Positron Emission-Computed Tomography, Cryobiopsy versus Bronchoalveolar Lavage and Computed Tomography Findings for Interstitial Lung Disease: A Long-Term Follow-Up.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.

Epithelial Ovarian Cancer: A Five Year Review.

Ovarian cancer is a malignant disease that affects thousands of patients every year. Currently, we use surgical techniques for early-stage cancer and chemotherapy treatment combinations for advanced stage cancer. Several novel therapies are currently being investigated, with gene therapy and stem cell therapy being the corner stone of this investigation. We conducted a thorough search on PubMed and gathered up-to-date information regarding epithelial ovarian cancer therapies. We present, in the current review, all novel treatments that were investigated in this field over the past five years, with a particular focus on local treatment.

Producing the appropriate model and drug for intratumoural ablation.

Local treatment is necessary for several cancer patients. There are situations where cancer tissue induces locally severe symptoms. Therefore, additional local disease control is necessary. There are two major issues for efficient local treatment: the method of application and the penetration of the drug formulation. We need efficient tools to guide the drug formulation to the target point, and an effective drug formulation that is diffused within the tumour microenvironment with a sustained-release effect.

Epidemiology of antenatal depression among women with high-risk pregnancies due to obstetric complications: a scoping review.

PURPOSE: Antenatal depression is a common mental health problem among pregnant women that negatively affects maternal and neonatal outcomes. Women with obstetric complications, defined as high-risk pregnancies, seem to be at particularly increased risk for developing depressive symptomatology. The purpose of this study was to review the prevalence of antenatal depression among pregnant women with obstetric complications and to identify possible associated factors. METHODS: A literature search was performed in the PubMed database and a scoping review was conducted to identify studies with data on the prevalence of antenatal depression and associated factors among high-risk pregnancies due to obstetric complications. The included studies were written in English and published up to 31/12/2018. RESULTS: The prevalence of antenatal depression among pregnant women with high-risk pregnancies ranges from 12.5 to 44.2% among the reviewed studies. The associated factors significantly associated with antenatal depression include maternal age, maternal education, dwelling place, relationship with the partner, previous psychiatric diagnosis, perceived stress, antenatal attachment, abortion thoughts, smoking, diabetes, parity, number of pregnancies, gestational age, threatened preterm labour, preeclampsia and oligohydramnios. CONCLUSIONS: Our findings indicate a high prevalence of depressive disorders in women with obstetric complications, suggesting the need for more rigorous screening among this population. The identification of associated factors also merits clinical attention. Further research is warranted to develop evidence-based effective screening strategies and relevant interventions.

Genes' Interactions: A Major Contributor to the Malignant Transformation of Endometriosis.

The genetic and epigenetic factors that contribute to the malignant transformation of endometriosis are still under investigation. The objective of the present study was to investigate the genetic link between endometriosis and cancer by examining and correlating the latest clinical observations with biological experimental data. We collected updated evidence about the genetic relationship between endometriosis and cancers by conducting a comprehensive search of PubMed and Scopus databases, focusing on the papers published between January 2018 and January 2019. New insights into the mechanism of the malignant transformation of endometriosis have been published recently. The use of state-of-the-art techniques and methods, such as the genome-wide association study analysis and the weighted gene co-expression analysis, have significantly altered our understanding of the association between endometriosis and endometriosis-associated cancer development. Interestingly, the interactions formed between genes seem to play a pivotal role in the phenotypic expression of mutations. Therefore, the effect of single nucleotide polymorphisms and the function of the expression quantitative trait loci on genes' expression have been the subject of many recent works. In addition, it has been discovered that genes, the mutations of which have been related to the development of endometriosis, play a role as hub genes. This may lead to new areas of research for understanding the mechanism of malignant transformation of the disease. Significant steps forward have been made towards the identification of factors that control the malignant transformation of endometriosis. Still, due to rarity of the event, a better-organized scheme for sampling on a global level should be adopted.

Inhaled Cisplatin for NSCLC: Facts and Results.

Although we have new diagnostic tools for non-small cell lung cancer, diagnosis is still made in advanced stages of the disease. However, novel treatments are being introduced in the market and new ones are being developed. Targeted therapies and immunotherapy have brought about a bloom in the treatment of non-small cell lung cancer. Still we have to find ways to administer drugs in a more efficient and safe method. In the current review, we will focus on the administration of inhaled cisplatin based on published data.

Pharmacologic and Non-Pharmacologic Interventions for HIV-Neuropathy Pain. A Systematic Review and a Meta-Analysis.

Background and Objectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.

Role of Memantine in Limiting Cochleotoxicity in Rats.

Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.

Chronic Obstructive Pulmonary Disease and Non-Small Cell Lung Cancer an association.

Objectives: Lung cancer is known to be associated with chronic obstructive pulmonary disease. Moreover; nutritional status is associated with chronic obstructive disease treatment and lung cancer. Our aim was to evaluate the interaction of the COPD status and treatment of non-small cell lung cancer. Methods: Eighty-two patients were enrolled in our multicenter study. Chronic obstructive disease stage, spirometry and treatment was recorded along with the treatment and Body Mass Index (BMI), Mediterranian Diet Score, Pack Years, Basic Metabolsim (RMR) (kcal/day), VO2 (ml/min), Ve (lt/min) and Physical Activity. The statistical analysis was performed using the JMP 14.3 (SAS Inc 2018) software. Results: The drug pairs showed a steady and unchanged by time health condition for 48 patients. Overall, 31 patients were recorded with worse COPD health conditions. The one-way ANOVA clearly indicated that chemotherapy induced the best FEV1-difference conditions with a positive effect of 8.56 mean FEV volume, the combined treatment simply did not have an effect (-0.9), while immunotherapy and patients receiving radiation decreased their FEV1 volume down to -4.23 and -5.15 mean values. Conclusions: Patients receiving chemotherapy alone had their chronic obstructive disease improved with less drugs and exacerbations, while patients receiving immunotherapy had their chronic obstructive disease stable, while all other treatment combinations worsened the patients chronic obstructive disease. Nutritional status did not affect the chronic obstructive disease of these patients in any way.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Pregabalin abuse after past substance-seeking behavior.

Pregabalin is a prescription drug, structurally related to the neurotransmitter GABA. Following the rapidly increasing use of pregabalin, data signaling its abuse liability have been published recently. We report a case of a 19-year-old man with a history of cannabis and alcohol-seeking behavior that showed similar drug-seeking behavior with pregabalin. This report highlights the potential for abuse of pregabalin in patients with a history of substance-seeking behavior. Considering that the drug has recently been proposed as a treatment for alcohol- and benzodiazepine-dependence a better clarification of its abuse potential is essential.

Pharmacologic Stewardship in a Rural Community Pharmacy.

BACKGROUND: Pharmacotherapy is an essential part of patient care. In order to achieve optimal health outcomes, safe and effective prescribing and administering of medications is crucial, especially since the process of pharmacotherapy can cause serious problems, mainly adverse events and/or interactions, that often pass undetected. OBJECTIVE(S): To investigate the feasibility of using community pharmacies as checkpoints to detect errors and failures in prescribing, as well as patients' compliance with pharmacotherapy. To this end, analysis and recording of the prescribing process was carried out and error-prone points were identified. METHODS: Patients and caregivers filling prescriptions during the first 4 weeks of November 2017 and February 2018 answered questions in order to evaluate their attendance of regular checkups and their compliance with prescribing instructions. All prescriptions filled at the pharmacy were examined for detection of prescription errors and drug-drug interactions. Statistical analyses, including calculations of the correlation coefficient phi (φ), chi-square, and confidence intervals, were carried out. Detected errors and failures were evaluated by application of the Health Failure Mode Effect Analysis (HFMEA) quality tool. RESULTS: A significant number of patients (16.7%) failed to regularly attend checkups regarding known health problems (95% CI: 10.6-22.7%), a corresponding percentage (16%, 95% CI: 10.1-21.9%) did not comply with prescribed pharmacotherapy, and a significant proportion of patients self-medicated regularly (32%, 95% CI: 24.5-39.5%). A total of 8.6% of prescriptions included medication combinations with a potential for severe drug-drug interactions (95% CI: 7.1-10.2%) while 58.7% of the prescriptions included combinations that could lead to moderate ones (95% CI: 56.1-61.4). The HFMEA indicated that all problems recorded required immediate interventions, except for prescribing errors. CONCLUSIONS: Community pharmacies can be potential checkpoints for the detection and evaluation of prescribing errors and pharmacotherapy failures.

Sotorasib after immune checkpoint inhibitor administration induces hepatotoxicity. True, false or just another adverse effect of NSCLC treatment.

Non-small cell lung cancer is still diagnosed at a late disease stage and systematic therapy is necessary. Currently we have three main treatment modalities; chemotherapy, targeted with tyrosine kinase inhibitors and immune check point inhibitors. In the recent years and based on new studies we can administer combination of chemotherapy and immunotherapy, or radiotherapy and immunotherapy. Every treatment approach is based on the specific gene expression of the tumor. Tyrosine kinase inhibitors have been used for more than a decade for epidermal growth factor positive tumors, the same for anaplastic lymphoma kinase and proto-oncogene 1. Programmed death-ligand 1 expression has been found to be associated with the efficiency of immune checkpoint inhibitors. However; there are still several subpopulations in non-small cell lung cancer patients. We will comment on the group with KRAS G12C mutation and the targeted therapy with sotorasib for its efficiency and toxicity based on new studies.

Immunotherapy for the elderly. Maybe the best option for lung cancer?

Lung cancer is usually diagnosed at advanced stage and systematic therapy is administered. New current diagnostic techniques such as the convex-endobronchial ultrasound, radial endobronchial ultrasound, cone beam ct, electromagnetic navigation and robotic bronchoscopy provide us with a high diagnostic yield. These techniques are minimal invasive and patients with comorbidities such as chronic obstructive pulmonary disease and heart failure can be diagnosed with minimal adverse effects. All these techniques provide sufficient sample for molecular investigation. Since immunotherapy was first administered, we have more and more information regarding the appropriate patient target group. Several published studies divided patients as elderly ≥75 and non-elderly ≤74 and investigated the adverse effects of different drugs and survival. In our current commentary we present information on patients receiving immunotherapy versus chemoimmunotherapy in two groups of elderly and non-elderly. Elderly patients can receive both combinations without differences between the two groups, however; more studies are needed to clarify certain aspects.

Salicylate- and Noise-induced Tinnitus. Different Mechanisms Producing the same Result? An Experimental Model.

PURPOSE: Tinnitus, the generation of phantom sounds, can be the result of noise exposure, however, understanding of its underlying mechanisms is limited. Purpose of the study was is to determine whether different concentrations of salicylate can cause tinnitus of different intensity. METHODS: For the purposes of this study 50 male Wistar rats were used. The animals were divided into 5 groups (10 rats in each group). The animals that did not receive any substance were allocated to the control group (Group A). The second group (Group B) of rats received salicylate (Sigma Aldrich) intraperitoneally for 7 days (300 mg/Kg/day). The 3rd group (Group C) received salicylate intraperitoneally for 7 days, but at twice the concentration of the animals in the second group (600 mg/kg/d). The 4th group (Group D) simultaneously received salicylate (300 mg/Kg/day) and pure Memantine (Sigma Aldrich, 10 mg/kg/d) intraperitoneally for 7 days. The 5th group (Group E) did not receive any substance but was exposed for 168 consecutive hours (7 days) to sound to induce tinnitus. Cochlear activity was evaluated with the use of Distortion Product Otoacoustic Emissions (DPOAEs). At the end of the experimental period, the animals were sacrificed, and the right cochlea was removed and prepared for further histological and immunohistochemical studies. RESULTS: The DPOAEs of animals treated either with salicylate as monotherapy or salicylate combined with memantine were indistinguishable from the noise floor, did not differ significantly compared to the animals of the control group or those expose to constant noise. The cochlear structures of Group E remained anatomically and functionally unaffected from the exposure to constant noise. Memantine does not seem to offer substantial protection to the cochlear structures, according to histological examination and hearing tests, however, the rats receiving it exhibited better results in behavioral tests. CONCLUSIONS: The administration of memantine does not contribute significantly to the reduction of tinnitus.

Inhaled nintentanib, pirfenidone and macitentan for pulmonary fibrosis: a laboratory experiment.

Aim: Idiopathic pulmonary fibrosis is a rare disease with few efficient drugs in the market. The consequences of this disease are mainly respiratory failure and pulmonary hypertension. Materials & methods: In our experiment we used the drugs pirfenidone, nintetanib and macitentan. We performed nebulization experiments with three jet nebulizers and three ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5 µm in mass median aerodynamic diameter. Results: Pirfenidone versus nintetanib had smaller droplet size formation at both inhaled technologies (1.37 < 2.23 and 1.92 < 3.11, jet and ultrasound respectively). Discussion: Pirfenidone and nintetanib can be administered as aerosol in any type of nebulization system.

Sentinel Lymph Node Staging in Early-Stage Cervical Cancer: A Comprehensive Review.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for the final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false-negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

Endobronchial Radiofrequency Ablation for pulmonary nodules with Radial-Ebus and Navigation: Pros and Cons.

Introduction: Pulmonary nodules are common in the everyday clinical practice. There is always a diagnostic issue with this imaging finding. Based on the size we can use a variety of imaging and diagnostic techniques. Moreover; in the case of primary lung cancer or metastasis we can use radiofrequency ablation endobronchially. Patients and Methods: We used the radial-endobronchial ultrasound with C-arm and Archemedes, Bronchus electromagnetic navigation in order to acquire biopsy sample and we also used rapid on-site evaluation as a rapid diagnosis for pulmonary nodules. After rapid diagnosis we used the radiofrequency ablation catheter in order to ablate central pulmonary nodules. Results: Both techniques provide efficient navigation, however, with the Bronchus system less time is needed. The new radiofrequency ablation catheter provides efficient results in central lesions with low watts ≤40. Conclusion: We provided in our research a protocol to diagnose and treat such lesions. Future larger studies will provide more data on this subject.

A health condition index for assessing disease progression.

INTRODUCTION: Currently immunotherapy is considered a cutting edge pharmaceutical treatment for non-small cell lung cancer. Tumor profile plays a crucial role in identifying the correct patient group. METHODS: Therefore, initial biopsies and re-biopsies are necessary in order to identify the expression of programmed death-ligand-1. RESULTS: This information is crucial and therefore all future immunotherapy studies have to be built upon a specific statistical model which associates the tumor profile and tumor profile expression along with treatment efficiency. DISCUSSION: We present a novel statistical methodology for future immunotherapy studies of non-small cell lung cancer.

Factors Affecting the Nuclei in Newborn and Children.

It is known that children are more sensitive to the effects of medical treatments and environment than adults. Today there is limited information regarding the differences in genotoxic effects in children. The micronucleus assay is a method that is used to monitor genotoxicity, and it was validated several years before. Today there is international interest for exfoliated buccal cells. Most of the micronuclei studies in children have been performed with the analyses of lymphocytes. However, there is vast interest in using exfoliated cells from the oral cavity. The reason is that other type of cells are acquired non-invasively, this is an important issue in paediatric cohorts. Unfortunately a limitation of measuring micronuclei frequency is that it has been observed to be low in newborns and on the other hand there are a large number of patients and cell sample counts. It has been observed that radiation exposure and environmental pollutants increase the micronuclei frequency in newborn and children. Regarding the medical treatments, there is little data and several studies are needed to optimise the doses. There is the need to observe if there is a relationship between micronuclei in lymphocytes and exfoliated cells and to identify the baseline of the micronuclei levels. Moreover, we evaluate the changes in response to the toxic agents. Prospective cohorts studies will clarify the predictive value of micronuclei for cancer and chronic diseases for both children and adults. Novel molecular technologies will assist in the elucidation of different biological pathways and molecular mechanisms connected with the micronulcei levels in newborn and children.