Difficulties in management of tuberculous pneumonia in a patient with liver failure in the course of chronic hepatitis B and concomitant failure of the transplanted kidney

A 62-year-old woman with liver failure in the course of chronic hepatitis B and concomitant failure of the transplanted kidney was treated for tuberculous pneumonia. The treatment was initiated with rifampin, isoniazid and pyrazinamide. Both renal and hepatic side effects required modification of this scheme. After 1 month of treatment sputum smears tested for acid-fast bacilli converted to a negative result and the chest X-ray demonstrated complete resolution of pulmonary infiltrates. Further therapy resulted in serious deterioration of the liver failure and fatal outcome.A 62-year-old woman with liver failure in the course of chronic hepatitis B and concomitant failure of the transplanted kidney was treated for tuberculous pneumonia. The treatment was initiated with rifampin, isoniazid and pyrazinamide. Both renal and hepatic side effects required modification of this scheme. After 1 month of treatment sputum smears tested for acid-fast bacilli converted to a negative result and the chest X-ray demonstrated complete resolution of pulmonary infiltrates. Further therapy resulted in serious deterioration of the liver failure and fatal outcome

How do relatives remember the dying of lung cancer patients after 2-8 years? A qualitative study based on in-depth interviews with family members

Background. The aim of our study was to assess how relatives remember the dying of lung cancer patients several years after their death. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with 2 researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire and to score the Quality of Dying Apgar. Results. Family members of 15 of the patients stated recognizing the dying of their loved one. They concluded this on the basis of exacerbation of symptoms, "typical" appearance, change in behaviour or particular words the patient said to them. The median score of the quality of dying was 6.5/10 (range 3-9). Lower scoring was observed for patients who died in hospital, without the family present at the moment of death and with uncontrolled symptoms. Only 5 of the relatives assessed pain and other symptom control as satisfactory. Other family members remembered pain (n = 9), dyspnoea (n = 8), delirium (n = 4) and other symptoms as disturbing the dying in a severe or moderate way. Three relatives assessed that their loved one's dying was not "dignified", mostly due to the severe physical suffering, the nursing being crucially remiss at the hospital and the patient's being alone at the moment of death. All family members were able to describe the healthcare professionals' attitudes and even repeat the statements they heard from them. Conclusion. We have demonstrated that several years after death many of the words and the behaviour of the dying patients were still alive in their relatives' memories. The family members remember how the healthcare professionals behaved and what they said to them. While caring for dying people, we should bear in mind that the way in which we behave may either give strength to the family or destroy their peace of mind for many years.Background. The aim of our study was to assess how relatives remember the dying of lung cancer patients several years after their death. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with 2 researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire and to score the Quality of Dying Apgar. Results. Family members of 15 of the patients stated recognizing the dying of their loved one. They concluded this on the basis of exacerbation of symptoms, "typical" appearance, change in behaviour or particular words the patient said to them. The median score of the quality of dying was 6.5/10 (range 3-9). Lower scoring was observed for patients who died in hospital, without the family present at the moment of death and with uncontrolled symptoms. Only 5 of the relatives assessed pain and other symptom control as satisfactory. Other family members remembered pain (n = 9), dyspnoea (n = 8), delirium (n = 4) and other symptoms as disturbing the dying in a severe or moderate way. Three relatives assessed that their loved one's dying was not "dignified", mostly due to the severe physical suffering, the nursing being crucially remiss at the hospital and the patient's being alone at the moment of death. All family members were able to describe the healthcare professionals' attitudes and even repeat the statements they heard from them. Conclusion. We have demonstrated that several years after death many of the words and the behaviour of the dying patients were still alive in their relatives' memories. The family members remember how the healthcare professionals behaved and what they said to them. While caring for dying people, we should bear in mind that the way in which we behave may either give strength to the family or destroy their peace of mind for many years

The last months of lung cancer patients’ lives, in the memory of their relatives. A qualitative study based on in-depth interviews with family members

Background. The aim of the study was to assess how family members remember the final months of their loved ones 2–8 years after their death. We focused particularly on their recognition of the patients’ physical, psychosocial and spiritual needs. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with two researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire. Results. Almost all the relatives interviewed in our study were able to recognize the beginning of the terminal phase. They connected the beginning of dying with the deterioration of the physical and/or psychological status of patients, such as the exacerbation of weakness and/or other symptoms or with clearly distinguished incidents such as cancer recurrence or hip fracture. The majority were able to define the length of this phase as being several months (median = 3, range 1–11 months). The most common physical symptoms mentioned by the relatives interviewed were, in sequential order: pain (n = 13) and fatigue (n = 13), anorexia (n = 9), dyspnoea (n = 7) and cachexia (n = 7). Of the 20 decedents, 18 regularly received painkillers at least at some period during their final months. Apart from medicines prescribed by the doctors, 9 patients were treated with “anticancer” herbs, or homeopathy, or by bioenergotherapy. From the relatives’ perspectives, the main approach was focused on the physical aspects of care while there was a lack of psychological and social support, the latter often causing severe financial burden. Most relatives believed that chaplains are the main source of spiritual comfort and there was easy access to such a service both in their parish and in the hospice or hospitals. Conclusion. Our study showed that the families remembered feelings of loneliness and helplessness when confronted with the psychological suffering of their loved ones and the financial burdens caused by the caregivers. Professionals involved in palliative care should acknowledge that holistic care requires sensitivity, not only to the physical but also to the psychosocial and spiritual aspects of end-of-life care.Background. The aim of the study was to assess how family members remember the final months of their loved ones 2–8 years after their death. We focused particularly on their recognition of the patients’ physical, psychosocial and spiritual needs. Methods. The family members of 45 non small-cell lung cancer patients who died up to 7 years after radical surgical treatment were telephoned and asked to meet the research team. Only 20 of them agreed to talk about the dying and death of their relatives; for the rest the issue was still too painful. During the meeting with two researchers, participants were asked to comment freely on the points of the Assessment of Dying in Lung Cancer Patients questionnaire. Results. Almost all the relatives interviewed in our study were able to recognize the beginning of the terminal phase. They connected the beginning of dying with the deterioration of the physical and/or psychological status of patients, such as the exacerbation of weakness and/or other symptoms or with clearly distinguished incidents such as cancer recurrence or hip fracture. The majority were able to define the length of this phase as being several months (median = 3, range 1–11 months). The most common physical symptoms mentioned by the relatives interviewed were, in sequential order: pain (n = 13) and fatigue (n = 13), anorexia (n = 9), dyspnoea (n = 7) and cachexia (n = 7). Of the 20 decedents, 18 regularly received painkillers at least at some period during their final months. Apart from medicines prescribed by the doctors, 9 patients were treated with “anticancer” herbs, or homeopathy, or by bioenergotherapy. From the relatives’ perspectives, the main approach was focused on the physical aspects of care while there was a lack of psychological and social support, the latter often causing severe financial burden. Most relatives believed that chaplains are the main source of spiritual comfort and there was easy access to such a service both in their parish and in the hospice or hospitals. Conclusion. Our study showed that the families remembered feelings of loneliness and helplessness when confronted with the psychological suffering of their loved ones and the financial burdens caused by the caregivers. Professionals involved in palliative care should acknowledge that holistic care requires sensitivity, not only to the physical but also to the psychosocial and spiritual aspects of end-of-life care

Jak najbliżsi pamiętają umieranie chorych na raka płuca po 2-8 latach? Badanie jakościowe oparte na wywiadach z członkami rodzin

Wstęp. Celem badania była ocena, jak bliscy pamiętają umieranie chorych na raka płuca kilka lat po ich śmierci. Materiał i metody. Zaproszenie do udziału w badaniu przekazano telefonicznie rodzinom 45 chorych, którzy zmarli do 7 lat po radykalnej resekcji niedrobnokomórkowego raka płuca. Tylko 20 z zaproszonych osób zgodziło się rozmawiać o umieraniu i śmierci ich najbliższych. Dla pozostałych ten temat był ciągle zbyt bolesny. Podczas spotkania z dwoma badaczami uczestników poproszono, aby w swobodny sposób odnieśli się do problemów poruszonych w kwestionariuszu Oceny Umierania Chorych na Raka Płuca oraz spróbowali okreslić jakość umierania według skali The Quality of Dying Apgar (QODA). Wyniki. Krewni 15 pacjentów uważali, że byli w stanie rozpoznać okres umierania ich bliskich na podstawie nasilenia objawów, „typowego” wyglądu, zmiany zachowania lub szczególnych słów, jakie od nich usłyszeli. Mediana punktacji w skali oceniającej jakość umierania według QODA wynosiła 6,5/10 (przedział 3-9). Niższe oceny zanotowano w przypadku pacjentów umierających w szpitalu, których rodziny były nieobecne w czasie zgonu, a także jeśli objawy leczono w niedostateczny sposób. Jedynie rodziny 5 pacjentów uważały łagodzenie bólu i innych objawów w ostatnich dniach życia za zadowalające. Pozostali pamiętali, że ból (n = 9), duszność (n = 8), splątanie (n = 4) lub inne objawy zaburzały umieranie w znacznym lub bardzo nasilonym stopniu. Krewni 3 chorych stwierdzili, że umieranie ich bliskich nie było „pełne godności” przede wszystkim z powodu bardzo nasilonych objawów fizycznych, drastycznych zaniedbań pielęgnacyjnych w szpitalu i poczucia opuszczenia w momencie zgonu. Wszyscy uczestnicy badania byli w stanie opisać postawę lekarzy i pielęgniarek, a nawet powtórzyć wypowiedzi, które od nich usłyszeli. Wnioski. W badaniu pokazano, że nawet po kilku latach wiele słów, gestów i zachowań chorych z okresu ich umierania przechowywanych jest w pamięci ich rodzin. Członkowie rodzin pamiętają też, jak zachowywał się personel medyczny i jakich słów używał. Opiekując się umierającymi, należy uwzględnić, że sposób, w jaki się to robi, ma dla ich bliskich duże znaczenie i może ich albo wzmacniać, albo osłabiać na długie lata

Combined clinical and genomic signatures for the prognosis of early stage non-small cell lung cancer based on gene copy number alterations

BACKGROUND: The development of a more refined prognostic methodology for early non-small cell lung cancer (NSCLC) is an unmet clinical need. An accurate prognostic tool might help to select patients at early stages for adjuvant therapies. RESULTS: A new integrated bioinformatics searching strategy, that combines gene copy number alterations and expression, together with clinical parameters was applied to derive two prognostic genomic signatures. The proposed methodology combines data from patients with and without clinical data with a priori information on the ability of a gene to be a prognostic marker. Two initial candidate sets of 513 and 150 genes for lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively, were generated by identifying genes which have both: a) significant correlation between copy number and gene expression, and b) significant prognostic value at the gene expression level in external databases. From these candidates, two panels of 7 (ADC) and 5 (SCC) genes were further identified via semi-supervised learning. These panels, together with clinical data (stage, age and sex), were used to construct the ADC and SCC hazard scores combining clinical and genomic data. The signatures were validated in two independent datasets (n = 73 for ADC, n = 97 for SCC), confirming that the prognostic value of both clinical-genomic models is robust, statistically significant (P = 0.008 for ADC and P = 0.019 for SCC) and outperforms both the clinical models (P = 0.060 for ADC and P = 0.121 for SCC) and the genomic models applied separately (P = 0.350 for ADC and P = 0.269 for SCC). CONCLUSION: The present work provides a methodology to generate a robust signature using copy number data that can be potentially used to any cancer. Using it, we found new prognostic scores based on tumor DNA that, jointly with clinical information, are able to predict overall survival (OS) in patients with early-stage ADC and SCC

BRCA1: A Novel Prognostic Factor in Resected Non-Small-Cell Lung Cancer

BACKGROUND: Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1). METHODOLOGY AND PRINCIPAL FINDINGS: We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04). CONCLUSIONS: Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated

Osimertinib – effective treatment of NSCLC with activating EGFR mutations after progression on EGFR tyrosine kinase inhibitors

Non-small cell lung cancer (NSCLC) driven by activating mutations in epidermal growth factor receptor (EGFR) constitutes up to 10% of NSCLC cases. According to the NCCN recommendations, all patients (with the exception of smoking patients with squamous cell lung cancer) should be screened for the presence of activating EGFR mutations, i.e. deletion in exon 19 or point mutation L858R in exon 21, in order to select the group that benefits from EGFR tyrosine kinase inhibitors (EGFR TKIs) treatment. Among approved agents there are the 1st generation reversible EGFR TKIs, erlotinib and gefitinib, and the 2nd generation irreversible EGFR TKI, afatinib. The objective response rates to these drugs in randomised clinical trials were in the range of 56–74%, and median time to progression 9–13 months. The most common determinant of resistance to these drugs is the clonal expansion of cancer cells with T790M mutation (Thr790Met) in exon 20 of EGFR. Osimertinib (Tagrisso™), a 3rd generation, irreversible EGFR tyrosine kinase inhibitor, constitutes a novel, highly efficacious treatment for NSCLC patients progressing on EGFR TKIs with T790M mutation confirmed as the resistance mechanism. Resistance mutation can be determined in tissue or liquid biopsy obtained after progression on EGFR TKIs. Osimertinib has a favourable toxicity profile, with mild rash and diarrhoea being the most common. In this article, we present three cases that were successfully treated with osimertinib after progression on 1st and 2nd generation EGFR TKIs

Analiza rokowniczego znaczenia mutacji genu TP53 u chorych na niedrobnokomorkowego raka pluca

The aim of this study was to assess the frequency and prognostic value of TP53 gene somatic mutations in non-small cell lung cancer. The study group included 240 NSCLC patients who underwent pulmonary resection at the Department of Thoracic Surgery, Medical University of Gdansk. Tumour samples were evaluated for the presence of TP53 gene mutations in exons 5-8. In 157 cases SSCP method was used as a screening followed by sequencing of positive samples. In the remaining 83 patients mutations were analysed by direct sequencing. A total of 76 mutations (32%) were found, of those a missense type was dominant (67%), followed by silent and null type mutations (14% and 10%, respectively). There was no correlation between mutations and clinical characteristics, including age, sex, histological subtype, differentiation, tumour size, lymph node metastases, pTNM stage and smoking status. A multivariate Cox analysis demonstrated that tumour differentiation and pTNM stage were independent prognostic factors, whereas TP53 gene mutations were not. The results of this study indicate that TP53 gene mutations in NSCLC patients are not correlated with clinical characteristics and have no impact on survival