Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: A Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

Circulating tumor cells help differentiate benign ovarian lesions from cancer before surgery: A literature review and proof of concept study using flow cytometry with fluorescence imaging.

Current tools are insufficient for distinguishing patients with ovarian cancer from those with benign ovarian lesions before extensive surgery. The present study utilized a readily accessible platform employing a negative selection strategy, followed by flow cytometry, to enumerate circulating tumor cells (CTCs) in patients with ovarian cancer. These counts were compared with those from patients with benign ovarian lesions. CTC counts at baseline, before and after anticancer therapy, and across various clinical scenarios involving ovarian lesions were assessed. A negative-selection protocol we proposed was applied to patients with suspected ovarian cancer and prospectively utilized in those subsequently confirmed to have malignancy. The protocol was implemented before anticancer therapy and at months 3, 6, 9 and 12 post-treatment. A cut-off value for CTC number at 4.75 cells/ml was established to distinguish ovarian malignancy from benign lesions, with an area under the curve of 0.900 (P<0.001). In patients with ovarian cancer, multivariate Cox regression analysis revealed that baseline CTC counts and the decline in CTCs within the first three months post-therapy were significant predictors of prolonged progression-free survival. Additionally, baseline CTC counts independently prognosticated overall survival. CTC counts obtained with the proposed platform, used in the present study, suggest that pre-operative CTC testing may be able to differentiate between malignant and benign tumors. Moreover, CTC counts may indicate oncologic outcomes in patients with ovarian cancer who have undergone cancer therapies.

Risk Factors for Isolated Sphenoid Sinusitis after Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

Clinical significance of regional constructive and wasted work in patients receiving cardiac resynchronization therapy.

Background: Previous studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT. Methods: We performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months. Results: At six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700-0.866) and 0.737 (95% CI: 0.644-0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755-0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07-3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38-4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up. Conclusion: LW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Noncanonical usage of stop codons in ciliates expands proteins with structurally flexible Q-rich motifs.

Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 26 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in 10 ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g. D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.

Investigating the role of undercoordinated Pt sites at the surface of layered PtTe2 for methanol decomposition.

Transition metal dichalcogenides, by virtue of their two-dimensional structures, could provide the largest active surface for reactions with minimal materials consumed, which has long been pursued in the design of ideal catalysts. Nevertheless, their structurally perfect basal planes are typically inert; their surface defects, such as under-coordinated atoms at the surfaces or edges, can instead serve as catalytically active centers. Here we show a reaction probability > 90 % for adsorbed methanol (CH3OH) on under-coordinated Pt sites at surface Te vacancies, produced with Ar+ bombardment, on layered PtTe2 - approximately 60 % of the methanol decompose to surface intermediates CHxO (x = 2, 3) and 35 % to CHx (x = 1, 2), and an ultimate production of gaseous molecular hydrogen, methane, water and formaldehyde. The characteristic reactivity is attributed to both the triangular positioning and varied degrees of oxidation of the under-coordinated Pt at Te vacancies.

Minimally invasive endoscopic evacuation with the novel, portable Axonpen neuroendoscopic system for spontaneous intracerebral hemorrhage.

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.

Nuance and profound impact: Evaluating the effects of the unmet full coma scale in patients with mild subdural hemorrhage.

INTRODUCTION: Patients with subdural hemorrhage (SDH) and a Glasgow Coma Scale (GCS) score of 13-15 are typically categorized as having mild traumatic brain injury. We hypothesize that patients without a maximum GCS score - specifically, patients with GCS scores of 13 and 14 - may exhibit poorer neurological outcomes. METHOD: Between January 1, 2019, and December 31, 2020, SDH patients with GCS scores ranging from 13 to 15 were retrospectively studied. We compared outcomes between patients with a maximum GCS score of 15 and those with scores of either 13 or 14. Independent factors associated with neurological deterioration among patients with a GCS score of 15 were evaluated using multivariate logistic regression (MLR) analysis. RESULTS: During the study period, 470 patients with SDH and GCS scores between 13 and 15 were examined. Compared to patients with a maximum GCS score (N = 375), those in the GCS 13-14 group (N = 95) showed significantly higher rates of neurological deterioration (33.7% vs. 10.4%, p value <0.001) and neurosurgical interventions (26.3% vs. 16.3%, p value <0.024). Moreover, the GCS 13-14 group had a significantly poorer prognosis than patients with a GCS score of 15 [mortality rate: 7.4% vs. 2.4%, p value <0.017; rate of impaired consciousness at discharge: 21.1% vs. 4.0%, p value <0.001; and rate of neurological disability at discharge: 29.5% vs. 6.9%, p value <0.001]. The MLR analysis revealed that SDH thickness (odds ratio = 1.127, p value = 0.006) was an independent risk factor for neurological disability at discharge in patients with a GCS score of 15. CONCLUSION: Among SDH patients with mild TBI, those with GCS scores of 13-14 exhibited poorer neurological outcomes than those with a maximum GCS score. The thickness of the SDH is positively associated with neurological disability in SDH patients with a maximum GCS score.

Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surface and act as a plasminogen receptor to facilitate cell migration via plasmin activation. Our proprietary ENO1 antibody, HL217, was screened for its specific binding to ENO1 and significant inhibition of cell migration and plasmin activation (patent: US9382331B2). METHODS: In this study, effects of HL217 were evaluated in vivo and in vitro for treating lung fibrosis. RESULTS: Elevated ENO1 expression was found in fibrotic lungs in human and in bleomycin-treated mice. In the mouse model, HL217 reduced bleomycin-induced lung fibrosis, inflammation, body weight loss, lung weight gain, TGF-ß upregulation in bronchial alveolar lavage fluid (BALF), and collagen deposition in lung. Moreover, HL217 reduced the migration of peripheral blood mononuclear cells (PBMC) and the recruitment of myeloid cells into the lungs. In vitro, HL217 significantly reduced cell-associated plasmin activation and cytokines secretion from primary human PBMC and endothelial cells. In primary human lung fibroblasts, HL217 also reduced cell migration and collagen secretion. CONCLUSIONS: These findings suggest multi-faceted roles of cell surface ENO1 and a potential therapeutic approach for pulmonary fibrosis.

High photoresponsivity MoS2phototransistor through enhanced hole trapping HfO2gate dielectric.

Phototransistor using 2D semiconductor as the channel material has shown promising potential for high sensitivity photo detection. The high photoresponsivity is often attributed to the photogating effect, where photo excited holes are trapped at the gate dielectric interface that provides additional gate electric field to enhance channel charge carrier density. Gate dielectric material and its deposition processing conditions can have great effect on the interface states. Here, we use HfO2gate dielectric with proper thermal annealing to demonstrate a high photoresponsivity MoS2phototransistor. When HfO2is annealed in H2atmosphere, the photoresponsivity is enhanced by an order of magnitude as compared with that of a phototransistor using HfO2without annealing or annealed in Ar atmosphere. The enhancement is attributed to the hole trapping states introduced at HfO2interface through H2annealing process, which greatly enhances photogating effect. The phototransistor exhibits a very large photoresponsivity of 1.1 × 107A W-1and photogain of 3.3 × 107under low light illumination intensity. This study provides a processing technique to fabricate highly sensitive phototransistor for low optical power detection.

Long-term follow-up and comparison of programmable and non-programmable ventricular cerebrospinal fluid shunts among adult patients with different hydrocephalus etiologies: a retrospective cohort study.

BACKGROUND: Programmable valve (PV) has been shown as a solution to the high revision rate in pediatric hydrocephalus patients, but it remains controversial among adults. This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients with different hydrocephalus etiologies. METHOD: We reviewed the chart of all patients with hydrocephalus receiving index ventricular cerebrospinal fluid (CSF) shunt operations conducted at a single institution from January 2017 to December 2017. Patients included in the study were followed up for at least 5 years. Statistical tests including independent t-test, chi-square test, and Fisher's exact test were used for comparative analysis, and Kaplan-Meier curve using log-rank test was performed to compare the revision-free survival between the PV and NPV groups. RESULTS: A total of 325 patients were included in the study, of which 181 patients were receiving PVs and 144 patients receiving NPV. There were 23 patients (12.8%) with PV and 22 patients (15.3%) with NPV receiving initial revision. No significant statistical difference in the initial revision rate was observed between the two groups (p = 0.52). No survival difference was found between the PV and NPV groups. However, better revision-free survival was noted in the PV group among idiopathic normal pressure hydrocephalus (iNPH) (p = 0.0274) and post-traumatic hydrocephalus (p = 0.017). CONCLUSIONS: The combination of the different etiologies of hydrocephalus and the features of PV and NPV results in different outcomes-revision rate and revision-free survival. PV use might be superior to NPV in iNPH and post-traumatic hydrocephalus patients. Further studies are needed to clarify the indications of PV use in adult hydrocephalus patients.

Long-term outcomes of coils embolization for superior hypophyseal artery aneurysms.

Objective: Superior hypophyseal artery (SHA) aneurysms are intradural, and their rupture can result in subarachnoid hemorrhage. Considering the related surgical difficulty and anatomical restrictions, endovascular treatment (EVT) is considered the most favorable modality for SHA aneurysms; however, the long-term outcomes of EVT have rarely been reported. The study assessed the incidence of and risk factors for recurrence of SHA aneurysms after EVT as well as the correlation factors for SHA aneurysm rupture. Methods: We included 112 patients with SHA aneurysms treated with EVT at our facility between 2009 and 2020. Here, EVT included non-stent-assisted (simple or balloon-assisted) or stent-assisted coiling. Flow diverter was not included because it was barely used due to its high cost under our national insurance's limitation, and a high proportion of ruptured aneurysms in our series. Univariate and multivariate logistic regression was performed to evaluate the correlation factors for SHA aneurysm rupture, along with the incidence of and risk factors for post-EVT SHA aneurysm recurrence and re-treatment. Results: In our patients, the mean angiographic follow-up period was 3.12 years. The presence of type IA or IB cavernous internal carotid artery (cICA) was strongly correlated with SHA aneurysm rupture. Recurrence occurred in 17 (13.4%) patients, of which only 1 (1.4%) patient had received stent-assisted coiling. All cases of recurrence were observed within 2 years after EVT. The multivariate logistic regression results showed that ruptured aneurysm and non-stent-assisted coiling were independent risk factors for aneurysm recurrence. Of the 17 cases of aneurysm recurrence, 9 (52.9%) received re-treatment. Moreover, aneurysm rupture was the only factor significantly correlated with re-treatment in multivariate logistic regression. No re-recurrence was observed when a recurrent aneurysm was treated with stent-assisted coiling. Conclusion: Type I cICA was common factor for aneurysm rupture. Although flow-diverter treatment serves as another suitable technique that was not compared with, coils embolization was effective treatment modality for SHA aneurysms, leading to low recurrence and complication rates, especially with stent use. All cases of recurrence occurred within 2 years after EVT; they were strongly associated with prior aneurysm rupture. Further stent-assisted coiling was noticed to prevent re-recurrence.

Rathke's cleft cyst classification and outcomes after endoscopic endonasal approach.

BACKGROUND: Rathke's cleft cyst is rare, with variable characteristics and no unified categorization system. This study aimed to evaluate long-term outcomes, based on different categorizations, of symptomatic Rathke's cleft cysts treated with endoscopic endonasal approach. METHODS: This retrospective study of 38 patients with symptomatic Rathke's cleft cyst treated with endoscopic endonasal approach from 2006/06-2021/08 recorded pre- and post-operative clinical presentation, endocrine and visual tests, radiological findings, and resection status. Rathke's cleft cysts were categorized by both cyst consistency and radiological features and clinical characteristics were analyzed. RESULTS: The most common pre-operative symptoms were visual field deficit (65.8%) and hypopituitarism (39.5 %). Visual field deficit improved in 84% of affected patients, and hyperprolactinemia improved in 80% of affected patients. Pre-operative hypothyroidism and hypogonadism were associated with radiological type 3 cysts, while headache was more common in type B and C. Type 3 cysts were also associated post-operative hypogonadism and hypothyroidism. Permanent Diabetes insipidus was found in 3 patients (7.9%). Cyst height was a significant factor related to pre-operative visual field deficit and post-operative Diabetes insipidus. Residual cysts were found in 11 cases (30.6%) and 9 patients experienced regrowth/recurrence. Residual cysts were a significant factor in regrowth/recurrence. Recurrence rate and post-operative complications were not correlated with different subtypes. CONCLUSIONS: Endoscopic endonasal approach for removal of Rathke's cleft cyst is a safe and effective intervention. It leads to significant improvement in visual field deficit and recovery of hyperprolactinemia. Although the incidence of post-operative Diabetes insipidus is high, it is usually temporary. Although different categorizations are not correlated to recurrence rate, they could help predict the status of hormone deficit.

Highly Active NiO-Ni(OH)2 -Cr2 O3 /Ni Hydrogen Evolution Electrocatalyst through Synergistic Reaction Kinetics.

High activity catalysts for hydrogen evolution reaction (HER) play a key role in converting renewable electricity to storable hydrogen fuel. Great effort has been devoted to the search for noble metal free catalysts to make electrolysis viable for practical applications. Here, a non-precious metal oxide/metal catalyst with high intrinsic activity comparable to Pt/C was reported. The electrocatalyst consisting of NiO, Ni(OH)2 , Cr2 O3 , and Ni metal exhibits a low overpotential of 27, 103, and 153 mV at current densities of 10, 100, and 200 mA cm-2 , respectively, in a 1.0 m NaOH electrolyte. The activity is much higher than that of NiOx /Ni or Cr2 O3 alone, showing the synergistic effect of NiOx /Ni and Cr2 O3 on catalyzing HER. Density functional theory calculations shows that NiO and Cr2 O3 on Ni surface lower the disassociation energy barrier for breaking H-OH bond, while Ni(OH)2 and Cr2 O3 create preferred sites on Ni surface with near-zero H* adsorption free energy to promote H* to gaseous H2 evolution. These synergistic effects of multiple-oxides/metal composition enhance the disassociation of H-OH and the evolution of H* to gaseous H2 , thus achieving high activity and demonstrating a promising composition design for noble metal free catalyst.

Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy.

Cancer-Associated Thrombosis: A Taiwanese Perspective on Therapeutic Options with Focus on Non-Vitamin K Antagonist Oral Anticoagulants.

Cancer-associated thrombosis (CAT) is a common complication of malignancies. Patients with CAT are at risk of venous thromboembolism recurrence, but also at risk of bleeding while anticoagulated. Taiwanese patients are perceived to have a lower incidence of CAT, likely leading to false reassurance for Taiwanese patients with cancer. Because of this, oncologists and cardiologists from multiple medical institutions in Taiwan have set forth to provide clinical consensus guidelines on the management of CAT, based on local clinical practices and guided by predominant international clinical practice guidelines. This paper aims to describe the current disease burden of cancer-associated venous thromboembolism in Taiwanese cancer patients, and discusses the unmet needs and gaps in the management of this medical complication. It also outlines diagnostic and management strategies relevant to the different treatment options available, such as non-vitamin K antagonist oral anticoagulants.

Adverse cardiovascular, limb, and renal outcomes in patients with diabetes after peripheral artery disease revascularization treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors.

AIMS: The effectiveness and limb safety of sodium glucose co-transporter 2 inhibitors (SGLT2i) for patients with type-2 diabetes (T2D) who have received peripheral artery disease (PAD) revascularization are unknown. METHODS AND RESULTS: In this nationwide retrospective cohort study, we identified a total of 2,455 and 8,695 patients with T2D who had undergone PAD revascularization and received first prescriptions for SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i), respectively, between May 1, 2016, and December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates between the two study groups. Patients were followed up from the drug index date until the occurrence of specified outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. After PSM, we observed that compared with DPP4i, SGLT2i were associated with comparable risks of ischemic stroke, acute myocardial infarction, and heart failure hospitalization but were associated with a lower risk of cardiac death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.40-0.90]; p = 0.0126). Regarding major limb outcomes, SGLT2i were associated with comparable risks of repeated revascularization and lower limb amputation compared with DPP4i. SGLT2i were associated with a lower risk of composite renal outcomes (HR: 0.40; 95% CI: 0.27-0.59; p < 0.0001) compared with DPP4i. CONCLUSION: In a real-world study of patients with T2D who had undergone PAD revascularization, SGLT2i were associated with lower risks of cardiac death and composite renal outcomes but not associated with increased risks of adverse limb events compared with DPP4i.