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Abstract Because of the water scarcity in many regions, different methods have been implemented to address this problem. The desalination technique is known as a practical solution among them. However, brine from the desalination process, which contains high concentrations of salts, minerals, and chemicals, will cause environmental harm to the sea, soil, and groundwater if it is not properly treated. Therefore, recovering critical resources from brine is essential for reducing brine disposal. This study aims to apply two hydrometallurgy systems, namely ion exchange and ionic liquid extraction, to circulate rubidium resources from brine. Dowex G26 resin was employed in the ion exchange system, and the adsorption isotherm model and saturated adsorption capacity were explored initially. The optimal parameters such as pH value, L/S ratio (liquid/solid), adsorption period, and adsorption temperature will then be investigated. In the ionic liquid extraction process, the t-BAMBP/C2mimNTf2 system (4-tert-Butyl-2-(α-methylbenzyl) phenol/1-ethyl-3-methylimidazolium bis(trifluoromethyls​ulfonyl)​imide) was used, and the parameters including pH value, concentrations of t-BAMBP, (O + I)/A ratio (organic + ionic liquid/aqueous), extraction time, and extraction temperature will be optimized as well. The results reveal that adsorption capacity and extraction efficiencies were 14.3 mg g− 1 and 86%, respectively. Furthermore, suitable reagents, including HCl and HNO3, were applied to desorb and strip rubidium from the Dowex G26 and t-BAMBP/C2mimNTf2 systems. To sum up, environmental hazards of desalination brine and rubidium resources can be reduced and recovered through the two different extraction systems.

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Objective: This study aims to investigate the relationship between body mass index (BMI) and molecular subtypes of endometrial carcinoma using an immunohistochemistry (IHC)-based classification approach. Methods: We analyzed a consecutive series of endometrial cancer cases undergoing surgical staging in southern Alberta (2019–2021). Molecular classification was determined through IHC-based molecular typing, incorporating p53 and mismatch repair (MMR), and further characterized with the addition of ER and PR. BMI associations with molecular classification were assessed using t-tests. Hormone receptor status was further examined in a separate cohort of MMRd endometrial cancer patients undergoing surgical staging at Foothills Medical Centre (Alberta, Canada). Results: Among 289 cases, comprising various histological subtypes, the pNSMP subtype exhibited the highest average BMI (33.93 kg/m2) compared to the p53 abnormal subtype (30.40 kg/m2, p = 0.02). The MMRd subtype had an average BMI of 33.22 kg/m2. While there were no significant BMI differences between FIGO grade 1 and grade 2/3 tumours in the pNSMP or MMRd, a trend toward higher BMI in grade 1 tumours versus grade 2/3 tumours in the MMRd was observed (p = 0.13). A separate cohort of 53 MMRd endometrial carcinomas revealed that FIGO grade 1 tumours were associated with higher BMI (p

ObjectivesOvarian carcinosarcoma (OCS) is a rare and lethal type of ovarian cancer. Despite its incredibly poor prognosis, it has received little research attention. In this study, we aim to evaluate the molecular features of OCS and elucidate their clinical significance.Study methodsWe examined 30 OCS by immunohistochemistry (IHC) and targeted panel sequencing collected from a single institution (2003–2013) as the initial molecularly characterized cohort (Cohort A). From November 2016 to April 2023, we collected an additional 67 OCS cases from three institutions across British Columbia and Alberta as the contemporary cohort (Cohort B) for clinical correlation. The Kaplan–Meier method was used to estimate overall and progression-free survival, and differences in survival rates were compared using the log-rank test. All tests were two-sided. A p-value of less than 0.05 was considered statistically significant.ResultsThe majority of OCS (82%) in the initial Cohort A were p53-mutated, and the carcinomatous component displayed the histological and molecular features of a high-grade tubo-ovarian serous carcinoma (HGSC-like). In a minority of OCS, the epithelial components were characteristics of endometrioid or clear cell carcinomas, and IHC staining was wild type for p53. In the contemporary Cohort B, we observed the same histological findings related to the p53 IHC staining pattern. The median overall survival of the p53-mutated HGSC-like OCS (47 patients) was significantly higher (43.5 months) compared with that of the p53 wild-type OCS (10 patients, 8.8 months; P < 0.01). Pathogenic BRCA1/2 germline/somatic mutations were observed in 7 patients (17.5%) of HGSC-like OCS, and all these patients were alive at 3 years from diagnosis compared to a 51% 3-year survival among the patients with BRCA1/2 wild-type HGSC-like OCS (33 patients) (p = 0.022). Majority of patients (6/7) with BRCA1/2-mutated OCS received poly (ADP-ribose) polymerase inhibitor as maintenance therapy in this cohort.ConclusionsMost OCSs have a morphologic and molecular profile resembling HGSC; however, some OCSs display a molecular profile that suggests origin through non-serous oncogenic pathways. This molecular distinction has both prognostic and treatment (predictive) implications. These findings underscore the importance of routine p53 IHC testing on all OCS and BRCA1/2 testing on p53-mutated OCS.

Abstract Mesonephric‐type (or ‐like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four‐marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four‐marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376–0.727) with the integration of the four‐marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first‐line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62–5.85; p

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

Abstract Although acid‐sensing ion channels (ASICs) are proton‐gated ion channels responsible for sensing tissue acidosis, accumulating evidence has shown that ASICs are also involved in neurosensory mechanotransduction. However, in contrast to Piezo ion channels, evidence of ASICs as mechanically gated ion channels has not been found using conventional mechanoclamp approaches. Instead, ASICs are involved in the tether model of mechanotransduction, with the channels gated via tethering elements of extracellular matrix and intracellular cytoskeletons. Methods using substrate deformation‐driven neurite stretch and micropipette‐guided ultrasound were developed to reveal the roles of ASIC3 and ASIC1a, respectively. Here we summarize the evidence supporting the roles of ASICs in neurosensory mechanotransduction in knockout mouse models of ASIC subtypes and provide insight to further probe their roles in proprioception.

Abstract Proprioceptors are non‐nociceptive low‐threshold mechanoreceptors. However, recent studies have shown that proprioceptors are acid‐sensitive and express a variety of proton‐sensing ion channels and receptors. Accordingly, although proprioceptors are commonly known as mechanosensing neurons that monitor muscle contraction status and body position, they may have a role in the development of pain associated with tissue acidosis. In clinical practice, proprioception training is beneficial for pain relief. Here we summarize the current evidence to sketch a different role of proprioceptors in ‘non‐nociceptive pain’ with a focus on their acid‐sensing properties.

Abstract Background Pathological fracture of the humerus causes severe pain, limited use of the hand, and decreased quality of life. This study aimed to compare the outcomes of intramedullary nailing and locking plate in treating metastatic pathological fractures of the proximal humerus. Methods This retrospective comparison study included 45 patients (22 male, 23 female) with proximal humerus metastatic pathological fractures who underwent surgical treatment between 2011 and 2022. All data were collected from medical records and were analyzed retrospectively. Seventeen cases underwent intramedullary nailing plus cement augmentation, and 28 cases underwent locking plate plus cement augmentation. The main outcomes were pain relief, function scores, and complications. Results Among 45 patients with mean age 61.7 ± 9.7 years, 23 (51.1%) had multiple bone metastases, and 28 (62.2%) were diagnosed with impending fractures. The nailing group had significantly lower blood loss [100 (60–200) versus 500 (350–600) ml, p

Abstract Background The second-and third-generation drug-eluting stents (DESs) in-stent restenosis (ISR) genetic risk score (GRS) model has been previously validated. However, the model has not been validated in geriatric patients. Therefore, we conducted this study to test the feasibility of the DES-ISR GRS model in geriatric patients with coronary artery disease (CAD) in Taiwan. Methods We conducted a retrospective, single-center cohort study and included geriatric patients (age ≥ 65 years) with CAD and second-or third-generation DES(s) deployment. Patients undergoing maintenance dialysis were excluded. ISR was defined as ≥ 50% luminal narrowing on the follow-up coronary arteriography. The DES-ISR GRS model included five selected exonic single-nucleotide polymorphisms (SNPs): CAMLG, GALNT2, C11orf84, THOC5, and SAMD11. The GRS was defined as the sum of the five selected SNPs for the risk allele. Results We enrolled 298 geriatric patients from January 2010 and December 2019 in this study. After propensity score matching, there were 192 geriatric patients with CAD in the final analysis, of which 32 patients had ISR. Patients were divided into two groups based on their GRS values: low (0–2) and high (≥ 3) GRS. A high GRS was significantly associated with DES-ISR in geriatric patients. Conclusion Those geriatric patients with a high GRS had significantly higher second-or third-generation DES ISR rates. The five SNP-derived DES-ISR GRS model could provide genetic information for interventional cardiologists to treat geriatric patients with CAD. Trial registration The primary study protocol was registered with clinicaltrials.org. with registration number: NCT03877614; on March 15, 2019. ( http://clinicaltrials.gov/ct2/show/NCT03877614 )

Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Abstract Infection is a common cause of hospitalization in patients with heart failure (HF). The impact of infection on long term cardiovascular outcome in HF is not well studied. The aim of this study was to compare the long term risk of major adverse cardiovascular events (MACE) in HF patients with or without prior hospitalization for infection. From 2009 to 2015, 310,485 patients with their first HF admissions were enrolled from the Taiwan National Health Insurance Research Database. Among the patients, those with readmission due to infection within one year after HF discharge were defined as infection group and those without any infection admission were controls. The propensity score matching method was used to balance covariates between the two groups. Patients were followed until the occurrence of any component of the MACE or the end date of the study, December 31, 2019. In a mean follow-up time of 4.29 ± 2.92 years, 86.19% of patients in the infection group and 63.63% of patients in the control group had MACE. Multivariate Cox proportional hazards analysis showed the infection group had a higher risk of MACE (HR 1.760, 95% CI 1.714–1.807), including all-cause mortality (HR 1.587, 95% CI 1.540–1.636), myocardial infarction (HR 1.332, 95% CI 1.224–1.450), stroke (HR 1.769, 95% CI 1.664–1.882) and hospitalization for HF (HR 1.993, 95% CI 1.922–2.066). In conclusion, many HF patients discharged from the hospital experienced acute infection that required readmission. The patients had worse cardiovascular outcome after readmission for infectious disease compared to those without any infection.

We presented the case of a patient with non-ST-elevation myocardial infarction with coronary arteries of an anomalous origin, an interarterial course of the LMCA, a unique wide-angle “right” main bifurcation lesion, and a high SYNTAX score. Management with contemporary PCI and imaging may be an alternative to surgery.

Abstract Background Coexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature. Case presentation A 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years. Conclusions This is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management.

Background/Purpose: Pharmacogenetics is a potential driver of the “East Asian paradox,” in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet. Methods: CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients. Results: Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel. Conclusion: Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

Abstract In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non‐MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non‐contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.

Proprioceptors are primary mechanosensory neurons to monitor the status of muscle contraction and/or body position (1). Although proprioceptors are known as non-nociceptive mechanoreceptors, they also express the pro-nociceptive acid-sensing ion channel 3 (ASIC3) (2-5). To probe the role for proprioceptors in sensing acidosis (or sngception) (6), we found that genetic deletion of Asic3 in proprioceptors but not in nociceptors abolished acid-induced chronic hyperalgesia in mice. Chemo-optogenetically activating proprioceptors resulted in hyperalgesic priming that favored chronic pain induced by acidosis. In humans, intramuscular acidification induced acid perception but not pain. Conversely, in a spinal cord-injured patient who lost pain sensation in the right leg, proprioception and sngception were remaining somatosensory functions, associated with the spinal dorsal column. Together, evidence from both mouse and human studies suggests a role for proprioceptors in sngception. [ABSTRACT FROM AUTHOR]

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing

Objectives Muscle soreness occurs after exercise and also in musculoskeletal diseases, such as fibromyalgia (FM). However, the nosography and pathoetiology of morbid soreness in FM remain unknown. This study aimed to investigate the morbid soreness of FM, evaluate its therapeutic responses and probe its pathophysiology with metabolomics profiling.Methods Patients with newly diagnosed FM were prospectively recruited and completed self-report questionnaires pertaining to musculoskeletal symptoms. The phenotypes and metabotypes were assessed with variance, classification and correlation analyses.Results Fifty-one patients and 41 healthy controls were included. Soreness symptoms were prevalent in FM individuals (92.2%). In terms of manifestations and metabolomic features, phenotypes diverged between patients with mixed pain and soreness symptoms (FM-PS) and those with pain dominant symptoms. Conventional treatment for FM did not ameliorate soreness severity despite its efficacy on pain. Moreover, despite the salient therapeutic efficacy on pain relief in FM-PS cases, conventional treatment did not improve their general disease severity. Metabolomics analyses suggested oxidative metabolism dysregulation in FM, and high malondialdehyde level indicated excessive oxidative stress in FM individuals as compared with controls (p=0.009). Contrary to exercise-induced soreness, lactate levels were significantly lower in FM individuals than controls, especially in FM-PS. Moreover, FM-PS cases exclusively featured increased malondialdehyde level (p=0.008) and a correlative trend between malondialdehyde expression and soreness intensity (r=0.337, p=0.086).Conclusions Morbid soreness symptoms were prevalent in FM, with the presentation and therapeutic responses different from FM pain conditions. Oxidative stress rather than lactate accumulation involved phenotype modulation of the morbid soreness in FM.Trial registration number NCT04832100.

Abstract The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas (EECs). Our objectives were to test the sensitivity of tumor morphology in capturing p53 abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) risk stratification. A total of 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019–2021) were retrieved and assigned to ESGO risk groups with and without p53 status. Three pathologists reviewed the representative H&E‐stained slides, predicted the p53 status, and indicated whether p53 immunohistochemistry (IHC) would be ordered. Population‐based survival for endometrial carcinomas diagnosed during 2008–2016 in Alberta was obtained from the Alberta Cancer Registry. The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC1/2; N = 218, 74.6%). One hundred and fifty‐two EEC1/2 (52.1% overall) were stage IA and 147 (50.3%) were low risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5 and 8.3%, respectively. The average sensitivity of predicting p53abn among observers was 83.6%. Observers requested p53 IHC for 39.4% with 98.5% sensitivity to detect p53abn (99.6% negative predictive value). Nuclear features including smudged chromatin, pleomorphism, atypical mitoses, and tumor giant cells accurately predicted p53abn. In 7/292 (2.4%), p53abn upgraded ESGO risk groups (2 to intermediate risk, 5 to high risk). EEC1/2/stage IA patients had an excellent disease‐specific 5‐year survival of 98.5%. Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.

This study investigated the antimicrobial resistance of isolates from patients with refractory Helicobacter pylori. The resistance rate was 34.1% for amoxicillin, 92.7% for clarithromycin, 65.9% for metronidazole, 85.4% for levofloxacin, and 29.3% for rifabutin. Dual resistance to both clarithromycin and levofloxacin was found in 73.2%. The antimicrobial resistance rate of refractory H. pylori was extremely high, which had become a major consideration in therapeutic challenge.

Hyperoxia plays a significant role in the pathogenesis of lung injury, such as bronchopulmonary dysplasia (BPD), in premature infants or newborns. BPD management aims to minimize further injury, provide an optimal environment to support growth and recovery. In clinic neonatal care, we need a new therapy for BPD. Heat shock protein 70 (Hsp70) inhibit cell apoptosis and promote cell repair allowing cells to survive lethal injury. We hypothesized that Hsp70 could be used to prevent hyperoxia related BPD in the neonatal rat model through its anti-apoptotic and anti-inflammatory effects. In this study, we explored the effect of Hsp70 on hyperoxia-induced lung injury using neonatal rats. Neonatal Wistar rats were delivered naturally at full term of gestation and were then pooled and randomly assigned to several groups to receive heat stimulation (41°C for 20 min) or room temperature conditions. The Hsp70 group received recombinant Hsp70 intraperitoneally (200 μg/kg, daily). All newborn rats were placed under hyperoxic conditions (85% oxygen) for 21 days. Survival rates in both heat-hyperoxia and Hsp70-hyperoxia groups were higher than those in the hyperoxia group (p < 0.05). Both endogenous and exogenous Hsp70 could reduce early apoptosis of alveolar cells under hyperoxia. Additionally, there were less macrophage infiltration in the lung of the Hsp70 groups (p < 0.05). Heat stress, heat shock proteins, and exogenous recombinant Hsp70 significantly increased the survival rate and reduced pathological hyperoxia induced lung injuries in the development of BPD. These results suggest that treating hyperoxia-induced lung injury with Hsp70 may reduce the risk of developing BPD.

Background: Blood glucose and serum sodium abnormalities in very low birth weight infants may cause increased morbidity and mortality, but data regarding the long-term outcomes are limited. This study aimed to investigate the association between the peak and nadir blood glucose and serum sodium levels and neurodevelopmental outcomes in very low birth weight infants. Methods: A single-center retrospective medical record of 284 infants with birth weight

This case report describes a successful balloon venoplasty to overcome a total occlusion from the brachiocephalic vein to the superior vena cava in a patient undergoing cardiac resynchronization therapy. It is crucial for implanting physicians to be familiar with strategies to overcome venous occlusion in lead implantation, especially balloon venoplasty, which is an effective and safe approach.

Abstract Dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UEC) is an endometrial cancer characterized by the presence of histologically undifferentiated carcinoma. Genomic inactivation of core switch/sucrose nonfermentable (SWI/SNF) complex proteins was recently identified in approximately two‐thirds of DDEC/UEC. The aim of this study was to delineate the clinical behavior of SWI/SNF‐deficient DDEC/UEC in comparison to SWI/SNF‐intact DDEC/UEC. The study cohort consisted of 56 SWI/SNF‐deficient DDEC/UEC (2 POLE‐mutated), which showed either SMARCA4 (BRG1) loss, ARID1A/1B co‐loss, or SMARCB1 (INI1) loss in the undifferentiated tumor, and 26 SWI/SNF‐intact DDEC/UEC (4 POLE‐mutated). The average age at diagnosis was 61 years for patients with SWI/SNF‐deficient tumors and 64 years for SWI/SNF‐intact tumors. Mismatch repair (MMR) protein deficiency was seen in 66% of SWI/SNF‐deficient and 50% of SWI/SNF‐intact tumors. At initial presentation, 55% of patients with SWI/SNF‐deficient tumors had extrauterine disease spread in contrast to 38% of patients with SWI/SNF‐intact tumors. The 2‐year disease specific survival (DSS) for stages I and II disease was 65% for SWI/SNF deficient tumors relative to 100% for SWI/SNF‐intact tumors (p = 0.042). For patients with stages III and IV disease, the median survival was 4 months for SWI/SNF‐deficient tumors compared to 36 months for SWI/SNF‐intact tumors (p = 0.0003). All six patients with POLE‐mutated tumors, including one with stage IV SWI/SNF‐deficient tumor were alive with no evidence of disease. Among the patients with advanced stage SWI/SNF‐deficient tumors, 68% (21 of 31) received adjuvant or neoadjuvant chemotherapy (platinum/taxane‐based) and all except the patient with a POLE‐mutated tumor (20 of 21) experienced disease progression either during chemotherapy or within 4 months after its completion. These findings show that core SWI/SNF‐deficiency defines a highly aggressive group of undifferentiated cancer characterized by rapid disease progression that is refractory to conventional platinum/taxane‐based chemotherapy. This underscores the importance of accurate clinical recognition of this aggressive tumor and the need to consider alternative systemic therapy for these tumors.

BackgroundGout or rapid reduction in serum uric acid level may increase the incidence of heart failure (HF). To compare the risk of HF between febuxostat and allopurinol in gout patients with coexisting cardiovascular (CV) diseases, the varying severity would be likely to confound the risk estimation. Gout and HF are both sex-related diseases, and the risk difference from the urate-lowering agents between women and men remains unknown.AimsTo evaluate the HF hospitalisations risk of febuxostat and allopurinol in gout patients in real-world settings.MethodsA population-based cohort enrolled patients with allopurinol or febuxostat initiation from 2011 to 2018. Participants were grouped into, without (low CV risk group) or with (high CV risk group) a history of recent major CV admission. The primary outcome was HF hospitalization. The secondary outcomes were composite CV events, all-cause mortality, and the cause of CV mortality. We used the ‘as-treated' analysis and Cox proportional hazards model after propensity score (PS) matching. Patients were further stratified into men and women to evaluate the gender differences.ResultsFebuxostat users had a significantly higher risk of HF hospitalization than allopurinol users in gout patients either with low CV risk [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.25–1.55] or high CV risk [HR 1.36; 95% CI 1.22–1.52]. Particularly, women with gout had a higher risk of HF hospitalization than men.ConclusionThe HF hospitalization risk was highest in gout women with high CV risk and febuxostat use. Monitoring of HF is warranted in these patients.

Background: The concept of parental nutritional care for premature infants has been applied and advanced over the past decade. This study compared the clinical outcomes before and after nutrition practice (NP) implementation and evaluated the effects of implementation on growth velocity and weight gain in premature infants. Methods: Descriptive data of premature infants (gestational age

Background: The aim of the study was to assess the impact of different types of parenteral emulsions on retinopathy of prematurity (ROP) in very low birth weight (VLBW, birth body weight

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD. An experimental model of AD was reproduced by systemic sensitization and local epicutaneous challenge with ovalbumin (OVA). Treatment of rHSP70 was performed by subcutaneous administration. The levels of OVA‐specific IgE, as well as cytokines, were detected by ELISA. Skin samples from patch areas were also taken for histologic examination. Injection of rHSP70 improved the histologic picture by reducing the thickness of epidermis and allergic inflammation. Skin sonography revealed rHSP70 ameliorated skin remodeling. rHSP70 also significantly decreased the protein expression of TSLP of skin from patch areas. Furthermore, in ex vivo studies also showed group of rHSP70 treatment decreased IL‐13, RANTES, MIP‐1β and increased IFN‐γ secreted from splenocytes stimulated with OVA. The rHSP70 intervention in the mouse model of AD reduced the skin expression of TSLP and attenuated the clinical appearance of OVA‐induced AD mice. The effect was achieved by suppressed Th2 immune response in injected skin tissue and enhanced systemic Th1 immune response. These results suggest that rHSP70 have potential as a promising protein for the treatment of AD.

Summary: The new generation, i.e., second- and third-generation, drug-eluting stents (DESs) remain a risk of in-stent restenosis (ISR). We evaluated the power of a genetic risk score (GRS) model to identify high-risk populations for new generation DES ISR. We enrolled patients with coronary artery disease (CAD) treated with new generations DESs by a single-center cohort study in Taiwan and evaluated their genetic profile. After propensity score matching, there were 343 patients and 153 patients in the derivation and validation cohorts, respectively. Five selected single-nucleotide polymorphisms (SNPs), i.e., SNPs in CAMLG, GALNT2, C11orf84, THOC5, and SAMD11, were included to calculate the GRS for new generation DES ISR. In the derivation and the validation cohorts, patients with a GRS greater than or equal to 3 had significantly higher new generation DES ISR rates. We provide biological information for interventional cardiologists prior to percutaneous coronary intervention by specific five SNP-derived GRS.

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical-sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not repress the ultrasound-mediated neuronal activation as efficiently. The ASIC1a-mediated ultrasound effects in mouse brain such as immediate response of ERK phosphorylation and DCX marked neurogenesis were statistically significantly compromised by ASIC1a gene deletion. Collated data suggest that ASIC1a is the molecular determinant involved in the mechano-signaling of low-intensity ultrasound that modulates neural activation in mouse brain.

Objectives: Ovarian carcinosarcoma (OCS) is a rare and lethal type of ovarian cancer. Despite its incredibly poor prognosis, it has received little research attention. In this study, we aim to evaluate the molecular features of OCS and elucidate their clinical significance. Study methods: We examined 30 OCS by immunohistochemistry (IHC) and targeted panel sequencing collected from a single institution (2003–2013) as the initial molecularly characterized cohort (Cohort A). From November 2016 to April 2023, we collected an additional 67 OCS cases from three institutions across British Columbia and Alberta as the contemporary cohort (Cohort B) for clinical correlation. The Kaplan–Meier method was used to estimate overall and progression-free survival, and differences in survival rates were compared using the log-rank test. All tests were two-sided. A p-value of less than 0.05 was considered statistically significant. Results: The majority of OCS (82%) in the initial Cohort A were p53-mutated, and the carcinomatous component displayed the histological and molecular features of a high-grade tubo-ovarian serous carcinoma (HGSC-like). In a minority of OCS, the epithelial components were characteristics of endometrioid or clear cell carcinomas, and IHC staining was wild type for p53. In the contemporary Cohort B, we observed the same histological findings related to the p53 IHC staining pattern. The median overall survival of the p53-mutated HGSC-like OCS (47 patients) was significantly higher (43.5 months) compared with that of the p53 wild-type OCS (10 patients, 8.8 months; P < 0.01). Pathogenic BRCA1/2 germline/ somatic mutations were observed in 7 patients (17.5%) of HGSC-like OCS, and all these patients were alive at 3 years from diagnosis compared to a 51% 3-year survival among the patients with BRCA1/2 wild-type HGSC-like OCS (33 patients) (p = 0.022). Majority of patients (6/7) with BRCA1/2-mutated OCS received poly (ADP-ribose) polymerase inhibitor as maintenance therapy in this cohort. Conclusions: Most OCSs have a morphologic and molecular profile resembling HGSC; however, some OCSs display a molecular profile that suggests origin through non-serous oncogenic pathways. This molecular distinction has both prognostic and treatment (predictive) implications. These findings underscore the importance of routine p53 IHC testing on all OCS and BRCA1/2 testing on p53-mutated OCS. [ABSTRACT FROM AUTHOR]

The article discusses the case of a domestic short-hair cat with abdominal distention. Topics discussed include the results of abdominal radiography, differential diagnosis including pyometra and adenocarcinoma of the pancreas, and ovariohysterectomy and surgical biopsy of the pancreas performed on the cat. Also discussed are the treatment and outcome of the veterinary patient.

Various risk factors are associated with neonatal sepsis; however, its relationship to maternal postpartum fever is unknown. This study aimed to determine the relationship between maternal postpartum fever and neonatal sepsis. Full-term and late preterm stable infants born from January 2019 to June 2021 and whose mothers developed intra- or post-partum fever were included in the study. After the newborns were transferred to the nursery, laboratory assessments were performed. Based on clinical conditions and data, the newborns were divided into unlikely sepsis and probable/proven sepsis groups. Maternal fever onset, duration, and maximum body temperature were recorded. We included 1059 newborns whose mothers developed fever intra-partum (n = 192), post-partum (n = 844), and intra- and post-partum (n = 23). The newborns were grouped into those with unlikely sepsis (n = 550) and those with probable/proven sepsis (n = 509). The incidence of intrapartum fever was higher in the probable/proven sepsis group than in the unlikely sepsis group (27.9% vs. 13.3%, p < 0.001). The incidence of postpartum fever was lower in the probable/proven sepsis group than in the unlikely sepsis group (74.7% vs. 88.5%, p < 0.001). Development of maternal fever within 1.8 h postpartum and a newborn respiratory rate of >60 breaths/min were positive predictors (91.6%) for neonatal probable/proven sepsis.

Background: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. Methods: Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. Results: The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, p < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. Conclusions: For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.

Background: Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD).Methods: This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay.Results: Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 (r = 0.47) and Day 28 of life (r = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death.Conclusions: Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.

Objective Preterm infants receive long-term parenteral nutrition (PN) for gastrointestinal immaturity. This study aimed to determine if mixed lipid emulsions containing fish oil decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect. Methods This retrospective cohort study enrolled 399 very low birth weight premature infants (gestational age ≤32 weeks) between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total PN with either mixed lipid emulsion including fish oil (SMOFlipid®, n = 195) or soybean oil-based lipid emulsion (Lipovenoes®, n = 204) for at least 7 days. We compared the outcomes of PN-associated cholestasis, comorbidities, and mortality between the groups. Results The incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than in the Lipovenoes group. The duration to full feeding days was significantly shorter in the SMOFlipid group compared with the Lipovenoes group. Relevant complications, such as severe retinopathy of prematurity and bronchopulmonary dysplasia, were also significantly reduced in the SMOFlipid group compared with the Lipovenoes group. Conclusion In premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.

Objectives: To investigate the survival rate of hydrops fetalis after fetal interventions and neonatal intensive care. Methods: We reviewed the medical records of patients diagnosed with hydrops fetalis from January 2009 to December 2019 at Changhua Christian Children’s Hospital. All cases had abnormal fluid accumulation in at least two body compartments during pre- and postnatal examination. The primary outcome measure was the mortality rate. We also collected information regarding disease etiology, duration of hospital stay, Apgar score, gestational age at birth, initial hydrops fetalis diagnosis, fetal intervention, first albumin and pH levels, and maternal history. Results: Of the 42 cases enrolled, 30 survived and 12 died; the mortality rate was 28.6%. Furthermore, 22 cases received fetal intervention, while 20 cases did not; there was no significant difference in their survival rates (75% and 68%, respectively). Survival rate was associated with gestational age at birth, initial diagnosis time, birthweight, Apgar score, initial albumin and pH levels, and gestational hypertension. Only one case was immune-mediated. Among the nonimmune-mediated cases, the three most common etiologies were lymphatic dysplasia (12/42), idiopathic disorders (10/42), and cardiovascular disorders (5/42). Conclusions: Overall, hydrops fetalis was diagnosed early, and fetal intervention was performed in a timely manner. Preterm births were more frequent, and birthweight was lower in the cases that underwent fetal intervention than in those that did not, but there was no significant between-group difference in mortality. The initial diagnosis time, gestational age at birth, birthweight, Apgar score, and first albumin and pH levels were independently associated with mortality.