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Pharmacological Reports : PR Aug 2023Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal... (Review)
Review
Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and Helicobacter pylori eradication therapy. The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response. Recently, there has been a problem with the over-prescription of such drugs. Although PPIs do not have many side effects, their long-term use can contribute to small intestinal bacterial overgrowth (SIBO) or C. difficile and other intestinal infections. Probiotic supplementation during PPIs therapy may provide some hope in the reduction of emerging therapy side effects. This review aims to present the most important effects of long-term PPI use and provides critical insights into the role of probiotic intervention in PPI therapy.
Topics: Humans; Proton Pump Inhibitors; Clostridioides difficile; Dysbiosis; Gastroesophageal Reflux; Probiotics; Immunity; Immunomodulation
PubMed: 37142877
DOI: 10.1007/s43440-023-00489-x -
Critical Care Medicine Feb 2024Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their...
OBJECTIVE
Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality.
DESIGN
Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up.
SETTING
A total of 591,207 patient datasets of a German healthcare insurer were screened.
PATIENTS
We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation.
INTERVENTIONS
The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge.
MEASUREMENTS AND MAIN RESULTS
Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15-1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08-1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23-1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08-1.27; p = 0.006).
CONCLUSIONS
These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.
Topics: Humans; Proton Pump Inhibitors; Cohort Studies; Retrospective Studies; Critical Illness; Propensity Score
PubMed: 38240505
DOI: 10.1097/CCM.0000000000006104 -
Annals of Palliative Medicine Nov 2023Given its sharp dose fall off and ability to spare healthy surrounding tissue, proton beam therapy (PBT) has traditionally been used to treat various types of... (Review)
Review
Given its sharp dose fall off and ability to spare healthy surrounding tissue, proton beam therapy (PBT) has traditionally been used to treat various types of malignancies in the definitive setting, with strong, empirical data supporting its utility and safety. In the palliative setting, however, photon therapy has generally remained the standard of care in radiation treatment delivery due to lower cost, and greater availability. However, recent data suggest that the use of PBT may provide benefit in terms of symptom management and disease control in patients with locally advanced or recurrent disease who do not qualify for definitive therapy or with metastatic disease. Additionally, due to its unique dosimetric properties, PBT may confer less overall toxicity, thus helping preserve or improve the quality of life in this patient population, especially for those who are nearing end of life. While there is a need for further study, initial data analyzed from both retrospective and prospective single-institution and multi-institution trials are promising. This review aims to explore the efficacy and safety of PBT in the palliative setting among adults and to summarize pertinent studies that support its usage. To the authors' knowledge, this is the first review of the literature pertaining to PBT used in the palliative setting across multiple disease sites.
Topics: Adult; Humans; Proton Therapy; Retrospective Studies; Quality of Life; Prospective Studies; Neoplasms
PubMed: 37574582
DOI: 10.21037/apm-23-230 -
Ugeskrift For Laeger Jan 2024The general population is aging, which expectedly will lead to a future increase in older patients with cancer. This review summarises the recent advances in... (Review)
Review
The general population is aging, which expectedly will lead to a future increase in older patients with cancer. This review summarises the recent advances in radiotherapy. Technological advances have led radiotherapy to be an efficient and well-tolerated treatment option in older patient with cancer. Studies show no difference in toxicity and disease control rates compared with the ones in younger patients with cancer. MR-guided radiotherapy, proton therapy, and integration of artificial intelligence in treatment planning represent the latest advances in the field of radiotherapy and hold potential to further improve the treatment of older patients with cancer.
Topics: Humans; Aged; Artificial Intelligence; Neoplasms; Proton Therapy; Aging
PubMed: 38305322
DOI: 10.61409/V06230381 -
JAMA Network Open Aug 2023Radiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness.... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Radiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness. However, whether proton therapy has greater benefit than photon therapy is still unclear.
OBJECTIVE
To evaluate whether proton was associated with better efficacy and safety outcomes, including dosimetric, prognosis, and toxic effects outcomes, compared with photon therapy and to evaluate the efficacy and safety of proton therapy singly.
DATA SOURCES
A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and China National Knowledge Infrastructure databases was conducted for articles published through November 25, 2021, and updated to March 25, 2023.
STUDY SELECTION
For the comparison of proton and photon therapy, studies including dosimetric, prognosis, and associated toxic effects outcomes were included. The separate evaluation of proton therapy evaluated the same metrics.
DATA EXTRACTION AND SYNTHESIS
Data on study design, individual characteristics, and outcomes were extracted. If I2 was greater than 50%, the random-effects model was selected. This meta-analysis is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
The main outcomes were organs at risk (OARs) dosimetric outcomes, prognosis (overall survival [OS], progression-free survival [PFS], and objective response rate [ORR]), and radiation-related toxic effects.
RESULTS
A total of 45 studies were included in the meta-analysis. For dosimetric analysis, proton therapy was associated with significantly reduced OARs dose. Meta-analysis showed that photon therapy was associated with poor OS (hazard ratio [HR], 1.31; 95% CI, 1.07-1.61; I2 = 11%), but no difference in PFS was observed. Subgroup analysis showed worse OS (HR, 1.42; 95% CI, 1.14-1.78; I2 = 34%) and PFS (HR, 1.48; 95% CI, 1.06-2.08; I2 = 7%) in the radical therapy group with photon therapy. The pathological complete response rate was similar between groups. Proton therapy was associated with significantly decreased grade 2 or higher radiation pneumonitis and pericardial effusion, and grade 4 or higher lymphocytopenia. Single-rate analysis of proton therapy found 89% OS and 65% PFS at 1 year, 71% OS and 56% PFS at 2 years, 63% OS and 48% PFS at 3 years, and 56% OS and 42% PFS at 5 years. The incidence of grade 2 or higher radiation esophagitis was 50%, grade 2 or higher radiation pneumonitis was 2%, grade 2 or higher pleural effusion was 4%, grade 2 or higher pericardial effusion was 3%, grade 3 or higher radiation esophagitis was 8%, and grade 4 or higher lymphocytopenia was 17%.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, proton therapy was associated with reduced OARs doses and toxic effects and improved prognosis compared with photon therapy for esophageal cancer, but caution is warranted. In the future, these findings should be further validated in randomized clinical trials.
Topics: Humans; Proton Therapy; Protons; Pericardial Effusion; Radiation Pneumonitis; Esophageal Neoplasms
PubMed: 37581887
DOI: 10.1001/jamanetworkopen.2023.28136 -
Child's Nervous System : ChNS :... Oct 2023In spite of the continuous progresses in pediatric neurosurgery, adamantinomatous craniopharyngioma (AC) remains a challenging tumor due to its proximity to optic... (Review)
Review
BACKGROUND
In spite of the continuous progresses in pediatric neurosurgery, adamantinomatous craniopharyngioma (AC) remains a challenging tumor due to its proximity to optic pathways, pituitary gland, hypothalamus, and Willis' circle, which can result in significant endocrine, cognitive, and neurological morbidity after treatment with subsequent impact on the patient's quality of life (QoL). The relevance that QoL has today explains the changes in the management of AC observed over the time. The goal of the present article is to provide a historical background, to show the milestones in the changes of the AC treatment, and to analyze the current main options to manage such a challenging tumor.
MATERIAL AND METHODS
The pertinent literature has been reviewed. Moreover, a comparison between the past and recent personal series is reported.
RESULTS
Three main eras have been identified. The first (named Cushing era) was characterized by the need to realize a harmless surgery and to define the best way to approach AC; the second (microscope era) was characterized by a tremendous technical and technological development, with remarkable results in term of safe tumor resection and control but relatively poor QoL outcomes; and the third one (current period) is characterized by an increasing integration between surgery and adjuvant treatments, with relatively minor tumor control but significant improvement of QoL (comparable overall survival). The authors' experience reflects these changes. Two groups of children were compared: 52 cases (mean follow-up: 17.5 years) belong to the historical series (group 1, 1985-2003, aggressive surgical management) and 41 (mean follow-up: 8.5 years) to the current one (Group 2, 2004-2021, integrated management). No significant differences between the two groups were detected about recurrence rate, surgical mortality, and overall survival. However, Group 2 showed significant lower rates of postoperative panhypopituitarism, obesity, and visual deterioration.
CONCLUSIONS
Radical surgery allows for a good AC control with a low rate of recurrence but high risk of permanent morbidity. Despite the greater number of recurrences and surgeries, the more conservative policy, based on a combination of treatments, seems to provide the same tumor control with a better QoL. The advances in trans-nasal and trans-ventricular endoscopy, in proton therapy and in the management of the AC cyst are the main factors that allowed such an improvement.
Topics: Child; Humans; Craniopharyngioma; Quality of Life; Treatment Outcome; Pituitary Neoplasms; Retrospective Studies
PubMed: 37728836
DOI: 10.1007/s00381-023-06143-4 -
Ugeskrift For Laeger Mar 2024In early breast cancer, adjuvant moderately hypofractionated regimens are recommended for both whole breast, partial breast and locoregional irradiation which... (Review)
Review
In early breast cancer, adjuvant moderately hypofractionated regimens are recommended for both whole breast, partial breast and locoregional irradiation which abbreviates the overall treatment time, as argued in this review. Gating is recommended as well as the use of a simultaneous integrated boost when indicated. A tangential field set-up is standard, however, for challenging cases volumetric modulated arc therapy techniques, or referral for proton therapy, may be considered. In the metastatic setting, stereotactic radiotherapy is a promising treatment option for oligometastatic disease.
Topics: Female; Humans; Breast Neoplasms; Radiotherapy, Intensity-Modulated
PubMed: 38533873
DOI: 10.61409/V02230106 -
Cancers Aug 2023Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce... (Review)
Review
BACKGROUND
Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce the risk of these side effects for this population without compromising treatment efficacy.
METHODS
We review the current literature describing the utility of proton beam radiation therapy in the treatment of central nervous system tumors, sarcomas, breast cancer and Hodgkin lymphoma for the adolescent and young adult cancer population.
RESULTS
Proton beam radiation therapy has utility for the treatment of certain cancers in the young adult population. Preliminary data suggest reduced radiation dose to normal tissues, which might reduce radiation-associated toxicities. Research is ongoing to further establish the role of proton therapy in this population.
CONCLUSION
This report highlights the potential utility of proton beam radiation for certain adolescent young adult cancers, especially with reducing radiation doses to organs at risk and thereby potentially lowering risks of certain treatment-associated toxicities.
PubMed: 37686545
DOI: 10.3390/cancers15174269 -
Clinical and Molecular Hepatology Oct 2023Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and external beam radiation therapy has emerged as a promising approach for managing HCC.... (Review)
Review
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and external beam radiation therapy has emerged as a promising approach for managing HCC. Proton beam therapy (PBT) offers dosimetric advantages over X-ray therapy, with superior physical properties known as the Bragg peak. PBT holds promise for reducing hepatotoxicity and allowing safe dose-escalation to the tumor. It has been tried in various clinical conditions and has shown promising local tumor control and survival outcomes. A recent phase III trial demonstrated the non-inferiority of PBT in local tumor control compared to current standard radiofrequency ablation in early-stage HCC. PBT also tended to show more favorable outcomes compared to transarterial chemoembolization in the intermediate stage, and has proven effective in-field disease control and safe toxicity profiles in advanced HCC. In this review, we discuss the rationale, clinical studies, optimal indication, and future directions of PBT in HCC treatment.
Topics: Humans; Carcinoma, Hepatocellular; Proton Therapy; Liver Neoplasms; Chemoembolization, Therapeutic
PubMed: 37822213
DOI: 10.3350/cmh.2023.0274 -
Clinical Kidney Journal Nov 2023Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and outcomes, leading to an expanding use in millions of patients worldwide. However, they can... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and outcomes, leading to an expanding use in millions of patients worldwide. However, they can cause a spectrum of immune-related adverse events (irAEs). Essentially, any organs can be affected by irAEs, which have emerged as therapy-limiting side effects. In the kidneys, ICI-associated acute interstitial nephritis (ICI-AIN) leads to acute kidney injury (AKI) in 2%-5% of patients on ICI therapy. AKI associated with ICI therapy pathologically presents with AIN in nearly 90% of the cases, but the pathophysiology of ICI-AIN remains to be defined. The generation of autoreactive T cells in patients receiving AIN-inducible drugs, such as proton pump inhibitors (PPIs), is one of the leading theories, supported by a higher incidence of ICI-AIN in patients on these AIN-inducible drugs. In this review, we will discuss our understanding of the incidence, potential pathophysiological mechanisms, clinical presentations, risk factors, diagnosis, and management of PPI-related AIN and its interaction with ICI therapy.
PubMed: 37915905
DOI: 10.1093/ckj/sfad109