Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT.

BACKGROUND: Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. METHODS: Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy-Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. RESULTS: Compared to CON, EX had a reduced time to complete a processing speed test (trail making test-A) (-14.2 seconds, P < .01; effect size 0.35). Compared to CON, there was no improvement in self-reported cognitive function and effect sizes were small. Interestingly, lack of between-group differences in Stroop behavioral performance was accompanied by functional changes in several brain regions of interest in EX compared to CON at 24 weeks. CONCLUSION: These findings provide preliminary proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment and will serve to inform the development of future trials.

Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.

BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. CONCLUSIONS: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.

Psychological distress and salivary secretory immunity.

Stress-induced impairments of mucosal immunity may increase susceptibility to infectious diseases. The present study investigated the association of perceived stress, depressive symptoms, and loneliness with salivary levels of secretory immunoglobulin A (S-IgA), the subclasses S-IgA1, S-IgA2, and their transporter molecule Secretory Component (SC). S-IgA/SC, IgA1/SC and IgA2/SC ratios were calculated to assess the differential effects of stress on immunoglobulin transport versus availability. This study involved 113 university students, in part selected on high scores on the UCLA Loneliness Scale and/or the Beck Depression Inventory. Stress levels were assessed using the Perceived Stress Scale. Unstimulated saliva was collected and analysed for total S-IgA and its subclasses, as well as SC and total salivary protein. Multiple linear regression analyses, adjusted for gender, age, health behaviours, and concentration effects (total protein) revealed that higher perceived stress was associated with lower levels of IgA1 but not IgA2. Perceived stress, loneliness and depressive symptoms were all associated with lower IgA1/SC ratios. Surprisingly, higher SC levels were associated with loneliness and depressive symptoms, indicative of enhanced transport activity, which explained a lower IgA1/SC ratio (loneliness and depression) and IgA2/SC ratio (depression). This is the first study to investigate the effects of protracted psychological stress across S-IgA subclasses and its transporter SC. Psychological stress was negatively associated with secretory immunity, specifically IgA1. The lower immunoglobulin/transporter ratio that was associated with higher loneliness and depression suggested a relative immunoglobulin depletion, whereby availability was not keeping up with enhanced transport demand.

Portable lysis apparatus for rapid single-step DNA extraction of Bacillus subtilis.

AIMS: To demonstrate and characterize a portable lysis apparatus for rapid single-step bacterial DNA extraction. METHODS AND RESULTS: Our portable lysis apparatus employed a novel design consisting of an annular piezo-element with perforated diaphragm. Using Bacillus subtilis as target bacteria, our portable lysis apparatus was able to achieve a normalized percent lysis as high as 66% within 30 s. This is comparable to that by microprobe ultrasonication and almost 7 times higher than that by conventional bead beating. The effect from adding glass beads was predictable. However, the results from the addition of sodium dodecyl sulphate (SDS) were counter-intuitive because a further increase from 0·5 to 1% concentration reduced the lysis performance. The portable lysis apparatus is also at least 1·5-5 times more power efficient than microprobe ultrasonication. CONCLUSIONS: Our portable lysis apparatus is capable of rapidly extracting bacterial DNA and is more power efficient than microprobe ultrasonication. The addition of glass beads or SDS concentration (up to 0·5%) improves its performance. SIGNIFICANCE AND IMPACT OF THE STUDY: The portable lysis apparatus provides a standalone, rapid, low cost and power efficient way of obtaining genomic constituents prior to a variety of bioassays used in the field of environmental, biomedical and other applied microbiology.

Patterns of practice with third-line anti-EGFR antibody for metastatic colorectal cancer.

BACKGROUND: Therapy with anti-epidermal growth factor receptor (egfr) monoclonal antibody improves outcomes for patients with metastatic colorectal cancer (mcrc) in the first-, second-, and third-line trial settings. In British Columbia, the use of egfr inhibitors (egfris) is confined to third-line therapy, which might lower the proportion of patients who receive this therapy. The objective of the present study was to describe egfri treatment patterns when those agents are limited to the third-line setting. The results will inform decisions about optimal use of egfri agents, including earlier in the course of therapy for metastatic disease. METHODS: All patients with newly diagnosed mcrc who were referred to BC Cancer Agency clinics in 2009 were included in the study. Prognostic and treatment information was prospectively collected; KRAS test results were determined by chart review. RESULTS: The study included 443 patients with a median age of 66 years. For the 321 patients who received systemic therapy, median survival was 22.3 months. Of the 117 patients who were treated with 5-fluorouracil, oxaliplatin, and irinotecan, and who were potentially eligible for egfri therapy, 90% (105 patients) were tested for KRAS status. Of the 60 patients with KRAS wild-type tumours, 82% (49 patients) received egfri therapy. CONCLUSIONS: When egfri therapy is limited to the third-line setting, only a small proportion of patients receive such therapy, with death and poor performance status preventing its use in the rest. Availability of egfri in earlier lines of therapy could increase the proportion of patients treated with all active systemic agents.

Personalized oncogenomics in the management of gastrointestinal carcinomas-early experiences from a pilot study.

BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. RESULTS: In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. SUMMARY: We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

Effect of curing time on the physicochemical and sensory properties of beef jerky replaced salt with soy sauce, red pepper paste and soybean paste.

This study was done to investigate the quality properties of beef jerky with soy sauce, red pepper paste, and soybean paste replacing salt. Sliced beef samples were cured in salt (control), soy sauce, red pepper paste, and soybean paste for 24 or 48 h and then dried at 70°C for 8 h. Treatments showed higher final moisture content and lower Na(+) concentration than the control after drying for 8 h. The lightness and shear force values were lower in all treatment samples than in the control during 48 h of curing time. In particular, lower lipid oxidation was found in the jerky cured with red pepper paste than in the control. Sensory evaluation showed that color, flavor, and tenderness of jerky samples were improved by replacing salt with soy sauce, red pepper paste and soybean paste, and higher likeability scores of the beef jerky were obtained among those treatments after 48 h of curing time.

Perioperative chemotherapy for gastroesophageal cancer in British Columbia: a multicentre experience.

BACKGROUND: In 2006, perioperative epirubicin, cisplatin, and 5-fluorouracil (ecf), compared with surgery alone, demonstrated a significant survival benefit in resectable gastroesophageal cancers. We report the results of our experience with that protocol. METHODS: The BC Cancer Agency (bcca) is a multicentre institution that treats most oncology patients for the province. Characteristics of the 83 bcca patients with localized gastric, gastroesophageal junction, or lower esophageal cancer who initiated perioperative chemotherapy either ecf or epirubicin, cisplatin, and capecitabine (ecx) from 2008 to 2011 were abstracted to an anonymous database and analyzed. RESULTS: Of the 83 patients in the cohort [66 men; median age: 62 years (range: 37-79 years)], 87.9% completed 3 cycles of perioperative chemotherapy, and 93.9% (n = 78) underwent an attempt at surgery (2 patients died of chemotherapy toxicities, 1 refused surgery, and 2 developed disease progression before surgery). In 11 of the surgeries (14.1%), tumours could not be resected because of unresectability (n = 1), liver metastasis (n = 1), and peritoneal carcinomatosis (n = 9). One patient died of surgical complications. The 6 patients (7.2%) who achieved a pathologic complete response are all alive and recurrence-free. Of 46 patients (55.4%) who subsequently began postoperative chemotherapy, 44.5% completed 3 cycles. Estimated median survival was 40.3 months. Weight loss was the only significant prognostic factor for worse overall survival. CONCLUSIONS: Our multicentre experience confirmed the feasibility of the magic protocol in a real-world scenario and showed that ecx is also an adequate regimen in the perioperative setting. Weight loss was the only significant prognostic factor for worse overall survival. All patients who achieved a pathologic complete response are recurrence-free after a median follow-up of 40.3 months.

Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities.

BACKGROUND: Acne scar causes problems cosmetically and psychologically. Although microscopic examination of acne scars is a necessity for understanding and treatment of them, and it is not easy to find a paper reporting the microscopic characterization of acne scars. OBJECTIVE: The aim of this study was to examine the microscopic findings of acne scars and to select a good therapeutic modality based on the findings. METHODS: Thirty-one atrophic scars obtained from five patients for cosmesis and 18 serial sections were made from each atrophic scar. The sections were stained with H&E, Masson-trichrome or Verhoeff van Gieson stains. Immunohistochemistry was done with antibodies against transforming growth factor-ß, metalloproteinase-1 (MMP-1), MMP-2, MMP-9 and MMP-13. The stained sections were examined under the microscope. RESULTS: The epidermis of the acne scar was characterized by keratin plugging in the hair follicle orifice (32%) and multi-channelled tracts (29%). The dermis of the acne scar had characteristics including a decrease in the dermal thickness and loss of pilosebaceous units. In addition, inflammatory cell infiltrates were seen in the dermis (77%), and insufficient dense collagen fibre deposition was found in the whole dermis (29%). Other findings such as calcium deposition and foreign body reaction were discovered. CONCLUSION: We have found the characteristics of acne scar through the serial sections of several atrophic scars, and suggest that the treatment must reflect several considerations, including the understanding of histopathological findings and the use of combination therapy.

Targeting the FGF/FGFR axis and its co-alteration allies.

BACKGROUND: We analyzed the FGF/FGFR and co-alteration cancer landscape, hypothesizing that combination therapy might be useful in the presence of co-drivers. MATERIALS AND METHODS: We describe FGF/FGFR-altered pathways, prognosis, and co-alterations [cBioPortal (N = 7574)] and therapeutic outcomes [University of California San Diego Molecular Tumor Board (MTB) (N = 16)]. RESULTS: Patients whose cancers harbored FGF/FGFR alterations (N = 1074) versus those without them (N = 6500) had shorter overall survival (OS) (median: 23.1 versus 26.4 months, P = 0.038) (cBioPortal). Only 6.1% (65/1074 patients) had no pathogenic co-alterations accompanying FGF/FGFR axis abnormalities. The most frequently co-altered pathways/genes involved: TP53 (70%); cell cycle (58%); PI3K (55%); and receptor tyrosine kinases and mitogen-activated protein kinase (MAPK) (65%). Harboring alterations in both FGF/FGFR and in the TP53 pathway or in the cell cycle pathway correlated with shorter OS (versus FGF/FGFR-altered without those co-altered signals) (P = 0.0001 and 0.0065). Four of 16 fibroblast growth factor receptor (FGFR) inhibitor-treated patients presented at MTB attained durable partial responses (PRs) (9, 12, 22+, and 52+ months); an additional two, stable disease (SD) of ≥6 months (13+ and 15 months) [clinical benefit rate (SD ≥ 6 months/PR) = 38%]. Importantly, six patients with cyclin pathway co-alterations received the CDK4/6 inhibitor palbociclib (75 mg p.o. 3 weeks on, 1 week off) and the multikinase FGFR inhibitor lenvatinib (10 mg p.o. daily); three (50%) achieved a PR [9 (ovarian), 12 (biliary), and 52+ months (osteosarcoma)]. Palbociclib and lenvatinib were tolerated well. CONCLUSIONS: FGF/FGFR alterations portend a poor prognosis and are frequently accompanied by pathogenic co-aberrations. Malignancies harboring co-alterations that activate both cyclin and FGFR pathways can be co-targeted by CDK4/6 and FGFR inhibitors.

Diagnosis of Pierce's disease using biomarkers specific to Xylella fastidiosa rRNA and Vitis vinifera gene expression.

Pierce's disease (PD), caused by Xylella fastidiosa, represents one of the most damaging diseases of cultivated grape. Management of PD in the vineyard often relies on the removal of infected individuals, which otherwise serve as a source of inoculum for nearby healthy vines. Effective implementation of such control measures requires early diagnosis, which is complicated by the fact that infected vines often harbor high titers of the pathogen in advance of visual symptom development. Here, we report a biomarker system that simultaneously monitors Xylella-induced plant transcripts as well as Xylella ribosomal (r)RNA. Plant biomarker genes were derived from a combination of in silico analysis of grape expressed sequence tags and validation by means of reverse-transcriptase polymerase chain reaction (RT-PCR). Four genes upregulated upon PD infection were individually multiplexed with an X. fastidiosa marker rRNA and scored using either real-time RT-PCR or gel-based conventional RT-PCR techniques. The system was sufficiently sensitive to detect both host gene transcript and pathogen rRNA in asymptomatic infected plants. Moreover, these plant biomarker genes were not induced by water deficit, which is a component of PD development. Such biomarker genes could have utility for disease control by aiding early detection and as a screening tool in breeding programs.

A comparison of consumption and recovery profiles according to anaesthetic circuit mode using a new multifunctional closed-circuit anaesthesia system during desflurane anaesthesia: a clinical study.

This clinical study compared induction time, consumed anaesthetic dose, and haemodynamic and recovery profiles when using a new type of multifunctional anaesthesia machine (Zeus) in semi-closed or closed circuit modes. Sixty female patients undergoing gynaecological surgery were randomly assigned to three groups and received desflurane anaesthesia through a semi-closed circuit (SCC) at fresh gas flow rates of 4 l/min (SCC 4 l/min) or 2 l/min (SCC 2 l/min), or through a closed circuit (CC). Anaesthesia was maintained at the minimum alveolar concentration for blocking the adrenergic response to painful stimulus (MAC(BAR)) (4.6% end-tidal desflurane) during each operation. The time required to reach MAC(BAR) was significantly shorter and the dose of desflurane was significantly smaller in the CC group compared with the other groups. There were no differences in haemodynamic and recovery profiles between the groups. It is concluded that the CC mode allowed a faster and more reliable induction, lower anaesthetic consumption and stable haemodynamic and recovery profiles.

Current locoregional therapies and treatment strategies in hepatocellular carcinoma.

Locoregional therapies (lrts) play an important role in the treatment of hepatocellular carcinoma (hcc), with the aim of increasing overall survival while preserving liver function. Various forms of lrt are available, and choosing the best one depends on technical aspects, liver morphology, tumour biology, and the patient's symptoms. The purpose of the present review article is to provide an overview of the current evidence relating to the use of percutaneous ablation, transarterial chemoembolization, and transarterial radioembolization for the curative or palliative treatment of hcc. Special situations are also reviewed, including the combined use of systemic therapy and lrt, indications and techniques for bridging to transplant and downstaging, and the use of lrt to treat patients with hcc and macrovascular invasion.

Chronic osteomyelitis induced by the placement of dental implants on cemento-osseous dysplasia.

Cemento-osseous dysplasia is a well-known condition in which healthy bone becomes sclerotic. Hypovascularity of the lesion (caused by cementum-like deposits) increases the risk of secondary infection and osteomyelitis, which can also be induced by the placement of implants.

Tau overexpression in transgenic mice induces glycogen synthase kinase 3beta and beta-catenin phosphorylation.

The abnormal phosphorylations of tau, GSK3beta, and beta-catenin have been shown to perform a crucial function in the neuropathology of Alzheimer's disease (AD). The primary objective of the current study was to determine the manner in which overexpressed htau23 interacts and regulates the behavior and phosphorylation characteristics of tau, GSK3beta, and beta-catenin. In order to accomplish this, transgenic mice expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE/htau23) were created. Transgenic mice evidenced the following: (i) tendency toward memory impairments at later stages, (ii) dramatic overexpression of the tau transgene, coupled with increased tau phosphorylation and paired helical filaments (PHFs), (iii) high levels of GSK3beta phosphorylation with advanced age, resulting in increases in the phosphorylations of tau and beta-catenin, (iv) an inhibitory effect of lithium on the phosphorylations of tau, GSK3beta, and beta-catenin, but not in the non-transgenic littermate group. Therefore, the overexpression of NSE/htau23 in the brains of transgenic mice induces abnormal phosphorylations of tau, GSK3beta, and beta-catenin, which are ultimately linked to neuronal degeneration in cases of AD. These transgenic mice are expected to prove useful for the development of new drugs for the treatment of AD.

Target-controlled propofol infusion for sedation in patients undergoing transrectal ultrasound-guided prostate biopsy.

The efficacy and safety of the routine use of target-controlled infusion of propofol for the sedation of patients undergoing transrectal ultrasound-guided prostate biopsy were assessed. The optimal level of sedation was also evaluated. A total of 250 patients were randomized into five groups according to sedation level determined by the Observer's Assessment of Alertness/Sedation (OAA/S) scale. As the level of sedation was increased, the overall pain and discomfort score decreased and the satisfaction rate tended to increase, although hypoxia meant that intervention occurred more frequently at higher sedation levels. Target-controlled infusion of propofol provided safe and effective sedation during transrectal ultrasound-guided prostate biopsy, particularly if moderate sedation (OAA/S score of 3) was achieved. The effect-site concentration of propofol for this level of sedation was about 1.5 microg/ml.

Bronchial angles are associated with nodular bronchiectatic non-tuberculous mycobacteria lung disease.

BACKGROUND: The nodular bronchiectatic (NB) form of non-tuberculous mycobacteria (NTM) lung disease usually involves the right middle lobe (RML) and the left upper lobe lingular segment. However, the reason underlying this preference is not known. METHODS: Fifty patients with NB NTM lung disease who had both positive NTM culture(s) and NB lesions in the RML or lingular segment on computed tomography (CT) of the chest, and 100 healthy subjects matched for sex, age, height and body weight with normal chest CT, were randomly selected. Using reconstructed curved multiplanar reformation (MPR) images, the lengths, diameters and angles of the RML and lingular bronchi were measured. RESULTS: Of the 150 individuals, 64% were female; the mean age was 55 years. The angles of the bronchi were significantly more acute in patients than in healthy subjects, both in the RML (patients, mean 46.75° ± standard deviation 8.87° vs. healthy subjects, mean 51.73° ± 7.76°; P = 0.001) and in the lingular segments (patients, mean 26.94° ± 8.16° vs. healthy subjects, mean 34.65° ± 9.75°; P < 0.001). In addition, the angles of the bronchi in the involved segments were more acute than those in the non-involved segments, both in the RML and the lingular segments. There were no differences in the lengths and bronchi diameters between groups. CONCLUSIONS: An acute angle (obtuse slope) of RML/lingular bronchi could be an anatomical risk factor for NB NTM lung disease.