The effect of surgical repair of the chest on postural stability among patients with pectus excavatum.

Pectus excavatum is the most encountered of chest wall deformities. It may produce respiratory and cardiovascular symptoms, hence surgical repair of this defect is performed. The procedure involving the insertion of metal bars under the sternum (the Nuss procedure) usually brings significant improvement to patients. However, the effect of the repair on the postural stability of patients has not been studied so far. To investigate the problem of patients' stability in the postoperative period male patients with pectus excavatum (n = 21) and healthy controls (n = 22) were included in the study. Using posturography methods, we showed a negative impact of the pectus excavatum repair surgery on patients' postural stability in the first postoperative phase. The centre of pressure displacement parameters used to measure postural stability were lower after the repair for both, the frontal and sagittal plane as well as for the velocity of displacements in the sagittal plane in the double stance with eyes open. Poorer postural stability was also found in patients with pectus excavatum when compared to healthy controls. Our findings may be useful for functional monitoring in the evaluation and surgical management of pectus excavatum patients and also when designing the rehabilitation of patients undergoing the Nuss procedure.

Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study.

Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10-19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04-20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC.

Detection of EGFR mutations in liquid biopsy samples using allele-specific quantitative PCR: A comparative real-world evaluation of two popular diagnostic systems.

PURPOSE: The detection of epidermal growth factor receptor (EGFR) mutations in plasma cell-free DNA (cfDNA) is an auxiliary tool for the molecular diagnosis of non-small cell lung cancer (NSCLC), especially when an adequate tumor tissue specimen cannot be obtained. We compared the diagnostic accuracy of two commonly used in vitro diagnostic-certified allele-specific quantitative PCR assays for detecting plasma cfDNA EGFR mutations. METHODS: We analyzed EGFR mutations in plasma cfDNA from 90 NSCLC patients (stages I-IV) before treatment (n â€‹= â€‹60) and after clinical progression on EGFR tyrosine kinase inhibitors (n â€‹= â€‹30) using the cobas EGFR mutation test v2 (Roche Molecular Systems, Inc.) and therascreen EGFR Plasma RGQ PCR kit (Qiagen GmbH). RESULTS: There was higher concordance between plasma cfDNA and matched tumor tissue EGFR mutations with cobas (66.67%) compared with therascreen (55.93%). The concordance rate increased to 90.00% with cobas (Cohen's kappa coefficient, κ â€‹= â€‹0.80; p â€‹< â€‹0.0001) and 73.33% with therascreen (κ â€‹= â€‹0.49; p â€‹= â€‹0.0009) in advanced NSCLC patients. In treatment-naïve patients, cobas was superior to therascreen (sensitivity: 82.35% vs. 52.94%; specificity: 100% vs. 100%). In patients with clinical progression on EGFR tyrosine kinase inhibitors, EGFR exon 20 p.T790M was detected in 30% and 23% of cfDNA samples by cobas and therascreen, respectively. CONCLUSIONS: Cobas was superior to therascreen for detection of plasma EGFR mutations in advanced NSCLC. Plasma cfDNA EGFR mutation analysis is complex; therefore, the diagnostic accuracy of commercially available assays should be validated.

Pulmonary tuberculosis in a male with sarcoidosis.

Tuberculosis and sarcoidosis are chronic systemic diseases that have similar pulmonary and extra-pulmonary manifestations. It is likely that infection with Mycobacterium tuberculosis (MTB) is a common pathophysiologic mechanism for tuberculosis and sarcoidosis. We present a case of a patient with a primary diagnosis of sarcoidosis. The patient did not receive any immunosuppressive treatment till that time. Subsequently, smear-negative pulmonary tuberculosis was discovered, confirmed with the positive culture of bronchial washings and treated with antituberculous agents without major side effects. Both sputum smears and cultures were negative at the end of the treatment. It is worth highlighting that these two diseases share both clinical and histopathological features. Though it can be genuinely challenging to distinguish them, the precise and rapid diagnosis is crucial because the treatment is so different. Therefore MTB infection should be kept in mind in a broad differential diagnosis.

The expression of circulating miR-504 in plasma is associated with EGFR mutation status in non-small-cell lung carcinoma patients.

MicroRNAs (miRNAs), key regulators of gene expression at the post-transcriptional level, are grossly misregulated in some human cancers, including non-small-cell lung carcinoma (NSCLC). The aberrant expression of specific miRNAs results in the abnormal regulation of key components of signalling pathways in tumour cells. MiRNA levels and the activity of the gene targets, including oncogenes and tumour suppressors, produce feedback that changes miRNA expression levels and indicates the cell's genetic activity. In this study, we measured the expression of five circulating miRNAs (miR-195, miR-504, miR-122, miR-10b and miR-21) and evaluated their association with EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) mutation status in 66 NSCLC patients. Moreover, we examined the discriminative power of circulating miRNAs for EGFR mutant-positive and -negative NSCLC patients using two different data normalisation approaches. We extracted total RNA from the plasma of 66 non-squamous NSCLC patients (31 of whom had tumours with EGFR mutations) and measured circulating miRNA levels using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The miRNA expression levels were normalised using two endogenous controls: miR-191 and miR-16. We found significant associations between the expression of circulating miR-504 and EGFR-activating mutations in NSCLC patients regardless of the normalisation approach used (p = 0.0072 and 0.0236 for miR-16 and miR-191 normalisation, respectively). The greatest discriminative power of circulating miR-504 was observed in patients with EGFR exon 19 deletions versus wild-type EGFR normalised to miR-191 (area under the curve (AUC) = 0.81, p < 0.0001). Interestingly, circulating miR-504 levels were significantly reduced in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated subgroup compared to EGFR-mutated patients (p < 0.0030) and those with EGFR/KRAS wild-type tumours (p < 0.0359). Our study demonstrated the feasibility and potential diagnostic value of plasma miR-504 expression analysis to distinguish between EGFR-mutated and wild-type NSCLC patients. However, quality control and normalisation strategies are very important and have a major impact on the outcomes of circulating miRNA analyses.

Pulmonary tuberculosis in a male with silicosis.

Silicosis, a preventable occupational lung disease, is associated with various diseases, including tuberculosis (TB). There is an increased lifelong risk for lung tuberculosis even if exposure to silica dust ceases. That association contributes in a large extent to very high rates of tuberculosis in countries with poor TB and silica exposure control. We report a case of a male with a prior diagnosis of silicosis who was diagnosed with and treated for TB. Anti-tuberculous treatment was extended due to a positive sputum smear in the six th month of treatment. However, the culture of the sputum was negative. This case report highlights the value of thorough screening for tuberculosis in silicotic patients. The clinical management of these patients may be challenging due to frequent overlapping radiological features and uncertain results of TB treatment.

Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non-small cell lung cancer in patients with common and rare EGFR gene mutations.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are routinely used to treat non-small cell lung cancer (NSCLC) in patients with common activating mutations of the EGFR gene. The aim of the study was to compare the efficacies of EGFR-TKIs in patients with common (exon 19 deletions and exon 21 p.Leu858Arg) and rare EGFR mutations. A retrospective analysis of 180 NSCLC patients with common (n=167) and rare (n=13) EGFR mutations treated with erlotinib (n=98), gefitinib (n=66) and afatinib (n=16) was performed. EGFR mutations were determined using RT-PCR and the EntroGen EGFR Mutations Analysis kit. Partial and complete response (PR and CR), progression-free survival (PFS), and overall survival (OS) were analyzed. Demographic and clinical factors had no impact on PFS or OS in patients treated with EGFR-TKIs. Erlotinib, gefitinib, and afatinib showed similar efficacies based on treatment response, median PFS, and OS. The type of EGFR mutation had no impact on median OS; however, median PFS was significantly longer in patients with the exon 19 deletion compared to patients with the exon 21 p.Leu858Arg substitution and rare EGFR gene mutations (P=0.013). Patients with common EGFR mutations showed significantly longer median PFS than those with rare EGFR mutations (10 vs. 5 months; P=0.009). Erlotinib, gefitinib, and afatinib show similar efficacies in NSCLC patients with both common and rare EGFR mutations. When undergoing EGFR-TKI treatment, patients with rare EGFR mutations showed similar OS but poorer PFS. Further investigation into the associations between particular rare EGFR mutations and EGFR-TKIs treatment outcomes is required.

Squamous cell lung cancer in a male with pulmonary tuberculosis.

Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.

The impact of resistance respiratory muscle training with a SpiroTiger(®) device on lung function, exercise performance, and health-related quality of life in respiratory diseases.

INTRODUCTION: There are studies demonstrating that respiratory muscles can be trained using proper stimulation. Positive effects have been achieved in patients with pulmonary diseases and in patients after thoracic surgery procedures using isocapnic hyperpnoea training with a SpiroTiger(®) device. The aim of this study was to investigate whether SpiroTiger(®) training has an impact on forced expiratory volume in one second (FEV1), exercise performance, respiratory muscle fitness, and health-related quality of life. MATERIAL AND METHODS: Search phrases "spirotiger" and "spiro tiger" were entered into the search engines of the following databases: Academic Search Complete, Medline, Ebscohost, and PubMed. RESULTS: One article about chronic obstructive pulmonary disease (COPD) and 4 articles about cystic fibrosis were found. CONCLUSIONS: The positive effect of SpiroTiger(®) training on FEV1 cannot be unequivocally confirmed as it was found only in two of the five analysed studies. SpiroTiger(®) training has a positive impact on exercise performance measured with the six-minute walk test; it increases breathing muscle fitness in patients with COPD and in patients after thoracic surgery procedures, and it improves health-related quality of life.

Tuberculosis and diabetes mellitus - an underappreciated association.

The current review presents up-to-date knowledge on tuberculosis (TB) in diabetic patients. On the basis of available literature, there is little doubt about the close relationship between these two conditions. Diabetes mellitus in this association may still contribute substantially to the burden of TB and negatively affect control of the latter. Chronic hyperglycemia at least to some extent may alter the clinical manifestation, radiological appearance, treatment outcome and prognosis of TB. Although the pathogenesis is not clear, diabetes may impair both innate and adaptive immune responses to Mycobacterium tuberculosis. Eventually, effective screening and dual management of the diseases have to be addressed both in low- and high-income countries in order to limit the negative effects of the forthcoming global diabetes epidemic.

Actual status of therapeutic vaccination in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide. Although treatment methods such as surgery, radiotherapy and/or chemotherapy have improved, prognosis remains unsatisfactory, and developing new therapeutic strategies is still an urgent matter. Immunotherapy is a novel therapeutic approach wherein activated immune cells can specifically kill tumour cells. Several lung cancer vaccines have demonstrated prolonged survival time in phase II and III trials, and several clinical trials are under investigation. However, many clinical trials involving cancer vaccination with defined tumour antigens have shown this method to work only in a small number of patients. Cancer immunotherapy is not completely effective in eradicating tumour cells because they evade host immune control.

Pulmonary embolism in a young male with tuberculosis and factor V Leiden.

There is no doubt that venous thromboembolism (VTE) is a complex and multicausal disease. Tuberculosis (TB) itself is found to have thrombogenic potential. There is an association between tuberculosis and VTE. We present a case of a 31-year-old male diagnosed with TB after a 2-month delay. He was treated with an anticoagulant for pulmonary embolism (PE) complicated by pulmonary infarction, and with antibiotics for presumed bacterial pneumonia. The patient did not improve despite in-hospital treatment. Finally, TB was diagnosed with positive sputum smear for acid fast bacilli and subsequent culture of Mycobacterium tuberculosis. Antituberculous therapy was uneventful and the patient was discharged home. Thrombophilia screening revealed a heterozygous factor V Leiden mutation. This case report emphasises that although there is a steady decline in active cases of TB, it should be still placed high on the list as a differential diagnosis in non-resolving lung infection or pulmonary infarction. This is especially relevant in cases with typical radiological findings located in the upper lobes. On the other hand, definitive diagnosis may be challenging in a case of concurrent TB, bacterial pneumonia and pulmonary infarction. Thromboembolic events may develop in TB patients without any clinical VTE risk factors. Therefore, thromboprophylaxis should be cautiously considered in this group of patients.

EGFR gene mutations in patients with adenosquamous lung carcinoma.

AIM: Adenosquamous (ADSQ) carcinoma accounts for 1-4% of non-small cell lung cancer (NSCLC). The origin of ADSQ carcinoma and its genetic background is not fully understood. Most studies concerning epidermal growth factor receptor (EGFR) mutation status are performed in adenocarcinoma, while there is limited information about the prevalence of this mutation in ADSQ-bearing Caucasian patients and the efficacy of EGFR tyrosine kinase inhibitors. METHODS: EGFR gene status has been examined in 1000 non-squamous NSCLC patients of Polish origin. Polymerase chain reaction (PCR) followed by DNA fragment length analysis and allele-specific PCR as well as real-time PCR technique were used to estimate EGFR gene status. Complete clinical data were obtained for all examined patients. RESULTS: In the group of 1000 non-squamous NSCLC patients, ADSQ was diagnosed in 14 (1.4%) cases. Activating mutations of EGFR were observed in 28.6% (four out of 14) of ADSQ-bearing patients and included deletions of 15 base-pairs in exon 19 in three cases (one man and two women) and substitution of L861Q with coexistence of G719X mutation in one non-smoking male patient. Deletions were diagnosed in two non-smoking patients and one current-smoking female patient (50 pack-years). One non-smoking man with deletion in exon 19 of EGFR gene was successfully treated with gefitinib in first-line therapy. CONCLUSIONS: EGFR gene mutations in ADSQ carcinoma patients may be more common than previously thought. EGFR mutation testing is appropriate in ADSQ-bearing patients, in which response for molecular-based therapy is predictable.

Biomechanics assessment of long term consequences of talocrural joint sprain in conservatively treated males.

The aim of the study was an assessment of isometric torque (IT) values under static conditions and relative torque (RT) for the plantar flexion muscles (PFM) and dorsal flexion muscles (DFM) and their mutual relations in males 5 years after talocrural joint sprain. IT measurements in PFM and DFM were performed using Biodex System 3. Group I consisted of 20 males on average 5 years after the sprain of the talocrural joint. Group II comprised 23 males with no history of talocrural joint injuries. The angles of measurement were: -15° of dorsiflexion (DF) and 0°, 15°, 30° and 45° for plantar flexion (PF) of the foot. In group I, the IT and RT obtained from PFM of involved leg were statistically significantly lower for most of the measured values of foot angle as compared to the contralateral joint and the results of the control group. The increase in the PF angle resulted in the decrease in IT values obtained from PFM, in favour of DFM. The IT values for PFM and DFM depend on the angle of foot and are represented by two different curves.

New onset diabetes in a patient with active tuberculosis.

The present report describes the coincidence of pulmonary tuberculosis (TB) and metabolic disorder such as diabetes. A patient's bronchoalveolar lavage was found to be positive for acid-fast bacilli (AFB) with following growth of Mycobacterium tuberculosis and complete sensitivity to first line anti-TB drugs. At the same time, the patient presented with typical diabetes manifestation and subsequently required insulin therapy. Combined treatment resulted in significant clinical improvement and gradual resolution of both TB and diabetes symptoms. Therefore, we would like to highlight the value of appropriate medical management of these disorders sharing at least some clinical symptoms and signs such as weight loss and fatigue. Moreover, a growing body of evidence indicates that diabetes may play a role as a risk factor for TB. Consequently, the increasing diabetes prevalence may be a danger to TB control.

Assessment of respiratory function in girls with scoliosis after thoracoplasty.

BACKGROUND: The aim of the study was to assess pulmonary function in patients after spinal fusion combined with thoracoplasty in comparison with subjects in whom thoracoplasty was not performed, but who underwent intensive rehabilitation. MATERIAL NA DMETHODS: The study population consisted of two groups of adolescent girls about two years after surgical correction of scoliosis by Cotrel-Dubousset method. The subjects in the first group (thoracoplasty group) underwent spinal fusion in combination with thoracoplasty, which consisted in subperiosteal resection of deformed segments of six ribs on top of the rib hump. Patients in the second group (rehabilitation group) had no thoracoplasty, but participated in a 4-week rehabilitation programme based on endurance training. Pulmonary function was assessed in all subjects with resting spirometry. Additionally, maximal oxygen uptake was determined using an indirect method. RESULTS: Spirometric parameters at rest were significantly higher in subjects participating in the rehabilitation program compared to the thoracoplasty patients. VO2max values were similar in both groups, indicating relatively good exercise capacity. CONCLUSIONS: Comprehensive motor rehabilitation based on endurance training has a favorable influence on pulmonary function in patients after surgical correction of scoliosis. A rehabilitation program should be included in the management of patients after spinal fusion combined with thoracoplasty.

Comparison of carbohydrate digestion between Japanese and Polish healthy subjects.

We have revealed that light environment affects digestion and absorption of dietary carbohydrates in the gastrointestinal tract. This experimental result supposes that the efficiency of carbohydrate absorption may differ among people who live in different latitudes, such as Japanese and Polish people, at the same calendar season. In order to prove this hypothesis, we have been comparing the efficiency of carbohydrate absorption using the breath hydrogen test in Japan and Poland. Here, we report the comparison of the result obtained in the summer of 2004 as the following; (1) Orocecal transit time (OCTT) for indigestible trisaccharide of Japanese subjects was significantly longer than that in Poland (p = 0.043). (2) On the ingestion of minestrone, the amount of unabsorbed carbohydrate of Japanese subjects (which was estimated as trisaccharide equivalent) was significantly larger than that of Polish subjects (p = 0.006).