Iatrogenic cerebral amyloid angiopathy in older adults.

BACKGROUND AND PURPOSE: An increasing number of cases of iatrogenic cerebral amyloid angiopathy (CAA) have now been reported worldwide. Proposed diagnostic criteria require a history of medical intervention with potential for amyloid-ß transmission, for example those using cadaveric dura mater or requiring instrumentation of the brain or spinal cord. Clinical presentation occurs after an appropriate latency (usually three or four decades); to date, most patients with iatrogenic CAA have had 'early-onset' disease (compared to sporadic, age-related, CAA), as a consequence of childhood procedures. RESULTS: We describe five cases of possible iatrogenic CAA in adults presenting in later life (aged 65 years and older); all had prior neurosurgical interventions and presented after a latency suggestive of iatrogenic disease (range 30-39 years). Use of cadaveric dura mater was confirmed in one case, and highly likely in the remainder. CONCLUSION: The presentation of iatrogenic CAA in older adults widens the known potential spectrum of this disease and highlights the difficulties of making the diagnosis in this age group, and particularly in differentiating iatrogenic from sporadic CAA. Increased vigilance for cases presenting at an older age is essential for furthering our understanding of the clinical phenotype and broader implications of iatrogenic CAA.

Fibrinogen Aα-chain amyloidosis outbreaks in Japanese squirrels (Sciurus lis): a potential disease model.

Fibrinogen Aα-chain amyloidosis is a hereditary systemic amyloidosis characterized by glomerular amyloid depositions, which are derived from the fibrinogen Aα-chain variant in humans. Despite its unique pathology, the pathogenic mechanisms of this disease are only partially understood. This is in part because comparative pathological studies on fibrinogen Aα-chain amyloidosis are currently unavailable as there is a lack of reported cases in animals other than humans. In this study, mass spectrometry-based proteomic analyses of Japanese squirrels (Sciurus lis) that died in five Japanese zoos showed that they developed glomerular-associated fibrinogen Aα-chain amyloidosis with an extremely high incidence rate (29/38 cases, 76.3%). The condition was found to be age-dependent in the Japanese squirrels, with 89% of individuals over 4 years of age affected. Mass spectrometry revealed that the C-terminal region of the fibrinogen Aα-chain was involved in amyloidogenesis in Japanese squirrels as well as humans. No gene variations were identified between amyloid-positive and amyloid-negative squirrels, which contrasted with the available data for humans. The results indicate that fibrinogen Aα-chain amyloidosis is a senile amyloidosis in Japanese squirrels. The results have also provided comparative pathological support that the amyloidogenic C-terminal region of the fibrinogen Aα-chain is involved in the characteristic glomerular pathology, regardless of the animal species. This study elucidates the potential causes of death in Japanese squirrels and will contribute to future comparative pathological studies of fibrinogen Aα-chain amyloidosis. © 2023 The Pathological Society of Great Britain and Ireland.

Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review.

Noonan syndrome-related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11 ; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.

Computed tomographic characteristics of testicular teratoma in a cat.

A 5-year-old intact male mixed-breed cat weighing 4.5 kg was referred to our hospital with a left testicular mass. CT revealed mild heterogeneous contrast enhancement and calcification in the testicular mass. A well-defined, contrast-enhancing, multiloculated mass with fluid-filled areas was extended from the testicular mass in the scrotum to the caudal aspect of the left kidney. The abdominal mass extended to the right crus of the diaphragm, and the gastrointestinal tract was compressed dorsally. Histopathology was consistent with teratoma. Characteristic CT findings in a feline testicular teratoma may include calcification and cystic areas.

[Investigation of the safety and usefulness of a renal biopsy for older elderly patients ≥75 years old].

AIM: We herein report the safety and usefulness of a kidney biopsy in older elderly patients (≥75 years old). METHODS: A retrospective observational study was conducted in older elderly patients who had received a renal biopsy at the Department of Nephrology, Shimane University Hospital, from January 1, 2008, to December 31, 2018. The native renal biopsy results of 52 later-stage elderly patients were analyzed (29 men and 23 women). RESULTS: The most common indication for a renal biopsy was nephrotic syndrome (n = 22), followed by rapidly progressive glomerulonephritis (n = 12) and asymptomatic urinary abnormalities (n = 12). The most common pathological diagnosis was membranous nephropathy (n = 12), followed by ANCA-associated nephritis (n= 8), minimal change nephrotic syndrome (6 case), membranoproliferative glomerulonephritis (n = 5), IgA nephropathy (n = 4), and diabetic nephropathy (n = 3). The concordance rate between the clinical and pathological diagnoses was 53.8%. The only complication of the renal biopsy was hemorrhaging requiring blood transfusion (1 patient; 1.9%). The hemoglobin level decreased by 0.5±0.05 d/dL after the biopsy. CONCLUSION: The rate of serious complications associated with a renal biopsy was comparable to that in previous reports in younger patient. Renal biopsies can therefore be safely performed even in older elderly patients. The concordance rate of the clinical and pathological diagnoses was about 50%. Therefore, renal biopsies should be performed in older elderly patients when necessary.

Assessment of tumor enhancement by contrast-enhanced CT in solid tumor-bearing dogs treated with toceranib phosphate.

In humans, contrast-enhanced CT (CECT) has been used to indirectly assess the antiangiogenic effects demonstrated by a number of tyrosine kinase inhibitors. This retrospective, cross-sectional study aimed to quantitatively evaluate changes in tumor contrast-enhancement (CE) using CECT in solid tumor-bearing dogs treated with toceranib phosphate (TOC). The changes in tumor size and CE were measured using the Hounsfield unit (HU) scale in CECT images before TOC treatment and between 30 and 90 days after initiating the treatment. Among the 36 dogs treated with TOC, eight (22.2%) showed a partial response, 22 (61.1%) showed stable disease, and six (16.7%) showed progressive disease. Thirty (83.3%) of 36 dogs showed a decrease in tumor CE (median: -20%, range: -1% to -48%) after initiating the treatment. The results indicated that tumor CE and size changes were observed in tumor-bearing dogs that were treated with TOC; however, tumor CE was not significantly correlated with tumor regression. We suggest that these results could serve as pilot data to evaluate the antiangiogenic effects associated with TOC.

A Tightly Stretched Ultralong Supramolecular Multiporphyrin Array Propagated by Double-Strand Formation.

A shape-programmed linearity through supramolecular polymerization is demonstrated by a step-growth double-strand formation of a telechelic oligomeric porphyrin array in which two alternating pyridyl-porphyrin sequenced units are held together by self-complementary ligand-to-metal coordination. The stiff rod-like structure and sufficiently large binding constant of the double-strand unit considerably extended a supramolecular array in the one dimension, which produced a tightly stretched string with a length that exceeded several micrometers.

Group 14 Dithienometallole-Linked Ethynylene-Conjugated Porphyrin Dimers.

The considerably conjugated π systems of the group 14 dithienometallole-linked ethynylene-conjugated porphyrin dimers (1Ms) were described based on comprehensive experimental and theoretical studies. The electronic absorption spectra of 1M displayed a large splitting in the Soret band and a red-shifted Q-band, indicating that the dithienometallole spacer was effective in facilitating the porphyrin-porphyrin electronic coupling. Torsional planarization behaviors of 1M were observed in the time-resolved fluorescence spectra. Density functional theory (DFT) calculations revealed that the dithienometallole spacer is an ideal partner for the ethynylene-conjugated porphyrin to produce fully delocalized highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels due to their similar HOMO and LUMO levels. Finally, 1M exhibited a strong propensity for the quinoidal-cummulenic conjugation in the dithienometallole spacer when in a photoexcited state.

Use of computed tomography to evaluate pelvic canal in cats.

The objective of this study was to establish an evaluation technique for the feline pelvic cavity using computed tomography (CT). Client-owned cats with a normal pelvis (n = 50) or pelvic stenosis (n = 3) were included. We categorized pelvic CT images in the normal pelvis group into two types according to pelvic cavity shape, then calculated the sacral index (SI), pelvic canal area (PCA), and PCA/sacral width index (PSI). The reference intervals of these variables were determined based on the results in the normal pelvis group. In the normal pelvis group, the PSI, unlike the SI and PCA, was not affected by body weight. In addition to high intraobserver and interobserver reproducibilities, the PSI showed no significant differences according to pelvic cavity shape. However, the SI exhibited significant differences among pelvic cavity shapes. In the stenosis group, the postoperative PSI in all cats was within the reference interval. However, the postoperative SI in one case was lower than the reference interval. The PSI may become a new method for evaluation of the pelvic cavity, including the pelvic floor.

A case of organizing pneumonia in rearranged during transfection fusion-positive lung adenocarcinoma treated with selpercatinib.

Selpercatinib is the first targeted therapy for rearranged during transfection (RET) fusion-positive unresectable non-small-cell lung cancer (NSCLC). The main adverse effects of selpercatinib include hypertension, liver dysfunction, diarrhea, and QT prolongation on electrocardiograms. However, instances of drug-induced interstitial lung disease (DI-ILD) are infrequently reported. We describe the first case of a patient with RET fusion-positive NSCLC treated with selpercatinib who developed DI-ILD, confirmed pathologically. The patient, a 72-year-old woman, initiated selpercatinib treatment following the postoperative recurrence of lung adenocarcinoma. After 15 months of treatment, computed tomography scans revealed multiple infiltrates and ground-glass opacities in both lungs. A thoracoscopic lung biopsy identified organizing pneumonia, attributed to DI-ILD caused by selpercatinib. Although she was asymptomatic, the patient's selpercatinib treatment was discontinued, leading to a gradual improvement in the lung infiltrates. Despite the lack of detailed reports, DI-ILD with selpercatinib represents a potentially serious adverse event and should be approached with caution.

Efgartigimod Successfully Ameliorated Acute Exacerbation of Myasthenia Gravis with Anti-muscle-specific Kinase Antibodies.

We herein report two patients with anti-muscle-specific kinase (MuSK) antibody-positive myasthenia gravis who experienced rapid deterioration of weakness, particularly respiratory muscle weakness, necessitating non-invasive positive pressure ventilation (NIPPV) and were treated with efgartigimod. After treatment initiation, a rapid reduction in IgG levels and recovery from clinical symptoms were observed. NIPPV was no longer required two to three weeks after the first infusion of efgartigimod. These findings suggest that the reduction of IgG levels using efgartigimod is a good treatment option in patients with myasthenia gravis positive for anti-MuSK antibodies, even during the acute phase of the disease.

Liposome-encapsulated progesterone efficiently suppresses B-lineage cell proliferation.

Progesterone suppresses several ancient pathways in a concentration-dependent manner. Based on these characteristics, progesterone is considered a candidate anticancer drug. However, the concentration of progesterone used for therapy should be higher than the physiological concentration, which makes it difficult to develop progesterone-based anticancer drugs. We previously developed liposome-encapsulated progesterone (Lipo-P4) with enhanced anticancer effects, which strongly suppressed triple-negative breast cancer cell proliferation in humanized mice. In this study, we aimed to clarify whether Lipo-P4 effectively suppresses the proliferation of B-lineage cancer cells. We selected six B-cell lymphoma and two myeloma cell lines, and analyzed their surface markers using flow cytometry. Next, we prepared liposome-encapsulated progesterone and examined its effect on cell proliferation in these B-lineage cancer cells, three ovarian clear cell carcinoma cell lines, two prostate carcinoma cell lines, and one triple-negative breast cancer adenocarcinoma cell line. Lipo-P4 suppressed the proliferation of all cancer cell lines. All B-lineage cell lines, except for the HT line, were more susceptible than the other cell types, regardless of the expression of differentiation markers. Empty liposomes did not suppress cell proliferation. These results suggest that progesterone encapsulated in liposomes efficiently inhibits the proliferation of B-lineage cells and may become an anticancer drug candidate for B-lineage cancers.

C-X-C chemokine receptor type 4 and cytokine expressions in cows of a dairy herd with high prevalence of calves persistently infected with bovine viral diarrhea virus.

Animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) play an important role in the spread of BVDV. Alteration of maternal C-X-C chemokine receptor type 4 (CXCR4) expression has been suspected as closely concerned with the production of PI calves. It is not clear what the influence of CXCR4 response to the prevalence of PI calves. We have previously reported a dairy herd with high prevalence of PI calves within a short period having a single origin of infection. CXCR4 and cytokine expressions in cows of this herd were investigated. There were no significant differences in CXCR4 and cytokine expressions between the dams of PI calves and the dams of non PI calves in the herd. In the comparison among the herds, CXCR4 expressions in the PI producing herds were significantly lower than the BVDV-free herd. Moreover, CXCR4 expressions in the high prevalence herd and the low prevalence herd were similar. These findings among herds corresponded with the previously reported experimental production of persistent infection with BVDV in cows. Based on the cytokine profile of these herds, IL-10 was significantly higher in the high prevalence herd and the BVDV-free herd. The combination of low expression of CXCR4 and high expression of IL-10 might be closely concerned with some bias for the production of PI calves.

Reconstruction of convex urethral stoma in a cat with prepubic urethrostomy.

An intact, male mixed-breed cat approximately 3 months of age was referred to Iwate University Veterinary Teaching Hospital with dysuria that developed after a traffic accident. At the initial visit, a cystostomy tube was placed as a temporal urinary diversion. Antegrade urethrography revealed severe stenosis of the intrapelvic urethra. A prepubic urethrostomy (PPU) with formation of a convex urethral stoma was performed 22 days after the first visit. Twenty-four months after surgery, the cat could urinate smoothly in a standing position, although a small amount of intermittent leakage was observed immediately after getting up. There was no evidence of peristomal dermatitis. Therefore, the formation of a convex urethral stoma may effectively prevent peristomal dermatitis in cats who undergo PPU.

Ventral onlay graft urethroplasty using bladder mucosa in a cat with a urethral stricture.

A 3-year-old, 4.0 kg, intact male domestic shorthair cat presented with postoperative dysuria following urethral resection and anastomosis for urethral rupture. Retrograde urethrography revealed a stricture in the pelvic urethra. Urethroplasty with bladder mucosa was performed following a bilateral pubic-ischial osteotomy. The bladder wall was resected to harvest an appropriately sized bladder mucosa graft. The graft was placed over the urethral defect in patch fashion and stabilized with interrupted sutures. The cat was able to urinate normally with no evidence of lower urinary tract signs 2 year postoperatively. Therefore, urethroplasty with an onlay bladder mucosa graft may be a feasible alternative to prepubic or subpubic urethrostomy for the treatment of pelvic urethral stricture in cats.

IPC prediction of patent documents using neural network with attention for hierarchical structure.

International patent classifications (IPCs) are assigned to patent documents; however, since the procedure for assigning classifications is manually done by the patent examiner, it takes a lot of time and effort to select some IPCs from about 70,000 IPCs. Hence, some research has been conducted on patent classification with machine learning. However, patent documents are very voluminous, and learning with all the claims (the part describing the content of the patent) as input would run out of the necessary memory, even if the batch size is set to a very small size. Therefore, most of the existing methods learn by excluding some information, such as using only the first claim as input. In this study, we propose a model that considers the contents of all claims by extracting important information for input. In addition, we focus on the hierarchical structure of the IPC, and propose a new decoder architecture to consider it. Finally, we conducted an experiment using actual patent data to verify the accuracy of the prediction. The results showed a significant improvement in accuracy compared to existing methods, and the actual applicability of the method was also discussed.

Cystatin C as a Potential Blood Biomarker for Sarcoidosis: A Case Report.

Sarcoidosis is a multi-organ medical condition that is characterized by the formation of granulomas. We aimed to identify a correlation between each sarcoidosis blood biomarker and cystatin C (Cys-C) in sarcoidosis patients. We report a case of a 60-year-old man with sarcoidosis. The correlation between his Cys-C and each blood biomarker level and that between each blood biomarker and serum creatinine levels were determined using linear regression. Serum Cys-C correlated with each blood biomarker of sarcoidosis, while creatinine did not. These findings suggest that Cys-C is a potential blood biomarker for sarcoidosis.

Simultaneous bilateral spontaneous pneumothorax in a patient with anorexia nervosa.

Anorexia nervosa causes various complications accompanying weight loss and malnutrition. Although bilateral spontaneous pneumothorax (SBSP) is uncommon, caution is needed in anorexia nervosa because this complication can be fatal. We encountered a 17-year-old girl with SBSP from emphysematous pulmonary changes due to anorexia nervosa. She was hospitalized with SBSP during treatment for anorexia nervosa. Chest tube drainage was started on admission, but no improvement was achieved. Surgery was therefore performed. Lung lesions on surgical specimens demonstrated malnutrition-induced emphysematous changes, a risk factor for SBSP. Attention should be paid to the occurrence of SBSP during the clinical course of anorexia nervosa.