Severe disseminated infection by hypermucoviscous Klebsiella pneumoniae successfully treated by intensive therapy with continuous hemodiafiltration using AN69ST: A case report and review of the literature.

Klebsiella pneumoniae (Kpn) is one of the most common gram-negative bacilli causing lung, urinary tract, and biliary tract infections. However, as a distinct entity from classic Kpn, hypervirulent Kpn causing liver abscess, endophthalmitis, and lung abscess with poor prognoses has been reported mainly in East and Southeast Asia since the mid-1980s. Although the definition of hypervirulent Kpn is unclear, the hypermucoviscosity of Kpn is considered an important feature of hypervirulence. We present a case of emphysematous pyelonephritis accompanied by septic shock and acute kidney injury caused by hypermucoviscous Kpn infection that was successfully treated by intensive treatment. A 70-year-old woman with type 2 diabetes mellitus was diagnosed with emphysematous pyelonephritis, and string test-positive Kpn was detected in blood and urine cultures and percutaneous catheter drainage fluid from the renal pelvis. The patient was treated with intensive therapies including antibiotics, ventilator management, and continuous hemodiafiltration (CHDF) using AN69ST, which can absorb cytokines. During the course of treatment, the infection was complicated by pyogenic spondylitis, which was cured by antimicrobial therapy, and the patient was transferred to another hospital for rehabilitation on day 119 after admission. Hypermucoviscous Kpn infection often has a severe course, and it is important to initiate multidisciplinary treatment at an early stage, including rifampicin, which is expected to inhibit the viscosity of hypermucoviscous Kpn. In the current case, immediate CHDF using AN69ST was also considered a life-saving treatment because it improved both volume overload and neutrophil-activated hypercytokinemia.

Sheet-like interstitial cells connect epithelial and smooth muscle cells in the mouse prostate.

Epithelial-stromal relationship in the prostate gland is crucial for maintaining homeostasis, including functional differentiation, proliferation, and quiescence. Pathological stromal changes are believed to cause benign prostatic hyperplasia (BPH). The prostate stromal tissue is known to have several subtypes of interstitial cells that connect the epithelium and smooth muscle. However, the characteristics of their morphology and connection patterns are not fully understood. Therefore, we aimed to investigated the three-dimensional morphology and intercellular interactions of interstitial cells in the prostate ventral lobe of mature wild-type mice using immunohistochemistry and focused ion beam-scanning electron microscopy tomography (FIB-SEM tomography). The prostate interstitial cells exhibited immunohistochemical subtypes, including PDGFRα single-positive, CD34 single-positive, and CD34 and PDGFRα double-positive. PDGFRα single-positive cells were observed as elongated cells just below the epithelium, CD34 single-positive cells were observed as polygonal cells in the area away from the epithelium, and double-positive cells were observed as elongated cells situated slightly deeper than PDGFRα single-positive cells. Furthermore, connexin43-immunoreactive puncta were observed on interstitial cells just beneath the epithelium, suggestive of possible electrical connections among the PDGFRα single-positive interstitial cells. Three-dimensional structural analysis using FIB-SEM tomography revealed sheet-like multilayered interstitial cells that appear to separate the glandular terminal from the deeper interstitial tissue, which includes smooth muscle and capillaries. Further, epithelial cells might be indirectly connected to the smooth muscle and nerve fibers via these sheet-like multilayered interstitial cellular networks. These findings suggest that the cellular network that separates the glandular terminals from the deep interstitial tissue functionally bridges the epithelium and smooth muscle, possibly playing a pivotal role in prostate tissue homeostasis through the epithelial-smooth muscle or epithelial-stromal relationships.

A metastatic ureteral tumor successfully treated with multidisciplinary therapy including radiotherapy.

Introduction: Metastatic ureteral tumors are difficult to diagnose pathologically. Treatment is only available for the primary disease, and prognosis is generally poor. Case presentation: A 63-year-old patient with a history of gastric cancer presented with asymptomatic right-sided hydronephrosis. Ureteroscopic examination revealed tissue in the ureter consistent with gastric cancer. The lesion was localized, and the patient was treated with chemotherapy and radiotherapy as part of a multidisciplinary treatment. The prognosis was better than in other reports. To the best of our knowledge, this is the first case of a patient with metastatic gastric cancer who received multidisciplinary treatment including radiotherapy and had a good prognosis. Conclusion: In cases where a localized metastatic ureteral tumor cannot be ruled out, ureteroscopy is an effective therapeutic strategy.

A case of emphysematous pyelonephritis caused by the hypermucoviscosity phenotype of Klebsiella pneumoniae.

A 70-year-old woman presented to our hospital with 38.2 °C fever. She was diagnosed with high-risk emphysematous pyelonephritis caused by string test-positive Klebsiella pneumoniae and treated with multidisciplinary therapy. The patient developed pyogenic spondylitis during the course of the disease. This is the first reported case of emphysematous pyelonephritis caused by the hypermucoviscosity phenotype of K. pneumoniae and the second reported case of pyogenic spondylitis. The hypermucoviscosity phenotype of K. pneumoniae should be considered as an etiologic agent of emphysematous pyelonephritis.

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04).

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC). METHODS: In this multicenter phase II clinical trial (January 2019-July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples. RESULTS: In total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6-64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1-86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1-61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples. CONCLUSION: Nab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

Doublet or Triplet Antiemetic Prophylaxis for Nausea and Vomiting Induced by Trastuzumab Deruxtecan: an Open-Label, Randomized, and Multicenter Exploratory Phase 2 Study.

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.

20-Gbit/s directly modulated photonic crystal nanocavity laser with ultra-low power consumption.

We have demonstrated an ultracompact buried heterostructure photonic crystal (PhC) laser, consisting of an InGaAsP-based active region (5.0 x 0.3 x 0.15 µm3) buried in an InP layer. By employing a buried heterostructure with an InP layer, we can greatly improve thermal resistance and carrier confinement. We therefore achieved a low threshold input power of 6.8 µW and a maximum output power in the output waveguide of -10.3 dBm by optical pumping. The output light is effectively coupled to the output waveguide with a high external differential quantum efficiency of 53%. We observed a clear eye opening for a 20-Gbit/s NRZ signal modulation with an absorbed input power of 175.2 µW, resulting in an energy cost of 8.76 fJ/bit. This is the smallest reported energy cost for any type of semiconductor laser.

All-optical memory based on injection-locking bistability in photonic crystal lasers.

We have demonstrated an all-optical memory by using InGaAsP/InP buried heterostructure photonic crystal (BH-PhC) lasers. We achieved distinct optical injection locking bistability in an ultra-compact active region (4 × 0.3 × 0.16 µm3) with only 25 µW pump power in the PhC waveguide, which is two orders less than previously reported optical memories based on other bistable semiconductor lasers. Dynamic memory operations were achieved with pump power of 100 µW and switching power of 22 µW and 71 µW in the PhC waveguide. Fast switching times of about 60 ps were achieved. To the authors' best knowledge, this is the first demonstration of PhC laser-based all-optical memory.

40-Gb/s directly-modulated photonic crystal lasers under optical injection-locking.

CMOS integrated circuits (IC) usually requires high data bandwidth for off-chip input/output (I/O) data transport with sufficiently low power consumption in order to overcome pin-count limitation. In order to meet future requirements of photonic network interconnect, we propose an optical output device based on an optical injection-locked photonic crystal (PhC) laser to realize low-power and high-speed off-chip interconnects. This device enables ultralow-power operation and is suitable for highly integrated photonic circuits because of its strong light-matter interaction in the PhC nanocavity and ultra-compact size. High-speed operation is achieved by using the optical injection-locking (OIL) technique, which has been shown as an effective means to enhance modulation bandwidth beyond the relaxation resonance frequency limit. In this paper, we report experimental results of the OIL-PhC laser under various injection conditions and also demonstrate 40-Gb/s large-signal direct modulation with an ultralow energy consumption of 6.6 fJ/bit.

[The 9th international conference of the asian clinical oncology society in Japan after a twenty year interval--what is the standpoint of Japan in Asia ?].

The 9th International Conference of the Asia Clinical Oncology Society(ACOS)was held at Gifu Grand Hotel, Gifu Japan on August 25, 26, and 27 2010. The Society was established in Osaka, Japan, in October 1991. Meeting have been held every two years, starting in Osaka, and then to Bangkok, Kunming, Bali, Taipei, Seoul, Beijing, Manila, and now to Gifu. There was a twenty year interval in Japan between meetings in Osaka and Gifu. The main theme of the 9th ACOS was titled "Talk to the Worldwide from Asia," and the sub-theme was titled "Multidisciplinary Treatment for Asian Cancer Patients "For this 9th ACOS, we gathered 42 councilors from Asian countries to serve on the ACOS committee and 365 doctors from Japan to serve on a local organizing committee. For congress program, we scheduled 161 special sessions for the president's lectures, key note lectures, special lectures, educational lectures, symposium, workshop, luncheon seminars, etc. We received about 500 abstracts for oral or poster presentations; among them, 140 abstracts came from Asian countries. As for speakers, 475 were from Japan, 85 from Korea, 34 from Taiwan, 27 from China, over 10 from India, Indonesia, Viet Nam, USA, and other countries. Finally a total of 704 speakers were gathered from 20 countries(from the outside Asia; UK, France, Germany, and Australia). The total number of registered investigators was 1, 136, and the total number of participants, including our congress staffs, volunteers, neighborhood doctors, Gifu citizens, patients, etc., was over 1, 500. In this 9th ACOS we discussed some new ideas, such as Asian cancer statistics, mission, vision and core values of ACOS, new anti-cancer drugs developed from Japan(TS-1 and Xeloda), Inter group clinical trials among Asian countries, less invasive surgery using endoscopic assisted operation, Asian traditional medicine, open workshops with citizens, etc. Moreover, we published a commemorative book entitled" Recent Advances of Cancer in Asian Countries.

All-optical wavelength-routing switch with monolithically integrated filter-free tunable wavelength converters and an AWG.

We present a compact 4x8 wavelength-routing switch that monolithically integrates fast tunable wavelength converters (TWCs) and an arrayed-waveguide grating (AWG) for optical packet switching. The TWC consists of a double-ring-resonator-coupled tunable laser which allows rapid and stable switching, and an optical gate based on a parallel amplifier structure which prevents an input optical signal from being routed through the AWG (filter-free operation). A deep-ridge waveguide technology, employed for the AWG and ring resonators, facilitates the fabrication of the switch and makes the device compact. The filter-free TWCs achieve low crosstalk of the input optical signal of less than -22 dB. The wavelength routing operation of a non-return-to-zero (NRZ) signal at 10 Gbit/s is achieved with a switching time of less than 5 ns.

Retroperitoneal abscess due to Achromobacter xylosoxidans presenting as femoral pain.

We describe the case of a 65-year-old patient who presented to our hospital with femoral pain. MRI and CT scan revealed a retroperitoneal abscess. We treated him with early surgical drainage and antibiotic treatment. The urine and draining pus cultures grew Achromobacter xylosoxidans. An iliopsoas abscess may show unique signs depending on its volume. To the best of our knowledge, this is the second reported case of retroperitoneal abscesses due to A. xylosoxidans. Surgical drainage appears to be effective when abscess is large.

Successful catheter ablation to accessory atrioventricular pathway as cardiac resynchronization therapy in a patient with dilated cardiomyopathy.

A 55-year-old man was admitted to our hospital for further examination of the abnormalities of chest X-ray and electrocardiogram. He was diagnosed with type B Wolff-Parkinson-White syndrome concomitant with dilated cardiomyopathy. Despite the medical therapy using enalapril and carvedilol for 20 months, his cardiac performance and brain natriuretic peptide (BNP) were not so improved. Because asynchronous septal motion caused by pre-excitation through a right-sided accessory pathway (AP) might deteriorate his cardiac performance, catheter ablation to the AP was performed. Successful procedure after 17 months improved left ventricular (LV) contraction, reduced LV volume, and decreased mitral regurgitation and BNP.

Skewing the Th cell phenotype toward Th1 alters the maturation of tumor-infiltrating mononuclear phagocytes.

Mononuclear phagocytes (MPCs) at the tumor site can be divided into subclasses, including monocyte-lineage myeloid-derived suppressor cells (MDSCs) and the immunosuppressive tumor-infiltrating macrophages (TIMs). Cancer growth coincides with the expansion of MDSCs found in the blood, secondary lymphoid organs, and tumor tissue. These MDSCs are thought to mature into macrophages and to promote tumor development by a combination of growth-enhancing properties and suppression of local antitumor immunoresponses. As little is known about either subset of MPCs, we investigated MPCs infiltrating into murine adenocarcinoma MCA38 tumors. We found that these MPCs displayed immunosuppressive characteristics and a MDSC cell-surface phenotype. Over 70% of the MPCs were mature (F4/80(+)Ly6C(-)) macrophages, and the rest were immature (F480(+) Ly6C(+)) monocytes. MPC maturation was inhibited when the cells infiltrated a tumor variant expressing IL-2 and soluble TNF type II receptor (sTNFRII). In addition, the IL-2/sTNFRII MCA38 tumor microenvironment altered the MPC phenotype; these cells did not survive culturing in vitro as a result of Fas-mediated apoptosis and negligible M-CSFR expression. Furthermore, CD4(+) tumor-infiltrating lymphocytes (TILs) in wild-type tumors robustly expressed IL-13, IFN-gamma, and GM-CSF, and CD4(+) TILs in IL-2/sTNFRII-expressing tumors expressed little IL-13. These data suggest that immunotherapy-altered Th cell balance in the tumor microenvironment can affect the differentiation and maturation of MPCs in vivo. Furthermore, as neither the designation MDSC nor TIM can sufficiently describe the status of monocytes/macrophages in this tumor microenvironment, we believe these cells are best designated as MPCs.

Malignant lymphoma of the bladder with bilateral hydronephrosis.

Lymphoma of the urinary bladder is uncommon, and upper urinary tract obstruction due to lymphoma is rare. Herein, we report a case of malignant lymphoma of the bladder with bilateral hydronephrosis in a 67-year-old female who presented with oliguria. Ultrasonography and computed tomography demonstrated a thickened posterior bladder wall and bilateral hydronephrosis. Whole-body positron emission tomography-computed tomography revealed abnormal accumulation in the right iliac internal lymph nodes. Trans-urethral bladder biopsy led to a histopathological diagnosis of non-Hodgkin diffuse large B-cell malignant lymphoma of the bladder. After bilateral nephrostomy, the patient was treated with six cycles of combination chemotherapy including rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisolone (R-CHOP) and two cycles of rituximab alone. Complete remission was maintained during the 3 years of follow-up.

Female urethral diverticulum containing large calculi.

Urinary stones in female urethral diverticulum are rarely seen. We report a 79-year-old woman who presented with irritative lower urinary tract symptoms and vaginal cystocele with incontinence. The urethral stones in the diverticulum were successfully extracted through the trans-urethral route and anterior tension-free vaginal mesh was applied one month later. The patient has been well, with no lower urinary symptoms or incontinence for 4 months.

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer.

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC.

Survival Outcomes of Retreatment with Trastuzumab and Cytotoxic Chemotherapy for HER2-Positive Recurrent Patients With Breast Cancer Who Had Been Treated with Neo/adjuvant Trastuzumab Plus Multidrug Chemotherapy: A Japanese Multicenter Observational Study.

BACKGROUND: There are little data on the usefulness of trastuzumab (TZM) retreatment as the first-line treatment for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer recurrence after perioperative treatment with TZM. AIM: To clarify the outcome and safety of TZM retreatment in patients with recurrent HER2-positive breast cancer. METHOD: An observational study was conducted on patients who relapsed after primary systemic therapy with TZM using the central registration system. The primary end point was progression-free survival (PFS). Secondary end points consisted of the response rate, overall survival (OS), and safety. RESULT: In total, 34 patients were registered between July 2009 and June 2012. The median follow-up time was 23.7 months (2-24 months). The 1- and 2-year PFS rates were 46.9% (95% confidence interval (95% CI): 29.2%-62.9%) and 29.8% (95% CI: 15.0%-46.3%), respectively (median 10.6 months). The median PFS time for patients receiving TZM combined with CTx was 13.9 months. The 1-and 2-year OR rates were 93.9 (95% CI: 77.9%-98.4%) and 84.8% (95% CI: 67.4%-93.4%). Trastuzumab-induced grade 3/4 adverse events were not observed. CONCLUSIONS: This study suggests that the PFS and OS in Japanese patients who relapsed after perioperative TZM therapy improved or were similar to those in previous reports. Differences in patient backgrounds and treatments must be considered when interpreting the results. Trastuzumab should be used combination with CTx and/or HTx for retreatment. Retreatment with TZM is safe.Trial registration: UMIN000002738.