Isolation, structural determination, and antiviral activities of a novel alanine-conjugated polyketide from Talaromyces sp.

Antiviral agents are highly sought after. In this study, a novel alkylated decalin-type polyketide, alaspelunin, was isolated from the culture broth of the fungus Talaromyces speluncarum FMR 16671, and its structure was determined using spectroscopic analyses (1D/2D NMR and MS). The compound was condensed with alanine, and its absolute configuration was determined using Marfey's method. Furthermore, the antiviral activity of alaspelunin against various viruses was evaluated, and it was found to be effective against both severe acute respiratory syndrome coronavirus 2 and pseudorabies (Aujeszky's disease) virus, a pathogen affecting pigs. Our results suggest that this compound is a potential broad-spectrum antiviral agent.

Characterization of genotype V Japanese encephalitis virus isolates from Republic of Korea.

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct in vitro phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. In vivo, NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood-brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct in vitro and in vivo characteristics.

Dissemination of the Flavivirus Subgenomic Replicon Genome and Viral Proteins by Extracellular Vesicles.

Extracellular vesicles (EVs) such as exosomes have been shown to play physiological roles in cell-to-cell communication by delivering various proteins and nucleic acids. In addition, several studies revealed that the EVs derived from the cells that are infected with certain viruses could transfer the full-length viral genomes, resulting in EVs-mediated virus propagation. However, the possibility cannot be excluded that the prepared EVs were contaminated with infectious viral particles. In this study, the cells that harbor subgenomic replicon derived from the Japanese encephalitis virus and dengue virus without producing any replication-competent viruses were employed as the EV donor. It was demonstrated that the EVs in the culture supernatants of those cells were able to transfer the replicon genome to other cells of various types. It was also shown that the EVs were incorporated by the recipient cells primarily through macropinocytosis after interaction with CD33 and Tim-1/Tim-4 on HeLa and K562 cells, respectively. Since the methods used in this study are free from contamination with infectious viral particles, it is unequivocally indicated that the flavivirus genome can be transferred by EVs from cell to cell, suggesting that this pathway, in addition to the classical receptor-mediated infection, may play some roles in the viral propagation and pathogenesis.

Role of Wnt5b-Ror1 signaling in the proliferation of pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory cancers with the worst prognosis. Although several molecules are known to be associated with the progression of PDAC, the molecular mechanisms underlying the progression of PDAC remain largely elusive. The Ror-family receptors, Ror1 and Ror2, which act as a receptor(s) for Wnt-family ligands, particularly Wnt5a, are involved in the progression of various types of cancers. Here, we show that higher expression of Ror1 and Wnt5b, but not Ror2, are associated with poorer prognosis of PDAC patients, and that Ror1 and Wnt5b are expressed highly in a type of PDAC cell lines, PANC-1 cells. Knockdown of either Ror1 or Wnt5b in PANC-1 cells inhibited their proliferation significantly in vitro, and knockout of Ror1 in PANC-1 cells resulted in a significant inhibition of tumor growth in vivo. Furthermore, we show that Wnt5b-Ror1 signaling in PANC-1 cells promotes their proliferation in a cell-autonomous manner by modulating our experimental setting in vitro. Collectively, these findings indicate that Wnt5b-Ror1 signaling might play an important role in the progression of some if not all of PDAC by promoting proliferation.

Photoacoustic microscopy for real-time monitoring of near-infrared optical absorbers inside biological tissue.

Significance: We developed a high-speed optical-resolution photoacoustic microscopy (OR-PAM) system using a high-repetition-rate supercontinuum (SC) light source and a two-axes Galvano scanner. The OR-PAM system enabled real-time imaging of optical absorbers inside biological tissues with excellent excitation wavelength tunability. Aim: In the near-infrared (NIR) wavelength range, high-speed OR-PAM faces limitations due to the lack of wavelength-tunable light sources. Our study aimed to enable high-speed OR-PAM imaging of various optical absorbers, including NIR contrast agents, and validate the performance of high-speed OR-PAM in the detection of circulating tumor cells (CTCs). Approach: A high-repetition nanosecond pulsed SC light source was used for OR-PAM. The excitation wavelength was adjusted by bandpass filtering of broadband light pulses produced by an SC light source. Phantom and in vivo experiments were performed to detect tumor cells stained with an NIR contrast agent within flowing blood samples. Results: The newly developed high-speed OR-PAM successfully detected stained cells both in the phantom and in vivo. The phantom experiment confirmed the correlation between the tumor cell detection rate and tumor cell concentration in the blood sample. Conclusions: The high-speed OR-PAM effectively detected stained tumor cells. Combining high-speed OR-PAM with molecular probes that stain tumor cells in vivo enables in vivo CTC detection.

Esthetic management of anterior implants in advanced periodontal defects. A case report

Achieving optimal implant prosthodontic outcomes in the esthetically demanding anterior region requires sufficient hard and soft tissue volume to provide adequate support and coverage to ensure that the implant restorations are functional and yield predictable, long-lasting treatment results. A comprehensive biologic understanding of the 3D relationships between hard and soft tissue is crucial when treating esthetically demanding areas. Various techniques, notably guided bone regeneration, have been developed and are well documented as being reliable methods for larger 3D bone augmentation procedures. Additionally, dental modification and tooth repositioning in proximity to prospective implant placement sites has been extensively discussed. Recently, orthodontic extrusion with deferred extraction has emerged as a predictable treatment strategy for gaining additional vertical hard and soft tissue. Implementing treatment sequences and the timing of combined treatment methodologies have also been subjects of discussion. Combining orthodontic treatment with staged or delayed tooth extractions has been shown to be beneficial in providing the necessary osseous foundation for implant sites that may not be as amenable to more conventional augmentation techniques. These augmentation techniques and treatment methods require adequately stable and predictable periodontal health since uncontrolled periodontal disease poses a significant challenge and is detrimental to successful outcomes. The purpose of the present clinical report is to demonstrate the staging and sequencing of vertical hard and soft tissue management techniques for a severe anterior periodontal defect to achieve an esthetically functional implant treatment result.

Double-sided entire papilla preservation technique in the combination periodontal regenerative therapy: A case report.

BACKGROUND: With the entire papilla preservation (EPP) technique, it is possible to perform regenerative therapy without incisions in the interdental papilla and to reduce the risk of papillary rupture. However, one limitation of the EPP is the sole access from the buccal side. Here, we present a case of periodontitis treated by the combination regenerative therapy employing the Double-sided (buccal-palatal) EPP (DEPP) technique, which adds a palatal vertical incision to the EPP. METHODS: A patient with 1-2 wall intrabony defects received the regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 and carbonate apatite (CO3 Ap). Using the DEPP technique, vertical incisions at buccal and palatal aspects were placed to gain adequate access to the 1-2 wall intrabony defects between #11 and #12 without incision in the interdental papilla. After debridement, rhFGF-2 and CO3 Ap were applied to the defect. Periodontal clinical parameters and radiographic images were evaluated at the first visit, following initial periodontal therapy (baseline), 6, 9, and 12 months postoperatively. RESULTS: Wound healing was uneventful. Scarring of the incision lines was minimal. At 12 months postoperatively, probing depth reduction was 4 mm, clinical attachment gain was 4 mm, and gingival recession was not observed. An improvement in radiopacity in the previous bone defect was observed. CONCLUSION: The DEPP is an innovative technique that allows approaching from both the buccal and palatal sides while ensuring flap extensibility without compromising the interdental papilla. This report suggests that the combination of regenerative therapy with the DEPP may be promising in the treatment of intrabony defects. KEY POINTS: Why is this case new information? The DEPP allows a direct visual approach to a 1-2 wall intrabony defect extending from the buccal to palatal sides, and increases flap extensibility, without compromising the papilla. What are the keys to the successful management of this case? Assessment of three-dimensional bone defect morphology is required. Computed tomography images are very useful. The flap elevation just under the interdental papilla should be carefully performed with a small excavator to avoid damage to the interdental papilla. What are the primary limitations to success in this case? Despite the addition of a palatal incision, it was not possible to obtain complete flexibility of the palatal gingiva. Caution must be taken in a case in which the distance between the interdental papilla is narrow. Even if the interdental papilla is ruptured during the operation, recovery is possible by continuing the operation and suturing the rupture at the end.

Supra-Alveolar Periodontal Tissue Reconstruction in a Case with Severe Periodontitis: Case Report with a 2-Year Follow-up.

Periodontal regeneration therapy has developed tremendously since its inception, becoming a clinical tool to preserve the periodontally compromised natural dentition. More challenging esthetic defects can often benefit from the combination of bone and soft tissue regeneration, such as the application of connective tissue grafts (CTGs) and techniques that approach the bone defect without interdental papillae incisions. However, periodontal tissue regeneration vertical to the alveolar bone crest in cases of severe periodontitis, with loss of both soft and hard tissues, has not been predictably established. This case report describes a patient with severe periodontitis that was treated with in supra-alveolar periodontal tissue reconstruction. This innovative surgical technique requires both horizontal buccal incisions and several vertical palatal incisions, avoiding the interdental papillae on the periodontal defect. Then, a space is created by suspending and fixating the flap coronally, and CTG and regenerative materials (such as recombinant human fibroblast growth factor-2) and bone graft material are applied. This technique has the potential to gain clinical attachment, achieve supra-/intraperiodontal regeneration, and enhance esthetic outcomes, including a reduced gingival recession and interdental papillae reconstruction. The clinical results of the present case were well maintained over the 2-year follow-up. Int J Periodontics Restorative Dent 2023;43:213-221. doi: 10.11607/prd.6241.

Adiponectin can be a good predictor of urodynamic detrusor underactivity: a prospective study in men with lower urinary tract symptoms.

PURPOSE: To investigate whether circulating adiponectin, which is considered a possible marker of anti-atherogenic effects, is a useful predictor of bladder function, especially detrusor underactivity (DU), in men with lower urinary tract symptoms (LUTS). METHODS: A total of 130 treatment-naïve men with non-neurogenic LUTS were prospectively stratified into two groups (the DU and non-DU groups) based on the presence or absence of DU, where DU is defined as a bladder contractility index < 100 and bladder outlet obstruction index (BOOI) < 40. The impact of serum adiponectin levels on urodynamic function, including DU, was assessed using univariate, binomial logistic regression, and receiver operating characteristic (ROC) curve analyses. RESULTS: In total, data from 118 men were analyzed; 39 (33.0%) had DU (DU group) and 79 (67.0%) did not have DU (non-DU group). The median serum adiponectin in the DU group was significantly lower than in the non-DU group (6.2 vs 12.6 µg/mL, p < 0.001). In the binomial logistic regression analysis, lower adiponectin, smaller intravesical prostatic protrusion, and lower bladder voiding efficiency were significant factors related to DU. In the ROC analyses, serum adiponectin had the highest area under the curve value for DU diagnosis (0.849). Additionally, a cutoff value of 7.9 µg/mL for serum adiponectin level was identified for DU, which yielded a sensitivity and specificity of 79% and 90%, respectively. CONCLUSIONS: The serum adiponectin level was significantly associated with bladder function and may be a useful marker for predicting DU in men with LUTS.

A VS ultrasound diagnostic system with kidney image evaluation functions.

PURPOSE: An inevitable feature of ultrasound-based diagnoses is that the quality of the ultrasound images produced depends directly on the skill of the physician operating the probe. This is because physicians have to constantly adjust the probe position to obtain a cross section of the target organ, which is constantly shifting due to patient respiratory motions. Therefore, we developed an ultrasound diagnostic robot that works in cooperation with a visual servo system based on deep learning that will help alleviate the burdens imposed on physicians. METHODS: Our newly developed robotic ultrasound diagnostic system consists of three robots: an organ tracking robot (OTR), a robotic bed, and a robotic supporting arm. Additionally, we used different image processing methods (YOLOv5s and BiSeNet V2) to detect the target kidney location, as well as to evaluate the appropriateness of the obtained ultrasound images (ResNet 50). Ultimately, the image processing results are transmitted to the OTR for use as motion commands. RESULTS: In our experiments, the highest effective tracking rate (0.749) was obtained by YOLOv5s with Kalman filtering, while the effective tracking rate was improved by about 37% in comparison with cases without such filtering. Additionally, the appropriateness probability of the ultrasound images obtained during the tracking process was also the highest and most stable. The second highest tracking efficiency value (0.694) was obtained by BiSeNet V2 with Kalman filtering and was a 75% improvement over the case without such filtering. CONCLUSION: While the most efficient tracking achieved is based on the combination of YOLOv5s and Kalman filtering, the combination of BiSeNet V2 and Kalman filtering was capable of detecting the kidney center of gravity closer to the kidney's actual motion state. Furthermore, this model could also measure the cross-sectional area, maximum diameter, and other detailed information of the target kidney, which meant it is more practical for use in actual diagnoses.

Isolation, structural determination, and antiviral activities of metabolites from vanitaracin A-producing Talaromyces sp.

Vanitaracin A, an anti-hepatitis B virus polyketide, has been previously isolated from Talaromyces sp. In the present study, we searched for novel compounds in the culture broth obtained from a vanitaracin A-producing fungus under various conditions. Three novel compounds (vanitaracin C, vanitaraphilone A, and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde) were isolated, and their structures were determined using spectroscopic methods (1D/2D NMR and MS). In addition, the antiviral spectrum of vanitaracin A was examined by measuring its antiviral activities against rabies virus, Borna disease virus 1, and bovine leukemia virus. This compound exhibited antiviral activity against bovine leukemia virus, which is the causative agent of enzootic bovine leukosis. The anti-bovine leukemia virus effects of other compounds isolated from the vanitaracin A-producing fungus, namely, vanitaracins B and C, vanitaraphilone A, and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde, were also evaluated. Vanitaracin B, vanitaraphilone A and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde were also found to exhibit activity against bovine leukemia virus. These findings reveal the broad-spectrum antiviral activity of the vanitaracin scaffold and suggest several candidates for the development of anti-bovine leukemia virus drugs.

Ror1 is expressed inducibly by Notch and hypoxia signaling and regulates stem cell-like property of glioblastoma cells.

Ror1 plays a crucial role in cancer progression by regulating cell proliferation and migration. Ror1 is expressed abundantly in various types of cancer cells and cancer stem-like cells. However, the molecular mechanisms regulating expression of Ror1 in these cells remain largely unknown. Ror1 and its putative ligand Wnt5a are expressed highly in malignant gliomas, especially in glioblastomas, and the extents of Ror1 expression are correlated positively with poorer prognosis in patients with gliomas. We show that Ror1 expression can be upregulated in glioblastoma cells under spheroid culture, but not adherent culture conditions. Notch and hypoxia signaling pathways have been shown to be activated in spheroid-forming glioblastoma stem-like cells (GSCs), and Ror1 expression in glioblastoma cells is indeed suppressed by inhibiting either Notch or hypoxia signaling. Meanwhile, either forced expression of the Notch intracellular domain (NICD) in or hypoxic culture of glioblastoma cells result in enhanced expression of Ror1 in the cells. Consistently, we show that both NICD and hypoxia-inducible factor 1 alpha bind to upstream regions within the Ror1 gene more efficiently in GSCs under spheroid culture conditions. Furthermore, we provide evidence indicating that binding of Wnt5a to Ror1, upregulated by Notch and hypoxia signaling pathways in GSCs, might promote their spheroid-forming ability. Collectively, these findings indicate for the first time that Notch and hypoxia signaling pathways can elicit a Wnt5a-Ror1 axis through transcriptional activation of Ror1 in glioblastoma cells, thereby promoting their stem cell-like property.

Flavivirus recruits the valosin-containing protein-NPL4 complex to induce stress granule disassembly for efficient viral genome replication.

Flaviviruses are human pathogens that can cause severe diseases, such as dengue fever and Japanese encephalitis, which can lead to death. Valosin-containing protein (VCP)/p97, a cellular ATPase associated with diverse cellular activities (AAA-ATPase), is reported to have multiple roles in flavivirus replication. Nevertheless, the importance of each role still has not been addressed. In this study, the functions of 17 VCP mutants that are reportedly unable to interact with the VCP cofactors were validated using the short-interfering RNA rescue experiments. Our findings of this study suggested that VCP exerts its functions in replication of the Japanese encephalitis virus by interacting with the VCP cofactor nuclear protein localization 4 (NPL4). We show that the depletion of NPL4 impaired the early stage of viral genome replication. In addition, we demonstrate that the direct interaction between NPL4 and viral nonstructural protein (NS4B) is critical for the translocation of NS4B to the sites of viral replication. Finally, we found that Japanese encephalitis virus and dengue virus promoted stress granule formation only in VCP inhibitor-treated cells and the expression of NS4B or VCP attenuated stress granule formation mediated by protein kinase R, which is generally known to be activated by type I interferon and viral genome RNA. These results suggest that the NS4B-mediated recruitment of VCP to the virus replication site inhibits cellular stress responses and consequently facilitates viral protein synthesis in the flavivirus-infected cells.

Adaptive optics with spatio-temporal lock-in detection for temporal focusing microscopy.

Wavefront distortion in temporal focusing microscopy (TFM) results in a distorted temporal profile of the excitation pulses owing to spatio-temporal coupling. Since the pulse duration is dramatically changed in the excitation volume, it is difficult to correct the temporal profile for a thick sample. Here, we demonstrate adaptive optics (AO) correction in a thick sample. We apply structured illumination microscopy (SIM) to an AO correction in wide-field TFM to decrease the change in the pulse duration in the signal detection volume. The AO correction with SIM was very successful in a thick sample for which AO correction with TFM failed.

Discovery of Selective Transforming Growth Factor ß Type II Receptor Inhibitors as Antifibrosis Agents.

Historically, modulation of transforming growth factor ß (TGF-ß) signaling has been deemed a rational strategy to treat many disorders, though few successful examples have been reported to date. This difficulty could be partially attributed to the challenges of achieving good specificity over many closely related enzymes that are implicated in distinct phenotypes in organ development and in tissue homeostasis. Recently, fresolimumab and disitertide, two peptidic TGF-ß blockers, demonstrated significant therapeutic effects toward human skin fibrosis. Therefore, the selective blockage of TGF-ß signaling assures a viable treatment option for fibrotic skin disorders such as systemic sclerosis (SSc). In this report, we disclose selective TGF-ß type II receptor (TGF-ßRII) inhibitors that exhibited high functional selectivity in cell-based assays. The representative compound 29 attenuated collagen type I alpha 1 chain (COL1A1) expression in a mouse fibrosis model, which suggests that selective inhibition of TGF-ßRII-dependent signaling could be a new treatment for fibrotic disorders.

Characterization of Prototheca CYP51/ERG11 as a possible target for therapeutic drugs.

Prototheca spp. are achlorophyllous algae, ubiquitous in nature. An increasing number of human and animal cases of Prototheca infection (protothecosis) are reported, and antifungal azoles, which inhibit sterol 14α-demethylase (CYP51/ERG11) involved in ergosterol biosynthesis, have empirically been used for the treatment of protothecosis. Although Prototheca, like fungi, has ergosterol in the cell membrane, efficacy of the antifungal azoles in the treatment of protothecosis is controversial. For investigating the interaction of azole drugs with Prototheca CYP51/ERG11, the CYP51/ERG11 genomic genes of four strains of P. wickerhamii and one strain each of P. cutis and P. miyajii were isolated and characterized in this study. Compared with the CYP51/ERG11 gene of chlorophyllous Auxenochlorella Protothecoides, it is possible that ProtothecaCYP51/ERG11 gene, whose exon-intron structure appeared to be species-specific, lost introns associated with the loss of photosynthetic activity. Analysis of the deduced amino acid sequences revealed that Prototheca CYP51/ERG11 and fungal CYP51/ERG11 are phylogenetically distant from each other although their overall structures are similar. Our basic in silico studies predicted that antifungal azoles could bind to the catalytic pocket of Prototheca CYP51/ERG11. It was also suggested that amino acid residues away from the catalytic pocket might affect the drug susceptibility. The results of this study may provide useful insights into the phylogenetic taxonomy of Prototheca spp. in relationship to the CYP51/ERG11 structure and development of novel therapeutic drugs for the treatment of protothecosis. LAY SUMMARY: Cases of infection by microalgae of Prototheca species are increasing. However, effective treatment has not been established yet. In this study, gene and structure of Prototheca's CYP51/ERG11, an enzyme which might serve as a target for therapeutic drugs, were characterized for the first time.

The influence of multiple oral administration on the pharmacokinetics and distribution profile of dalcetrapib in rats.

We investigated the influence of multiple oral administration on the accumulation of dalcetrapib (JTT-705/RO4607381), a novel cholesteryl ester transfer protein inhibitor, in rats. It is well known that orally administered dalcetrapib is rapidly hydrolysed to its active form, which has a sulfhydryl group, in the body. The active form then binds covalently to endogenous thiols via mixed disulfide bonds. Following multiple once daily oral administration of 14C-dalcetrapib for seven days to rats, the concentration of radioactivity in the plasma and almost all tissues reached the steady state by day 4. At 24 h after the last dose, there was a relatively high concentration of radioactivity in the mesenteric lymph nodes, liver, adrenal glands and fat. After the last dose to rats, the radioactivity was almost completely recovered in the urine and faeces, indicating that dalcetrapib is not retained in the body, probably due to the reversibility of the disulfide bonds despite being covalent bonds.

Vertical Ridge Augmentation With a Honeycomb Structure Titanium Membrane: A Technical Note for a 3-Dimensional Curvature Bending Method.

Guided bone regeneration is the most commonly used technique for vertical ridge augmentation (VRA), and it is popular because it is less invasive and highly formative. Since the augmented site is exposed to external pressure, it is preferable to support the membrane using a framework to maintain the shape of the VRA. Recently, a titanium framework-reinforced ultrafine titanium membrane was developed by laser processing technology. The technique allows microperforations to be made (φ20 µm) into a titanium membrane, which is expected to prevent fibrous tissue ingrowth from outside the membrane. In addition, significant bone regeneration was confirmed on ridge defects in previous animal studies. However, the membrane tends to crumple during the bending process, because it is very thin (20 nµm); thus, the bending procedures are technically sensitive. Since this titanium honeycomb membrane was first approved for clinical use in Japan, no international clinical reports have been published. The purpose of this case report is to describe a technical note for a 3-dimensional curvature bending method in VRA using the newly developed honeycomb structure titanium membrane.

A Benign Appendiceal-Colonic Fistula, Diagnosed and Managed Laparoscopically: A Case Report.

BACKGROUND Treatment methods for appendiceal-colonic fistulas differ greatly depending on whether lesions are benign or malignant. If the tumor is malignant, appendectomy with lymph node resection (ileocecal resection or right hemicolectomy) should be performed. There is no consensus on the method of surgery for organs infiltrated by appendiceal cancer. Furthermore, there are no reported laparoscopic cases that could be prevented from over-surgery by laparoscopy examination or rapid intraoperative pathological examination. CASE REPORT A 76-year-old man presented with positive fecal occult blood. Lower endoscopy revealed a 10-mm tumor in the rectosigmoid colon accompanied by white moss. A biopsy showed inflammatory granulation and no malignancy. Fluorodeoxyglucose-positron emission tomography showed highly increased accumulation at the tip of the appendix, and the standardized uptake value max was 7.3. We suspected a benign lesion rather than appendiceal cancer with infiltration into the rectosigmoid colon; therefore, we performed laparoscopic appendectomy and wedge-shaped resection of the rectum of the sigmoid colon. An intraoperative rapid pathological examination showed no appearance of malignancy; therefore, additional resection was omitted, and an ileostomy was created in the right lower quadrant. A permanent pathological examination showed complicated appendicitis, with no appearance of malignancy. The ileostomy was closed on postoperative day 25, and the patient was discharged on postoperative day 32. CONCLUSIONS In cases where there is difficulty in identifying whether the appendiceal-colonic fistula lesion is benign or malignant, laparoscopy and intraoperative rapid pathological examination may be useful in avoiding excessive treatment.

The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study.

BACKGROUND: The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. METHODS: We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. RESULTS: Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007). CONCLUSIONS: Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.