Can life satisfaction be considered a predictor of quality of life in patients with lung cancer?

OBJECTIVE: To evaluate the association between satisfaction with life and Quality of Life (QoL) in lung cancer patients, and to analyze the correlations of selected variables with QoL. PATIENTS AND METHODS: 250 patients with lung cancer were enrolled into the study, with a mean age of 63.2± 9.4, and who were treated at the Regional Lung Hospital in Poland between January and June 2019. 110 patients (43.9%) were moderately satisfied with their life (18-23 points from SWLS). 72 (28.8%) had a high level of satisfaction, and 68 (27.2%) had a low level of satisfaction with life. RESULTS: Patients with a high level of satisfaction with life had a better QoL (p<0.001) and experienced less severe symptoms, with the exception of constipation, haemoptoe, soreness in the mouth, dysphagia, hair loss, and pain in the arms. Patients with a high level of satisfaction with life have a significantly lower intensity of behaviors associated with anxious preoccupation (p<0.001) and helplessness/hopelessness (p<0.001). Destructive coping styles increase as satisfaction with life decreases (p<0.001). Patients with a high level of satisfaction with life were more accepting of their illness (p<0.001). CONCLUSIONS: Patients being treated for lung cancer have a moderate level of satisfaction with life. QoL is associated with satisfaction with life and increases depending on the level of satisfaction. Symptoms are less severe when patients are more satisfied with their life. Satisfaction with life was associated with acceptance of the illness and coping strategies. Not smoking, chest pain, time from diagnosis, performance status, and symptomatic treatment adversely affected satisfaction with life. Conversely, a lack of family history of cancer positively affected satisfaction with life.

Active middle-ear implant fixation in an unusual place: clinical and audiological outcomes.

OBJECTIVE: The Vibrant Soundbridge is an active middle-ear implant for hearing rehabilitation that is usually placed in the long process of the incus or round window. This study reports on the unusual implant attachment to the short process of the incus in a patient with ear malformation, and describes their audiological and clinical outcomes. METHODS: Case report and literature review. RESULTS: Audiological evaluation with the Vibrant Soundbridge implant showed a pure tone average of 31 dB. The speech test, at 65 dB HL, revealed correct recognition of 92 per cent of disyllabic words. The Glasgow Hearing Aid Benefit Profile showed high levels of satisfaction, hearing aid use and benefit. CONCLUSION: Fixation of the Vibrant Soundbridge implant on the short process of the incus is a feasible option, with good clinical and audiological outcomes. Coupling the floating mass transducer to the short process of the incus is a good surgical option, especially when the long process and the oval or round window are inaccessible.

Synergy against fungal pathogens: working together is better than working alone.

Opportunistic fungi are the most important pathogens in modern world. They are responsible for severe infections in majority of immunocompromised patients. These microorganisms are commonly present in our environment which is natural reservoir of new, resistant species. For this reason mycoses are mainly chronic or long-lasting diseases. Our arsenal of antifungal drugs is growing but still insufficient for emerging resistant pathogens. An alternative for novel chemical entity drugs is the multidrug approach. This exploiting the drugs being currently on market applying simultaneously for better efficacy or to eradicate resistance. Synergy is the term that describes the phenomenon of increased potency of two or more drugs administered in combination. In the last decades it gains more interest and numbers of synergy claimed reports is growing exponentially. However these have rather low impact on clinical trials or practical use of antimycotics. In present review we wish to discuss current status of synergy between antifungal drugs. Both theoretical point of view and practical applicability in clinical terms are covered. There are serious differences between the assumptions, methods and interpretations of the results and sometimes even obvious mistakes in the procedure that was applied or in the outcomes discussed. On the other hands the specificity of fungal infections introduce dozens of factors affecting the observed results. Shift form in vitro studies to clinical trials reveals further difficulties. Hopefully multi-drug approach seems to be effective even if no strong synergy is displayed.

Evaluation of antioxidant treatment in presbyacusis: prospective, placebo-controlled, double-blind, randomised trial.

OBJECTIVE: There are many well-known aetiological mechanisms of presbyacusis, and free radicals have been shown to play an important role. This study aimed to evaluate the effect of antioxidant agents on the hearing threshold of patients with presbyacusis. METHODS: One hundred and twenty individuals were divided into four groups and received one of the following treatment schemes: ginkgo biloba dry extract, α-lipoic acid plus vitamin C, papaverine chlorhydrate plus vitamin E, or placebo. All participants were evaluated at recruitment and after six months, using pure tone audiometry (at isolated and average frequencies), speech recognition threshold and percentage index of speech recognition. RESULTS: The various treatments had no effect on any of the evaluated measures of hearing, either between groups or over time. CONCLUSION: There was no statistically significant change in the hearing threshold after treatment with any of the tested drugs, during the study period.

Privileged structures - dream or reality: preferential organization of azanaphthalene scaffold.

The concept of privileged structures/substructures (PS) is the idea that certain structural features produce biological effects more often than others. The PS method can be seen as an offspring of fragonomics, which is based on recent experimental measurements of protein-ligand interactions. If PS prove to be true, then chemical motives that enrich biological activity can be used when designing new drugs. However, PS remain controversial because we cannot be sure whether the excess of active structures does not result from an abundance in chemical libraries. In this review, we will focus, in particular, on the preferential organization of azanaphthalene scaffolds (AN) in drugs and natural products (NP), which are preferred by Nature in evolution. We will show that knowledge discovery in molecular databases can reveal interesting time-trends profiles for important classes of potentially privileged scaffolds. The chemical library of AN is dominated by monoaza-compounds, among which quinoline appears to be the most frequently investigated scaffold; however; more sophisticated database mining seems to indicate different PS patterns within the AN scaffold family.

Pharmacophore-based database mining for probing fragmental drug-likeness of diketo acid analogues.

A number of the structurally diverse chemical compounds with functional diketo acid (DKA) subunit(s) have been revealed by combined online and MoStBiodat 3D pharmacophore-guided ZINC and PubChem database screening. We used the structural data available from such screening to analyse the similarities of the compounds containing the DKA fragment. Generally, the analysis by principal component analysis and self-organizing neural network approaches reveals four families of compounds complying with the chemical constitution (aromatic, aliphatic) of the compounds. From a practical point of view, similar studies may reveal potential bioisosteres of known drugs, e.g. raltegravir/elvitegravir. In this context, it seems that mono-halogenated aryl substructures with para group show the closest similarity to these compounds, in contrast to structures where the aromatic ring is halogenated in both ortho- and para-locations.

Bilateral narrow duplication of the internal auditory canal.

AIM: To demonstrate diagnostic imaging of an extremely rare presentation of bilateral narrow duplication of the internal auditory canal. CASE REPORT: An adolescent boy with profound sensorineural hearing loss presented for hearing rehabilitation. Imaging studies (i.e. multidetector computed tomography and magnetic resonance imaging) clearly demonstrated bilateral duplication of the internal auditory canals, with narrowing of the lower canals, unilateral cochlear and vestibular dysplasia, bilateral superior semicircular canal malformation, and bilateral absence of the posterior semicircular canals. CONCLUSION: To our knowledge, this is only the third such case described in the literature. Considering that the vestibulocochlear nerve has been unable to be demonstrated in almost all cases of duplicated internal auditory canal (unilateral and bilateral), our case supports the hypothesis that vestibulocochlear nerve aplasia or hypoplasia leads to internal auditory canal stenosis. We consider this rare presentation of bilateral narrow duplication of the internal auditory canal to represent a contraindication for cochlear implantation.

Quinoline-based antifungals.

Although the assortment of antifungal drugs is broad, the most commonly used agents have major drawbacks. Toxicity, serious side effects or the emergence of drug resistance are amongst them. New drugs and drug candidates under clinical trials do not guarantee better pharmacological parameters. These new medicines may appear effective; however; they may cause serious side effects. This current review is focused on the recent findings in the design of quinoline based antifungal agents. This field seems to be especially interesting as 8-hydroxyquinoline and its metal complexes have been well known as antifungals for years. Structural similarities between quinoline based antifungals and allylamines or homoallylamines, e.g. terbinafine is another interesting fact. Quinoline can be identified in a number of synthetic and natural antifungals, which indicates nature's preference for this fragment and identifying it as one of the so-called privileged structures. We have discussed new trends in the design of quinolines with antifungal properties, their possible targets and the structure activity relationships within the antifungal series developed.

Post-traumatic otosclerosis: coincidence or trigger factor?

OBJECTIVE: The etiology of otosclerosis is poorly understood and environmental as well as genetic factors have been implicated. In this paper we will present 3 cases of otosclerosis with a clinical history of trauma and we will discuss with a literature review the place of trauma in otosclerosis etiology. CLINICAL CASES: 3 patients with clinically diagnosed otosclerosis, operated, and with a clinical history of previous head trauma. DISCUSSION AND CONCLUSION: It is probable that environmental factors could be involved in the development of the disease and we think that trauma could be one of them. The mechanisms by which it could results in otosclerosis remain unknown. However these cases appear to be rare and under studied.

1,161 patients with adrenal incidentalomas: indications for surgery.

BACKGROUND AND AIMS: The aim of this study is to analyze the clinical data and criteria for surgery in a group of over 1,100 patients with adrenal incidentalomas (AI) observed at the Department of Endocrinology. PATIENTS AND METHODS: The material consisted of 1,161 patients (842 women and 319 men, 10-87 years old) with AI ranging in size from 1.0 to 23.0 cm. The methods included clinical examination, imaging studies, hormonal determinations in the blood and in the urine as well as histological and immunocytochemical investigations in 390 patients treated by surgery. RESULTS: Basing on these studies, we diagnosed 112 patients with primary malignant adrenal tumors (100 with carcinoma), 45 with metastatic infiltrations, and 1,004 with probable benign AI. Imaging phenotypes (especially high density on computed tomography, CT) were characteristic of malignant and chromaffin tumors. Subclinical adrenal hyperactivity was found in 8% of the patients with pre-Cushing's syndrome as the most frequent form (6.5%). Chromaffin tumors were detected in 3%. CONCLUSIONS: (1) Indications for surgery include malignant tumors (both primary and metastatic), tumors with subclinical hyperfunction, and chromaffin tumors. High density on CT, >20 HU, appeared to be an important indication for surgery. (2) A slight prevalence of oncological indications over endocrinological indications (14 vs. 11%) was found.

Investigating the antiproliferative activity of quinoline-5,8-diones and styrylquinolinecarboxylic acids on tumor cell lines.

The structure-activity relationships of new quinoline based compounds were investigated. Quinoline-5,8-dione and styrylquinoline scaffolds were used for the design of potentially active compounds. The novel analogues had comparable antiproliferative activity to cisplatin when evaluated in a bioassay against the P388 leukemia cell line. However, these compounds appeared far less efficient against SK-N-MC neuroepithelioma cells. Analogues without the 5,8-dione structure but containing the 8-carboxylic acid group were also found to induce antiproliferative activity. Hydrophobicity as measured by HPLC did not correlate with antiproliferative activity.

Vascular-endothelial growth factor (VEGF) in patients with peripheral ischemia.

Vascular endothelial growth factor (VEGF) is a key cytokine responsible for the spontaneous new blood vessel formation in the course of peripheral ischemia. It has repeatedly been observed in patients with critical leg ischemia that their clinical status does not reflect any effective local neovascularization processes as well as VEGF system up-regulation. Therefore, the aim of present study was to compare the proangiogenic status, assessed as the serum VEGF concentration, in patients with mild, moderate, and severe peripheral ischemia and to analyze to what extend it is influenced by the therapy applied. Serum VEGF level was evaluated by ELISA method in 31 patients with peripheral ischemia at different time points throughout the treatment. On Day 0 (before treatment), Day 2, and Day 7, VEGF concentration was significantly higher in subjects with critical leg ischemia (Group I) than in other groups (P<0.001). In Group I, VEGF decline was reported on Day 30 following radical surgery, while in a group of moderate disease treated by revascularization surgery a significant increase in serum VEGF concentration was observed (Day 7 and Day 30) (P=0.02). Serum cytokine level in the patients with mild ischemia (Group III) on pharmacotherapy was stable throughout the observation period. Interestingly, the increase in VEGF levels throughout the study period from Day 0 to Day 30 was significantly greater in unsuccessfully treated patients compared with subjects who positively responded to therapy or did not show any response at all. We conclude that mechanisms other than hypoxia might drive the observed up-regulation of VEGF production in peripheral ischemia.

Analogues of the styrylquinoline and styrylquinazoline HIV-1 integrase inhibitors: design and synthetic problems.

In our work, leading to new styrylquinoline and styrylquinazoline inhibitors of HIV integrase, we analyzed virtual combinatorial library that includes these compounds. Using this method we were able to find interesting synthetic targets. We optimized synthetic procedure yielding such compounds and obtained a couple of new analogues. Their activity will be evaluated in the near future.

Human cystic and alveolar echinococcoses as indication to liver transplantation.

The human cystic and alveolar echinococcoses are zoonotic diseases caused by larval stages of the tapeworms Echinococcus granulosus and E multilocularis. In man the liver form of the diseases develops most frequently. Recent epidemiological data indicate that the distribution of E multilocularis in the central Europe is wider than was previously anticipated; more cases of human alveococcosis during the last years have also been noted in Poland. In the present paper we analyzed several cases of human echinococcoses from Poland with respect to diagnosis and treatment as well as the indications for liver transplantation.

Adrenal ganglioneuroblastoma in pregnant woman: diagnosis with three-dimensional ultrasound.

The diagnostic approach for evaluation of adrenal tumour in pregnant women is a problem. This article presents the multifactorial diagnosis of rare, incidentally detected massive adrenal tumour with 2D and 3D US. Grey-scale 2D and 3D US with tissue harmonic imaging showed inhomogeneous, encapsulated, solid tumour of the right adrenal region. Three-dimensional colour Doppler and power Doppler studies showed ample neovascularization in the tumour and the adrenal vein draining to the inferior vena cava similarly to angiographic studies performed in the past.

Liver cystadenocarcinoma--case report.

A 69-year-old woman was admitted to our Department with the diagnosis of liver cyst. She had previously undergone liver cyst fenestration 10 years before. After abdominal spiral CT, the patient was qualified for laparotomy. A cystic formation was localized in the central part of the liver, in the 4th segment and was found to compress the hilar bile ducts. A 4.5 bisegmentectomy was performed. During the postoperative course, a biliary fistula was observed, which resolved spontaneously. The treatment was also complicated by myocardial infarction. The patient was discharged in good condition 30 days postoperatively. The pathological diagnosis revealed cystadenocarcinoma.

Risk factors for morbidity following liver surgery.

The aim of this study is to define risk factors for severe complications following anatomical liver resections. The study material consists of the first 50 patients (26 women, 24 men, at mean age 50.6 years) treated at 3rd Department of Surgery 2nd Faculty of Medicine, Medical University in Warsaw. The indications for resection included benign neoplasm in 19 cases and malignancy in 31 cases. All the patients underwent anatomical liver resection in accordance with Couinaund's segmental division. In order to define prognostic factors for severe postoperative complications, a multi-factor statistical analysis was conducted. The following parameters were analysed: patient's age, the levels of bilirubin, total protein, albumin, prothrombin time, kaolin-kephalin time, range of resection and blood loss during operation. Eleven patients (22%) died in postoperative period. In 8 cases the death was caused by liver failure. Statistical analysis showed that blood loss, albumin level on fifth postoperative day and kaolin-kephalin time before and after surgery are independent risk factors predisposing to the development of complications.

Liver regeneration after anatomical resections.

BACKGROUND: The authors present the results of investigation of liver regeneration after partial parenchyma resection. MATERIAL AND METHODS: 20 patients (16 females, 4 male) aged 31-67 years were operated on because of metastatic colon cancer (7 cases), cavernous hemangioma (6 cases), hepatocellular carcinoma (1), alveococcosis (2), metastases of malignant melanoma (1), gall bladder carcinoma (1), FNH (1) and mucous cystadenocarcinoma (1). The resection according to anatomical segments by Couinaud were performed. Spiral CTs including liver volumetry were taken before and 30 days after the operation. on the 7-th day after the surgery, liver biopsy was performed and the material was examined under light and electron microscope. RESULTS: There was no postoperative mortality. We observed transient elevation of transaminases, bilirubin levels and decrease of albumin level. Control spiral CT revealed increased liver volume in 15 cases (75 percent). In 16 cases (80 percent), electron microscopy investigations showed regeneration of the liver (mitotic figures). CONCLUSIONS: Our material shows that hyperplasia as well as blood vessel and bile duct neogenesis play a very important role in liver regeneration process.

Self-organizing neural networks for screening and development of novel artificial sweetener candidates.

The use of Kohonen feature maps for the visualization of various aspects of molecular similarity is briefly reviewed and illustrated. It is shown that a specific feature of self-organizing maps (SOM) makes them of special interest for the screening of compounds. In particular, these methods were used to design candidates for new sweeteners, which were then synthesized.

The non-grid technique for modeling 3D QSAR using self-organizing neural network (SOM) and PLS analysis: application to steroids and colchicinoids.

A novel method for modeling 3D QSAR has been developed. The method involves a multiple training of a series of self-organizing networks (SOM). The obtained networks have been used for processing the data of one reference molecule. A scheme for the analysis of such data with the PLS analysis has been proposed and tested using the steroids data with corticosteroid binding globulin (CBG) affinity. The predictivity of the CBG models measured with the SDEP parameter is among the best one reported. Although 3-D QSAR models for colchicinoid series is far less predictive, it allows for a discussion on the relative influence of the structural motifs of these compounds.