Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy.

There are a growing number of studies linking the composition of the human microbiome to disease states and treatment responses, especially in the context of cancer. This has raised significant interest in developing microbes and microbial products as cancer immunotherapeutics that mimic or recapitulate the beneficial effects of host-microbe interactions. Bacterial extracellular vesicles (bEVs) are nano-sized, membrane-bound particles secreted by essentially all bacteria species and contain a diverse bioactive cargo of the producing cell. They have a fundamental role in facilitating interactions among cells of the same species, different microbial species, and even with multicellular host organisms in the context of colonization (microbiome) and infection. The interaction of bEVs with the immune system has been studied extensively in the context of infection and suggests that bEV effects depend largely on the producing species. They thus provide functional diversity, while also being nonreplicative, having inherent cell-targeting qualities, and potentially overcoming natural barriers. These characteristics make them highly appealing for development as cancer immunotherapeutics. Both natively secreted and engineered bEVs are now being investigated for their application as immunotherapeutics, vaccines, drug delivery vehicles, and combinations of the above, with promising early results. This suggests that both the intrinsic immunomodulatory properties of bEVs and their ability to be modified could be harnessed for the development of next-generation microbe-inspired therapies. Nonetheless, there remain major outstanding questions regarding how the observed preclinical effectiveness will translate from murine models to primates, and humans in particular. Moreover, research into the pharmacology, toxicology, and mass manufacturing of this potential novel therapeutic platform is still at early stages. In this review, we highlight the breadth of bEV interactions with host cells, focusing on immunologic effects as the main mechanism of action of bEVs currently in preclinical development. We review the literature on ongoing efforts to develop natively secreted and engineered bEVs from a variety of bacterial species for cancer therapy and finally discuss efforts to overcome outstanding challenges that remain for clinical translation.

Correlates of Smoking, Work Stress, and Mindful Awareness among Private Hospital Workers in Istanbul.

Background: The recent increase in workload and stress experienced by healthcare workers (HCW) is a significant global concern. Mindfulness enables one to be aware of emotions, thoughts, and present moment experiences. Objectives: The primary objective of this research is to investigate the correlates between smoking, occupational stress, and mindful awareness levels, among HCWs within the private healthcare sector. This study was conducted at a tertiary-level university-affiliated hospital in Istanbul between January - February 2023. 208 HCW participated, yielding a response rate of 20%. The participants were requested to complete a 61-item questionnaire consisting of demographics, General Work Stress Scale(GWS), Mindful Attention Awareness Scale (MAAS) and Test to Assess the Psychological Dependence on Smoking (TAPDS). Results: Smokers had significantly higher levels of mean GWS scores than nonsmokers. The mean MAAS scores of smokers were the lowest in the group with the highest scores of psychological dependence; it was highest in the group with the lowest scores. A negative correlation was found between general work stress and mindful awareness levels and between psychological dependence on smoking and mindfulness levels. HCWs aged 45 and older had significantly lower general stress than others. Conclusion: This study showed that the general work stress levels of smoker HCWs were higher than those of nonsmokers. Mindful awareness level was the lowest in the group, with the highest scores in psychological dependence on smoking. There was a negative correlation between psychological dependence on smoking and both work stress and mindful awareness levels. This study demonstrated that high work stress and low mindful awareness levels are not only related to each other but also to high psychological dependence on smoking.

Comparison of tacrolimus vs. cyclosporine in pediatric hematopoietic stem cell transplantation for thalassemia.

OBJECTIVES: Graft-versus-host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia. MATERIALS AND METHODS: This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020. RESULTS: Despite the GvHD prophylaxis, grade II-IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI-related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p = .013). There was no significant difference between the groups in terms of engraftment syndrome, veno-occlusive disease, CMV reactivation, PRES, or graft rejection. CONCLUSION: Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI.

Mechanical thrombectomy for the treatment of large vessel occlusion due to cancer-related cerebral embolism: A systematic review.

BACKGROUND: Cancer-related cerebral embolism due to direct tumor embolization results in a rare acute ischemic stroke with large vessel occlusion (LVO). Despite the established status of mechanical thrombectomy (MT) in LVO management, its effectiveness and safety remains inadequately explored in this specific patient group. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the Nested Knowledge AutoLit software, encompassing databases like Embase, PubMed, Scopus, and Web of Science, from their inception up to 9 May 2023. RESULTS: In the review of 35 studies encompassing 37 cases, mean patient age was 52 years, and 30% were female. Cardiac myxoma (29.7%), cardiac papillary fibroelastoma (16.2%), and squamous cell carcinoma of the lung (8.1%) were the most frequent underlying cancers. The left middle cerebral artery was the most commonly affected occlusion site (24.3%). Of the patients, 67.5% underwent MT alone, while 32.5% received MT combined with intravenous thrombolysis. Successful reperfusion (thrombolysis in cerebral infarction (TICI) 2b-3) was achieved in 89.1% of cases, with 59.4% reaching TICI 3. Functional independence was observed in 29.7% of patients. CONCLUSION: While limitations exist, this comprehensive study highlights the potential benefits of MT in a patient group historically excluded from major trials, warranting further investigation.

Discoidin domain receptor 1 as a promising biomarker for high-grade gliomas.

Background: Two fundamental challenges in the current therapeutic approach for central nervous system tumors are the tumor heterogeneity and the absence of specific treatments and biomarkers that selectively target the tumor tissue. Therefore, we aimed to investigate the potential relationship between discoidin domain receptor 1 (DDR1) expression and the prognosis and characteristics of glioma patients. Materials and Methods: Tissue and serum samples from 34 brain tumor patients were evaluated for DDR1 messenger ribonucleic acid levels in comparison to 10 samples from the control group, and Kaplan-Meier survival analysis has performed. Results: DDR1 expression was observed in both tissue and serum samples of the patient and control groups. DDR1 expression levels in tissue and serum samples from patients were higher in comparison to the control group, although not statistically significant (P > 0.05). A significant correlation between tumor size and DDR1 serum measurements at the level of 0.370 was reported (r = 0.370; P = 0.034). The levels of DDR1 in serum showed a positive correlation with the increasing size of tumor. The results of the 5-year survival analysis depending on the DDR1 tissue levels showed a significantly higher survival rate (P = 0.041) for patients who have DDR1 tissue levels above cutoff value. Conclusions: DDR1 expression was significantly higher among brain tumor tissues and serum samples and its levels showed a positive correlation with the increased size of tumor. This study can be a starting point, since it investigated and indicated, for the first time, that DDR1 can be a novel therapeutic and prognostic target for aggressive high-grade gliomas.

Role Of Il-6 In The Adjustment Of The Medical Treatment Of Patients With Covid-19 Associated Acute Respiratory Distress Syndrome.

BACKGROUND: Many cytokines propose to play a role in the pathogenesis of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) associated COVID-19 disease. High interleukin-6 (IL-6) levels are associated with mortality and other poor clinical outcomes in COVID-19. METHODS: In this retrospective study, the correlation of IL-6 level with clinical and other inflammatory parameters, its role in treatment change and its relationship with mortality in COVID-19 patients developing acute respiratory distress syndrome (ARDS) were investigated. RESULTS: Totally 76 patients were included in the study; Thirty-four (44.7%) patients were female and 42 (55.3%) patients were male. All patients had IL-6 levels above the upper reference value (>5.9 pg/mL). Overall, 48 patients (63.1%) had a severe clinical presentation (tachypnoea, tachycardia, fever) that was clinically compatible with IL-6 values, and medical treatment was changed for COVID-19 in this group. A positive correlation was detected between IL-6 and CRP on the day of the change in treatment (p=0.035, r=0.76). There was no decrement observed in IL-6 level on the 3rd day in patients that was clinically thought to have cytokine storm and whose treatment was changed. Mortality was higher in the group whose treatment was changed. CONCLUSIONS: We believe that IL-6 level alone is insufficient to decide on a change in treatment, and correlation of IL-6 with the patient's clinical status is more significant in such decision.

Is every microorganism detected in the intensive care unit a nosocomial infection? Isn't prevention more important than detection?

The present letter to the editor is related to the study entitled "Multidrug-resistant organisms in intensive care units and logistic analysis of risk factors." Not every microorganism grown in samples taken from critically ill patients can be considered as an infectious agent. Accurate and adequate information about nosocomial infections is essential in introducing effective prevention programs in hospitals. Therefore, the development and implementation of care bundles for frequently used medical devices and invasive treatment devices (e.g., intravenous catheters and invasive ventilation), adequate staffing not only for physicians, nurses, and other medical staff but also for housekeeping staff, and infection surveillance and motivational feedback are key points of infection prevention in the intensive care unit.

A Glance Into Healthcare Delivery During COVID-19 Pandemic: A Survey Among Turkish Medical Doctors.

The coronavirus 2019 (COVID-19) pandemic had an enormous impact on healthcare delivery globally. We conducted a cross-sectional online survey in Turkey to evaluate the impact of COVID-19 on healthcare services in Turkey. A 35-item anonymized online survey was completed by HCPs (medical doctors, MD) who continued their clinical practice during the COVID-19 pandemic in Turkey, regardless of their specialties or degrees. Overall, 209 HCPs participated in the study. Forty-two percent of the participants stated that their current workload intensity has been increased compared with the pre-pandemic era. More than half of the participants (54.6%) were using telemedicine services during their clinical practice, however, the effectiveness of telemedicine for first-time patients and follow-up patients was rated as low. The majority of participants (59.3%) reported that during the peak period of the pandemic, they encountered only a small variety of cases, other than COVID-19. Fifty-two percent of the participants agreed that they occasionally had patients who received misdiagnosis in the first admission due to the suspicion of a possible COVID-19 infection predominating the diagnostic process (eg., not excluding COVID-19 even though the PCR test is negative). For the distribution of possible late-diagnosed diseases, 25.8% of HCPs selected chest diseases, followed by infectious diseases, heart diseases, and cancer. In general, participants agreed that there was an increase in the negligence in the follow-up of various diseases and/or complication rates due to COVID-19 pandemic. Sixty percent of the HCPs agreed that HCPs are being much more rigorous to diagnose/treating COVID-19 than other important diseases. Fifty-seven percent of the participants stated that the diagnosis and follow-up of chronic diseases are affected, while 57.9% of the HCPs stated that some diseases that show similar signs and symptoms as COVID-19 are not diagnosed correctly during COVID-19 pandemic. Findings from this study emphasize that COVID-19 pandemic has significantly caused delayed diagnoses and interruption in the management of chronic diseases, and also increased the risk of missing out the diagnosis of non-COVID-19 diseases. The study genuinely aims to yield the floor to a permanent improvement in post-pandemic clinical management and it also shows the need for a focused approach in distinct areas of medical care. Policymaking is required to drive changes to better support HCPs in Turkey.

Hematological manifestations of COVID-19 acute respiratory distress syndrome patients and the impact of thrombocytopenia on disease outcomes: A retrospective study.

Background: Platelet count is a simple and readily available biomarker, in which thrombocytopenia was shown to be independently associated with disease severity and risk of mortality in the critical coronavirus disease-19 (COVID-19) patients. The aim of this study was to investigate the impact of thrombocytopenia on disease progression in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) admitted to a medical intensive care unit (ICU). Methods: COVID-19-associated ARDS patients in our research hospitals' ICU were retrospectively investigated. Patients were divided into two groups as thrombocytopenic (<150 × 109/ml) patients on admission or those who developed thrombocytopenia during ICU follow-up (Group 1) and those without thrombocytopenia during ICU course and follow-up (Group 2). Results: The median platelet count of all patients was 240 × 109/ml, and the median D-dimer was 1.16 mg/ml. On admission, 32 (18.3%) patients had thrombocytopenia. The mean platelet count of Group 1 was 100.0 ± 47.5 × 109/ml. Group 1 was older and their Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores were higher. Group 1 had lower hemoglobin, neutrophil, and lymphocyte counts and higher ferritin and procalcitonin level. Invasive mechanical ventilation was more commonly needed, and disseminated intravascular coagulation (DIC) was more frequently observed in Group 1. The ICU and hospital length of stay of Group 1 was longer with higher mortality. Conclusion: Patients with thrombocytopenia had increased inflammatory markers, frequency of DIC, duration of ICU stay, and mortality. The presence of thrombocytopenia may reflect the progression of COVID-19 toward an unfavorable outcome.

Bibliometric analysis of acute respiratory distress syndrome (ARDS) studies published between 1980 and 2020.

BACKGROUND: Acute respiratory distress syndrome (ARDS), an acute respiratory failure caused by noncardiogenic pulmonary edema, was first defined by Ashbaugh et al. in 1967. The number of publications increased enormously after the Berlin definition of ARDS was first described in 2012. OBJECTIVES: This article intends to provide the physicians and the scientists with a reference guide to assess the most influential publications written about ARDS. MATERIAL AND METHODS: We performed an exhaustive bibliometric analysis to identify publication trends by year, and the most influential research articles, authors, co-authors, journals, and countries. Articles on ARDS published in Science Citation Index (SCI) and Emerging Sources Citation Index (ESCI) journals between 1980 and 2020 were examined. On December 20, 2020, the keywords "ARDS" and "acute respiratory distress syndrome" were searched using the Web of Science Core Collection (WoSCC) database, and data including titles, author information, abstracts, journals, and references were analyzed. RESULTS: A total of 4564 articles related to ARDS published between 1980 and 2020 were identified. After excluding 192 proceedings papers, 19 early access papers, 1 book chapter, 1 research paper, and 1 retracted article, 4350 articles published in SCI and ESCI journals were analyzed. The largest number of articles (n = 557, 12.8%) appeared in 2020. The average citations per article was 38.21, and 4350 articles were cited 166,885 times altogether. The USA was at the top of the list of the most productive countries with 5025 articles. Harvard University was the most contributing institution with 244 articles. M.A. Matthay ranked as the most productive author in ARDS research with 87 published publications. CONCLUSION: The present study provided a comprehensive, illustrative analysis of ARDS articles published in SCI and ESCI journals over the past 40 years.

Acute Exacerbation of Rheumatoid Arthritis Misdiagnosed as COVID-19: A Case Report.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory connective tissue disease that affects 1-2% of the population worldwide. Pulmonary manifestations including interstitial lung disease (ILD), airway disease, pleural and vascular disease can be seen in up to 30-40% of patients with RA, which are recognized as the second most frequent cause of death in RA patients. The simultaneous occurrence of COVID-19 in RA patients with or without ILD, and the similarities and differences between RA-related ILD and COVID-19 lung findings have been reported in the literature. However, there was no reported case on differentiation of clinical findings of a patient with RA exacerbation causing a new diagnosis of ILD during the pandemic conditions. Case Presentation: Here, we presented a patient with RA who was misdiagnosed as COVID-19 twice due to non-specific respiratory symptoms and ground-glass opacities observed in high-resolution CT. The misdiagnosis led to a delayed diagnosis of ILD and prolonged pulmonary symptoms. Discussion: Clinicians must critically review patients throughout the diagnostic workup by thinking other diseases besides COVID-19, particularly in the absence of a confirmatory result. The link between ILD or ILD exacerbation and COVID-19 remains to be determined. While research continues in the field, it is important to consider the importance of COVID-19 in cases of ILD exacerbation, and vice versa. Conclusion: Distinguishing lung imaging findings of COVID-19 from ILD is a major concern. Even though the primary manifestation of COVID-19 consists of respiratory symptoms, clinicians should be vigilant for other common conditions having the same symptoms. Clinicians should carefully distinguish a differential diagnosis between COVID-19 and a flare of rheumatic disease.

Impact of corona-phobia on attitudes and acceptance towards COVID-19 vaccine among cancer patients: a single-center study.

Aim: This study aimed to assess the impact of COVID-19 phobia and related factors on attitude towards COVID-19 vaccine in cancer patients. Methods: A prospective cross-sectional descriptive study was conducted with 300 adult patients using a validated COVID-19 Phobia Scale (C19P-S) and related survey to determine the factors affecting vaccine acceptance between May-June 2021. Results: Regarding the COVID-19 vaccine willingness, 86.7% accepted vaccination, 6.3% were hesitant and 7% refused vaccination. Patients that accepted vaccination had significantly higher C19P-S scores in general, and in psychological and psychosomatic subdivisions. Univariate analysis revealed that increased age, being retired, and being married were significantly associated with willingness to be vaccinated against COVID-19. Conclusion: The majority of patients had high 'coronophobia' levels which were associated with increased willingness for the COVID-19 vaccines. Minimizing negative attitudes towards vaccines will most likely be achieved by raising awareness in the cancer population about COVID-19 vaccine.

Plain language summary Cancer patients are considered among the privileged group for the COVID-19 vaccination. The investigators conducted a survey assessing the relationship between 'coronaphobia' and related factors and vaccine acceptance among patients with cancer. A total of 300 patients completed a questionnaire assessing the factors affecting vaccine acceptance. Most (86.7%) patients accepted vaccination and have higher levels of fear against COVID-19, while 7% refused vaccination. Patients who have increased age, are retired and married had a higher tendency to accept vaccination against COVID-19. The main reason for acceptance was the willingness to get protection, whereas the main reason for refusal was the fear of adverse effects.

Current situation in ARDS in the light of recent studies: Classification, epidemiology and pharmacotherapeutics.

In the last 50 years, there have been great research and developments in the definition and pathophysiology of acute respiratory distress syndrome (ARDS), the most progressive form of acute hypoxemic respiratory failure. Although there are various discussions and recommendations, the definition of ARDS is still based on the Berlin 2012 diagnostic criteria. Despite various studies in recent years, there is still no effective pharmacotherapeutic agent for the treatment of ARDS. Lung protective mechanical ventilation (low tidal volume, low plateau pressure, low driving pressure) in all ARDS patients, prone position, neuromuscular blockade (cisatracurium) in moderate-severe ARDS patients, and hydrocortisone therapy in sepsis-associated ARDS patients are treatments that contribute to survival. In this review, current changes in the definition and epidemiology of ARDS, recent pharmacotherapeutic research and mesenchymal stem cell therapies will be discussed in the light of newly introduced ARDS phenotypes.

Role of serological rapid antibody test in the management of possible COVID-19 cases.

BACKGROUND: Although the detection of viral particles by reverse transcription polymerase chain reaction (RT-PCR) is the gold standard diagnostic test for coronavirus disease 2019 (COVID-19), the false-negative results constitute a big challenge. AIM: To examine a group of patients diagnosed and treated as possible COVID-19 pneumonia whose multiple nasopharyngeal swab samples were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR but then serological immunoglobulin M/immunoglobulin G (IgM/IgG) antibody against SARS-CoV-2 were detected by rapid antibody test. METHODS: Eighty possible COVID-19 patients who had at least two negative consecutive COVID-19 RT-PCR test and were subjected to serological rapid antibody test were evaluated in this study. RESULTS: The specific serological total IgM/IgG antibody against SARS-CoV-2 was detected in twenty-two patients. The mean age of this patient group was 63.2± 13.1-years-old with a male/female ratio of 11/11. Cough was the most common symptom (90.9%). The most common presenting chest computed tomography findings were bilateral ground glass opacities (77.2%) and alveolar consolidations (50.1%). The mean duration of time from appearance of first symptoms to hospital admission, to hospital admission, to treatment duration and to serological positivity were 8.6 d, 11.2 d, 7.9 d, and 24 d, respectively. Compared with reference laboratory values, serologically positive patients have shown increased levels of acute phase reactants, such as C-reactive protein, ferritin, and procalcitonin and higher inflammatory markers, such as erythrocyte sedimentation rate, lactate dehydrogenase enzyme, and fibrin end-products, such as D-dimer. A left shift on white blood cell differential was observed with increased neutrophil counts and decreased lymphocytes. CONCLUSION: Our study demonstrated the feasibility of a COVID-19 diagnosis based on rapid antibody test in the cases of patients whose RT-PCR samples were negative. Detection of antibodies against SARS-CoV-2 with rapid antibody test should be included in the diagnostic algorithm in patients with possible COVID-19 pneumonia.

The role of endotheliitis in COVID-19: Real-world experience of 11 190 patients and literature review for a pathophysiological map to clinical categorisation.

OBJECTIVE: COVID-19 may yield a variety of clinical pictures, differing from pneumonitis to Acute Respiratory Distress Syndrome along with vascular damage in the lung tissue, named endotheliitis. To date, no specific treatment strategy was approved for the prevention or treatment of COVID-19 in terms of endotheliitis-related comorbidities. Here, we presented our treatment strategies for 11 190 COVID-19 patients depending on categorisation by the severity of both the respiratory and vascular distress and presented the manifestations of endotheliitis in skin, lung and brain tissues according to the different phases of COVID-19. METHODS: After a retrospective examination, patients were divided into three groups according to their repercussions of vascular distress, which were represented by radiological, histopathological and clinical findings. We presented the characteristics and courses of seven representative and complicated cases which demonstrate different phases of the disease and discussed the treatment strategies in each group. RESULTS: Among 11 190 patients, 9294 patients met the criteria for Group A, and 1376 patients were presented to our clinics with Group B characteristics. Among these patients, 1896 individuals (Group B and Group C) were hospitalised. While 1220 inpatients were hospitalised within the first 10 days after the diagnosis, 676 of them were worsened and hospitalised 10 days after their diagnosis. Among hospitalised patients, 520 of them did not respond to group A and B treatments and developed hypoxemic respiratory failure (Group C) and 146 individuals needed ventilator support and were followed in the intensive care unit, and 43 (2.2%) patients died. CONCLUSION: Distinctive manifestations in each COVID-19 patient, including non-respiratory conditions in the acute phase and the emerging risk of long-lasting complications, suggest that COVID-19 has endotheliitis-centred thrombo-inflammatory pathophysiology. Daily evaluation of clinical, laboratory and radiological findings of patients and deciding appropriate pathophysiological treatment would help to reduce the mortality rate of COVID-19.

Leprosy suspect presenting at a chest clinic.

Leprosy is an ancient ailment, also known as Hansen's disease. It primarily involves the superficial peripheral nerves, skin, upper respiratory tract mucosa, eyes, bones and testicles, but not the lungs. Although leprosy patients are not included in the study area of pulmonology, here we present an undiagnosed leprosy patient with a history of smoking, who was referred owing to upper respiratory tract symptoms and bilateral pleural effusions. From this undiagnosed case, we would like to draw specific attention of pulmonologists, since a patient with leprosy can present in this way due to hypoalbuminemia resulting from a systemic inflammatory state, which may then progress to sepsis. Collaboration of different specialists may be required to clinch extra-neurological and extra-cutaneous features of leprosy.