients.

Fibroepithelial Polyps Originating from the Posterior Nasal Septum: A Case Report.

Fibroepithelial polyps are benign tumors of mesodermal origin. They rarely occur in the nasal cavity, with only four such cases reported in the relevant English literature. The location was the inferior turbinate in three cases and anterior nasal septum in one case. The etiology has been suggested in other organs; however, it is entirely unknown in the nasal cavity. Pathological findings play an essential role in the diagnosis of fibroepithelial polyps. We report the case of a 76-year-old woman with fibroepithelial polyps originating from the posterior part of the nasal septum. The fibroepithelial polyps were white-yellow lobular masses that differed from a common inflammatory polyp. We made the diagnosis by excluding the other possible tumors based on a pathological examination. This is the first report about fibroepithelial polyps arising from the posterior nasal septum. She had no potential risk factors that might trigger fibroepithelial polyps in the nasal cavity. This case is a valuable example when considering the potential causes (e.g., female hormones and mechanical pressure) of nasal fibroepithelial polyps.

Severe Inflammatory Idiopathic Multicentric Castleman's Disease Coexisting with Advanced Renal Cancer: A Case Report.

The present case study was conducted on a 74-year-old man who visited our department due to a left renal and retroperitoneal tumor on computed tomography (CT). The patient was diagnosed with left renal cancer lymph node metastasis and was hospitalized a few weeks prior to surgery due to fever, malaise, and severe appetite loss. Biochemical laboratory findings at admission showed markedly high levels of inflammation. The cause of high inflammatory response was paraneoplastic syndrome. Tumor resection was considered necessary, and left nephrectomy and lymphadenectomy were performed; however, it did not improve the inflammatory response. After operation, positron emission tomography-CT revealed hyperaccumulation of 18F-fluorodeoxyglucose in the bone marrow throughout the body. Pathological examination of the resected specimen and bone marrow aspiration revealed the coexistence of idiopathic multicentric Castleman disease (CD) and renal cancer. Prednisolone and tocilizumab were administered for idiopathic multicentric CD and a tyrosine kinase inhibitor for renal cancer; however, they had poor therapeutic effect, and the patient died. CD is characterized by systemic symptoms due to the overproduction of interleukin-6. Treatment for idiopathic multicentric CD involves steroid and anti-interleukin-6 therapy. The diagnostic criteria for CD require the exclusion of malignant tumors although there are some cases in which CD and malignant tumors coexist. The prognosis for CD is relatively good; however, as in this case, the prognosis of CD coexisting with uncontrollable renal cancer is insufficient due to poor improvement in the inflammatory response.

[A Case of Fournier's Gangrene during Second-Line IRIS plus Bevacizumab Chemotherapy for Rectal and Anal Canal Cancer].

A 52-year-old man diagnosed with Stage ⅢA rectal and anal canal cancer underwent abdominal perineal resection using Miles's method. Two years later, local recurrence and lung metastases were detected using contrasted CT imaging. First-line chemotherapy of XELOX was administered for 4 months until the disease progressed and lung metastases developed. After 4 courses of second-line IRIS plus bevacizumab chemotherapy, fever and swelling of the right buttock appeared; he visited and was admitted to our hospital. A CT scan revealed a pelvic abscess which resulted in septic shock. Swelling and pain extended to the right scrotum, and acute necrotizing fasciitis was suspected, and emergency surgery was performed. An incision was made from the right buttock to the right scrotum, bloody purulent drainage with a foul odor was observed, and a diagnosis of Fournier's gangrene was made. Although typical CT findings such as emphysema due to gas-producing bacteria were not observed in this case, early diagnosis and intervention of systemic management including early surgical drainage and operation were effective. For pelvic infections occurring during bevacizumab chemotherapy, Fournier's gangrene should considered for differential diagnosis, even if CT findings are atypical.

Advanced colorectal cancer subtypes (aCRCS) help select oxaliplatin-based or irinotecan-based therapy for colorectal cancer.

Oxaliplatin (OX) and irinotecan (IRI) are used as key drugs for the first-line treatment of metastatic colorectal cancer (mCRC). However, no biomarkers have been identified to decide which of the drugs is initially used. In this translational research (TR) of the TRICOLORE trial, the advanced colorectal cancer subtype (aCRCS) was analyzed as a potential biomarker for the selection of OX or IRI. We collected 335 (68.8%) formalin-fixed, paraffin-embedded (FFPE) primary tumor specimens from 487 patients registered in the TRICOLORE trial and performed direct sequencing and immunohistochemical staining of CRC-related genes, comprehensive gene-expression analysis, and genome-wide methylation analysis. The progression-free survival (PFS) of the IRI group was significantly better compared with the OX group in BRAF wild-type (WT), PTEN-positive, and aCRCS A1 patients. Among the molecular factors, aCRCS were only associated with the PFS of OX and IRI groups. The PFS of the IRI group was significantly better compared with the OX group in aCRCS A1 + B1 (hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.41-0.82; P = .0023). In contrast, the OX group had better PFS compared with the IRI group in aCRCS B2, although this was not statistically significant (HR = 1.66; 95% CI = 0.94-2.96; P = .083). Nearly half of patients with mCRC (46.8%, aCRCS A1 + B1) respond well to IRI, while only about 18.5% (aCRCS B2) of patients with mCRC responded well to OX. In conclusion, the aCRCS might be a predictive factor for the clinical outcomes of OX-based and IRI-based therapies.

Type XVII collagen interacts with the aPKC-PAR complex and maintains epidermal cell polarity.

Type XVII collagen (COL17) is a transmembrane protein expressed in the basal epidermis. COL17 serves as a niche for epidermal stem cells, and although its reduction has been implicated in altering cell polarity and ageing of the epidermis, it is unknown how COL17 affects epidermal cell polarity. Here, we uncovered COL17 as a binding partner of the aPKC-PAR complex, which is a key regulating factor of cell polarity. Immunoprecipitation-immunoblot assay and protein-protein binding assay revealed that COL17 interacts with aPKC and PAR3. COL17 deficiency or epidermis-specific aPKCλ deletion destabilized PAR3 distribution in the epidermis, while aPKCζ knockout did not. Asymmetrical cell division was pronounced in COL17-null neonatal paw epidermis. These results show that COL17 is pivotal for maintaining epidermal cell polarity. Our study highlights the previously unrecognized role of COL17 in the basal keratinocytes.

Effect of Diastolic Flow Reversal Patterns on Clinical Outcomes Following Transcatheter Aortic Valve Implantation　- An Intraprocedural Echocardiography Study.

BACKGROUND: Although diastolic flow reversal (DFR) in the descending aorta, assessed via transesophageal echocardiography (TEE), is a simple and easy indicator for evaluating aortic regurgitation, the association between DFR pattern and clinical outcomes following transcatheter aortic valve implantation (TAVI) is unclear. The purpose of this study was to evaluate the effect of DFR patterns on clinical outcomes following TAVI.Methods and Results:Two-hundred and eleven patients (mean age, 83.6±5.7 years; 69% female) who underwent TAVI were retrospectively assessed via intraprocedural TEE. DFR was evaluated using pulsed-wave Doppler in the descending aorta before and after TAVI. The primary endpoint was major adverse cardio-cerebrovascular events (MACCEs). Although only 7 patients (3.3%) had moderate or severe paravalvular leak, as assessed by color Doppler echocardiography, holo-DFR (HDFR) was observed in 33 patients (16.0%) after TAVI. MACCEs occurred in 40 patients during the median follow up of 282 days (interquartile range: 160-478 days). The estimated cumulative MACCE-free survival at 1 year was significantly lower in patients with HDFR than in those without HDFR. A Cox proportional hazards analysis revealed that HDFR after TAVI was independently associated with MACCEs. CONCLUSIONS: HDFR was associated with an increased risk of MACCEs after TAVI. DFR evaluated by intraprocedural echocardiography could serve as a simple and easy method for predicting clinical outcomes.