Lung Cancer Clinical Trials in Latin America in the Era of Cooperative Groups: A 20-Year Analysis.

PURPOSE: The aim of this study is to characterize lung cancer treatment clinical trials in Latin America before (January 2001-December 2011) and after (January 2012-December 2021) the organization of major Latin American oncology cooperative groups. MATERIALS AND METHODS: Interventional clinical trials were identified in ClinicalTrials.gov using the search terms "lung cancer," country filters for 20 Latin American countries, and study start dates January 1, 2001-December 31, 2011, and January 1, 2012-December 31, 2021. Clinical trials were categorized as either originating in Latin America (LA) or outside Latin America (non-LA) with participation of Latin American countries. Descriptive statistics, two-sided Z-scores, and chi-square analyses with 95% CIs were calculated. RESULTS: Overall, 273 clinical trials involving Latin American countries between 2001 and 2021 were identified. Comparing 2001-2011 with 2012-2021, there was an increase in total clinical trials (100 v 173; P < .001). Only 9% (26 of 273) of all trials were LA trials. There was a marked decrease in the proportion of LA trials (14% v 7%, P = .058) and estimated enrollment to LA trials (3,245 v 1,190 patients; P < .001). Recruiting of patients with EGFR (29% v 7%; P < .01) and KRAS (18% v 2%; P < .01) driver mutations also decreased. Trial participation was highest in Brazil, Mexico, Argentina, Chile, and Peru and increased over time: Brazil (61 v 108; 77% increase), Mexico (40 v 88; 120% increase), Argentina (50 v 78; 56% increase), Chile (25 v 57; 128% increase), and Peru (14 v 37; 164% increase). CONCLUSION: There was a significant increase in clinical trial participation by Latin American countries, from 2001-2011 to 2012-2021. However, there were few clinical trials which originated in Latin America or focused on patients with driver mutations.

From Soy Waste to Bioplastics: Industrial Proof of Concept.

The global plastic waste problem is pushing for the development of sustainable alternatives, encouraged by stringent regulations combined with increased environmental consciousness. In response, this study presents an industrial-scale proof of concept to produce self-standing, transparent, and flexible bioplastic films, offering a possible solution to plastic pollution and resource valorization. We achieve this by combining amyloid fibrils self-assembled from food waste with methylcellulose and glycerol. Specifically, soy whey and okara, two pivotal protein-rich byproducts of tofu manufacturing, emerge as sustainable and versatile precursors for amyloid fibril formation and bioplastic development. An exhaustive industrial-scale feasibility study involving the transformation of 500 L of soy whey into ∼1 km (27 kg) of bioplastic films underscores the potential of this technology. To extend the practicality of our approach, we further processed a running kilometer of film at the industrial scale into transparent windows for paper-based packaging. The mechanical properties and the water interactions of the novel film are tested and compared with those of commercially used plastic films. By pioneering the large-scale production of biodegradable bioplastics sourced from food byproducts, this work not only simultaneously addresses the dual challenges of plastic pollution and food waste but also practically demonstrates the feasibility of biopolymeric building block valorization for the development of sustainable materials in real-world scenarios.

Endoscopic Olecranon Bursectomy in the Treatment of Recalcitrant Olecranon Bursitis: Patient Selection and Operative Technique.

Olecranon bursitis is the most common form of bursitis. While it can commonly be treated using noninvasive measures, a surgical approach is indicated for cases of recalcitrant olecranon bursitis, which fail such treatment options. Traditionally, recalcitrant olecranon bursitis has been treated with an open bursectomy. Recently, arthroscopy has been proposed as an alternative method. Contraindications for this approach are cases where the bursa is massively enlarged and contains copious amounts of gouty tophi. While a unanimous consensus regarding which surgical approach is optimal has yet to be made, the endoscopic approach could potentially reduce issues inherent to open bursectomies such as improper wound healing and recurrence. This would reduce patient discomfort and allow them to return to activity sooner. We present a technique for treating recalcitrant olecranon bursitis using endoscopic resection.

Combined flat-field and frequency filter approach to correcting artifacts of multichannel two-photon microscopy.

Significance: Multiphoton microscopy (MPM) is a useful biomedical imaging tool for its ability to probe labeled and unlabeled depth-resolved tissue biomarkers at high resolution. Automated MPM tile scanning allows for whole-slide image acquisition but can suffer from tile-stitching artifacts that prevent accurate quantitative data analysis. Aim: We have investigated postprocessing artifact correction methods using ImageJ macros and custom Python code. Quantitative and qualitative comparisons of these methods were made using whole-slide MPM autofluorescence and second-harmonic generation images of human duodenal tissue. Approach: Image quality after artifact removal is assessed by evaluating the processed image and its unprocessed counterpart using the root mean square error, structural similarity index, and image histogram measurements. Results: Consideration of both quantitative and qualitative results suggest that a combination of a custom flat-field-based correction and frequency filtering processing step provide improved artifact correction when compared with each method used independently to correct for tiling artifacts of tile-scan MPM images. Conclusions: While some image artifacts remain with these methods, further optimization of these processing steps may result in computational-efficient methods for removing these artifacts that are ubiquitous in large-scale MPM imaging. Removal of these artifacts with retention of the original image information would facilitate the use of this imaging modality in both research and clinical settings, where it is highly useful in collecting detailed morphologic and optical properties of tissue.

Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 µg/kg (range, 30-232.7 µg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Meta-analysis reveals differential gene expression in tetralogy of Fallot versus controls.

OBJECTIVES: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect in the United States. We aimed to identify genetic variations associated with TOF using meta-analysis of publicly available digital samples to spotlight targets for prevention, screening, and treatment strategies. METHODS: We used the Search Tag Analyze Resource for Gene Expression Omnibus (STARGEO) platform to identify 39 TOF and 19 non-TOF right ventricle tissue samples from microarray data and identified upregulated and downregulated genes. Associated gene expression data were analyzed using ingenuity pathway analysis and restricted to genes with a statistically significant (p < .05) difference and an absolute experimental log ratio >0.1 between disease and control samples. RESULTS: Our analysis identified 220 genes whose expression profiles were significantly altered in TOF vs. non-TOF samples. The most striking differences identified in gene expression included genes FBXO32, PTGES, MYL12a, and NR2F2. Some top associated canonical pathways included adrenergic signaling, estrogen receptor signaling, and the role of NFAT in cardiac hypertrophy. In general, genes involved in adaptive, defensive, and reparative cardiovascular responses showed altered expression in TOF vs. non-TOF samples. CONCLUSIONS: We introduced the interpretation of open "big data" using the STARGEO platform to define robust genomic signatures of congenital heart disease pathology of TOF. Overall, our meta-analysis results indicated increased metabolism, inflammation, and altered gene expression in TOF patients. Estrogen receptor signaling and the role of NFAT in cardiac hypertrophy represent unique pathways upregulated in TOF patients and are potential targets for future pharmacologic treatments.

The growing impact of air quality on lung-related illness: a narrative review.

Background and Objective: Poor air quality can be harmful to human well-being. There are a variety of respiratory disorders associated with toxins present within the atmosphere, such as bronchitis and asthma, which eventually lead to heart or lung complications over time. Fine particles like particulate matter 2.5 (PM2.5) accumulate in the small airways of the lung. These irritants can cause epigenetic modifications in gene regulation, leading to changes responsible for both benign and malignant lung diseases. In this review we will discuss known associations between environmental factors and pulmonary complications, consider preventative measures and offer further areas for future investigation. This review presents a summary of the literature outlining the current work done on air quality and its effects on lung-related illnesses. We discuss regional differences in air quality and consider the causes, such as manufacturing, traffic density, increase in fuel usage and natural events. We further explore disparities based on geography, race, and other social determinants. Methods: A comprehensive literature review was performed using keywords related to air quality, pollution and lung disease within the PubMed database as well as MEDLINE and Google Scholar. Key Content and Findings: The Clean Air Act of 1970 marked an essential transition for air quality improvement. The legislation led to decreased emissions and control measures to address atmosphere contamination. Despite these actions, poor atmospheric conditions still persist today and have become an ongoing issue. These poor conditions affect individuals living in metropolitan areas more significantly than suburban or rural areas. Pollution from industrial operations and transportation vehicles have led to increased emission outputs recently. Climate change further aggravates air quality problems by raising pollutant and allergen concentrations. The detrimental consequences of poor air quality include increased incidence of disease processes like asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. To keep up with the well-being of people globally, it is important that actions be taken to battle contamination in the climate so its impact on public health can be limited. Conclusions: Poor air quality and recent worsening of industrial emissions have had a negative impact on lung-related illnesses. Future mitigation strategies should be taken to reduce pollution and treat diseases earlier in their course. Some of these strategies include more reliance on alternative energy sources, creation of mass transit systems and increased rates of recycling.

Design, fabrication, and preclinical testing of a miniaturized, multispectral, chip-on-tip, imaging probe for intraluminal fluorescence imaging of the gastrointestinal tract.

Gastrointestinal cancers continue to account for a disproportionately large percentage of annual cancer deaths in the US. Advancements in miniature imaging technology combined with a need for precise and thorough tumor detection in gastrointestinal cancer screenings fuel the demand for new, small-scale, and low-cost methods of localization and margin identification with improved accuracy. Here, we report the development of a miniaturized, chip-on-tip, multispectral, fluorescence imaging probe designed to port through a gastroscope working channel with the aim of detecting cancerous lesions in point-of-care endoscopy of the gastrointestinal lumen. Preclinical testing has confirmed fluorescence sensitivity and supports that this miniature probe can locate structures of interest via detection of fluorescence emission from exogenous contrast agents. This work demonstrates the design and preliminary performance evaluation of a miniaturized, single-use, chip-on-tip fluorescence imaging system, capable of detecting multiple fluorochromes, and devised for deployment via the accessory channel of a standard gastroscope.

A Case of Acute Purulent Streptococcus pneumoniae Pericarditis Causing Tamponade and Cardiac Arrest in a COVID-19-Infected Patient.

Purulent pericarditis due to Streptococcus pneumoniae (S. pneumoniae) has been increasingly rare since the advent of antibiotics; however, it still carries a high mortality rate, especially in the setting of tamponade. Bedside transthoracic echocardiogram (TTE) is a useful, cheap, and underutilized tool that can aid in the diagnosis, treatment, and further management of patients presenting to the emergency department with chest pain, as well as during cardiac resuscitation. In this report, we present a case of an acute purulent S. pneumoniae pericarditis of an unknown primary source in a patient coinfected with coronavirus disease 2019 (COVID-19) pneumonia, resulting in cardiac tamponade and cardiac arrest that resolved with the aid of bedside echocardiography-guided pericardiocentesis. We attempt to highlight the importance of clinicians using echocardiography to aid in their clinical decision-making, demonstrating it as a fast and effective tool capable of providing instantaneous feedback.

Reported Beliefs About COVID-19 Vaccines Among Unvaccinated Hispanic Adults Utilizing a Free Clinic in Orlando, Florida.

BACKGROUND: Subgroups of the general population including Hispanic/Latinx individuals report higher rates of COVID-19 vaccine hesitancy than non-Hispanic White individuals. The purpose of this study was to identify factors that influence attitudes toward COVID-19 vaccines among unvaccinated Hispanic adults utilizing a free community clinic in Orlando, Florida, USA. METHODS: From May 2021 to July 2021, we used convenience sampling to recruit 20 self-identified Hispanic adults who were unvaccinated to complete an individual, semi-structured interview. Interview questions were derived from constructs from the Health Belief Model. Interviews were audio-recorded, transcribed, translated (when necessary), and qualitatively analyzed using inductive content analysis to identify recurring themes. RESULTS: Of the 20 participants in this study, 65% were female (n=13) and they ranged from 21 to 73 years of age (median age =42.5). We identified three primary themes in participant responses regarding their beliefs about COVID-19 vaccines. Primary theme 1: trust and clarity of COVID-19 vaccine information, with subthemes (1a) source trustworthiness, and (1b) clarity of COVID-19 vaccine information. Primary theme 2: personal contextual factors, with subthemes (2a) underlying health conditions, (2b) personal experiences with COVID-19, and (2c) immigration. Primary theme 3: lack of confidence, yet willingness to be vaccinated, with subthemes (3a) fear and distrust and (3b) willingness to be vaccinated. In summary, participants felt hesitant, although not completely opposed, to receiving COVID-19 vaccinations due to the information they gathered on vaccines from various sources received in the context of important personal factors (e.g., immigration, underlying health concerns, etc.). CONCLUSIONS: Overcoming vaccine hesitancy in vulnerable populations such as the Hispanic communities may require addressing issues of message clarity through trusted sources while considering personal contextual factors. Healthcare professionals can begin by initiating discussions with patients to understand individual circumstances and concerns and provide information on COVID-19 vaccines that clarify areas of confusion.

Tetralogy of Fallot Associated With Right Aortic Arch and Isolated Left Brachiocephalic Artery.

A newborn presented with tetralogy of Fallot (TOF), right aortic arch (RAA), and isolated left brachiocephalic artery. The RAA supplied the right common carotid artery, right vertebral artery, and right subclavian artery, in that order. The left common carotid and left subclavian arteries were in continuity with no aortic origin. Ultrasound demonstrated retrograde flow in the left vertebral artery supplying antegrade flow to the diminutive left subclavian artery (ie, "steal phenomenon"). The patient underwent repair of TOF without intervention on the left common carotid or left subclavian arteries and is being followed conservatively.

Combined multiphoton microscopy and somatostatin receptor type 2 imaging of pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs) are a rare but increasingly more prevalent cancer with heterogeneous clinical and pathological presentation. Surgery is the preferred treatment for all hormone-expressing PNETs and any PNET greater than 2 cm, but difficulties arise when tumors are multifocal, metastatic, or small in size due to lack of effective surgical localization. Existing techniques such as intraoperative ultrasound provide poor contrast and resolution, resulting in low sensitivity for such tumors. Somatostatin receptor type 2 (SSTR2) is commonly overexpressed in PNETs and presents an avenue for targeted tumor localization. SSTR2 is often used for pre-operative imaging and therapeutic treatment, with recent studies demonstrating that somatostatin receptor imaging (SRI) can be applied in radioguided surgery to aid in removal of metastatic lymph nodes and achieving negative surgical margins. However not all PNETs express SSTR2, indicating labeled SRI could benefit from using a supplemental label-free technique such as multiphoton microscopy (MPM), which has proven useful in improving the accuracy of diagnosing more common exocrine pancreatic cancers. Our work tests the suitability of combined SRI and MPM for localizing PNETs by imaging and comparing samples of PNETs and normal pancreatic tissue. Specimens were labeled with a novel SSTR2-targeted contrast agent and imaged using fluorescence microscopy, and subsequently imaged using MPM to collect four autofluorescent channels and second harmonic generation. Our results show that a combination of both SRI and MPM provides enhanced contrast and sensitivity for localizing diseased tissue, suggesting that this approach could be a valuable clinical tool for surgical localization and treatment of PNETs.

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy.

BACKGROUND: Duodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTs is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins. Multiphoton microscopy can capture high-resolution images of biological tissue with contrast generated from endogenous fluorescence (autofluorescence [AF]) through two-photon excited fluorescence (2PEF). Second harmonic generation is another popular method of generating image contrast with multiphoton microscopy (MPM) and is a light-scattering phenomenon that occurs predominantly from structures such as collagen in biological samples. Some molecules that contribute to AF change in abundance from processes related to the cancer disease process (e.g., metabolic changes, oxidative stress, and angiogenesis). STUDY DESIGN/MATERIALS AND METHODS: MPM was used to image 12 separate patient samples of formalin-fixed and paraffin-embedded duodenal gastrinoma slides with a second-harmonic generation (SHG) channel and four 2PEF channels. The excitation and emission profiles of each 2PEF channel were tuned to capture signal dominated by distinct fluorophores with well-characterized fluorescent spectra and known connections to the physiologic changes that arise in cancerous tissue. RESULTS: We found that there was a significant difference in the relative abundance of signal generated in the 2PEF channels for regions of DGASTs in comparison to the neighboring tissues of the duodenum. Data generated from texture feature extraction of the MPM images were used in linear discriminant analysis models to create classifiers for tumor versus all other tissue types before and after principal component analysis (PCA). PCA improved the classifier accuracy and reduced the number of features required to achieve maximum accuracy. The linear discriminant classifier after PCA distinguished between tumor and other tissue types with an accuracy of 90.6%-93.8%. CONCLUSIONS: These results suggest that multiphoton microscopy 2PEF and SHG imaging is a promising label-free method for discriminating between DGASTs and normal duodenal tissue which has implications for future applications of in vivo assessment of resection margins with endoscopic MPM.

Idiopathic Pericardial Effusions in Children: Workup and Final Diagnoses.

Pediatric idiopathic pericardial effusions are common and often have a prolonged clinical course. We hypothesized that these effusions have no standardized diagnostic workup, and ultimately have a final etiology not initially appreciated. To test these hypotheses, a hospital system-wide retrospective (1/1/1990-10/1/2019) cohort study of pericardial effusions in children (< 18 years) was conducted. Effusions were grouped by etiology and patients receiving an initial idiopathic diagnosis were further analyzed. Effusion size, diagnostic workup, final diagnosis, and time to resolution were abstracted. In total, 42/366 effusions were initially diagnosed as idiopathic. Workup was not standardized and included up to six laboratory tests including pericardial fluid analysis and infectious, metabolic, rheumatologic and thyroid workups. Treatment course involved 1 readmission in 24%, and > 1 readmission in 12%. Resolution of effusion occurred in 83% of patients within a median of 1 admission (range 1-4). Of those effusions initially deemed idiopathic, 12/42 (29%) were later found to have an underlying etiologic diagnosis including: autoimmune (7, 58%), neoplastic (2, 16%), infectious (2, 16%), and renal (1, 8%). Children initially diagnosed with idiopathic pericardial effusions have an underlying etiologic diagnosis 29% of the time, and a standardized workup may prevent delays in definitive diagnosis and treatment.

Congenital Left Main Coronary Atresia: Rare Cause of Sudden Cardiac Arrest.

A 13-month-old male sustained cardiac arrest under general anesthesia and was found to have left main coronary artery atresia with collateralization from the right coronary artery. After protracted recovery, the patient underwent coronary ostioplasty. Postoperative imaging confirmed patency of the newly established artery without stenosis. At 12 months, no changes in the vessel were noted. Ventricular function remains mildly decreased and stable.

Editorial Commentary: Dermal Allografts Are Indicated for Repair of Irreparable Rotator Cuff Tears and for Revision Surgery, and May Be Cost-Effective for Primary Repair.

Improving rotator cuff repair results is the goal of all shoulder surgeons. The addition of a biologic graft may speed healing, allow accelerated rehabilitation, and increase healing rates. Recent research suggests that augmentation of rotator cuff repair using dermal allograft may be cost-effective. Indications for dermal allografts are revision rotator cuff repairs and primary cuff repairs in which a tensionless repair cannot be accomplished. Allografts act as a load-sharing device to allow tendons to heal without tension. They also serve to fill the gap in irreparable cuff tears. It is important to understand that augmentation will not compensate for advanced muscle fatty atrophy or neurapraxia. Precautions to prevent Cutibacterium acne nosocomial infection are essential. The healing time or dermal grafts is considerably longer than the repaired native cuff tendon, requiring supervised rehabilitation. Dermal allografts are a crucial tool for repair of irreparable rotator cuff tears and for revision surgery. From an economic standpoint, they now also may be considered for use in primary rotator cuff repair surgery.

Editorial Commentary: Don't Let Cuff Tears With Adhesive Capsulitis Give You the Cold Shoulder.

Despite vastly different rehabilitation goals, adhesive capsulitis and a rotator cuff tear of the shoulder can be treated concomitantly with good outcomes. In the face of adhesive capsulitis, rotator cuff tears can be safely repaired with manipulation under anesthesia and/or capsular release without a substantial increase in complication rates compared with patients undergoing rotator cuff repair alone. Adhesive capsulitis pathology causes the cuff to heal rapidly, and we recommend aggressive passive range of motion as part of a traditional but accelerated rehabilitation that can be monitored and thus adjusted on a case-by-case basis.