Penetrant-induced plasticization in microporous polymer membranes.

Penetrant-induced plasticization has prevented the industrial deployment of many polymers for membrane-based gas separations. With the advent of microporous polymers, new structural design features and unprecedented property sets are now accessible under controlled laboratory conditions, but property sets can often deteriorate due to plasticization. Therefore, a critical understanding of the origins of plasticization in microporous polymers and the development of strategies to mitigate this effect are needed to advance this area of research. Herein, an integrative discussion is provided on seminal plasticization theory and gas transport models, and these theories and models are compared to an exhaustive database of plasticization characteristics of microporous polymers. Correlations between specific polymer properties and plasticization behavior are presented, including analyses of plasticization pressures from pure-gas permeation tests and mixed-gas permeation tests for pure polymers and composite films. Finally, an evaluation of common and current state-of-the-art strategies to mitigate plasticization is provided along with suggestions for future directions of fundamental and applied research on the topic.

Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.

OBJECTIVES: Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions. DESIGN: Ambidirectional multisite cohort study. SETTING: Four tertiary children's hospitals. PATIENTS: Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication ( p < 0.0001) and contributed to a decision to consult palliative care ( p < 0.02). CONCLUSIONS: In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.

MOF-Based Membranes for Gas Separations.

Metal-organic frameworks (MOFs) represent the largest known class of porous crystalline materials ever synthesized. Their narrow pore windows and nearly unlimited structural and chemical features have made these materials of significant interest for membrane-based gas separations. In this comprehensive review, we discuss opportunities and challenges related to the formation of pure MOF films and mixed-matrix membranes (MMMs). Common and emerging separation applications are identified, and membrane transport theory for MOFs is described and contextualized relative to the governing principles that describe transport in polymers. Additionally, cross-cutting research opportunities using advanced metrologies and computational techniques are reviewed. To quantify membrane performance, we introduce a simple membrane performance score that has been tabulated for all of the literature data compiled in this review. These data are reported on upper bound plots, revealing classes of MOF materials that consistently demonstrate promising separation performance. Recommendations are provided with the intent of identifying the most promising materials and directions for the field in terms of fundamental science and eventual deployment of MOF materials for commercial membrane-based gas separations.

Impact of pre-existing drug resistance on risk of virological failure in South Africa.

OBJECTIVES: There is conflicting evidence on the impact of pre-existing HIV drug resistance mutations (DRMs) in patients infected with non-B subtype virus. METHODS: We performed a case-cohort substudy of the AIDS Drug Resistance Surveillance Study, which enrolled South African patients initiating first-line efavirenz/emtricitabine/tenofovir. Pre-ART DRMs were detected by Illumina sequencing of HIV pol and DRMs present at <20% of the viral population were labelled as minority variants (MVs). Weighted Cox proportional hazards models estimated the association between pre-ART DRMs and risk of virological failure (VF), defined as confirmed HIV-1 RNA ≥1000 copies/mL after ≥5 months of ART. RESULTS: The evaluable population included 178 participants from a randomly selected subcohort (16 with VF, 162 without VF) and 83 additional participants with VF. In the subcohort, 16% of participants harboured ≥1 majority DRM. The presence of any majority DRM was associated with a 3-fold greater risk of VF (P = 0.002), which increased to 9.2-fold (P < 0.001) in those with <2 active drugs. Thirteen percent of participants harboured MV DRMs in the absence of majority DRMs. Presence of MVs alone had no significant impact on the risk of VF. Inclusion of pre-ART MVs with majority DRMs improved the sensitivity but reduced the specificity of predicting VF. CONCLUSIONS: In a South African cohort, the presence of majority DRMs increased the risk of VF, especially for participants receiving <2 active drugs. The detection of drug-resistant MVs alone did not predict an increased risk of VF, but their inclusion with majority DRMs affected the sensitivity/specificity of predicting VF.

Leveraging Free Volume Manipulation to Improve the Membrane Separation Performance of Amine-Functionalized PIM-1.

Gas-separation polymer membranes display a characteristic permeability-selectivity trade-off that has limited their industrial use. The most comprehensive approach to improving performance is to devise strategies that simultaneously increase fractional free volume, narrow free volume distribution, and enhance sorption selectivity, but generalizable methods for such approaches are exceedingly rare. Here, we present an in situ crosslinking and solid-state deprotection method to access previously inaccessible sorption and diffusion characteristics in amine-functionalized polymers of intrinsic microporosity. Free volume element (FVE) size can be increased while preserving a narrow FVE distribution, enabling below-upper bound polymers to surpass the H2 /N2 , H2 /CH4 , and O2 /N2 upper bounds and improving CO2 -based selectivities by 200 %. This approach can transform polymers into chemical analogues with improved performance, thereby overcoming traditional permeability-selectivity trade-offs.

Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function.

OBJECTIVES: Here we examine the association between shift work sleep disorder (SWSD) and erectile dysfunction (ED) in shift workers. METHODS: Men presenting to a single andrology clinic between January 2014 and July 2017 completed validated questionnaires: International Index of Erectile Function (IIEF), Patient Health Questionnaire-9 (PHQ-9), and the nonvalidated SWSD Questionnaire. Men were also asked about shift work schedule, comorbidities, phosphodiesterase 5 (PDE5) inhibitor use, and testosterone use. Serum total testosterone values were determined for each visit. Linear regression was performed controlling for testosterone use, testosterone levels, PDE5 inhibitor use, age, and comorbidities to determine the effect of SWSD on ED as assessed using the IIEF. RESULTS: Of the 754 men completing questionnaires, 204 reported nonstandard shift work (begins before 7 am or after 6 pm, regularly extends out of that frame, or rotates frequently) and 48 were found to have SWSD using a screening questionnaire. Nonstandard shift work alone did not result in worse IIEF-EF scores (P = .31), but those who worked nonstandard shifts and had SWSD demonstrated IIEF-EF scores 2.8 points lower than men without SWSD (P < .01). When assessing for the type of shift work performed, men who worked night shifts had IIEF-EF scores 7.6 points lower than men who worked during the day or evening (P < .01). Testosterone use improved IIEF-EF scores for men with SWSD by 2.9 points, ameliorating the effect of SWSD on ED. However, baseline testosterone levels were not associated with worse erectile function in this cohort. CONCLUSION: Men with SWSD have worse erectile function, with men who work night shifts having even poorer erectile function. These findings suggest that circadian rhythm disturbance may significantly impact erectile function. While testosterone therapy may partly reverse the effects of SWSD, shift work is a potential risk factor for ED and should be assessed for as part of the evaluation of men with ED. Rodriguez KM, Kohn TP, Kohn JR, et al. Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function. J Sex Med 2020;17:1687-1693.

Increased Risk of Incident Disease in Men with Peyronie's Disease: Analysis of U.S. Claims Data.

BACKGROUND: The subsequent health risks associated with Peyronie's disease (PD) are unknown. AIM: This cohort study assesses the risk of developing auto-immune conditions and common chronic health conditions after a diagnosis of PD. We hypothesize that an increase in auto-immune disease will be evident in men with PD, as has been suggested in smaller studies. METHODS: We determined the longitudinal incidence of 13 auto-immune diseases and 25 common chronic conditions in a cohort from the Truven Health Analytics (Ann Arbor, Michigan, USA) database from 2007-2013. The cohort included men with 1 of 3 exposures in 2007: (1) men with PD, (2) men with erectile dysfunction (ED) but not PD, and (3) men without PD or ED, matched on age and follow-up duration. OUTCOMES: To assess incidence, we utilized a Cox regression model adjusting for age, smoking, obesity, health care visits per year, urology visits per year, and years of follow-up. RESULTS: We included 8,728 men with PD; 204,147 men with ED; and 87,280 controls. Men with PD had an increased risk of developing benign prostatic hyperplasia (hazard ratio [HR] 1.21, 95% CI 1.16-1.27), prostatitis (HR 1.21, 95% CI 1.12-1.31), and lower urinary tract symptoms (HR 1.10, 95% CI 1.05-1.16) when compared to both men with ED and age-matched controls without ED or PD even when controlling for the number of urology visits per year. Compared to controls, men with PD also had an increased risk of developing keloids. No significant risk for any auto-immune disease was observed. CLINICAL IMPLICATIONS: Clinicians should have heightened awareness for these relevant co-morbidities when treating men with PD. STRENGTHS & LIMITATIONS: Utilizing a claims database provides one of the largest cohorts of men with PD ever published but claims databases lack some individual patient data such as risk factors and demographic information relevant to PD, including: penile injury, history of urologic procedures, and other lifestyle factors. CONCLUSION: Men with PD had a higher risk of benign prostatic hyperplasia, lower urinary tract symptoms, prostatitis, and keloids after a diagnosis of PD, but no increased risk of auto-immune conditions. These findings suggest a common etiology for these conditions that may manifest itself in diseases at different times in men's life cycle. Pastuszak AW, Rodriguez KM, Solomon ZJ, et al. Increased Risk of Incident Disease in Men with Peyronie's Disease: Analysis of U.S. Claims Data. J Sex Med 2018;15:894-901.

The Role of Testosterone Therapy in the Setting of Prostate Cancer.

PURPOSE OF REVIEW: The role of testosterone in the development of prostate cancer and the safety of testosterone therapy (TTh) after prostate cancer treatment, or in the setting of active surveillance, remains controversial. There are many concerns about using TTh in men, particularly those with a history of prostate cancer, ranging from a possible increased risk of cardiovascular disease to cancer progression or recurrence. With many prostate cancer patients living longer, and hypogonadism having significant morbidity, much care must go into the decision to treat. Here, we review the literature investigating the effects of testosterone on the prostate as well as the efficacy and safety of exogenous testosterone in men with a history of prostate cancer. RECENT FINDINGS: The improvement in quality of life with TTh is well studied and understood, while the argument for significantly increased risk of cancer or other adverse effects is much less robust. Neither increased rates of prostate cancer, cancer recurrence, or cardiovascular risk have been well established. In men with high-risk prostate cancer, evidence in the setting of TTh is very limited, and TTh should be used with caution. The fears of TTh causing or worsening prostate cancer do not appear to be well supported by available data. Though more studies are needed to definitively determine the safety of TTh in men with prostate cancer, consideration should be given to treatment of hypogonadal men with a history of CaP.

Peptide multifunctionalized gold nanorods decrease toxicity of ß-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease.

The properties of nanometric materials make nanotechnology a promising platform for tackling problems of contemporary medicine. In this work, gold nanorods were synthetized and stabilized with polyethylene glycols and modified with two kinds of peptides. The D1 peptide that recognizes toxic aggregates of Aß, a peptide involved in Alzheimer's disease (AD); and the Angiopep 2 that can be used to deliver nanorods to the mammalian central nervous system. The nanoconjugates were characterized using absorption spectrophotometry, dynamic light scattering, and transmission electron microscopy, among other techniques. We determined that the nanoconjugate does not affect neuronal viability; it penetrates the cells, and decreases aggregation of Aß peptide in vitro. We also showed that when we apply our nanosystem to a Caenorhabditis elegans AD model, the toxicity of aggregated Aß peptide is decreased. This work may contribute to the development of therapies for AD based on metallic nanoparticles.

Differences in the survival of patients with recurrent versus de novo metastatic KRAS-mutant and EGFR-mutant lung adenocarcinomas.

BACKGROUND: Prognostic variables are independently associated with survival and are fundamental to clinical trial design. In the current study, the authors evaluated the impact of stage of disease at the time of the initial diagnosis on overall survival (OS) in 2 independent, oncogene-defined cohorts. METHODS: All patients with epidermal growth factor receptor (EGFR)-mutant and KRAS-mutant metastatic lung adenocarcinomas were identified through routine molecular testing from January 2005 through January 2011. Clinical characteristics were obtained. OS from the date of diagnosis of recurrent or de novo metastatic disease was estimated using the Kaplan-Meier method. RESULTS: A total of 635 patients with KRAS-mutant and 496 patients with EGFR-mutant metastatic lung adenocarcinomas were identified. Among patients with KRAS-mutant lung adenocarcinomas, those with de novo metastatic disease were found to have a shorter median OS compared with those with recurrent metastatic disease (13 months vs 18 months; P = .003). In a multivariable analysis of patients with KRAS-mutant lung adenocarcinomas, de novo metastatic disease at the time of diagnosis (TNM stage IV vs stage I-III: hazard ratio, 1.5 [95% confidence interval, 1.2-1.8]; P<.001) was independently associated with shorter OS. In patients with EGFR-mutant lung adenocarcinomas, after controlling for age and Karnofsky performance status, de novo metastatic disease at the time of diagnosis (stage IV vs stage I-III: hazard ratio, 1.3 [95% confidence interval, 1.0-1.7]; P = .03) was found to be independently associated with shorter OS. CONCLUSIONS: Among patients with KRAS-mutant lung adenocarcinomas, stage of disease at diagnosis was associated with OS from the time of diagnosis of recurrent/metastatic disease. In multivariable analyses, in both patients with EGFR-mutant and KRAS-mutant lung adenocarcinomas, advanced stage at the time of diagnosis was found to be independently associated with shorter survival. Stage at diagnosis is a prognostic variable that should be accounted for in prospective studies in patients with metastatic lung adenocarcinomas.

Unraveling Ritlecitinib: an in-depth analysis of JAK3 inhibitor for the treatment of alopecia areata.

INTRODUCTION: Alopecia Areata (AA), characterized by non-scarring hair loss due to the dysregulation of the JAK/STAT pathway, has long lacked effective treatment. In 2023, Ritlecitinib, a novel Janus kinase (JAK) 3 and tyrosine kinase family inhibitor, received its first approval from the US FDA to treat AA, followed by approvals in Japan, Europe, China, and the UK. This development aims to address the challenges faced by millions of individuals affected by this condition globally. AREAS COVERED: This review offers an overview of Ritlecitinib's pharmacological properties, biological targets, and development strategies. It examines its mechanism of action, pharmacokinetics, pharmacodynamics, and clinical trial insights. Additionally, it covers the drug's chemical synthesis, contraindications, drug interactions, and potential adverse effects, with special attention to its use in adolescents, pregnant women, and the elderly. EXPERT OPINION: Ritlecitinib represents a significant advancement in treating AA, offering a targeted approach with promising efficacy and a favorable safety profile. While long-term safety data and real-world effectiveness studies are needed, its oral administration and efficacy in both adults and adolescents position it as a potentially transformative therapy. Ongoing research should focus on optimizing treatment strategies, identifying predictive biomarkers, and assessing cost-effectiveness to fully realize Ritlecitinib's potential in improving outcomes.

Point of Care Ultrasound as a Key Tool in the Evaluation of a Woman with Syncope.

Using point of care ultrasound (POCUS) to evaluate patients with syncope in the emergency department facilitates the timely diagnosis of life-threatening pathologies. Case: A 56-year-old woman presented to the emergency department of a hospital in Bogotá, Colombia, for a syncopal episode. Vital signs, physical examination, electrocardiogram, and routine laboratory tests were normal. Cardiac POCUS was performed, which identified an echogenic mass located in the left atrium, measuring 35x28mm, which in left atrial systole appeared to occupy the entire chamber. She underwent surgical resection of the mass and histopathology revealed atrial myxoma. Conclusions: POCUS was useful in the rapid diagnosis of atrial myxoma in a woman presenting with syncope.

Pathogen kinetics and detection by next-generation sequencing in pediatric complicated pneumonia.

Pediatric pneumonia can be severe and result in empyema. Next-generation sequencing (NGS) may broadly detect pathogens though, optimal timing and impact of sample type on diagnostic yield is unknown. This is a prospective, single-center pilot study of children aged 3 months through 17 years admitted to the PICU with a primary diagnosis of complicated pneumonia. Plasma, endotracheal, nasopharyngeal, and pleural fluid samples were collected at three time points during hospitalization. After nucleic acid extraction, combined libraries were enriched with an NGS enrichment panel kit (RPIP, Illumina), sequenced and quantitative organism detections were analyzed. NGS identified the same bacterial pathogen as traditional testing in all samples, regardless of antibiotic pre-treatment or time collected. Conventional culture methods only identified the pathogen reliably in invasively obtained pleural fluid or endotracheal aspirates. Future application of NGS may allow for non-invasive pathogen detection at a broader range of time points and more targeted antibiotic coverage.

Impaired Skeletal Development by Disruption of Presenilin-1 in Pigs and Generation of Novel Pig Models for Alzheimer's Disease.

Background: Presenilin 1 (PSEN1) is one of the genes linked to the prevalence of early onset Alzheimer's disease. In mice, inactivation of Psen1 leads to developmental defects, including vertebral malformation and neural development. However, little is known about the role of PSEN1 during the development in other species. Objective: To investigate the role of PSEN1 in vertebral development and the pathogenic mechanism of neurodegeneration using a pig model. Methods: CRISPR/Cas9 system was used to generate pigs with different mutations flanking exon 9 of PSEN1, including those with a deleted exon 9 (Δexon9). Vertebral malformations in PSEN1 mutant pigs were examined by X-ray, micro-CT and micro-MRI. Neuronal cells from the brains of PSEN1 mutant pigs were analyzed by immunoflourescence, followed by image analysis including morphometric evaluation via image J and 3D reconstruction. Results: Pigs with a PSEN1 null mutation (Δexon9-12) died shortly after birth and had significant axial skeletal defects, whereas pigs carrying at least one Δexon9 allele developed normally and remained healthy. Effects of the null mutation on abnormal skeletal development were also observed in fetuses at day 40 of gestation. Abnormal distribution of astrocytes and microglia in the brain was detected in two PSEN1 mutant pigs examined compared to age-matched control pigs. The founder pigs were bred to establish and age PSEN1ΔE9/+ pigs to study their relevance to clinical Alzheimer's diseases. Conclusions: PSEN1 has a critical role for normal vertebral development and PSEN1 mutant pigs serves as novel resources to study Alzheimer's disease.

Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Engineering the Polymer-MOF Interface in Microporous Composites to Address Complex Mixture Separations.

Poor interfacial compatibility remains a pressing challenge in the fabrication of high-performance polymer-MOF composites. In response, introducing compatible chemistries such as a carboxylic acid moiety has emerged as a compelling strategy to increase polymer-MOF interactions. In this work, we leveraged compatible functionalities in UiO-66-NH2 and a carboxylic acid-functionalized PIM-1 to fabricate mixed-matrix membranes (MMMs) with improved separation performance compared to PIM-1-based MMMs in industrially relevant conditions. Under pure-gas conditions, PIM-COOH-based MMMs retained selectivity with increasing MOF loading and showed increased permeability due to increased diffusion. The composites were further investigated under industrially relevant conditions, including CO2/N2, CO2/CH4, and H2S/CO2/CH4 mixtures, to elucidate the effects of competitive sorption and plasticization. Incorporation of UiO-66-NH2 in PIM-COOH and PIM-1 mitigated the effects of CO2- and H2S-induced plasticization typically observed in linear polymers. In CO2-based binary mixed-gas tests, all samples showed similar performance as that in pure-gas tests, with minimal competitive sorption contributions associated with the amine functional groups of the MOF. In ternary mixed-gas tests, improved plasticization resistance and interfacial compatibility resulted in PIM-COOH-based MMMs having the highest H2S/CH4 and CO2/CH4 selectivity combinations among the films tested in this study. These findings demonstrate that selecting MOFs and polymers with compatible functional groups is a useful strategy in developing high-performing microporous MMMs that require stability under complex and industrially relevant conditions.

Clinicopathologic and Survival After Cystectomy Outcomes in Squamous Cell Carcinoma of the Bladder.

BACKGROUND: Squamous cell carcinoma of the bladder (SqCC) is a rare disease with limited management data. Thus, we sought to characterize the clinicopathologic and survival outcomes amongst patients with SqCC and explore the association of squamous differentiation within urothelial carcinoma (UC w/Squam), as compared to muscle invasive pure UC. METHODS: We conducted a single-center retrospective cohort study of patients, stratified by histology, who underwent cystectomy for MIBC. Baseline clinicopathologic characteristics were compared, and overall survival was assessed using Kaplan-Meier method. RESULTS: We identified 1,034 patients; 37 (3.58%) with SqCC histology, 908 (87.81%) with UC histology, and 89 (8.61%) with UC w/ Squam histology. Among SqCC patients, a higher proportion were Black and similarly a higher proportion were women; amongst patients with UC w/ Squam a higher proportion had lower BMI; and amongst patients with UC a higher proportion had lower clinical (c) T, cN, pathological (p) T, and pN stages. Patients presenting with UC were more likely to receive intravesical therapy; patients presenting with SqCC were less likely to receive neoadjuvant chemotherapy (NAC). Adjuvant chemotherapy rates were similar. With post-hoc Bonferroni analysis, overall survival, cancer-specific survival, and recurrence-free survival were significantly worse for the UC w/ Squam cohort. CONCLUSIONS: UC w/ Squam histology was associated with worse survival outcomes after cystectomy for muscle invasive bladder cancer compared to UC. Our results suggest that UC w/ Squam is associated with more advanced disease compared to UC, warranting further prospective work on consideration of combination therapies for patients with this disease state.

Glutathione supports lipid abundance in vivo.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Plasma cell free next-generation sequencing detects an unusual pneumonia pathogen in an immunocompetent adolescent with acute respiratory distress syndrome.

This case details a rapid diagnosis of legionella pneumonia causing severe acute respiratory distress syndrome (ARDS) in an otherwise healthy adolescent through plasma microbial cell-free DNA next generation sequencing (mcfDNA-NGS). Diagnosis by mcfDNA-NGS of this unexpected pathogen led to narrowing of antimicrobials and the addition of glucocorticoids as adjunctive therapy for ARDS.

Adrenal pheochromocytoma in a patient with Lynch Syndrome.

Lynch Syndrome (LS), or hereditary non-polyposis colorectal cancer, is the most common cause of hereditary colorectal cancer. There are well described extra-colonic manifestations of LS, including gynecologic and upper urinary tract malignancies. Other extra-colonic manifestations of LS are less understood. Here we present an unusual case of a functional adrenal pheochromocytoma in a 31-year old man with LS.