As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management of patients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, \"Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?\" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITY and ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic review and meta-analysis on antacid and antireflux surgery in IPF negate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

In the current study, Lactobacillus acidophilus was encapsulated in sodium alginate and whey protein isolate, with the addition of antacids CaCO3 or Mg(OH)2. The obtained microgels were observed by scanning electron microscopy. Encapsulated and free probiotics were subjected to vitality assay under stressed conditions. Furthermore, dried apple snack was evaluated as a carrier for probiotics for 28 days. A significant (p ≤ .05) effect of antacid with an encapsulating agent was observed under different stressed conditions. During exposure to simulated gastrointestinal conditions, there were observations of 1.24 log CFU and 2.17 log CFU, with corresponding 0.93 log CFU and 2.63 log CFU decrease in the case of SA + CaCO3 and WPI + CaCO3 respectively. Likewise, high viability was observed under thermal and refrigerated conditions for probiotics encapsulated with SA + CaCO3. In conclusion, the results indicated that alginate microgels with CaCO3 are effective in prolonging the viability of probiotics under stressed conditions.

Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID-19) infection and is associated with increased mortality in critically ill COVID-19 patients. It remains unclear whether acidosis further promotes SARS-CoV-2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis-related pH of 6.8 increases SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS-CoV-2 pseudovirus infection. Based on this, we synthesized polyglutamic acid-PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO3-NPs) nanoantidote to neutralize excess hydrogen ions (H+), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO3-NPs effectively prevented the heightened SARS-CoV-2 infection efficiency due to pH 6.8. Our study reveals that acidosis-related pH promotes SARS-CoV-2 infection, which suggests the existence of a positive feedback loop in which SARS-CoV-2 infection-induced acidosis enhances SARS-CoV-2 infection. Therefore, antacid therapy for acidosis COVID-19 patients is necessary. CaCO3-NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

The use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised.
We conducted a prospective cohort study using data collected from the Nurses\' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias).
Among 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13-1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17-1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02-1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12-1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10-2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97-1.11; cancer: HR, 1.07; 95% CI, 0.89-1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81-1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95-1.50; digestive diseases: HR, 1.38; 95% CI, 0.88-2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality.
After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.

OBJECTIVE: We assessed the impact of acid suppression therapy (i.e., ranitidine or proton pump inhibitors) on iron supplementation and its ability to maintain or alter laboratory values that are commonly associated with anemia.
METHODS: This was a prospective, observational trial. The primary outcome was changes in serum iron levels from baseline. Secondary outcomes were changes in hemoglobin (Hgb) and hematocrit (Hct), transfusions, and maintenance of an alkalotic gastric pH.
RESULTS: Thirty-four patients (mean 24 ± 43 months) met inclusion criteria. The serum iron levels increased to 50.9 ± 24.6 mcg/dL by day 3. The mean difference from baseline was 1.5 mcg/dL (95% CI, 1.14-1.98, p = 0.0056). Gastric pH increased to 4.68 ± 1.49 on day 5. The mean Hgb and Hct increased on day 5 to 10 ± 1.06 g/dL and 29.6% ± 3.27%, respectively. The mean difference of Hgb was 1.15 g/dL (95% CI, 0.51-1.78, p = 0.0009). The mean difference of Hct was 3.04% (95% CI, 1.11-4.97, p = 0.0032).
CONCLUSIONS: The use of antacids along with oral ferrous sulfate supplementation did not affect the absorption of iron. Serum iron, Hgb, and Hct all showed statistically significant increases despite combined antacid and iron therapy. Thus, despite use of antacids, combination use showed increases in iron absorption.

BACKGROUND: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting.
METHODS: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs).
RESULTS: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75-1.35) or multivariable analysis (HR 0.98, 95% CI 0.71-1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66-2.65) or AEs (OR 1.07, 95% CI 0.54-2.12) in multivariable analysis.
CONCLUSIONS: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

Calcium carbonate (CaCO3)-based materials have received notable attention for biomedical applications owing to their safety and beneficial characteristics, such as pH sensitivity, carbon dioxide (CO2) gas generation, and antacid properties. Herein, to additionally incorporate antioxidant and anti-inflammatory functions, we prepared tannylated CaCO3 (TA-CaCO3) materials using a simple reaction between tannic acid (TA), calcium (Ca2+), and carbonate (CO32-) ions. TA-CaCO3 synthesized at a molar ratio of 1:75 (TA:calcium chloride (CaCl2)/sodium carbonate (Na2CO3)) showed 3-6 μm particles, comprising small nanoparticles in a size range of 17-41 nm. The TA-CaCO3 materials could efficiently neutralize the acid solution and scavenge free radicals. In addition, these materials could significantly reduce the mRNA levels of pro-inflammatory factors and intracellular reactive oxygen species, and protect chondrocytes from toxic hydrogen peroxide conditions. Thus, in addition to their antacid property, the prepared TA-CaCO3 materials exert excellent antioxidant and anti-inflammatory effects through the introduction of TA molecules. Therefore, TA-CaCO3 materials can potentially be used to treat inflammatory cells or diseases.

BACKGROUND: Calcium carbonate antacids are potent over-the-counter antacids, made more effective by adding magnesium carbonate (as in Rennie, Bayer). However, published studies on their onset of action are scarce. Therefore, we carried out an in vitro study comparing Rennie and placebo under simulated conditions of the human stomach (artificial stomach model) to reconfirm the onset of action of Rennie.
METHODS: The validated Simulator of the Human Intestinal Microbial Ecosystem apparatus (SHIME, ProDigest, Belgium) was used, comprising five reactors simulating different parts of the human gastrointestinal tract. Both Rennie and placebo were dosed at two tablets per incubation over six independent, 2-h stomach incubations each.
OBJECTIVE: to evaluate the time required to achieve pH 3.0, 3.5, 4.0 and 4.5, as well as the maximum pH reached.
OBJECTIVE: to evaluate pepsin activity over the entire 2-h gastric incubation.
RESULTS: After addition of Rennie, the gastric medium reached a pH of 3.0 within 40 s. The maximum pH of 5.24 was maintained for almost 10 min. In contrast, the maximum pH with placebo was 1.28 during the entire gastric simulation. Furthermore, Rennie strongly reduced the activity of mucosa-damaging pepsin during the period of increased pH. With placebo, the lower pH resulted in consistently high loads of digested peptides, reflecting the high cumulative and instantaneous pepsin activity.
CONCLUSIONS: New data is a critical component in informed decision making. Our data confirm the high efficacy and fast onset of acid-neutralizing action of Rennie, which begins to work within seconds.

BACKGROUND: Reflux occurs in 50% of healthy infants at some point. This is most often a physiological condition and does not require drug treatment. Various studies have shown that the use of drugs affecting gastric acidity (DAGAs) in infants is increasing. This entails disadvantages such as unnecessary exposure of infants to medication and their side effects and a higher cost to society.
OBJECTIVE: To get an image of the current practice in Flanders regarding diagnosis and treatment of gastro-oesophageal reflux disease (GORD) in infants and the associated use of DAGAs. To this end, we determined both parents\' and health care providers\' experiences and perceptions about these treatments.
METHODS: An observational cross-sectional study was conducted in April and May 2019. We developed a questionnaire for parents and three different questionnaires for health care providers (HCPs), including midwives, general practitioners, paediatricians and community pharmacists (CPs). The questionnaire for parents was only available through an online platform. HCPs were questioned face-to-face and through an online platform.
RESULTS: This study made clear that the counselling of children with GORD is multidisciplinary as the median number of counselling HCPs is 3 (interquartile range (IQR) = 2-4). 63% of the included 251 parents also seek support through online forums and groups. 60% of parents report that no physical tests were performed before DAGAs were prescribed and 39% of parents additionally state they perceived no effect of the prescribed DAGAs. Although parents reported to understand HCPs well (average score 7.4/10), satisfaction with care and information provision was scored lower (between 4.8 and 6.1/10). On the other hand, 234 HCPs answered the questionnaire, of which 89 midwives, 78 community pharmacists and 67 physicians. Only 45 HCPs indicate that guidelines to diagnose or treat GORD are clear. Physicians confirm they perform very little physical testing before starting DAGAs. Provided nonmedical measures to patients are largely in line with the European guidelines, however perceived effectiveness is moderate.
CONCLUSIONS: Parents are in need for more information about tests, nutrition and (non)medical measures. HCPs on the other hand are in need for clear guidelines on diagnosing and treating GORD.