Helping Others Facilitates Well-Being for Indigenous Peoples Living With HIV/AIDS in Canada.

Research has found that helping others facilitates well-being for Indigenous peoples living with HIV and AIDS, but limited research exists that investigates the mechanism(s) underlying this relationship. Indigenous perspectives posit that helping others facilitates well-being through the development of an individual's spiritual, physical, emotional, and mental aspects (four aspects). Similarly, self-determination theory posits that helping others facilitates well-being by satisfying basic psychological needs. In the present study, we examined if helping others facilitates well-being through the fulfillment of the spiritual, physical, emotional, and mental aspects among Indigenous peoples living with HIV and AIDS. We used a convergent parallel mixed methods design, coupled with a community-engaged approach grounded in the United Nations Greater Involvement of People Living with HIV and AIDS principles and Indigenous and decolonizing research methodologies. Survey (n = 117) and interview data (n = 9) collected by an Indigenous-led HIV/AIDS organization in Canada were employed to examine the relationship between helping, the four aspects, and well-being. Participants were primarily First Nations leaders and mentors who live with HIV/AIDS, with some Métis and Inuit. A parallel multiple mediation model and reflexive thematic analysis were used to analyze the relationship between helping, the four aspects, and well-being. Mixed-methods findings support the idea that helping others promotes well-being by fulfilling the emotional and mental aspects. Qualitative findings demonstrated this relationship for all four aspects. This research may facilitate the development of programs to support Indigenous peoples living with HIV/AIDS well-being and contribute to the literature on integrating Indigenous perspectives and methodologies within psychological research.

Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter EXPRESS study.

OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.

ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib.

OBJECTIVE: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases. MATERIALS AND METHODS: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH. RESULTS: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC+/FISH+) and 16 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010. CONCLUSION: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.

Transesophageal endoscopic ultrasound/fine-needle aspiration diagnosis of a malignant adrenal gland in a patient with non-small cell lung cancer and a negative CT scan.

Adrenal metastasis is only seen on CT scan is less than 5% of patients with otherwise resectable NSCLS, but this diagnosis has a major impact on treatment and prognosis. We present a case of a patient with NSCLC and an adrenal metastasis, which was diagnosed by EUS/FNA of an enlarged adrenal gland, who had false-negative CT scan for adrenal metastasis. PET was not performed. Prospective studies are needed to assess the incremental yield of EUS/FNA over upper abdominal CT scan and PET for detecting left adrenal metastasis in patients with suspected or proven otherwise respectable NSCLC.

Communications: high dermal mast cell prevalence is a predisposing factor for basal cell carcinoma in humans.

Ultraviolet B radiation (280-320 nm) can initiate skin cancer as well as suppress the immune system, thereby preventing the rejection of ultraviolet-B-induced tumors. Recently we reported that there was not only a correlation but also a functional link between dermal mast cell prevalence and susceptibility to ultraviolet-B-induced systemic immunosuppression in multiple strains of mice. In this study, we investigated whether increased dermal mast cell prevalence is a significant predisposing factor for basal cell carcinoma development in humans. In 21 Danes with a history of basal cell carcinoma and 20 control subjects of similar age, sex, skin phototype, and recreational sun exposure over the past 12 mo, dermal mast cell prevalence was quantified on non-sun-exposed buttock skin. We investigated this skin site in order to avoid any changes in mast cell prevalence caused by sun exposure and assumed that the prevalence of mast cells in buttock skin correlated with that at sun-exposed sites at critical times in the development of basal cell carcinomas. Patients with a history of basal cell carcinoma had a significantly higher median dermal mast cell prevalence than control subjects (p = 0.01, Mann-Whitney U ). No correlation was observed between dermal mast cell prevalence and age of basal cell carcinoma patients and control subjects. These results suggest that increased dermal mast cell prevalence is a predisposing factor for basal cell carcinoma development in humans. We hypothesize that mast cells function in humans, as in mice, by initiating immunosuppression and thereby allowing a permissive environment for basal cell carcinoma development.

Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer.

Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation system, and compare the levels of uPA, PAI-1 and uPAR in extracts of NSCLC-tissue and SCLC-tissue. A statistically significant difference, P = 0.037, was found between uPA-levels in NSCLC-patients (n = 75) and SCLC-patients (n = 8), the highest levels being found in NSCLC. No such difference was found for the two other components investigated, although a trend towards increased uPAR-levels was observed in SCLC, P = 0.055. The relationship between the levels of each of the components and other known clinical parameters was also analysed. No relationship was found between any of the components and the clinical parameters. This is the first report of a study using a quantitative method to compare levels of the components of the plasminogen activation system in tissue extracts from the two major lung cancer groups. The study shows that uPA, PAI-1 and uPAR are present in SCLC-tissue, suggesting that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology.

ME1-antibody labelling of primary bronchogenic tumours and extrapulmonary malignancies.

ME1 is a monoclonal antibody which is generated by the use of a mesothelioma cell line (SPCIII). The antibody has a preferential reaction to antigens on mesothelial and mesothelioma cells. In a prospective study we determined the reactivity in frozen sections from malignant mesotheliomas (two cases, positive controls), lung tumours (115 cases) and other malignant tumours (23 cases). The two malignant mesotheliomas were immunoreactive in most of the tumour cells. The reaction was strong, often with a diffuse staining of the cytoplasm and in some tumour cells there was heavy staining of the cell membrane. Five adenocarcinomas of the lung (9%), one large cell carcinoma (10%) and 18 squamous cell carcinomas of the lung (41%) were positive (defined as tumours containing more than 10% positive tumour cells with a strong reaction). The same was true for seven out of 23 (30%) extrapulmonary malignancies. The overall nosologic specificity of ME1 was 76%. Twenty out of the 26 ME1-positive lung tumours and six out of seven ME1-positive extrapulmonary malignancies were also positive for one or more markers, which is considered characteristic of carcinomas. The six negative lung tumours were squamous cells carcinomas and the negative extrapulmonary tumour was a meningeoma; all of them with a morphology different to malignant mesothelioma. In conclusion, when frozen sections are available, ME1 might be useful in the differential diagnosis of malignant tumours. However, a positive reaction is not specific for malignant mesothelioma.

Levels of plasminogen activator inhibitor type 1 and urokinase plasminogen activator receptor in non-small cell lung cancer as measured by quantitative ELISA and semiquantitative immunohistochemistry.

The components of the plasminogen activation system have been reported to have prognostic impact in several cancer types, e.g. breast-, colon-, gastric- and lung cancer. Most of these studies have used quantification by enzyme-linked immunosorbent assay (ELISA) on tumour tissue extracts. However, results in non-small cell lung cancer (NSCLC) studies obtained by quantitative ELISA and semiquantitative immunohistochemistry differ. If the prognostic value of the components of the plasminogen activation system is to be exploited clinically in the future, it is important to choose an easy and valid methodology. In the present study we investigated levels of plasminogen activator inhibitor type 1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), as quantitated by ELISA in tumour extracts from 64 NSCLC patients (38 squamous cell carcinomas, 26 adenocarcinomas), and compared them to staining intensity as semiquantitated by immunohistochemistry for PAI-1 and uPAR on corresponding cryostat sections. A significant association (r = 0.49, P < 0.0001) was found between the PAI-1 levels measured by ELISA and semiquantitated by immunohistochemistry. No association was found for uPAR. When correlating levels of PAI-1 and uPAR determined by ELISA and immunohistochemistry, respectively, to survival status, no significant correlation was found for any of the subgroups. At present neither of the methods examined in the present study can be recommended as superior for quantitating PAI-1 and uPAR with the aim of predicting prognosis. In conclusion, a larger comparative study is needed to clarify the relationship between ELISA and immunohistochemical results, before a methodology for clinical use can be chosen in non-small cell lung cancer.

Are pathologists biased by clinical information?: A blinded cross-over study of the histopathological diagnosis of mesothelial tumours versus pulmonary adenocarcinoma.

In a blinded cross-over design, we studied whether three pathologists were biased by clinical information when making histopathological diagnoses of adenocarcinoma of the lung and benign and malignant mesothelial tumours. Furthermore, the interobserver variation of these diagnoses was assessed. Forty-one cases of adenocarcinoma of the lung and mesothelial tumours were assessed by three pathologists in four rounds. In the first two rounds, slides stained by H&E and clinical information were available. Slides and information were matched so that a specific slide in one round was given clinical information suggesting adenocarcinoma and in the other round, the clinical information suggested mesothelial tumour. In the third and fourth rounds, a panel of immunohistochemical stains was added. The clinical information was matched in the same way as in the first and second rounds. Bias by clinical information was observed when the diagnoses were made on slides stained by H&E, while no bias could be demonstrated when immunohistochemical reactions were included. The reproducibility also improved significantly when these slides were available.

Genotoxicity testing of the herbicide Roundup and its active ingredient glyphosate isopropylamine using the mouse bone marrow micronucleus test, Salmonella mutagenicity test, and Allium anaphase-telophase test.

The genotoxic potential of the herbicide Roundup and its active agent, glyphosate isopropylamine salt, was studied in three different assays. No clastogenic effects were found in the mouse bone marrow micronucleus test for either of the two agents. In the Salmonella assay only Roundup was tested. It showed a weak mutagenic effect for the concentrations 360 micrograms/plate in TA98 (without S9) and 720 micrograms/plate in TA100 (with S9). These concentrations are close to the toxic level. The anaphase-telophase Allium test showed no effect for the glyphosate isopropylamine salt, but a significant increase in chromosome aberrations appeared after treatment with Roundup at concentrations of 1.44 and 2.88 mg/l when calculated as glyphosate isopropylamine. The most frequent aberrations observed could be characterized as disturbances of the spindle.

An experimental study of hot air thermocoagulation in cardiac surgery.

Recently a thermocoagulator using hot air has been developed. It has been used for haemostatic purposes in a number of cases of liver, pulmonary and retroperitoneal cancer surgery. An experimental animal study was undertaken to evaluate the use of the thermocoagulator during cardiac surgery. Since the thermocoagulator produces coagulation necrosis, the epi-/myocardium including the epicardial coronary arteries was investigated microscopically for acute and chronic histopathological changes. The investigation demonstrated that the thermocoagulator is an effective hemostatic tool during cardiac surgery. The histological examination of the hearts has shown that the technique does not damage the myocardium or the coronary arteries neither at the time of application nor in the long term.

Carcinoid tumor of the middle ear.

Carcinoid tumor of the middle ear is a very rare benign neoplasm, which may be mistaken for a malignant tumor. We present two new cases together with a review of 28 previously reported cases. Nearly all patients had progressive hearing loss, most often of the conductive type. About half of the patients complained of tinnitus and fullness of the ear. The typical otoscopic picture was erythema or lateral bulging of the tympanic membrane, which was intact in most patients. The tumor was most often localized to the middle ear with varying degree of extensions into neighboring areas. It often encapsulated the ossicles, which sometimes were eroded. Systemic symptoms were only reported in two cases. The tumor is clinically benign and total excision of the tumor and affected ossicles is an adequate treatment. The correct diagnosis, which should be considered in case of any adenomatous tumor of the middle ear, requires immunohistochemical and ultrastructural procedures.

[Autofluorescence bronchoscopy: Laser imaging fluorescence endoscope]. / Autofluorescensbronkoskopi: "Laser imaging fluorescense endoscope".

The LIFE (laser imaging fluorescence endoscope) system has been shown to increase the diagnosis of dysplasia and carcinoma in situ when used in combination with conventional bronchoscopy. A doubling to tripling of the rate of early centrally located lung cancer diagnosis is a step forward in the detection of early lung cancer. A wide spectrum of interventional procedures for endoluminal treatment of lung cancer in functionally inoperable patients makes it possible to treat this group of patients. The LIFE system works without exogenous sensitisers, with no increase in complications as compared to conventional bronchoscopy, and takes only a little longer in examination time.

[Heterotopic thyroid tissue localized to the pelvis]. / Heterotopt thyreoideavaev lokaliseret intrapelvint.

A case of well encapsulated thyroid tissue localized to the pelvis and without relation to the ovaries is presented. This anomaly is interpreted as a monodermal extragonadal teratoma. In cases of unusual localization of thyroid tissue, the following should be considered in the differential diagnosis: ectopia, metastasis from an occult carcinoma of the thyroid gland and teratoma. When thyroid tissue of teratoid origin is found, surgical removal is advised on account of the malignant potentialities of these tumors.

[Study of the elimination of residues and local tissue injury following intramuscular injection of a solution of the combination trimethoprim/sulfatroxazole in pigs]. / Onderzoek naar de eliminatie van residuen en lokale weefselbeschadiging na intramusculaire injectie van een oplossing van de combinatie van trimethoprim/sulfatroxazol bij varkens.

Two different studies are described. The first study deals with the elimination of residues of trimethoprim (TMP), sulfatroxazole (STX) and its main metabolite N4-acetyl-sulfatroxazole (N4-acetyl-STX) in pigs. Thirty -six pigs were treated with trimethoprim/sulfatroxazole IM in the nec k at a dosage of 16 mg/kg body weight for five days. Groups of four pig s were slaughtered at different time intervals. The study showed that concentration of STX, N4-acetyl-STX and TMP in edible tissues and at the injection sites were below 0.1 ppm on day nine after the last injection. S TX was eliminated the slowest, and STX can therefore be selected as a marker for residues of the trimethoprim/sulfatroxazole formulation in the tissues. The second study deals with irritation aspects of this trimethoprim /sulfatroxazole formulation. Four pigs of 32-35 kg were treated IM w with trimethoprim/sulfatroxazole and benzylpenicillin sodium. Each pig received the same injection volume, namely four trimethoprim/sulfatroxazole injections (16 mg/kg body weight per injection site), two in the back and two in the neck muscle, and two benzylpenicillin sodium injections (20,000 I.U./kg body weight per injection site), in the back muscle. All pigs were slaughtered 14 days after treatment and the extent of the irritation was compared. There were no differences between trimethoprim/sulfatroxazole and benzylpenicillin sodium with regard to irritation at the injection site in the back muscle. The irritation in the neck site was statistically less prominent than that in the back muscle and was considered not to affect the quality of the meat.

Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy.

BACKGROUND: Survival benefit of non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is predicted by high EGFR gene copy number and by strong EGFR protein expression. Clinical relevance of these features in patients treated with chemotherapy has not been reported. PATIENTS AND METHODS: This study included 82 NSCLC patients treated with chemotherapy. There were 45% of females, 6% of never smokers and 45% of patients diagnosed with adenocarcinoma. EGFR gene copy number was evaluated by fluorescence in situ hybridization and EGFR protein level by immunohistochemistry. RESULTS: High EGFR gene copy number and protein level were found in 33% and 71% of patients, respectively. Both markers were significantly associated (P = 0.01). For objective response and disease control, there was no difference between patients defined as negative or positive for both EGFR gene copy number (P = 0.39 and P = 1.00, respectively) and for EGFR protein (P = 1.00 and P = 0.80, respectively). There were no differences in progression-free and overall survival according to EGFR gene copy number (P = 0.76 and P = 0.82, respectively) and protein level (P = 0.67 and P = 0.62, respectively). CONCLUSION: In chemotherapy-treated NSCLC patients, EGFR gene copy number was positively associated with protein level but none of the features were predictive for either treatment response or survival.