Chronic use of PPIs as a potential cause of anemia: case reports and review of the literature

Proton pump inhibitors (PPIs) are drugs commonly used for many diseases of the gastrointestinal tract, such as gastroesophageal reflux disease, erosive esophagitis, and peptic ulcers of the stomach and duodenum. Used for about 30 years, they are currently the most effective drugs that reduce the gastric secretion of hydrochloric acid. However, a dramatic increase in their consumption has been recently observed. Very often, they are used not in accordance with the guidelines. The consequences of the long-term use of PPIs may be various, with the most common side effects being bone fractures, cardiovascular events, recurrent infections, and vitamin and mineral deficiencies. Case report: An 82-year-old and a 58-year-old patients who had been taking omeprazole, a PPI for several years, developed vitamin B12 and iron deficiency anemia. Both patients were administered PPI orally for nonspecific dyspeptic symptoms. An evaluation of the gastrointestinal tract did not reveal the evident causes of gastrointestinal blood loss. They were also screened negative for infection. Conclusions: There are no definitive pieces of evidence that the long-term use of PPIs can induce anemia, but our cases strongly suggest this thesis. Physicians should be aware of this potential side effect and consider monitoring in high-risk patients

Wpływ mikroflory jelitowej na skuteczność immunoterapii z wykorzystaniem przeciwciał przeciwko immunologicznym punktom kontroli — opis przypadku i przegląd literatury

Inhibitory immunologicznych punktów kontroli (IPK), do których należą przeciwciała anty-PD-1 i anty-PD-L1, wykazują skuteczność u chorych na niedrobnokomórkowego raka płuca (NDRP) i znacząco wydłużają przeżycie pacjentów. Dotychczas nie zidentyfikowano czynników predykcyjnych, które pozwoliłyby na precyzyjną kwalifikację chorych na nowotwory do immunoterapii. Najlepiej zbadana pod tym względem jest ekspresja cząsteczki PD-L1 na komórkach nowotworowych, której występowanie wiąże się z częstszą odpowiedzią na immunoterapię oraz dłuższym czasem do progresji u chorych poddanych temu leczeniu. Ostatnio pojawiają się doniesienia, że skład mikroflory jelitowej chorego, obecność stanu zapalnego oraz stosowanie antybiotykoterapii przed lub w trakcie immunoterapii mogą mieć wpływ na skuteczność przeciwciał anty-PD-1 lub anty-PD-L1. Zachwianie naturalnej równowagi organizmu w wyniku działania antybiotyków może się wiązać z brakiem stymulacji układu immunologicznego przez antygeny pochodzące z bakterii występujących naturalnie w jelitach. Uzupełnienie mikroflory o niezbędne składniki może poprawić efektywność immunoterapii. Celem na przyszłość staje się opracowanie tzw. probiotyków immunoterapeutycznych, których stosowanie mogłoby wzmocnić efekt immunoterapii chorych na nowotwory

The impact of intestinal microflora on the effectiveness of immunotherapy with antibodies against immune checkpoints — case report and literature review

Inhibitors of immune checkpoints (anti-PD-1 or anti-PD-L1 monoclonal antibodies) are effective in non-small cell lung cancer treatment, significantly extending the overall survival of some patients. However, there are no predictive factors, which could allow precise qualification of cancer patients to immunotherapy. The best evaluated in this regard is the expression of PD-L1 molecule on tumour cells, the occurrence of which is associated with higher response rate and prolonged time to progression in patients undergoing immunotherapy. Some recent reports indicate that the composition of the patient’s intestinal microflora, the presence of inflammation, and antibiotic therapy used before or during immunotherapy may affect the effectiveness of anti-PD-1 or anti-PD-L1 antibodies. Disturbance of the body’s natural balance, e.g. due to the use of antibiotics, may reduce the effectiveness of immunotherapy. This may be due to a lack of stimulation of the immune system by antigens from bacteria found naturally in the gut. On the other hand, supplementing the microflora with the necessary ingredients can improve the effectiveness of immunotherapy. The future goal is to develop so-called “immunotherapeutic probiotics”, the use of which could enhance the effect of cancer immunotherapy

Current dietary recommendations for patients with cystic fibrosis

Cystic fibrosis (CF) is classified as metabolic and multisystem disease with autosomal recessive inheritance caused by mutations in the gene located on chromosome 7 encoding cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is a transmembrane chloride channel of epithelial cells and affects the activity of the mucous membrane of the sweat glands, airway epithelium, pancreatic ducts, vas deferens, bile ducts and intestines. In CF, increased concentration of chlorides in the sweat, pancreatic insufficiency and impaired absorption are observed as well as changes in the respiratory system related to, among others, impaired airway patency, weakening of the mucociliary clearance mechanism and the development of bacterial infections. CF is a chronic condition requiring comprehensive therapy. Nutritional treatment is an essential element of CF therapy. Malnutrition is a common complication in patient with CF and eating disorders. The majority of patients with CF have higher energy, protein and fat needs. In addition, supplementation with enzyme preparations, vitamins, sodium chloride, as well as the use of high-energy nutrients is recommended. The aim of the study was to evaluate current nutritional recommendations of patients with CF

Czy stosujemy spersonalizowane leczenie raka płuca? Wykorzystanie badań molekularnych w planowaniu wielu linii leczenia u chorego na gruczolakoraka płuca

W wielodyscyplinarnym podejściu do leczenia chorych na raka płuca coraz większą rolę odgrywają terapie ukierunkowane molekularnie, które można zastosować w genetycznie wyselekcjonowanej grupie chorych. Personalizacja leczenia zwiększa liczbę opcji terapeutycznych, wydłuża przeżycie chorych oraz zmniejsza ryzyko wystąpienia efektów ubocznych terapii, mogących zagrażać życiu. W niniejszym opracowaniu przenalizowano proces leczenia 57-letniego mężczyzny chorego na gruczolakoraka płuca, u którego wykryto mutację aktywującą w genie EGFR. Oprócz diagnostycznej segmentektomii oraz paliatywnej hemipelwektomii i radioterapii przerzutu do stawu biodrowego, a także operacji cytoredukcyjnej guza pierwotnego, u chorego zastosowano sześć linii leczenia systemowego opartych zarówno na nowoczesnych terapiach ukierunkowanych molekularnie i immunoterapeutykach, jak i standardowych cytostatykach, co pozwoliło uzyskać trzyletnie przeżycie pacjenta. Niezależnie od dobrego stanu ogólnego i dobrej tolerancji leczenia uporczywość kontynuowania terapii mimo braku dłuższej stabilizacji choroby pozostaje dyskusyjna

Effectiveness and safety of ixazomib–lenalidomide–dexamethasone in high-cytogenetic-risk relapsed/refractory multiple myeloma — results of the Polish Myeloma Group observational study

The survival of patients with multiple myeloma (MM) has significantly improved in recent years due to the introduction of new drugs such as proteasome inhibitors (PI) or immunomodulatory drugs (ImiDs). However, MM is still an incurable condition, with very variable clinical course. The group of patients with especially poor prognosis are individuals with relapsed/refractory multiple myeloma (RRMM) with specific cytogenetic disorders — del(17p), t(4;14), t(14;16). Among the therapies that are currently in use the ixazomib–lenalidomid–dexamethasone (IRd) is considered as a candidate to improve outcome. In this study, we analyzed the cases of patients diagnosed with high-risk molecular RRMM, who have been treated with the IRd chemotherapy regimen. An aggressive case report with no known cytogenetic data was also added. The data was collected from four centers in Poland as part of the Polish Myeloma Group observational study. The results suggest high efficacy and good safety profile of IRd therapy in patients with RRMM and unfavorable cytogenetics

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

Lung cancer remains a leading cause of cancer-related deaths worldwide, overtaking colon, breast, and prostate cancer-related deaths. Due to the limited diagnostic possibilities, it is often diagnosed after it has reached an advanced stage. The delayed diagnosis significantly worsens the patient’s prognosis. In recent years, we have observed an increased interest in the use of microRNAs (miRNAs) as diagnostic, predictive, and prognostic markers in non-small-cell lung cancer (NSCLC). The abnormal expression levels of the miRNAs could be used to detect NSCLC in its early stages while it is still asymptomatic. This could drastically improve the clinical outcome. Furthermore, some miRNAs could serve as promising predictive and prognostic factors for NSCLC. Some of the currently available studies have shown a correlation between the miRNAs’ levels and the sensitivity of tumour cells to different treatment regimens. Analysing and modulating the miRNAs’ expression could be a way to predict and improve the treatment’s outcome

Methylation of DROSHA and DICER as a Biomarker for the Detection of Lung Cancer

Background: Lung cancer is the leading cause of cancer-related deaths. Early diagnosis may improve the prognosis. Methods: Using quantitative methylation-specific real-time PCR (qMSP-PCR), we assessed the methylation status of two genes (in two subsequent regions according to locations in their promoter sequences) related to carcinogenesis, DICER and DROSHA, in 101 plasma samples (obtained prior to the treatment) of lung cancer patients and 45 healthy volunteers. Results: The relative level of methylation of DROSHA was significantly lower (p = 0.012 for first and p < 0.00001 for the second region) and DICER significantly higher (p = 0.029 for the first region) in cancer patients. The relative level of methylation of DROSHA was significantly (p = 0.037) higher in patients with early-stage NSCLC (IA-IIIA) and could discriminate them from healthy people with a sensitivity of 71% and specificity of 76% (AUC = 0.696, 95% CI: 0.545–0.847, p = 0.011) for the first region and with a sensitivity of 60% and specificity of 85% (AUC = 0.795, 95% CI: 0.689–0.901, p < 0.0001) for the second region. Methylation analysis of the first region of the DICER enabled the distinction of NSCLC patients from healthy individuals with a sensitivity of 96% and specificity of 60% (AUC = 0.651, 95% CI: 0.517–0.785, p = 0.027). The limitations of the study include its small sample size, preliminary nature, being an observational type of study, and the lack of functional experiments allowing for the explanation of the biologic backgrounds of the observed associations. Conclusion: The obtained results indicate that the assessment of DICER and DROSHA methylation status can potentially be used as a biomarker for the early detection of lung cancer

Polymorphism of Baculoviral Inhibitor of Apoptosis Repeat-Containing 5 (BIRC5) Can Be Associated with Clinical Outcome of Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) comprises about 85% of all lung cancers. Currently, NSCLC therapy is based on the analysis of specific predictors, whose presence qualifies patients for appropriate treatment. Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5), also known as “survivin”, is a protein whose expression is characteristic for most malignant tumors and fetal tissue, while absent in mature cells. The biological role of BIRC5 is to counteract apoptosis by inhibiting the initiating and effector activities of caspases and binding to microtubules of the mitotic spindle. In our study, we looked for a relationship between BIRC5 gene polymorphism and the effectiveness of platinum-based chemotherapy. The study group consisted of 104 patients with newly diagnosed locally advanced or metastatic NSCLC. DNA was isolated from pretreatment blood samples, and SNPs of BIRC5 gene were analyzed. All patients received first-line platinum-based chemotherapy. Univariate analysis showed that a specific BIRC5 genotype was significantly associated with a higher risk of early progression (homozygous GG vs. heterozygous CG or CC: 28.9% vs. 11.9%). The presence of a homozygous GG genotype of the BIRC5 gene was insignificantly related to PFS shortening and TTP shortening. Moreover, significantly higher risk of overall survival shortening was associated with the BIRC5 homozygous GG genotype. Thus, studies on polymorphisms of selected genes affecting apoptosis may have a practical benefit for clinicians who monitor and treat NSCLC

Pleural Neoplasms—What Could MRI Change?

The primary pleural neoplasms constitute around 10% of the pleural tumors. The currently recommended method for their imaging is CT which has been shown to have certain limitations. Strong development of the MRI within the last two decades has provided us with a number of sequences that could potentially be superior to CT when it comes to the pleural malignancies’ detection and characterization. This literature review discusses the possible applications of the MRI as a diagnostic tool in patients with pleural neoplasms. Although selected MRI techniques have been shown to have a number of advantages over CT, further research is required in order to confirm the obtained results, broaden our knowledge on the topic, and pinpoint the sequences most optimal for pleural imaging, as well as the best methods for reading and analysis of the obtained data