"Loss of Bone Signal" on 99mTc-Labeled Pyrophosphate Scintigraphy in a Patient With Wild-Type Transthyretin Amyloidosis.

ABSTRACT: 99mTc-3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy and 99mTc-pyrophosphate (PYP) scintigraphy are highly sensitive modalities for imaging both myocardial and extracardiac amyloid transthyretin in patients with wild-type transthyretin (ATTRwt) amyloidosis. "Loss of bone signal" on planar imaging of 99mTc-DPD scintigraphy, in which the tracer uptake in bone is obscured by marked tracer uptake in the overlying skeletal muscles, is reported. However, this phenomenon has not yet been documented on 99mTc-PYP scintigraphy. We describe an 89-year-old woman with ATTRwt amyloidosis in whom "loss of bone signal" together with marked tracer uptake into the skeletal muscles was clearly demonstrated on 99mTc-PYP scan.

Discovery of a Plant 14-3-3 Inhibitor Possessing Isoform Selectivity and In Planta Activity.

Synthetic modulators for plant 14-3-3s are promising chemical tools both for understanding the 14-3-3-related signaling pathways and controlling plant physiology. Here, we describe a novel small-molecule inhibitor for 14-3-3 proteins ofArabidopsis thaliana. The inhibitor was identified from unexpected products in DMSO stock solution of an in-house chemical library. Mass spectroscopy, mutant-based analyses, fluorescence polarization assays, and thermal shift assaysrevealed that the inhibitor covalently binds to an allosteric site of 14-3-3 with isoform selectivity. Moreover, infiltration of the inhibitor to Arabidopsis leaves suppressed the stomatal aperture. The inhibitor should provide a new insight into the design of potent and isoform-selective 14-3-3 modulators.

Asymptomatic Pneumoperitoneum With a Large Amount of Gas Appeared During Endoscopic Ultrasound-Guided Biliary Drainage.

We report a case in which a large amount of intraperitoneal free gas developed during endoscopic ultrasound-guided biliary drainage with the rendezvous technique. A 62-year-old woman presented with obstructive jaundice caused by a pancreatic head tumor. Endoscopic retrograde cholangiopancreatography was attempted but failed due to difficulty cannulating the bile duct. Consequently, endoscopic ultrasound-guided hepaticogastrostomy was performed using a fully covered metal stent. Subsequently, the rendezvous technique was employed to access the biliary system and perform an endoscopic sphincterotomy. Finally, a fully covered metal stent was placed transpapillary. Fluoroscopic imaging during the procedure revealed a large amount of gas between the liver and diaphragm. Despite the pneumoperitoneum, the patient experienced no abdominal pain or fever. One week later, a computed tomography scan confirmed the disappearance of free air in the intraperitoneal cavity. The patient's subsequent clinical course remained uneventful, and she was discharged from the hospital. This case highlights the potential for pneumoperitoneum to develop during endoscopic ultrasound-guided biliary drainage, particularly when using the rendezvous technique. It is crucial to differentiate this finding from gastrointestinal perforation based on clinical presentation and imaging features.

Salivary gland-type cancers: cross-organ demographics of a rare cancer.

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

Relationship between abdominal circumference and the incidence of hyperuricemia in the general Japanese population.

In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; Ptrend < 0.001) and women (5.5 for tertile 1, 6.3 for tertile 2 and 11.9 for tertile 3; Ptrend < 0.001). Significant associations were identified after adjustment for potential confounders (men: Ptrend < 0.001; women: Ptrend = 0.014). In conclusion, both men and women with larger waist circumferences were at higher risks of subsequent hyperuricemia.

Parathyroid Hormone-Related Peptide-Producing Gallbladder Cancer Presenting With Humoral Hypercalcemia of Malignancy: A Case Report.

Humoral hypercalcemia of malignancy (HHM) is often reported in cancers derived from the squamous epithelium; however, there are very few reports of HHM in patients with gallbladder cancer. We report a case of a parathyroid hormone-related protein (PTHrP)-producing gallbladder cancer presenting with HHM. A 43-year-old woman presented with appetite loss, nausea, and brown-colored urine. Blood tests revealed that she had hypercalcemia, high serum bilirubin, and high serum parathyroid hormone. Contrast-enhanced computed tomography revealed a gallbladder tumor, liver metastasis, and bile duct obstruction caused by the gallbladder tumor in the hilar region. No bone metastasis was observed. Endoscopic retrograde cholangiopancreatography revealed pancreaticobiliary maljunction. Metal biliary stents were placed, and a transpapillary biopsy of the gallbladder tumor revealed a pathological diagnosis of adenocarcinoma. The patient was diagnosed with HHM due to gallbladder cancer with liver metastasis. Although her hypercalcemia and jaundice improved, her appetite loss and nausea did not improve. Subsequently, the patient developed disseminated intravascular coagulation, and her general condition gradually deteriorated. Due to her poor general condition, chemotherapy could not be administered. The patient died six weeks after visiting our hospital. Although rare, some gallbladder cancers cause HHM due to PTHrP production.

Phosphorylation of plasma membrane H+-ATPase Thr881 participates in light-induced stomatal opening.

Plasma membrane (PM) H+-ATPase is crucial for light-induced stomatal opening and phosphorylation of a penultimate residue, Thr948 (pen-Thr, numbering according to Arabidopsis AHA1) is required for enzyme activation. In this study, a comprehensive phosphoproteomic analysis using guard cell protoplasts from Vicia faba shows that both red and blue light increase the phosphorylation of Thr881, of PM H+-ATPase. Light-induced stomatal opening and the blue light-induced increase in stomatal conductance are reduced in transgenic Arabidopsis plants expressing mutant AHA1-T881A in aha1-9, whereas the blue light-induced phosphorylation of pen-Thr is unaffected. Auxin and photosynthetically active radiation induce the phosphorylation of both Thr881 and pen-Thr in etiolated seedlings and leaves, respectively. The dephosphorylation of phosphorylated Thr881 and pen-Thr are mediated by type 2 C protein phosphatase clade D isoforms. Taken together, Thr881 phosphorylation, in addition of the pen-Thr phosphorylation, are important for PM H+-ATPase function during physiological responses, such as light-induced stomatal opening in Arabidopsis thaliana.

The impact of vascular division sequence and epithelial-mesenchymal transition status on postoperative recurrence in lung adenocarcinoma.

BACKGROUND: The vascular division sequence in video-assisted thoracic surgery (VATS) lung resection is usually determined by the handling difficulty due to the limited surgical view through the scope. However, upfront pulmonary vein division is theoretically desirable to avoid tumor cells spreading by surgical manipulation. Epithelial-mesenchymal transition (EMT) is associated with poor prognosis and an increased number of circulating tumor cells. The purpose of this study is to evaluate the effect of vascular division sequence and EMT on postoperative recurrence. METHODS: We retrospectively investigated tissue microarrays of 282 lung adenocarcinomas surgically resected between 2001 and 2007. We excluded the cases with segmentectomy, wedge resection, dissemination, insufficient material for staining, or lack of medical records. The effect of vascular division sequence and clinicopathologic factors on recurrence was evaluated in 195 cases. RESULTS: The upfront pulmonary vein division (V-first) was performed in 60 patients, and the upfront pulmonary artery division (A-first) was performed in 135 patients. The recurrence was observed in 67 patients (13 in V-first and 54 in A-first). Epithelial-mesenchymal transition activation was observed in 104 patients. Multivariable analysis with 195 patients revealed that lymph node metastasis and pleural invasion were risk factors for the recurrence. The stratified multivariable analysis showed that vascular division sequence (A-first) was a risk factor only in the EMT-negative group (91 patients). In the EMT-negative subset, the 5-year relapse-free survival rate was significantly lower in the A-first group than the V-first group (72.6% vs. 92.2%, p = 0.0136). CONCLUSIONS: The upfront pulmonary artery division might be a risk factor in patients without EMT activation.

Penetration of duodenal wall by proximal end of biliary straight plastic stent in a patient with ampullary carcinoma.

A 70-year-old woman presented to our hospital with abdominal discomfort. Gastrointestinal endoscopy revealed an ampullary tumor, while a biopsy revealed a pathological diagnosis of adenocarcinoma. No distant metastases were observed and neoadjuvant chemotherapy and surgical resection were planned. Shortly thereafter, she developed obstructive jaundice due to the ampullary carcinoma. The patient underwent endoscopic retrograde cholangiopancreatography, during which a straight plastic stent was placed in the bile duct. The patient was discharged without complications. Neoadjuvant chemotherapy was initiated. Two months later, she was readmitted for surgery while asymptomatic. Endoscopic retrograde cholangiopancreatography was scheduled to replace the stent with a nasobiliary drainage tube for the surgery. Endoscopic imaging revealed that the proximal end of the stent had penetrated the duodenum on the oral side of the ampullary carcinoma. The distal end of the stent was grasped with forceps and the stent was successfully removed. A catheter was inserted into the bile duct orifice and cholangiography was performed, which revealed that the distal bile duct and the duodenum had formed a fistula. A guidewire was placed in the bile duct via the papilla and a nasobiliary drainage tube was placed. After endoscopic retrograde cholangiopancreatography, the patient exhibited smooth progress without issue. Pancreaticoduodenectomy was performed on the fourth day after the nasobiliary drainage tube placement, and the patient's postoperative course was uneventful. The proximal end of a biliary stent penetrating the duodenal wall is an infrequent phenomenon. This case report highlights a rare but noteworthy adverse event associated with straight biliary plastic stent placement.

Dysbiosis of Gut Microbiota in Patients with Chronic Kidney Disease.

Objective The gut bacterial microbiota is altered in patients with chronic kidney disease (CKD). However, the bacterial composition at each stage of CKD is unclear in these patients, including those receiving renal replacement therapy. We herein report the changes in the gut microbiota among patients with CKD. Methods A total of 93 individuals were recruited for the study. Seventy-three patients had stage 3-5 CKD, including those receiving renal replacement therapy (CKD group), and 20 were age- and sex-matched controls (CKD stage 1-2). The gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol. Results At the genus level, the butyrate-producing bacteria Lachnospira, Blautia, Coprococcus, Anaerostipes, and Roseburia were more abundant in the control group (linear discriminant analysis score of >3) than in the CKD group. Lachnospira was more abundant in the control group than in patients with CKD stage 3a. Compared to the control group, multiplex butyrate-producing bacteria were deficient in patients with CKD stage 3b-5D, including in patients receiving renal replacement therapy. Conclusion Our findings highlight the fact that the gut bacterial composition, including butyrate-producing bacteria, deteriorates from CKD stage 3b. Even after renal replacement therapy, the bacterial composition did not change.

Technetium-99m-pyrophosphate imaging-based computed tomography-guided core-needle biopsy of internal oblique muscle in wild-type transthyretin cardiac amyloidosis.

BACKGROUND: Technetium-99m-pyrophosphate (99mTc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition. OBJECTIVE: This study aimed to assess the safety and efficacy of 99mTc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits. METHODS: Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99mTc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022. RESULTS: All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99mTc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results. CONCLUSION: In wild-type ATTR-CA, 99mTc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

Identification of the Vessels Causing Myocardial Ischemia by a Synthesized 18-Lead Electrocardiogram Obtained After the Master Two-Step Exercise Test in a Patient With Effort Angina.

A synthesized 18-lead electrocardiograph is a specialized technology that mathematically computes the virtual electrocardiographic waveforms of the right chest leads (V3R, V4R, and V5R) and posterior leads (V7, V8, and V9) based on a standard 12-lead electrocardiograph input without additional lead placement or techniques. Synthesized 18-lead electrocardiography is a useful test for the identification of the culprit coronary arteries in patients with ST-segment elevation myocardial infarction of the right ventricular wall or the posterior/lateral left ventricular wall, which are often missed on standard 12-lead electrocardiography. However, few studies have examined the usefulness of this modality during exercise stress testing. We present a case of a 78-year-old man with a two-month history of typical angina. The synthesized 18-lead electrocardiogram obtained just after the Master two-step exercise test revealed ST-segment shifts in multiple leads, including synthesized V4R, V5R, and V7-9 leads, and U-wave changes in some leads, including the synthesized V9 lead. The diagnosis of the culprit coronary arteries causing exercise-induced myocardial ischemia is discussed with reference to coronary angiographic findings. This modality could potentially increase the sensitivity and specificity for the detection of coronary artery disease and accurately pinpoint the site of the lesion. If an electrocardiograph can display a synthesized 18-lead electrocardiogram, it should be used when evaluating the waveform due to myocardial ischemia.

A case of lymphatic flow evaluation using indocyanine green fluorescence imaging for recurrence of anastomotic site after laparoscopic right hemicolectomy.

BACKGROUND: Anastomotic recurrence of colorectal cancer is rare, but reoperation improves prognosis. However, there is no clear evidence regarding the extent of dissection, and there are few reports on the details of surgery. We used intraoperative lymphatic flow imaging with indocyanine green (ICG) fluorescence as a reference to determine the range of additional resection. CASE PRESENTATION: The patient was a 75-year-old man who underwent laparoscopic right hemicolectomy and extracorporeal functional terminal anastomosis for ascending colon cancer 4 years ago. Histopathological examination revealed a well-differentiated tubular adenocarcinoma, T4aN0M0, pathological stageIIB. During follow-up, anemia was observed, and colonoscopy indicated anastomotic recurrence, so additional laparoscopic resection was performed. Intraoperatively, ICG was injected into the anastomotic site, and the operation proceeded under near-infrared light observation. Lymphatic vessels along the middle colonic artery were visualized down to the root of the vessel. Using this as an indicator, the vessel was ligated from the root. Using the fact that the lymphatic vessels were also depicted in the small intestinal mesentery on the oral side of the anastomosis as an indicator, the small intestine and mesentery were resected about 7 cm from the anastomosis. CONCLUSIONS: The optimal surgical approach for anastomotic recurrence of colorectal cancer has not been defined. Intraoperative ICG fluorescence imaging can provide images of lymphatic flow from the site of recurrence and may be an indicator of lymph node dissection in the case of anastomotic recurrence.

A Gluteus Medius Muscle Biopsy to Confirm Amyloid Transthyretin Deposition in Wild-type Transthyretin Cardiac Amyloidosis: A Report of Two Cases.

In patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), the uptake of the tracer on technetium-99m-labeled pyrophosphate (99mTc-PYP) scintigraphy, which indicates amyloid transthyretin (ATTR) per se, is often observed in skeletal muscles, such as the abdominal oblique and gluteal muscles. Among extracardiac biopsies for confirming ATTR deposition in ATTRwt-CA, a 99mTc-PYP imaging-based computed tomography (CT)-guided core needle biopsy of the internal oblique muscle has relatively high sensitivity. In some patients, the 99mTc-PYP uptake is more pronounced in the gluteal muscles than in oblique muscles. We herein report two cases of ATTRwt-CA in which a CT-guided biopsy of the gluteus medius muscle with 99mTc-PYP uptake confirmed the presence of ATTR deposits.

Safety of endoscopic ultrasound-guided fine-needle aspiration for pancreatic solid mass in the elderly: A single-center retrospective study.

AIM: There are few reports on the safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the elderly. In this study, we investigated the safety of EUS-FNA for pancreatic solid masses in patients aged ≥80 years. METHODS: This is a single-center retrospective study. A total of 600 patients with pancreatic solid masses who underwent EUS-FNA under midazolam-based sedation at our institution between September 2016 and December 2022 were enrolled in this study. Eligible patients were divided into two groups: an elderly group aged ≥80 (n = 84), as well as a nonelderly group aged ≤79 (n = 516). These two groups were compared. RESULTS: The elderly group required significantly fewer midazolam doses for sedation (P < 0.001). Adverse events occurred in eight patients (1.3%), including one (1.2%) and seven (1.4%) in the elderly and nonelderly groups, respectively (P = 0.90). There were no cases of early adverse events in the elderly group and six cases (1.2%) in the nonelderly group (P = 0.32). There was one case of late adverse events in both the elderly and nonelderly groups (P = 0.14), and both were needle tract seeding. There was no significant difference between the two groups in the proportion of cases in which percutaneous oxygen saturation decreased to ≤90% during the EUS-FNA. CONCLUSIONS: Our analysis suggests that EUS-FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years. Geriatr Gerontol Int 2023; 23: 836-841.

Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD).

OBJECTIVE: We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population. SETTING: Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan. PARTICIPANTS: A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3-16 U/L in men and 3-13 U/L in women), group 2 (17-21 U/L in men and 14-16 U/L in women), group 3 (22-29 U/L in men and 17-22 U/L in women) and group 4 (30-428 U/L in men and 23-268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies). RESULTS: After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p<0.001 for trend). This association was significant after adjustment for other risk factors including age, sex, obesity, hypertension, dyslipidaemia, smoking, current daily alcohol intake and regular exercise (p<0.001 for trend). Comparable associations were observed between men and women (p=0.459 for interaction). CONCLUSION: Serum ALT levels were associated with future development of diabetes in the general Japanese population.

Sequential administration of PD­1 inhibitor and cetuximab causes pneumonia.

Severe drug-induced lung injury (DLI) has been reported to be associated with sequential administration of osimertinib, a third-generation tyrosine kinase inhibitor, following a programmed cell death ligand 1 (PD-L1) inhibitor. However, the relationship of sequential treatment with an anti-epidermal growth factor receptor (EGFR) antibody and PD-1 inhibitor with the risk of DLI remains to be elucidated. The present study conducted a retrospective review of the medical records of a total of 179 patients with head and neck cancer who had received treatment with cetuximab and/or a PD-1 inhibitor (nivolumab or pembrolizumab) at Chiba University Hospital (Chiba, Japan) between September 2014 and December 2020. The incidence of pneumonia and the clinical background characteristics of the patients were analyzed. The patients were classified into subgroups for analysis of the outcomes in this study: Patients who had received sequential, but not concurrent, cetuximab and PD-1 inhibitor treatment (Group C+P; n=43); patients who had received cetuximab-containing chemotherapy, but not a PD-1 inhibitor (Group C; n=101); and patients who had received PD-1 inhibitor-containing chemotherapy, but not cetuximab (Group P; n=35). The rates of DLI in the three groups were: Group C+P, 18.6%; Group C, 7.9%; and Group P, 11.4%. Prior use of ICI was not associated with any increase in the risk of DLI. DLI is seen frequently in patients receiving sequential PD-1 inhibitor and anti-EGFR antibody therapy.