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Background: Circulating prorenin contributes to the pathogenesis of tissue damage leading to cardiovascular disease (CVD) in hypertension and diabetic mellitus (DM) by activating the tissue renin-angiotensin-aldosterone (RAS) system; however, little is known about its roles in hemodialysis (HD) patients., Methods: We evaluated plasma prorenin level and prorenin receptor [(P)RR] expression in peripheral blood mononuclear cells (PBMCs) in 49 nondiabetic HD (non-DM-HD) patients. Then we investigated the association between plasma prorenin level or (P)RR expression level in PBMCs and CVD-predictive biomarkers., Results: The plasma prorenin level increased in non-DM-HD patients [147.1 ± 118.9 pg/ml (standard value <100 pg/ml)]. The (P)RR mRNA expression level in PBMCs also increased 1.41 ± 0.39-fold in non-DM-HD patients compared with that in healthy control subjects (p < 0.001). Although plasma prorenin level did not correlate with plasma BNP level and plasma high-sensitivity C-reactive protein level, it significantly correlated with plasma 8-hydroxydeoxyguanosine (8-OHdG) level (r = 0.535, p < 0.001). The plasma prorenin level did not correlate with plasma renin activity (PRA), plasma angiotensin I (AT I) level, plasma angiotensin II (AT II) level and plasma aldosterone (Ald) level. PRA, plasma AT I level, plasma AT II level and plasma Ald level did not correlate with the level of any CVD predictive biomarker. (P)RR expression level in PBMCs did not correlate with the level of any CVD predictive biomarker., Conclusions: The plasma prorenin level and (P)RR expression level in PBMCs increased, and the plasma prorenin level was associated with plasma 8-OHdG level independent of circulating RAS in non-DM-HD patients.

Background: Bone disease is caused not only by increased bone turnover accompanying secondary hyperparathyroidism but also by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis in hemodialysis patients. In this study, we investigated the effects of raloxifene on bone turnover markers and bone mineral density (BMD) in female hemodialysis patients to determine involvement of estrogen deficiency in bone disease., Methods: The subjects were 47 female patients on maintenance hemodialysis. Raloxifene hydrochloride (60 mg) was administered to 21 patients for 1 year, and these patients were compared with a control group of 26 patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone were measured, and BMD was determined by quantitative heel ultrasound as the speed of sound (SOS) in the calcaneus over this period., Results: NTx decreased after treatment with raloxifene for 1 year, but significantly increased in the control group. SOS increased after treatment with raloxifene for 1 year, but significantly decreased in the control group. Treatment with raloxifene resulted in a significant decrease of NTx and a significant increase of SOS in subgroups of patients aged <60 and ≥ 60 years., Conclusions: Treatment with raloxifene can suppress a rise in NTx and increase bone mineral density in patients around the time of menopause and in postmenopausal patients of advanced age. A reduction in bone mineral density caused by estrogen deficiency may be involved in the development of bone disease in female hemodialysis patients.

Paraneoplastic nephropathy is a rare complication of malignant disease. We present a case of cervical cancer with biopsy-proven membranous nephropathy and associated nephrotic syndrome. Irradiation to the specific neoplasm site and to the metastatic paraaortic lymph node tissues lead to regression of the nephrotic syndrome without causing severe adverse events. Radiation therapy can be the first choice in the treatment of paraneoplastic nephrotic syndrome if the primary neoplasm is unresectable. Invasiveness of intervention and patient prognosis should be carefully deliberated in the management of the two diseases.

Simple Summary: This investigation describes the results of the analysis of the microbiological quality of raw ovine milk in the Banat region of Romania, emphasizing monitoring the human infective potential and antimicrobial resistance of the isolated Escherichia coli strains. Overall, 4.2% (3/72) of the processed bulk tank milk samples exceeded the regulatory limit (6.18 log10 CFU/mL) for total aerobic mesophilic bacteria imposed by European Union legislation. E. coli was detected in 66.6% of the processed samples. Of the 48 isolated strains, 18.8% demonstrated pathogenic potential, and 18.5% were multidrug-resistant. Resistance was found against ampicillin (45.8%), gentamicin (20.8%), ticarcillin–clavulanic acid (18.8%), cephalexin (18.8%), amoxicillin–clavulanic acid (8.3%), and trimethoprim–sulfamethoxazole (2.1%), but all strains were susceptible to imipenem. This study provides important hygienic quality and safety data on raw ovine milk in Romania. This study investigated the bacteriological quality of raw ovine milk produced by farms located in the Banat region of Romania. Additionally, the pathogenic potential and antimicrobial resistance of the isolated Escherichia coli strains were evaluated. A total of 95.8% (69/72) of the screened bulk tank milk samples, collected at the farm level immediately after milking, demonstrated appropriate total aerobic mesophilic bacteria (TMB) counts, varying from 3.32 to 6.09 log10 CFU/mL. However, 4.2% (3/72) of the samples were above the regulatory limit of 6.18 log10 CFU/mL. E. coli was identified in 66.6% of the examined samples, and from the total number (n = 48) of isolates, 18.8% harbored the stx2 gene, highlighting pathogenic potential. Antimicrobial susceptibility testing with the Vitek2 system of the isolated E. coli strains revealed resistance against ampicillin (45.8%), gentamicin (20.8%), ticarcillin–clavulanic acid (18.8%), cephalexin (18.8%), amoxicillin–clavulanic acid (8.3%), and trimethoprim–sulfamethoxazole (2.1%). Additionally, 64.6% of the strains showed intermediate resistance against amoxicillin–clavulanic acid, while no resistance was recorded against imipenem. Five (18.5%) strains were multidrug-resistant. This study's results underline hygienic sanitary deficiencies during the milking phase and indicate that raw ovine milk can be contaminated with pathogenic and multidrug-resistant E. coli strains, highlighting a potential risk to public health. Further studies are encouraged to better understand the risk posed to the consumer via the consumption of ovine milk and derived products. [ABSTRACT FROM AUTHOR]

Objective: To predict postoperative anastomotic leakage (AL) following radical resection of esophageal squamous cell carcinoma (ESCC) based on clinical data and preoperative enhanced Computed tomography(CT) radiomics of the esophagus. Method: We retrospectively analyzed the clinicopathological and radiological data of 213 patients with ESCC who received radical resection at Xiangyang No.1 People's Hospital from July 2011 to February 2024. 3D slicer software was used in combination with Lasso extraction and 10-fold cross-validation to extract texture parameters from contrast-enhanced CT images and generate Delta-Radscores. Several models were built using logistic regression to predict postoperative AL in ESCC. Results: In the training set, the univariate analysis confirmed that duration of surgery, surgical method, delta radscore 1, delta radscore 2, contrast enhancement patterns, peripheral lymph node metastasis, post thoracotomy pulmonary infection(PTPI), and hot pot were risk factors for ESCC-AL (P<0.05 for both). The multivariate analysis showed that delta radscore 1, delta radscore 2, PTPI, and hot pot were independent risk factors for AL (P<0.05 for all). These results were verified by the XGboost machine learning model. The combinational model based on all of the above risk factors [AUC 0.900, OR 0.0282, 95%CI 0.841-0.943] outperformed either the clinical model[AUC 0.759, OR 0.0392, 95% 0.683-0.825,P<0.05] or the imaging model[AUC 0.869, OR 0.0335, 95%0.804- 0.918,P=0.1277] alone in predictive efficacy. The decision curve proved that the combinational model had a higher clinical net benefit. The nomogram generated via the combinational model simplified the predictive process. The same predictions were verified in the testing set. Conclusion: Delta radscore 1, delta radscore 2, PTPI, and hot pot were related to ESCC-AL. The novel nomogram created using enhanced CT radiomics informed perioperative management and improved the survival quality of ESCC patients. [ABSTRACT FROM AUTHOR]

Purpose: The usability of a new surgical navigation system that provides patient-specific vascular information for robotic gastrectomy in gastric cancer remains unexplored for laparoscopic gastrectomy owing to differences in surgical environments. This study aimed to evaluate the applicability and safety of this navigation system in laparoscopic gastrectomy and to compare the post-operative outcomes between procedures with and without its use. Materials and Methods: Between June 2022 and July 2023, 38 patients across 2 institutions underwent laparoscopic gastrectomy using a navigation system (navigation group). The technical feasibility, safety, and accuracy of detecting variations in vascular anatomy were measured. The perioperative outcomes were compared with 114 patients who underwent laparoscopic gastrectomy without a navigation system (non-navigation group) using 1:3 propensity score matching during the same study period. Results: In all patients in the navigation group, no adverse events associated with the navigation system occurred during surgery in any patient in the navigation group. No accidental vessel injuries necessitate auxiliary procedures. All vessels encountered during the gastrectomy were successfully reconstructed and visualized. Patient demographics and operative data were comparable between the 2 groups. The navigation group exhibited a significantly lower overall complication rate (10.5%) than the non-navigation group (26.3%, P=0.043). Notably, pancreas-related complications were absent in the navigation group but occurred in eight cases in the non-navigation group (7.0%, P=0.093), although the difference was not statistically significant. Conclusions: The patient-specific surgical navigation system demonstrated clinical feasibility and safety for laparoscopic gastrectomy for gastric cancer, potentially reducing complication rates compared with laparoscopic gastrectomy without its use. [ABSTRACT FROM AUTHOR]

Background: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. Methods: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I–IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. Results: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61–1.25). Although, the 3-year P-CRT group progression–free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04–1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38–0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1–2 (HR 0.61, 95% CI 0.29–1.26) and cStage I–II (HR 0.50, 95% CI 0.24–1.07) subgroups, although this trend was not evident in other populations, such as cT3–4 and cStage III–IVA. Conclusions: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1–2 and cStage I–II disease, proton-based CRT has the potential to serve as a first-line treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: Sarcopenia contributes to a poor prognosis in patients with esophageal cancer; thus, any clinical support that prevents loss of skeletal muscle mass preoperatively and postoperatively should be actively investigated. This study aimed to evaluate physical activity during the perioperative period and its impact on postoperative skeletal muscle mass. Patients and Methods: Sixty-two patients who underwent esophagostomy at the Hamamatsu University School of Medicine between 2019 and 2023 were evaluated. The physical activity (measured by the step count) of patients scheduled for esophagectomy was assessed preoperatively using a fitness tracker. The percentage change in skeletal muscle mass index (SMI) was calculated preoperatively and 6 months postoperatively. Factors associated with decreased SMI 6 months after esophagectomy were analyzed using multivariate analysis. Results: The median decrease in SMI was -6.2%. Multivariate analysis revealed that factors associated with the reduction of SMI were age >69 years [odds ratio (OR)=7.21, 95% confidence interval (CI)=1.36-38.19, p=0.020], preoperative step count <7,800 steps/day (OR=5.17, 95% CI=1.38-19.33, p=0.015), and postoperative step count <2,400 steps/day (OR=3.55, 95% CI=1.01-12.45, p=0.048). Conclusion: A low perioperative step count and older age were significant risk factors for skeletal muscle loss in patients with esophageal cancer undergoing surgery. For patients with a low number of steps in the perioperative period or for older patients, interventions to increase the number of steps may prevent skeletal muscle loss. [ABSTRACT FROM AUTHOR]

We describe a case of cyclic thrombocytopenia and thrombocytosis, whose cytokine levels, granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-6 (IL-6) in plasma, fluctuated in synchrony with platelet count. The levels of the two cytokines correlated significantly with the platelet count for 11 observations over an 8-month period (r = 0.79, p < 0.01 for GM-CSF and r = 0.87, p < 0.001 for IL-6). No inverse relationship between platelet-associated immunoglobulin G (PAIgG) and platelet count was observed (r = 0.39, p > 0.20). These findings suggest that the fluctuation of platelet count in this case may result from an aberration of the cytokine network regulating megakaryopoiesis and platelet formation.

TSH-secreting pituitary adenoma with calcification and proliferation of the collagen fibers was presented. A 42-year-old man had shown general fatigue and thyroid hypertrophy caused by hyperthyroidism for 3 years. CT and MRI revealed pituitary adenoma with calcification extending into the cavernous sinus and sphenoid sinus. The patient was operated on using the transsphenoidal route twice, but the tumor was not able to be removed totally, partly due to the hardness of the tumor. The tumor in- and around the left cavernous sinus as well as the hardest part of the tumor itself due to the calcification could not be removed. Histopathological examination revealed chromophobe adenoma with proliferation of the collagen fibers. Immunohistological and electronmicroscopic examination demonstrated TSH-secreting adenoma. Postoperatively, thyroid function improved and the patient's symptoms due to hyperthyroidism disappeared.

For several years, alpha klotho has been considered as a candidate biomarker in chronic kidney disease (CKD), progression of CKD and CKD mineral bone disorders (CKD-MBD). The evidence on the relationship between klotho and kidney function is controversial in some areas. The aim of the study was to identify the influence of age, sex and breed on urinary alpha klotho, values in the early stages of CKD within the studied population and determine a reference interval in a group of healthy dogs. Significantly higher values were measured in older dogs over 6 years old (p = 0.026, p = 0.0007) and in the breed German Shepherd than Belgian Shepherd (p = 0.0401). On the basis of sex and in small breed dogs, no significant differences were noted. In dogs with CKD stage 2, alpha klotho values were significantly lower (p = 0.0135) than in healthy dogs. Within the studied population, a reference interval for urinary klotho to creatinine ratio (UrKl/Cr) was determined in the range of 3.94–23.55 pg/gCr. Since our findings show that alpha klotho is associated with older age, we assume that this may have influenced the results in the group of dogs with CKD stage 1 due to the presence of predominantly old dogs in this group. Future studies would be needed to consider age as a factor affecting urinary alpha klotho in dogs with CKD. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is an important strategy for the treatment of advanced gastric cancer (GC), while the radioresistance limits its effectiveness. Nucleolar and spindle associated protein 1 (NUSAP1) was implicated in cancer progression and chemoresistance. However, the underlying mechanisms of NUSAP1 influencing GC radioresistance remain largely unknown. Methods: Meta-analysis was conducted to systematically evaluate the prognostic value of NUSAP1 in human cancers. Gene set enrichment analysis (GSEA) was conducted using The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) datasets. MRNA and protein expressions were detected by qRT-PCR and western blot, respectively. The radiosensitivity of GC cells was observed by colony formation, flow cytometry, comet, immunofluorescence, and animal assays. Immunoprecipitation assay and mass spectrometry were utilized to identify protein associations. MiRNAs binding with NUSAP1 were determined by starbase prediction, luciferase reporter, and RNA immunoprecipitation (RIP) assays. Results: NUSAP1 high expression predicted worse overall survival (OS) and disease-free survival (DFS) with no statistical heterogeneity through the meta-analysis. Downregulation of NUSAP1 significantly increased GC radiosensitivity by inhibiting colony formation, DNA damage repair, and promoting apoptosis following irradiation. Additionally, NUSAP1 silencing combined with radiation resulted in a synergistic anti-tumor effect in xenograft mouse model. Mechanistically, NUSAP1 interacted with ANXA2, protecting it against protein degradation via impeding its ubiquitination process. NUSAP1 was confirmed as a target of miR-129-5p and negatively regulated by it. Conclusion: Our results suggested that NUSAP1 enhanced the radioresistance of GC cells. NUSAP1 could be a promising target to increase GC radiosensitivity. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m2 per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Protein tyrosine kinases (PTKs) are classified into two groups: one group includes tyrosine kinases, and the second group includes serine/threonine kinases. The group of tyrosine kinases includes both receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs) that function as "on" or "off" switches for many cellular functions. NRTKs are kinase enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions, including cell growth and progression and their dependent mechanisms and the associated signaling pathways. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the members of the serine/threonine kinases. The group of tyrosine kinases is subdivided into subgroups: one of them includes the member of receptor tyrosine kinases (RTKs), while the other subgroup includes the member of non-receptor tyrosine kinases (NRTKs). Both these kinase groups function as an "on" or "off" switch in many cellular functions. NRTKs are enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions in response to extracellular signaling-dependent mechanisms. NRTK-mediated different cellular functions are regulated by kinase-dependent and kinase-independent mechanisms either in the cytoplasm or in the nucleus. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. This review deals with the structure and mechanistic role of NRTKs in tumor progression and resistance and their importance as therapeutic targets in tumor therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Post-pancreaticoduodenectomy complications are still a major concern nowadays, and we focused on one of the most catastrophic conditions observed from clinical practice, the postoperative biliary infection, which may cause postoperative intensive care unit admission or mortality. Evaluating the impact on postoperative biliary tract infection from endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography and drainage before surgery is important to clinical circumstances. Biliary pathogens identified with a positive yield of intra-operative bile culture in patients undergoing pancreaticoduodenectomy were also investigated. The result showed that performing endoscopic retrograde cholangiopancreatography enhances the likelihood of achieving a positive yield from intraoperative biliary culture. Thus, PTCD emerges as a potentially favorable option for patients with obstructive jaundice and is indicated for pancreaticoduodenectomy. Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) can occur as a paraneoplastic disorder in association with various types of carcinoma. However, paraneoplastic nephrotic syndrome (PNS) is often misdiagnosed as idiopathic nephrotic syndrome or as an adverse effect of oncology treatment, leading to delayed diagnosis and suboptimal treatment. The characteristics of NS associated with solid malignancies are not yet elucidated. We systematically summarized the clinical data for 128 cases of NS combined with solid malignancies with the aim of informing the clinical management of PNS. Methods: We searched the PubMed database for articles published from the date of inception through to October 2023 using the following keywords: "cancer" or "malignant neoplasms" or "neoplasia" or "tumors" and "nephrotic syndrome", "nephrotic" or "syndrome, nephrotic". All data were extracted from case reports and case series, and the extraction included a method for identifying individual-level patient data. Results: A literature search yielded 105 cases of PNS and 23 of NS induced by cancer therapy. The median age at diagnosis was 60 years, with a male to female ratio of 1.8:1. In patients with PNS, manifestations of NS occurred before, concomitantly with, or after diagnosis of the tumor (in 36%, 30%, and 34% of cases, respectively). Membranous nephropathy (49%) was the most prevalent renal pathology and found particularly in patients with lung, colorectal, or breast carcinoma. Regardless of whether treatment was for cancer alone or in combination with NS, the likelihood of remission was high. Conclusion: The pathological type of NS may be associated with specific malignancies in patients with PNS. Prompt identification of PNS coupled with suitable therapeutic intervention has a significant impact on the outcome for patients. [ABSTRACT FROM AUTHOR]

Kartagener’s Syndrome, alternatively known as Primary Ciliary Dyskinesia (PCD) is a rare and intricate inherited disorder that impacts the structure and function of cilia, leading to compromised mucociliary clearance. The defining features of this condition consist of chronic sinusitis, situs inversus totalis, and bronchiectasis, forming a characteristic triad. Kartagener’s Syndrome presents numerous challenges in its diagnosis and management, and its clinical implications have significant ramifications for affected individuals. This review aims to comprehensively review and analyse the clinical impact of this syndrome, focusing on the diagnosis, treatment, and management modalities. The ciliary dysfunction in Kartagener’s Syndrome disrupts the mucus clearance and pathogens from the respiratory tract, resulting in chronic infections, progressive lung damage, and respiratory failure in severe cases. Through a narrative review of literature, reviews, and case studies, the authors have explored clinicians’ diagnostic challenges and the advances in genetic testing methods that aid in early and accurate diagnosis. The authors have discussed the multidisciplinary approach to manage Kartagener’s Syndrome, which involves respiratory therapies, antibiotics, and surgical interventions to improve the patient’s quality of life and prevent complications. The review paper also includes in-depth case studies of individuals with Kartagener’s Syndrome, highlighting the variability in clinical presentations and treatment outcomes. These case studies provide valuable insights into the diverse manifestations of this syndrome, further enhancing the existing understanding of the disease and its management. Ultimately, this review is directed to raise awareness among healthcare professionals about Kartagener’s Syndrome, its clinical implications, and its diagnostic and treatment challenges. By shedding light on this rare and intricate genetic disorder, the authors here promote early recognition and proactive management, leading to improved outcomes and better quality of life for individuals with Kartagener’s Syndrome. [ABSTRACT FROM AUTHOR]

The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators of cytokine signaling. SOCS1 is the prototypical member of the SOCS family and functions in a classic negative-feedback loop to inhibit signaling in response to interferon, interleukin-12 and interleukin-2 family cytokines. These cytokines have a critical role in orchestrating our immune defence against viral pathogens and cancer. The ability of SOCS1 to limit cytokine signaling positions it as an important immune checkpoint, as evidenced by the detection of detrimental SOCS1 variants in patients with cytokine-driven inflammatory and autoimmune disease. SOCS1 has also emerged as a key checkpoint that restricts anti-tumor immunity, playing both a tumor intrinsic role and impacting the ability of various immune cells to mount an effective antitumor response. In this review, we describe the mechanism of SOCS1 action, focusing on the role of SOCS1 in autoimmunity and cancer, and discuss the potential for new SOCS1-directed cancer therapies that could be used to enhance adoptive immunotherapy and immune checkpoint blockade. [ABSTRACT FROM AUTHOR]

We previously reported that sodium–glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (−1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin–angiotensin–aldosterone and sympathetic nervous systems. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway's role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce blood pressure (BP) in patients with hypertension, yet the precise molecular mechanisms remain elusive. SGLT2i inhibits proximal tubule (PT) NHE3-mediated sodium reabsorption in normotensive rodents, yet no hypotensive effect is observed under this scenario. This study examined the effect of empagliflozin (EMPA) on renal tubular sodium transport in normotensive and spontaneously hypertensive rats (SHRs). It also tested the hypothesis that EMPA-mediated PT NHE3 inhibition in normotensive rats is associated with upregulation of distal nephron apical sodium transporters. EMPA administration for 14 days reduced BP in 12-wk-old SHRs but not in age-matched Wistar rats. PT NHE3 activity was inhibited by EMPA treatment in both Wistar and SHRs. In Wistar rats, EMPA increased NCC activity, mRNA expression, protein abundance, and phosphorylation levels, but not in SHRs. SHRs showed higher NKCC2 activity and an abundance of cleaved ENaC α and γ subunits compared with Wistar rats, none of which were affected by EMPA. Another set of male Wistar rats was treated with EMPA, the NCC inhibitor hydrochlorothiazide (HCTZ), and EMPA combined with HCTZ or vehicle for 14 days. In these rats, BP reduction was observed only with combined EMPA and HCTZ treatment, not with either drug alone. These findings suggest that NCC upregulation counteracts EMPA-mediated inhibition of PT NHE3 in male normotensive rats, maintaining their baseline BP. Moreover, the reduction of NHE3 activity without further upregulation of major apical sodium transporters beyond the PT may contribute to the BP-lowering effect of SGLT2i in experimental models and patients with hypertension. NEW & NOTEWORTHY: This study suggests that reduced NHE3-mediated sodium reabsorption in the renal proximal tubule may account, at least in part, for the BP-lowering effect of SGLT2 inhibitors in the setting of hypertension. It also demonstrates that chronic treatment with SGLT2 inhibitors upregulates NCC activity, phosphorylation, and expression in the distal tubule of normotensive but not hypertensive rats. SGLT2 inhibitor-mediated upregulation of NCC seems crucial to counteract proximal tubule natriuresis in subjects with normal BP. [ABSTRACT FROM AUTHOR]

Few studies have quantified longitudinal changes in swallowing in patients undergoing esophagectomy for esophageal cancer. This study longitudinally analyzed the changes in the Modified Barium Swallow Study Impairment Profile (MBSImP™) scores, swallowing kinematic measurements, and swallowing-related symptoms in patients undergoing esophagectomy. We also examined the association between identified swallowing impairment and aspiration pneumonia after surgery. We included consecutive patients who underwent esophagectomy and completed laryngoscopy and videofluoroscopy before, two weeks, and three months after surgery. We analyzed physiological impairments using the MBSImP. We also assessed the swallowing kinematics on a 5 mL thickened liquid bolus at three time points. Vocal fold mobility was assessed using a laryngoscope. Repeated measures were statistically examined for longitudinal changes in swallowing function. The association between the significant changes identified after esophagectomy and aspiration pneumonia was tested. Twenty-nine patients were included in this study. Preoperative swallowing function was intact in all participants. The timing of swallowing initiation and opening of the pharyngoesophageal segment remained unchanged after surgery. Tongue base retraction and pharyngeal constriction ratio worsened two weeks after surgery but returned to baseline levels three months after surgery. Three months after surgery, hyoid displacement and vocal fold immobility did not fully recover. Aspiration pneumonia occurred in nine patients after surgery and was associated with postoperative MBSImP pharyngeal residue scores. Decreased hyoid displacement and vocal fold immobility were observed postoperatively and persisted for a long time. The postoperative pharyngeal residue was associated with pneumonia and thus should be appropriately managed after surgery. [ABSTRACT FROM AUTHOR]

Background: Lymphovascular invasion (LVI) is reported to correlate with postoperative prognosis in esophageal squamous cell carcinoma (ESCC). However, reports analyzing lymphatic and venous invasion separately are rare, and no studies have examined the correlation in resected specimens after neoadjuvant chemotherapy (NAC). This study evaluated the postoperative prognosis and distant metastatic recurrence patterns in ESCC patients who underwent esophagectomy after NAC., Methods: This retrospective study analyzed 427 ESCC patients who underwent radical esophagectomy after NAC. The study examined the association of LVI patterns with postoperative overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). The study also evaluated the correlation with postoperative distant metastasis patterns., Results: Multivariate analyses showed that patients with venous invasion (VI) alone had significantly worse OS (HR, 2.99; p < 0.001), RFS (HR, 2.92; p < 0.001), and DMFS (HR, 3.63; p < 0.001) than patients without LVI. Patients with both lymphatic invasion (LI) and VI had the worst OS (HR, 4.23; p < 0.001), RFS (HR, 3.38; p < 0.001), and DMFS (HR, 4.59; p < 0.001) among all groups. For the ypN0 patients, VI positivity was the only independent risk factor for DMFS (HR, 5.33; p < 0.001). Regarding distant organ metastasis, liver, brain, and bone metastasis were more frequently detected in patients with both LI and VI than in patients with other LVI patterns., Conclusions: The study showed that ESCC patients treated with NAC who have resected specimens positive for VI, especially those also with positive lymphatic invasion, have a worse postoperative prognosis and a higher risk for postoperative distant metastases than those without LVI. More aggressive postoperative adjuvant therapy may be suitable for improving the prognosis of such patients., Competing Interests: Disclosure: Daisuke Kajiyama, Naoto Fujiwara, Takashi Shigeno, Kazuma Sato, Masayuki Yamaguchi, Shingo Sakashita, Hiroyuki Daiko, and Takeo Fujita have no conflicts of interest to declare in relation to this work., (© 2024. Society of Surgical Oncology.)

Background: Patients with esophageal squamous cell carcinoma (ESCC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy a viable option for patients with incurable ESCC., Objective: We aimed to assess the safety and efficacy of conversion therapy for ESCC with distant metastases., Methods: Conversion therapy was defined as surgery or chemoradiotherapy (CRT) used to cure tumors that were previously considered incurable because of distant metastasis. We conducted a retrospective review of patients who underwent ESCC conversion therapy and assessed the treatment outcomes, including adverse events and survival rates., Results: A total of 147 patients from 22 institutions were included. Systemic chemotherapy was initially administered to all patients. The most common M1 factor was the para-aortic lymph node, accounting for 55% of cases. Following the initial treatment, 116 patients underwent surgery, with 31 receiving CRT as conversion therapy. Postoperative complications in surgery patients included pneumonia (16%), anastomotic leakage (7%), and recurrent laryngeal nerve palsy (6%). During CRT, 18% of patients developed grade 3 or higher non-hematological toxicities. The 5-year overall survival (OS) rate was 31.7%. Pathological responders had significantly longer OS than non-responders (hazard ratio 0.493, p = 0.012). The distribution of distant metastasis, regimen type, clinical response, and conversion therapy modality did not have a significant impact on OS., Conclusions: Conversion therapy can be safely performed for ESCC with distant metastasis and has a favorable prognosis., Competing Interests: Disclosure: Motoo Nomura has received honoraria from ONO, BMS, and MSD, and advisory board fees from ONO. Shun Yamamoto has received honoraria from ONO, BMS, MSD, and Taiho; advisory board fees from ONO; and expert testimony fees from Hokuto. Katsuyuki Sakanaka has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Novartis Pharma, and support for attending meetings and/or travel from MSD. Ken Kato reports funding, paid to the institution, from MSD, Ono Pharmaceuticals, BMS, Beigene, Shionogi, Merck Biopharma, Oncolys BioPharma, Daiichi Sankyo, Novartis, Taiho Pharmaceutical, Janssen, AstraZeneca, and Chugai. Takayuki Tsuji, Satoru Matsuda, Yuta Sato, Koji Tanaka, Ken Sasaki, Masaya Watanabe, Yoichi Hamai, Motomi Nasu, Zenichiro Saze, Yuichiro Nakashima, Eisuke Booka, Koshiro Ishiyama, Takeo Bamba, Takahiro Tsushima, Hiroya Takeuchi, and Hirofumi Kawakubo have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Background: Esophageal cancer is highly prevalent in China, predominantly represented by squamous cell carcinoma. This retrospective study sought to evaluate the diagnostic efficacy of four staining protocols in identifying early stage esophageal squamous cell carcinoma (ESCC)., Methods: A consecutive series of ninety biopsy samples of esophageal mucosa, collected retrospectively from March 2016 to December 2019, were obtained at Beijing Chao-Yang Hospital, a tertiary care facility in Beijing, China. These samples were categorized into four groups: non-neoplastic squamous lesions (Non-NSL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and early stage ESCC. Baseline, molecular analyses (p53 by immunohistochemistry and Ki-67 by immunohistochemistry), and staining analyses (hematoxylin & eosin (HE) and periodic acid-Schiff (PAS) were conducted across the categories. The staining protocols included HE, HE + p53 + Ki-67, HE + p53 + Ki-67 + PAS, and HE + p53/PAS + Ki-67/PAS., Results: Patients with HGD and ESCC were significantly older and had larger lesions. Elevated p53 and Ki-67 mutation rates were observed in HGD and ESCC, while increased PAS positivity was noted in RE and LGD. The p53, Ki-67, and PAS staining results showed mostly no correlation among the four groups. Abnormal Ki-67 basal layer distribution pattern correlated with histological grades, with higher proportions in HGD and ESCC. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS demonstrated complete consistency with the reference standard, with weighted κ values of 1. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS protocols exhibited 100% accuracy, sensitivity, and specificity for diagnosing ESCC or ESCC combined with HGD, outperforming the other protocols., Conclusions: Incorporating specific staining protocols, particularly HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS, enhances the diagnostic accuracy for early stage ESCC, showing promise in advancing the pathology diagnostic pathway., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Beijing Chao-Yang Hospital (No. 2023–598). Since this was a retrospective study and involved no direct patient intervention, informed consent was waived. However, all patient data were anonymized, and confidentiality was maintained throughout the study., (© 2024. The Author(s).)

Background: Patients with esophageal squamous cell carcinoma (ESCC) frequently develop synchronous head and neck squamous cell carcinoma (HNSCC). With advances in endoscopic technology and widespread screening of synchronous cancers, the detection of synchronous HNSCC and superficial ESCC (SESCC) is increasing. We aimed to evaluate the impact of preceding HNSCC treatment on synchronous SESCC., Methods: This single-center retrospective study enrolled patients with synchronous HNSCC and SESCC who were treated between January 2010 and December 2023. Tumor size and depth of SESCC before and after HNSCC treatment were evaluated. The factors associated with SESCC progression were investigated., Results: Of the 299 patients with synchronous HNSCC and SESCC, 134 who underwent preceding HNSCC treatment with follow-up esophagogastroduodenoscopy (EGD) for SESCC were evaluated. Chemoradiotherapy was the most common treatment for HNSCC (56.0%), followed by surgery (17.2%), radiotherapy (14.9%), local resection (7.5%), and chemotherapy (4.5%). The tumor size of SESCC increased after HNSCC treatment in 18 patients (13.4%). Multivariate analysis revealed that an EGD interval of ≥ 120 days was significantly associated with increased tumor size in SESCC (odds ratio, 6.64; 95% confidence interval, 1.91-23.1). Tumor regrowth was observed in 70.6% of SESCCs that shrank with HNSCC treatment, mostly within six months. Tumor depth aggravation was rare (2.2%), but progression to advanced ESCC was observed in two patients., Conclusions: Timely endoscopic follow-up, preferably within 120 days, is crucial for managing synchronous SESCC after HNSCC treatment to prevent tumor progression. Tumor regrowth should be monitored when SESCC shrinks with HNSCC treatment., Competing Interests: Declarations. Conflict of interest: Ryu Ishihara has received honoraria from Olympus, FUJIFILM Medical, Daiichi-Sankyo, Miyarisan Pharmaceutical, AI Medical Service, Astra Zeneca, MSD, and Ono Pharmaceutical. Satoki Shichijo has received honoraria from Olympus, EA Pharma, Astra Zeneca, AI Medical Service, Janssen Pharmaceutical, and FUJIFILM Medical. Takashi Kanesaka has received honoraria from Olympus, AstraZeneca, and AI Medical Service. Sachiko Yamamoto has received honoraria from Ono Pharmaceutical and MSD. Noriya Uedo has received honoraria from Olympus, FUJIFILM Medical, Boston Scientific, Daiichi-Sankyo, Takeda Pharmaceutical, EA Pharma, Otsuka Pharmaceutical, AstraZeneca, Miyarisan Pharmaceutical, and AI Medical Service. Takashi Fujii has received honoraria from Merck Biopharma, Taiho Pharmaceutical, Rakuten Medical, MSD, and Medtronic. The other authors have no financial relationships to disclose., (© 2024. Japanese Society of Gastroenterology.)

Background: The association between tumor-infiltrating lymphocytes and tumor immunity has long been recognized. Among T-cell types, CD45RO-positive memory T cells (CD45RO + ) are reported to correlate with survival in several cancer types, but clinical evidence is lacking in esophageal squamous cell carcinoma (ESCC)., Methods: In surgical specimens from 162 preoperatively untreated patients, immunohistochemistry for CD45RO was performed to evaluate the density of CD45RO + in the tumor core (CT) and invasive margin (IM) using an auto-count method. Patients were classified into high- versus low-CD45RO + groups based on CD45RO + density in CT and IM separately and combined. The relationship between CD45RO + density and clinicopathological factors, including prognosis, was evaluated., Results: Average CD45RO + density was 133/mm 2 in CT and 372/mm 2 in IM. No significant differences in clinicopathological factors according to high- versus low-CD45RO + scores were identified. Using CT scores, the CD45RO + -high group had a better 5-year overall survival (OS) rate (77.2% vs. 54.7% CD45RO + -low, P = 0.0433), but OS rates did not differ statistically between the two groups by IM scores (75.7% vs. 50.3%, P = 0.0576). Using immunohistochemical scores for CT+IM, the survival difference was significant, with a 5-year OS rate of 73.7% for the CD45RO + -high group versus 46.3% for the CD45RO + -low group (P = 0.0141). Multivariate analysis identified CD45RO + CT+IM density as an independent prognostic variable in OS (hazard ratio 2.27, 95% confidence interval 1.43-3.62, P = 0.0006)., Conclusions: Density of CD45RO + expression in the CT and IM might be a predictor of long-term survival in ESCC., Competing Interests: Disclosures: There are no conflicts of interest., (© 2024. The Author(s).)

Purpose: This study investigated the prevalence and risk factors of acute kidney injury (AKI) and chronic kidney disease (CKD) in cancer patients with the aim of providing guidance for clinical treatment of cancer patients., Methods: A retrospective study was conducted on all cancer and hematological malignancy patients admitted to Xuanwu Hospital, Capital Medical University, from January 2018 to July 2023. The study population included patients aged 18-80 years with a confirmed cancer or malignancy diagnosis. Chi-square tests, Spearman's correlation, and logistic regression were used to evaluate the relationships between demographic factors, comorbidities, cancer types, antitumor drugs and the prevalence of AKI/CKD., Results: Among the 2438 participants, the prevalence rates of AKI and CKD were 3.69% and 7.88%, respectively. Patients with diabetes had higher prevalence of AKI/CKD than those without diabetes (OR = 1.66, 95% CI 1.01-2.68, p = 0.040; OR = 1.60, 95% CI 1.10-2.31, p = 0.012, respectively). In addition, a higher prevalence of CKD was observed in patients with hypertension (OR = 3.49, 95% CI 2.43-5.06, p < 0.001). Underweight patients were more likely to develop AKI (OR = 2.66, 95% CI 1.03-6.08, p = 0.029). Anthracyclines may contribute to a higher risk of AKI, and antimetabolites and immunomodulators may be associated with the development of CKD. Overall, patients with hematological malignancies had significantly higher rates of AKI/CKD than those with solid tumors. Among solid tumor patients, the prevalence of AKI/CKD was low in patients with lung and breast cancer., Conclusions: AKI and CKD prevalence varies across cancer types, influenced by factors, such as diabetes, hypertension, body weight, and antitumor drugs. Tailored treatment plans are essential for improving cancer patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

While the importance of conversion surgery has increased with the development of systemic chemotherapy for gastric cancer (GC), reports of conversion surgery for patients with GC with distant metastasis and tumor thrombus are extremely scarce, and a definitive surgical strategy has yet to be established. Herein, we report a 67-year-old man with left abdominal pain referred to our hospital following a diagnosis of unresectable GC. Esophagogastroduodenoscopy and contrast-enhanced abdominal computed tomography (CT) revealed advanced GC with splenic metastasis. A splenic vein tumor thrombus (SVTT) and a continuous thrombus to the main trunk of the portal vein were detected. The patient was treated with anticoagulation therapy and systemic chemotherapy comprising S-1 and oxaliplatin. One year following chemotherapy initiation, a CT scan revealed progressive disease (PD); therefore, the chemotherapy regimen was switched to ramucirumab with paclitaxel. After 10 courses of chemotherapy resulting in primary tumor and SVTT shrinkage, the patient underwent laparoscopic total gastrectomy (LTG) and distal pancreaticosplenectomy (DPS). He was discharged without complications and remained alive 6 months postoperatively without recurrence. In summary, the wait-and-see approach was effective in a patient with GC with splenic metastasis and SVTT, ultimately leading to an R0 resection performed via LTG and DPS. [ABSTRACT FROM AUTHOR]

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Copyright of Journal of Modern Medicine & Health is the property of Journal of Modern Medicine & Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial roles in many cellular functions, regardless of any specific mutation. Many BET inhibitors (BETi) are currently in pre-clinical and early clinical development, but acquisition of resistance continues to remain an obstacle for the drug class. Novel methods to circumvent this development of resistance could be instrumental for the future use of BET inhibitors in AML, both as monotherapy and in combination. To date, many investigations into possible drug combinations of BETi with CDK inhibitors have focused on CDK9, which has a known physical and functional interaction with the BET protein BRD4. Therefore, we wished to investigate possible synergy and additive effects between inhibitors of these targets in AML. Here, we describe combination therapy with the multi-CDK inhibitor dinaciclib and the BETi PLX51107 in pre-clinical models of AML. Dinaciclib and PLX51107 demonstrate additive effects in AML cell lines, primary AML samples, and in vivo. Further, we demonstrate novel activity of dinaciclib through inhibition of the canonical/β-catenin dependent Wnt signaling pathway, a known resistance mechanism to BETi in AML. We show dinaciclib inhibits Wnt signaling at multiple levels, including downregulation of β-catenin, the Wnt co-receptor LRP6, as well as many Wnt pathway components and targets. Moreover, dinaciclib sensitivity remains unaffected in a setting of BET resistance, demonstrating similar inhibitory effects on Wnt signaling when compared to BET-sensitive cells. Ultimately, our results demonstrate rationale for combination CDKi and BETi in AML. In addition, our novel finding of Wnt signaling inhibition could have potential implications in other cancers where Wnt signaling is dysregulated and demonstrates one possible approach to circumvent development of BET resistance in AML. [ABSTRACT FROM AUTHOR]

The heart, once considered a mere blood pump, is now recognized as a multifunctional metabolic and endocrine organ. Its function is tightly regulated by various metabolic processes, at the same time it serves as an endocrine organ, secreting bioactive molecules that impact systemic metabolism. In recent years, research has shed light on the intricate interplay between the heart and other metabolic organs, such as adipose tissue, liver, and skeletal muscle. The metabolic flexibility of the heart and its ability to switch between different energy substrates play a crucial role in maintaining cardiac function and overall metabolic homeostasis. Gaining a comprehensive understanding of how metabolic disorders disrupt cardiac metabolism is crucial, as it plays a pivotal role in the development and progression of cardiac diseases. The emerging understanding of the heart as a metabolic and endocrine organ highlights its essential contribution to whole body metabolic regulation and offers new insights into the pathogenesis of metabolic diseases, such as obesity, diabetes, and cardiovascular disorders. In this review, we provide an in-depth exploration of the heart’s metabolic and endocrine functions, emphasizing its role in systemic metabolism and the interplay between the heart and other metabolic organs. Furthermore, emerging evidence suggests a correlation between heart disease and other conditions such as aging and cancer, indicating that the metabolic dysfunction observed in these conditions may share common underlying mechanisms. By unraveling the complex mechanisms underlying cardiac metabolism, we aim to contribute to the development of novel therapeutic strategies for metabolic diseases and improve overall cardiovascular health. [ABSTRACT FROM AUTHOR]

Nephrotic edema stands out as one of the most common complications of nephrotic syndrome. The effective management of hypervolemia is paramount in addressing this condition. Initially, "the underfill hypothesis" suggested that proteinuria and hypoalbuminemia led to fluid extravasation into the interstitial space, causing the intravascular hypovolemia and activation of neurohormonal compensatory mechanisms, which increased the retention of salt and water. Consequently, the recommended management involved diuretics and human-albumin infusion. However, recent findings from human and animal studies have unveiled a kidney-limited sodium-reabsorption mechanism, attributed to the presence of various serine proteases in the tubular lumen-activating ENaC channels, thereby causing sodium reabsorption. There is currently no standardized guideline for diuretic therapy. In clinical practice, loop diuretics continue to be the preferred initial choice. It is noteworthy that patients often exhibit diuretic resistance due to various factors such as high-sodium diets, poor drug compliance, changes in pharmacokinetics or pharmacodynamics, kidney dysfunction, decreased renal flow, nephron remodeling and proteasuria. Considering these challenges, combining diuretics may be a rational approach to overcoming diuretic resistance. Despite the limited data available on diuretic treatment in nephrotic syndrome complicated by hypervolemia, ENaC blockers emerge as a potential add-on treatment for nephrotic edema. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumor (GIST) is the most common sarcoma located in gastrointestinal tract and derived from the interstitial cell of Cajal (ICC) lineage. Both ICC and GIST cells highly rely on KIT signal pathway. Clinically, about 80-90% of treatment-naive GIST patients harbor primary KIT mutations, and special KIT-targeted TKI, imatinib (IM) showing dramatic efficacy but resistance invariably occur, 90% of them was due to the second resistance mutations emerging within the KIT gene. Although there are multiple variants of KIT mutant which did not show complete uniform biologic characteristics, most of them have high KIT expression level. Notably, the high expression level of KIT gene is not correlated to its gene amplification. Recently, accumulating evidences strongly indicated that the gene coding, epigenetic regulation, and pre- or post- protein translation of KIT mutants in GIST were quite different from that of wild type (WT) KIT. In this review, we elucidate the biologic mechanism of KIT variants and update the underlying mechanism of the expression of KIT gene, which are exclusively regulated in GIST, providing a promising yet evidence-based therapeutic landscape and possible target for the conquer of IM resistance. 4PRyVFa8kwZXvTW_ZJMwbg Video Abstract [ABSTRACT FROM AUTHOR]

Suppressor of cytokine signaling 1 (SOCS1) is a potent regulator immune cell responses and a proven tumor suppressor. Inhibition of SOCS1 in T cells can boost antitumor immunity, whereas its loss in tumor cells increases tumor aggressivity. Investigations into the tumor suppression mechanisms so far focused on tumor cell-intrinsic functions of SOCS1. However, it is possible that SOCS1 expression in tumor cells also regulate antitumor immune responses in a cell-extrinsic manner via direct and indirect mechanisms. Here, we discuss the evidence supporting the latter, and its implications for antitumor immunity. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth most common malignancy worldwide having the fourth highest mortality rate. Energy metabolism is key and closely linked to tumour development. Most important in the reprogramming of cancer metabolism is the Warburg effect, which suggests that tumour cells will utilise glycolysis even with normal oxygen levels. Various molecules exert their effects by acting on enzymes in the glycolytic pathway, integral to glycolysis. Second, mitochondrial abnormalities in the reprogramming of energy metabolism, with consequences for glutamine metabolism, the tricarboxylic acid cycle and oxidative phosphorylation, abnormal fatty acid oxidation and plasma lipoprotein metabolism are important components of tumour metabolism. Third, inflammation-induced oxidative stress is a danger signal for cancer. Fourth, patterns of signalling pathways involve all aspects of metabolic transduction, and many clinical drugs exert their anticancer effects through energy metabolic signalling. This review summarises research on energy metabolism genes, enzymes and proteins and transduction pathways associated with gastric cancer, and discusses the mechanisms affecting their effects on postoperative treatment resistance and prognoses of gastric cancer. We believe that an in-depth understanding of energy metabolism reprogramming will aid the diagnosis and subsequent treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

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