Acid Therapy Research Articles

Lipid-Lowering Therapy Associated Erectile Dysfunction and Testicular Pain: A Rare Case Report

Lipid-lowering therapy (LLT) includes a diverse group of pharmaceuticals designed to reduce blood levels of cholesterol and triglyceride (TG), helping to prevent cardiovascular diseases like myocardial infarction and stroke. LLT includes treatment with several lipid-lowering drugs (LLD), including hydroxymethylglutaryl (HMG-CoA) reductase inhibitors (statin), PCSK9 Inhibitors, cholesterol-absorbing inhibitors (Ezetimibe), Bile Acid Sequestrants, Fibrates, Niacin (Vitamin B3), Omega-3 Fatty Acids, Bempedoic Acid, and combination therapy. The efficacy and safety of these molecules vary widely. Statins are the first-line LLD for treating hypercholesterolemia and are widely used for cardiovascular disease prevention. Common side effects include muscle-related issues such as myalgia, muscle atrophy, and, rarely, rhabdomyolysis. However, adverse effects on male reproductive health are infrequent and often underreported. Other medication classes employed in LLT mostly share many of the ADRs seen with statins, although individual classes may have unique ADRs depending on the pharmacokinetics and pharmacodynamics. Here, we are reporting a unique case of a 50-year-old male patient with no prior history of sexual dysfunction or testicular issues and other comorbidities or habits, who developed loss of libido, erectile dysfunction (ED) and testicular pain with most of the LLD, which promptly resolved on discontinuation of the LLT. This case highlights the importance of considering potential reproductive side effects when prescribing LLT and monitoring male patients for symptoms of sexual dysfunction.

Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 2: hematologic malignancy.

Disseminated intravascular coagulation (DIC) associated with hematologic malignancies, particularly acute promyelocytic leukemia (APL), is characterized by marked fibrinolytic activation, which leads to severe bleeding complications. Therefore, appropriate diagnosis and management of DIC are crucial for preventing bleeding-related mortality. However, to date, no clinical guidelines have specifically addressed hematologic malignancy-associated DIC. Therefore, we developed diagnostic and management algorithms for DIC based on a systematic literature review. Notably, these guidelines recommend using the JSTH DIC diagnostic criteria (2017 version) or the former Ministry of Health and Welfare DIC diagnostic criteria (1983 version) to diagnose DIC. Furthermore, in the management of DIC, it is essential to treat the underlying disease through transfusion of platelet concentrates and fresh frozen plasma, if necessary. A systematic review of antifibrinolytic and anticoagulant therapies concluded that tranexamic acid therapy is not strongly recommended for patients with APL undergoing treatment with all-trans retinoic acid (Grade 1C). The use of recombinant thrombomodulin is weakly recommended (Grade 2B), whereas the use of other anticoagulants, including heparin and serine protease inhibitors, is weakly not recommended (Grade 2C). Therefore, we hope that these guidelines will help physicians find the best possible solutions in clinical practice.

Nanotechnology-Based Approaches for the Management of Diabetes Mellitus: An Innovative Solution to Long-Lasting Challenges in Antidiabetic Drug Delivery

Diabetes is a widespread metabolic illness. Mismanagement of diabetes can lead to severe complications that tremendously impact patients’ quality of life. The assimilation of nanotechnology in diabetes care holds the potential to revolutionize treatment paradigms, improve patient outcomes, and reduce the economic burden associated with this pervasive disease. This manuscript explores the multifaceted utilization of nanomaterials in diabetes care, emphasizing the unique features of nano-based medication delivery methods and smart drug delivery mechanisms. Additionally, this paper talks about research on nanocarrier-integrated oral, transdermal, and inhalable insulin delivery; dendrimer- and nanocarrier-coupled antisense oligonucleotide-driven gene therapy; the implementation of gold nanoparticles and quantum dots for glucose surveillance; and nucleic acid therapies. There are certain restrictions when using medication delivery methods that are commonly available to handle diabetes. In order to increase efficacy and safety, the rapidly developing science of nanotechnology is also being explored and employed in medical biology. Nanomaterials like liposomes, dendrimers, niosomes, polymeric and metallic nanocarriers, and solid lipid nanoparticles are among the nanocarriers that have been developed for better delivery of various oral hypoglycemic agents in comparison to conventional therapies. These nanocarriers provide great control over elevated blood glucose levels, making them one of the most intriguing and promising technologies available today. Furthermore, adding additional ligands to nanocarriers allows for more focused distribution while protecting the encapsulated hypoglycemic drugs.

Platelet-rich fibrin associated to bovine bone induces bone regeneration in model of critical-sized calvaria defect of rats submitted to Zoledronic Acid therapy: PRF induces bone healing

Reconstruction of bone defects prior to implant installation is a challenge, especially when the patient uses bisphosphonates. Given this difficulty, many studies investigate biomaterials that can improve the bone regeneration process. In this context, this study aimed to investigate the effect of platelet-rich fibrin (PRF) and Bio-Oss (BO) on bone regeneration of rats submitted to critical-sized calvaria defects and treated with ZA. Thirty Wistar rats received a single dose of ZA (120 μg/kg) and after 7 days, were submitted to an 8 mm calvaria defect. The animals were divided into 5 groups (n=6): ZA, BO, PRF or BO+PRF; animals from control group did not receive ZA. All animals were euthanized 12 weeks after surgical procedure and calvaria collected to histological, histomorphometric and micro-CT analyses. BO+PRF increased the number of osteoblasts (33%) and osteoclasts (58%), as well as blood vessels (70%) and Type I collagen (52%) (p<0.05) compared to ZA group. In summary, the association of BO+PRF improved bone healing of large bone defect in rats receiving ZA and this may be an interesting approach for the treatment to be tested in patients under anti-resorptive therapy.

Unveiling the Mechanism of Retinoic Acid Therapy for Cutaneous Warts: Insights from Multi-Omics Integration

Unveiling the Mechanism of Retinoic Acid Therapy for Cutaneous Warts: Insights from Multi-Omics Integration

Safety and efficacy of early versus delayed acetylsalicylic acid after surgery for spontaneous intracerebral haemorrhage in China (E-start): a prospective, multicentre, open-label, blinded-endpoint, randomised trial

Patients with non-traumatic intracerebral haemorrhage have a substantial risk of major adverse cardiovascular and cerebrovascular events, including ischaemic stroke, after surgery. The optimal timing of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage in patients at high risk of postoperative ischaemic events has not been characterised. We aimed to investigate the safety and efficacy of early versus late initiation of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage. This prospective, open-label, blinded-endpoint, randomised trial was done at eight stroke centres in China. Eligible patients were aged 18-70 years, undergoing surgery for the evacuation of spontaneous intracerebral haemorrhage, and had a high risk of postoperative ischaemic events. Using the minimisation method in an online randomisation system, patients were randomly assigned (1:1) to receive 100 mg acetylsalicylic acid once per day in either the early-start group (starting on the third day after surgery until the 90th day after surgery) or the late-start group (starting on the 30th day after surgery until the 90th day after surgery). Medication was taken orally or delivered via a feeding tube. The primary efficacy outcome was a composite of new major ischaemic cardiovascular, cerebrovascular, or peripheral vascular events within 90 days and the primary safety outcome was any intracranial bleeding within 90 days, both measured in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04820972, and is complete. From May 1, 2021, to May 1, 2023, 7323 patients were screened, of whom 269 (4%) were enrolled and randomly assigned: 134 to the early-start group and 135 to the late-start group. 195 (72%) patients were male, 74 (28%) were female, and the median age was 60·2 years (IQR 52·0-66·5). Haematomas were supratentorial and deep in most (170 [63%] of 269) patients. Ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events occurred within 90 days after surgery in 27 (20%) of 134 patients in the early-start group and 42 (31%) of 135 patients in the late-start group (odds ratio 0·56 [95% CI 0·32-0·98]; p=0·041). Intracranial bleeding occurred in one (1%) of 134 patients in the early-start group and four (3%) of 135 patients in the late-start group. Non-bleeding serious adverse events occurred in 57 (42%) of 134 patients in the early-start group and 57 (42%) of 135 patients in the late-start group. Starting acetylsalicylic acid on the third day after surgery for spontaneous intracerebral haemorrhage in Chinese patients at high risk of postoperative ischaemic events resulted in fewer postoperative ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events than starting acetylsalicylic acid therapy at 30 days, with no increased risk of intracranial bleeding. Whether early initiation of acetylsalicylic acid therapy is safe and improves clinical outcomes for broader populations of patients with spontaneous intracerebral haemorrhage requires further research. The National Key Research and Development Program of China.

Engineering Nano-Pills to Inhibit Ovarian Cancer Proliferation and Migration through a Combination of Chemical/Nucleic Acid Therapy.

Ovarian cancer (OC) is the most fatal of all gynecological malignancies, presenting a significant threat to women's health. Its treatment is complicated by severe dose-dependent chemotherapy toxicity, drug resistance, and tumor migration. Herein, an intelligent combination strategy of chemotherapy and nucleic acid therapy, named ApMEmiR&D is developed. This integrated system consists of three parts: the nano-pill, the protective membrane, and the navigation element. Nano-pills are nanospheres assembled from miRNA and doxorubicin (DOX) with the help of ferrous ions (Fe2+). The protective membrane is derived from tumor-associated macrophages (TAMs membrane) originating from the primary tumor microenvironment (TME). The navigation element is the cholesterol-conjugated AS1411 aptamer. The resulting ApMEmiR&D nanoparticles exhibit uniform size, a well-defined nanosphere structure, robust serum stability, and ultra-high drug loading efficiency and capacity. The system can efficiently accumulate in the tumor, allowing for the synergistic inhibition of tumor growth and metastasis without apparent systemic toxicity. The results demonstrate the homing effect of tumor microenvironment-derived macrophage cell membrane and the targeting effect of aptamer, leading to precise drug targeting and immune compatibility, thereby enhancing therapeutic efficacy. The success of this strategy paves the way for metastasis inhibition and targeted cancer therapy.

Inhibition of the ANGPTL3/8 Complex for the Prevention and Treatment of Atherosclerotic Cardiovascular Disease.

Dyslipidemia is a casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with dyslipidemias. Angiopoietin-like protein 3 (ANGPTL3) and ANGPTL8 play key roles in triglyceride trafficking and energy balance in humans. We review the functional role of these ANGPTL proteins in the regulation of lipoprotein metabolism, and recent clinical trials targeting ANGPTL3 and ANGPTL3/8 with monoclonal antibody and/or nucleic acid therapies, including antisense oligonucleotides and small interfering RNA. Cumulative evidence supports the roles of ANGPTL3 and ANGPTL8 in lipid metabolism through inhibition of lipoprotein lipase and endothelial lipase activity. ANGPTL3 and ANGPTL3/8 inhibitors are effective in lowering plasma triglycerides and low-density lipoprotein (LDL)-cholesterol, with the possible advantage of raising high-density lipoprotein (HDL)-cholesterol with the inhibition of ANGPTL3/8. Therapeutic inhibition of ANGPTL3 and ANGPTL3/8 can lower plasma triglyceride and LDL-cholesterol levels possibly by lowering production and upregulating catabolism of triglyceride-rich lipoprotein and LDL particles. However, the effect of these novel agents on HDL metabolism remains unclear. The cardiovascular benefits of ANGPTL3 and ABGPTL3/8 inhibitors may also include improvement in vascular inflammation, but this requires further investigation.

Gallic Acid Induces HeLa Cell Lines Apoptosis via the P53/Bax Signaling Pathway.

Cervical cancer is a type of cancer that originates from the endometrium and is more common in developed countries and its incidence is increasing day by day in developing countries. The most commonly prescribed chemotherapeutic drugs limit their use due to serious side effects and the development of drug resistance. For this reason, interest in new active ingredients obtained from natural products is increasing. This study aimed to reveal the apoptotic and antiproliferative effects of gallic acid and doxorubicin combination therapy against the HeLa cell line. We investigated the anti-cancer effects of doxorubicin and gallic acid in the human HeLa cervical cell line by using the MTT test, Nucblue staining for the identification of apoptotic cells due to nuclear condensation using fluorescent substance, and apoptotic markers P53 and Bax for the RT-PCR test. The highest cytotoxic effect obtained in the study, the highest increase in apoptotic induction, and a significant difference in P53/Bax levels were seen in the gallic acid/doxorubicin combination. Additionally, it was determined that gallic acid exhibited an effective cytotoxic effect on HeLa and HaCat cells within 48 and 72 h of application. The obtained findings show that the gallic acid/doxorubicin combination applied to HeLa cells may be an alternative treatment against both the cytotoxic effect size and the side effects of the chemotherapy agent.

Abstract B006: Rescuing expression of a tumor suppressor gene – restoring FH in Hereditary leiomyomatosis and renal cell carcinoma

Abstract Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a disorder characterized by the loss of fumarate hydratase (FH) activity, leading to the development of cutaneous leiomyomas, uterine leiomyomas, and aggressive early-onset type 2 papillary renal cell carcinoma. In HLRCC, the disease is driven by the somatic loss of the remaining functional FH allele in individuals carrying a germline pathogenic variant in one copy of the FH gene. The complete loss of FH activity disrupts the tricarboxylic acid (TCA) cycle, resulting in the accumulation of fumarate, which disrupts signaling pathways and contributes to the oncogenic phenotype. We recently identified a single nucleotide polymorphism (SNP) in an intronic region of the fumarate hydratase (FH) gene that leads to the loss of FH activity (Crooks et al., 2023). This SNP introduces a novel splice-acceptor site, resulting in the inclusion of an aberrant exon between wild-type exons 9 and 10. This ‘poison-like’ exon encodes a premature STOP codon, producing a nonfunctional truncated FH protein. Previous studies have shown that restoring FH activity can abrogate pathogenic behavior in patient-derived cells, highlighting the potential for therapeutic interventions targeting FH activity restoration. Our goal is to restore FH enzymatic activity by preventing the inclusion of this cryptic exon in carriers of this variant. To achieve this, we are exploring strategies to restore functional FH production by interfering with the inclusion of the pathogenic intron during splicing by removing the splice acceptor using CRISPR-Cas9 or base editing technologies. We tested these approaches by generating a reporter cell line that recapitulates the splicing pattern observed in patients, where expression of GFP depends on correct splicing between exon 9 and 10. We successfully identified antisense oligonucleotide (ASO) and single-guide RNA (sgRNA) sequences that restore GFP expression in our reporter cell lines. We are now evaluating the efficacy of these reagents in patient-derived cells. An alternative approach involves using synthetic RNA to restore FH expression. The expression of proteins from synthetic RNAs is a promising strategy for treating cancer and infectious diseases. We are currently investigating the efficiency of restoring FH activity through in-vitro transcribed (IVT) mRNA. This approach has the advantage of enabling FH function restoration in cells with mutations that are not amenable to antisense oligonucleotide (ASO) or gene editing techniques. This work serves as an avenue to investigate the application of nucleic acid therapies to restoring activity tumor suppressor genes in kidney cancer. Citation Format: Siddhardha S. Maligireddy, Mariana D. Mandler, Jodie C. Lunger, Christina M. Fitzsimmons, Daniel R. Crooks, Geetha M. Cawthon, Christopher J. Ricketts, Cathy D. Vocke, W. Marson Linehan, Pedro J. Batista. Rescuing expression of a tumor suppressor gene – restoring FH in Hereditary leiomyomatosis and renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B006.

Treatment of acute pharyngitis in children: an Italian intersociety consensus (SIPPS-SIP-SITIP-FIMP-SIAIP-SIMRI-FIMMG).

Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery.

The Effect of Adjuvant Therapy on Metabolic Syndrome in Schizophrenia Patients at Madani Hospital

Background: Schizophrenia is a mental disorder that impacts behavior, emotions, and communication. In recent years, atypical antipsychotics have been increasingly prescribed because they significantly reduce both positive and negative symptoms. However, the long-term effects of atypical can cause metabolic syndrome. Additional therapy is provided to maximize the primary therapy and reduce the side effects. Method: This study used a quasi-experimental design with a single-blind, pretest-posttest approach. Patients who had been using atypical antipsychotics, either monotherapy or combination therapy, for more than 3 were examined pretest to determine metabolic syndrome levels. Group A received adjuvant therapy, while Group B did not receive adjuvant therapy. Based on this data, an analysis of the reduction in metabolic syndrome categories was conducted. Result: The percentage of schizophrenia patients by gender was dominated by males (60%). By age, the majority were adults (87%). In Group A, the incidence of metabolic syndrome decreased from 53% in the pretest to 40% in the posttest after being given vitamin A, B, and folic acid therapy. The most commonly used other medication was THP (38%). Conclusion: The administration of adjuvant therapy with vitamins A, B, E, and folic acid can reduce the value of one or two of the five metabolic syndrome criteria for schizophrenia patients (p = 0.052) compared to the group of patients who did not receive vitamins A, B, E, and folic acid adjuvant therapy. Future research should use a longer duration to observe the effects of vitamins A, B, E, and folic acid and evaluate their therapeutic doses. Additionally, it should narrow down the criteria for medication use, focusing solely on the atypical antipsychotic’s clozapine or olanzapine.

Hyaluronic Acid Combined with Ozone in Dental Practice.

Topical applications have long been regarded as precise methods for delivering drugs to soft tissues, such as the periodontal ligament, as well as hard structures, including the alveolar bone and cementum. Recently, the combination of hyaluronic acid (HA) and ozone therapy has gained popularity as a supportive treatment for chronic inflammation, in addition to its established role in enhancing healing after dental procedures. To gather the necessary research for our study, we conducted a systematic search across several databases, including PubMed, Google Scholar, and Ovid. Our study was registered under Prospero number CRD42024569641. The research, which began in June 2015 and concluded in May 2024, systematically examined the potential benefits of topical HA application in the management of both acute and chronic inflammatory diseases. Using relevant keywords and Medical Subject Headings, we selected 28 pertinent studies: three related to gingivitis, thirteen on chronic periodontitis, seven involving dental surgeries such as implants and sinus lifts, and three on oral ulcers. The risk of bias among the analyzed studies was assessed using the RoB 2 tool. Regarding the randomization process, 75% of the studies exhibited a high risk of bias. However, all studies (100%) had a low risk of bias concerning allocation concealment. Only 25% of the studies adequately addressed performance bias, and another 25% reported all outcome data. Nevertheless, 85% of the included studies showed a low risk of reporting bias. The results indicate that the use of topical HA in combination with ozone therapy is highly effective not only in promoting post-operative healing following dental procedures but also in providing positive outcomes for individuals dealing with chronic gingivitis, periodontal inflammation, and oral ulcers.

Middle meningeal artery embolization and tranexamic acid therapy for subdural hematoma in a patient with hereditary hemorrhagic telangiectasia: illustrative case.

Subdural hematoma is a rare manifestation of hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease. Here, the authors present a patient with HHT and a large chronic subdural hematoma, for whom nonsurgical management was pursued. A 49-year-old right-handed male with a history of hypertension and familial HHT presented with complaints of mild confusion and left hemiparesis over several days. Noncontrast head computed tomography images demonstrated a large chronic right hemisphere subdural hematoma compressing the right cerebral hemisphere and causing a 1.3-cm midline shift. Due to concerns about surgical complications arising from hemorrhages of cryptic telangiectasias, the patient was treated conservatively with middle meningeal artery embolization and adjuvant tranexamic acid. There was clinical and radiological resolution several months later. This case highlights the rarity of a subdural hematoma as a manifestation of HHT and the nonsurgical treatment strategy as a mechanism to avoid hemorrhagic complications of surgical evacuation. https://thejns.org/doi/10.3171/CASE24483.

Ultrasound-guided interventions in elite soccer players.

In the world of elite soccer, or football as we call it in the UK, a player who cannot play for any length of time costs the team money and team performance. The time to return to play (RTP) is crucial in any player's career, and the use of ultrasound-guided ultrasound injections has become important in the management of injury. In this article, I will explain the importance of good practice when performing these procedures and the use of steroids, sodium hyaluronic acid, platelet-rich plasma (PRP), and other therapies in achieving the goal of decreasing the time of RTP for the footballer. KEY POINTS: •Injection therapies are routine practice in maintaining and treating soccer injuries. •Injection therapies can be safely performed under ultrasound guidance.

Foreign-body granuloma formation in the lower eyelid after injection of poly-D,L-lactic acid as a collagen stimulator: a case report

Poly-D,L-lactic acid (PDLLA) is widely used in facial rejuvenation as a collagen stimulator, with a lower risk of granuloma formation compared to poly-L-lactic acid (PLLA). However, granulomas may still occur. In this case, a 58-year-old woman developed firm, non-tender, bilateral infraorbital granulomas 2 months after her third PDLLA injection for infraorbital hollowing. The lesions were unresponsive to intralesional trichloroacetic acid (TCA) and intense pulsed light therapy, necessitating surgical removal. Histopathological analysis confirmed foreign-body granulomas caused by the PDLLA filler. This case highlights the need for caution when injecting PDLLA into thin-skinned areas like the infraorbital region, where granulomas can be more visible due to limited tissue volume. Although PDLLA fillers are generally safe, granuloma formation remains a potential complication. Early diagnosis and treatment with non-surgical methods, such as intralesional TCA, should be prioritized. If these methods fail, surgical excision, aimed at preserving as much normal tissue as possible, may be necessary for optimal outcomes.

Spleen Targeting Nucleic Acid Delivery Vector Based on Metal-Organic Frameworks.

Nucleic acids have attracted increasing attention as drugs due to their fascinating advantages, such as long-term efficacy and ease of preparation compared to proteins. The nucleic acid therapy relies heavily on delivery vectors, which can prevent the degradation of nucleic acids while assisting them in cellular internalization. However, commonly used nonviral vector liposomes easily accumulate in the liver, which can limit their application in extrahepatic diseases. Herein, a potential spleen targeting vector for nucleic acids is developed based on the metal-organic frameworks. The plasmids are encapsulated inside the nanoscale zeolitic imidazolate framework (ZIF) via coprecipitation. The co-encapsulation of the cationic polymer poly(ether imide) (PEI) and the stabilizer polyvinylpyrrolidone (PVP) can significantly improve particle dispersion and stability. The prepared nanoparticles allow efficient transfection in vitro, mainly through clathrin-mediated and caveolae-mediated endocytosis. The biodistribution in mice shows that 46% of the nanoparticles accumulate in the spleen, which is much higher than that of the liposomes. The vector can successfully deliver plasmids to extrahepatic organs for protein synthesis and even induce an immune response. The elaborate ZIF-based nanoparticle may offer a new route for extrahepatic, especially spleen targeting delivery for the nucleic acids.

High-dose IV ascorbic acid therapy for patients with CCUS with TET2 mutations

AbstractThis phase 2 trial assessed high-dose IV ascorbic acid in TET2 mutant clonal cytopenia. Eight of 10 patients were eligible for response assessment, with no responses at week 20 by International Working Group Myelodysplasia Syndromes/Neoplasms criteria. This trial was registered at www.clinicaltrials.gov as #NCT03418038.

Recent Advances and Prospects of Nucleic Acid Therapeutics for Anti-Cancer Therapy

Nucleic acid therapeutics are promising alternatives to conventional anti-cancer therapy, such as chemotherapy and radiation therapy. While conventional therapies have limitations, such as high side effects, low specificity, and drug resistance, nucleic acid therapeutics work at the gene level to eliminate the cause of the disease. Nucleic acid therapeutics treat diseases in various forms and using different mechanisms, including plasmid DNA (pDNA), small interfering RNA (siRNA), anti-microRNA (anti-miR), microRNA mimics (miRNA mimic), messenger RNA (mRNA), aptamer, catalytic nucleic acid (CNA), and CRISPR cas9 guide RNA (gRNA). In addition, nucleic acids have many advantages as nanomaterials, such as high biocompatibility, design flexibility, low immunogenicity, small size, relatively low price, and easy functionalization. Nucleic acid therapeutics can have a high therapeutic effect by being used in combination with various nucleic acid nanostructures, inorganic nanoparticles, lipid nanoparticles (LNPs), etc. to overcome low physiological stability and cell internalization efficiency. The field of nucleic acid therapeutics has advanced remarkably in recent decades, and as more and more nucleic acid therapeutics have been approved, they have already demonstrated their potential to treat diseases, including cancer. This review paper introduces the current status and recent advances in nucleic acid therapy for anti-cancer treatment and discusses the tasks and prospects ahead.

Analysis of bleeding outcomes in patients with hypoproliferative thrombocytopenia in the A-TREAT clinical trial.

Despite prophylactic platelet transfusions, hypoproliferative thrombocytopenia is associated with bleeding; historical risk factors include hematocrit (HCT) 25%, activated partial thromboplastin time 30 s, international normalized ratio 1.2, and platelets 5000/μL. We performed a post hoc analysis of bleeding outcomes and risk factors in participants with hematologic malignancy and hypoproliferative thrombocytopenia enrolled in the American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) and randomized to receive either tranexamic acid (TXA) or placebo. World Health Organization (WHO) grade 2+ bleeding occurred in 46% of 330 participants, with no difference between the TXA (44%) and placebo (47%) groups (p = 0.66). Overall, the most common sites of bleeding were oronasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%). Among participants of childbearing potential, 28% experienced vaginal bleeding. Platelets ≤5000/μL and HCT < 21% (after adjusting for severe thrombocytopenia) were independently associated with increased bleeding risk (HR 3.78, 95% CI 2.16-6.61; HR 2.67, 95% CI 1.35-5.27, respectively). Allogeneic stem cell transplant was associated with nonsignificant increased risk of bleeding versus chemotherapy alone (HR 1.34, 95% CI 0.94-1.91). The overall rate of WHO grade 2+ bleeding was similar to previous reports, albeit with lower rates of gastrointestinal bleeding. Vaginal bleeding was common in participants of childbearing potential. Platelets ≤5000/μL remained a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT < 21%, suggesting a red blood cell transfusion threshold above 21% should be considered to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this population.