Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers.

BACKGROUND: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. METHODS: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as high expression (TPS ≥ 50%), low expression (TPS 1%-49%) and no expression (TPS < 1%). RESULTS: 101 (52.9%) of 191 advanced NSCLC patients were never smokers. EGFR mutations were more common in never smokers (64.4%) than in smokers (17.8%) with advanced NSCLC (P < 0.0001). A higher proportion of smokers (26.7%) had high PD-L1 expression compared to never smokers (13.9%) (P = 0.042). There was a trend for a higher proportion of male NSCLC patients [28 of 115 (24.3%)] than female patients [10 of 76 (13.2%)] to have high PD-L1 expression (P = 0.087]. High PD-L1 expression was seen in 32 of 110 (29.1%) patients with EGFR wild-type NSCLC but only in 6 of 81 (7.4%) patients with EGFR-mutant tumors (P < 0.0001). Among the 90 smokers with NSCLC, a higher proportion of heavy smokers (35.8%) than non-heavy smokers (13.5%) had high PD-L1 expression (P = 0.034). In patients with adenocarcinoma, high PD-L1 expression was seen in 25 of 77 (32.5%) patients with EGFR wild-type tumors but only in 4 of 70 (5.7%) patients with EGFR-mutant tumors (P < 0.0001). Among patients with adenocarcinoma, a significantly higher proportion of ever smokers (29.3%) than never smokers (13.5%) had high PD-L1 expression (P = 0.032). Among smokers with adenocarcinoma, a significantly higher proportion of heavy smokers (44.1%) than non-heavy smokers (8.3%) had high PD-L1 expression (P = 0.004). On multivariate analysis, after adjusting for gender and smoking status, heavy smoking and EGFR wild-type tumors remained significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma. CONCLUSIONS: Heavy smoking and EGFR wild-type tumors were significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma.

Ibuprofen dosing measurement accuracy using infants' versus children's ibuprofen: a randomized crossover comparison.

BACKGROUND: Ibuprofen liquid comes in two pediatric concentrations: 200 mg/5 mL for infants and 100 mg/5 mL for children. This study aimed to investigate the misdosing of ibuprofen liquid products by comparing administration accuracy with differing pediatric concentrations and dosages. METHODS: Subject selection included 116 volunteers. Participants were provided with the children's ibuprofen package including the dosing cup, the infants' ibuprofen package including the infant dosing dropper, and a 5 mL syringe. Each subject drew up a specified dose of infants' ibuprofen and children's ibuprofen and deposited each sample into a graduated cylinder. The dose (70 or 100 mg) and order of concentration usage (infants' first or children's first) were randomized. RESULTS: A total of 116 subjects, with a mean age of 32 ± 14 years, participated in the study. Mean absolute dosing errors for all trials, including those who made no errors, were significantly higher for infants' ibuprofen compared to children's ibuprofen: 39 vs. 27 mg (p = 0.036). A total of 31% of all ibuprofen dosage experiments (71 of 232 trials) had greater than 50% error of the assigned dose. CONCLUSION: Dosage errors using infants' ibuprofen were significantly higher than the children's ibuprofen. This suggests that removing the infant form from consumer availability may help reduce dosing errors when administering ibuprofen to pediatric patients. IMPACT: Pediatric misdosing is a significant problem with over-the-counter medications, such as ibuprofen. A previous study found that 51% of patients under the age of 10 were inaccurately dosed with antipyretic medication, including ibuprofen, with an increased incidence in infants. We found significantly more dosing errors with the infant concentration (200 mg/5 mL) as opposed to the children's concentration (100 mg/5 mL), 39 vs. 27 mg, respectively (p = 0.036). We believe that this research is beneficial to pediatric patient caregivers, clinicians, and policymakers to identify the problem of inaccurate ibuprofen dosing and to propose a way to mitigate this by having one concentration easily accessible.

The Utility of N-Terminal Pro-Brain Natriuretic Peptide as an Adjunct Diagnostic Tool for Acute Heart Failure in Acute Dyspneic Patients Coming to the Emergency Department: A Retrospective Review of Our Early Experience.

Acute dyspnea is one of the prevalent reasons for admission to the emergency department. The use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunct for assessing acute dyspnea is not a common practice in many public hospitals in Malaysia. This retrospective review is part of our clinical audit to determine the utility of NT-proBNP as an adjunct to non-standardised clinical evaluation in identifying acute heart failure (HF) in patients with persistent dyspnea (24 h) post-admission. In this cohort of 30 patients with acute dyspnea, NT-proBNP was positive in 20 patients (87%) with acute HF. Three patients (13%) who were treated for septic shock recorded a NT-proBNP false-positive. NT-proBNP demonstrated an overall sensitivity of 90%, a specificity of 70%, a positive predictive value of 85.7% and a negative predictive value of 77.8% in identifying acute HF. These results reinforce that age-stratified NT-proBNP cut-off values are useful for ruling-in or -out acute HF. Thus, NT-proBNP should be considered a crucial point of care, testing to decifer the conundrum of acute dyspneic patients.

Dental technician pneumoconiosis mimicking pulmonary tuberculosis: a case report.

BACKGROUND: Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported. CASE PRESENTATION: We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation. CONCLUSIONS: This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.

Gastric adenocarcinoma location and postoperative complication rates in Asian patients: A 2014-2019 NSQIP analysis.

BACKGROUND: Asian gastric cancer patients have higher long-term survival rates post-gastrectomy. This study compares 30-day post-gastrectomy outcomes between Asians and non-Asians. METHODS: Gastric cancer patients undergoing elective gastrectomies were identified in 2014-2019 NSQIP datasets (n â€‹= â€‹1,438). Demographics, comorbidities, and postoperative outcomes were analyzed. RESULTS: Asians had lower odds of total gastrectomy (AOR â€‹= â€‹0.52, p â€‹= â€‹0.003), age ≥65 (AOR â€‹= â€‹0.60, p â€‹= â€‹0.006), smoking history (AOR â€‹= â€‹0.35, p â€‹< â€‹0.001), dyspnea (AOR â€‹= â€‹0.25, p â€‹= â€‹0.01), and hypoalbuminemia (AOR â€‹= â€‹0.62, p â€‹= â€‹0.025); they also had lower BMI (p â€‹< â€‹0.001). Postoperative outcomes were not significantly different aside from a shorter median length of hospital stay in days (LOS) (Asians: 7 (6, 11); non-Asians: 8 (6, 11); p â€‹< â€‹0.001). CONCLUSIONS: Asian gastric cancer patients have significantly lower odds of having select preoperative comorbidities and have shorter hospital LOS.

Impact Deceleration Differences on Natural Grass Versus Synthetic Turf High School Football Fields.

American football has the highest rate of concussions in United States high school sports. Within American football, impact against the playing surface is the second-most common mechanism of injury. The objective of this study was to determine if there is a difference in impact deceleration between natural grass and synthetic turf high school football fields. A Century Body Opponent Bag (BOB) manikin was equipped with a Riddell football helmet and 3 accelerometers were placed on the forehead, apex of the head, and right ear. The manikin was dropped from a stationary position onto its front, back, and left side onto natural grass (n = 10) and synthetic turf (n = 9) outdoor football fields owned and maintained by public and private institutions on O'ahu, Hawai'i. Data was collected on 1,710 total drops. All accelerometers in forward and backward falls, and 1 accelerometer in side falls showed significantly greater impact deceleration on synthetic turf compared to the natural grass surfaces (P < .05). The results of this study provide evidence-based rationale to inform youth sports policies, particularly those aimed at injury prevention through safer playing environments and equipment.

An explorative analysis on the optimal cryo-passes and freezing time of the ultrathin cryoprobe in endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy.

EBUS-guided transbronchial mediastinal cryobiopsy (TBMC) has emerged as a promising biopsy tool for diagnosing hilar and mediastinal pathologies. However, several fundamental technical aspects of TBMC remain unexplored. This study aims to determine the optimal number of cryo-passes and freezing time of the ultrathin cryoprobe in EBUS-TBMC concerning specimen size and procedural diagnostic yield. We conducted a retrospective chart review of patients with mediastinal and hilar lesions who underwent EBUS-TBMC between January 2021 and April 2023 across three hospitals in Malaysia. A total of 129 EBUS-TBMC procedures were successfully completed, achieving an overall diagnostic yield of 88.4%. Conclusive TBMC procedures were associated with larger specimen sizes (7.0 vs. 5.0 mm, p < 0.01). Specimen size demonstrated a positive correlation with diagnostic yield (p < 0.01), plateauing at specimen size of 4.1-6.0 mm. A significant positive correlation was also observed between the number of cryo-passes and both specimen size (p < 0.01) and diagnostic yield (p < 0.05). Diagnostic yield plateaued after 2-3 cryo-passes. In contrast, longer freezing times trended towards smaller specimens and lower diagnostic yield, though not reaching statistical significance. The highest diagnostic yield was recorded at the 3.1-4.0 s freezing time. The safety profile of TBMC remains favourable, with one case (0.8%) of pneumothorax and nine cases (7%) of self-limiting bleeding. In our cohort, TBMC performance with 2-3 cryo-passes and a 3.1-4.0 s freezing time to achieve a total aggregate specimen size of 4.1-6.0 mm appeared optimal. Further prospective studies are needed to validate these findings.

Pathological complete response in an advance stage IIIB non-small cell lung cancer secondary to neoadjuvant osimertinib targeted therapy: A case report and review of literature.

Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non-small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC. A 67-year-old woman had a left lower lobe lung mass measuring 5.0 × 5.1 × 7.0 cm with an enlarged subcarinal lymph node (LN) on her positron emission tomography scan. Following biopsy, a diagnosis of stage IIIB N2 (cT3N2M0) EGFR exon 19 deletion mutation-positive lung adenocarcinoma was established. NTT using osimertinib 80 mg once daily was commenced. Subsequent re-imaging at 3 months (ycT2bN2M0), 6 months (ycT1cN2M0) and 9 months showed tumour downstaging and resolution of the subcarinal LN (ycT1cN0M0). She underwent left lower lobectomy with systematic nodal dissection. All surgical specimens demonstrated no evidence of malignant cells (ypT0N0). Osimertinib could be the preferred NTT for potentially resectable NSCLC.

Bonuses and pitfalls of a paperless drive-through screening and COVID-19: A field report.

As the world witnessed the rapid spread of SARS-CoV-2, the World Health Organization has called for governing bodies worldwide to intensify case findings, contact tracing, monitoring, and quarantine or isolation of contacts with COVID-19. Drive-through (DT) screening is a form of case detection which has recently gain preference globally. Proper implementation of this system can help remediate the outbreak.

Naegleria fowleri: Protein structures to facilitate drug discovery for the deadly, pathogenic free-living amoeba.

Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain's frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen's high mortality is the lack of sensitivity of N. fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N. fowleri. The genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N. fowleri research. In 2017, 178 N. fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.

Telehealth: "virtual" lifeline for home-ventilated patients during the COVID-19 pandemic.

Telehealth appears useful to fill in the void for home-ventilated patients to maintain the much-needed connectivity with their healthcare team during the #COVID19 pandemic https://bit.ly/3ftvjxW.

Indwelling pleural catheter and successful autopleurodesis of refractory inflammatory lupus effusion.

Indwelling pleural catheter (IPC) is a useful tool for refractory malignant pleural effusions (MPEs). It allows palliation by intermittent symptomatic relief of the effusion and improves quality of life. Its use in benign pleural effusions comes mainly from retrospective studies, case series, and case reports. Lupus effusion is common, causes minimal symptoms, and usually responds to either steroid therapy or immunosuppressants. Refractory lupus effusion is less common and treatment may require invasive surgical pleurectomy. We describe a 52-year-old woman whose first presentation of systemic lupus erythematosus (SLE) was a pleural effusion refractory to steroids and immunosuppressants. She successfully achieved spontaneous pleurodesis with intermittent IPC drainage at three months.

Resolution of refractory chylothorax with a combination of talc pleurodesis and CPAP.

Chylothorax is an uncommon cause of pleural effusion. Recurrent chylous effusions are often resistant to conservative treatment and many need surgical intervention. We report a 69-year-old woman with refractory idiopathic chylothorax resistant to medium-chain triglyceride diet and intermittent thoracentesis. Lymphangiography and lymphoscintigraphy failed to identify the site of leakage. We initiated continuous positive airway pressure (CPAP) 12 h before and 48 hours after talc pleurodesis. Chest drain was removed at day 3 and she was discharged at day 5. To our knowledge, this is the first case of successful resolution of idiopathic refractory chylothorax with CPAP ventilation used in tandem with talc pleurodesis.

What happens when we treat the "Typhoid Mary" of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was declared a pandemic on 11 March 2020. We have since seen its fast spread worldwide. A likely contributing factor was the lack of symptoms of some of the carriers, making them unaware of their risk of spreading to other more vulnerable individuals. The other important finding has been the reported cases of infectivity despite lack of symptoms. We describe the SARS-CoV-2 pneumonia patterns in asymptomatic individuals. The common computed tomography (CT) thorax patterns found are peripheral ground-glass opacification (GGO) with upper or lower lobe predominance. We believe screening for 2019-novel coronavirus (COVID-19) in high-risk individuals may help identify the patients needing longer follow-up.

Toward a structome of Acinetobacter baumannii drug targets.

Acinetobacter baumannii is well known for causing hospital-associated infections due in part to its intrinsic antibiotic resistance as well as its ability to remain viable on surfaces and resist cleaning agents. In a previous publication, A. baumannii strain AB5075 was studied by transposon mutagenesis and 438 essential gene candidates for growth on rich-medium were identified. The Seattle Structural Genomics Center for Infectious Disease entered 342 of these candidate essential genes into our pipeline for structure determination, in which 306 were successfully cloned into expression vectors, 192 were detectably expressed, 165 screened as soluble, 121 were purified, 52 crystalized, 30 provided diffraction data, and 29 structures were deposited in the Protein Data Bank. Here, we report these structures, compare them with human orthologs where applicable, and discuss their potential as drug targets for antibiotic development against A. baumannii.

Silicone pneumonitis after gluteal filler: a case report and literature review.

Liquid silicone (polydimethylsiloxane) is an inert material that is commonly used for cosmetic purpose. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis as a consequence of the injection of nonmedical-grade liquid silicone. We describe a case of severe silicone pneumonitis complicated with acute respiratory distress syndrome and bilateral pneumothorax secondary to silicone gluteal augmentation. In this case report, we aim to discuss our experience and approach in managing an uncommon case of SES.

Endobronchial and endoscopic ultrasound: it only takes an echobronchoscope to tango.

Endobronchial ultrasound (EBUS) is indispensable when it comes to evaluation of mediastinal lesion and staging of lung cancer. The incorporation of endoscopic ultrasound using an echobronchoscope (EUS-B) further extends this capability to the paraoesophageal and subdiaphragmatic structures. When combined, EBUS with EUS-B increases the diagnostic yield. Both procedures can be done in a single session and by a single operator; this translates into an overall reduction in the healthcare cost.

Cluster Analysis Evaluating PM2.5, Occupation Risk and Mode of Transportation as Surrogates for Air-pollution and the Impact on Lung Cancer Diagnosis and 1-Year Mortality.

Objective: Epidemiological studies have reported the close relationship between risk for lung cancers and air pollution in particular, for non-smoking related lung cancers. However, most studies used residential address as proxies which may not estimate accurately an individual's air pollution exposure. Therefore, the aim of this study was to identify risk factors such as occupation and mode of transportation associated with lung cancer diagnosis and death. Methods: Subjects with lung cancer (n=514) were evaluated both by chart reviews for clinical data and interviews to determine residential address for ten years, main occupation and main mode of transportation. Annual particulate matter with diameter size less than 2.5 micrometre (PM2.5) concentration were calculated based on particulate matter with diameter size less than 10 micrometre (PM10) data recorded by Malaysian Department of Environment. Logistic regression analysis, cluster analysis and the Cox regression analysis were performed to the studied variables. Results: This study concurred with previous studies that lung adenocarcinoma were diagnosed in predominantly younger, female non-smokers compared to the other types of lung cancers. Lung adenocarcinoma subjects had annual PM2.5 that was almost twice higher than squamous cell carcinoma, small cell carcinoma and other histological subtypes (p=0.024). Independent of smoking, the κ -means cluster analysis revealed two clusters in which the high risk cluster involves occupation risk with air pollution of more than four hours per day, main transportation involving motorcycle and trucks and mean annual PM2.5 concentration of more than 30 based on residential address for more than ten years. The increased risk for the high-risk cluster was more than five times for the diagnosis of lung adenocarcinoma (OR=5.69, 95% CI=3.14-7.21, p<0.001). The hazard ratio for the high-risk cluster was 3.89 (95% CI=2.12-4.56, p=0.02) for lung adenocarcinoma mortality at 1 year. Conclusion: High-risk cluster including PM2.5, occupation risk and mode of transportation as surrogates for air-pollution exposure was identified and highly associated with lung adenocarcinoma diagnosis and 1-year mortality.