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Exploration (Beijing, China) Apr 2024Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia,...
Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascade-responsive dual cycling amplification of •SO /•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the NaSO nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra-sulphide cleavage of nanoreactors to explosively release Na/SO /Fe and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO (Fe-catalyzed SO oxidation), proton (•SO -catalyzed HO decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe will be in turn recovered into Fe by excessive EG to circularly amplify •SO /•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na overload and weaken the ROS-scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk-shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.
PubMed: 38855614
DOI: 10.1002/EXP.20230054 -
Cureus May 2024Dual antiplatelet therapy (DAPT), vital post-percutaneous coronary intervention (PCI) to prevent cardiovascular events (CVEs) via aspirin and P2Y12 receptor antagonists,...
INTRODUCTION
Dual antiplatelet therapy (DAPT), vital post-percutaneous coronary intervention (PCI) to prevent cardiovascular events (CVEs) via aspirin and P2Y12 receptor antagonists, faces controversy when combined with proton pump inhibitors (PPIs) due to potential impacts on bleeding risk and antiplatelet efficacy, prompting the need for further research to determine optimal co-administration practices. This work evaluated the effects of PPIs on CVEs and inflammatory factors in patients with upper gastrointestinal bleeding (UGIB) undergoing DAPT after PCI.
MATERIALS AND METHODS
The data of 166 patients who underwent PCI and developed UGIB while on DAPT from April 2021 to April 2023 were retrospectively analyzed. The patients were rolled into two groups: those who received PPI treatment and those who did not, namely, the PPI and non-PPI group, respectively. Clinical data from these patients was analyzed, intending to provide relevant theoretical evidence for clinical practice. Furthermore, the occurrence of CVEs and the levels of inflammatory factors of patients in all groups were statistically analyzed.
RESULTS
Melena was the most common clinical symptom observed in all UGIB patients. The incidence of CVEs in the PPI group was not greatly different from that in the non-PPI group (>0.05). The distribution of CVEs occurrence among different PPI drugs also exhibited no obvious difference (>0.05). The PPI group exhibited greatly lower C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) based on the non-PPI group (<0.05).
CONCLUSION
Melena was the most frequent clinical manifestation in UGIB patients. The use of PPIs did not increase the risk of CVEs, and different PPI drugs did not affect the occurrence of CVEs. Furthermore, PPIs lowered CRP and TNF-α levels in serum of these patients.
PubMed: 38854272
DOI: 10.7759/cureus.59925 -
Physica Medica : PM : An International... Jun 2024Image-driven dose escalation to tumor subvolumes has been proposed to improve treatment outcome in head and neck cancer (HNC). We used F-fluorodeoxyglucose (FDG)...
BACKGROUND
Image-driven dose escalation to tumor subvolumes has been proposed to improve treatment outcome in head and neck cancer (HNC). We used F-fluorodeoxyglucose (FDG) positron emission tomography (PET) acquired at baseline and into treatment (interim) to identify biologic target volumes (BTVs). We assessed the feasibility of interim dose escalation to the BTV with proton therapy by simulating the effects to organs at risk (OARs).
METHODS
We used the semiautomated just-enough-interaction (JEI) method to identify BTVs in F-FDG-PET images from nine HNC patients. Between baseline and interim FDG-PET, patients received photon radiotherapy. BTV was identified assuming that high standardized uptake value (SUV) at interim reflected tumor radioresistance. Using Eclipse (Varian Medical Systems), we simulated a 10% (6.8 Gy(RBE)) and 20% (13.6 Gy(RBE)) dose escalation to the BTV with protons and compared results with proton plans without dose escalation.
RESULTS
At interim F-FDG-PET, radiotherapy resulted in reduced SUV compared to baseline. However, spatial overlap between high-SUV regions at baseline and interim allowed for BTV identification. Proton therapy planning demonstrated that dose escalation to the BTV was feasible, and except for some 20% dose escalation plans, OAR doses did not significantly increase.
CONCLUSION
Our in silico analysis demonstrated the potential for interim F-FDG-PET response-adaptive dose escalation to the BTV with proton therapy. This approach may give more efficient treatment to HNC with radioresistant tumor subvolumes without increasing normal tissue toxicity. Studies in larger cohorts are required to determine the full potential for interim F-FDG-PET-guided dose escalation of proton therapy in HNC.
PubMed: 38852365
DOI: 10.1016/j.ejmp.2024.103404 -
Journal of Chemical Information and... Jun 2024The human voltage-gated proton channel, hH1, is highly expressed in various cell types including macrophages, B lymphocytes, microglia, sperm cells and also in various...
The human voltage-gated proton channel, hH1, is highly expressed in various cell types including macrophages, B lymphocytes, microglia, sperm cells and also in various cancer cells. Overexpression of H1 has been shown to promote tumor formation by highly metastatic cancer cells, and has been associated with neuroinflammatory diseases, immune response disorders and infertility, suggesting a potential use of hH1 inhibitors in numerous therapeutic areas. To identify compounds targeting this channel, we performed a structure-based virtual screening on an open structure of the human H1 channel. Twenty selected virtual screening hits were tested on Chinese hamster ovary (CHO) cells transiently expressing hH1, with compound showing strong block of the proton current with an IC value of 8.5 μM. Biological evaluation of twenty-three additional analogs of led to the discovery of six other compounds that blocked the proton current by more than 50% at 50 μM concentration. This allowed for an investigation of structure-activity relationships. The antiproliferative activity of the selected promising hH1 inhibitors was investigated in the cell lines MDA-MB-231 and THP-1, where compound inhibited growth with an IC value of 9.0 and 8.1 μM, respectively. The identification of a new structural class of H1 inhibitors contributes to our understanding of the structural requirements for inhibition of this ion channel and opens up the possibility of investigating the role of H1 inhibitors in various pathological conditions and in cancer therapy.
Topics: Humans; Ion Channels; CHO Cells; Cricetulus; Animals; Structure-Activity Relationship; Drug Evaluation, Preclinical; Cell Line, Tumor; Cell Proliferation; User-Computer Interface; Molecular Docking Simulation
PubMed: 38850237
DOI: 10.1021/acs.jcim.4c00240 -
Scientific Reports Jun 2024To assess the effectiveness and safety of combining Saccharomyces boulardii powder with triple therapy as a primary approach for eradicating H. pylori infection, a total... (Randomized Controlled Trial)
Randomized Controlled Trial
To assess the effectiveness and safety of combining Saccharomyces boulardii powder with triple therapy as a primary approach for eradicating H. pylori infection, a total of 144 patients who tested positive for H. pylori and diagnosed with non-ulcer dyspepsia underwent endoscopy at two national centers between June 2017 and March 2019 were included. The patients were categorized into three groups using a subsection randomization method and received initial H. pylori eradication treatments. Microbial composition, eradication rates, symptom alleviation, and adverse reactions were monitored on the 14th and 44th days post-treatment. According to PP analysis showed the eradication rates for the SRAC group was 75%, BRAC was 93.18% and RAC was 65.2%. Group BRAC exhibited a marginally higher eradication rate compared to other groups. However, patients receiving Saccharomyces boulardii treatment exhibited an overall reduction in initial dyspepsia symptoms by the end of the treatment period. When employed as a primary strategy, the combination of Saccharomyces boulardii powder with triple therapy displayed notable efficacy and smaller gastrointestinal side effects in eradicating initial H. pylori infections among non-ulcer dyspepsia patients. Moreover, this approach demonstrated advantages in alleviating symptoms, exhibited favorable tolerance, and maintained a high level of clinical safety.
Topics: Humans; Saccharomyces boulardii; Helicobacter Infections; Male; Female; Helicobacter pylori; Middle Aged; Probiotics; Drug Therapy, Combination; Dyspepsia; Adult; Anti-Bacterial Agents; Gastrointestinal Microbiome; Treatment Outcome; Proton Pump Inhibitors; Aged; Amoxicillin
PubMed: 38849408
DOI: 10.1038/s41598-024-63894-z -
Medicine Jun 2024To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes... (Observational Study)
Observational Study
To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) undergoing treatment with Semaglutide for 6months. This single-arm pilot study included 21 patients with MASLD who received semaglutide for T2DM. Body weight, metabolic parameters, liver enzymes, fibrosis markers, skeletal muscle index (cm2/m2), and fat fraction (%) at the L3 level using the two-point Dixon method on magnetic resonance imaging (MRI), as well as liver steatosis and liver stiffness assessed using MRI-based proton density fat fraction (MRI-PDFF) and MR elastography, respectively, were prospectively examined before and 6 months after semaglutide administration. The mean age of the patients was 53 years and 47.6% were females. The median liver steatosis-fraction (%) and skeletal muscle steatosis-fraction values (%) significantly decreased (22.0 vs 12.0; P = .0014) and (12.8 vs 9.9; P = .0416) at baseline and 6 months, respectively, while maintaining muscle mass during treatment. Semaglutide also dramatically reduced hemoglobin A1c (%) (6.8 vs 5.8, P = .0003), AST (IU/L) (54 vs 26, P < .0001), ALT (IU/L) (80 vs 34, P = .0004), and γ-GTP (IU/L) levels (64 vs 34, P = .0007). Although not statistically significant, Body weight (kg) (79.9 vs 77.4), body mass index (BMI) (kg/m2) (28.9 vs 27.6), and liver stiffness (kPa) (28.9 vs 27.6) showed a decreasing trend. Fibrosis markers such as M2BPGi, type IV collagen, and skeletal muscle area did not differ. Semaglutide demonstrated favorable effects on liver and skeletal muscle steatosis, promoting improved liver function and diabetic status.
Topics: Humans; Female; Middle Aged; Male; Diabetes Mellitus, Type 2; Prospective Studies; Muscle, Skeletal; Glucagon-Like Peptides; Pilot Projects; Liver; Hypoglycemic Agents; Fatty Liver; Adult; Glucagon-Like Peptide-1 Receptor; Magnetic Resonance Imaging; Elasticity Imaging Techniques; Glycated Hemoglobin; Aged
PubMed: 38847728
DOI: 10.1097/MD.0000000000038444 -
Medecine Tropicale Et Sante... Mar 2024Accidental ingestion of a foreign body into the gastrointestinal tract is not uncommon, however the development of hepatic abscesses secondary to digestive perforation...
Accidental ingestion of a foreign body into the gastrointestinal tract is not uncommon, however the development of hepatic abscesses secondary to digestive perforation by a foreign body is rare. We report the case of pyogenic hepatic abscesses secondary to gastric perforation by a fishbone complicated by acute peritonitis. A 53-year-old patient was admitted to our hospital with the main complaints: diffuse abdominal pain with vomiting in a context of fever and physical asthenia. A painful febrile hepatomegaly with jaundice was objectified, as well as a non-specific biological inflammatory syndrome. An initial abdominopelvic CT scan revealed multifocal liver abscesses. Faced with the initial therapeutic failure associating parenteral antibiotic therapy and abscess drainage, a second abdominal CT scan identified a foreign body straddling the antropyloric wall and segment I of the liver.A xypho-pelvic midline laparotomy was performed with nearly 200 cc of peritoneal fluid coming out. A fishbone approximately 5 cm long was extracted by laparotomy, followed by gastric closure with omentum, peritoneal cleansing and drainage. Symptomatic adjuvant treatment was initiated, including a proton pump inhibitor (Pantoprazole). He also benefited from transfusion support in the face of anemia. Antibiotic therapy was continued for a total of 2 weeks after surgery. The evolution was favorable with follow-up imaging at 3 months, showing complete resorption of the hepatic abscesses.
Topics: Humans; Middle Aged; Peritonitis; Male; Liver Abscess, Pyogenic; Foreign Bodies; Acute Disease; Senegal; Stomach
PubMed: 38846121
DOI: 10.48327/mtsi.v4i1.2024.390 -
Medecine Tropicale Et Sante... Mar 2024Caustic ingestion in children is a public health problem; it is mainly due to domestic accidents due to improper packaging and storage of caustic products. It is a...
[Results of emergency management of esophageal lesions related to caustic ingestion in children in the emergency department of the General Reference Hospital of Niamey (Niger)].
INTRODUCTION
Caustic ingestion in children is a public health problem; it is mainly due to domestic accidents due to improper packaging and storage of caustic products. It is a medical and surgical emergency whose management is multidisciplinary. The lesions caused by the accidental ingestion of caustics can affect the functional and vital prognosis in 10% of cases.
METHODOLOGY
A retrospective, descriptive study from January 2020 to December 2022 (2 years), carried out in the emergency department of the General Reference Hospital of Niamey (Niger). The study included patients less than 15 years old admitted for ingesting a caustic product.
RESULTS
Our study included 17 patients. The average age was 5 years, with age extremes of 2 to 11 years. We noted a male predominance with a sex ratio (M/F) of 2.4. Ingestion of caustic products was accidental in all cases. The caustic product was caustic soda in 59%. The average quantity of product ingested was 5 ml (2 ml to 20 ml). The average consultation time was 3 days (3 hours to 15 days). Clinically, dysphagia was the most functional sign, represented by 13 cases, or 76%. Regarding general signs, 3 patients (18%) were admitted with fever; blood pressure was normal in 15 patients (88%); and 2 patients (18%) were admitted in a state of shock. The respiratory rate was normal in 14 patients (82%). Four patients (24%) were admitted in a state of deterioration in the general condition associated with severe malnutrition and dehydration. On physical examination, 2 patients (12%) presented with abdominal defense at the epigastric level. Examination of the ENT sphere revealed benign buccopharyngeal ulcerations in 2 patients (12%). Esogastroduodenal fibroscopy was performed in 4 patients (24%). The caustic lesions observed in the esophagus were: Zargar stage I at 25%, stage Ila at 50%, and stage Illb at 25%. In the stomach, the lesions were Zargar stage I in 75% of cases and stage III in 25% of cases. An injected thoracic-abdominopelvic computed tomography (CT) was performed in 3 patients (18%). It revealed a lack of enhancement of the esophageal wall compatible with esophageal necrosis in one patient. An esophagogastroduodenal transit was performed in 8 patients (47%) admitted more than 72 hours after ingestion of the caustic. They showed esophageal stenoses longer than 3 cm in 3 patients, multiple esophageal stenoses in 2 patients, a single esophageal stenosis in 2 patients, and a single antropyloric stenosis in 1 patient. Therapeutically, all patients benefited from antiemetics to avoid vomiting and proton pump inhibitors. Intravenous antibiotic prophylaxis with third-generation cephalosporin was administered to 12 patients (71%). Corticosteroid therapy based on IV prednisolone at a dose of 1 g/1.73 m per day was used to limit or prevent stenoses in 9 patients (53%). Parenteral nutrition was administered to 7 patients (41%). Endoscopic dilations were performed in 2 patients (12%). Emergency surgical treatment was performed in 7 patients (41%): 3 patients underwent transitional feeding gastrostomies; in 3 others, esophagoplasties by colon transplant were performed, and 1 patient was treated by stripping of the esophagus associated with total gastrectomy. The postoperative course was marked by a leak of esocolic anastomosis in one patient for whom conservative treatment was performed with good progress. The average length of hospital stay was 5 days (1-32 days).
CONCLUSION
Accidental caustic ingestions can have serious consequences. Preventing these accidents relies on raising public awareness of the dangers associated with improper storage of these products.
Topics: Humans; Male; Female; Child; Child, Preschool; Caustics; Retrospective Studies; Burns, Chemical; Emergency Service, Hospital; Esophagus; Esophageal Diseases
PubMed: 38846116
DOI: 10.48327/mtsi.v4i1.2024.399 -
Technology in Cancer Research &... 2024The aim of this matched-pair cohort study was to evaluate the potential of intensity-modulated proton therapy (IMPT) for sparring of the pelvic bone marrow and thus...
The aim of this matched-pair cohort study was to evaluate the potential of intensity-modulated proton therapy (IMPT) for sparring of the pelvic bone marrow and thus reduction of hematotoxicity compared to intensity-modulated photon radiotherapy (IMRT) in the setting of postoperative irradiation of gynaecological malignancies. Secondary endpoint was the assessment of predictive parameters for the occurrence of sacral insufficiency fractures (SIF) when applying IMPT. Two cohorts were analyzed consisting of 25 patients each. Patients were treated with IMPT compared with IMRT and had uterine cervical (n = 8) or endometrial cancer (n = 17). Dose prescription, patient age, and diagnosis were matched. Dosimetric parameters delivered to the whole pelvic skeleton and subsites (ilium, lumbosacral, sacral, and lower pelvis) and hematological toxicity were evaluated. MRI follow-up for evaluation of SIF was only available for the IMPT group. In the IMPT group, integral dose to the pelvic skeleton was significantly lower (23.4GyRBE vs 34.3Gy; < 0.001), the average V, V, and V were reduced by 40%, 41%, and 28%, respectively, compared to the IMRT group ( < 0.001). In particular, for subsites ilium and lower pelvis, the low dose volume was significantly lower. Hematotoxicity was significantly more common in the IMRT group (80% vs 32%; = 0009), especially hematotoxicity ≥ CTCAE II (36% vs 8%; = 0.037). No patient in the IMPT group experienced hematotoxicity > CTCAE II. In the IMPT cohort, 32% of patients experienced SIF. Overall SIF occurred more frequently with a total dose of 50.4 GyRBE (37.5%) compared to 45 GyRBE (22%). No significant predictive dose parameters regarding SIF could be detected aside from a trend regarding V50Gy to the lumbosacral subsite. Low-dose exposure to the pelvic skeleton and thus hematotoxicity can be significantly reduced by using IMPT compared to a matched photon cohort. Sacral insufficiency fracture rates appear similar to reported rates for IMRT in the literature.
Topics: Humans; Female; Radiotherapy, Intensity-Modulated; Proton Therapy; Bone Marrow; Middle Aged; Aged; Genital Neoplasms, Female; Radiotherapy Dosage; Adult; Radiotherapy Planning, Computer-Assisted; Organs at Risk; Organ Sparing Treatments
PubMed: 38845139
DOI: 10.1177/15330338241252622 -
Journal of the Canadian Association of... Jun 2024Updated 2016 consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC)...
BACKGROUND
Updated 2016 consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days.
OBJECTIVES
This was a retrospective cohort study to describe and compare the efficacy of anti- treatment regimens over the periods 2007-2015 and 2016-2021 as well as antibiotic resistance.
METHODS
A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients.
RESULTS
-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016-2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) ( < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7-26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016-2021 and sequential therapy in 2007-2015 (83% [66/80]) ( = 0.535, RD 4%, 95% CI -8.5-16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016-2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007-2015 to 2016-2021 (28% [13/46] to 61% [35/57], < 0.05, RD 33%, 95% CI 11.6-54.4%).
CONCLUSIONS
Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50-57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.
PubMed: 38841147
DOI: 10.1093/jcag/gwad051